02667nas a2200409 4500008004100000022001400041245005900055210005300114260001300167300001100180490000600191520161900197653000901816653003001825653002101855653002601876653001101902653001801913653001101931653002501942653000901967653002501976653002002001653001702021653001802038100001502056700001702071700001502088700001702103700001602120700001802136700001602154700001702170700002102187700001402208856003502222 1991 eng d a1047-279700aThe Cardiovascular Health Study: design and rationale.0 aCardiovascular Health Study design and rationale c1991 Feb a263-760 v13 a
The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.
10aAged10aCerebrovascular Disorders10aCoronary Disease10aEpidemiologic Methods10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aPhysical Examination10aResearch Design10aRisk Factors10aUnited States1 aFried, L P1 aBorhani, N O1 aEnright, P1 aFurberg, C D1 aGardin, J M1 aKronmal, R, A1 aKuller, L H1 aManolio, T A1 aMittelmark, M, B1 aNewman, A uhttps://chs-nhlbi.org/node/89702078nas a2200397 4500008004100000022001400041245014100055210006900196260001300265300001200278490000700290520092000297653001601217653000901233653002101242653002101263653002801284653002901312653001101341653001101352653004401363653004001407653000901447653002401456653002001480100001701500700001601517700001801533700001501551700001401566700001301580700001501593700001901608700001701627856003601644 1991 eng d a0039-249900aUse of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group.0 aUse of sonography to evaluate carotid atherosclerosis in the eld c1991 Sep a1155-630 v223 aCarotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.
10aAge Factors10aAged10aArteriosclerosis10aCarotid Arteries10aCarotid Artery Diseases10aCarotid Artery, Internal10aFemale10aHumans10aImage Interpretation, Computer-Assisted10aImage Processing, Computer-Assisted10aMale10aProspective Studies10aUltrasonography1 aO'Leary, D H1 aPolak, J, F1 aWolfson, S, K1 aBond, M, G1 aBommer, W1 aSheth, S1 aPsaty, B M1 aSharrett, A, R1 aManolio, T A uhttps://chs-nhlbi.org/node/108202695nas a2200349 4500008004100000022001400041245018200055210006900237260001300306300001100319490000700330520167100337653000902008653002202017653003002039653002102069653002002090653002102110653001102131653001102142653000902153653002402162653001702186653001802203100001502221700001102236700001702247700001602264700001702280700001302297856003502310 1992 eng d a0895-435600aAssessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. The Cardiovascular Health Study Collaborative Research Group.0 aAssessing the use of medications in the elderly methods and init c1992 Jun a683-920 v453 aThe Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary heart disease and stroke, recruited 5201 community-dwelling adults aged 65 years or older. To assess the prevalence of medication use at baseline, we used the method of medication inventory and transcribed information about drug names and doses from prescription bottles. Using a specially-written computer program, persons without a knowledge of drug nomenclature coded 10,511 (89%) of the 11,846 medicines entered. We compared the results of the medication inventory and answers to questions on specific medications for reliability and validity. The use of beta-blockers and beta-agonists assessed by the method of medication inventory, but not by the method of directed recall, was associated with a significant effect on mean heart rate. Among 5197 participants with medication data, 76.1% were taking at least one medicine, and the mean number of drugs per person was 2.28. Among those with a reported history of high blood pressure, participants with cardiovascular disease (CVD) were more likely to be treated, and they were more likely to be taking beta-blockers and calcium-channel blockers than those without CVD. Daily aspirin use was also more common among those with CVD (30.5% of women and 43.2% of men) than among those without CVD (14.0% of women and 14.0% of men). The prevalence of post-menopausal estrogen use differed significantly among the four clinical centers (range = 5.5%-22.5% of women). We conclude that this method of assessing medications was easy to use and provided estimates of exposure to drugs that may affect risk of cardiovascular disease.
10aAged10aAged, 80 and over10aCerebrovascular Disorders10aCoronary Disease10aData Collection10aDrug Utilization10aFemale10aHumans10aMale10aProspective Studies10aRisk Factors10aUnited States1 aPsaty, B M1 aLee, M1 aSavage, P, J1 aRutan, G, H1 aGerman, P, S1 aLyles, M uhttps://chs-nhlbi.org/node/84803587nas a2200421 4500008004100000022001400041245015700055210006900212260001300281300001200294490000700306520239900313653000902712653002102721653001702742653002802759653003002787653002102817653001102838653001102849653000902860653002002869653001502889653002402904653001702928653002002945100001702965700001602982700001802998700001803016700001503034700001803049700001403067700001603081700001603097700001703113856003503130 1992 eng d a0039-249900aDistribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.0 aDistribution and correlates of sonographically detected carotid c1992 Dec a1752-600 v233 aBACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years.
METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history.
RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation.
CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.
10aAged10aArteriosclerosis10aCardiomegaly10aCarotid Artery Diseases10aCerebrovascular Disorders10aCoronary Disease10aFemale10aHumans10aMale10aMedical Records10aPrevalence10aRegression Analysis10aRisk Factors10aUltrasonography1 aO'Leary, D H1 aPolak, J, F1 aKronmal, R, A1 aKittner, S, J1 aBond, M, G1 aWolfson, S, K1 aBommer, W1 aPrice, T, R1 aGardin, J M1 aSavage, P, J uhttps://chs-nhlbi.org/node/74902024nas a2200385 4500008004100000022001400041245014300055210006900198260001300267300001100280490000600291520096300297653003901260653001601299653000901315653002801324653001901352653001501371653001601386653001101402653001501413653001101428653000901439653001601448653001701464100001501481700001701496700001501513700001301528700001401541700001601555700001501571700001701586856003501603 1992 eng d a1047-279700aThe distribution of coagulation factors VII and VIII and fibrinogen in adults over 65 years. Results from the Cardiovascular Health Study.0 adistribution of coagulation factors VII and VIII and fibrinogen c1992 Jul a509-190 v23 aThe Cardiovascular Health Study (CHS) was designed to examine cardiovascular disease and its risk factors in older adults. We report here the distributions of the coagulation factors fibrinogen, factor VII, and factor VIII in a population-based cohort of men and women 65 years or older. In other studies of middle-aged individuals, these factors were shown to be associated with cardiovascular risk. In the CHS cohort, all three factors were elevated, compared to levels reported in middle-aged individuals, and fibrinogen and factor VIII values were higher in each successive age group; factor VII values, in contrast, declined slightly with age in the CHS cohort. Compared to white subjects, blacks had higher values for fibrinogen and factor VIII and lower values for factor VII. While women had markedly higher values for factor VII and factor VIII than men at all ages in the CHS, mean fibrinogen values were not different between men and women.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aCardiovascular Diseases10aCohort Studies10aFactor VII10aFactor VIII10aFemale10aFibrinogen10aHumans10aMale10aMiddle Aged10aRisk Factors1 aTracy, R P1 aBovill, E, G1 aFried, L P1 aHeiss, G1 aLee, M, H1 aPolak, J, F1 aPsaty, B M1 aSavage, P, J uhttps://chs-nhlbi.org/node/74703489nas a2200433 4500008004100000022001400041245011000055210006900165260001600234300001000250490000800260520229000268653001602558653000902574653002202583653003002605653002102635653002102656653003002677653001102707653001102718653002502729653002502754653000902779653002302788653003002811653001702841653001802858100001702876700001702893700001402910700001502924700001702939700001602956700001502972700001702987700001603004856003503020 1992 eng d a0003-481900aEligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study.0 aEligibility for cholesterol referral in communitydwelling older c1992 Apr 15 a641-90 v1163 aOBJECTIVES: To assess the proportion of community-dwelling adults aged 65 years or older who are eligible for referral for lipoprotein analysis and intervention according to the National Cholesterol Education Program (NCEP) guidelines.
DESIGN: Cross-sectional study based on examinations and questionnaires collected in 1989 and 1990.
SETTING: Four communities in the U.S. in the Cardiovascular Health Study (CHS), a study of risk factors for heart disease and stroke in older adults.
PARTICIPANTS: A sample of 4810 men and women ages 65 to 100 randomly selected and recruited from Health Care Financing Administration Medicare eligibility lists for the four communities; not institutionalized, not wheelchair-bound, not currently receiving therapy for cancer, not currently taking lipid-lowering medications, and not having eaten in the preceding 9 hours.
MEASUREMENTS: Total cholesterol and lipoprotein analysis measured in all participants.
RESULTS: Total cholesterol levels were less than 5.17 mmol/L (200 mg/dL) in 37% of participants, 5.17 to 6.19 mmol/L (200 to 239 mg/dL) in 39%, and 6.20 mmol/L (240 mg/dL) or greater in 24%. Compared with their counterparts, older participants, especially those over 80 years of age, were more likely to have levels below 5.17 mmol/L, as were men, nonwhites, and those with coronary heart disease or two or more coronary heart disease risk factors (P less than 0.008 for all values). Based on this screening measurement, 2174 participants were eligible for lipoprotein analysis, 80% were eligible for dietary or drug therapy using NCEP guidelines. Overall, 46% of CHS participants were eligible for lipoprotein analysis and 36% for intervention by NCEP guidelines, based on a single cholesterol measurement.
CONCLUSION: A substantial proportion of older adults in this community sample were eligible for lipoprotein analysis and intervention. Prospective studies of elderly persons are needed to determine the risk for incident coronary heart disease according to NCEP classifications and the benefits of lipid-lowering treatments in persons in this age group so that intervention strategies may best be targeted to an appropriately high-risk group.
10aAge Factors10aAged10aAged, 80 and over10aCerebrovascular Disorders10aCholesterol, LDL10aCoronary Disease10aEligibility Determination10aFemale10aHumans10aHypercholesterolemia10aLongitudinal Studies10aMale10aPrimary Prevention10aReferral and Consultation10aRisk Factors10aUnited States1 aManolio, T A1 aFurberg, C D1 aWahl, P W1 aTracy, R P1 aBorhani, N O1 aGardin, J M1 aFried, L P1 aO'Leary, D H1 aKuller, L H uhttps://chs-nhlbi.org/node/80803412nas a2200469 4500008004100000022001400041245014500055210006900200260001600269300001200285490000800297520208700305653000902392653002202401653001702423653002802440653002802468653003002496653002102526653002802547653002102575653002402596653001102620653001102631653001702642653000902659653002602668653002402694653001702718653001202735100001502747700001702762700001602779700001702795700002102812700001702833700001502850700001502865700001502880700001202895856003502907 1992 eng d a0098-748400aIsolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study.0 aIsolated systolic hypertension and subclinical cardiovascular di c1992 Sep 09 a1287-910 v2683 aOBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above.
DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg.
MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis.
RESULTS: Among the 2189 men and women in this analysis, 195 (9%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001).
CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.
10aAged10aAged, 80 and over10aCardiomegaly10aCardiovascular Diseases10aCarotid Artery Diseases10aCerebrovascular Disorders10aCoronary Disease10aCross-Sectional Studies10aEchocardiography10aElectrocardiography10aFemale10aHumans10aHypertension10aMale10aMyocardial Infarction10aProspective Studies10aRisk Factors10aSystole1 aPsaty, B M1 aFurberg, C D1 aKuller, L H1 aBorhani, N O1 aRautaharju, P, M1 aO'Leary, D H1 aBild, D, E1 aRobbins, J1 aFried, L P1 aReid, C uhttps://chs-nhlbi.org/node/74803982nas a2200421 4500008004100000022001400041245012400055210006900179260001300248300001100261490000700272520282000279653000903099653001003108653002803118653004303146653002103189653002103210653002803231653001103259653001803270653001103288653001103299653001703310653000903327653002603336653001803362100001903380700001403399700001603413700001503429700001503444700001703459700001703476700001503493700001703508856003503525 1992 eng d a0009-732200aLipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group.0 aLipoprotein lipids in older people Results from the Cardiovascul c1992 Sep a858-690 v863 aBACKGROUND: Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old.
METHODS AND RESULTS: Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease.
CONCLUSIONS: Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use.
10aAged10aAging10aCardiovascular Diseases10aCardiovascular Physiological Phenomena10aCholesterol, HDL10aCholesterol, LDL10aCross-Sectional Studies10aFemale10aHealth Status10aHumans10aLipids10aLipoproteins10aMale10aMultivariate Analysis10aTriglycerides1 aEttinger, W, H1 aWahl, P W1 aKuller, L H1 aBush, T, L1 aTracy, R P1 aManolio, T A1 aBorhani, N O1 aWong, N, D1 aO'Leary, D H uhttps://chs-nhlbi.org/node/78102586nas a2200409 4500008004100000022001400041245017300055210006900228260001600297300001200313490000700325520141600332653001601748653000901764653002201773653002501795653002801820653002401848653001101872653001901883653001101902653002001913653000901933653001501942653001701957653001601974653001801990100001702008700001702025700001502042700001502057700001702072700001402089700001702103700002102120856003502141 1992 eng d a0002-914900aMajor electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.0 aMajor electrocardiographic abnormalities in persons aged 65 year c1992 May 15 a1329-350 v693 aElectrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29% in the entire cohort, 19% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease.
10aAge Factors10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aChi-Square Distribution10aElectrocardiography10aFemale10aHeart Diseases10aHumans10aLogistic Models10aMale10aPrevalence10aRisk Factors10aSex Factors10aUnited States1 aFurberg, C D1 aManolio, T A1 aPsaty, B M1 aBild, D, E1 aBorhani, N O1 aNewman, A1 aTabatznik, B1 aRautaharju, P, M uhttps://chs-nhlbi.org/node/83503340nas a2200361 4500008004100000022001400041245011200055210006900167260001300236300001100249490000700260520237100267653000902638653001002647653001302657653001502670653001102685653001802696653001102714653002902725653000902754653002602763653002802789653001502817653001702832100001602849700001702865700001502882700001802897700001302915700001502928856003502943 1992 eng d a0194-911X00aOrthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.0 aOrthostatic hypotension in older adults The Cardiovascular Healt c1992 Jun a508-190 v193 aThe purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.
10aAged10aAging10aDementia10aDemography10aFemale10aHealth Status10aHumans10aHypotension, Orthostatic10aMale10aMultivariate Analysis10aNervous System Diseases10aPrevalence10aRisk Factors1 aRutan, G, H1 aHermanson, B1 aBild, D, E1 aKittner, S, J1 aLaBaw, F1 aTell, G, S uhttps://chs-nhlbi.org/node/84103864nas a2200373 4500008004100000022001400041245012500055210006900180260001300249300001200262490000700274520283300281653003103114653002103145653000903166653002203175653002803197653001103225653001103236653000903247653001503256653002103271653002603292100001503318700001903333700001503352700001503367700001503382700001303397700001403410700001603424700001403440856003603454 1993 eng d a0002-861400aAge-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study.0 aAgerelated trends in cardiovascular morbidity and physical funct c1993 Oct a1047-560 v413 aOBJECTIVE: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older.
DESIGN: Observational population-based study.
SETTING: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania.
PARTICIPANTS: 5,201 men and women aged 65 years and older.
MEASUREMENTS: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined.
MAIN RESULTS: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups.
CONCLUSIONS: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.
10aActivities of Daily Living10aAge Distribution10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aHumans10aMale10aPrevalence10aSex Distribution10aSocioeconomic Factors1 aBild, D, E1 aFitzpatrick, A1 aFried, L P1 aWong, N, D1 aHaan, M, N1 aLyles, M1 aBovill, E1 aPolak, J, F1 aSchulz, R uhttps://chs-nhlbi.org/node/144203948nas a2200385 4500008004100000022001400041245015000055210006900205260001300274300001100287490000700298520283000305653000903135653001003144653000803154653002103162653003303183653002803216653001103244653001103255653000903266653002603275653003303301653002803334653003003362653001703392100001703409700002003426700001703446700001303463700001503476700001703491700001803508856003603526 1993 eng d a0009-732200aAnkle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.0 aAnklearm index as a marker of atherosclerosis in the Cardiovascu c1993 Sep a837-450 v883 aBACKGROUND: Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD.
METHODS AND RESULTS: The AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (< 0.8, > or = 0.8 to < 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4% of participants < 0.8, 12.4% < 0.9, and 23.6% < 1.0. participants with an AAI < 0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P < .01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P < .01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of < 1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P < .01).
CONCLUSIONS: There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD.
10aAged10aAnkle10aArm10aArteriosclerosis10aBlood Pressure Determination10aCardiovascular Diseases10aFemale10aHumans10aMale10aMultivariate Analysis10aPeripheral Vascular Diseases10aPopulation Surveillance10aPredictive Value of Tests10aRisk Factors1 aNewman, A, B1 aSiscovick, D, S1 aManolio, T A1 aPolak, J1 aFried, L P1 aBorhani, N O1 aWolfson, S, K uhttps://chs-nhlbi.org/node/144101917nas a2200325 4500008004100000022001400041245007800055210006900133260001300202300001000215490000600225520105000231653000901281653002201290653003001312653001901342653002101361653001101382653001101393653003101404653002501435653000901460653001501469100001601484700001301500700001501513700001301528700001401541856003601555 1993 eng d a1047-279700aAssessment of cerebrovascular disease in the Cardiovascular Health Study.0 aAssessment of cerebrovascular disease in the Cardiovascular Heal c1993 Sep a504-70 v33 aThe Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.
10aAged10aAged, 80 and over10aCerebrovascular Disorders10aCohort Studies10aCoronary Disease10aFemale10aHumans10aIschemic Attack, Transient10aLongitudinal Studies10aMale10aPrevalence1 aPrice, T, R1 aPsaty, B1 aO'Leary, D1 aBurke, G1 aGardin, J uhttps://chs-nhlbi.org/node/143102954nas a2200397 4500008004100000022001400041245015100055210006900206260001300275300001200288490000700300520182900307653000902136653001002145653002802155653002102183653002102204653002402225653003302249653001102282653001002293653002102303653001102324653002302335653001702358653001202375653002002387100001702407700001702424700001702441700001502458700001702473700001502490700001502505856003602520 1993 eng d a0009-732200aAssociations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group.0 aAssociations of postmenopausal estrogen use with cardiovascular c1993 Nov a2163-710 v883 aBACKGROUND: Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women.
METHODS AND RESULTS: Present and past estrogen use was ascertained in 2955 women > or = 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12% of these women and past use by an additional 26.5%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P < .0001). Estrogen users also had lower levels of subclinical disease as measured by carotid intimal-medial thickness, carotid stenosis grade, ECG left ventricular mass, and Doppler mitral peak flow velocities (each P < .02). Relations were similar in younger and older women (65 to 74 versus > or = 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids.
CONCLUSIONS: Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life.
10aAged10aAging10aCardiovascular Diseases10aCarotid Arteries10aCarotid Stenosis10aElectrocardiography10aEstrogen Replacement Therapy10aFemale10aHeart10aHeart Ventricles10aHumans10aPatient Compliance10aRisk Factors10aSmoking10aUltrasonography1 aManolio, T A1 aFurberg, C D1 aShemanski, L1 aPsaty, B M1 aO'Leary, D H1 aTracy, R P1 aBush, T, L uhttps://chs-nhlbi.org/node/143502674nas a2200397 4500008004100000022001400041245009300055210006900148260001300217300001100230490000700241520160300248653000901851653002201860653001001882653002801892653004301920653001601963653001101979653001801990653001102008653002502019653000902044653001502053653001602068653002402084653001702108100001702125700001902142700001502161700001602176700001702192700001602209700001502225856003602240 1993 eng d a0009-732200aEpidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study.0 aEpidemiology of low cholesterol levels in older adults The Cardi c1993 Mar a728-370 v873 aBACKGROUND: Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths.
METHODS AND RESULTS: This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes.
CONCLUSIONS: Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies.
10aAged10aAged, 80 and over10aAging10aCardiovascular Diseases10aCardiovascular Physiological Phenomena10aCholesterol10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aPrevalence10aProbability10aRegression Analysis10aRisk Factors1 aManolio, T A1 aEttinger, W, H1 aTracy, R P1 aKuller, L H1 aBorhani, N O1 aLynch, J, C1 aFried, L P uhttps://chs-nhlbi.org/node/144502897nas a2200457 4500008004100000022001400041245009500055210006900150260001600219300001000235490000800245520167300253653001601926653000901942653002201951653000901973653001501982653002801997653002402025653001102049653001902060653001102079653002502090653000902115653001302124653001902137653001902156653001702175653002802192653001502220653003102235100002102266700001502287700002102302700001502323700001702338700001502355700001602370700001702386856003602403 1993 eng d a0002-926200aPrevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study.0 aPrevalence of cardiovascular diseases among older adults The Car c1993 Feb 01 a311-70 v1373 aThe Cardiovascular Health Study is a population-based longitudinal study of 5,201 adults aged 65 years and older. Prevalences of myocardial infarction, angina pectoris, congestive heart failure, peripheral artery disease, stroke, and transient ischemic attack were ascertained between June 1989 and May 1990 in participants recruited from Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pennsylvania. A medical history was taken to obtain self-reports of prevalent disease. For all participants, use of nitrates was ascertained to document angina, electrocardiograms were used to document prevalent myocardial infarction, and ankle-arm blood pressure studies were used to document peripheral artery disease. Self-reports of disease that were not confirmed by examination findings were further investigated by examination of medical records. Reported disease that was confirmed by examination findings or by medical records was classified as "definite." Disease that was documented by examination, but not reported by the participant, was classified as "unreported." The prevalence rates of definite myocardial infarction and angina were 11% and 15%, respectively, among men aged 65-69 years, 18% and 17% among men aged 80-84 years, 4% and 8% among women aged 65-69 years, and 3% and 13% among women aged 80-84 years. Twenty-three percent of men and 38% of women with electrocardiographic evidence of myocardial infarction did not report it. These results suggest that prevalent disease estimates based only on self-report may underestimate the prevalence of cardiovascular diseases in older Americans.
10aAge Factors10aAged10aAged, 80 and over10aBias10aCalifornia10aCardiovascular Diseases10aElectrocardiography10aFemale10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aMaryland10aMass Screening10aNorth Carolina10aPennsylvania10aPopulation Surveillance10aPrevalence10aReproducibility of Results1 aMittelmark, M, B1 aPsaty, B M1 aRautaharju, P, M1 aFried, L P1 aBorhani, N O1 aTracy, R P1 aGardin, J M1 aO'Leary, D H uhttps://chs-nhlbi.org/node/144602616nas a2200301 4500008004100000022001400041245009700055210006900152260001300221300001100234490000600245520179400251653000902045653002202054653002802076653001902104653002602123653001102149653001102160653000902171100001502180700001502195700001702210700001702227700001702244700001702261856003602278 1993 eng d a1047-279700aRecruitment of adults 65 years and older as participants in the Cardiovascular Health Study.0 aRecruitment of adults 65 years and older as participants in the c1993 Jul a358-660 v33 aFew large-scale epidemiologic studies have enrolled older adults; hence, little is known about the feasibility of recruiting this group for long-term population-based studies. In this article we present the recruitment experience of the Cardiovascular Health Study (CHS), a population-based, longitudinal study of cardiovascular diseases in adults 65 years and older. Participants were sampled from the Health Care Financing Administration's (HCFA) Medicare eligibility lists in four US communities. Letters were mailed to 11,955 sampled individuals. Persons recruited were required to complete an extensive home interview and then a 4-hour in-clinic examination. Excluded were persons who were expected to be able to complete the baseline examination and who were not expected to return for the 3-year follow-up. Some 3654 participants were recruited from those randomly selected from the Medicare sampling frame. In addition, 1547 other age-eligible persons living in the household with the sampled individuals also participated, yielding a total of 5201 participants. Of those who were contacted, 9.6% were ineligible and 34.9% refused participation. Among those eligible, 38.6% refused and 57.3% were enrolled (the remaining did not refuse but were not enrolled before the recruitment ended). Data from a subsample indicate that compared to those who were ineligible or who refused, enrolled participants were younger, more highly educated, more likely to be married, and less likely to report limitations in activity. Compared to those who were eligible but refused, enrolled participants were less likely to have high blood pressure and stroke and more likely to have quit smoking and to perceive their health status as very good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aEpidemiologic Methods10aFemale10aHumans10aMale1 aTell, G, S1 aFried, L P1 aHermanson, B1 aManolio, T A1 aNewman, A, B1 aBorhani, N O uhttps://chs-nhlbi.org/node/143603121nas a2200325 4500008004100000022001400041245008700055210006900142260001300211300001100224490000700235520222600242653000902468653002202477653001102499653001702510653002702527653001602554653001102570653001202581653000902593653001902602653003002621653003202651100001702683700001902700700002202719700001802741856003602759 1993 eng d a0002-861400aSerum fructosamine as a screening test for diabetes in the elderly: a pilot study.0 aSerum fructosamine as a screening test for diabetes in the elder c1993 Oct a1090-40 v413 aOBJECTIVE: To determine the value of serum glycated protein, measured as serum fructosamine, as a screening test for diabetes in the elderly.
DESIGN: Cross-sectional pilot study.
SETTING: Ambulatory research clinic in university setting.
PATIENTS: One hundred fifty-seven consecutive community-dwelling participants in the Cardiovascular Health Study, average age 71.8 + 5 (mean +/- SD, range 65-88 years).
MEASUREMENTS: Serum fructosamine levels (first and second generation assay) were obtained. All subjects who did not have a diagnosis of diabetes were given a 75-g glucose tolerance test (GTT).
RESULTS: Twenty-six subjects (17%) (10 previously diagnosed, 16 undiagnosed and asymptomatic) had diabetes mellitus, and 38 subjects (24%) had impaired glucose tolerance by history or by the GTT (WHO criteria). Only the 16 asymptomatic diabetics were included in the analysis for the pilot study. There was a significant difference in the fasting fructosamine level between non-diabetics and asymptomatic diabetics for the first generation (2.06 +/- .21 vs 2.53 +/- .49 mMol/L, P < 0.0015) and second generation assay (221 +/- 27 vs 269 +/- 48 mMol/L, P < 0.0012). Receiver operator curves were constructed to evaluate the test characteristics of serum fructosamine. Using a point of > or = 2.3 mMol/L for the first-generation assay, the sensitivity to detect asymptomatic diabetes was 75%, specificity 83%, and positive predictive value 35%. To detect both diabetes and impaired glucose tolerance using a cutpoint of > or = 2.3 mMol/L, the sensitivity was 24%, specificity 95%, and positive predictive value 68%. Employing a cut point of 250 muMol/L for the second generation assay, the sensitivity to detect diabetes was 81%, specificity 87%, and positive predictive value 43%. However, to detect diabetes and glucose intolerance using the second generation assay, the sensitivity was 39% and specificity was 86%.
CONCLUSION: This study demonstrated that a single measurement of either first or second generation fructosamine showed promise as a screening test for diabetes, but not impaired glucose tolerance, in older people.
10aAged10aDiabetes Mellitus10aFemale10aFructosamine10aGlucose Tolerance Test10aHexosamines10aHumans10aInsulin10aMale10aPilot Projects10aPredictive Value of Tests10aSensitivity and Specificity1 aCefalu, W, T1 aEttinger, W, H1 aBell-Farrow, A, D1 aRushing, J, T uhttps://chs-nhlbi.org/node/144303196nas a2200445 4500008004100000022001400041245008900055210006900144260001600213300001100229490000800240520194100248653003902189653000902228653002202237653001802259653002802277653002802305653004002333653001102373653002902384653001102413653001802424653000902442653001502451653002402466653002102490653003102511653001702542653001202559653001802571653001902589100001802608700001802626700001802644700001902662700002002681700001302701856003602714 1993 eng d a0098-748400aSmoking and lung function in elderly men and women. The Cardiovascular Health Study.0 aSmoking and lung function in elderly men and women The Cardiovas c1993 Jun 02 a2741-80 v2693 aOBJECTIVE: To investigate relationships between cigarette smoking and pulmonary function in elderly men and women.
DESIGN: Cross-sectional analysis of baseline data from a prospective, population-based study of risk factors, preclinical, and overt cardiovascular and pulmonary disease.
SETTING: Defined communities in Forsyth County, North Carolina; Pittsburgh, Pa; Sacramento County, California; and Washington County, Maryland.
POPULATION: A total of 5201 noninstitutionalized men and women 65 years of age and older.
MAIN OUTCOME MEASURES: Pulmonary function; means of forced expiratory volume in 1 second (FEV1) and forced vital capacity and prevalence of low FEV1 levels.
RESULTS: Prevalence of cigarette smoking was 10% to 20% and higher in women than men and in blacks than whites. Forced vital capacity and FEV1 levels were related positively to height and white race and negatively to age and waist girth. Age- and height-adjusted FEV1 means were 23% and 18% lower in male and female current smokers, respectively, than in never smokers but not reduced in never smokers currently living with a smoker. Smokers who quit before age 40 years had FEV1 levels similar to never smokers, but FEV1 levels were lower by 7% and 14% in smokers who quit at ages 40 to 60 years and older than 60 years, respectively. Lung function was related inversely to pack-years of cigarette use. Prevalence rates of impaired lung function were highest in current smokers and lowest in never smokers. Regression coefficients for the smoking variables were smaller in persons without cardiovascular or respiratory conditions than in the total cohort.
CONCLUSIONS: Cigarette smoking is associated with reduced pulmonary function in elderly men and women. However, smokers who quit, even after age 60 years, have better pulmonary function than continuing smokers.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aAnthropometry10aCardiovascular Diseases10aCross-Sectional Studies10aEuropean Continental Ancestry Group10aFemale10aForced Expiratory Volume10aHumans10aLung Diseases10aMale10aPrevalence10aProspective Studies10aReference Values10aRespiratory Function Tests10aRisk Factors10aSmoking10aUnited States10aVital Capacity1 aHiggins, M, W1 aEnright, P, L1 aKronmal, R, A1 aSchenker, M, B1 aAnton-Culver, H1 aLyles, M uhttps://chs-nhlbi.org/node/144802397nas a2200385 4500008004100000022001400041245015100055210006900206260001300275300001100288490000800299520128200307653000901589653002101598653002801619653002901647653002101676653003001697653001101727653001101738653003101749653000901780653002001789100001601809700001701825700001801842700001801860700001501878700001501893700001601908700001801924700001601942700001701958856003601975 1993 eng d a0033-841900aSonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack.0 aSonographic evaluation of carotid artery atherosclerosis in the c1993 Aug a363-700 v1883 aDoppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.
10aAged10aArteriosclerosis10aCarotid Artery Diseases10aCarotid Artery, Internal10aCarotid Stenosis10aCerebrovascular Disorders10aFemale10aHumans10aIschemic Attack, Transient10aMale10aUltrasonography1 aPolak, J, F1 aO'Leary, D H1 aKronmal, R, A1 aWolfson, S, K1 aBond, M, G1 aTracy, R P1 aGardin, J M1 aKittner, S, J1 aPrice, T, R1 aSavage, P, J uhttps://chs-nhlbi.org/node/144001879nas a2200325 4500008004100000022001400041245010200055210006900157260001300226300001100239490000800250520097700258653003901235653000901274653002201283653001101305653002901316653001101345653000901356653002101365653001201386653001501398653001901413100001801432700001801450700001501468700001601483700001801499856003601517 1993 eng d a0003-080500aSpirometry reference values for women and men 65 to 85 years of age. Cardiovascular health study.0 aSpirometry reference values for women and men 65 to 85 years of c1993 Jan a125-330 v1473 aPulmonary function was assessed by spirometry in 5,201 ambulatory elderly participants of the Cardiovascular Health Study, sampled from four communities. A stringent quality assurance program exceeded American Thoracic Society (ATS) recommendations for spirometry. Less than 6% of the participants were unable to perform three acceptable spirometry maneuvers. A "healthy" subgroup of 777 women and men 65 to 85 yr of age was identified by excluding smokers and those with lung disease and other factors determined to independently, significantly, and negatively influence the FEV1. Results from black participants were examined separately. Reference equations and normal ranges for FEV1, FVC, and the FEV1/FVC ratio were determined from the healthy group. The results demonstrate differences in predicted values as great as 20% (0.5 to 1 L) for elderly patients when compared with the spirometry reference equations that are most commonly used in the United States.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aFemale10aForced Expiratory Volume10aHumans10aMale10aReference Values10aSmoking10aSpirometry10aVital Capacity1 aEnright, P, L1 aKronmal, R, A1 aHiggins, M1 aSchenker, M1 aHaponik, E, F uhttps://chs-nhlbi.org/node/144403802nas a2200469 4500008004100000022001400041245011400055210006900169260001600238300001200254490000800266520247300274653003202747653000902779653002502788653004502813653002802858653002902886653001902915653001402934653002102948653001102969653002202980653001103002653001703013653001803030653002003048653000903068653001303077653003503090653001503125653001803140653002303158100001503181700001703196700001503213700001603228700001703244700001603261700001903277856003603296 1993 eng d a0098-748400aTemporal patterns of antihypertensive medication use among elderly patients. The Cardiovascular Health Study.0 aTemporal patterns of antihypertensive medication use among elder c1993 Oct 20 a1837-410 v2703 aOBJECTIVES: To estimate the incidence of newly treated hypertension and to describe the patterns of antihypertensive medication use among those aged 65 years and older.
DESIGN: Medicare eligibility lists from four US communities (Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pa) were used to obtain a representative sample of 5201 community-dwelling elderly for the Cardiovascular Health Study, a prospective cohort study of risk factors for coronary heart disease and stroke. Participants were examined at baseline and again 1 year later. The two examinations included standardized questionnaires, blood pressure measurements, and the assessment of medication use by medication inventory. In this cohort analysis, we excluded 231 subjects (4.4%) who did not return for follow-up, 69 (1.3%) who had missing data for medications, and another 495 (9.5%) who were taking "antihypertensive" medications for an indication other than high blood pressure.
INTERVENTIONS: None.
RESULTS: Among the 4406 participants, 1613 used antihypertensive medications at both visits. Between the two visits, 144 started and 115 stopped antihypertensive therapy. Among nonusers at baseline, the annual incidence of newly treated hypertension was 5.2% in women and 5.6% in men. Due to the number of participants who stopped therapy, the overall prevalence of antihypertensive treatment increased only slightly, from 40.7% to 41.1% in women and from 37.1% to 38.2% in men, during 1 year of follow-up. After adjustment for age, systolic blood pressure, number of antihypertensive drugs, diabetes, and cardiovascular disease, the newly treated hypertensives were about half as likely as the previously treated hypertensives to receive diuretics (odds ratio [OR], 0.59; P = .008) or beta-blockers (OR, 0.52; P = .01); and they were about twice as likely to receive calcium channel blockers (OR, 1.88; P < .004) or angiotensin converting enzyme inhibitors (OR, 2.40; P < .001). A similar pattern of within-person changes over time was apparent among the continuous users.
CONCLUSIONS: Between June 1990 and June 1991, physicians were increasingly prescribing angiotensin converting enzyme inhibitors and calcium channel blockers in place of diuretics and beta-blockers for the treatment of hypertension in elderly patients, especially for those just starting therapy.
10aAdrenergic beta-Antagonists10aAged10aAnalysis of Variance10aAngiotensin-Converting Enzyme Inhibitors10aAntihypertensive Agents10aCalcium Channel Blockers10aCohort Studies10aDiuretics10aDrug Utilization10aFemale10aFollow-Up Studies10aHumans10aHypertension10aLinear Models10aLogistic Models10aMale10aMedicare10aPractice Patterns, Physicians'10aRecurrence10aUnited States10aVasodilator Agents1 aPsaty, B M1 aSavage, P, J1 aTell, G, S1 aPolak, J, F1 aHirsch, C, H1 aGardin, J M1 aMcDonald, R, H uhttps://chs-nhlbi.org/node/142903088nas a2200397 4500008004100000022001400041245012000055210006900175260001600244300001100260490000700271520197200278653000902250653002202259653002502281653002802306653002102334653003602355653001102391653001102402653002002413653002502433653000902458653001502467653001702482653001602499100001702515700001702532700002102549700001702570700001702587700001702604700001602621700001702637856003602654 1994 eng d a0735-109700aCardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study.0 aCardiac arrhythmias on 24h ambulatory electrocardiography in old c1994 Mar 15 a916-250 v233 aOBJECTIVES: This study describes the prevalence and correlates of cardiac arrhythmias in older persons.
BACKGROUND: Cardiac arrhythmias are frequent in selected samples of elderly persons, but their prevalence and association with cardiovascular disease and its risk factors have not been examined in a large population-based sample.
METHODS: In 1,372 participants in the Cardiovascular Health Study, a population-based study of cardiovascular disease risk factors, 24-h ambulatory electrocardiography was performed.
RESULTS: Serious arrhythmias, such as sustained ventricular tachycardia and complete atrioventricular block, were uncommon, but brief episodes of ventricular tachycardia (> or = 3 consecutive ventricular depolarizations) were detected in 4.3% of women and 10.3% of men. Ventricular arrhythmias as a group (excluding ectopic beats < 15/h) were more common in men than in women but were not significantly associated with age. The same patterns were true for bradycardia/conduction blocks. Supraventricular arrhythmias as a group (excluding ectopic beats < 15/h), in contrast, did not differ by gender but were strongly associated with increased age. Multivariate analyses showed associations with arrhythmias to differ by gender, with only one association (increased age and supraventricular arrhythmias) present in both women and men. Ventricular arrhythmias, particularly in men, were associated with a higher prevalence of cardiovascular disease and its risk factors and with subclinical disease, as measured by increased left ventricular mass and impaired left ventricular function.
CONCLUSIONS: Arrhythmias are common in the elderly, and their association with cardiovascular disease differs by gender. Although risk related to arrhythmias can only be determined by prospective study, such studies should have adequate power to examine potential gender differences in associations.
10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aCardiovascular Diseases10aCircadian Rhythm10aElectrocardiography, Ambulatory10aFemale10aHumans10aLogistic Models10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors10aSex Factors1 aManolio, T A1 aFurberg, C D1 aRautaharju, P, M1 aSiscovick, D1 aNewman, A, B1 aBorhani, N O1 aGardin, J M1 aTabatznik, B uhttps://chs-nhlbi.org/node/143002942nas a2200373 4500008004100000022001400041245016600055210006900221260001300290300001000303490000700313520187400320653000902194653002202203653001002225653001902235653001902254653002102273653001102294653001902305653001102324653003402335653000902369653002402378653001802402100001502420700001602435700001802451700001502469700001602484700001502500700001702515856003602532 1994 eng d a0194-911X00aCorrelates of blood pressure in community-dwelling older adults. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group.0 aCorrelates of blood pressure in communitydwelling older adults T c1994 Jan a59-670 v233 aAlthough elevated blood pressure is an important predictor of cardiovascular disease and stroke in the elderly, little information exists on the distribution and risk factor correlates of blood pressure in this group. As part of the Cardiovascular Health Study, a population-based cohort study of 5201 men and women aged 65 to 101 years, we investigated correlates of systolic and diastolic blood pressure. Multiple regression analyses were conducted for all participants and a subgroup of 2482 without coronary heart disease and not on antihypertensive therapy (the "healthier" subgroup). In the total group, independent predictors of diastolic blood pressure included heart rate, aortic root dimension, creatinine, hematocrit, alcohol use, and black race (positive associations) and internal carotid artery wall thickness, mitral early/late peak flow velocity, white blood cell count, cigarette smoking, and age (negative associations). Positive predictors of systolic blood pressure included mitral late peak flow velocity, left ventricular mass, common carotid artery wall thickness, serum albumin, factor VII, diabetes, alcohol use, and age; negative predictors were coronary heart disease, uric acid, height, and smoking. In the healthier subgroup, positive predictors of diastolic blood pressure included heart rate, hematocrit, serum albumin, creatinine, and body weight, whereas mitral early/late peak flow velocity, serum potassium, smoking, and age inversely related to diastolic pressure. For the same group, common carotid artery wall thickness, left ventricular mass, serum albumin, factor VII, high-density lipoprotein cholesterol, and age were directly related to systolic blood pressure, whereas serum potassium was inversely related. Both systolic and diastolic pressures varied considerably by geographic site.(ABSTRACT TRUNCATED AT 250 WORDS)
10aAged10aAged, 80 and over10aAging10aBlood Pressure10aCohort Studies10aCoronary Disease10aFemale10aHealth Surveys10aHumans10aHypertrophy, Left Ventricular10aMale10aRegression Analysis10aUnited States1 aTell, G, S1 aRutan, G, H1 aKronmal, R, A1 aBild, D, E1 aPolak, J, F1 aWong, N, D1 aBorhani, N O uhttps://chs-nhlbi.org/node/143700860nas a2200289 4500008004100000022001400041245014300055210006900198260001600267300001300283490000700296653000900303653002200312653001100334653001100345653002000356653002100376653002500397653000900422653001600431100002100447700001700468700001500485700001700500700001700517856003600534 1994 eng d a0002-914900aCorrelates of QT prolongation in older adults (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.0 aCorrelates of QT prolongation in older adults the Cardiovascular c1994 May 15 a999-10020 v7310aAged10aAged, 80 and over10aFemale10aHumans10aLogistic Models10aLong QT Syndrome10aLongitudinal Studies10aMale10aSex Factors1 aRautaharju, P, M1 aManolio, T A1 aPsaty, B M1 aBorhani, N O1 aFurberg, C D uhttps://chs-nhlbi.org/node/143302266nas a2200385 4500008004100000022001400041245008900055210006900144260001300213300001100226490000600237520123600243653000901479653002201488653002001510653002801530653003001558653001501588653000901603653001701612653002801629653001101657653001101668653000901679653002001688653002401708653001701732653001601749100001701765700001501782700001701797700001301814700001701827856003601844 1994 eng d a1047-279700aEating patterns of community-dwelling older adults: the Cardiovascular Health Study.0 aEating patterns of communitydwelling older adults the Cardiovasc c1994 Sep a404-150 v43 aWe analyzed eating patterns of 4643 adults (1988 men and 2655 women) aged 65 years and older at the time of their enrollment in the Cardiovascular Health Study. Diet was assessed with a qualitative, picture-sort food frequency questionnaire along with supplemental questions on other eating pattern variables. Consumption of high fat foods and low fiber foods was more frequent in older participants, men, minorities, and persons with body mass index > or = 30 kg/m2 and less common among persons who reported following self-prescribed or medically prescribed special diets. Few associations of consumption of specific food groups with disease status were identified. Participants with coronary heart disease, diabetes, hypertension, and cardiovascular disease were significantly more likely to report following a special diet and using low-calorie or low-sodium food products, however. Although the percentage of participants with prevalent disease who reported following special diets was relatively low from a clinical perspective, it was sufficiently high to suggest that controlling for dietary modifications may be important when attempting to identify associations of diet with prevalent disease in older populations.
10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aCerebrovascular Disorders10aDemography10aDiet10aDiet Surveys10aDiet, Sodium-Restricted10aFemale10aHumans10aMale10aMinority Groups10aProspective Studies10aRisk Factors10aSex Factors1 aKumanyika, S1 aTell, G, S1 aShemanski, L1 aPolak, J1 aSavage, P, J uhttps://chs-nhlbi.org/node/142502981nas a2200433 4500008004100000022001400041245007100055210006900126260001300195300001200208490000700220520183300227653000902060653002202069653002102091653001602112653002102128653001602149653002102165653002102186653001902207653002102226653002802247653001702275653001102292653001102303653001202314653002202326653002302348653002302371653000902394653001602403653002602419100001902445700001802464700001402482700001502496856003602511 1994 eng d a0022-142200aHigh density lipoprotein cholesterol subfractions in older people.0 aHigh density lipoprotein cholesterol subfractions in older peopl c1994 May aM116-220 v493 aBACKGROUND: High density lipoprotein (HDL) may be an important risk factor for cardiovascular disease in older people. HDL is heterogeneous with several subfractions. This article describes the distribution and correlates of HDL2 cholesterol (C) and HDL3-C in older people.
METHODS: HDL subfraction cholesterols were measured in 1,127 females and 825 males > or = 65 years old who participated in the Cardiovascular Health Study. Distributions of HDL subfraction cholesterols and bivariate and multivariate relationships were determined in cross-sectional analyses.
RESULTS: Mean (+/- SD) concentrations of HDL subfractions were: HDL3-C (M .98 +/- .25, F 1.2 +/- .29 mmol/l), HDL2-C (M .09 +/- .08, F .13 +/- .09 mmol/l). HDL2-C, but not HDL3-C, was slightly higher with age. Using multivariate analysis, both HDL2-C and HDL3-C (in females) were inversely correlated with triglyceride, body weight, and fasting insulin; HDL3-C was inversely correlated with central fat distribution in women. Both HDL2-C and HDL3-C were lower in participants with prevalent cardiovascular disease. However, only HDL3-C was significantly inversely related to carotid stenosis, as measured by ultrasound.
CONCLUSIONS: The slight increase in HDL-C with age appears to be due to an increase in the HDL2-C subfraction. HDL-C subfractions are independently related to triglyceride levels, body weight, and insulin concentrations in older people, all potentially modifiable risk factors. Both HDL2-C and HDL3-C are lower in older people with prevalent cardiovascular disease, although only HDL3-C was correlated with carotid atherosclerosis. These findings are consistent with the hypothesis that HDL subfractions are important risk factors for atherosclerotic cardiovascular disease in the elderly.
10aAged10aAged, 80 and over10aAlcohol Drinking10aBody Weight10aCarotid Stenosis10aCholesterol10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aCoronary Disease10aCross-Sectional Studies10aDrug Therapy10aFemale10aHumans10aInsulin10aLipoproteins, HDL10aLipoproteins, HDL210aLipoproteins, HDL310aMale10aSex Factors10aSocioeconomic Factors1 aEttinger, W, H1 aVerdery, R, B1 aWahl, P W1 aFried, L P uhttps://chs-nhlbi.org/node/143202941nas a2200421 4500008004100000022001400041245011400055210006900169260001300238300001100251490000700262520179700269653001602066653000902082653002202091653002502113653001202138653001002150653002402160653003002184653001102214653001102225653003102236653000902267653002402276653001702300653001602317100001702333700001802350700001602368700001502384700001702399700001602416700001502432700002002447700001602467856003602483 1994 eng d a0039-249900aMagnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.0 aMagnetic resonance abnormalities and cardiovascular disease in o c1994 Feb a318-270 v253 aBACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease.
METHODS: Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors.
RESULTS: Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound.
CONCLUSIONS: Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.
10aAge Factors10aAged10aAged, 80 and over10aAnalysis of Variance10aAtrophy10aBrain10aCerebral Ventricles10aCerebrovascular Disorders10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aRegression Analysis10aRisk Factors10aSex Factors1 aManolio, T A1 aKronmal, R, A1 aBurke, G, L1 aPoirier, V1 aO'Leary, D H1 aGardin, J M1 aFried, L P1 aSteinberg, E, P1 aBryan, R, N uhttps://chs-nhlbi.org/node/143803595nas a2200493 4500008004100000022001400041245012300055210006900178260001300247300001200260490000700272520218400279653000902463653001002472653002402482653002402506653003002530653001902560653002102579653002802600653002802628653002402656653001102680653001102691653004402702653001402746653002502760653003102785653000902816653001902825653002302844653001902867653002402886653001702910653001802927100001602945700001702961700001802978700001602996700001803012700001703030700001803047856003603065 1994 eng d a0195-610800aA method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.0 amethod for using MR to evaluate the effects of cardiovascular di c1994 Oct a1625-330 v153 aPURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history.
METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9.
RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77% of the participants with histories of stroke but was also present in 23% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm.
CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.
10aAged10aBrain10aCerebral Infarction10aCerebral Ventricles10aCerebrovascular Disorders10aCohort Studies10aCoronary Disease10aCross-Sectional Studies10aDiagnosis, Differential10aFeasibility Studies10aFemale10aHumans10aImage Interpretation, Computer-Assisted10aIncidence10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMass Screening10aObserver Variation10aPilot Projects10aProspective Studies10aRisk Factors10aUnited States1 aBryan, R, N1 aManolio, T A1 aSchertz, L, D1 aJungreis, C1 aPoirier, V, C1 aElster, A, D1 aKronmal, R, A uhttps://chs-nhlbi.org/node/142003415nas a2200385 4500008004100000022001400041245011100055210006900166260001300235300001100248490000700259520232400266653003102590653000902621653002202630653002002652653002102672653003302693653001102726653002502737653001102762653002002773653000902793653003702802653001702839653001602856653002602872653001802898100001502916700001902931700001202950700001702962700001402979856003602993 1994 eng d a0895-435600aPhysical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.0 aPhysical disability in older adults a physiological approach Car c1994 Jul a747-600 v473 aMeasures of physical function have been developed primarily to assess health status, prognosis, and service needs. They are now, increasingly, being used as outcome measures in studies seeking to determine the causes of disability. However, the extent to which these standardized measures, as they currently are constituted, are meaningful for the evaluation of underlying pathophysiology is not defined. To assess evidence for an etiologic rationale for these measures, we evaluated self-report of difficulty in physical function in the Cardiovascular Health Study, a study of 5201 men and women 65 years and older in four U.S. communities. We determined (by factor analysis) that self-reported difficulty with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in one task is associated with having difficulty in the other tasks in the group. These groups include (1) activities primarily dependent on mobility and exercise tolerance; (2) complex activities heavily dependent on cognition and sensory input; (3) selected basic self-care activities; and (4) upper extremity activities. Groups 2 and 3 are similar, but not identical, to Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL), respectively. We then tested whether these groupings were associated with different underlying impairments. Multiple logistic regression analyses indicate that there are constellations of physiologic and disease characteristics significantly (p < 0.01) associated with difficulty in each of these four groups of activities, among 15 chronic diseases and conditions ascertained. Some diseases are uniquely associated with difficulty in one group of tasks; some overlap, and are associated with 2, 3 or 4 groups of tasks. The associations found with difficulty in performing tasks in groups 2 and 3 were frequently stronger than those with the larger groups of ADL or IADL tasks, suggesting increased specificity of associations found with these new groupings. These results suggest that re-grouping of tasks of daily life may provide a more refined physiologically-based outcome measure for use in evaluating causes of disability. The ability to define risk factors for disability may be enhanced by choosing outcome measures with a demonstrated physiologic rationale.
10aActivities of Daily Living10aAged10aAged, 80 and over10aChronic Disease10aDisabled Persons10aFactor Analysis, Statistical10aFemale10aGeriatric Assessment10aHumans10aLogistic Models10aMale10aOutcome Assessment (Health Care)10aRisk Factors10aSex Factors10aSocioeconomic Factors10aUnited States1 aFried, L P1 aEttinger, W, H1 aLind, B1 aNewman, A, B1 aGardin, J uhttps://chs-nhlbi.org/node/141701804nas a2200385 4500008004100000022001400041245010100055210006900156260001300225300001100238490000600249520076700255653000901022653002801031653002001059653001101079653001601090653002501106653001801131653001101149653000901160653002601169653002401195653002001219653001601239653001801255100001401273700001801287700001501305700001601320700001701336700001401353700001601367856003501383 1994 eng d a0898-264300aPredictors of perceived health status in elderly men and women. The Cardiovascular Health Study.0 aPredictors of perceived health status in elderly men and women T c1994 Nov a419-470 v63 aBaseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.
10aAged10aCardiovascular Diseases10aData Collection10aFemale10aForecasting10aGeriatric Assessment10aHealth Status10aHumans10aMale10aMultivariate Analysis10aRegression Analysis10aSelf-Assessment10aSex Factors10aUnited States1 aSchulz, R1 aMittelmark, M1 aKronmal, R1 aPolak, J, F1 aHirsch, C, H1 aGerman, P1 aBookwala, J uhttps://chs-nhlbi.org/node/58702851nas a2200397 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520176400267653000902031653002202040653001502062653001902077653001102096653001102107653001802118653000902136653001302145653002602158653001902184653001702203653001502220653001402235653003102249653001502280653003102295100001802326700001802344700001802362700001902380700001802399856003602417 1994 eng d a0012-369200aPrevalence and correlates of respiratory symptoms and disease in the elderly. Cardiovascular Health Study.0 aPrevalence and correlates of respiratory symptoms and disease in c1994 Sep a827-340 v1063 aSpirometry was performed by 5,201 elderly participants of the Cardiovascular Health Study during their baseline examination and a subset of the ATS/DLD-78 respiratory questionnaire was administered by trained interviewers. In never smokers (46 percent of the cohort), the overall prevalence of chronic cough was 9 percent, chronic phlegm was 13 percent, attacks of wheezing with dyspnea were 8 percent, and grade 3 dyspnea on exertion was 10 percent. The prevalence of lung disease in current smokers (12 percent of the cohort) was 8/7 percent (men/women) with chronic bronchitis and 14/5 percent with emphysema. Overall, 6 percent reported asthma (a physician-confirmed history) and 12 percent reported hay fever. Using a logistic regression model, attacks of wheezing with dyspnea were strongly associated with a lower FEV1, coronary heart disease, heart failure, and a large waist size (in participants without a diagnosis of asthma, chronic bronchitis, or emphysema). Undiagnosed airways obstruction was twice as likely in women and those with lower income, and was associated with current and former smoking, pack-years of smoking, and chronic cough. Dyspnea on exertion (DOE) was three times or more likely if a participant reported heart failure, coronary heart disease, or emphysema; and much more likely if their FEV1 or FVC was substantially reduced. Dyspnea on exertion was also positively associated with older age, chronic bronchitis or asthma, a larger waist or hip size, pack-years of smoking, and less education. We conclude that DOE and attacks of wheezing with dyspnea are commonly associated with cardiovascular disease and a low FEV1 in those over 65 years and that airways obstruction frequently remains undiagnosed in the elderly.
10aAged10aAged, 80 and over10aCalifornia10aCohort Studies10aFemale10aHumans10aLung Diseases10aMale10aMaryland10aMultivariate Analysis10aNorth Carolina10aPennsylvania10aPrevalence10aPrognosis10aRespiratory Tract Diseases10aSpirometry10aSurveys and Questionnaires1 aEnright, P, L1 aKronmal, R, A1 aHiggins, M, W1 aSchenker, M, B1 aHaponik, E, F uhttps://chs-nhlbi.org/node/142802395nas a2200397 4500008004100000022001400041245009300055210006900148260001600217300001100233490000700244520129700251653000901548653002201557653002701579653001901606653002401625653001801649653002801667653002801695653002101723653002401744653001101768653001101779653000901790653001501799653002401814653002101838100001701859700001501876700001701891700001601908700001601924700002101940856003601961 1994 eng d a0002-914900aPrevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study).0 aPrevalence of atrial fibrillation in elderly subjects the Cardio c1994 Aug 01 a236-410 v743 aAtrial fibrillation (AF) is a common arrhythmia in elderly persons and a common cause of embolic stroke. Most studies of the prevalence and correlates of AF have used selected, hospital-based populations. The Cardiovascular Health Study is a population-based, longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years. AF was diagnosed in 4.8% of women and in 6.2% of men at the baseline examination, and prevalence was strongly associated with advanced age in women. Prevalence of AF was 9.1% in men and women with clinical cardiovascular disease, 4.6% in patients with evidence of subclinical but no clinical cardiovascular disease, and only 1.6% in subjects with neither clinical nor subclinical cardiovascular disease. A history of congestive heart failure, valvular heart disease and stroke, echocardiographic evidence of enlarged left atrial dimension, abnormal mitral or aortic valve function, treated systemic hypertension, and advanced age were independently associated with the prevalence of AF. The low prevalence of AF in the absence of clinical and subclinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called "lone atrial fibrillation" in the elderly.
10aAged10aAged, 80 and over10aAnti-Arrhythmia Agents10aAnticoagulants10aAtrial Fibrillation10aBlood Glucose10aCardiovascular Diseases10aChi-Square Distribution10aCoronary Disease10aElectrocardiography10aFemale10aHumans10aMale10aPrevalence10aRegression Analysis10aSampling Studies1 aFurberg, C D1 aPsaty, B M1 aManolio, T A1 aGardin, J M1 aSmith, V, E1 aRautaharju, P, M uhttps://chs-nhlbi.org/node/142702432nas a2200373 4500008004100000022001400041245014300055210006900198260001600267300001200283490000800295520139700303653000901700653002201709653002101731653002801752653001101780653001101791653002001802653002501822653000901847653001501856653001701871653001801888100001401906700001501920700001501935700001401950700001501964700001501979700001301994700001502007856003602022 1994 eng d a0002-926200aPrevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study.0 aPrevalence of subclinical atherosclerosis and cardiovascular dis c1994 Jun 15 a1164-790 v1393 aThe prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.
10aAged10aAged, 80 and over10aArteriosclerosis10aCardiovascular Diseases10aFemale10aHumans10aLogistic Models10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors10aUnited States1 aKuller, L1 aBorhani, N1 aFurberg, C1 aGardin, J1 aManolio, T1 aO'Leary, D1 aPsaty, B1 aRobbins, J uhttps://chs-nhlbi.org/node/143402834nas a2200325 4500008004100000022001400041245019000055210006900245260001300314300001100327490000700338520187600345653000902221653002202230653002102252653002102273653001902294653001102313653001102324653000902335653001202344653002002356100001502376700001602391700001502407700001802422700001702440700001502457856003602472 1994 eng d a0009-732200aRelation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group.0 aRelation of smoking with carotid artery wall thickness and steno c1994 Dec a2905-80 v903 aBACKGROUND: Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease.
METHODS AND RESULTS: We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001).
CONCLUSIONS: These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.
10aAged10aAged, 80 and over10aCarotid Arteries10aCarotid Stenosis10aCohort Studies10aFemale10aHumans10aMale10aSmoking10aUltrasonography1 aTell, G, S1 aPolak, J, F1 aWard, B, J1 aKittner, S, J1 aSavage, P, J1 aRobbins, J uhttps://chs-nhlbi.org/node/142602295nas a2200373 4500008004100000022001400041245012500055210006900180260001300249300001000262490000800272520124200280653000901522653002201531653001001553653002201563653002801585653001101613653001101624653000901635653002401644653002101668653003101689653002401720653001701744653002401761653001201785100001801797700001801815700001701833700001901850700001601869856003601885 1994 eng d a1073-449X00aRespiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group.0 aRespiratory muscle strength in the elderly Correlates and refere c1994 Feb a430-80 v1493 aMaximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FEV1 less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The reference equations derived from this group of healthy 65 to 85-yr-olds may be used by pulmonary function laboratories and respiratory therapists who evaluate the respiratory muscle strength of elderly patients.
10aAged10aAged, 80 and over10aAging10aBody Constitution10aCardiovascular Diseases10aFemale10aHumans10aMale10aProspective Studies10aReference Values10aRespiratory Function Tests10aRespiratory Muscles10aRisk Factors10aSex Characteristics10aSmoking1 aEnright, P, L1 aKronmal, R, A1 aManolio, T A1 aSchenker, M, B1 aHyatt, R, E uhttps://chs-nhlbi.org/node/143903435nas a2200457 4500008004100000022001400041245013200055210006900187260001300256300001200269490000700281520215700288653003102445653000902476653002202485653001402507653002802521653002002549653001902569653002802588653002102616653001102637653001802648653001902666653001902685653001102704653001802715653000902733653002302742653003102765653001702796653001602813653001802829100001902847700001502866700001402881700001702895700001402912700001502926856003602941 1994 eng d a0002-861400aSelf-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group.0 aSelfreported causes of physical disability in older people the C c1994 Oct a1035-440 v423 aOBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people.
DESIGN: Cross sectional analyses of data obtained in an observational cohort study.
SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA.
PARTICIPANTS: 5201 community-dwelling people > or = 65 years old.
RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status.
CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.
10aActivities of Daily Living10aAged10aAged, 80 and over10aArthritis10aCardiovascular Diseases10aChronic Disease10aCohort Studies10aCross-Sectional Studies10aDisabled Persons10aFemale10aHealth Status10aHealth Surveys10aHeart Diseases10aHumans10aLung Diseases10aMale10aObserver Variation10aReproducibility of Results10aRisk Factors10aSex Factors10aUnited States1 aEttinger, W, H1 aFried, L P1 aHarris, T1 aShemanski, L1 aSchulz, R1 aRobbins, J uhttps://chs-nhlbi.org/node/142402199nas a2200397 4500008004100000022001400041245015300055210006900208260001300277300001200290490000700302520104400309653003901353653000901392653002801401653002101429653004001450653001101490653002501501653001101526653000901537653002601546653001501572653002401587653001701611653001601628100001701644700001601661700001501677700001701692700001201709700001201721700001501733700001701748856003601765 1995 eng d a0895-435600aBlack-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group.0 aBlackwhite differences in subclinical cardiovascular disease amo c1995 Sep a1141-520 v483 aCardiovascular and all-cause mortality are higher in black than white Americans, but racial differences in clinical and subclinical cardiovascular disease (CVD) have not been examined in older adults. Clinical and subclinical CVD and its risk factors were compared in 4926 white and 244 black men and women aged 65 years and older. Black participants had lower socioeconomic status and generally higher prevalences of CVD and its risk factors, except for adverse lipid profiles. Common carotid wall thickness was greater in black than white women, and ankle-arm blood pressure ratios were lower in black women and men (p < 0.01). After adjustment for CVD risk factors, common carotid walls were significantly thicker and ankle-arm ratios were lower in blacks than whites of both sexes, while internal carotid walls were significantly thinner in black women. Racial differences in clinical and subclinical CVD in older adults are similar to those reported in younger populations and do not appear to be explained by CVD risk factors.
10aAfrican Continental Ancestry Group10aAged10aCardiovascular Diseases10aCarotid Arteries10aEuropean Continental Ancestry Group10aFemale10aGeriatric Assessment10aHumans10aMale10aMultivariate Analysis10aPrevalence10aRegression Analysis10aRisk Factors10aSex Factors1 aManolio, T A1 aBurke, G, L1 aPsaty, B M1 aNewman, A, B1 aHaan, M1 aPowe, N1 aTracy, R P1 aO'Leary, D H uhttps://chs-nhlbi.org/node/141400936nas a2200349 4500008004100000022001400041245008100055210006900136260001300205300001000218490000700228653001600235653000900251653002500260653002300285653002500308653001600333653001100349653001500360653001100375653002500386653001700411653001800428653001800446653000900464100001900473700001400492700001800506700001300524700001300537856003600550 1995 eng d a0002-861400aEvidence for inflammation as a cause of hypocholesterolemia in older people.0 aEvidence for inflammation as a cause of hypocholesterolemia in o c1995 Mar a264-60 v4310aAge Factors10aAged10aAnalysis of Variance10aC-Reactive Protein10aCase-Control Studies10aCholesterol10aFemale10aFibrinogen10aHumans10aHypolipoproteinemias10aInflammation10aInterleukin-110aInterleukin-610aMale1 aEttinger, W, H1 aHarris, T1 aVerdery, R, B1 aTracy, R1 aKouba, E uhttps://chs-nhlbi.org/node/142302401nas a2200409 4500008004100000022001400041245010300055210006900158260001300227300001000240490000700250520132900257653001601586653000901602653002501611653001501636653002801651653001901679653001101698653001801709653001101727653000901738653001301747653001601760653001901776653001701795653002101812653001701833653002401850100001501874700001201889700001401901700001501915700001201930700001301942856003601955 1995 eng d a0002-861400aHematological and biochemical laboratory values in older Cardiovascular Health Study participants.0 aHematological and biochemical laboratory values in older Cardiov c1995 Aug a855-90 v433 aOBJECTIVE: To define reference hematologic and biochemical lab values in older individuals.
DESIGN: Randomly selected, age- and gender-stratified participants.
SETTING: Visits by participants to four research clinics.
PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home.
MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count.
RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories.
CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice.
10aAge Factors10aAged10aAnalysis of Variance10aCalifornia10aCardiovascular Diseases10aCohort Studies10aFemale10aHealth Status10aHumans10aMale10aMaryland10aMiddle Aged10aNorth Carolina10aPennsylvania10aReference Values10aRisk Factors10aSex Characteristics1 aRobbins, J1 aWahl, P1 aSavage, P1 aEnright, P1 aPowe, N1 aLyles, M uhttps://chs-nhlbi.org/node/141302895nas a2200361 4500008004100000022001400041245009200055210006900147260001300216300001100229490000700240520190600247653000902153653002202162653002002184653002802204653002102232653002102253653002102274653002802295653002202323653001102345653001102356653001902367653001702386653000902403653001502412653001702427100001602444700001802460700001902478856003602497 1995 eng d a0002-861400aHigh density lipoprotein cholesterol is associated with serum cortisol in older people.0 aHigh density lipoprotein cholesterol is associated with serum co c1995 Dec a1345-90 v433 aOBJECTIVE: To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people.
DESIGN: A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS).
POPULATION: A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina.
METHODS: Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound.
RESULTS: Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes.
CONCLUSION: Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.
10aAged10aBody Constitution10aBody Mass Index10aCardiovascular Diseases10aCarotid Stenosis10aCholesterol, HDL10aCoronary Disease10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aHumans10aHydrocortisone10aHypertension10aMale10aPrevalence10aRisk Factors1 aVarma, V, K1 aRushing, J, T1 aEttinger, W, H uhttps://chs-nhlbi.org/node/141202745nas a2200529 4500008004100000022001400041245011300055210006900168260001300237300001100250490000700261520128200268653001601550653000901566653002501575653002401600653001501624653002101639653002501660653002401685653003601709653001101745653001901756653001101775653003401786653002001820653000901840653001301849653002601862653002601888653002401914653001901938653001201957653001501969653001701984653001502001653001702016653002402033100002102057700001702078700001702095700001702112700001702129700001702146700001602163856003602179 1995 eng d a0167-527300aIschemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the Cardiovascular Health Study.0 aIschemic episodes in 24h ambulatory electrocardiograms of elderl c1995 Sep a165-750 v513 aWe examined correlates of ischemic episodes in 24-h ambulatory electrocardiograms (ECG) in a sample of 1511 men and women 65 years old and older. Ischemic episodes had a high prevalence period during early afternoon and also during morning hours after awakening, and the overall prevalence was 13% in men and 9% in women (P < 0.001 for gender difference). The prevalence was 9.6% in participants with no history of myocardial infarction and no major or minor resting ECG abnormalities. In multivariate analysis by logistic regression, being on digitalis medication was associated with over a three-fold risk of ischemic episodes, with an odds ratio (95% confidence limits) of 3.21 (1.80 to 5.74). Left ventricular hypertrophy by ECG and atrial fibrillation had almost a three-fold excess risk of ischemic episodes, with odds ratios 2.81 (1.37 to 5.74) and 2.63 (1.17 to 5.91), respectively. Isolated ST-T abnormalities had almost a two-fold excess of ischemic episodes, with an odds ratio of 1.89 (1.01 to 3.54). Being overweight was associated with a 33% reduced likelihood of ischemic episodes after adjustment for other factors, with an odds ratio of 0.67 (0.46 to 0.98). It is concluded that the prevalence of silent ischemic episodes is high in older men and women.
10aAge Factors10aAged10aArrhythmias, Cardiac10aAtrial Fibrillation10aCalifornia10aCircadian Rhythm10aDigitalis Glycosides10aElectrocardiography10aElectrocardiography, Ambulatory10aFemale10aHealth Surveys10aHumans10aHypertrophy, Left Ventricular10aLogistic Models10aMale10aMaryland10aMultivariate Analysis10aMyocardial Infarction10aMyocardial Ischemia10aNorth Carolina10aObesity10aOdds Ratio10aPennsylvania10aPrevalence10aRisk Factors10aSex Characteristics1 aRautaharju, P, M1 aManolio, T A1 aFurberg, C D1 aSiscovick, D1 aNewman, A, B1 aBorhani, N O1 aGardin, J M uhttps://chs-nhlbi.org/node/145102886nas a2200445 4500008004100000022001400041245009400055210006900149260001300218300001000231490000600241520166800247653000901915653003001924653001901954653002101973653002401994653002602018653002902044653001102073653001102084653000902095653002802104653001502132653002402147653003102171653001702202653002002219653001802239100001502257700001602272700001202288700001602300700001802316700001802334700001602352700002102368700001502389856003602404 1995 eng d a1047-279700aMethods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study.0 aMethods of assessing prevalent cardiovascular disease in the Car c1995 Jul a270-70 v53 aThe objective of this article is to describe the methods of assessing cardiovascular conditions among older adults recruited to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke. Medicare eligibility lists from four US communities were used to obtain a representative sample of 5201 community-dwelling elderly, who answered standardized questionnaires and underwent an extensive clinic examination at baseline. For each cardiovascular condition, self-reports were confirmed by components of the baseline examination or, if necessary, by a validation protocol that included either the review of medical records or surveys of treating physicians. Potential underreporting of a condition was detected either by the review of medical records at baseline for other self-reported conditions or, during prospective follow-up, by the investigation of potential incident events. For myocardial infarction, 75.5% of the self-reports in men and 60.6% in women were confirmed. Self-reported congestive heart failure was confirmed in 73.3% of men and 76.6% of women; stroke, in 59.6% of men and 53.8% of women; and transient ischemic attack, in 41.5% of men and 37.0% of women. Underreporting was also common. During prospective follow-up of an average of about 3 years per person, approximately 50% of men and 38% of women were hospitalized or investigated for at least one potential incident event; for each cardiovascular condition, about 1 to 4% of those investigated during prospective follow-up were found to have had the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)
10aAged10aCerebrovascular Disorders10aCohort Studies10aCoronary Disease10aElectrocardiography10aEpidemiologic Methods10aFalse Negative Reactions10aFemale10aHumans10aMale10aPopulation Surveillance10aPrevalence10aProspective Studies10aReproducibility of Results10aRisk Factors10aSelf Disclosure10aUnited States1 aPsaty, B M1 aKuller, L H1 aBild, D1 aBurke, G, L1 aKittner, S, J1 aMittelmark, M1 aPrice, T, R1 aRautaharju, P, M1 aRobbins, J uhttps://chs-nhlbi.org/node/144902656nas a2200361 4500008004100000022001400041245015500055210006900210260001300279300001000292490000800302520159900310653001601909653000901925653002201934653002101956653001101977653002901988653001102017653001702028653003402045653000902079653001602088653003102104653001902135100001802154700001802172700001602190700001602206700001902222700001702241856003602258 1995 eng d a0012-369200aReduced vital capacity in elderly persons with hypertension, coronary heart disease, or left ventricular hypertrophy. The Cardiovascular Health Study.0 aReduced vital capacity in elderly persons with hypertension coro c1995 Jan a28-350 v1073 aThe Cardiovascular Health Study provided the opportunity to determine the association of subclinical and clinical cardiovascular disease with pulmonary function in a population sample of elderly adults. Included were 2,955 women and 2,246 men over age 64 years who were recruited for this observational study from four communities and completed extensive examinations that included spirometry, echocardiograms, and blood pressure. Current smokers, past smokers with >20 pack-years of smoking, and persons with a history of asthma, chronic bronchitis, or emphysema were excluded from this analysis, leaving 2,784 (55%) of the cohort. Systolic hypertension or coronary artery disease was associated with 40- to 100-mL decrements in FEV1, and 50- to 150-mL decrements in FVC, while a history of congestive heart failure was associated with 200 to 300 mL lower FEV1 and FVC values (p < 0.0001), after correcting for age, height, and waist size. Higher left ventricular (LV) mass was also significantly associated with a decrease in FEV1 and FVC in multivariate models. This relationship was strongest with the end-diastolic LV posterior wall thickness component of LV mass. In summary, FEV1 and FVC are reduced in elderly persons with hypertension, ischemic heart disease, higher disease, higher LV mass, and congestive heart failure, though the magnitude of these associations is relatively small unless heart failure supervenes. Substantial decrements in percent predicted FEV1 and FVC should not be attributed to the presence of uncomplicated ischemic heart disease or hypertension alone.
10aAge Factors10aAged10aAged, 80 and over10aCoronary Disease10aFemale10aForced Expiratory Volume10aHumans10aHypertension10aHypertrophy, Left Ventricular10aMale10aMiddle Aged10aVentricular Function, Left10aVital Capacity1 aEnright, P, L1 aKronmal, R, A1 aSmith, V, E1 aGardin, J M1 aSchenker, M, B1 aManolio, T A uhttps://chs-nhlbi.org/node/141903702nas a2200409 4500008004100000022001400041245015600055210006900211260001600280300001200296490000700308520256000315653001602875653000902891653002202900653001002922653001902932653002102951653002102972653001102993653001103004653003403015653000903049653001603058653001203074100001603086700001703102700002003119700001603139700001603155700002303171700001703194700001303211700001503224700001703239856003603256 1995 eng d a0009-732200aSex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study.0 aSex age and disease affect echocardiographic left ventricular ma c1995 Mar 15 a1739-480 v913 aBACKGROUND: Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older.
METHODS AND RESULTS: M-mode LV mass adjusted for body weight increased modestly with age (P < .0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both P < .001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group, P < .001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all P < .001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (P < .0001). Multivariate analyses revealed male sex and presence of clinical CHD (both P < .001) to be independent predictors of LV akinesis or dyskinesis.
CONCLUSIONS: Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly.
10aAge Factors10aAged10aAged, 80 and over10aAging10aCohort Studies10aCoronary Disease10aEchocardiography10aFemale10aHumans10aHypertrophy, Left Ventricular10aMale10aSex Factors10aSystole1 aGardin, J M1 aSiscovick, D1 aAnton-Culver, H1 aLynch, J, C1 aSmith, V, E1 aKlopfenstein, H, S1 aBommer, W, J1 aFried, L1 aO'Leary, D1 aManolio, T A uhttps://chs-nhlbi.org/node/142202686nas a2200409 4500008004100000022001400041245008200055210006900137260001600206300001000222490000700232520161900239653000901858653002801867653001901895653002101914653001101935653001101946653001401957653002501971653000901996653002602005653001502031653002102046653001702067100001602084700001702100700001502117700001702132700001402149700001502163700001702178700001702195700001502212700001302227856003602240 1995 eng d a0009-732200aSubclinical disease as an independent risk factor for cardiovascular disease.0 aSubclinical disease as an independent risk factor for cardiovasc c1995 Aug 15 a720-60 v923 aBACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study.
METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes.
CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.
10aAged10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aMyocardial Infarction10aOdds Ratio10aReference Values10aRisk Factors1 aKuller, L H1 aShemanski, L1 aPsaty, B M1 aBorhani, N O1 aGardin, J1 aHaan, M, N1 aO'Leary, D H1 aSavage, P, J1 aTell, G, S1 aTracy, R uhttps://chs-nhlbi.org/node/141502025nas a2200385 4500008004100000022001400041245009400055210006900149260001300218300001100231490000600242520098000248653000901228653003001237653002101267653002601288653001101314653002001325653001101345653001401356653002501370653000901395653002801404653002001432653001801452100001501470700002201485700001501507700001501522700001601537700001801553700001701571700001501588856003601603 1995 eng d a1047-279700aSurveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study.0 aSurveillance and ascertainment of cardiovascular events The Card c1995 Jul a278-850 v53 aWhile previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.
10aAged10aCerebrovascular Disorders10aCoronary Disease10aEpidemiologic Methods10aFemale10aHospitalization10aHumans10aIncidence10aLongitudinal Studies10aMale10aPopulation Surveillance10aQuality Control10aUnited States1 aIves, D, G1 aFitzpatrick, A, L1 aBild, D, E1 aPsaty, B M1 aKuller, L H1 aCrowley, P, M1 aCruise, R, G1 aTheroux, S uhttps://chs-nhlbi.org/node/145003221nas a2200385 4500008004100000022001400041245015700055210006900212260001600281300001100297490000800308520208200316653000902398653002802407653002902435653003702464653002802501653001102529653001102540653001702551653000902568653003502577653001802612100001502630700001902645700001602664700001502680700001702695700001802712700001702730700001602747700002002763700001602783856003602799 1995 eng d a0098-748400aTemporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?0 aTemporal patterns of antihypertensive medication use among older c1995 May 10 a1436-80 v2733 aOBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults.
DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3.
RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%) and period 3 (+2.8%).
CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.
10aAged10aAntihypertensive Agents10aClinical Trials as Topic10aData Interpretation, Statistical10aDrug Utilization Review10aFemale10aHumans10aHypertension10aMale10aPractice Patterns, Physicians'10aUnited States1 aPsaty, B M1 aKoepsell, T, D1 aYanez, N, D1 aSmith, N L1 aManolio, T A1 aHeckbert, S R1 aBorhani, N O1 aGardin, J M1 aGottdiener, J S1 aRutan, G, H uhttps://chs-nhlbi.org/node/141802703nas a2200457 4500008004100000022001400041245019200055210006900247260001600316300001100332490000800343520141800351653002101769653000901790653002201799653002501821653002801846653001901874653001501893653001601908653001101924653001501935653001101950653001801961653002001979653000901999653001502008653001702023653002102040653001802061100001502079700001302094700001502107700001502122700001302137700001102150700001602161700001702177700001502194856003602209 1996 eng d a0002-926200aAssociation of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators.0 aAssociation of fibrinogen and coagulation factors VII and VIII w c1996 Apr 01 a665-760 v1433 aThe cross-sectional correlates of three hemostatic factors--fibrinogen, factor VII, and factor VIII--were examined in the Cardiovascular Health Study, a population-based cohort study of 5,201 subjects over age 65 years. Subjects were recruited in 1989-1990 in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. In multivariate linear regression models, cardiac risk factors significantly associated with fibrinogen were current smoking, race, lipids, and white blood count. In women, alcohol use, obesity, physical activity, and insulin level were also significant, while in men hypertension was correlated. The significant correlates of factor VII were lipids and white blood count in men and estrogen use, alcohol use, race, lipids, insulin level, white blood count, and obesity in women. The independent correlates of factor VIII were insulin, glucose, and race in both sexes; low density lipoprotein cholesterol, white blood count, and diuretic use in men; and alcohol use in women. In multivariate models, factors known to be modifiable risk factors for cardiovascular disease accounted for more of the population variance of these hemostatic factors in women than in men, especially for factor VII. The hemostatic factors may mediate some effects of risk factors on disease, and this should be considered in longitudinal studies.
10aAge Distribution10aAged10aAged, 80 and over10aAnalysis of Variance10aCardiovascular Diseases10aCohort Studies10aFactor VII10aFactor VIII10aFemale10aFibrinogen10aHumans10aLinear Models10aLogistic Models10aMale10aPrevalence10aRisk Factors10aSex Distribution10aUnited States1 aCushman, M1 aYanez, D1 aPsaty, B M1 aFried, L P1 aHeiss, G1 aLee, M1 aPolak, J, F1 aSavage, P, J1 aTracy, R P uhttps://chs-nhlbi.org/node/145702420nas a2200349 4500008004100000022001400041245012300055210006900178260000900247300001000256490000700266520147600273653000901749653002201758653001101780653002801791653001901819653001101838653001101849653000901860653000901869653002601878653001501904653001701919653002101936653001201957100001801969700001501987700001502002700001702017856003602034 1996 eng d a0277-090300aAsthma and its association with cardiovascular disease in the elderly. The Cardiovascular Health Study Research Group.0 aAsthma and its association with cardiovascular disease in the el c1996 a45-530 v333 aCardiovascular disease (CVD) is more prevalent in elderly than in middle-aged patients. Symptoms such as intermittent wheezing with dyspnea may then be due to either CVD or asthma. The objective of this study was to determine the prevalence and correlates of asthma in the elderly and their associations with CVD and CVD risk factors. A community sample of 5201 elderly persons from the Cardiovascular Health Study was asked if they had a physician diagnosis of asthma, and multiple cardiovascular risk and disease variables were measured. Six percent of the participants (309) recalled a history of asthma, and half of these were never smokers. Thirty percent of those with asthma were currently taking a bronchodilator, 14% inhaled steroids, and 10% oral prednisone. Men and women with asthma who were cigarette smokers were more likely to report a concurrent diagnosis of congestive heart failure than smokers without asthma (p = .04). However, when we determined the independent CVD correlates of asthma in this cohort, controlling for smoking status, age, gender, and diagnoses of chronic bronchitis and emphysema, only higher levels of high-density lipoprotein cholesterol (HDL-C) and higher plasma fibrinogen levels were significantly associated with asthma. It was concluded that asthma is as prevalent in the elderly as in middle-aged persons and is associated with higher HDL-C and higher fibrinogen levels, but not with prevalent cardiovascular disease.
10aAged10aAged, 80 and over10aAsthma10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aLung10aMale10aMultivariate Analysis10aPrevalence10aRisk Factors10aSex Distribution10aSmoking1 aEnright, P, L1 aWard, B, J1 aTracy, R P1 aLasser, E, C uhttps://chs-nhlbi.org/node/145502240nas a2200337 4500008004100000022001400041245014400055210006900199260001600268300001100284490000700295520126800302653000901570653002101579653001901600653001101619653002101630653001101651653003401662653000901696653002401705653001701729653002001746100001801766700001601784700001701800700001601817700001601833700001701849856003601866 1996 eng d a0002-914900aCarotid artery measures are strongly associated with left ventricular mass in older adults (a report from the Cardiovascular Health Study).0 aCarotid artery measures are strongly associated with left ventri c1996 Mar 15 a628-330 v773 aAssociations of carotid artery diameter and intimal-medial thickness by ultrasound with echocardiographic left ventricular (LV) structure were examined in 3,409 participants in the Cardiovascular Health Study, a population-based study of risk factors for coronary heart disease and stroke in men and women aged > or = 65 years. At baseline, sector-guided M-mode echocardiography and B-mode ultrasound were used to evaluate the left ventricle and carotid arteries, respectively. Common carotid artery diameter and intimal-medial thickness were significantly related to LV mass in correlational analysis (r=0.40 and 0.20, respectively, p<0.01), and each was independently associated with LV mass after adjustment for age, gender, weight, systolic and diastolic blood pressure, antihypertensive medication use, prior coronary heart disease, electrocardiographic abnormalities, high-density lipoprotein, and factor VII. We speculate that changes in the arterial wall affect impedance to LV ejection leading to increases in LV mass. Further follow-up of this cohort is in progress and will help to determine whether such carotid artery measures could, by exacerbating LV hypertrophy, constitute another important risk factor for adverse cardiovascular outcomes.
10aAged10aCarotid Arteries10aCohort Studies10aFemale10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aMale10aRegression Analysis10aRisk Factors10aUltrasonography1 aKronmal, R, A1 aSmith, V, E1 aO'Leary, D H1 aPolak, J, F1 aGardin, J M1 aManolio, T A uhttps://chs-nhlbi.org/node/145403022nas a2200433 4500008004100000022001400041245014400055210006900199260001300268300001200281490000700293520181400300653001602114653000902130653001002139653001902149653001002168653002802178653003002206653001902236653001102255653001102266653003102277653003102308653000902339653002602348653001702374653001602391100002002407700001702427700001402444700001602458700001302474700001902487700001802506700001502524700001302539856003602552 1996 eng d a0039-249900aClinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study.0 aClinical correlates of white matter findings on cranial magnetic c1996 Aug a1274-820 v273 aBACKGROUND AND PURPOSE: Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people.
METHODS: Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information.
RESULTS: Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P < .01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV1), and income less than $50,000 per year. If excluded, FEV1 was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination. Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function.
CONCLUSIONS: White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function.
10aAge Factors10aAged10aAging10aBlood Pressure10aBrain10aCardiovascular Diseases10aCerebrovascular Disorders10aCohort Studies10aFemale10aHumans10aIschemic Attack, Transient10aMagnetic Resonance Imaging10aMale10aMultivariate Analysis10aRisk Factors10aSex Factors1 aLongstreth, W T1 aManolio, T A1 aArnold, A1 aBurke, G, L1 aBryan, N1 aJungreis, C, A1 aEnright, P, L1 aO'Leary, D1 aFried, L uhttps://chs-nhlbi.org/node/146002751nas a2200373 4500008004100000022001400041245016800055210006900223260001300292300001100305490000700316520167800323653000902001653001902010653002702029653002802056653002102084653001102105653002102116653001102137653001702148653000902165653001802174653001702192100001602209700001802225700001502243700001702258700001702275700001602292700001602308700001702324856003602341 1996 eng d a0039-249900aCompensatory increase in common carotid artery diameter. Relation to blood pressure and artery intima-media thickness in older adults. Cardiovascular Health Study.0 aCompensatory increase in common carotid artery diameter Relation c1996 Nov a2012-50 v273 aBACKGROUND AND PURPOSE: Common carotid artery (CCA) diameter is thought to increase as a consequence of hypertension and may increase as the thickness of the arterial wall increases. The purpose of this study was to determine CCA dimensions and correlate them with clinical features.
METHODS: We performed a cross-sectional, community-based study of adults 65 years of age and older, measuring inner and outer diameter of the CCA in vivo with carotid sonography. Findings were correlated against risk factors for atherosclerosis, CCA intima-media thickness (IMT), and echocardiographically determined left ventricular (LV) mass.
RESULTS: Independent variables showing strong positive associations with outer and inner CCA diameter included age, male sex, height, weight, and systolic blood pressure. As an independent variable, LV mass (r = .40 and r = .37, respectively; P < .00001) had a strong positive relation to inner and outer CCA diameters. The relationship between diameter and IMT was different. In a model that controlled for age, sex, and estimated LV mass, an increase of 1 mm in CCA IMT corresponded to a 1.9 mm increase in the outer diameter of the artery (P < .00001) but was not significantly related to the inner diameter (slope = +0.07 mm; P = .26).
CONCLUSIONS: Increase in the outer diameter of the CCA is associated with subject size, sex, age, echocardiographically estimated LV mass, and CCA IMT. Increases in internal diameter of the CCA have similar relationships but are not related to IMT. This supports the hypothesis that the human CCA dilates as the thickness of the artery wall increases.
10aAged10aBlood Pressure10aCarotid Artery, Common10aCross-Sectional Studies10aEchocardiography10aFemale10aHeart Ventricles10aHumans10aHypertension10aMale10aTunica Intima10aTunica Media1 aPolak, J, F1 aKronmal, R, A1 aTell, G, S1 aO'Leary, D H1 aSavage, P, J1 aGardin, J M1 aRutan, G, H1 aBorhani, N O uhttps://chs-nhlbi.org/node/146602360nas a2200337 4500008004100000022001400041245009700055210006900152260001300221300001100234490000700245520147900252653000901731653001501740653002801755653001901783653001101802653001501813653001101828653000901839653001701848653001301865100001501878700001501893700001201908700001701920700001801937700001601955700001501971856003601986 1996 eng d a1079-564200aCorrelates of thrombin markers in an elderly cohort free of clinical cardiovascular disease.0 aCorrelates of thrombin markers in an elderly cohort free of clin c1996 Sep a1163-90 v163 aStudies suggest that thrombosis is important in the progression of atherosclerotic lesions. The biochemical markers prothrombin fragment 1-2 and fibrinopeptide A reflect in vivo thrombin generation and activity, respectively. As such, they are markers that might be associated with cardiovascular risk. From the Cardiovascular Health Study, a cohort study of 5201 persons over 65 years of age, 399 persons free of clinical cardiovascular disease (CVD) at the baseline examination were selected for study of specialized markers of hemostasis. We report the cross-sectional relationships of the thrombin markers to CVD risk factors and measures of subclinical CVD. The range of fragment 1-2 2 was 0.12 to 0.85 nmol/L. The range of fibrinopeptide A was 0.9 to 44.1 micrograms/L. High levels of fragment 1-2 and fibrinopeptide A were associated with age, with levels higher in women than men. Fragment 1-2 was associated with smoking; high levels of triglyceride, creatinine, and C-reactive protein; and low levels of glucose. Fibrinopeptide A was associated with high C-reactive protein and apolipoprotein(a) and lower ankle-brachial index. There were no significant associations of the thrombin markers with race, fibrinogen, alcohol consumption, diabetes, or most measures of subclinical CVD. Study findings support a hypothesis that there are physiological interrelationships between cardiac risk factors, hemostasis, inflammation, and progression of atherosclerosis.
10aAged10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aFemale10aHemostasis10aHumans10aMale10aRisk Factors10aThrombin1 aCushman, M1 aPsaty, B M1 aMacy, E1 aBovill, E, G1 aCornell, E, S1 aKuller, L H1 aTracy, R P uhttps://chs-nhlbi.org/node/146403350nas a2200481 4500008004100000022001400041245018700055210006900242260001300311300001100324490000600335520193200341653000902273653002102282653002102303653002102324653001902345653002502364653002802389653002302417653003002440653003302470653001402503653001102517653002902528653001102557653001502568653001502583653002502598653002002623653001802643653001902661100001602680700001802696700001502714700001702729700001802746700001502764700001502779700001802794700002002812856003602832 1996 eng d a1047-279700aCurrent estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.0 aCurrent estrogenprogestin and estrogen replacement therapy in el c1996 Jul a314-230 v63 aThe cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.
10aAged10aArteriosclerosis10aCarotid Arteries10aCarotid Stenosis10aCohort Studies10aConfidence Intervals10aCross-Sectional Studies10aDatabases, Factual10aDrug Therapy, Combination10aEstrogen Replacement Therapy10aEstrogens10aFemale10aHealth Status Indicators10aHumans10aOdds Ratio10aProgestins10aReproductive History10aUltrasonography10aUnited States10aWomen's Health1 aJonas, H, A1 aKronmal, R, A1 aPsaty, B M1 aManolio, T A1 aMeilahn, E, N1 aTell, G, S1 aTracy, R P1 aRobbins, J, A1 aAnton-Culver, H uhttps://chs-nhlbi.org/node/146500813nas a2200301 4500008004100000022001400041245010000055210006900155260001300224300001000237490000700247653000900254653001000263653002100273653001100294653001100305653001100316653001700327653000900344653002400353653001700377653001600394100001800410700001700428700001500445700001500460856003600475 1996 eng d a0091-674900aLipoprotein levels in elderly patients with asthma. Cardiovascular Health Study Research Group.0 aLipoprotein levels in elderly patients with asthma Cardiovascula c1996 Aug a467-90 v9810aAged10aAging10aArteriosclerosis10aAsthma10aFemale10aHumans10aLipoproteins10aMale10aProspective Studies10aRisk Factors10aSex Factors1 aEnright, P, L1 aLasser, E, C1 aWard, B, J1 aTracy, R P uhttps://chs-nhlbi.org/node/146202815nas a2200337 4500008004100000022001400041245009000055210006900145260001300214300001100227490000700238520189200245653000902137653002202146653002102168653003702189653001702226653001102243653001102254653001102265653002402276653000902300653001802309653003102327100001702358700001502375700001302390700001702403700002102420856003602441 1996 eng d a0002-822300aPicture-sort method for administering a food frequency questionnaire to older adults.0 aPicturesort method for administering a food frequency questionna c1996 Feb a137-440 v963 aOBJECTIVE: To assess the validity of a picture-sort approach to administering the National Cancer Institute food frequency questionnaire to older adults.
DESIGN: A picture-sort interview was conducted in each respondent's home. After the picture sort, a 24-hour recall interview was administered on the same occasion. Five additional in-home recall interviews were subsequently conducted at approximately 1-month intervals.
SUBJECTS/SETTING: Forty-seven female and 49 male volunteers aged 66 to 100 years were recruited from among Cardiovascular Health Study participants from Maryland and North Carolina.
MAIN OUTCOME MEASURES: Estimates from the picture sort and the recall for intakes of macronutrients, cholesterol, fiber, and selected vitamins and minerals exclusive of supplements.
STATISTICAL ANALYSES: Comparison of means estimated by the two methods and correlation analyses were used. Correlations were adjusted under varied assumptions about the nature of the information contained in the six 24-hour recalls relative to respondents' usual intakes.
RESULTS: After correction for attenuation, Pearson correlation coefficients for macronutrients ranged from .41 for protein to .74 for saturated fat and cholesterol. For vitamins and minerals, correlations ranged from .26 for beta carotene to .62 for calcium.
APPLICATIONS: Picture-sort estimates of mean nutrient intakes were comparable with estimates based on 24-hour recalls, and correlations with reference data were similar to those reported in the literature for conventionally administered food frequency questionnaires. This dietary assessment method may, therefore, offer a way to simplify or structure responses to improve ease of administration and increase respondents' liking for the interview without loss of data quality.
10aAged10aAged, 80 and over10aAudiovisual Aids10aData Interpretation, Statistical10aDiet Records10aEating10aFemale10aHumans10aInterviews as Topic10aMale10aMental Recall10aSurveys and Questionnaires1 aKumanyika, S1 aTell, G, S1 aFried, L1 aMartel, J, K1 aChinchilli, V, M uhttps://chs-nhlbi.org/node/145202798nas a2200397 4500008004100000022001400041245008400055210006900139260001300208300001000221490000700231520175700238653003101995653001602026653000902042653002802051653001602079653001102095653001102106653001402117653001802131653000902149653001502158653001502173653002202188653001602210653002602226653001202252100001802264700001702282700001402299700001702313700001802330700001602348856003602364 1996 eng d a0161-810500aPrevalence and correlates of snoring and observed apneas in 5,201 older adults.0 aPrevalence and correlates of snoring and observed apneas in 5201 c1996 Sep a531-80 v193 aThe objectives of this study were to describe the prevalence of snoring, observed apneas, and daytime sleepiness in older men and women, and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases (CVD). A cross-sectional design was employed to study sleep problems, CVD, general health, psychosocial factors, and medication use. The subjects were participants in the Cardiovascular Health Study, which included 5,201 adults, aged 65 and older, who were recruited from a random sample of Medicare enrollees in four U.S. communities. Study measures employed were sleep questions, echocardiography, carotid ultrasound, resting electrocardiogram, cognitive function, cardiopulmonary symptoms and diseases, depression, independent activities of daily living (IADLs), and benzodiazepine use. Thirty-three percent of the men and 19% of the women reported loud snoring, which was less frequent in those over age 75. Snoring was positively associated with younger age, marital status, and alcohol use in men, and obesity, diabetes, and arthritis in women. Snoring was not associated, however, with cardiovascular risk factors or clinical CVD in men or women. Observed apneas were reported much less frequently (13% of men and 4% women) than snoring, and they were associated with alcohol use, chronic bronchitis, and marital status in men. Observed apneas were associated with depression and diabetes in women. In both men and women, daytime sleepiness was associated with poor health, advanced age, and IADL limitations. The conclusions of the study were that loud snoring, observed apneas, and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons.
10aActivities of Daily Living10aAge Factors10aAged10aCardiovascular Diseases10aComorbidity10aFemale10aHumans10aIncidence10aLung Diseases10aMale10aNarcolepsy10aPrevalence10aRandom Allocation10aSex Factors10aSleep Apnea Syndromes10aSnoring1 aEnright, P, L1 aNewman, A, B1 aWahl, P W1 aManolio, T A1 aHaponik, E, F1 aBoyle, P, J uhttps://chs-nhlbi.org/node/146702779nas a2200409 4500008004100000022001400041245010900055210006900164260001300233300001100246490000700257520166200264653000901926653001801935653003101953653001901984653002802003653001902031653001602050653001102066653001102077653000902088653001602097653001902113653001502132653003102147653001702178653001202195653002002207653001802227100001702245700001802262700002202280700001602302700001502318856003602333 1996 eng d a1079-564200aRisk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.0 aRisk factors for abdominal aortic aneurysms in older adults enro c1996 Aug a963-700 v163 aB-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5% (451/4741) overall, with a prevalence among men of 14.2% (278/1956) and prevalence among women of 6.2% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.
10aAged10aAnthropometry10aAortic Aneurysm, Abdominal10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aHumans10aMale10aMiddle Aged10aPilot Projects10aPrevalence10aReproducibility of Results10aRisk Factors10aSmoking10aUltrasonography10aUnited States1 aAlcorn, H, G1 aWolfson, S, K1 aSutton-Tyrrell, K1 aKuller, L H1 aO'Leary, D uhttps://chs-nhlbi.org/node/145903089nas a2200409 4500008004100000022001400041245009500055210006900150260001300219300001200232490000700244520195700251653001602208653000902224653004302233653003002276653001902306653001102325653001802336653001102354653001402365653002502379653000902404653002602413653001402439653003202453653002402485653001702509653001602526653001702542100001702559700001802576700001602594700001702610700001602627856003602643 1996 eng d a0039-249900aShort-term predictors of incident stroke in older adults. The Cardiovascular Health Study.0 aShortterm predictors of incident stroke in older adults The Card c1996 Sep a1479-860 v273 aBACKGROUND AND PURPOSE: Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease.
METHODS: Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study.
RESULTS: During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft. frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P < .001). Aspirin users had a 52% higher risk of stroke (relative risk, 1.52; 95% confidence interval, 1.1 to 2.0; P < .007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84% higher risk (relative risk, 1.84; 95% confidence interval, 1.2 to 2.8).
CONCLUSIONS: Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.
10aAge Factors10aAged10aCardiovascular Physiological Phenomena10aCerebrovascular Disorders10aCohort Studies10aFemale10aHealth Status10aHumans10aIncidence10aLongitudinal Studies10aMale10aMultivariate Analysis10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSex Factors10aTime Factors1 aManolio, T A1 aKronmal, R, A1 aBurke, G, L1 aO'Leary, D H1 aPrice, T, R uhttps://chs-nhlbi.org/node/146302041nas a2200325 4500008004100000022001400041245010800055210006900163260001300232300001200245490000800257520110600265653003901371653000901410653002201419653004001441653001101481653002901492653001101521653000901532653002101541653001501562653001801577653001901595100001801614700001401632700001701646700001601663856003601679 1996 eng d a0012-369200aSpirometry reference values for healthy elderly blacks. The Cardiovascular Health Study Research Group.0 aSpirometry reference values for healthy elderly blacks The Cardi c1996 Dec a1416-240 v1103 aPulmonary function was assessed by spirometry in 497 black and 2,980 white ambulatory elderly male and female participants of the Cardiovascular Health Study. The quality assurance program prompted technicians to exceed American Thoracic Society recommendations for spirometry. A "healthy" subgroup of 235 black and 1,227 white participants age 65 years and older was identified by excluding current and former smoker, and those with self-reported asthma or emphysema, congestive heart failure, and poor-quality results of spirometry tests, since those factors were associated with a lower FEV1. Reference equations and normal ranges for elderly blacks for measurements of FEV1, FVC, and the FEV1/FVC ratio were then determined from the healthy group. These elderly blacks had an FVC about 6% lower than elderly whites, even after correcting for standing height, sitting height (trunk length), and age. The popular use of spirometry reference values from studies of middle-aged white subjects by applying a 12% race correction factor for black patients appears to overestimate predicted values.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aEuropean Continental Ancestry Group10aFemale10aForced Expiratory Volume10aHumans10aMale10aReference Values10aSpirometry10aUnited States10aVital Capacity1 aEnright, P, L1 aArnold, A1 aManolio, T A1 aKuller, L H uhttps://chs-nhlbi.org/node/147201871nas a2200313 4500008004100000022001400041245008200055210006900137260001300206300001100219490000700230520101000237653003101247653003001278653000901308653002801317653001501345653001101360653002501371653001101396653000901407653002601416653001401442653002301456653001201479100001601491700001401507856003601521 1996 eng d a0882-797400aSpousal similarity in subjective well-being: the Cardiovascular Health Study.0 aSpousal similarity in subjective wellbeing the Cardiovascular He c1996 Dec a582-900 v113 aThis study examines the extent to which one spouse's subjective well-being predicts that of the partner (N = 1,040 spousal pairs, 65 years or older). Prior research is extended in two ways: (a) The similarity of both affective domains (depressive symptoms, feelings about life as a whole, and satisfaction with the meaning and purpose of life) and nonaffective domains (perceived health) are examined, and (b) known predictors of well-being in older adults (sociodemographic variables, self and spouse health status variables, and exposure to common environmental events) are statistically controlled. Results indicate that one spouse's assessments of well-being and depression predict the other's well-being even after controlling for known predictors of these outcomes. Given the similarity of findings for affective and nonaffective domains, multiple mechanisms, including contagion, mate selection, and common environmental influences, are speculated as likely to contribute to this phenomenon.
10aActivities of Daily Living10aAdaptation, Psychological10aAged10aCardiovascular Diseases10aDepression10aFemale10aGeriatric Assessment10aHumans10aMale10aPersonal Satisfaction10aSick Role10aSocial Environment10aSpouses1 aBookwala, J1 aSchulz, R uhttps://chs-nhlbi.org/node/147403950nas a2200565 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520238100294653001002675653000902685653002102694653001902715653002702734653002902761653002102790653002102811653001902832653002102851653002202872653002602894653002402920653001102944653001102955653000902966653002702975653002503002653002403027653002403051653001703075653002403092653001203116653001803128653001703146653002003163100001703183700001603200700001803216700001703234700001703251700001803268700001303286700001603299700001603315700001703331856003603348 1996 eng d a0039-249900aThickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group.0 aThickening of the carotid wall A marker for atherosclerosis in t c1996 Feb a224-310 v273 aBACKGROUND AND PURPOSE: We investigated the relationships between prevalent coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD), and major established risk factors for atherosclerosis and intima-media thickness (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA) separately and in combination in older adults. We wished to determine whether a noninvasive measurement can serve as an indicator of clinically manifest atherosclerotic disease and to determine which of the two variables, CCA IMT or ICA IMT, is a better correlate.
METHODS: IMT of the CCA and ICA was measured with duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular Health Study, a study of the risk factors and the natural history of cardiovascular disease in adults aged 65 years or more. Histories of CHD, peripheral arterial disease, and cerebrovascular disease were obtained during baseline examination. Risk factors included cholesterol levels, cigarette smoking, elevated blood pressure, diabetes, age, and sex. Relationships between risk factors and IMT were studied by multiple regression analysis and canonical variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs and ICAs were made by logistic regression, adjusting for age and sex.
RESULTS: IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD than those without, even after controlling for sex (P < .001). IMT measurements in the ICA were greater than those in the CCA. Risk factors for ASD accounted for 17% and 18% of the variability in IMT in the CCA and ICA, respectively. These same risk factors accounted for 25% of the variability of a composite measurement consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to 1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to 1.13] and 1.17 [1.09 to 1.25]).
CONCLUSIONS: Whereas CCA IMT is associated with major risk factors for atherosclerosis and existing CHD and ASD in older adults, this association is not as strong as that for ICA IMT. The combination of these measures relates more strongly to existing CHD and ASD and cerebrovascular disease risk factors than either taken alone.
10aAdult10aAged10aArteriosclerosis10aBlood Pressure10aCarotid Artery, Common10aCarotid Artery, Internal10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aCoronary Disease10aDiabetes Mellitus10aDiabetic Angiopathies10aElectrocardiography10aFemale10aHumans10aMale10aMedical History Taking10aPhysical Examination10aProspective Studies10aRegression Analysis10aRisk Factors10aSex Characteristics10aSmoking10aTunica Intima10aTunica Media10aUltrasonography1 aO'Leary, D H1 aPolak, J, F1 aKronmal, R, A1 aSavage, P, J1 aBorhani, N O1 aKittner, S, J1 aTracy, R1 aGardin, J M1 aPrice, T, R1 aFurberg, C D uhttps://chs-nhlbi.org/node/145303068nas a2200433 4500008004100000022001400041245015200055210006900207260001300276300000900289490000700298520186600305653001602171653000902187653002102196653002402217653001102241653001102252653003402263653001802297653000902315653002702324653001202351653001502363653001402378653001702392653001602409653002402425100002102449700001702470700001702487700001502504700001602519700001502535700001702550700001702567700001402584856003602598 1996 eng d a0194-911X00aUtility of new electrocardiographic models for left ventricular mass in older adults. The Cardiovascular Health Study Collaborative Research Group.0 aUtility of new electrocardiographic models for left ventricular c1996 Jul a8-150 v283 aSeveral multivariate statistical models have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements. The validity of these algorithms has not been adequately evaluated. The objective of this investigation was to compare the associations between echocardiographic and electrocardiographic left ventricular mass values with clinical and subclinical indexes of coronary heart disease. The evaluation was performed with participants of the Cardiovascular Health Study, a population-based sample of 5201 men and women aged 65 years and older. Echocardiographic M-mode measurements of left ventricular mass were performed from videotape recordings with the use of a strictly standardized protocol. Electrocardiographic algorithms of the Novacode program and new algorithms derived from the Cardiovascular Health Study population were used for left ventricular mass prediction. Echocardiographic and electrocardiographic determinations of left ventricular mass were technically successful in 3410 (65.6%) and 5013 (96.4%) participants, respectively. The Novacode model overestimated echocardiographic left ventricular mass. Compared with the Novacode model, the new Cardiovascular Health Study electrocardiographic model, which includes adjustment for body weight, eliminated left ventricular mass prediction bias and improved the correlation between echocardiographic and electrocardiographic left ventricular mass from .33 to .54 in women and from .46 to .51 in men. Echocardiographic and electrocardiographic models both demonstrated similar and about equally strong associations with overt and subclinical disease and with risk factors for left ventricular hypertrophy. These observations demonstrate the potential utility of electrocardiographic models for left ventricular mass estimation.
10aAge Factors10aAged10aEchocardiography10aElectrocardiography10aFemale10aHumans10aHypertrophy, Left Ventricular10aLinear Models10aMale10aModels, Cardiovascular10aObesity10aOdds Ratio10aPrognosis10aRisk Factors10aSex Factors10aVideotape Recording1 aRautaharju, P, M1 aManolio, T A1 aSiscovick, D1 aZhou, S, H1 aGardin, J M1 aKronmal, R1 aFurberg, C D1 aBorhani, N O1 aNewman, A uhttps://chs-nhlbi.org/node/145802390nas a2200397 4500008004100000022001400041245016800055210006900223260001600292300001200308490000800320520125500328653002101583653000901604653002201613653003001635653001101665653001101676653002001687653001701707653002501724653000901749653002601758653001501784653002101799653001701820653001801837100001701855700001501872700001301887700001601900700001401916700001201930700001401942856003601956 1996 eng d a0002-926200aWhite blood cell counts in persons aged 65 years or more from the Cardiovascular Health Study. Correlations with baseline clinical and demographic characteristics.0 aWhite blood cell counts in persons aged 65 years or more from th c1996 Jun 01 a1107-150 v1433 aA higher white blood cell (WBC) count has been shown to be a risk factor for myocardial infarction and stroke in middle-aged populations. This study evaluated the relation between baseline WBC count and other risk factors, as well as subclinical and prevalent disease, in the Cardiovascular Health Study, an epidemiologic study of coronary heart disease and stroke in 5,201 persons aged 65 years or older. Baseline data were collected over a 12-month period in 1989-1990. WBC counts were statistically significantly higher in people with prevalent and subclinical atherosclerotic cardiovascular disease than in those who were free of disease. WBC counts correlated (p < 0.01) positively with coagulation factors, measures of glucose metabolism, creatinine, smoking, and triglycerides. In contrast, WBC counts correlated negatively with high density lipoprotein cholesterol, forced expiratory volume, forced vital capacity, and height. The correlations between WBC counts and risk factors were similar in both the entire cohort and the subgroup of persons who had never smoked. The authors conclude that WBC counts in the elderly are associated with prevalent and subclinical atherosclerotic cardiovascular disease, as well as its risk factors.
10aAge Distribution10aAged10aAged, 80 and over10aCerebrovascular Disorders10aFemale10aHumans10aLeukocyte Count10aLeukocytosis10aLongitudinal Studies10aMale10aMyocardial Infarction10aPrevalence10aReference Values10aRisk Factors10aUnited States1 aBovill, E, G1 aBild, D, E1 aHeiss, G1 aKuller, L H1 aLee, M, H1 aRock, R1 aWahl, P W uhttps://chs-nhlbi.org/node/145603061nas a2200433 4500008004100000022001400041245014300055210006900198260001300267300001200280490000700292520182800299653003202127653000902159653002202168653002802190653001002218653002902228653001402257653001902271653002802290653001402318653001102332653002502343653001102368653003102379653000902410653001702419100001802436700002002454700001502474700001702489700001502506700001702521700002102538700001502559700001702574856003602591 1997 eng d a0002-861400aThe association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.0 aassociation of antihypertensive agents with MRI white matter fin c1997 Dec a1423-330 v453 aOBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults.
DESIGN: Cross-sectional study.
SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older.
PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension.
MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings).
RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors.
CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.
10aAdrenergic beta-Antagonists10aAged10aAged, 80 and over10aAntihypertensive Agents10aBrain10aCalcium Channel Blockers10aCognition10aCohort Studies10aCross-Sectional Studies10aDiuretics10aFemale10aGeriatric Assessment10aHumans10aMagnetic Resonance Imaging10aMale10aRisk Factors1 aHeckbert, S R1 aLongstreth, W T1 aPsaty, B M1 aMurros, K, E1 aSmith, N L1 aNewman, A, B1 aWilliamson, J, D1 aBernick, C1 aFurberg, C D uhttps://chs-nhlbi.org/node/149102719nas a2200301 4500008004100000022001400041245009800055210006900153260001300222300001200235490000700247520191200254653000902166653002802175653001902203653001502222653001102237653001102248653000902259100001502268700001502283700001802298700001902316700001602335700001602351700001402367856003602381 1997 eng d a0895-706100aThe association of antihypertensive medication with serum creatinine changes in older adults.0 aassociation of antihypertensive medication with serum creatinine c1997 Dec a1368-770 v103 aMany of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.
10aAged10aAntihypertensive Agents10aCohort Studies10aCreatinine10aFemale10aHumans10aMale1 aSmith, N L1 aPsaty, B M1 aHeckbert, S R1 aLemaitre, R, N1 aKates, D, M1 aRutan, G, H1 aBleyer, A uhttps://chs-nhlbi.org/node/149302820nas a2200409 4500008004100000022001400041245020700055210006900262260001300331300001100344490000700355520163100362653000901993653001902002653002202021653001602043653002802059653002102087653001102108653001802119653001102137653001202148653002502160653000902185653001602194653001502210653001502225653001702240653002402257100001602281700001702297700001502314700001202329700001702341700001602358856003602374 1997 eng d a0002-916500aCarrying the burden of cardiovascular risk in old age: associations of weight and weight change with prevalent cardiovascular disease, risk factors, and health status in the Cardiovascular Health Study.0 aCarrying the burden of cardiovascular risk in old age associatio c1997 Oct a837-440 v663 aMeasured weight in old age, reported weight at age 50 y, and weight change from age 50 y to old age were studied in association with prevalent cardiovascular disease (CVD), CVD risk factors, and health status in a population of 4954 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). Heavier weight (i.e., generally weight in the fourth quartile for the cohort) at age 50 y was more closely associated with prevalent CVD than was current weight, with these associations stronger in women than in men. Heavier current weight and heavier weight at age 50 y were associated with cardiovascular risk factors, including higher blood pressure, lower high-density-lipoprotein cholesterol, and higher fasting insulin. Heavier weight at both time points was related to mobility problems in both men and women and to lower current physical activity levels; among women, strong associations were also seen with lower education and current income. Remaining within 10% of reported weight at age 50 y was associated with better health status as measured by reported health, mobility difficulty, number of medications, and prevalent CVD in men. Paradoxically, most cardiovascular risk factors were lowest for weight losers despite an association of weight loss with poorer health. In this cohort of persons aged > or = 65 y, heavier weight was associated with CVD and CVD risk factors, suggesting that prevention of overweight may prove beneficial in improving cardiovascular risk in older persons. Weight stability from age 50 y to old age was associated with better health status than was weight gain or loss.
10aAged10aBlood Pressure10aBody Constitution10aBody Weight10aCardiovascular Diseases10aCholesterol, LDL10aFemale10aHealth Status10aHumans10aInsulin10aLongitudinal Studies10aMale10aMiddle Aged10aOdds Ratio10aPrevalence10aRisk Factors10aSex Characteristics1 aHarris, T B1 aSavage, P, J1 aTell, G, S1 aHaan, M1 aKumanyika, S1 aLynch, J, C uhttps://chs-nhlbi.org/node/148702470nas a2200373 4500008004100000022001400041245009700055210006900152260001600221300001000237490000700247520147100254653000901725653002201734653001701756653002601773653001501799653001101814653002501825653001101850653000901861653002401870653001701894653001401911100001801925700001701943700001501960700001601975700002001991700001602011700001802027700001502045856003602060 1997 eng d a0735-109700aClinical factors associated with calcific aortic valve disease. Cardiovascular Health Study.0 aClinical factors associated with calcific aortic valve disease C c1997 Mar 01 a630-40 v293 aOBJECTIVES: The aim of this study was to determine the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortic valve disease.
BACKGROUND: Several lines of evidence suggest that degenerative aortic valve disease is not an inevitable consequence of aging and may be associated with specific clinical factors.
METHODS: In 5,201 subjects > or = 65 years of age enrolled in the Cardiovascular Health Study, the relation between aortic sclerosis or stenosis identified on echocardiography and clinical risk factors for atherosclerosis was evaluated by using stepwise logistic regression analysis.
RESULTS: Aortic valve sclerosis was present in 26% and aortic valve stenosis in 2% of the entire study cohort; in subjects > or = 75 years of age, sclerosis was present in 37% and stenosis in 2.6%. Independent clinical factors associated with degenerative aortic valve disease included age (twofold increased risk for each 10-year increase in age), male gender (twofold excess risk), present smoking (35% increase in risk) and a history of hypertension (20% increase in risk). Other significant factors included height and high lipoprotein(a) and low density lipoprotein cholesterol levels.
CONCLUSIONS: Clinical factors associated with aortic sclerosis and stenosis can be identified and are similar to risk factors for atherosclerosis.
10aAged10aAged, 80 and over10aAortic Valve10aAortic Valve Stenosis10aCalcinosis10aFemale10aHeart Valve Diseases10aHumans10aMale10aProspective Studies10aRisk Factors10aSclerosis1 aStewart, B, F1 aSiscovick, D1 aLind, B, K1 aGardin, J M1 aGottdiener, J S1 aSmith, V, E1 aKitzman, D, W1 aOtto, C, M uhttps://chs-nhlbi.org/node/147602375nas a2200337 4500008004100000022001400041245012700055210006900182260001300251300000900264490000800273520142100281653000901702653002201711653001001733653001901743653002801762653001901790653001101809653001101820653002501831653003101856653000901887100001401896700002001910700001701930700001901947700001701966700001801983856003602001 1997 eng d a0033-841900aClinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study.0 aClinically serious abnormalities found incidentally at MR imagin c1997 Jan a41-60 v2023 aPURPOSE: To determine the prevalence of clinically serious findings unrelated to stroke on cranial magnetic resonance (MR) images in a population of community-dwelling elderly people.
MATERIALS AND METHODS: Neuroradiologists reviewed MR images of 3,672 people aged 65 years and older who were enrolled in a longitudinal, population-based study of cardiovascular and cerebrovascular disease. The neuroradiologists alerted MR imaging field centers about potentially serious abnormalities. Clinical information was obtained from clinical examinations performed before MR imaging, hospital discharge summaries, and the field centers at which MR imaging was performed.
RESULTS: On 3,672 image sets, 64 (1.74%) clinically serious abnormalities were found. Among the presumptive diagnoses were 19 meningiomas (0.52%), six pituitary adenomas (0.16%), five cavernous malformations (0.14%), eight vascular stenoses (0.22%), four aneurysms (0.11%), two intraventricular masses (0.05%), two subdural fluid collections (0.05%), and two other tumors (0.05%). Only nine participants with these abnormalities required surgery. All but one of the meningiomas were in women, and the prevalence of the tumor decreased with increasing age.
CONCLUSION: Physicians should be alert to the possible presence of clinically serious conditions in otherwise asymptomatic elderly individuals.
10aAged10aAged, 80 and over10aBrain10aBrain Diseases10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale1 aYue, N, C1 aLongstreth, W T1 aElster, A, D1 aJungreis, C, A1 aO'Leary, D H1 aPoirier, V, C uhttps://chs-nhlbi.org/node/147002941nas a2200385 4500008004100000022001400041245011300055210006900168260001300237300001300250490000700263520190800270653001002178653001802188653004302206653001102249653000902260653001802269653001802287653001102305653000902316653001602325653001902341653001202360653001302372653002402385653001602409100001702425700001502442700001402457700001902471700001502490700001402505856003602519 1997 eng d a1079-500600aCorrelates of performance-based measures of muscle function in the elderly: the Cardiovascular Health Study.0 aCorrelates of performancebased measures of muscle function in th c1997 Jul aM192-2000 v523 aBACKGROUND: It is unknown how much age-related changes in muscle performance represent normal aging versus the effects of chronic disease and life style. We examined the correlates of four performance measures-gait speed, timed chair stands (TCS), grip strength, and maximal inspiratory pressure (MIP)-using baseline data from the Cardiovascular Health Study (CHS), a population-based study of risk factors for heart disease and stroke in persons > or = age 65.
METHODS: We analyzed data from the 5,201 CHS participants. Variables were arranged into nine categories: Personal Characteristics, Anthropometry, Physical Condition, Reported Functional Status, Subjective Health, Psychological Factors, Symptoms, Cognitive Status, Habits and Lifestyle, and Prevalent Disease. Independent correlates were identified using stepwise linear regression.
RESULTS: The regression models explained 17.7-25.4% of the observed variability. Although age significantly correlated with each measure, it explained little of the variability (< or = 5.7%). Anthropometric features plus physical condition explained 14.0-17.4% of the variability for grip strength and MIP, but 2.8-12.9% of the variability for gait speed and the log of TCS. Subjective health and psychological factors explained 1.8-9.4% of the variability in gait speed and the log of TCS, but < or = 1.2% of the variability in grip strength and MIP. Variables for prevalent disease explained < or = 1.3% of the variability in each measure.
CONCLUSIONS: After age 64, age explained little of the variability in muscle performance in a large sample of mostly functionally intact, community-dwelling older persons. Complex measures such as gait speed were more associated with subjective factors than were direct measures of strength. Prevalent disease contributed surprisingly little to muscle performance.
10aAging10aAnthropometry10aCardiovascular Physiological Phenomena10aFemale10aGait10aHand Strength10aHealth Status10aHumans10aMale10aMiddle Aged10aMotor Activity10aMuscles10aPressure10aRegression Analysis10aRespiration1 aHirsch, C, H1 aFried, L P1 aHarris, T1 aFitzpatrick, A1 aEnright, P1 aSchulz, R uhttps://chs-nhlbi.org/node/148503351nas a2200373 4500008004100000022001400041245014100055210006900196260001300265300001000278490000800288520229500296653000902591653002402600653001902624653002202643653002102665653001102686653002702697653001102724653000902735653001702744653003002761653003102791100001102822700001602833700001602849700001602865700001502881700001702896700001302913700001502926856003602941 1997 eng d a0002-870300aDiabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The Cardiovascular Health Study.0 aDiabetes mellitus and echocardiographic left ventricular functio c1997 Jan a36-430 v1333 aThis report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak flow velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated flow-velocity curve but not for the integral of the early peak flow velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease.
10aAged10aBlood Flow Velocity10aBlood Pressure10aDiabetes Mellitus10aEchocardiography10aFemale10aGlucose Tolerance Test10aHumans10aMale10aMitral Valve10aResidence Characteristics10aVentricular Function, Left1 aLee, M1 aGardin, J M1 aLynch, J, C1 aSmith, V, E1 aTracy, R P1 aSavage, P, J1 aSzklo, M1 aWard, B, J uhttps://chs-nhlbi.org/node/147502217nas a2200301 4500008004100000022001400041245005400055210005200109260001300161300001600174490000700190520146000197653000901657653002101666653000901687653001101696653000901707653001101716653000901727653002501736653003101761100002001792700001501812700001701827700001401844700002101858856003601879 1997 eng d a0002-916500aDietary assessment using a picture-sort approach.0 aDietary assessment using a picturesort approach c1997 Apr a1123S-1129S0 v653 aFood-frequency questionnaires are usually administered as a list of foods to be checked off by the respondent or interviewer. Techniques in which participants sort into categories cards on which names or pictures of foods are printed can also be used to assess food intake. Food-frequency scores were obtained from a five-category picture sort administered to 4643 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). This one-step (qualitative) assessment yielded significant associations in expected directions between frequency scores and sex, age, race or ethnicity, body mass index, and use of a special diet. In the two-step (semiquantitative) version of this instrument, an interviewer documented specific frequencies and portion-size information for the foods in each sorting category. A substudy of the two-step version with 96 CHS participants indicated relative validity similar to that of conventionally administered food-frequency questionnaires. The one-step version may be broadly applicable to situations in which general food-pattern data can be informative and cost and time limitations are great. When it is feasible, the two-step picture sort may offer certain methodologic advantages because respondents have a chance to change their responses and the format may simplify the cognitive-response task. Sorting or picture-sort procedures deserve systematic attention in research on dietary assessment methods.
10aAged10aAudiovisual Aids10aDiet10aFemale10aFood10aHumans10aMale10aNutrition Assessment10aSurveys and Questionnaires1 aKumanyika, S, K1 aTell, G, S1 aShemanski, L1 aMartel, J1 aChinchilli, V, M uhttps://chs-nhlbi.org/node/147803565nas a2200517 4500008004100000022001400041245022800055210006900283260001300352300001300365490000700378520201100385653002202396653003902418653000902457653001002466653002102476653002002497653004302517653002602560653002102586653002102607653002102628653001902649653004002668653001102708653001502719653001802734653001102752653001702763653000902780653001602789653002402805653001702829653001602846653001202862653001802874653001702892653002002909100001402929700001702943700001602960700001802976700001702994856003603011 1997 eng d a0039-249900aDoes the association of risk factors and atherosclerosis change with age? An analysis of the combined ARIC and CHS cohorts. The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) investigators.0 aDoes the association of risk factors and atherosclerosis change c1997 Sep a1693-7010 v283 aINTRODUCTION: A decrease in the estimated relative risk of cerebrovascular and cardiovascular diseases associated with known disease risk factors has been observed among elderly cohorts, perhaps suggesting that continued risk factor management in the elderly may not be as efficacious as with younger age groups. In this paper, the differential magnitude of the association of risk factors with atherosclerosis across the age spectrum from 45 years to older than 75 years is presented.
METHODS: Subclinical atherosclerosis as measured by carotid ultrasonography and risk factor prevalence were assessed using similar methods among participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study and among participants 65 years and older in the Cardiovascular Health Study (CHS). Pooling these two cohorts provided data on the relationship of risk factors and atherosclerosis on nearly 19,000 participants over a broad age range. Regression analyses were used to assess the consistency of the magnitude of the association of risk factors with atherosclerosis across the age spectrum separately for black and white participants in cross-sectional analyses.
RESULTS: As expected, each of the risk factors was globally (across all ages) associated with increased atherosclerosis. However, the magnitude of the association did not differ across the age spectrum for hypertension, low density lipoprotein cholesterol (LDL-c), fibrinogen, or body mass index (BMI). For whites, there was a significantly greater impact of smoking and HDL-C among older age strata but a smaller impact of diabetes. For black women, the impact of HDL-C decreased among the older age strata.
CONCLUSIONS: These data suggest that most risk factors continue to be associated with increased atherosclerosis at older ages, possibly suggesting a continued value in investigation of strategies to reduce atherosclerosis by controlling risk factors at older ages.
10aAfrican Americans10aAfrican Continental Ancestry Group10aAged10aAging10aArteriosclerosis10aBody Mass Index10aCardiovascular Physiological Phenomena10aCardiovascular System10aCarotid Arteries10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aHealth Status10aHumans10aHypertension10aMale10aMiddle Aged10aRegression Analysis10aRisk Factors10aSex Factors10aSmoking10aTunica Intima10aTunica Media10aUltrasonography1 aHoward, G1 aManolio, T A1 aBurke, G, L1 aWolfson, S, K1 aO'Leary, D H uhttps://chs-nhlbi.org/node/148602784nas a2200373 4500008004100000022001400041245011100055210006900166260001600235300001100251490000800262520178100270653000902051653002802060653002802088653002202116653001302138653001102151653001502162653001102177653001202188653001502200653002502215653000902240653001502249653001702264100002002281700001302301700001802314700001302332700001202345700001702357856003602374 1997 eng d a0002-926200aExercise intensity and subclinical cardiovascular disease in the elderly. The Cardiovascular Health Study.0 aExercise intensity and subclinical cardiovascular disease in the c1997 Jun 01 a977-860 v1453 aThe authors assessed the cross-sectional association between intensity of exercise in later life and coronary heart disease risk factors and subclinical disease among 2,274 men and women, 65 years of age and older, who were participants in the Cardiovascular Health Study (CHS) during 1989-1990. Subjects were free of prior clinical cardiovascular disease or impairment of physical function. Exercise intensity was characterized as low, moderate, or high, based on highest intensity exercise reported over the 2 weeks prior to the CHS baseline examination. After adjustment for age, education, and postmenopausal hormone therapy (among women), there was an inverse dose-response relationship of exercise intensity with selected risk factors. By low, moderate, and high exercise intensity, respectively: fasting insulin-men, 15.6 microU/ml, 14.1 microU/ml, and 12.6 microU/ml, p for trend <0.001; women, 14.8 microU/ml, 13.8 microU/ml, and 12.0 microU/ml, p for trend = 0.01; serum fibrinogen-men, 316.2 mg/dl, 315.4 mg/dl, and 300.0 mg/dl, p for trend = 0.01; women, 327.3 mg/dl, 317.0 mg/dl, and 310.7 mg/dl, p for trend = 0.01; lower extremity arterial disease by percent with ankle-arm index <0.9-men, 18.3, 5.5, and 3.7, p for trend = 0.01; women, 10.0, 5.7, and 2.8, p for trend = 0.02; evidence of myocardial injury by cardiac infarction/injury score (CIIS)-men, 8.0, 6.0, 3.9, p for trend <0.001; women, 4.6, 3.9, and 3.6, p for trend = 0.03. Adjustment for smoking, alcohol consumption, and total kilocalories expended in exercise altered the findings only slightly. The authors conclude that intensity of exercise in later life is associated with favorable coronary disease risk factor levels and a reduced prevalence of several markers of subclinical disease.
10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aEnergy Metabolism10aExercise10aFemale10aFibrinogen10aHumans10aInsulin10aLife Style10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors1 aSiscovick, D, S1 aFried, L1 aMittelmark, M1 aRutan, G1 aBild, D1 aO'Leary, D H uhttps://chs-nhlbi.org/node/148202262nas a2200421 4500008004100000022001400041245012500055210006900180260001600249300001000265490000700275520108600282653003101368653000901399653001201408653002801420653001501448653003001463653002101493653002001514653001101534653002501545653002001570653001801590653001101608653000901619653003201628653001701660653001201677653002601689100001401715700001401729700001801743700001401761700001401775700001501789856003601804 1997 eng d a0883-661200aHealth effects of caregiving: the caregiver health effects study: an ancillary study of the Cardiovascular Health Study.0 aHealth effects of caregiving the caregiver health effects study c1997 Spring a110-60 v193 aWe propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used and the definition of what constitutes caregiving. Samples are often recruited through self-referral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.
10aActivities of Daily Living10aAged10aArousal10aCardiovascular Diseases10aCaregivers10aCerebrovascular Disorders10aCoronary Disease10aCost of Illness10aFemale10aGeriatric Assessment10aHealth Behavior10aHealth Status10aHumans10aMale10aPsychophysiologic Disorders10aRisk Factors10aSpouses10aStress, Psychological1 aSchulz, R1 aNewsom, J1 aMittelmark, M1 aBurton, L1 aHirsch, C1 aJackson, S uhttps://chs-nhlbi.org/node/150602732nas a2200361 4500008004100000022001400041245005100055210005000106260001300156300001000169490000700179520180100186653002101987653000902008653003002017653004002047653001102087653001802098653001102116653003102127653000902158653001602167653001902183100001702202700001602219700001802235700002002253700001402273700001702287700001502304700001502319856003602334 1997 eng d a0039-249900aHealth status of individuals with mild stroke.0 aHealth status of individuals with mild stroke c1997 Apr a740-50 v283 aBACKGROUND AND PURPOSE: Diminished quality of life and limitations in higher levels of physical functioning are often underestimated in stroke and are not fully captured by measures such as the Barthel Index and the Rankin Outcome Scale. This study used additional measures to assess the health status of 304 persons with mild stroke and to compare these individuals with 184 persons with transient ischemic attack and 654 persons without history of stroke/transient ischemic attack but at elevated risk for stroke (asymptomatic group).
METHODS: Subjects were recruited from the Academic Medical Center Consortium (inpatients), the Cardiovascular Health Study (population-based sample of community-dwelling persons 65 years and older), and United HealthCare (inpatients and outpatients typically younger than 65 years). Subjects were interviewed by telephone or in person to assess activities of daily living (Barthel Index), depression (Center for Epidemiological Studies Depression Scale), health status (MOS-36), and utility for current health state.
RESULTS: Most respondents were independent on all Barthel items. The stroke group was more impaired on the MOS-36 than the asymptomatic group but similar to the group with transient ischemic attack. Health-related quality of life was lowest for persons with stroke. While symptom status and Barthel Index score were the strongest predictors of health status, the Barthel Index showed a consistent ceiling effect when compared with the physical function subscale of the MOS-36.
CONCLUSIONS: The consequences of even mild stroke affect all dimensions of health except pain. Standardized assessment of persons with stroke must evaluate across the entire continuum of health-related functions.
10aAge Distribution10aAged10aCerebrovascular Disorders10aEuropean Continental Ancestry Group10aFemale10aHealth Status10aHumans10aIschemic Attack, Transient10aMale10aMiddle Aged10aSocial Support1 aDuncan, P, W1 aSamsa, G, P1 aWeinberger, M1 aGoldstein, L, B1 aBonito, A1 aWitter, D, M1 aEnarson, C1 aMatchar, D uhttps://chs-nhlbi.org/node/147903067nas a2200457 4500008004100000022001400041245007500055210006900130260001600199300001200215490000700227520187100234653001002105653000902115653002402124653001802148653001902166653003002185653001902215653002102234653002402255653001102279653002202290653002102312653001102333653001402344653000902358653002402367653001702391653001802408100001502426700001702441700001602458700001802474700001502492700001502507700001302522700001702535700002102552856003602573 1997 eng d a0009-732200aIncidence of and risk factors for atrial fibrillation in older adults.0 aIncidence of and risk factors for atrial fibrillation in older a c1997 Oct 07 a2455-610 v963 aBACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up.
METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF.
CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.
10aAdult10aAged10aAtrial Fibrillation10aBlood Glucose10aBlood Pressure10aCerebrovascular Disorders10aCohort Studies10aCoronary Disease10aElectrocardiography10aFemale10aFollow-Up Studies10aHospital Records10aHumans10aIncidence10aMale10aProspective Studies10aRisk Factors10aUnited States1 aPsaty, B M1 aManolio, T A1 aKuller, L H1 aKronmal, R, A1 aCushman, M1 aFried, L P1 aWhite, R1 aFurberg, C D1 aRautaharju, P, M uhttps://chs-nhlbi.org/node/148802876nas a2200361 4500008004100000022001400041245015100055210006900206260001300275300001000288490000800298520184500306653000902151653001002160653002802170653002402198653001902222653001102241653001102252653002502263653003102288653000902319653001502328100001602343700001602359700001702375700001702392700001902409700001802428700001502446700001702461856003602478 1997 eng d a0033-841900aInfarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study.0 aInfarctlike lesions in the brain prevalence and anatomic charact c1997 Jan a47-540 v2023 aPURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images.
MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images.
RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1% (86 of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of lesions, respectively.
CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.
10aAged10aBrain10aCardiovascular Diseases10aCerebral Infarction10aCohort Studies10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aPrevalence1 aBryan, R, N1 aWells, S, W1 aMiller, T, J1 aElster, A, D1 aJungreis, C, A1 aPoirier, V, C1 aLind, B, K1 aManolio, T A uhttps://chs-nhlbi.org/node/147102746nas a2200385 4500008004100000022001400041245006700055210006600122260001300188300001100201490000700212520176100219653001001980653000901990653002201999653001402021653003002035653001102065653001102076653001402087653000902101653001602110653002602126653001702152100001602169700001602185700002002201700001702221700001702238700001502255700001902270700001702289700001802306856003602324 1997 eng d a0039-249900aKnowledge of risk among patients at increased risk for stroke.0 aKnowledge of risk among patients at increased risk for stroke c1997 May a916-210 v283 aBACKGROUND AND PURPOSE: Patients who recognize their increased risk for stroke are more likely to engage in (and comply with) stroke prevention practices than those who do not. We describe perceived risk of stroke among a nationally diverse sample of patients at increased risk for stroke and determine whether patients' knowledge of their stroke risk varied according to patients' demographic and clinical characteristics.
METHODS: Respondents were recruited from the Academic Medical Center Consortium (n = 621, five academic medical centers, inpatients of varying age); the Cardiovascular Health Study (n = 321, population-based sample of persons aged 65+ years); and United HealthCare (n = 319, five health plans, inpatients and outpatients typically younger than 65 years). The primary outcome was awareness of being at risk for stroke.
RESULTS: Only 41% of respondents were aware of their increased risk for stroke (including less than one half of patients with previous minor stroke). Approximately 74% of patients who recalled being told of their increased stroke risk by a physician acknowledged this risk in comparison with 28% of patients who did not recall being informed by a physician. Younger patients, depressed patients, those in poor current health, and those with a history of TIA were most likely to be aware of their stroke risk.
CONCLUSIONS: Over one half of patients at increased risk of stroke are unaware of their risk. Healthcare providers play a crucial role in communicating information about risk, and successful communication encourages adoption of stroke prevention practices. Educational messages should be targeted toward patients least likely to be aware of their risk.
10aAdult10aAged10aAged, 80 and over10aAwareness10aCerebrovascular Disorders10aFemale10aHumans10aKnowledge10aMale10aMiddle Aged10aMultivariate Analysis10aRisk Factors1 aSamsa, G, P1 aCohen, S, J1 aGoldstein, L, B1 aBonito, A, J1 aDuncan, P, W1 aEnarson, C1 aDeFriese, G, H1 aHorner, R, D1 aMatchar, D, B uhttps://chs-nhlbi.org/node/148103691nas a2200409 4500008004100000022001400041245007500055210006900130260001300199300001300212490000700225520259400232653000902826653002202835653001902857653001602876653002802892653001902920653002102939653001102960653001102971653003402982653000903016653002403025653001703049653003103066100001603097700001403113700002003127700001503147700001503162700002303177700001703200700001303217700001503230856003603245 1997 eng d a0194-911X00aLeft ventricular mass in the elderly. The Cardiovascular Health Study.0 aLeft ventricular mass in the elderly The Cardiovascular Health S c1997 May a1095-1030 v293 aLeft ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.
10aAged10aAged, 80 and over10aBlood Pressure10aBody Weight10aCardiovascular Diseases10aCohort Studies10aEchocardiography10aFemale10aHumans10aHypertrophy, Left Ventricular10aMale10aProspective Studies10aRisk Factors10aVentricular Function, Left1 aGardin, J M1 aArnold, A1 aGottdiener, J S1 aWong, N, D1 aFried, L P1 aKlopfenstein, H, S1 aO'Leary, D H1 aTracy, R1 aKronmal, R uhttps://chs-nhlbi.org/node/148003130nas a2200337 4500008004100000022001400041245017000055210006900225260001300294300001200307490000700319520215600326653000902482653002002491653002302511653002802534653001102562653001102573653000902584653002602593653001702619653001202636100001502648700001502663700001202678700001702690700001502707700001802722700001602740856003602756 1997 eng d a1079-564200aLifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects.0 aLifetime smoking exposure affects the association of Creactive p c1997 Oct a2167-760 v173 aBlood levels of C-reactive protein (CRP), a marker of inflammation, are related to cardiovascular disease risk. To determine cross-sectional correlates in the elderly, we measured CRP in 400 men and women older than 65 years and free of clinical cardiovascular disease at baseline as part of the Cardiovascular Health Study. Only 2% of the values were greater than 10 mg/L, the cut-point usually used to identify inflammation. CRP levels appeared tightly regulated, since there were strong bivariate correlations between CRP and the following: inflammation-sensitive proteins such as fibrinogen (r = .52); measures of fibrinolysis such as plasmin-antiplasmin complex (r = .23); pack-years of smoking (r = .30); and body mass index (r = .24; all P values < or = .001). The association with pack-years was independent of the length of time since cessation of smoking. CRP levels were also associated with coagulation factors VIIc, IXc, and Xc; HDL cholesterol (negative) and triglyceride; diabetes status; diuretic use; ECG abnormalities; and level of exercise. Because of effect modification, two multiple linear regression prediction models were developed for CRP, one each for never smokers and ever smokers. An a priori physiologic model was used to guide these analyses, which disallowed the use of other inflammation-sensitive variables such as fibrinogen. In never smokers, the independent predictors were body mass index (+), diabetes status (+), plasmin-antiplasmin complex (+), and the presence of ECG abnormalities (+); this model predicted 15% of the CRP population variance. In ever smokers, the predictors were body mass index (+), plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL cholesterol (-), and ankle-arm blood pressure index (-); this model predicted 42% of the population variance. We conclude that levels of CRP in the healthy elderly are tightly regulated and reflect lifetime exposure to smoking as well as level of obesity, ongoing level of fibrinolysis, diabetes status, and level of subclinical atherothrombotic disease. Moreover, exposure to smoking affects the relation of CRP to these other factors.
10aAged10aBody Mass Index10aC-Reactive Protein10aCardiovascular Diseases10aFemale10aHumans10aMale10aMultivariate Analysis10aRisk Factors10aSmoking1 aTracy, R P1 aPsaty, B M1 aMacy, E1 aBovill, E, G1 aCushman, M1 aCornell, E, S1 aKuller, L H uhttps://chs-nhlbi.org/node/149002836nas a2200481 4500008004100000022001400041245005800055210005700113260001700170300001000187490000700197520157700204653003101781653000901812653002201821653002501843653001501868653002501883653002801908653002501936653001301961653001101974653002001985653001802005653001902023653001102042653003002053653001502083653002002098653000902118653001502127653003102142653001402173653001902187653001202206653001802218100001702236700001702253700001402270700001702284700001702301856003602318 1997 eng d a0091-743500aPreventive health behaviors among spousal caregivers.0 aPreventive health behaviors among spousal caregivers c1997 Mar-Apr a162-90 v263 aBACKGROUND: The physical and emotional burden of caring for a functionally impaired spouse may adversely affect the preventive health behavior of the caregiver. This study explores the relationship between caregiving and lifestyle health behaviors and use of preventive services.
METHODS: The Caregiver Health Effects Study identified spousal caregivers among a sample of more than 3,000 married, community-dwelling older persons, from four counties in the United States, who were enrollees in the Cardiovascular Health Study. High-level caregivers were defined as having a spouse with an ADL impairment (n = 212) and moderate-level caregivers, a spouse with one or more IADL impairments (n = 222). For each caregiver, a control, matched for age and gender, was selected (n = 385). Structured interviews were conducted in the home, following enrollment.
RESULTS: Being a high-level caregiver significantly increased the odds of not getting enough rest, not having enough time to exercise, not having time to rest to recuperate from illness, and forgetting to take prescription medications, compared with noncaregivers. These findings did not hold for moderate-level caregivers. The odds were not significantly different for either level of caregiver compared with noncaregivers for missing meals, missing doctor appointments, missing flu shots, and not refilling medications. Larger proportions of caregivers with a strong sense of control had good preventive health behaviors, compared with caregivers with a weak sense of control.
10aActivities of Daily Living10aAged10aAged, 80 and over10aAnalysis of Variance10aCaregivers10aCase-Control Studies10aChi-Square Distribution10aConfidence Intervals10aExercise10aFemale10aHealth Behavior10aHealth Status10aHealth Surveys10aHumans10aInternal-External Control10aLife Style10aLogistic Models10aMale10aOdds Ratio10aPreventive Health Services10aSelf Care10aSocial Support10aSpouses10aUnited States1 aBurton, L, C1 aNewsom, J, T1 aSchulz, R1 aHirsch, C, H1 aGerman, P, S uhttps://chs-nhlbi.org/node/147702957nas a2200349 4500008004100000022001400041245017400055210006900229260001300298300001100311490000700322520194700329653000902276653001002285653002302295653002802318653002502346653001102371653001102382653000902393653002402402653001602426100001502442700001902457700001502476700001502491700001602506700001502522700001802537700001602555856003602571 1997 eng d a1079-564200aRelationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project.0 aRelationship of Creactive protein to risk of cardiovascular dise c1997 Jun a1121-70 v173 aMarkers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.
10aAged10aAging10aC-Reactive Protein10aCardiovascular Diseases10aCase-Control Studies10aFemale10aHumans10aMale10aProspective Studies10aSex Factors1 aTracy, R P1 aLemaitre, R, N1 aPsaty, B M1 aIves, D, G1 aEvans, R, W1 aCushman, M1 aMeilahn, E, N1 aKuller, L H uhttps://chs-nhlbi.org/node/148402781nas a2200337 4500008004100000022001400041245019200055210006900247260001300316300001200329490000700341520176600348653000902114653002202123653002402145653001402169653001102183653001102194653003102205653000902236653002702245100001602272700001702288700001802305700001802323700001402341700001502355700002002370700001702390856003602407 1997 eng d a0039-249900aSilent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.0 aSilent brain infarction on magnetic resonance imaging and neurol c1997 Jun a1158-640 v283 aBACKGROUND AND PURPOSE: Infarctlike lesions are frequently detected in symptomatic and asymptomatic older persons undergoing cerebral MRI, but their significance in older adults has not been examined. We determined the prevalence of MRI infarcts in a population-based sample of men and women aged > or = 65 years and related these findings to demographic, cognitive, and neurological status.
METHODS: MRI scanning was performed in 3660 Cardiovascular Health Study (CHS) participants after brief neurological examinations and tests of cognitive function. MRIs were read centrally for the presence of an infarct > or = 3 mm in diameter or smaller infarctlike lesions.
RESULTS: MRI infarcts were detected in 1131 of 3647 participants with readable infarct information (31%) and in 961 of the subgroup of 3397 participants (28%) without known prior stroke ("silent" MRI infarcts). Smaller infarctlike lesions were found in 196 of 2516 participants who had no MRI infarcts > or = 3 mm. MRI infarcts were more common in participants who were older, had prior stroke, impaired cognition, visual field deficits, slowed repetitive finger tapping (all P < .0001), weakness on toe and heel walking, and history of memory loss, coma, or migraine headaches. Multivariate analysis in those without prior stroke showed strong associations of silent MRI infarcts with older age, history of migraines, lower digit symbol scores, and more abnormalities on neurological examination.
CONCLUSIONS: MRI evidence of brain infarction is common in older men and women without a clinical history of stroke. Their strong associations with impaired cognition and neurological deficits suggest that they are neither silent nor innocuous.
10aAged10aAged, 80 and over10aCerebral Infarction10aCognition10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aNeurologic Examination1 aPrice, T, R1 aManolio, T A1 aKronmal, R, A1 aKittner, S, J1 aYue, N, C1 aRobbins, J1 aAnton-Culver, H1 aO'Leary, D H uhttps://chs-nhlbi.org/node/148303373nas a2200421 4500008004100000022001400041245013000055210006900185260001300254300000800267490000700275520218600282653000902468653002202477653002802499653002802527653001502555653001102570653002502581653001902606653001102625653000902636653001502645653002302660653002202683653001702705653001602722653002502738653001902763653003102782653001802813100001702831700001802848700001702866700001802883700001402901856003602915 1997 eng d a0002-861400aSleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study.0 aSleep disturbance psychosocial correlates and cardiovascular dis c1997 Jan a1-70 v453 aOBJECTIVES: To describe the prevalence of self reported sleep disturbances in older men and women and to describe their relationships with health status and cardiovascular disease (CVD).
DESIGN: Cross-sectional study of sleep disturbance, CVD, general health, psychosocial factors, physical function, and use of psychotropic medications.
SETTING: Participants of the Cardiovascular Health Study, 5201 adults aged 65 and older recruited from a random sample of noninstitutionalized Medicare enrollees in four US communities.
MEASURES: Self-reported sleep disturbances and standardized questionnaires for cardiopulmonary symptoms and diseases, depression, social support, activities of daily living, physical activity, cognitive function, and current medications, spirometry, ECG, echocardiography, and carotid ultrasound.
RESULTS: Women were twice as likely as men to report difficulty falling asleep (30% vs 14%). Daytime sleepiness, difficulty falling asleep, and frequent awakenings increased in prevalence with age. All symptoms were related strongly to depression. Symptoms of daytime sleepiness were also related strongly to poor health and limitations in activities of daily living in men and women. In multivariate analysis, men taking benzodiazepines were likely to report difficulty falling asleep and daytime sleepiness, whereas women taking benzodiazepines reported difficulty falling asleep and waking up too early. After accounting for these factors, the only cardiovascular disease independently associated with sleep disturbances was angina. Men and women with confirmed angina were 1.6 times more likely to report trouble falling asleep. Independent relationships between sleep disturbances and cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes were relatively weak and inconsistent, though smokers were less likely to report frequent awakenings.
CONCLUSIONS: Sleep disturbances are relatively common in older men and women and are associated with poor health, depression, angina, limitations in activities of daily living, and the use of benzodiazepines.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCross-Sectional Studies10aDepression10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aMale10aPrevalence10aPsychotropic Drugs10aRandom Allocation10aRisk Factors10aSex Factors10aSleep Wake Disorders10aSocial Support10aSurveys and Questionnaires10aUnited States1 aNewman, A, B1 aEnright, P, L1 aManolio, T A1 aHaponik, E, F1 aWahl, P W uhttps://chs-nhlbi.org/node/147302729nas a2200469 4500008004100000022001400041245006600055210005800121260001300179300001200192490000700204520152300211653001001734653000901744653002201753653002101775653001901796653002101815653001101836653001101847653001701858653002501875653000901900653001601909653002001925653003401945653002401979653002002003653002602023100001502049700001702064700001202081700001602093700001602109700001902125700001902144700001502163700001502178700001602193700001402209856003602223 1997 eng d a0161-810500aThe Sleep Heart Health Study: design, rationale, and methods.0 aSleep Heart Health Study design rationale and methods c1997 Dec a1077-850 v203 aThe Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.
10aAdult10aAged10aAged, 80 and over10aArteriosclerosis10aCohort Studies10aCoronary Disease10aFemale10aHumans10aHypertension10aLongitudinal Studies10aMale10aMiddle Aged10aPolysomnography10aPositive-Pressure Respiration10aProspective Studies10aResearch Design10aSleep Apnea Syndromes1 aQuan, S, F1 aHoward, B, V1 aIber, C1 aKiley, J, P1 aNieto, F, J1 aO'Connor, G, T1 aRapoport, D, M1 aRedline, S1 aRobbins, J1 aSamet, J, M1 aWahl, P W uhttps://chs-nhlbi.org/node/149902375nas a2200409 4500008004100000022001400041245012700055210006900182260001300251300000900264490000800273520122000281653000901501653002201510653001001532653001001542653002801552653002401580653001901604653003401623653001101657653001101668653002501679653003101704653000901735653003101744653001601775100001401791700001701805700002001822700001701842700001901859700001701878700001801895700001601913856003601929 1997 eng d a0033-841900aSulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.0 aSulcal ventricular and white matter changes at MR imaging in the c1997 Jan a33-90 v2023 aPURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex.
MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex.
RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race.
CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.
10aAged10aAged, 80 and over10aAging10aBrain10aCardiovascular Diseases10aCerebral Ventricles10aCohort Studies10aContinental Population Groups10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aReproducibility of Results10aSex Factors1 aYue, N, C1 aArnold, A, M1 aLongstreth, W T1 aElster, A, D1 aJungreis, C, A1 aO'Leary, D H1 aPoirier, V, C1 aBryan, R, N uhttps://chs-nhlbi.org/node/146903026nas a2200325 4500008004100000022001400041245008700055210006900142260001600211300001200227490000700239520212700246653001602373653000902389653002102398653002902419653001902448653001402467653001102481653001102492653001802503653003202521653001702553100002202570700001702592700001702609700001802626700002002644856003602664 1997 eng d a0008-543X00aUse of calcium channel blockers and breast carcinoma risk in postmenopausal women.0 aUse of calcium channel blockers and breast carcinoma risk in pos c1997 Oct 15 a1438-470 v803 aBACKGROUND: The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age > or = 65 years.
METHODS: Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers.
RESULTS: In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08).
CONCLUSIONS: Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers.
10aAge Factors10aAged10aBreast Neoplasms10aCalcium Channel Blockers10aCohort Studies10aEstrogens10aFemale10aHumans10aPostmenopause10aProportional Hazards Models10aRisk Factors1 aFitzpatrick, A, L1 aDaling, J, R1 aFurberg, C D1 aKronmal, R, A1 aWeissfeld, J, L uhttps://chs-nhlbi.org/node/148903216nas a2200421 4500008004100000022001400041245010600055210006900161260001300230300001100243490000700254520204600261653000902307653001202316653001902328653002802347653002402375653003002399653001902429653003002448653003702478653001102515653002202526653001102548653001402559653000902573653002402582653001702606653001602623653001702639100001802656700001502674700001702689700001802706700002002724700001402744856003602758 1998 eng d a0039-249900aAspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group.0 aAspirin use and incident stroke in the cardiovascular health stu c1998 May a887-940 v293 aBACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study.
METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years.
RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003).
CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.
10aAged10aAspirin10aBrain Ischemia10aCardiovascular Diseases10aCerebral Hemorrhage10aCerebrovascular Disorders10aCohort Studies10aCyclooxygenase Inhibitors10aDose-Response Relationship, Drug10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aRegression Analysis10aRisk Factors10aSex Factors10aTime Factors1 aKronmal, R, A1 aHart, R, G1 aManolio, T A1 aTalbert, R, L1 aBeauchamp, N, J1 aNewman, A uhttps://chs-nhlbi.org/node/150402708nas a2200361 4500008004100000022001400041245015500055210006900210260001300279300001100292490000700303520165900310653000901969653002401978653002902002653002102031653003002052653001902082653001102101653001102112653000902123653001502132653001702147653001202164653002902176100002002205700001702225700001702242700001702259700001602276700001802292856003602310 1998 eng d a0039-249900aAsymptomatic internal carotid artery stenosis defined by ultrasound and the risk of subsequent stroke in the elderly. The Cardiovascular Health Study.0 aAsymptomatic internal carotid artery stenosis defined by ultraso c1998 Nov a2371-60 v293 aBACKGROUND AND PURPOSE: We sought in this study to relate carotid ultrasound findings in asymptomatic older adults to the 5-year risk of various cerebrovascular outcomes used in the Asymptomatic Carotid Atherosclerosis Study (ACAS).
METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years and older. Analyses of internal carotid artery stenosis defined by multiple different cutoffs of peak systolic velocity, rather than one particular cutoff, were performed in the 5441 participants who underwent carotid ultrasound and lacked a history of transient ischemic attack or stroke. The 5-year risks of 7 cerebrovascular disease outcomes used in ACAS were estimated for each cutoff.
RESULTS: Associations with the 5-year risk of outcomes were substantially elevated only at cutoffs with high peak systolic velocities. In this population, the number of people with such high velocities was small. For example, with a cutoff of approximately 2.5 m/s, suggesting a stenosis of >70%, the 5-year risk of an ipsilateral fatal or nonfatal stroke was 5%, and only 0.5% of the group had velocities at least this high.
CONCLUSIONS: In a group of older adults likely to participate in a screening program, as evidenced by willingness to participate in CHS, high peak systolic velocities consistent with high-grade carotid stenosis were uncommon and risk of subsequent cerebrovascular disease outcomes was relatively low. These findings do not suggest that similar populations of older adults would benefit from a program using ultrasound to screen for asymptomatic carotid stenosis.
10aAged10aBlood Flow Velocity10aCarotid Artery, Internal10aCarotid Stenosis10aCerebrovascular Disorders10aCohort Studies10aFemale10aHumans10aMale10aPrevalence10aRisk Factors10aSystole10aUltrasonography, Doppler1 aLongstreth, W T1 aShemanski, L1 aLefkowitz, D1 aO'Leary, D H1 aPolak, J, F1 aWolfson, S, K uhttps://chs-nhlbi.org/node/151702255nas a2200421 4500008004100000022001400041245009500055210006900150260001300219300001000232490000700242520114200249653002101391653000901412653002001421653002801441653001901469653001901488653001101507653001101518653002001529653000901549653001401558653003001572653001701602653002101619653001201640653002201652653001801674653001601692100001301708700001501721700001601736700001501752700001701767700001301784856003601797 1998 eng d a0090-003600aBody mass index and mortality in nonsmoking older adults: the Cardiovascular Health Study.0 aBody mass index and mortality in nonsmoking older adults the Car c1998 Apr a623-90 v883 aOBJECTIVES: This study assesses the relationship of body mass index to 5-year mortality in a cohort of 4317 nonsmoking men and women aged 65 to 100 years.
METHODS: Logistic regression analyses were conducted to predict mortality as a function of baseline body mass index, adjusting for demographic, clinical, and laboratory covariates.
RESULTS: There was an inverse relationship between body mass index and mortality; death rates were higher for those who weighed the least. Inclusion of covariates had trivial effects on these results. People who had lost 10% or more of their body weight since age 50 had a relatively high death rate. When that group was excluded, there was no remaining relationship between body mass index and mortality.
CONCLUSIONS: The association between higher body mass index and mortality often found in middle-aged populations was not observed in this large cohort of older adults. Over-weight does not seem to be a risk factor for 5-year mortality in this age group. Rather, the risks associated with significant weight loss should be the primary concern.
10aAge Distribution10aAged10aBody Mass Index10aCardiovascular Diseases10aCause of Death10aCohort Studies10aFemale10aHumans10aLogistic Models10aMale10aMortality10aPredictive Value of Tests10aRisk Factors10aSex Distribution10aSmoking10aSurvival Analysis10aUnited States10aWeight Loss1 aDiehr, P1 aBild, D, E1 aHarris, T B1 aDuxbury, A1 aSiscovick, D1 aRossi, M uhttps://chs-nhlbi.org/node/150201909nas a2200361 4500008004100000022001400041245008500055210006900140260001300209300001100222490000700233520091800240653003101158653000901189653001501198653002001213653001501233653002101248653003301269653001101302653002101313653001101334653003001345653002501375653000901400653002401409653001701433653001201450653001801462100001701480700001401497856003601511 1998 eng d a0278-613300aCaregiving from the recipient's perspective: negative reactions to being helped.0 aCaregiving from the recipients perspective negative reactions to c1998 Mar a172-810 v173 aThis study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.
10aActivities of Daily Living10aAged10aCaregivers10aChronic Disease10aDepression10aDisabled Persons10aFactor Analysis, Statistical10aFemale10aHelping Behavior10aHumans10aInternal-External Control10aLongitudinal Studies10aMale10aRegression Analysis10aSelf Concept10aSpouses10aUnited States1 aNewsom, J, T1 aSchulz, R uhttps://chs-nhlbi.org/node/150103022nas a2200337 4500008004100000022001400041245008300055210006900138260001300207300001100220490000700231520210300238653000902341653002202350653002002372653002802392653002102420653001102441653001102452653000902463653003502472653002602507100001802533700001402551700001502565700001702580700001802597700001802615700001502633856003602648 1998 eng d a0884-873400aCorrelates and prevalence of benzodiazepine use in community-dwelling elderly.0 aCorrelates and prevalence of benzodiazepine use in communitydwel c1998 Apr a243-500 v133 aOBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older.
DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study.
PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria.
MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7).
CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.
10aAged10aAged, 80 and over10aBenzodiazepines10aCross-Sectional Studies10aDrug Utilization10aFemale10aHumans10aMale10aPractice Patterns, Physicians'10aSocioeconomic Factors1 aGleason, P, P1 aSchulz, R1 aSmith, N L1 aNewsom, J, T1 aKroboth, P, D1 aKroboth, F, J1 aPsaty, B M uhttps://chs-nhlbi.org/node/150302969nas a2200457 4500008004100000022001400041245009200055210006900147260001300216300001000229490000700239520177600246653000902022653002202031653002502053653001902078653002102097653001502118653002802133653002702161653001102188653001102199653001702210653000902227653001502236653001402251653001402265653002102279653001702300653001502317100001902332700001502351700001502366700001602381700001602397700002002413700001502433700001202448700001502460856003602475 1998 eng d a0340-624500aCorrelates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.0 aCorrelates of antithrombin protein C protein S and TFPI in a hea c1998 Jul a134-90 v803 aThe majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.
10aAged10aAged, 80 and over10aAnalysis of Variance10aAnticoagulants10aAntithrombin III10aBiomarkers10aCross-Sectional Studies10aDisease Susceptibility10aFemale10aHumans10aLipoproteins10aMale10aPrevalence10aProtein C10aProtein S10aReference Values10aRisk Factors10aThrombosis1 aSakkinen, P, A1 aCushman, M1 aPsaty, B M1 aKuller, L H1 aBajaj, S, P1 aSabharwal, A, K1 aBoineau, R1 aMacy, E1 aTracy, R P uhttps://chs-nhlbi.org/node/157003916nas a2200469 4500008004100000022001400041245009500055210006900150260000900219300001000228490000700238520259600245653003102841653002102872653000902893653002202902653001002924653002802934653002102962653002402983653001903007653003403026653002803060653003803088653002403126653001103150653001803161653001903179653001103198653003103209653000903240653002903249653001503278653002103293100001803314700001803332700001703350700001503367700001303382700001503395856003603410 1998 eng d a0161-810500aCorrelates of daytime sleepiness in 4578 elderly persons: the Cardiovascular Health Study.0 aCorrelates of daytime sleepiness in 4578 elderly persons the Car c1998 a27-360 v213 aOBJECTIVES: To describe the prevalence of self-reported daytime sleepiness in older men and women and to describe their relationships with demographic factors, nocturnal complaints, health status, and cardiovascular diseases (CVD).
DESIGN: Cross-sectional survey and clinical exam.
SETTING: Participants in the Cardiovascular Health Study, 4578 adults aged 65 and older, recruited from a random sample of non-institutionalized Medicare enrollees in four U.S. communities.
MEASURES: Daytime sleepiness measured by the Epworth Sleepiness Scale (ESS), magnetic resonance imaging of the brain (MRI), cognitive function tests, and standardized questionnaires for cardiopulmonary symptoms and diseases, depressive symptoms, social support, activities of daily living, physical activity, and current medications.
RESULTS: Approximately 20% of the participants reported that they were "usually sleepy in the daytime". Although elderly black men were less likely to report frequent awakenings than those in the other three race and gender groups, they had significantly higher mean ESS scores. The following were independently associated with higher ESS scores in gender-specific models: non-white race, depression, loud snoring, awakening with dyspnea or snorting, frequent nocturnal awakenings, medications used to treat congestive heart failure, non-use of sleeping pills, a sedentary lifestyle, and limitation of activities of daily living in both men and women; additional correlates included hip circumference and current smoking in men, and hayfever in women. The following were not independently associated with ESS in the models: age, education, use of wine or beer to aid sleep, use of tricyclic antidepressants, long- or short-acting benzodiazepines, asthma, angina, myocardial infarction, congestive heart failure itself, forced vital capacity, social support, cognitive function, or MRI evidence of global brain atrophy or white matter abnormality.
CONCLUSIONS: Daytime sleepiness is common in the elderly, probably due to nocturnal disturbances such as frequent awakenings and snoring. The occasional use of sleeping pills for insomnia is associated with reduced daytime sleepiness in the elderly, while the use of medications for congestive heart failure is associated with daytime sleepiness. Surprisingly, anatomic abnormalities such as evidence of previous strokes and brain atrophy (as seen on brain MRI scans) were not associated with daytime sleepiness in these non-institutionalized elderly persons.
10aActivities of Daily Living10aAge Distribution10aAged10aAged, 80 and over10aBrain10aCardiovascular Diseases10aCircadian Rhythm10aCognition Disorders10aCohort Studies10aContinental Population Groups10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aElectrocardiography10aFemale10aHealth Status10aHealth Surveys10aHumans10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aPrevalence10aSex Distribution1 aWhitney, C, W1 aEnright, P, L1 aNewman, A, B1 aBonekat, W1 aFoley, D1 aQuan, S, F uhttps://chs-nhlbi.org/node/149702980nas a2200349 4500008004100000022001400041245014500055210006900200260001600269300001100285490000800296520197300304653002202277653000902299653002202308653001902330653002202349653001102371653002702382653001102409653000902420653001502429653002302444653003002467100001402497700001702511700001502528700001802543700001802561700001502579856003602594 1998 eng d a0140-673600aDiabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification.0 aDiabetes in older adults comparison of 1997 American Diabetes As c1998 Sep 26 a1012-50 v3523 aBACKGROUND: We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people.
METHODS: We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93.
FINDINGS: In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001).
INTERPRETATION: Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose-tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications.
10aAfrican Americans10aAged10aAged, 80 and over10aCohort Studies10aDiabetes Mellitus10aFemale10aGlucose Tolerance Test10aHumans10aMale10aPrevalence10aSocieties, Medical10aWorld Health Organization1 aWahl, P W1 aSavage, P, J1 aPsaty, B M1 aOrchard, T, J1 aRobbins, J, A1 aTracy, R P uhttps://chs-nhlbi.org/node/151502651nas a2200385 4500008004100000022001400041245015400055210006900209260001300278300001100291490000700302520153000309653002201839653000901861653004301870653001901913653004001932653001101972653001801983653001102001653000902012653002602021653001502047653002402062653001702086653002202103100001402125700001402139700001802153700001302171700001502184700001502199700001502214856003602229 1998 eng d a1079-564200aDifferences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study.0 aDifferences in prevalence of and risk factors for subclinical va c1998 Feb a283-930 v183 aA composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.
10aAfrican Americans10aAged10aCardiovascular Physiological Phenomena10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHealth Status10aHumans10aMale10aMultivariate Analysis10aPrevalence10aRegression Analysis10aRisk Factors10aVascular Diseases1 aKuller, L1 aFisher, L1 aMcClelland, R1 aFried, L1 aCushman, M1 aJackson, S1 aManolio, T uhttps://chs-nhlbi.org/node/149601777nas a2200361 4500008004100000022001400041245013300055210006900188260001300257300001000270490000700280520082700287653001001114653001601124653000901140653001301149653001301162653001101175653001101186653000901197653001601206653001301222653001701235653001501252100001501267700002001282700001501302700001501317700001601332700001601348700001501364856003601379 1998 eng d a0340-624500aFactor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study.0 aFactor V Leiden is not a risk factor for arterial vascular disea c1998 May a912-50 v793 aCoagulation factor V Leiden is a risk marker for venous thrombosis. For arterial thrombosis no large study to date has included population-based elderly patients. The Cardiovascular Health Study is a longitudinal study of 5,201 men and women over age 65. With 3.4-year follow-up, we studied 373 incident cases of myocardial infarction (MI), angina, stroke. or transient ischemic attack (TIA), and 482 controls. The odds ratios for each event with heterozygous factor V Leiden were: MI, 0.46 (95% CI 0.17 to 1.25); angina, 1.0 (95% CI 0.45 to 2.23); stroke, 0.77 (95% CI 0.35 to 1.70): TIA, 1.33 (95% CI 0.5 to 3.55); any outcome, 0.83 (95% CI 0.48 to 1.44). Adjustment for cardiovascular risk factors did not change relationships. In older adults factor V Leiden is not a risk factor for future arterial thrombosis.
10aAdult10aAge Factors10aAged10aArteries10aFactor V10aFemale10aHumans10aMale10aMiddle Aged10aMutation10aRisk Factors10aThrombosis1 aCushman, M1 aRosendaal, F, R1 aPsaty, B M1 aCook, E, F1 aValliere, J1 aKuller, L H1 aTracy, R P uhttps://chs-nhlbi.org/node/150802604nas a2200397 4500008004100000022001400041245012700055210006900182260001300251300001100264490000700275520149800282653001901780653000901799653002201808653002101830653002801851653002601879653001101905653002501916653001901941653001101960653000901971653001201980653003001992653001202022100001402034700001602048700001902064700001702083700001802100700001502118700002102133700001602154856003602170 1998 eng d a0002-916500aHigh body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study.0 aHigh body fatness but not low fatfree mass predicts disability i c1998 Sep a584-900 v683 aUsing data from the Cardiovascular Health Study, we studied the relation between body composition (fat mass and fat-free mass, assessed by bioelectrical impedance) and self-reported, mobility-related disability (difficulty walking or stair climbing) in 2714 women and 2095 men aged 65-100 y. In a cross-sectional analysis at baseline (1989-1990), disability was reported by 26.5% of the women and 16.9% of the men. A positive association was observed between fat mass and disability. The odds ratio for disability in the highest quintile of fat mass was 3.04 (95% CI: 2.18, 4.25) for women and 2.77 (95% CI: 1.82, 4.23) for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. In a longitudinal analysis among persons not reporting disability at baseline, 20.3% of the women and 14.8% of the men reported disability 3 y later. Fat mass at baseline was predictive of disability 3 y later, with odds ratios of 2.83 (95% CI: 1.80, 4.46) for women and 1.72 (95% CI: 1.03, 2.85) for men in the highest quintile of fat. The increased risk was not explained by age, physical activity, chronic disease, or other potential confounders. Low fat-free mass was not predictive of disability. The results showed that high body fatness is an independent predictor of mobility-related disability in older men and women. These findings suggest that high body fatness in old age should be avoided to decrease the risk of disability.
10aAdipose Tissue10aAged10aAged, 80 and over10aBody Composition10aCross-Sectional Studies10aDisability Evaluation10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aMale10aObesity10aPredictive Value of Tests10aWalking1 aVisser, M1 aLanglois, J1 aGuralnik, J, M1 aCauley, J, A1 aKronmal, R, A1 aRobbins, J1 aWilliamson, J, D1 aHarris, T B uhttps://chs-nhlbi.org/node/151202829nas a2200397 4500008004100000022001400041245016100055210006900216260001300285300001100298490000800309520163400317653000901951653002201960653002901982653002102011653003002032653001902062653001102081653001102092653003402103653000902137653003202146653000902178653003702187653004302224100001602267700001702283700001702300700001702317700001602334700001702350700001602367700001202383856003602395 1998 eng d a0033-841900aHypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study.0 aHypoechoic plaque at US of the carotid artery an independent ris c1998 Sep a649-540 v2083 aPURPOSE: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US).
MATERIALS AND METHODS: A cohort of 4, 886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk factors: age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressure, elevated low-density lipoprotein cholesterol level.
RESULTS: Incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1,42,4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (p = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36,5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28, 7.41) were associated with ipsilateral, nonfatal stroke.
CONCLUSION: In asymptomatic adults aged 65 years or older, that risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%.
10aAged10aAged, 80 and over10aCarotid Artery, Internal10aCarotid Stenosis10aCerebrovascular Disorders10aCohort Studies10aFemale10aHumans10aIntracranial Arteriosclerosis10aMale10aProportional Hazards Models10aRisk10aUltrasonography, Doppler, Duplex10aUltrasonography, Doppler, Transcranial1 aPolak, J, F1 aShemanski, L1 aO'Leary, D H1 aLefkowitz, D1 aPrice, T, R1 aSavage, P, J1 aBrant, W, E1 aReid, C uhttps://chs-nhlbi.org/node/151102759nas a2200313 4500008004100000022001400041245011600055210006900171260001300240300001200253490000700265520187400272653000902146653002402155653001102179653001102190653002502201653003102226653000902257653002602266653001702292100002002309700001502329700001702344700001302361700001902374700001602393856003602409 1998 eng d a0003-994200aLacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study.0 aLacunar infarcts defined by magnetic resonance imaging of 3660 e c1998 Sep a1217-250 v553 aOBJECTIVE: To identify risk factors for and functional consequences of lacunar infarct in elderly people.
METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings.
RESULTS: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts.
CONCLUSIONS: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.
10aAged10aCerebral Infarction10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMultivariate Analysis10aRisk Factors1 aLongstreth, W T1 aBernick, C1 aManolio, T A1 aBryan, N1 aJungreis, C, A1 aPrice, T, R uhttps://chs-nhlbi.org/node/151403226nas a2200397 4500008004100000022001400041245008800055210006900143260001600212300001100228490000700239520213100246653000902377653002202386653002502408653002402433653002802457653001902485653001302504653003002517653002402547653001102571653001802582653002102600653001102621653000902632653003102641100001602672700001702688700001502705700001602720700001502736700002302751700001802774856003602792 1998 eng d a0002-914900aLeft ventricular diastolic filling in the elderly: the cardiovascular health study.0 aLeft ventricular diastolic filling in the elderly the cardiovasc c1998 Aug 01 a345-510 v823 aChanges in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.
10aAged10aAged, 80 and over10aAnalysis of Variance10aBlood Flow Velocity10aCardiovascular Diseases10aCohort Studies10aDiastole10aEchocardiography, Doppler10aElectrocardiography10aFemale10aHealth Status10aHeart Ventricles10aHumans10aMale10aVentricular Function, Left1 aGardin, J M1 aArnold, A, M1 aBild, D, E1 aSmith, V, E1 aLima, J, A1 aKlopfenstein, H, S1 aKitzman, D, W uhttps://chs-nhlbi.org/node/151002031nas a2200361 4500008004100000022001400041245006200055210006100117260001300178300001100191490000700202520109800209653000901307653002201316653002601338653001101364653001601375653002101391653001801412653001101430653002001441653001601461653000901477653001601486653003201502653001601534100001301550700001801563700001501581700001601596700002101612856003601633 1998 eng d a0895-435600aPredicting future years of healthy life for older adults.0 aPredicting future years of healthy life for older adults c1998 Apr a343-530 v513 aCost-effectiveness studies often need to compare the cost of a program to the lifetime benefits of the program, but estimates of lifetime benefits are not routinely available, especially for older adults. We used data from two large longitudinal studies of older adults (ages 65-100) to estimate transition probabilities from one health state to another, and used those probabilities to estimate the mean additional years of healthy life that an older adult of specified age, sex, and health status would experience. We found, for example, that 65-year-old women in excellent health can expect 16.8 years of healthy life in the future, compared to only 8.5 years for women in poor health. We also provide estimates of discounted years of healthy life and future life expectancy. These estimates may be used to extend the effective length of the study period in cost-effectiveness studies, to examine the impact of chronic diseases or risk factors on years of healthy life, or to investigate the relationship of years of life to years of healthy life. Several applications are described.
10aAged10aAged, 80 and over10aCost-Benefit Analysis10aFemale10aForecasting10aHealth Promotion10aHealth Status10aHumans10aLife Expectancy10aLife Tables10aMale10aProbability10aQuality-Adjusted Life Years10aSex Factors1 aDiehr, P1 aPatrick, D, L1 aBild, D, E1 aBurke, G, L1 aWilliamson, J, D uhttps://chs-nhlbi.org/node/150003278nas a2200481 4500008004100000022001400041245010400055210006900159260001300228300001100241490000700252520195900259653003902218653000902257653002202266653001002288653002802298653002402326653001402350653002402364653004002388653001102428653001302439653001802452653001102470653003102481653000902512653002702521653003002548653001702578653001602595653001802611100001602629700001702645700001502662700001202677700001302689700001302702700001602715700001302731700001602744856003602760 1998 eng d a0039-249900aRelationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study.0 aRelationship between ApoE MRI findings and cognitive function in c1998 Feb a388-980 v293 aBACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores.
METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years.
RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]).
CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.
10aAfrican Continental Ancestry Group10aAged10aApolipoproteins E10aBrain10aCardiovascular Diseases10aCerebral Infarction10aCognition10aCognition Disorders10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aPolymerase Chain Reaction10aRisk Factors10aSex Factors10aUnited States1 aKuller, L H1 aShemanski, L1 aManolio, T1 aHaan, M1 aFried, L1 aBryan, N1 aBurke, G, L1 aTracy, R1 aBhadelia, R uhttps://chs-nhlbi.org/node/149402386nas a2200301 4500008004100000022001400041245010700055210006900162260001300231300000900244490000700253520156300260653002101823653000901844653001001853653002001863653001101883653001101894653003101905653000901936653002101945653001701966100001501983700002001998700001302018700001702031856003602048 1998 eng d a0003-994200aRelationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults.0 aRelationship between balance and abnormalities in cerebral magne c1998 Jan a73-90 v553 aBACKGROUND: Falling is a major cause of disability and morbidity among older adults. Because poor balance is a major reason for frequent falls, assessment of balance and its risk factors are important. In this study, we postulated that cerebral changes identified on magnetic resonance (MR) imaging are related to balance, and that older adults with balance problems would have significantly greater prevalence of such brain abnormalities than older adults without balance problems.
DESIGN AND MEASUREMENTS: Several measures of balance were examined in more than 700 community-dwelling older men and women, blacks and whites. Balance measures included dynamic posturography, functional reach, Romberg and 1-foot stand tests, tandem stand, and 1-foot stand. Cerebral MR imaging assessments included ventricular size, sulcal widening, white matter disease, and ischemic infarctions. Cardiovascular disease and hypertension were determined and controlled for in the analyses.
RESULTS: A summary of the balance measures was significantly related to each of the 4 MR imaging measures, with those with poorer balance having more disease. The strongest associations with balance were seen for white matter disease and ventricular size. All but the ischemic infarction variable remained significantly associated with balance after adjustments for sex, race, age, cardiovascular disease, and hypertension.
CONCLUSION: Cerebral changes identified by MR imaging are associated with poorer balance among older adults.
10aAccidental Falls10aAged10aAging10aCerebral Cortex10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aPostural Balance10aRisk Factors1 aTell, G, S1 aLefkowitz, D, S1 aDiehr, P1 aElster, A, D uhttps://chs-nhlbi.org/node/149203834nas a2200409 4500008004100000022001400041245008800055210006900143260001600212300001100228490000800239520272800247653002202975653000902997653002203006653002803028653001903056653001103075653002203086653001903108653001103127653000903138653001403147653003203161653002403193653001703217653001803234100001503252700001803267700001703285700001503302700002103317700001603338700001803354700001603372856003603388 1998 eng d a0098-748400aRisk factors for 5-year mortality in older adults: the Cardiovascular Health Study.0 aRisk factors for 5year mortality in older adults the Cardiovascu c1998 Feb 25 a585-920 v2793 aCONTEXT: Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known.
OBJECTIVE: To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older.
DESIGN: Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up.
SETTING: Four US communities.
PARTICIPANTS: A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively.
MAIN OUTCOME MEASURES: Five-year mortality.
RESULTS: In the main cohort, 646 deaths (12%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (< or = 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (< or = 37 g/L), elevated creatinine level (> or = 106 micromol/L [1.2 mg/dL]), low forced vital capacity (< or = 2.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohorts.
CONCLUSIONS: Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease.
10aAfrican Americans10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHealth Surveys10aHumans10aMale10aMortality10aProportional Hazards Models10aProspective Studies10aRisk Factors10aUnited States1 aFried, L P1 aKronmal, R, A1 aNewman, A, B1 aBild, D, E1 aMittelmark, M, B1 aPolak, J, F1 aRobbins, J, A1 aGardin, J M uhttps://chs-nhlbi.org/node/149801938nas a2200277 4500008004100000022001400041245011500055210006900170260001300239300001200252490000700264520116100271653000901432653001501441653001501456653001101471653001101482653000901493653002301502653001601525653002701541653002601568100001601594700001401610856003601624 1998 eng d a1079-501400aThe role of neuroticism and mastery in spouse caregivers' assessment of and response to a contextual stressor.0 arole of neuroticism and mastery in spouse caregivers assessment c1998 May aP155-640 v533 aData from more than 300 spousal caregivers and their care recipients were analyzed to demonstrate the effects of caregivers' personality attributes--neuroticism and mastery--on their assessment of a contextual stressor (the care recipient's behavioral and functional impairment) and on their experience of distress associated with that stressor. Caregivers who were high in neuroticism and/or low in mastery reported higher levels of behavioral and functional impairment in their disabled spouse and experienced more strain and depressive symptoms associated with caregiving relative to caregivers with lower neuroticism or higher mastery scores. We further showed that the widely reported association between caregiver-assessed impairment of the care recipient and caregiver outcomes can in part be explained by caregivers' personality attributes, such as neuroticism and mastery. Our findings that caregivers' personality variables are related to their assessment of a given objective stressor and their response to a given level of stress have implications for interventions targeting caregivers and for the use of caregivers as proxy informants.
10aAged10aCaregivers10aDepression10aFemale10aHumans10aMale10aNeurotic Disorders10aPersonality10aPersonality Assessment10aStress, Psychological1 aBookwala, J1 aSchulz, R uhttps://chs-nhlbi.org/node/150502583nas a2200409 4500008004100000022001400041245008500055210006900140260001300209300001100222490000700233520149400240653002101734653000901755653002201764653001001786653001201796653001001808653002401818653003301842653001101875653001801886653001101904653003101915653000901946653002401955653002401979653002102003100001702024700001602041700001702057700001602074700001702090700001402107700001602121856003602137 1998 eng d a0003-994200aSex differences in brain aging: a quantitative magnetic resonance imaging study.0 aSex differences in brain aging a quantitative magnetic resonance c1998 Feb a169-790 v553 aBACKGROUND: Little is known about the effect of sex on age-related changes in brain structure.
METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained.
RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex.
CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.
10aAge Distribution10aAged10aAged, 80 and over10aAging10aAtrophy10aBrain10aCerebrospinal Fluid10aDiagnosis, Computer-Assisted10aFemale10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aRegression Analysis10aSex Characteristics10aSex Distribution1 aCoffey, C, E1 aLucke, J, F1 aSaxton, J, A1 aRatcliff, G1 aUnitas, L, J1 aBillig, B1 aBryan, R, N uhttps://chs-nhlbi.org/node/149502912nas a2200337 4500008004100000022001400041245015700055210006900212260001600281300001200297490000800309520192700317653000902244653004502253653002102298653001102319653001802330653001102348653002002359653000902379653001802388653002202406653001802428100001502446700001502461700001202476700001202488700002002500700001802520856003602538 1998 eng d a0003-992600aTemporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.0 aTemporal patterns in the medical treatment of congestive heart f c1998 May 25 a1074-800 v1583 aBACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown.
METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed.
RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26% of prevalent CHF cases were treated in 1989-1990 compared with 36% of prevalent cases in 1994-1995. This 10% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were using ACE inhibitors. This 2% decrease was not statistically significant (P=.68).
CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.
10aAged10aAngiotensin-Converting Enzyme Inhibitors10aDrug Utilization10aFemale10aHeart Failure10aHumans10aLogistic Models10aMale10aStroke Volume10aTreatment Outcome10aUnited States1 aSmith, N L1 aPsaty, B M1 aPitt, B1 aGarg, R1 aGottdiener, J S1 aHeckbert, S R uhttps://chs-nhlbi.org/node/150703367nas a2200361 4500008004100000022001400041245010800055210006900163260001600232300001100248490000800259520237700267653000902644653002902653653002102682653001902703653001102722653001102733653002502744653000902769653001502778653001702793653001802810100001902828700001702847700001702864700001702881700001702898700002002915700001902935700001502954856003602969 1998 eng d a0003-992600aTime trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.0 aTime trends in the use of cholesterollowering agents in older ad c1998 Sep 14 a1761-80 v1583 aOBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older.
SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit.
RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy.
CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.
10aAged10aAnticholesteremic Agents10aCholesterol, LDL10aCohort Studies10aFemale10aHumans10aHypercholesterolemia10aMale10aPrevalence10aRisk Factors10aUnited States1 aLemaitre, R, N1 aFurberg, C D1 aNewman, A, B1 aHulley, S, B1 aGordon, D, J1 aGottdiener, J S1 aMcDonald, R, H1 aPsaty, B M uhttps://chs-nhlbi.org/node/151302285nas a2200445 4500008004100000022001400041245011300055210006900168260001300237300001100250490000800261520108000269653001001349653002101359653000901380653002201389653002301411653001101434653001801445653001101463653004101474653000901515653001601524653002001540653002101560653003101581653001801612100001601630700001801646700001701664700001401681700001701695700001601712700001501728700001401743700001301757700001501770700001801785856003601803 1998 eng d a0002-870300aUtilities for major stroke: results from a survey of preferences among persons at increased risk for stroke.0 aUtilities for major stroke results from a survey of preferences c1998 Oct a703-130 v1363 aBACKGROUND: Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward hypothetical major stroke.
METHODS AND RESULTS: Respondents were obtained from the Academic Medical Center Consortium (n = 621), the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45% of respondents considered major stroke to be a worse outcome than death, 15% were willing to trade off little or no survival to avoid a major stroke.
CONCLUSIONS: Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable.
10aAdult10aAge Distribution10aAged10aAged, 80 and over10aAttitude to Health10aFemale10aHealth Status10aHumans10aIntracranial Embolism and Thrombosis10aMale10aMiddle Aged10aQuality of Life10aSex Distribution10aSurveys and Questionnaires10aUnited States1 aSamsa, G, P1 aMatchar, D, B1 aGoldstein, L1 aBonito, A1 aDuncan, P, W1 aLipscomb, J1 aEnarson, C1 aWitter, D1 aVenus, P1 aPaul, J, E1 aWeinberger, M uhttps://chs-nhlbi.org/node/151602677nas a2200409 4500008004100000022001400041245014500055210006900200260001600269300001000285490000800295520154400303653001001847653000901857653002501866653002801891653001601919653001701935653001101952653001701963653001501980653001101995653001702006653000902023653001602032653002402048653002602072653001702098100001902115700001502134700001702149700001802166700001602184700001602200700001502216856003602231 1999 eng d a0002-926200aAnalytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.0 aAnalytical and biologic variability in measures of hemostasis fi c1999 Feb 01 a261-70 v1493 aAn increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have established biovariability characteristics. When biovariability data have been reported, they usually represent a short time period, and, in any case, there is little consensus on how the information should be used. The authors performed a long-term (6-month) repeated measures study on 26 healthy individuals, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVI), and between individual (CVG) variability of 12 procoagulant, fibrinolysis, and inflammation assays, including total cholesterol for comparison. The results suggest acceptable analytical variability (CVA < or = 1/2 CVI) for all assays. However, there was a large range of intraindividual variation as a proportion of total variance (2-78%), and adjusting for intraindividual and between individual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays showed a significant increase in intraindividual variation over 6 months (p < 0.05). While these findings suggest that most of these assays have biovariability characteristics similar to cholesterol, there is variation among assays. Some assays may be better suited to epidemiologic studies, and knowledge of an assay's biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.
10aAdult10aAged10aAnalysis of Variance10aCardiovascular Diseases10aCholesterol10aEpidemiology10aFemale10aFibrinolysis10aHemostasis10aHumans10aInflammation10aMale10aMiddle Aged10aModels, Statistical10aMultivariate Analysis10aRisk Factors1 aSakkinen, P, A1 aMacy, E, M1 aCallas, P, W1 aCornell, E, S1 aHayes, T, E1 aKuller, L H1 aTracy, R P uhttps://chs-nhlbi.org/node/152202941nas a2200421 4500008004100000022001400041245015000055210006900205260001300274300001100287490000700298520175900305653002102064653000902085653002202094653001002116653000802126653003302134653002802167653001902195653001102214653001102225653001702236653000902253653003002262653001702292653002102309653002202330100001702352700001702369700001702386700001502403700001802418700001602436700001502452700001702467856003502484 1999 eng d a1079-564200aAnkle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group.0 aAnklearm index as a predictor of cardiovascular disease and mort c1999 Mar a538-450 v193 aPeripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.
10aAge Distribution10aAged10aAged, 80 and over10aAnkle10aArm10aBlood Pressure Determination10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aHypertension10aMale10aPredictive Value of Tests10aRisk Factors10aSex Distribution10aSurvival Analysis1 aNewman, A, B1 aShemanski, L1 aManolio, T A1 aCushman, M1 aMittelmark, M1 aPolak, J, F1 aPowe, N, R1 aSiscovick, D uhttps://chs-nhlbi.org/node/58602852nas a2200409 4500008004100000022001400041245012300055210006900178260001300247300001100260490000700271520173400278653000902012653001802021653002802039653001902067653002202086653001702108653001102125653002202136653001102158653002402169653001202193653000902205653002402214653001702238653001702255653001802272100001502290700001802305700001802323700001702341700001902358700001502377700001502392856003502407 1999 eng d a0149-599200aAntidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.0 aAntidiabetic treatment trends in a cohort of elderly people with c1999 May a736-420 v223 aOBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort.
RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes.
RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997.
CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.
10aAged10aBlood Glucose10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aDrug Therapy10aFemale10aFollow-Up Studies10aHumans10aHypoglycemic Agents10aInsulin10aMale10aProspective Studies10aRisk Factors10aTime Factors10aUnited States1 aSmith, N L1 aHeckbert, S R1 aBittner, V, A1 aSavage, P, J1 aBarzilay, J, I1 aDobs, A, S1 aPsaty, B M uhttps://chs-nhlbi.org/node/59103341nas a2200421 4500008004100000022001400041245010200055210006900157260001600226300001000242490000800252520218300260653000902443653002002452653001702472653001502489653002802504653003002532653001102562653001802573653002502591653001102616653000902627653001402636653002602650653002402676653000902700653001702709653002002726653001802746653003602764100001502800700001502815700001802830700001602848700002002864856003502884 1999 eng d a0028-479300aAssociation of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.0 aAssociation of aorticvalve sclerosis with cardiovascular mortali c1999 Jul 15 a142-70 v3413 aBACKGROUND: Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events.
METHODS: We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke.
RESULTS: There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves.
CONCLUSIONS: Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.
10aAged10aAngina Pectoris10aAortic Valve10aCalcinosis10aCardiovascular Diseases10aCerebrovascular Disorders10aFemale10aHeart Failure10aHeart Valve Diseases10aHumans10aMale10aMortality10aMyocardial Infarction10aProspective Studies10aRisk10aRisk Factors10aUltrasonography10aUnited States10aVentricular Outflow Obstruction1 aOtto, C, M1 aLind, B, K1 aKitzman, D, W1 aGersh, B, J1 aSiscovick, D, S uhttps://chs-nhlbi.org/node/59603458nas a2200469 4500008004100000022001400041245016100055210006900216260001600285300001000301490000800311520210300319653001602422653000902438653001802447653002802465653002802493653002702521653002202548653001202570653001102582653002402593653001102617653002502628653000902653653002402662653001702686653003202703653002302735653001802758653003002776100001902806700002102825700001402846700001602860700001502876700001702891700001202908700001602920700001702936856003502953 1999 eng d a0140-673600aCardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.0 aCardiovascular disease in older adults with glucose disorders co c1999 Aug 21 a622-50 v3543 aBACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly.
METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria.
FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%).
INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.
10aAge Factors10aAged10aBlood Glucose10aCardiovascular Diseases10aCross-Sectional Studies10aDiabetes Complications10aDiabetes Mellitus10aFasting10aFemale10aGlucose Intolerance10aHumans10aLongitudinal Studies10aMale10aProspective Studies10aRisk Factors10aSensitivity and Specificity10aSocieties, Medical10aUnited States10aWorld Health Organization1 aBarzilay, J, I1 aSpiekerman, C, F1 aWahl, P W1 aKuller, L H1 aCushman, M1 aFurberg, C D1 aDobs, A1 aPolak, J, F1 aSavage, P, J uhttps://chs-nhlbi.org/node/60003320nas a2200373 4500008004100000022001400041245008300055210006900138260001600207300001100223490000800234520230600242653003102548653000902579653002202588653001502610653002102625653001102646653001802657653001702675653001102692653000902703653001402712653003202726653002402758653001702782653002602799653001202825653002602837653001802863100001402881700001602895856003502911 1999 eng d a0098-748400aCaregiving as a risk factor for mortality: the Caregiver Health Effects Study.0 aCaregiving as a risk factor for mortality the Caregiver Health E c1999 Dec 15 a2215-90 v2823 aCONTEXT: There is strong consensus that caring for an elderly individual with disability is burdensome and stressful to many family members and contributes to psychiatric morbidity. Researchers have also suggested that the combination of loss, prolonged distress, the physical demands of caregiving, and biological vulnerabilities of older caregivers may compromise their physiological functioning and increase their risk for physical health problems, leading to increased mortality.
OBJECTIVE: To examine the relationship between caregiving demands among older spousal caregivers and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline.
DESIGN: Prospective population-based cohort study, from 1993 through 1998 with an average of 4.5 years of follow-up.
SETTING: Four US communities.
PARTICIPANTS: A total of 392 caregivers and 427 noncaregivers aged 66 to 96 years who were living with their spouses.
MAIN OUTCOME MEASURE: Four-year mortality, based on level of caregiving: (1) spouse not disabled; (2) spouse disabled and not helping; (3) spouse disabled and helping with no strain reported; or(4) spouse disabled and helping with mental or emotional strain reported.
RESULTS: After 4 years of follow-up, 103 participants (12.6%) died. After adjusting for sociodemographic factors, prevalent disease, and subclinical cardiovascular disease, participants who were providing care and experiencing caregiver strain had mortality risks that were 63% higher than noncaregiving controls (relative risk [RR], 1.63; 95% confidence interval [CI], 1.00-2.65). Participants who were providing care but not experiencing strain (RR, 1.08; 95 % CI, 0.61-1.90) and those with a disabled spouse who were not providing care (RR, 1.37; 95% CI, 0.73-2.58) did not have elevated adjusted mortality rates relative to the noncaregiving controls.
CONCLUSIONS: Our study suggests that being a caregiver who is experiencing mental or emotional strain is an independent risk factor for mortality among elderly spousal caregivers. Caregivers who report strain associated with caregiving are more likely to die than noncaregiving controls.
10aActivities of Daily Living10aAged10aAged, 80 and over10aCaregivers10aDisabled Persons10aFemale10aHealth Status10aHome Nursing10aHumans10aMale10aMortality10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSocioeconomic Factors10aSpouses10aStress, Psychological10aUnited States1 aSchulz, R1 aBeach, S, R uhttps://chs-nhlbi.org/node/60503311nas a2200385 4500008004100000022001400041245017500055210006900230260001600299300001000315490000800325520216900333653000902502653002102511653003002532653002602562653001102588653001102599653001402610653000902624653002602633653003202659653002402691653001702715653001802732653001702750653002002767100001702787700001602804700001802820700001702838700001602855700001802871856003602889 1999 eng d a0028-479300aCarotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.0 aCarotidartery intima and media thickness as a risk factor for my c1999 Jan 07 a14-220 v3403 aBACKGROUND: The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease.
METHODS: Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years.
RESULTS: The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point.
CONCLUSIONS: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.
10aAged10aCarotid Arteries10aCerebrovascular Disorders10aDisease-Free Survival10aFemale10aHumans10aIncidence10aMale10aMyocardial Infarction10aProportional Hazards Models10aProspective Studies10aRisk Factors10aTunica Intima10aTunica Media10aUltrasonography1 aO'Leary, D H1 aPolak, J, F1 aKronmal, R, A1 aManolio, T A1 aBurke, G, L1 aWolfson, S, K uhttps://chs-nhlbi.org/node/152002554nas a2200349 4500008004100000022001400041245008800055210006900143260001300212300001200225490000700237520157600244653003101820653000901851653001001860653002801870653003001898653002801928653001501956653001101971653001101982653002001993653003102013653000902044653002902053653001702082100001902099700001602118700001902134700001602153856003502169 1999 eng d a0039-249900aCerebrovascular disease and depression symptoms in the cardiovascular health study.0 aCerebrovascular disease and depression symptoms in the cardiovas c1999 Oct a2159-660 v303 aBACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study.
METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score.
RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions.
CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.
10aActivities of Daily Living10aAged10aBrain10aCardiovascular Diseases10aCerebrovascular Disorders10aCross-Sectional Studies10aDepression10aFemale10aHumans10aLogistic Models10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aRisk Factors1 aSteffens, D, C1 aHelms, M, J1 aKrishnan, K, R1 aBurke, G, L uhttps://chs-nhlbi.org/node/60202817nas a2200397 4500008004100000022001400041245011500055210006900170260001300239300001000252490000700262520171300269653001601982653000901998653002002007653001502027653001102042653004302053653001702096653001702113653002202130653001702152653001102169653000902180653002602189653003802215653001702253100001502270700001902285700001602304700001502320700001502335700001902350700001502369856003502384 1999 eng d a1079-564200aFibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.0 aFibrinolytic activation markers predict myocardial infarction in c1999 Mar a493-80 v193 aCoagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.
10aAge Factors10aAged10aAngina Pectoris10aBiomarkers10aFemale10aFibrin Fibrinogen Degradation Products10aFibrinolysin10aFibrinolysis10aFollow-Up Studies10aHeart Arrest10aHumans10aMale10aMyocardial Infarction10aPlasminogen Activator Inhibitor 110aRisk Factors1 aCushman, M1 aLemaitre, R, N1 aKuller, L H1 aPsaty, B M1 aMacy, E, M1 aSharrett, A, R1 aTracy, R P uhttps://chs-nhlbi.org/node/58402974nas a2200373 4500008004100000022001400041245008000055210006900135260001300204300001000217490000700227520198600234653000902220653001502229653002502244653002802269653001402297653001102311653001502322653003202337653001102369653001702380653001502397653002202412653001902434653001802453100001502471700001802486700001502504700001602519700001502535700001502550856003502565 1999 eng d a1079-564200aHormone replacement therapy, inflammation, and hemostasis in elderly women.0 aHormone replacement therapy inflammation and hemostasis in elder c1999 Apr a893-90 v193 aLipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
10aAged10aBiomarkers10aCase-Control Studies10aCross-Sectional Studies10aEstrogens10aFemale10aHemostasis10aHormone Replacement Therapy10aHumans10aInflammation10aProgestins10aRandom Allocation10aUnited Kingdom10aUnited States1 aCushman, M1 aMeilahn, E, N1 aPsaty, B M1 aKuller, L H1 aDobs, A, S1 aTracy, R P uhttps://chs-nhlbi.org/node/58803000nas a2200409 4500008004100000022001400041245008400055210006900139260001600208300001200224490000700236520195300243653001902196653000902215653001802224653002202242653002102264653002502285653001102310653001102321653001402332653001202346653000902358653002402367653000902391653001802400653001202418100001702430700001702447700001602464700001602480700001502496700001502511700001202526700001702538856003502555 1999 eng d a0027-887400aIncreased blood glucose and insulin, body size, and incident colorectal cancer.0 aIncreased blood glucose and insulin body size and incident color c1999 Jul 07 a1147-540 v913 aBACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer.
METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided.
RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02).
CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.
10aAdipose Tissue10aAged10aBlood Glucose10aBody Constitution10aCholesterol, HDL10aColorectal Neoplasms10aFemale10aHumans10aIncidence10aInsulin10aMale10aProspective Studies10aRisk10aTriglycerides10aViscera1 aSchoen, R, E1 aTangen, C, M1 aKuller, L H1 aBurke, G, L1 aCushman, M1 aTracy, R P1 aDobs, A1 aSavage, P, J uhttps://chs-nhlbi.org/node/59402473nas a2200373 4500008004100000022001400041245009600055210006900151260001600220300001100236490000800247520142800255653003101683653000901714653002201723653001801745653002401763653001401787653002801801653001501829653001101844653002501855653001101880653001801891653003101909653000901940653003701949653001701986653001802003100001202021700001602033700001502049856003502064 1999 eng d a0002-926200aNeuroanatomic and functional correlates of depressed mood: the Cardiovascular Health Study.0 aNeuroanatomic and functional correlates of depressed mood the Ca c1999 Nov 01 a919-290 v1503 aAlthough a number of studies suggest an association between stroke and depression, few have examined the relation between magnetic resonance imaging (MRI)-identified lesions and depression among community-dwelling older adults. This cross-sectional study sought to assess the association between MRI infarcts in the basal ganglia and non-basal-ganglia areas, potential functional consequences of these lesions, and depressive symptomatology in 3,371 US men and women aged 65 years or older who participated in the Cardiovascular Health Study between 1992 and 1994. By using multiple linear regression models, the authors found that after adjustment for age, gender, and stroke history, Center for Epidemiologic Studies Depression Scale scores were independently associated with non-basal-ganglia lesions (p = 0.04) but were not independently associated with basal ganglia lesions (p = 0.11). When measures of physical disability and cognitive impairment were added to the models, these measures displaced MRI-identified infarcts in their association with depressive symptoms. In additional models, hemispheric location and size of the basal ganglia lesion were found to have no relation to depression levels. These results suggest that the functional consequences of cerebrovascular disease may be the causal pathway by which basal ganglia and non-basal-ganglia lesions are associated with depressive symptomatology.
10aActivities of Daily Living10aAged10aAged, 80 and over10aBasal Ganglia10aCerebral Infarction10aCognition10aCross-Sectional Studies10aDepression10aFemale10aGeriatric Assessment10aHumans10aLinear Models10aMagnetic Resonance Imaging10aMale10aPsychiatric Status Rating Scales10aRisk Factors10aUnited States1 aSato, R1 aBryan, R, N1 aFried, L P uhttps://chs-nhlbi.org/node/60402903nas a2200421 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520175200267653002502019653000902044653001902053653002402072653003002096653002802126653001102154653001102165653002002176653000902196653001502205653003302220653002402253653000902277653001702286653001302303100001602316700001902332700001502351700001702366700001602383700001802399700001402417700001502431856003502446 1999 eng d a0002-934300aOral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.0 aOral anticoagulation in patients with atrial fibrillation adhere c1999 Feb a165-710 v1063 aPURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation.
SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995.
RESULTS: In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0).
CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.
10aAdministration, Oral10aAged10aAnticoagulants10aAtrial Fibrillation10aCerebrovascular Disorders10aCross-Sectional Studies10aFemale10aHumans10aLogistic Models10aMale10aOdds Ratio10aPractice Guidelines as Topic10aProspective Studies10aRisk10aRisk Factors10aWarfarin1 aWhite, R, H1 aMcBurnie, M, A1 aManolio, T1 aFurberg, C D1 aGardin, J M1 aKittner, S, J1 aBovill, E1 aKnepper, L uhttps://chs-nhlbi.org/node/59002885nas a2200421 4500008004100000022001400041245016500055210006900220260001300289300001000302490000700312520165200319653000901971653001001980653002801990653002402018653002802042653001102070653001102081653003102092653003102123653000902154653001502163653002802178653003002206653001502236653002402251653001702275653001802292100001902310700001602329700001602345700001702361700001702378700001502395700001702410856003602427 1999 eng d a0039-249900aPrevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study.0 aPrevalence and associations of MRIdemonstrated brain infarcts in c1999 Feb a383-80 v303 aBACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA.
METHODS: Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA.
RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%; P<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima-media thickness (P=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis.
CONCLUSIONS: MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.
10aAged10aBrain10aCardiovascular Diseases10aCerebral Infarction10aCross-Sectional Studies10aFemale10aHumans10aIschemic Attack, Transient10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPopulation Surveillance10aPredictive Value of Tests10aPrevalence10aProspective Studies10aRisk Factors10aUnited States1 aBhadelia, R, A1 aAnderson, M1 aPolak, J, F1 aManolio, T A1 aBeauchamp, N1 aKnepper, L1 aO'Leary, D H uhttps://chs-nhlbi.org/node/152403060nas a2200385 4500008004100000022001400041245009800055210006900153260001600222300001100238490000700249520200000256653000902256653002202265653001202287653001002299653002002309653002402329653002302353653001102376653002602387653001802413653001102431653003102442653000902473653002702482653002402509653002402533100001702557700001702574700001602591700001602607700001602623856003502639 1999 eng d a0028-387800aRelation of education to brain size in normal aging: implications for the reserve hypothesis.0 aRelation of education to brain size in normal aging implications c1999 Jul 13 a189-960 v533 aOBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults.
BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure.
METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained.
RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume.
CONCLUSIONS: The authors' findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.
10aAged10aAged, 80 and over10aAtrophy10aBrain10aCerebral Cortex10aCerebrospinal Fluid10aEducational Status10aFemale10aFunctional Laterality10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aRegression Analysis10aSex Characteristics1 aCoffey, C, E1 aSaxton, J, A1 aRatcliff, G1 aBryan, R, N1 aLucke, J, F uhttps://chs-nhlbi.org/node/59802701nas a2200397 4500008004100000022001400041245009100055210006900146260001300215300001000228490000800238520158700246653000901833653002801842653002801870653003801898653001101936653001101947653000901958653001601967653002001983653001602003653002602019653003002045653002602075653003102101100001902132700001802151700001802169700001202187700001602199700001602215700001602231700002002247856003602267 1999 eng d a1073-449X00aRelation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.0 aRelation of sleepiness to respiratory disturbance index the Slee c1999 Feb a502-70 v1593 aObstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.
10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aRespiration10aRetrospective Studies10aSeverity of Illness Index10aSleep Apnea Syndromes10aSurveys and Questionnaires1 aGottlieb, D, J1 aWhitney, C, W1 aBonekat, W, H1 aIber, C1 aJames, G, D1 aLebowitz, M1 aNieto, F, J1 aRosenberg, C, E uhttps://chs-nhlbi.org/node/152302513nas a2200325 4500008004100000022001400041245016700055210006900222260001300291300001200304490000700316520158200323653000901905653002801914653001501942653001601957653001101973653001501984653001101999653000902010653002602019653001702045100001502062700001702077700001602094700001302110700001502123700001402138856003502152 1999 eng d a1079-564200aThe relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study.0 arelationship of fibrinogen and factors VII and VIII to incident c1999 Jul a1776-830 v193 aLittle is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.
10aAged10aCardiovascular Diseases10aFactor VII10aFactor VIII10aFemale10aFibrinogen10aHumans10aMale10aMultivariate Analysis10aRisk Factors1 aTracy, R P1 aArnold, A, M1 aEttinger, W1 aFried, L1 aMeilahn, E1 aSavage, P uhttps://chs-nhlbi.org/node/59503503nas a2200445 4500008004100000022001400041245010400055210006900159260001300228300001200241490000700253520222500260653000902485653002202494653002402516653002802540653003702568653001902605653002102624653003002645653004002675653001102715653001702726653001702743653001102760653002302771653000902794653002602803653002602829653003802855653001702893100001902910700001502929700001502944700001702959700001502976700001602991700001503007856003503022 1999 eng d a1079-564200aRelationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.0 aRelationship of plasmin generation to cardiovascular disease ris c1999 Mar a499-5040 v193 aPlasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, =0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.
10aAged10aAged, 80 and over10aalpha-2-Antiplasmin10aAntifibrinolytic Agents10aAsian Continental Ancestry Group10aCohort Studies10aCoronary Disease10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aFemale10aFibrinolysin10aFibrinolysis10aHumans10aInsulin Resistance10aMale10aMultivariate Analysis10aMyocardial Infarction10aPlasminogen Activator Inhibitor 110aRisk Factors1 aSakkinen, P, A1 aCushman, M1 aPsaty, B M1 aRodriguez, B1 aBoineau, R1 aKuller, L H1 aTracy, R P uhttps://chs-nhlbi.org/node/58502916nas a2200397 4500008004100000022001400041245017200055210006900227260001300296300001100309490000700320520176400327653000902091653002102100653001002121653002602131653002802157653002402185653001902209653002802228653002402256653001102280653001802291653001102309653003102320653000902351653001502360100001702375700001602392700001702408700001302425700001702438700001502455700001202470856003602482 1999 eng d a1079-564200aRelationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group.0 aRelationships of cerebral MRI findings to ultrasonographic carot c1999 Feb a356-650 v193 aCerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3%) and measurable carotid plaque in 2745 (75.3%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis.
10aAged10aArteriosclerosis10aBrain10aCardiovascular System10aCarotid Artery Diseases10aCerebral Infarction10aCohort Studies10aCross-Sectional Studies10aEchoencephalography10aFemale10aHealth Status10aHumans10aMagnetic Resonance Imaging10aMale10aPrevalence1 aManolio, T A1 aBurke, G, L1 aO'Leary, D H1 aEvans, G1 aBeauchamp, N1 aKnepper, L1 aWard, B uhttps://chs-nhlbi.org/node/152502461nas a2200421 4500008004100000022001400041245011000055210006900165260001300234300001200247490000700259520128200266653001601548653000901564653002201573653002801595653002301623653001101646653001101657653001801668653001101686653002801697653001801725653002501743653000901768653003001777653001601807653001901823653002601842653003101868653001701899653001801916100001801934700001401952700002101966700001701987856003502004 1999 eng d a1079-501400aStability and change in older adults' social contact and social support: the Cardiovascular Health Study.0 aStability and change in older adults social contact and social s c1999 Sep aS302-110 v543 aOBJECTIVES: The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life.
METHODS: Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time.
RESULTS: Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time.
DISCUSSION: The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.
10aAge Factors10aAged10aAged, 80 and over10aCross-Sectional Studies10aEducational Status10aFamily10aFemale10aHealth Status10aHumans10aInterpersonal Relations10aLinear Models10aLongitudinal Studies10aMale10aPredictive Value of Tests10aSex Factors10aSocial Support10aSocioeconomic Factors10aSurveys and Questionnaires10aTime Factors10aUnited States1 aMartire, L, M1 aSchulz, R1 aMittelmark, M, B1 aNewsom, J, T uhttps://chs-nhlbi.org/node/60302278nas a2200361 4500008004100000022001400041245008600055210006900141260001300210300001100223490000700234520128400241653000901525653002001534653001101554653002201565653001801587653001101605653002001616653000901636653003201645653004201677653002001719653001601739653002201755653001701777653002201794100001301816700001801829700001601847700001801863856003501881 1999 eng d a0197-245600aSurvival versus years of healthy life: which is more powerful as a study outcome?0 aSurvival versus years of healthy life which is more powerful as c1999 Jun a267-790 v203 aStudies of interventions that are intended to improve patients' health are often evaluated with survival as the primary outcome, even when a measure adjusted for quality of survival, such as years of healthy life (YHL), would seem more appropriate. The purpose of this article is to determine whether studies based on survival are more or less powerful than studies based on YHL in clinical trials where either measure might be appropriate. We used data from the Cardiovascular Health Study (CHS) to estimate the sample size that would be needed in studies of 156 different health conditions, for the two outcome measures. The median sample size for a 5-year study was 687 if survival was the endpoint and 484 for YHL. YHL usually required lower sample sizes than survival, although survival was more powerful for some health conditions. We also found that lengthy studies, and studies with many follow-up measures per person, did not have appreciably higher power than less intensive studies. We conclude that clinical investigations in which the goal is to improve health may often be performed more efficiently with YHL rather than survival as the primary outcome measure. Such studies can be short in duration, with relatively few measures per person of health status.
10aAged10aAngina Pectoris10aFemale10aFollow-Up Studies10aHealth Status10aHumans10aLife Expectancy10aMale10aQuality-Adjusted Life Years10aRandomized Controlled Trials as Topic10aResearch Design10aSample Size10aSurvival Analysis10aTime Factors10aTreatment Outcome1 aDiehr, P1 aPatrick, D, L1 aBurke, G, L1 aWilliamson, J uhttps://chs-nhlbi.org/node/59202834nas a2200385 4500008004100000022001400041245009400055210006900149260001600218300001100234490000800245520182100253653000902074653001902083653001202102653002402114653003002138653001702168653002402185653001102209653001102220653001402231653000902245653001502254653002202269653001302291100001502304700001502319700001702334700001302351700001502364700001702379700001702396856003502413 1999 eng d a0003-992600aTemporal trends in the use of anticoagulants among older adults with atrial fibrillation.0 aTemporal trends in the use of anticoagulants among older adults c1999 Jul 26 a1574-80 v1593 aBACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.
METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.
RESULTS: The use of warfarin increased 4-fold from 13% in 1990 to 50% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.
CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.
10aAged10aAnticoagulants10aAspirin10aAtrial Fibrillation10aCerebrovascular Disorders10aDrug Therapy10aElectrocardiography10aFemale10aHumans10aIncidence10aMale10aPrevalence10aTreatment Outcome10aWarfarin1 aSmith, N L1 aPsaty, B M1 aFurberg, C D1 aWhite, R1 aLima, J, A1 aNewman, A, B1 aManolio, T A uhttps://chs-nhlbi.org/node/59903636nas a2200397 4500008004100000022001400041245015700055210006900212260001600281300001200297490000800309520249400317653002102811653000902832653001102841653002202852653001102874653001402885653000902899653002602908653002602934653003002960653003202990653000903022653001703031653002103048100001503069700001703084700001603101700001503117700002103132700001603153700001403169700002003183856003503203 1999 eng d a0003-992600aTraditional risk factors and subclinical disease measures as predictors of first myocardial infarction in older adults: the Cardiovascular Health Study.0 aTraditional risk factors and subclinical disease measures as pre c1999 Jun 28 a1339-470 v1593 aBACKGROUND: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease.
METHODS: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model.
RESULTS: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women.
CONCLUSIONS: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.
10aAge Distribution10aAged10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMultivariate Analysis10aMyocardial Infarction10aPredictive Value of Tests10aProportional Hazards Models10aRisk10aRisk Factors10aSex Distribution1 aPsaty, B M1 aFurberg, C D1 aKuller, L H1 aBild, D, E1 aRautaharju, P, M1 aPolak, J, F1 aBovill, E1 aGottdiener, J S uhttps://chs-nhlbi.org/node/59302787nas a2200337 4500008004100000022001400041245010800055210006900163260001300232300001100245490000800256520186600264653001602130653000902146653002202155653001102177653001102188653001102199653000902210653003002219653002002249653001702269653001502286653001902301100001802320700002102338700001702359700001902376700001902395856003502414 1999 eng d a0012-369200aUnderdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group.0 aUnderdiagnosis and undertreatment of asthma in the elderly Cardi c1999 Sep a603-130 v1163 aOBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons.
PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study.
MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow.
RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40% were taking a sympathomimetic bronchodilator, 30% inhaled corticosteroids, 21% theophylline, and 18% oral corticosteroids; 39% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not.
CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.
10aAge Factors10aAged10aAged, 80 and over10aAsthma10aFemale10aHumans10aMale10aPeak Expiratory Flow Rate10aQuality of Life10aRisk Factors10aSpirometry10aVital Capacity1 aEnright, P, L1 aMcClelland, R, L1 aNewman, A, B1 aGottlieb, D, J1 aLebowitz, M, D uhttps://chs-nhlbi.org/node/60102940nas a2200373 4500008004100000022001400041245009900055210006900154260001600223300001100239490000800250520194800258653000902206653002102215653001502236653002402251653001102275653002902286653001102315653000902326653001502335653001502350653001702365653001202382653002602394653001802420100001402438700001602452700001502468700001802483700001602501700001402517856003502531 2000 eng d a0003-992600aAssociation between depression and mortality in older adults: the Cardiovascular Health Study.0 aAssociation between depression and mortality in older adults the c2000 Jun 26 a1761-80 v1603 aBACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals.
OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors.
METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality.
RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46).
CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.
10aAged10aAlcohol Drinking10aDepression10aDepressive Disorder10aFemale10aHealth Status Indicators10aHumans10aMale10aMotivation10aPrevalence10aRisk Factors10aSmoking10aSocioeconomic Factors10aUnited States1 aSchulz, R1 aBeach, S, R1 aIves, D, G1 aMartire, L, M1 aAriyo, A, A1 aKop, W, J uhttps://chs-nhlbi.org/node/61803847nas a2200421 4500008004100000022001400041245013700055210006900192260001600261300001200277490000800289520270400297653001003001653000903011653001903020653002803039653001103067653001103078653001703089653002003106653000903126653001603135653001203151653002003163653002603183653001203209100001603221700001603237700001503253700001403268700001603282700001503298700002103313700001703334700001903351700002003370856003503390 2000 eng d a0098-748400aAssociation of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.0 aAssociation of sleepdisordered breathing sleep apnea and hyperte c2000 Apr 12 a1829-360 v2833 aCONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.
OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.
DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.
PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female).
MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.
RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.
CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.
10aAdult10aAged10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aHypertension10aLogistic Models10aMale10aMiddle Aged10aObesity10aPolysomnography10aSleep Apnea Syndromes10aSnoring1 aNieto, F, J1 aYoung, T, B1 aLind, B, K1 aShahar, E1 aSamet, J, M1 aRedline, S1 aD'Agostino, R, B1 aNewman, A, B1 aLebowitz, M, D1 aPickering, T, G uhttps://chs-nhlbi.org/node/61302915nas a2200457 4500008004100000022001400041245019400055210006900249260001600318300001200334490000800346520158700354653001001941653001601951653000901967653002601976653002202002653002502024653002902049653002102078653002002099653001102119653002502130653001902155653001102174653002102185653000902206653002602215653001702241100002002258700001902278700001302297700001902310700001402329700001502343700001502358700001502373700001602388700001802404856003502422 2000 eng d a1524-453900aChlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.0 aChlamydia pneumoniae herpes simplex virus type 1 and cytomegalov c2000 Nov 07 a2335-400 v1023 aBACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy.
METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4).
CONCLUSIONS: Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.
10aAdult10aAge Factors10aAged10aAntibodies, Bacterial10aAntibodies, Viral10aCase-Control Studies10aChlamydophila pneumoniae10aCoronary Disease10aCytomegalovirus10aFemale10aHerpesvirus 1, Human10aHIV Antibodies10aHumans10aImmunoglobulin G10aMale10aMyocardial Infarction10aRisk Factors1 aSiscovick, D, S1 aSchwartz, S, M1 aCorey, L1 aGrayston, J, T1 aAshley, R1 aWang, S, P1 aPsaty, B M1 aTracy, R P1 aKuller, L H1 aKronmal, R, A uhttps://chs-nhlbi.org/node/62502448nas a2200493 4500008004100000022001400041245018100055210006900236260001700305300001000322490000700332520103400339653002101373653001601394653000901410653001001419653002401429653003401453653002801487653002701515653001101542653001101553653001601564653001801580653003101598653000901629653002601638653001701664653003001681653002101711653001601732653001201748653001101760100002001771700001701791700001701808700001601825700001301841700001901854700001501873700001801888700001301906856003501919 2000 eng d a0251-535000aClinical correlates of ventricular and sulcal size on cranial magnetic resonance imaging of 3,301 elderly people. The Cardiovascular Health Study. Collaborative Research Group.0 aClinical correlates of ventricular and sulcal size on cranial ma c2000 Jan-Feb a30-420 v193 aTo identify potential risk factors for and clinical manifestations of ventricular and sulcal enlargement on cranial magnetic resonance imaging (MRI), 3,301 community-dwelling people 65 years or older without a history of stroke or transient ischemic attack underwent extensive standardized evaluations and MRI. In the multivariate model, increased age and white matter grade on MRI were the dominant risk factors for ventricular and sulcal grade. For ventricular grade, other than race, for which non-Blacks had higher grades, models for men and women shared no other factors. For sulcal grades, models for men and women shared variables reflecting cigarette smoking and diabetes. Clinical features were correlated more strongly with ventricular than sulcal grade and more strongly for women than men. Significant age-adjusted correlations between ventricular grade and the Digit-Symbol Substitution Test were found for men and women. Prospective studies will be needed to extend findings of this cross-sectional analysis.
10aAge Distribution10aAge Factors10aAged10aAging10aCerebral Ventricles10aContinental Population Groups10aCross-Sectional Studies10aDiabetes Complications10aFemale10aHumans10aHypertrophy10aLinear Models10aMagnetic Resonance Imaging10aMale10aMultivariate Analysis10aRisk Factors10aSeverity of Illness Index10aSex Distribution10aSex Factors10aSmoking10aStroke1 aLongstreth, W T1 aArnold, A, M1 aManolio, T A1 aBurke, G, L1 aBryan, N1 aJungreis, C, A1 aO'Leary, D1 aEnright, P, L1 aFried, L uhttps://chs-nhlbi.org/node/60802678nas a2200409 4500008004100000022001400041245013000055210006900185260001600254300001200270490000800282520152900290653000901819653002201828653001301850653002201863653002801885653002101913653003301934653001501967653001101982653001501993653001702008653001102025653001702036653002302053653000902076653001602085653003802101653001702139100001902156700001202175700001502187700001602202700001502218856003502233 2000 eng d a0002-926200aClustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome.0 aClustering of procoagulation inflammation and fibrinolysis varia c2000 Nov 15 a897-9070 v1523 aThe known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65-100 years) participating in the Cardiovascular Health Study during 1989-1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities.
10aAged10aAged, 80 and over10aAntigens10aBlood Coagulation10aCardiovascular Diseases10aCluster Analysis10aFactor Analysis, Statistical10aFactor VII10aFemale10aFibrinogen10aFibrinolysis10aHumans10aInflammation10aInsulin Resistance10aMale10aMiddle Aged10aPlasminogen Activator Inhibitor 110aRisk Factors1 aSakkinen, P, A1 aWahl, P1 aCushman, M1 aLewis, M, R1 aTracy, R P uhttps://chs-nhlbi.org/node/62601750nas a2200325 4500008004100000022001400041245011800055210006900173260001700242300001000259490000700269520085900276653000901135653002801144653002401172653001101196653001101207653001701218653000901235653003001244653002001274100001401294700001601308700001401324700001301338700001301351700001101364700001401375856003501389 2000 eng d a0251-535000aCognitive test performance and presence of subclinical cardiovascular disease in the cardiovascular health study.0 aCognitive test performance and presence of subclinical cardiovas c2000 Nov-Dec a312-90 v193 aThe purpose of the present study was to investigate the relationship between performance on a comprehensive battery of neuropsychological tests and the presence of clinical, subclinical or no cardiovascular disease in an elderly community-dwelling population. The results confirm previous reports of significant associations of age, education and gender with test performance. When performance was examined controlling for these variables, significant associations of disease group were seen with five measures emphasizing speed of performance; Parts A and B of the Trail Making Test, the WAIS-R Digit Symbol and Block Design subtests and category verbal fluency. These results add to the evidence that, in addition to other health implications, cardiovascular disease is related to cognitive functioning in the elderly even at subclinical levels.
10aAged10aCardiovascular Diseases10aCognition Disorders10aFemale10aHumans10aHypertension10aMale10aSeverity of Illness Index10aWechsler Scales1 aSaxton, J1 aRatcliff, G1 aNewman, A1 aBelle, S1 aFried, L1 aYee, J1 aKuller, L uhttps://chs-nhlbi.org/node/62401920nas a2200277 4500008004100000022001400041245016700055210006900222260001300291300001100304490000700315520111000322653000901432653001001441653001501451653002401466653001101490653001801501653001101519653000901530653001201539653002601551100001601577700001401593856003501607 2000 eng d a0882-797400aA comparison of primary stressors, secondary stressors, and depressive symptoms between elderly caregiving husbands and wives: the Caregiver Health Effects Study.0 acomparison of primary stressors secondary stressors and depressi c2000 Dec a607-160 v153 aThe present study examined gender differences in the experience of primary and secondary caregiving stressors, depressive symptoms, and their interrelationships using a sample of 283 elderly spouse caregivers (145 women, 138 men). Two primary stressors, two secondary stressors, and depressive symptoms were assessed. In general, t-tests indicated that caregiving husbands experience fewer stressors and depressive symptoms than their female counterparts. Multiple group analysis revealed that the primary stressors were more useful in explaining variance associated with the secondary stressors for women than men and that the path coefficients linking amount of caregiving assistance to caregivers' activity restriction was significantly different across men and women. Other paths linking primary stressors, secondary stressors, and depressive symptoms, however, were statistically equivalent across men and women. Hence, although caregiving women and men may vary in their reports of caregiving stressors, the complexity of the caregiving experience appears to be quite uniform for both groups.
10aAged10aAging10aCaregivers10aDepressive Disorder10aFemale10aHealth Status10aHumans10aMale10aSpouses10aStress, Psychological1 aBookwala, J1 aSchulz, R uhttps://chs-nhlbi.org/node/62703286nas a2200373 4500008004100000022001400041245011100055210006900166260001300235300001100248490000700259520223100266653000902497653001002506653002502516653001502541653002802556653002802584653002802612653002102640653001102661653001102672653000902683653001702692653003002709653003102739100001702770700001502787700002202802700001902824700001802843700001602861856003502877 2000 eng d a0002-861400aCoronary artery calcification in older adults with minimal clinical or subclinical cardiovascular disease.0 aCoronary artery calcification in older adults with minimal clini c2000 Mar a256-630 v483 aBACKGROUND: Coronary artery calcification (CAC) reflects the extent of coronary artery atherosclerosis. The extent of coronary artery calcification is not well described in older adults.
OBJECTIVE: To determine the extent of CAC in older adults participating in a large population study of cardiovascular disease (CVD), especially those characterized as having minimal clinical or subclinical cardiovascular disease.
DESIGN: An observational epidemiologic study.
POPULATION: Participants in the Cardiovascular Health Study Cohort, mean age 78 years, who had electron beam computed tomography (EBT) scan of the heart (n = 133); included were 106 persons with no prior evidence of clinical or subclinical CVD.
MEASUREMENTS: Total CAC score was measured using cardiac EBT. Cardiovascular disease and risk factors, as well as carotid ultrasound, electrocardiogram, echocardiogram, and ankle-arm index, had been measured previously to define subclinical disease. Previous cerebral magnetic resonance imaging was also evaluated.
RESULTS: Overall, the CAC scores were higher in those with clinical cardiovascular disease or evidence of subclinical cardiovascular disease than in those with no evidence of disease. For the 106 participants without evidence of clinical or subclinical disease, the median score was 176, compared with 367 in those with subclinical disease and 923 in those with clinical CVD. Seventeen persons had scores of zero. There was little difference in risk factors across quartiles of CAC in the subgroup of 106 with prior characterization of minimal CVD despite the broad range of CAC scores. There was a higher proportion of those with white matter grade > or = 2 by magnetic resonance imaging among those with higher CAC scores (P = .025). Infarct-like lesions prevalence ranged from 12.5% in the lowest group to 47.1% in the highest CAC group (P = .019).
CONCLUSIONS: Older adults with evidence of clinical or subclinical CVD have higher total CAC scores. Though the extent of coronary artery calcification was lower in those with minimal evidence of CVD, the range was broad and not explained by CVD risk factors.
10aAged10aAging10aAnalysis of Variance10aCalcinosis10aCardiovascular Diseases10aChi-Square Distribution10aCoronary Artery Disease10aCoronary Disease10aFemale10aHumans10aMale10aRisk Factors10aStatistics, Nonparametric10aTomography, X-Ray Computed1 aNewman, A, B1 aNaydeck, B1 aSutton-Tyrrell, K1 aEdmundowicz, D1 aGottdiener, J1 aKuller, L H uhttps://chs-nhlbi.org/node/61204727nas a2200481 4500008004100000022001400041245013400055210006900189260001300258300001100271490000700282520339800289653001603687653000903703653002203712653002803734653001903762653001103781653001803792653001803810653001103828653001403839653000903853653002603862653002603888653001503914653001703929653001603946653002603962653001703988653002504005653001204030653003104042653001804073100001704091700002104108700001504129700001704144700001504161700001904176700001504195856003504210 2000 eng d a0002-861400aDaytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.0 aDaytime sleepiness predicts mortality and cardiovascular disease c2000 Feb a115-230 v483 aINTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD.
SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease.
METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure.
RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95% CI = 1.03, 1.76) in men and was 1.66 (95% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95% CI, 1.12- 1.98) and in women, was 2.21 (95% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men.
CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.
10aAge Factors10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aFemale10aHealth Status10aHeart Failure10aHumans10aIncidence10aMale10aMultivariate Analysis10aMyocardial Infarction10aOdds Ratio10aRisk Factors10aSex Factors10aSleep Apnea Syndromes10aSleep Stages10aSleep Wake Disorders10aSnoring10aSurveys and Questionnaires10aUnited States1 aNewman, A, B1 aSpiekerman, C, F1 aEnright, P1 aLefkowitz, D1 aManolio, T1 aReynolds, C, F1 aRobbins, J uhttps://chs-nhlbi.org/node/61002728nas a2200349 4500008004100000022001400041245015400055210006900209260001600278300001100294490000800305520174600313653000902059653002202068653001902090653002102109653001502130653001102145653001102156653000902167653002402176653001702200653001802217100001602235700001202251700001702263700001902280700001502299700001202314700001702326856003502343 2000 eng d a1524-453900aDepressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group.0 aDepressive symptoms and risks of coronary heart disease and mort c2000 Oct 10 a1773-90 v1023 aBACKGROUND: Several epidemiological studies have associated depressive symptoms with cardiovascular disease. We investigated whether depressive symptoms constituted a risk for coronary heart disease (CHD) and total mortality among an apparently healthy elderly cohort.
METHODS AND RESULTS: In a prospective cohort of 5888 elderly Americans (>/=65 years) who were enrolled in the Cardiovascular Health Study, 4493 participants who were free of cardiovascular disease at baseline provided annual information on their depressive status, which was assessed using the Depression Scale of the Center for Epidemiological Studies. These 4493 subjects were followed for 6 years for the development of CHD and mortality. The cumulative mean depression score was assessed for each participant up to the time of event (maximum 6-year follow-up). Using time-dependent, proportional-hazards models, the unadjusted hazard ratio associated with every 5-unit increase in mean depression score for the development of CHD was 1.15 (P:=0.006); the ratio for all-cause mortality was 1.29 (P:<0.0001). In multivariate analyses adjusted for age, race, sex, education, diabetes, hypertension, cigarette smoking, total cholesterol, triglyceride level, congestive heart failure, and physical inactivity, the hazard ratio for CHD was 1.15 (P:=0.006) and that for all-cause mortality was 1.16 (P:=0.006). Among participants with the highest cumulative mean depression scores, the risk of CHD increased by 40% and risk of death by 60% compared with those who had the lowest mean scores.
CONCLUSIONS: Among elderly Americans, depressive symptoms constitute an independent risk factor for the development of CHD and total mortality.
10aAged10aAged, 80 and over10aCohort Studies10aCoronary Disease10aDepression10aFemale10aHumans10aMale10aProspective Studies10aRisk Factors10aUnited States1 aAriyo, A, A1 aHaan, M1 aTangen, C, M1 aRutledge, J, C1 aCushman, M1 aDobs, A1 aFurberg, C D uhttps://chs-nhlbi.org/node/62202742nas a2200409 4500008004100000022001400041245012700055210006900182260001300251300001000264490000700274520158300281653000901864653002101873653002101894653003001915653003001945653002601975653001102001653001102012653001402023653000902037653002602046653002602072653001502098653003202113653001702145653002102162653001102183100001602194700001702210700001602227700002002243700001702263700001702280856003502297 2000 eng d a1079-564200aDiabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality.0 aDiabetes mellitus subclinical cardiovascular disease and risk of c2000 Mar a823-90 v203 aPreviously diagnosed diabetes mellitus, newly diagnosed diabetes mellitus, and impaired glucose tolerance are important determinants of the risk of clinical cardiovascular disease (CVD). We have evaluated the relation of patients with subclinical CVD, diabetes, and impaired glucose tolerance and "normal" subjects and the risk of clinical CVD in the Cardiovascular Health Study. Diabetes (1343), impaired glucose tolerance (1433), and normal (2421) were defined by World Health Organization criteria at baseline in 1989 to 1990. The average follow-up was 6.4 years (mean age 73 years). Diabetics had a higher prevalence of clinical and subclinical CVD at baseline. Compared with diabetes in the absence of subclinical disease, the presence of subclinical CVD and diabetes was associated with significant increased adjusted relative risk of death (1.5, CI 0.93 to 2.41), relative risk of incident coronary heart disease (1.99, CI 1.25 to 3.19), and incident myocardial infarction (1.93, CI 0.96 to 3.91). The risk of clinical events was greater for participants with a history of diabetes compared with newly diagnosed diabetics at baseline. Compared with nondiabetic nonhypertensive subjects without subclinical disease, patients with a combination of diabetes, hypertension, and subclinical disease had a 12-fold increased risk of stroke. Fasting blood glucose levels were a weak predictor of incident coronary heart disease as were most other risk factors. Subclinical CVD was the primary determinant of clinical CVD among diabetics in the Cardiovascular Health Study.
10aAged10aArteriosclerosis10aCoronary Disease10aDiabetes Mellitus, Type 110aDiabetes Mellitus, Type 210aDiabetic Angiopathies10aFemale10aHumans10aIncidence10aMale10aMultivariate Analysis10aMyocardial Infarction10aPrevalence10aProportional Hazards Models10aRisk Factors10aSex Distribution10aStroke1 aKuller, L H1 aVelentgas, P1 aBarzilay, J1 aBeauchamp, N, J1 aO'Leary, D H1 aSavage, P, J uhttps://chs-nhlbi.org/node/61102877nas a2200361 4500008004100000022001400041245008300055210006900138260001300207300001100220490000800231520194700239653001002186653000902196653001202205653001902217653002802236653001102264653001102275653000902286653001602295653002002311653001702331653002902348653001202377653001602389100001902405700001102424700001502435700001102450700001902461856003502480 2000 eng d a1073-449X00aDoes snoring predict sleepiness independently of apnea and hypopnea frequency?0 aDoes snoring predict sleepiness independently of apnea and hypop c2000 Oct a1512-70 v1623 aObstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.
10aAdult10aAged10aArousal10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aRisk Factors10aSleep Apnea, Obstructive10aSnoring10aWakefulness1 aGottlieb, D, J1 aYao, Q1 aRedline, S1 aAli, T1 aMahowald, M, W uhttps://chs-nhlbi.org/node/62302519nas a2200445 4500008004100000022001400041245010200055210006900157260001300226300001100239490000800250520134300258653001001601653000901611653002201620653001201642653002801654653001101682653001101693653002901704653000901733653001601742653002301758653001101781653001901792653002001811653001701831653002601848100001501874700001601889700001801905700001501923700001901938700001901957700001801976700001601994700001602010700001202026856003502038 2000 eng d a1073-449X00aEffects of varying approaches for identifying respiratory disturbances on sleep apnea assessment.0 aEffects of varying approaches for identifying respiratory distur c2000 Feb a369-740 v1613 aVarying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.
10aAdult10aAged10aAged, 80 and over10aArousal10aDiagnosis, Differential10aFemale10aHumans10aLung Volume Measurements10aMale10aMiddle Aged10aObserver Variation10aOxygen10aOxyhemoglobins10aPolysomnography10aRisk Factors10aSleep Apnea Syndromes1 aRedline, S1 aKapur, V, K1 aSanders, M, H1 aQuan, S, F1 aGottlieb, D, J1 aRapoport, D, M1 aBonekat, W, H1 aSmith, P, L1 aKiley, J, P1 aIber, C uhttps://chs-nhlbi.org/node/60903047nas a2200409 4500008004100000022001400041245016200055210006900217260001300286300001100299490000700310520188400317653000902201653002202210653001202232653001002244653002102254653003302275653001102308653001102319653002302330653001502353653003102368653002802399653001502427653002402442653001702466653001802483100001302501700001502514700001502529700001602544700001502560700001402575700001302589856003502602 2000 eng d a0002-861400aEstrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study.0 aEstrogen replacement therapy and MRIdemonstrated cerebral infarc c2000 May a467-720 v483 aOBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women.
DESIGN: A population-based prospective study (Cardiovascular Health Study).
SETTING: Four regions in the United States.
PARTICIPANTS: A total of 2133 (62.9% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994.
MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (> or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates.
RESULTS: Current use of ERT was reported by 15% and past use by another 23% of participants; 35% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE.
CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear.
10aAged10aAged, 80 and over10aAtrophy10aBrain10aBrain Infarction10aEstrogen Replacement Therapy10aFemale10aHumans10aIntelligence Tests10aLife Style10aMagnetic Resonance Imaging10aPopulation Surveillance10aPrevalence10aProspective Studies10aSocial Class10aUnited States1 aLuoto, R1 aManolio, T1 aMeilahn, E1 aBhadelia, R1 aFurberg, C1 aCooper, L1 aKraut, M uhttps://chs-nhlbi.org/node/61603163nas a2200337 4500008004100000022001400041245008900055210006900144260001600213300001200229490000700241520223900248653000902487653002202496653002202518653002202540653002102562653003302583653001102616653001302627653001102640653002702651653002902678653001702707100001302724700001202737700001302749700001402762700001402776856003502790 2000 eng d a0028-387800aEstrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.0 aEstrogen use APOE and cognitive decline evidence of geneenvironm c2000 May 23 a1949-540 v543 aOBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline.
METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening.
RESULTS: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke.
CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.
10aAged10aAlzheimer Disease10aApolipoprotein E410aApolipoproteins E10aCarotid Stenosis10aEstrogen Replacement Therapy10aFemale10aGenotype10aHumans10aMental Status Schedule10aNeuropsychological Tests10aRisk Factors1 aYaffe, K1 aHaan, M1 aByers, A1 aTangen, C1 aKuller, L uhttps://chs-nhlbi.org/node/61703361nas a2200421 4500008004100000022001400041245008200055210006900137260001300206300000900219490000700228520217000235653000902405653002202414653001002436653001902446653001702465653001702482653001802499653002302517653003002540653001102570653001502581653002702596653002802623653001102651653002502662653000902687653002202696653003402718653005702752100001902809700002402828700002202852700001602874700001402890856003502904 2000 eng d a0012-179700aEvidence of islet cell autoimmunity in elderly patients with type 2 diabetes.0 aEvidence of islet cell autoimmunity in elderly patients with typ c2000 Jan a32-80 v493 aIn light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.
10aAged10aAged, 80 and over10aAging10aAutoantibodies10aAutoantigens10aAutoimmunity10aBlood Glucose10aC-Reactive Protein10aDiabetes Mellitus, Type 210aFemale10aFibrinogen10aGlucose Tolerance Test10aGlutamate Decarboxylase10aHumans10aIslets of Langerhans10aMale10aMembrane Proteins10aProtein Tyrosine Phosphatases10aReceptor-Like Protein Tyrosine Phosphatases, Class 81 aPietropaolo, M1 aBarinas-Mitchell, E1 aPietropaolo, S, L1 aKuller, L H1 aTrucco, M uhttps://chs-nhlbi.org/node/60601932nas a2200349 4500008004100000022001400041245013700055210006900192260001300261300001100274490000700285520098400292653000901276653001201285653001501297653001501312653002101327653001101348653002001359653001801379653001101397653002501408653000901433653001801442653001601460653001201476100001601488700001401504700001401518700001501532856003501547 2000 eng d a0882-797400aNegative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.0 aNegative and positive health effects of caring for a disabled sp c2000 Jun a259-710 v153 aData from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.
10aAged10aAnxiety10aCaregivers10aDepression10aDisabled Persons10aFemale10aHealth Behavior10aHealth Status10aHumans10aLongitudinal Studies10aMale10aMental Health10aRisk-Taking10aSpouses1 aBeach, S, R1 aSchulz, R1 aYee, J, L1 aJackson, S uhttps://chs-nhlbi.org/node/61901497nas a2200325 4500008004100000022001400041245008500055210006900140260001300209300001100222490000700233520062700240653000900867653002200876653002200898653001100920653001100931653000900942653002900951653002800980653002101008100001401029700001601043700001601059700001701075700001701092700001301109700001401122856003501136 2000 eng d a1385-404600aNormative data on the Boston Naming Test and two equivalent 30-item short forms.0 aNormative data on the Boston Naming Test and two equivalent 30it c2000 Nov a526-340 v143 aBecause of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer's disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.
10aAged10aAged, 80 and over10aAlzheimer Disease10aFemale10aHumans10aMale10aNeuropsychological Tests10aPopulation Surveillance10aReference Values1 aSaxton, J1 aRatcliff, G1 aMunro, C, A1 aCoffey, E, C1 aBecker, J, T1 aFried, L1 aKuller, L uhttps://chs-nhlbi.org/node/64103300nas a2200385 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520225600248653000902504653002202513653002102535653001102556653002502567653001802592653001102610653003102621653000902652653002402661653001702685653001802702100002002720700001702740700002002757700001602777700001502793700001802808700001602826700001902842700001802861856003502879 2000 eng d a0735-109700aPredictors of congestive heart failure in the elderly: the Cardiovascular Health Study.0 aPredictors of congestive heart failure in the elderly the Cardio c2000 May a1628-370 v353 aOBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population.
BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics.
METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained.
RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%).
CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.
10aAged10aAged, 80 and over10aCoronary Disease10aFemale10aGeriatric Assessment10aHeart Failure10aHumans10aIschemic Attack, Transient10aMale10aProspective Studies10aRisk Factors10aSurvival Rate1 aGottdiener, J S1 aArnold, A, M1 aAurigemma, G, P1 aPolak, J, F1 aTracy, R P1 aKitzman, D, W1 aGardin, J M1 aRutledge, J, E1 aBoineau, R, C uhttps://chs-nhlbi.org/node/61502729nas a2200385 4500008004100000022001400041245011700055210006900172260001300241300001100254490000700265520167500272653000901947653001901956653002101975653002801996653002302024653002402047653001102071653002202082653001102104653000902115653002602124653001402150653001702164653001102181653001802192100001802210700001602228700001602244700001502260700001602275700001702291856003502308 2000 eng d a0735-109700aPrevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly.0 aPrevalence predisposing factors and prognosis of clinically unre c2000 Jan a119-260 v353 aOBJECTIVES: This study was designed to determine the prevalence of unrecognized myocardial infarction (UMI), as well as risk factors, and to compare prognosis after detection of previously UMI to that after recognized myocardial infarction (RMI).
BACKGROUND: Past studies revealed that a significant proportion of MIs escape recognition, and that prognosis after such events is poor, but the epidemiology of UMI has not been reassessed in the contemporary era.
METHODS: The Cardiovascular Health Study (CHS) database, composed of individuals > or =65, was queried for participants who, at entry, demonstrated electrocardiographic evidence of a prior Q-wave MI, but who lacked a history of this diagnosis. The features and outcomes of this group were compared to those of individuals with prevalent RMI.
RESULTS: Of 5,888 participants, 901 evidenced a past MI, and 201 (22.3%) were previously unrecognized. The independent predictors of UMI were the absence of angina and the absence of congestive heart failure (CHF). Six-year mortality did not significantly differ between the two groups.
CONCLUSIONS: 1) In the elderly, UMI continues to represent a significant proportion of all MIs; 2) associations with angina and CHF may reflect complex neurological issues, but they also may represent diagnosis bias; 3) these individuals can otherwise not be distinguished from those with recognized infarctions; and 4) mortality rates after UMI and RMI are similar. Future studies should address screening for UMI, risk stratification after detection of previously UMI, and the role of standard post-MI therapies.
10aAged10aCause of Death10aCoronary Disease10aCross-Sectional Studies10aDatabases, Factual10aElectrocardiography10aFemale10aFollow-Up Studies10aHumans10aMale10aMyocardial Infarction10aPrognosis10aRisk Factors10aStroke10aSurvival Rate1 aSheifer, S, E1 aGersh, B, J1 aYanez, N, D1 aAdes, P, A1 aBurke, G, L1 aManolio, T A uhttps://chs-nhlbi.org/node/60702927nas a2200385 4500008004100000022001400041245020200055210006900257260001300326300001100339490000700350520174100357653003902098653001602137653000902153653001802162653002402180653004002204653001102244653001102255653003402266653000902300653003002309653001502339653001602354653002002370100002102390700001502411700002002426700001702446700001502463700001302478700001502491856003502506 2000 eng d a0022-073600aRace- and sex-specific ECG models for left ventricular mass in older populations. Factors influencing overestimation of left ventricular hypertrophy prevalence by ECG criteria in African-Americans.0 aRace and sexspecific ECG models for left ventricular mass in old c2000 Jul a205-180 v333 aThe validity of the reported high prevalence of left ventricular hypertrophy (LVH) among African-American men and women has been questioned owing to conflicting echocardiographic evidence. We used echocardiographic left ventricular mass (LVM) from M-mode measurements to evaluate associations between LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and African-American men and women 65 years of age and older who were participants of the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were substantially higher in African-Americans, with apparent LVH prevalence 2 to 3 times higher in African American men and women than in white men and women, although there was no significant racial difference in echocardiographic LVM. The higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men is in part owing to smaller lateral chest diameter. In women, reasons for racial differences in ECG LVH prevalence remain largely unexplained although a small part of the excess LVH in African-American women by the Sokolow-Lyon criteria appears to be owing to a larger lateral chest semidiameter in white women. ECG variables alone were too inaccurate for LVM prediction, and it was necessary to incorporate in all ECG models body weight that was properly adjusted for race and sex. This resulted in modest LVM prediction accuracy, with R-square values ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM estimation with an appropriate adjustment for body size differences are expected to facilitate evaluation of LVH status in contrasting racial population groups.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aAnthropometry10aElectrocardiography10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertrophy, Left Ventricular10aMale10aPredictive Value of Tests10aPrevalence10aSex Factors10aUltrasonography1 aRautaharju, P, M1 aPark, L, P1 aGottdiener, J S1 aSiscovick, D1 aBoineau, R1 aSmith, V1 aPowe, N, R uhttps://chs-nhlbi.org/node/62102727nas a2200409 4500008004100000022001400041245013200055210006900187260001600256300001000272490000700282520157300289653001601862653002801878653002701906653002101933653002301954653002201977653001101999653001102010653000902021653001602030653001202046653002002058653002402078653003002102653001602132653002602148100001602174700001902190700001802209700001502227700001202242700001202254700001602266856003502282 2000 eng d a0161-810500aRates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing.0 aRates of sensor loss in unattended home polysomnography the infl c2000 Aug 01 a682-80 v233 aOBJECTIVES: To evaluate study failure and sensor loss in unattended home polysomnography and their relationship to age, gender, obesity, and severity of sleep-disordered breathing (SDB).
DESIGN: A cross-sectional analysis of data gathered prospectively for the Sleep Heart Health Study (SHHS).
SETTING: Unattended polysomnography was performed in participants' homes by the staff of the sites that are involved in SHHS.
PARTICIPANTS: 6,802 individuals who met the inclusion criteria (age >40 years, no history of treatment of sleep apnea, no tracheostomy, no current home oxygen therapy) for SHHS.
RESULTS: A total of 6802 participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%) were acceptable. Obesity was associated with a decreased likelihood of a successful initial study. After one or more attempts, 6440 participants (94.7%) had studies that were judged as acceptable. The mean duration of scorable signals for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects of age, gender, BMI, and RDI on specific signal durations were not clinically significant.
CONCLUSION: Unattended home PSG as performed for SHHS was usually successful. Participant characteristics had very weak associations with duration of scorable signal. This study suggests that unattended home PSG, when performed with proper protocols and quality controls, has reasonable success rates and signal quality for the evaluation of SDB in clinical and research settings.
10aAge Factors10aCross-Sectional Studies10aElectroencephalography10aElectromyography10aElectrooculography10aEquipment Failure10aFemale10aHumans10aMale10aMiddle Aged10aObesity10aPolysomnography10aProspective Studies10aSeverity of Illness Index10aSex Factors10aSleep Apnea Syndromes1 aKapur, V, K1 aRapoport, D, M1 aSanders, M, H1 aEnright, P1 aHill, J1 aIber, C1 aRomaniuk, J uhttps://chs-nhlbi.org/node/62002566nas a2200385 4500008004100000022001400041245011500055210006900170260001300239300001100252490000700263520149700270653003901767653000901806653001001815653001901825653001501844653004001859653001101899653001101910653001701921653001101938653000901949653002401958653002601982653001702008653001202025653002202037100001702059700002002076700001602096700001702112700001602129856003502145 2000 eng d a0085-253800aTobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population.0 aTobacco hypertension and vascular disease risk factors for renal c2000 May a2072-90 v573 aBACKGROUND: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population.
METHODS: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase.
RESULTS: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness.
CONCLUSIONS: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.
10aAfrican Continental Ancestry Group10aAged10aAging10aCohort Studies10aCreatinine10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension10aKidney10aMale10aRegression Analysis10aRetrospective Studies10aRisk Factors10aSmoking10aVascular Diseases1 aBleyer, A, J1 aShemanski, L, R1 aBurke, G, L1 aHansen, K, J1 aAppel, R, G uhttps://chs-nhlbi.org/node/61403233nas a2200445 4500008004100000022001400041245014200055210006900197260001300266300001200279490000700291520198100298653000902279653001002288653002102298653001202319653001002331653001902341653002402360653001602384653001502400653001102415653001902426653001102445653002002456653002502476653003102501653000902532653002902541653001502570653002402585653003202609653001802641100001802659700002002677700002002697700001502717700002002732856003502752 2001 eng d a1524-462800aAlcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.0 aAlcohol consumption and subclinical findings on magnetic resonan c2001 Sep a1939-460 v323 aBACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings.
METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics.
RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007).
CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.
10aAged10aAging10aAlcohol Drinking10aAtrophy10aBrain10aBrain Diseases10aCerebral Infarction10aComorbidity10aDemography10aFemale10aHealth Surveys10aHumans10aLogistic Models10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aNerve Fibers, Myelinated10aOdds Ratio10aProspective Studies10aSensitivity and Specificity10aUnited States1 aMukamal, K, J1 aLongstreth, W T1 aMittleman, M, A1 aCrum, R, M1 aSiscovick, D, S uhttps://chs-nhlbi.org/node/66003312nas a2200409 4500008004100000022001400041245014600055210006900201260001600270300001200286490000800298520218500306653000902491653001902500653001102519653001102530653000902541653002602550653001402576653003202590653002402622653001702646653001102663653001802674653001802692100001502710700001702725700001602742700001502758700001702773700001402790700001702804700001602821700001602837700001402853856003502867 2001 eng d a0003-992600aAssociation between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.0 aAssociation between blood pressure level and the risk of myocard c2001 May 14 a1183-920 v1613 aBACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure.
METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified.
RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension.
CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.
10aAged10aBlood Pressure10aFemale10aHumans10aMale10aMyocardial Infarction10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke10aSurvival Rate10aUnited States1 aPsaty, B M1 aFurberg, C D1 aKuller, L H1 aCushman, M1 aSavage, P, J1 aLevine, D1 aO'Leary, D H1 aBryan, R, N1 aAnderson, M1 aLumley, T uhttps://chs-nhlbi.org/node/64702679nas a2200385 4500008004100000022001400041245010300055210006900158260001600227300001100243490000800254520164800262653000901910653002501919653001501944653002301959653002801982653001602010653001102026653001502037653001102052653001702063653002002080653000902100653002202109653001602131653001202147100001802159700001502177700001602192700001602208700001902224700001502243856003502258 2001 eng d a0002-926200aAssociation between physical activity and markers of inflammation in a healthy elderly population.0 aAssociation between physical activity and markers of inflammatio c2001 Feb 01 a242-500 v1533 aHigher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.
10aAged10aAnalysis of Variance10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aFactor VIII10aFemale10aFibrinogen10aHumans10aInflammation10aLeukocyte Count10aMale10aPhysical Exertion10aSex Factors10aSmoking1 aGeffken, D, F1 aCushman, M1 aBurke, G, L1 aPolak, J, F1 aSakkinen, P, A1 aTracy, R P uhttps://chs-nhlbi.org/node/62803637nas a2200517 4500008004100000022001400041245008300055210006900138260001300207300001000220490000700230520224400237653002702481653000902508653002502517653001702542653002002559653001702579653002902596653001502625653002802640653001502668653002202683653001302705653001102718653002202729653002002751653001102771653001802782653000902800653001702809653001702826653002802843653003702871653002502908653001702933653002102950653002402971653001702995100001503012700001403027700001503041700001403056700001403070856003503084 2001 eng d a0002-861400aThe association of bone mineral density and depression in an older population.0 aassociation of bone mineral density and depression in an older p c2001 Jun a732-60 v493 aOBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population.
DESIGN: Population-based, cross-sectional study.
SETTING: Study subjects were participants in the Cardiovascular Health Study (CHS), a longitudinal, long-term, follow-up study, at the University of California Davis (Sacramento, California) and the University of Pittsburgh (Pittsburgh, Pennsylvania) clinical centers.
PARTICIPANTS: A random sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS.
MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry (DEXA), after adjustment for multiple covariates, was compared with depression evaluated with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for osteoporosis were compared in depressed and nondepressed participants. Potential correlates were entered into a regression model. Depression scores were compared in normal, osteopenic, and osteoporotic individuals.
RESULTS: Sixteen percent of participants were clinically depressed; 9% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm2 lower in those with clinical depression. High CES-Dm scores were associated with lower BMD (P < .001) when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen use, gender, race, smoking and drinking. When stratified by race, this remained true for all Caucasians (P < .01), all African Americans (P < .05), and when stratified by race and gender the association remained only for all Caucasian women (P < .001). In women and Caucasian men there was an increase in depression scores among individuals with osteoporotic-range BMDs.
CONCLUSIONS: A significant association was found between BMD and depressive symptoms after adjustment for osteoporosis risk factors. In Caucasians, depressive symptoms were associated with both osteoporotic and osteopenic levels of BMD. Causality cannot be ascribed, with only one measurement of BMD. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression.
10aAbsorptiometry, Photon10aAged10aAnalysis of Variance10aBlack People10aBody Mass Index10aBone Density10aBone Diseases, Metabolic10aCalifornia10aCross-Sectional Studies10aDepression10aEnergy Metabolism10aExercise10aFemale10aFollow-Up Studies10aFractures, Bone10aHumans10aLinear Models10aMale10aOsteoporosis10aPennsylvania10aPopulation Surveillance10aPsychiatric Status Rating Scales10aRadionuclide Imaging10aRisk Factors10aSex Distribution10aSingle-Blind Method10aWhite People1 aRobbins, J1 aHirsch, C1 aWhitmer, R1 aCauley, J1 aHarris, T uhttps://chs-nhlbi.org/node/65602779nas a2200421 4500008004100000022001400041245012300055210006900178260001600247300001100263490000700274520157800281653001001859653002801869653002001897653002101917653003801938653001101976653001801987653001102005653000902016653001602025653002002041653002802061653001502089653002002104653001702124653003002141653002602171653001802197100001802215700001902233700001602252700001902268700002002287700001502307856003502322 2001 eng d a0161-810500aThe association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study.0 aassociation of sleepdisordered breathing and sleep symptoms with c2001 Feb 01 a96-1050 v243 aThis study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6%) were significantly more likely to have SDB compared to women (5.6%), while women (42.4%) were significantly more likely to report DIMS than men (32.5%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.
10aAdult10aCardiovascular Diseases10aChronic Disease10aCircadian Rhythm10aDisorders of Excessive Somnolence10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPolysomnography10aPopulation Surveillance10aPrevalence10aQuality of Life10aRisk Factors10aSeverity of Illness Index10aSleep Apnea Syndromes10aUnited States1 aBaldwin, C, M1 aGriffith, K, A1 aNieto, F, J1 aO'Connor, G, T1 aWalsleben, J, A1 aRedline, S uhttps://chs-nhlbi.org/node/63303119nas a2200457 4500008004100000022001400041245015400055210006900209260001300278300001100291490000600302520185400308653001502162653001002177653001602187653000902203653002202212653002202234653002002256653001102276653001102287653000902298653001602307653002302323653002802346653003102374653001602405653001702421653002302438100002102461700001102482700001202493700001602505700001702521700001702538700001602555700001902571700001702590700001902607856003502626 2001 eng d a1350-627700aBrachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter.0 aBrachial flowmediated vasodilator responses in populationbased r c2001 Oct a319-280 v83 aBACKGROUND: Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform.
METHODS: We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4,040 ultrasound examinations from subjects aged 14 to 98 years.
RESULTS: Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 +/- 0.10% (mean +/- standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 +/- 0.87 mm and 0.15 +/- 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P< 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2,315) had significantly larger per cent change in diameter than men (n=1,725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001).
CONCLUSIONS: Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.
10aAdolescent10aAdult10aAge Factors10aAged10aAged, 80 and over10aBlood Circulation10aBrachial Artery10aFemale10aHumans10aMale10aMiddle Aged10aObserver Variation10aPopulation Surveillance10aReproducibility of Results10aSex Factors10aVasodilation10aVasodilator Agents1 aHerrington, D, M1 aFan, L1 aDrum, M1 aRiley, W, A1 aPusser, B, E1 aCrouse, J, R1 aBurke, G, L1 aMcBurnie, M, A1 aMorgan, T, M1 aEspeland, M, A uhttps://chs-nhlbi.org/node/66503361nas a2200385 4500008004100000022001400041245015700055210006900212260001600281300001100297490000800308520223600316653000902552653002202561653003102583653001902614653002802633653002402661653001102685653001102696653001402707653002502721653000902746653001402755653003202769653001702801653002002818653001802838100001702856700001702873700001602890700001702906700001702923856003502940 2001 eng d a0003-481900aCardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.0 aCardiovascular disease and mortality in older adults with small c2001 Feb 06 a182-900 v1343 aBACKGROUND: Persons with abdominal aortic aneurysm are more likely to have a higher prevalence of risk factors for and clinical manifestations of cardiovascular disease. It is unknown whether these factors explain the high mortality rate associated with abdominal aortic aneurysm.
OBJECTIVE: To describe the risk for mortality, cardiovascular mortality, and cardiovascular morbidity in persons screened for abdominal aortic aneurysm.
DESIGN: Longitudinal cohort study.
SETTING: Four communities in the United States.
PARTICIPANTS: 4734 men and women older than 65 years of age recruited from Medicare eligibility lists.
MEASUREMENTS: Abdominal ultrasonography was used to measure the aortic diameter and the ratio of infrarenal to suprarenal measurement of aortic diameter in 1992-1993. Abdominal aortic aneurysm was defined as aortic diameter of 3 cm or greater or infrarenal-to-suprarenal ratio of 1.2 or greater. Mortality, cardiovascular disease mortality, incident cardiovascular disease, and repair or rupture were assessed after 4.5 years.
RESULTS: The prevalence of aneurysm was 8.8%, and 87.7% of aneurysms were 3.5 cm or less in diameter. Rates of total mortality (65.1 vs. 32.8 per 1000 person-years), cardiovascular mortality (34.3 vs. 13.8 per 1000 person-years), and incident cardiovascular disease (47.3 vs. 31.0 per 1000 person-years) were higher in participants with aneurysm than in those without aneurysm; after adjustment for age, risk factors, and presence of other cardiovascular disease, the respective relative risks were 1.32, 1.36, and 1.57. Rates of repair and rupture were low.
CONCLUSIONS: Rates of total mortality, cardiovascular disease mortality, and incident cardiovascular disease were higher in participants with abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease, and extent of atherosclerosis detected by noninvasive testing. Persons with smaller aneurysms detected by ultrasonography should be advised to modify risk factors for cardiovascular disease while under surveillance for increase in the size of the aneurysm.
10aAged10aAged, 80 and over10aAortic Aneurysm, Abdominal10aAortic Rupture10aCardiovascular Diseases10aDisease Progression10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aMortality10aProportional Hazards Models10aRisk Factors10aUltrasonography10aUnited States1 aNewman, A, B1 aArnold, A, M1 aBurke, G, L1 aO'Leary, D H1 aManolio, T A uhttps://chs-nhlbi.org/node/63002959nas a2200373 4500008004100000022001400041245013300055210006900188260001300257300001100270490000700281520185200288653000902140653001002149653002402159653003002183653002102213653001902234653002602253653001102279653001102290653002502301653003102326653000902357653001702366100002002383700001302403700001702416700002002433700001902453700001702472710006102489856003502550 2001 eng d a0003-994200aCluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study.0 aCluster analysis and patterns of findings on cranial magnetic re c2001 Apr a635-400 v583 aOBJECTIVE: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis.
SUBJECTS AND METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations.
RESULTS: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected.
CONCLUSIONS: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.
10aAged10aBrain10aCerebral Infarction10aCerebrovascular Disorders10aCluster Analysis10aCohort Studies10aDiscriminant Analysis10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRisk Factors1 aLongstreth, W T1 aDiehr, P1 aManolio, T A1 aBeauchamp, N, J1 aJungreis, C, A1 aLefkowitz, D1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/64402533nas a2200493 4500008004100000022001400041245009000055210006900145260001600214300001200230490000800242520121300250653002101463653001601484653000901500653002201509653001701531653001501548653001201563653001901575653001601594653002501610653002801635653002101663653001501684653001101699653001101710653002001721653000901741653003001750653001501780653001701795653002101812653001601833653003101849653001701880100001701897700001801914700002201932700001501954700001901969700001601988856003502004 2001 eng d a1524-453900aCoronary artery calcification in older adults to age 99: prevalence and risk factors.0 aCoronary artery calcification in older adults to age 99 prevalen c2001 Nov 27 a2679-840 v1043 aBACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied.
METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile.
CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.
10aAge Distribution10aAge Factors10aAged10aAged, 80 and over10aBlack People10aCalcinosis10aCalcium10aCohort Studies10aComorbidity10aCoronary Angiography10aCoronary Artery Disease10aCoronary Vessels10aDemography10aFemale10aHumans10aLogistic Models10aMale10aPredictive Value of Tests10aPrevalence10aRisk Factors10aSex Distribution10aSex Factors10aTomography, X-Ray Computed10aWhite People1 aNewman, A, B1 aNaydeck, B, L1 aSutton-Tyrrell, K1 aFeldman, A1 aEdmundowicz, D1 aKuller, L H uhttps://chs-nhlbi.org/node/66702660nas a2200397 4500008004100000022001400041245006800055210006700123260001300190300001100203490000800214520152600222653000901748653002201757653001001779653001101789653001101800653001801811653001101829653000901840653002701849653003001876653003001906653004301936653002101979653003302000653001702033653004102050653001502091100001802106700002102124700001602145700001902161710004702180856003502227 2001 eng d a0012-369200aCorrelates of peak expiratory flow lability in elderly persons.0 aCorrelates of peak expiratory flow lability in elderly persons c2001 Dec a1861-80 v1203 aOBJECTIVE: To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly.
METHODS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study completed an asthma questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum - PEF minimum)/mean PEF.
RESULTS: Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18% in those with current asthma (n = 165) vs 12% in healthy nonsmokers (upper limit of normal, 29%). Approximately 26% of those with asthma and 14% of the other participants had abnormally high PEF lability (> 29%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability.
CONCLUSIONS: Measurement of PEF lability at home is highly successful in elderly persons. PEF lability > or = 30% is abnormal in the elderly and is associated with asthma.
10aAged10aAged, 80 and over10aAging10aAsthma10aFemale10aHeart Failure10aHumans10aMale10aMonitoring, Ambulatory10aPeak Expiratory Flow Rate10aPredictive Value of Tests10aPulmonary Disease, Chronic Obstructive10aReference Values10aRhinitis, Allergic, Seasonal10aRisk Factors10aSignal Processing, Computer-Assisted10aSpirometry1 aEnright, P, L1 aMcClelland, R, L1 aBuist, A, S1 aLebowitz, M, D1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/67102826nas a2200493 4500008004100000022001400041245010900055210006900164260001600233300001000249490000800259520145500267653001001722653001601732653000901748653001901757653002801776653003701804653002101841653001101862653002901873653001101902653003501913653001801948653000901966653001601975653001201991653002302003653002002026653002402046653001602070653002602086653003202112653001902144100001702163700001702180700001602197700001202213700001902225700001602244700001902260700001802279856003502297 2001 eng d a1073-449X00aEchocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study.0 aEchocardiographic features of the right heart in sleepdisordered c2001 Sep 15 a933-80 v1643 aThe effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.
10aAdult10aAge Factors10aAged10aCohort Studies10aCross-Sectional Studies10aData Interpretation, Statistical10aEchocardiography10aFemale10aForced Expiratory Volume10aHumans10aHypertrophy, Right Ventricular10aLinear Models10aMale10aMiddle Aged10aObesity10aObserver Variation10aPolysomnography10aProspective Studies10aSex Factors10aSleep Apnea Syndromes10aVentricular Function, Right10aVital Capacity1 aGuidry, U, C1 aMendes, L, A1 aEvans, J, C1 aLevy, D1 aO'Connor, G, T1 aLarson, M G1 aGottlieb, D, J1 aBenjamin, E J uhttps://chs-nhlbi.org/node/66202661nas a2200397 4500008004100000022001400041245008800055210006900143260001300212300001200225490000700237520156200244653000901806653002201815653002501837653002001862653002801882653003001910653003301940653001401973653001101987653001101998653002502009653001502034653001702049653002002066653001702086100002102103700001902124700001702143700001702160700001602177700001902193700001602212856003502228 2001 eng d a1524-463600aEstrogen replacement and brachial artery flow-mediated vasodilation in older women.0 aEstrogen replacement and brachial artery flowmediated vasodilati c2001 Dec a1955-610 v213 aIt remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.
10aAged10aAged, 80 and over10aAnalysis of Variance10aBrachial Artery10aCardiovascular Diseases10aDrug Therapy, Combination10aEstrogen Replacement Therapy10aEstrogens10aFemale10aHumans10aLongitudinal Studies10aProgestins10aRisk Factors10aUltrasonography10aVasodilation1 aHerrington, D, M1 aEspeland, M, A1 aCrouse, J, R1 aRobertson, J1 aRiley, W, A1 aMcBurnie, M, A1 aBurke, G, L uhttps://chs-nhlbi.org/node/67003278nas a2200517 4500008004100000022001400041245007600055210006900131260001300200300001100213490000700224520194300231653000902174653002202183653001002205653002802215653001902243653000902262653001302271653001102284653001802295653001102313653001402324653001502338653002502353653003102378653000902409653001402418653001602432653002102448653001702469653002102486653002602507653001802533653001802551100001602569700001702585700001502602700001502617700001502632700001402647700001202661700001502673710003702688856003502725 2001 eng d a0002-861400aFactors associated with healthy aging: the cardiovascular health study.0 aFactors associated with healthy aging the cardiovascular health c2001 Mar a254-620 v493 aOBJECTIVES: To identify factors associated with remaining healthy in older adults.
DESIGN: Longitudinal cohort study.
SETTING: Data were collected at the four Cardiovascular Health Study field centers.
PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study.
MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes.
RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults.
CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.
10aAged10aAged, 80 and over10aAging10aCardiovascular Diseases10aCohort Studies10aDiet10aExercise10aFemale10aHealth Status10aHumans10aIncidence10aLife Style10aLongitudinal Studies10aLung Diseases, Obstructive10aMale10aNeoplasms10aProbability10aReference Values10aRisk Factors10aSex Distribution10aSocioeconomic Factors10aSurvival Rate10aUnited States1 aBurke, G, L1 aArnold, A, M1 aBild, D, E1 aCushman, M1 aFried, L P1 aNewman, A1 aNunn, C1 aRobbins, J1 aCHS Collaborative Research Group uhttps://chs-nhlbi.org/node/64604256nas a2200469 4500008004100000022001400041245005500055210005300110260001300163300001200176490000700188520307600195653000903271653002203280653001903302653002103321653001203342653001103354653001803365653001103383653001403394653000903408653002003417653001403437653001503451653002103466653001803487653001603505100001503521700001703536700001503553700001703568700001403585700001803599700001403617700001303631700001403644700001303658700001903671710006103690856003503751 2001 eng d a1079-500600aFrailty in older adults: evidence for a phenotype.0 aFrailty in older adults evidence for a phenotype c2001 Mar aM146-560 v563 aBACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.
METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.
RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).
CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.
10aAged10aAged, 80 and over10aCohort Studies10aDisabled Persons10aFatigue10aFemale10aFrail Elderly10aHumans10aIncidence10aMale10aMuscle Weakness10aPhenotype10aPrevalence10aSex Distribution10aUnited States10aWeight Loss1 aFried, L P1 aTangen, C, M1 aWalston, J1 aNewman, A, B1 aHirsch, C1 aGottdiener, J1 aSeeman, T1 aTracy, R1 aKop, W, J1 aBurke, G1 aMcBurnie, M, A1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/63902445nas a2200349 4500008004100000022001400041245010300055210006900158260001600227300001100243490000700254520148900261653000901750653002201759653002901781653001101810653001101821653002501832653000901857653003001866653001101896653002201907653001801929100002001947700001501967700001901982700001502001700001502016700001202031700001702043856003502060 2001 eng d a0028-387800aFrequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study.0 aFrequency and predictors of stroke death in 5888 participants in c2001 Feb 13 a368-750 v563 aBACKGROUND: Few population-based studies have examined in detail issues of stroke-related deaths in elderly people.
METHODS: Participants in the Cardiovascular Health Study (CHS) are 65 years of age or older, have had extensive baseline evaluations, and have been followed-up for fatal and nonfatal cardiovascular and cerebrovascular disease outcomes. Investigators adjudicated these outcomes and classified strokes by types and subtypes.
RESULTS: Over 7 years, 1,310 (22.2%) of 5,888 participants died, and 455 (7.7%) experienced incident stroke. For the 5,888, stroke mortality was 3.2 per 1,000 person-years. For the 455, it was 36.1 per 1,000 person-years, with the most lethal type being hemorrhagic and the ischemic subtype being cardioembolic. After controlling for age and stroke type, the only other independent predictor of death after any stroke was poor performance on a timed walk measured before the incident stroke. Considering only ischemic stroke, the independent predictors of death were African American race and poor performance on timed walk.
CONCLUSION: In CHS, death attributable to stroke is common. As in other studies, the most lethal stroke type was hemorrhagic, and ischemic stroke subtype, cardioembolic. Slow walking, possibly a measure of frailty, was associated with an increased risk of death of stroke. Finally, African Americans faced a greater risk of death than others after an ischemic stroke.
10aAged10aAged, 80 and over10aClinical Trials as Topic10aFemale10aHumans10aLongitudinal Studies10aMale10aPredictive Value of Tests10aStroke10aSurvival Analysis10aUnited States1 aLongstreth, W T1 aBernick, C1 aFitzpatrick, A1 aCushman, M1 aKnepper, L1 aLima, J1 aFurberg, C D uhttps://chs-nhlbi.org/node/62902473nas a2200373 4500008004100000022001400041245005700055210005500112260001300167300001200180490000700192520153600199653000901735653002201744653001001766653001601776653001601792653002801808653002601836653001101862653000901873653001101882653000901893653003001902653001701932653001701949653001201966100001601978700001601994700001302010700002402023700001702047856003502064 2001 eng d a0002-861400aGait variability in community-dwelling older adults.0 aGait variability in communitydwelling older adults c2001 Dec a1646-500 v493 aOBJECTIVES: To describe gait variability at usual and fast walking speeds in community-dwelling older adults and to describe the effects of increasing gait speed on gait variability.
DESIGN: Cross-sectional, descriptive study.
SETTING: The Cardiovascular Health Study at the University of Pittsburgh.
PARTICIPANTS: Ninety-five community-living older adults, 54 women and 41 men, age 65 and older (mean age +/- standard deviation 79.4 +/- 3.37).
MEASUREMENTS: Gait measured at participant's usual and fast walking speed collected using an instrumented walkway. Step-length and step-width variability were determined using the coefficient of variation.
RESULTS: Step-length variability was greatest in those who walked the slowest (r = -0.66, P < .001); step-width variability was smallest in those who walked the slowest (r -0.37, P < .001). Individuals who could not increase their walking speed (<0.10 m/second) on command had an increase in step-length variability and a decrease in step-width variability, whereas those who could increase their speed (>0.10 m/second) had an increase in step-width variability when walking at a faster speed.
CONCLUSIONS: Step-length and step-width variability have opposite associations with gait speed in older adults. Improvement in step-length and step-width variability with attempted acceleration might be a key factor to examine in future studies of disability risk and therapeutic interventions.
10aAged10aAged, 80 and over10aAging10aBody Height10aBody Weight10aCross-Sectional Studies10aDisability Evaluation10aFemale10aGait10aHumans10aMale10aResidence Characteristics10aRisk Factors10aTime Factors10aWalking1 aBrach, J, S1 aBerthold, R1 aCraik, R1 aVanSwearingen, J, M1 aNewman, A, B uhttps://chs-nhlbi.org/node/67902295nas a2200325 4500008004100000022001400041245008100055210006900136260001300205300001000218490000800228520137300236653000901609653002201618653001901640653003301659653001101692653002901703653001101732653002501743653001501768653001901783100001801802700001501820700001801835700001701853700001701870710004701887856003501934 2001 eng d a1073-449X00aHormone replacement therapy is associated with higher FEV1 in elderly women.0 aHormone replacement therapy is associated with higher FEV1 in el c2001 Feb a423-80 v1633 aEstrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.
10aAged10aAged, 80 and over10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aForced Expiratory Volume10aHumans10aLongitudinal Studies10aSpirometry10aVital Capacity1 aCarlson, C, L1 aCushman, M1 aEnright, P, L1 aCauley, J, A1 aNewman, A, B1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63103552nas a2200469 4500008004100000022001400041245015000055210006900205260001600274300001000290490000700300520219200307653000902499653002202508653002502530653002802555653003002583653001102613653001802624653001802642653001102660653002002671653002502691653000902716653001502725653001702740653003102757653001802788653003102806100001802837700001602855700002002871700001402891700001502905700001702920700001702937700001302954700001502967700001802982710004703000856003503047 2001 eng d a0002-914900aImportance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study.0 aImportance of heart failure with preserved systolic function in c2001 Feb 15 a413-90 v873 aAlthough congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6%) to age > or = 85 years (14%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55% of subjects with CHF had normal left ventricular systolic function and 80% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67% vs 42%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.
10aAged10aAged, 80 and over10aAnalysis of Variance10aChi-Square Distribution10aEchocardiography, Doppler10aFemale10aHealth Status10aHeart Failure10aHumans10aLogistic Models10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors10aSurveys and Questionnaires10aUnited States10aVentricular Function, Left1 aKitzman, D, W1 aGardin, J M1 aGottdiener, J S1 aArnold, A1 aBoineau, R1 aAurigemma, G1 aMarino, E, K1 aLyles, M1 aCushman, M1 aEnright, P, L1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63202409nas a2200337 4500008004100000022001400041245011900055210006900174260001300243300001000256490000700266520148600273653002101759653000901780653003001789653002101819653001101840653001801851653001101869653001401880653000901894653003001903100001801933700001601951700001301967700001501980700001201995700001202007700001702019856003502036 2001 eng d a0027-968400aIncidence and predictors of coronary heart disease among older African Americans--the Cardiovascular Health Study.0 aIncidence and predictors of coronary heart disease among older A c2001 Nov a423-90 v933 aAlthough coronary heart disease (CHD) is the leading cause of death and morbidity in older African Americans, relatively little is known about the incidence and predictors of CHD in this population. This study was undertaken to determine the incidence and predictors of CHD in African-American men and women aged 65 years and older. The participants in this study included a total of 924 African-American men and women aged 65 years of age and older who participated in the Cardiovascular Health Study (CHS). The overall CHD incidence was 26.6 per 1,000 person-years of risk. Rates were higher in men than women (35.3 vs. 21.6) and in those 75 years or older than in those less than 75 years (31.3 vs. 24.5). In multivariate analysis, factors associated with higher risk of incident disease were male gender [relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.1, 2.7], diabetes mellitus (RR = 1.9, 95% CI = 1.2, 2.9), total cholesterol (RR for 40 mg/dL increment = 1.3, 95% CI = 1.0, 1.5), and low (i.e., <0.9) ankle-arm index (RR = 2.1, 95% CI = 1.3, 3.4) after adjusting for age. Within this cohort of older African Americans, male gender, diabetes mellitus, total cholesterol, and low ankle-arm index and were independently predictive of incident events. These results suggest that the ankle-arm index, a measure of advanced atherosclerosis, should be further evaluated for its efficacy in identifying older African Americans at risk for incident clinical events.
10aAge Distribution10aAged10aBlack or African American10aCoronary Disease10aFemale10aHealth Status10aHumans10aIncidence10aMale10aPredictive Value of Tests1 aJackson, S, A1 aBurke, G, L1 aThach, C1 aCushman, M1 aIves, D1 aPowe, N1 aManolio, T A uhttps://chs-nhlbi.org/node/66804047nas a2200409 4500008004100000022001400041245011700055210006900172260001600241300001100257490000800268520296800276653000903244653002203253653002603275653001603301653001503317653001003332653001503342653001103357653002203368653002003390653001103410653000903421653002603430653001203456653001603468100001403484700001603498700001203514700001803526700001503544700001403559700001503573700001403588856003503602 2001 eng d a0098-748400aInvolvement in caregiving and adjustment to death of a spouse: findings from the caregiver health effects study.0 aInvolvement in caregiving and adjustment to death of a spouse fi c2001 Jun 27 a3123-90 v2853 aCONTEXT: Most deaths in the United States occur among older persons who have 1 or more disabling conditions. As a result, many deaths are preceded by an extended period during which family members provide care to their disabled relative.
OBJECTIVE: To better understand the effect of bereavement on family caregivers by examining predeath vs postdeath changes in self-reported and objective health outcomes among elderly persons providing varying levels of care prior to their spouse's death.
DESIGN AND SETTING: Prospective, population-based cohort study conducted in 4 US communities between 1993 and 1998.
PARTICIPANTS: One hundred twenty-nine individuals aged 66 to 96 years whose spouse died during an average 4-year follow-up. Individuals were classified as noncaregivers (n = 40), caregivers who reported no strain (n = 37), or strained caregivers (n = 52).
MAIN OUTCOME MEASURES: Changes in depression symptoms (assessed by the 10-item Center for Epidemiological Studies-Depression [CES-D] scale), antidepressant medication use, 6 health risk behaviors, and weight among the 3 groups of participants.
RESULTS: Controlling for age, sex, race, education, prevalent cardiovascular disease at baseline, and interval between predeath and postdeath assessments, CES-D scores remained high but did not change among strained caregivers (9.44 vs 9.19; P =.76), while these scores increased for both noncaregivers (4.74 vs 8.25; F(1,116) = 14.33; P<.001) and nonstrained caregivers (4.94 vs 7.13; F(1,116) = 4.35; P =.04). Noncaregivers were significantly more likely to be using nontricyclic antidepressant medications following the death than the nonstrained caregiver group (odds ratio [OR], 12.85; 95% confidence interval [CI], 1.02-162.13; P =.05). The strained caregiver group experienced significant improvement in health risk behaviors following the death of their spouse (1.47 vs 0.66 behaviors; F(1,118) = 20.23; P<.001), while the noncaregiver and nonstrained caregiver groups showed little change (0.27 vs 0.27 [P =.99] and 0.46 vs 0.27 [P =.39] behaviors, respectively). Noncaregivers experienced significant weight loss following the death (149.1 vs 145.3 lb [67.1 vs 65.4 kg]; F(1,101) = 8.12; P =.005), while the strained and nonstrained caregiving groups did not show significant weight change (156.2 vs 155.2 lb [70.3 vs 69.8 kg] [P =.41] and 156.2 vs 154.0 lb [70.3 vs 69.3 kg] [P =.12], respectively).
CONCLUSIONS: These data indicate that the impact of losing one's spouse among older persons varies as a function of the caregiving experiences that precede the death. Among individuals who are already strained prior to the death of their spouse, the death itself does not increase their level of distress. Instead, they show reductions in health risk behaviors. Among noncaregivers, losing one's spouse results in increased depression and weight loss.
10aAged10aAged, 80 and over10aAntidepressive Agents10aBereavement10aCaregivers10aDeath10aDepression10aFemale10aFollow-Up Studies10aHealth Behavior10aHumans10aMale10aSocioeconomic Factors10aSpouses10aWeight Loss1 aSchulz, R1 aBeach, S, R1 aLind, B1 aMartire, L, M1 aZdaniuk, B1 aHirsch, C1 aJackson, S1 aBurton, L uhttps://chs-nhlbi.org/node/65303165nas a2200421 4500008004100000022001400041245020300055210006900258260001600327300001100343490000700354520191300361653000902274653002202283653002502305653002102330653003002351653001102381653001802392653001102410653001402421653000902435653003002444653003202474653002402506653001702530653001102547100001602558700001802574700001502592700001502607700001402622700002302636700001502659700001602674700001802690856003502708 2001 eng d a0002-914900aM-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).0 aMmode echocardiographic predictors of six to sevenyear incidence c2001 May 01 a1051-70 v873 aPrevious studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86% vs 97%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.
10aAged10aAged, 80 and over10aAnalysis of Variance10aCoronary Disease10aEchocardiography, Doppler10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aPredictive Value of Tests10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke1 aGardin, J M1 aMcClelland, R1 aKitzman, D1 aLima, J, A1 aBommer, W1 aKlopfenstein, H, S1 aWong, N, D1 aSmith, V, E1 aGottdiener, J uhttps://chs-nhlbi.org/node/64802959nas a2200385 4500008004100000022001400041245009100055210006900146260001300215300001000228490000700238520192700245653000902172653002802181653001902209653001002228653001102238653002202249653001802271653002902289653001802318653002002336653001102356653001802367653002502385653000902410653002202419653001702441100001302458700001802471700001802489700001502507700001602522856003502538 2001 eng d a0002-861400aPatterns of self-rated health in older adults before and after sentinel health events.0 aPatterns of selfrated health in older adults before and after se c2001 Jan a36-440 v493 aOBJECTIVES: To describe and compare patterns of change in self-rated health for older adults before death and before and after stroke, myocardial infarction, congestive heart failure, cardiac procedure, hospital admission for cancer, and hip fracture.
DESIGN: "Event cohort," measuring time in months before and after the event.
SETTING: Four U.S. communities.
PARTICIPANTS: 5888 participants in the Cardiovascular Health Study (CHS), sampled from Medicare rolls and followed up to 8 years. Mean age at baseline was 73.
MEASUREMENTS: Self-rated health, including a category for death, assessed at 6-month intervals, and ascertainment of events.
METHODS: We examined the percentage that was healthy each month in the 5 years before death and in the 2 years before and after the other events, and compared the patterns to a "no event" group and to one another, using graphs and linear regression.
RESULTS: For people who died, health status declined slowly until about 9 months before death, when it dropped steeply. Comparing persons equally far from death, health was unrelated to age, but men and whites were healthier than women and blacks. Health for other events declined before the event, dropped steeply at the event, showed some recovery, and then declined further after the event. About 65% to 80% of the subjects were healthy 2 years before their event, but only 35% to 65% were healthy two years afterwards. Patterns were similar although less extreme for the "no event" group.
CONCLUSION: Visualizing trajectories of health helps us understand how serious health events changes health. Conclusions about change must be drawn with care because of a variety of possible biases. We have described the trajectories in detail. Work is now needed to explain, predict, and possibly prevent such changes in health.
10aAged10aCardiovascular Diseases10aCohort Studies10aDeath10aFemale10aFollow-Up Studies10aHealth Status10aHealth Status Indicators10aHip Fractures10aHospitalization10aHumans10aLinear Models10aLongitudinal Studies10aMale10aRandom Allocation10aTime Factors1 aDiehr, P1 aWilliamson, J1 aPatrick, D, L1 aBild, D, E1 aBurke, G, L uhttps://chs-nhlbi.org/node/63402371nas a2200373 4500008004100000022001400041245010300055210006900158260001300227300001000240490000800250520135500258653000901613653001801622653001701640653002001657653002801677653003301705653001101738653001101749653002001760653001801780653001501798653001401813653001701827653002201844653001701866100001501883700001501898700001801913700001501931700001601946856003501962 2001 eng d a0007-104800aPost-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women.0 aPostmenopausal hormone therapy and concentrations of protein C a c2001 Jul a162-80 v1143 aThe effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109% for each vs. 115% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.
10aAged10aAntithrombins10aBlack People10aBody Mass Index10aCross-Sectional Studies10aEstrogen Replacement Therapy10aFemale10aHumans10aLogistic Models10aPostmenopause10aProgestins10aProtein C10aRisk Factors10aVenous Thrombosis10aWhite People1 aCushman, M1 aPsaty, B M1 aMeilahn, E, N1 aDobs, A, S1 aKuller, L H uhttps://chs-nhlbi.org/node/65903182nas a2200397 4500008004100000022001400041245014300055210006900198260001600267300001100283490000700294520205200301653001602353653000902369653002202378653001302400653002102413653001102434653002202445653001802467653001102485653000902496653002602505653002702531653003002558653001402588653003202602653001702634653001202651100002002663700002002683700001702703700001402720700001502734856003502749 2001 eng d a0735-109700aPredictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study.0 aPredictive value of systolic and diastolic function for incident c2001 Mar 15 a1042-80 v373 aOBJECTIVES: We sought to assess the ability of echocardiographic indices of systolic and diastolic function to predict incident congestive heart failure (CHF).
BACKGROUND: Noninvasive indices of subclinical systolic and/or diastolic dysfunction that can be used to identify patients in a transition phase between normal cardiac function and clinical CHF would be valuable. Though midwall shortening and Doppler mitral inflow patterns are seemingly well suited to predict subsequent CHF, the predictive value of these indices has not been investigated.
METHODS: We studied 2,671 participants in the Cardiovascular Health Study who were free of coronary heart disease, CHF or atrial fibrillation. Clinical and quantitative echocardiographic data were obtained in all participants.
RESULTS: At a mean follow-up of 5.2 years (range 0 to 6 years), 170 participants (6.4% of the cohort) developed CHF. Although 96% of these participants had normal or borderline ejection fraction (EF) at baseline, only 57% had normal or borderline EF at the time of hospitalization. In multivariate modeling, fractional shortening at the endocardium (relative risk [RR] 1.85 per 10-unit decrease, confidence interval [CI] 1.27 to 2.39), fractional shortening at the midwall (RR 1.29 per five-unit decrease, 95% CI 1.11-1.51) and peak Doppler peak E (RR 1.15 for each 0.1 M/s increment; CI 1.02 to 1.21) independently predicted incident CHF. Both high and low Doppler E/A ratios were predictive of incident CHF.
CONCLUSIONS: Roughly half the occurrences of CHF in this population are associated with normal or borderline EF. Echocardiographic findings suggestive of subclinical contractile dysfunction and diastolic filling abnormalities are both predictive of subsequent CHF. The standard (FSendo) and refined (FSmw) parameters of systolic function performed similarly in this regard, though subjects with left ventricular hypertrophy and depressed FSmw are at particularly high risk for subsequent CHF.
10aAge Factors10aAged10aAged, 80 and over10aDiastole10aEchocardiography10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aMale10aMultivariate Analysis10aMyocardial Contraction10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aRisk Factors10aSystole1 aAurigemma, G, P1 aGottdiener, J S1 aShemanski, L1 aGardin, J1 aKitzman, D uhttps://chs-nhlbi.org/node/64202599nas a2200337 4500008004100000022001400041245008900055210006900144260001300213300000900226490000800235520167700243653001601920653000901936653002201945653002801967653001101995653002902006653001102035653002502046653000902071653002902080653000902109100001902118700001902137700001702156700001702173700001802190700001802208856003502226 2001 eng d a1073-449X00aPredictors of loss of lung function in the elderly: the Cardiovascular Health Study.0 aPredictors of loss of lung function in the elderly the Cardiovas c2001 Jan a61-80 v1633 aPulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.
10aAge Factors10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aForced Expiratory Volume10aHumans10aLongitudinal Studies10aLung10aLung Volume Measurements10aMale1 aGriffith, K, A1 aSherrill, D, L1 aSiegel, E, M1 aManolio, T A1 aBonekat, H, W1 aEnright, P, L uhttps://chs-nhlbi.org/node/63703104nas a2200469 4500008004100000022001400041245014800055210006900203260001300272300001100285490000700296520173400303653000902037653002002046653002802066653003002094653001902124653002202143653003002165653003002195653002402225653001102249653002402260653001902284653001102303653000902314653003302323653001502356653001802371100001902389700002102408700001602429700001602445700001502461700002002476700001902496700001802515700001702533700001702550710003202567856003502599 2001 eng d a0149-599200aPrevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.0 aPrevalence of clinical and isolated subclinical cardiovascular d c2001 Jul a1233-90 v243 aOBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes.
RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease.
RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes.
CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.
10aAged10aAngina Pectoris10aCardiovascular Diseases10aCerebrovascular Disorders10aCohort Studies10aDiabetes Mellitus10aDiabetes Mellitus, Type 110aDiabetes Mellitus, Type 210aElectrocardiography10aFemale10aGlucose Intolerance10aHeart Diseases10aHumans10aMale10aPeripheral Vascular Diseases10aPrevalence10aUnited States1 aBarzilay, J, I1 aSpiekerman, C, F1 aKuller, L H1 aBurke, G, L1 aBittner, V1 aGottdiener, J S1 aBrancati, F, L1 aOrchard, T, J1 aO'Leary, D H1 aSavage, P, J1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/65202203nas a2200289 4500008004100000022001400041245007000055210006900125260000900194300001100203490000700214520146600221653001601687653000901703653001001712653001101722653001801733653001101751653000901762653001601771653002001787653002401807653001601831100001301847700001801860856003501878 2001 eng d a0962-934300aProbabilities of transition among health states for older adults.0 aProbabilities of transition among health states for older adults c2001 a431-420 v103 aGOAL: To estimate the probabilities of transition among self-rated health states for older adults, and examine how they vary by age and sex.
METHODS: We used self-rated health (excellent, very good, good, fair, poor, dead) collected in two longitudinal studies of older adults (mean age 75) to estimate the probability of transition in 2 years. We used the estimates to project future health for selected cohorts.
FINDINGS: These older adults were most likely to be in the same health state 2 years later, but a substantial proportion changed in both directions. Transition probabilities varied by initial health state, age and sex. Men were more likely than women to transition to excellent or dead. Women were more likely than men to transition to good or fair health. Although women aged 70 will have more years of life and more years of healthy life than men, they also have more years of unhealthy life, and the proportion of remaining life that is healthy is slightly higher for men. When observed and predicted years of healthy life (YHL) were compared in various subgroups, the YHL of persons with less favorable baseline characteristics was lower than predicted, and vice-versa. Differences, however, were small (about 5%).
CONCLUSIONS: These transition probability estimates can be used to predict the future health of individuals or groups as a function of current age, sex, and self-rated health.
10aAge Factors10aAged10aAging10aFemale10aHealth Status10aHumans10aMale10aProbability10aQuality of Life10aRegression Analysis10aSex Factors1 aDiehr, P1 aPatrick, D, L uhttps://chs-nhlbi.org/node/67303483nas a2200433 4500008004100000022001400041245013200055210006900187260001300256300001300269490000700282520226300289653000902552653002202561653001902583653002102602653001502623653002802638653002102666653001102687653001702698653001102715653001702726653003402743653000902777653002102786653001702807653001802824653001802842653001702860653003102877100001702908700001802925700002002943700001702963700001802980700001602998856003503014 2001 eng d a0263-635200aRelation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study.0 aRelation of hemodynamics and risk factors to ventricularvascular c2001 Oct a1893-9030 v193 aOBJECTIVE: To investigate the interaction between left ventricular (LV) geometry, carotid structure and arterial compliance in relation to hemodynamic stimuli and risk factors (plasma cholesterol, body mass index, insulin resistance, smoking habit, age, sex and race).
DESIGN: Cross-sectional.
METHODS: Echocardiography and carotid ultrasound were performed in 2375 elderly subjects without signs or history of prevalent cardiovascular disease, diabetes or renal disease (795 men; 298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health Study. Arterial compliance was estimated by the prognostically validated ratio of stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from the value predicted by individual age, heart rate and body weight.
RESULTS: Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH) in normotensive and hypertensive subjects and was greatest in the presence of concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the presence of LVH (and was greatest with eccentric LVH, in association with relatively high values for stroke volume). After adjusting for blood pressure, maximum carotid lumen diameter was directly correlated with stroke volume, and IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum carotid lumen diameter, independently of prevalent risk factors (P < 0.001). SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P < 0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not affect these associations in normotensives, but made them insignificant in hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P < 0.001), independently of risk factors, whereas no significant relation was found in hypertensives.
CONCLUSIONS: The magnitudes of carotid intima-medial thickness and lumen diameter parallel levels of LV mass and geometry, and are directly related to stroke volume and arterial stiffness; this interaction is most evident in the presence of normal blood pressure, whereas it is affected by other cardiovascular risk factors when arterial hypertension is present.
10aAged10aAged, 80 and over10aBlood Pressure10aCarotid Arteries10aCompliance10aCross-Sectional Studies10aEchocardiography10aFemale10aHemodynamics10aHumans10aHypertension10aHypertrophy, Left Ventricular10aMale10aReference Values10aRisk Factors10aStroke Volume10aTunica Intima10aTunica Media10aVentricular Function, Left1 ade Simone, G1 aMcClelland, R1 aGottdiener, J S1 aCelentano, A1 aKronmal, R, A1 aGardin, J M uhttps://chs-nhlbi.org/node/66402810nas a2200397 4500008004100000022001400041245013300055210006900188260001300257300001100270490000700281520171100288653000901999653001502008653001802023653002302041653002802064653001902092653002202111653001102133653001102144653001702155653001702172653002502189653000902214653002102223653001702244100001902261700001502280700001802295700001502313700001602328700001802344700001502362856003502377 2001 eng d a0012-179700aThe relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.0 arelation of markers of inflammation to the development of glucos c2001 Oct a2384-90 v503 aSeveral studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.
10aAged10aBiomarkers10aBlood Glucose10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aHumans10aHypoglycemia10aInflammation10aLongitudinal Studies10aMale10aReference Values10aRisk Factors1 aBarzilay, J, I1 aAbraham, L1 aHeckbert, S R1 aCushman, M1 aKuller, L H1 aResnick, H, E1 aTracy, R P uhttps://chs-nhlbi.org/node/66102542nas a2200421 4500008004100000022001400041245011300055210006900168260001600237300000900253490000800262520136000270653001001630653000901640653002501649653002801674653002801702653002801730653001101758653001101769653001801780653002501798653000901823653001601832653002001848653001701868653002601885653001801911100001701929700001601946700001401962700001501976700001501991700002002006700001502026710004402041856003502085 2001 eng d a0002-926200aRelation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.0 aRelation of sleepdisordered breathing to cardiovascular disease c2001 Jul 01 a50-90 v1543 aAssociations between sleep-disordered breathing and cardiovascular disease (CVD) may be mediated by higher cardiovascular risk factor levels in those with sleep-disordered breathing. The authors examined these relations in the Sleep Heart Health Study, a multiethnic cohort of 6,440 men and women over age 40 years conducted from October 1995 to February 1998 and characterized by home polysomnography. In 4,991 participants who were free of self-reported CVD at the time of the sleep study, moderate levels of sleep-disordered breathing were common, with a median Respiratory Disturbance Index (RDI) of 4.0 (interquartile range, 1.25-10.7). The level of RDI was associated cross-sectionally with age, body mass index, waist-to-hip ratio, hypertension, diabetes, and lipid levels. These relations were more pronounced in those under age 65 years than in those over age 65. Women under age 65 years with RDI in the higher quartiles were more obese than men with similar RDI. Although the pattern of associations was consistent with greater obesity in those with higher RDI, higher body mass index did not explain all of these associations. If sleep-disordered breathing is shown in future follow-up to increase the risk for incident CVD events, part of the risk is likely to be due to the higher cardiovascular risk factors in those with higher RDI.
10aAdult10aAged10aAnalysis of Variance10aCardiovascular Diseases10aChi-Square Distribution10aCross-Sectional Studies10aFemale10aHumans10aLinear Models10aLongitudinal Studies10aMale10aMiddle Aged10aPolysomnography10aRisk Factors10aSleep Apnea Syndromes10aUnited States1 aNewman, A, B1 aNieto, F, J1 aGuidry, U1 aLind, B, K1 aRedline, S1 aPickering, T, G1 aQuan, S, F1 aSleep Heart Health Study Research Group uhttps://chs-nhlbi.org/node/65403470nas a2200469 4500008004100000022001400041245012400055210006900179260001300248300001100261490000700272520212500279653003102404653002102435653000902456653002202465653004402487653001902531653001202550653002802562653001102590653003202601653002002633653001102653653001402664653000902678653002602687653003002713653003202743653002402775653001702799653001202816653001802828100001702846700001802863700001902881700001702900700001602917700001702933700001502950856003502965 2001 eng d a0002-861400aRisk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.0 aRisk factors for hospitalized gastrointestinal bleeding among ol c2001 Feb a126-330 v493 aOBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors.
DESIGN: Prospective cohort study.
SETTING: The Cardiovascular Health Study (CHS).
PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS.
MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up.
RESULTS: Among CHS participants (mean baseline age 73.3 years, 42% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 % CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease.
CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.
10aActivities of Daily Living10aAge Distribution10aAged10aAged, 80 and over10aAnti-Inflammatory Agents, Non-Steroidal10aAnticoagulants10aAspirin10aCardiovascular Diseases10aFemale10aGastrointestinal Hemorrhage10aHospitalization10aHumans10aIncidence10aMale10aMultivariate Analysis10aPredictive Value of Tests10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSmoking10aUnited States1 aKaplan, R, C1 aHeckbert, S R1 aKoepsell, T, D1 aFurberg, C D1 aPolak, J, F1 aSchoen, R, E1 aPsaty, B M uhttps://chs-nhlbi.org/node/63502111nas a2200385 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520101100248653000901259653002001268653003201288653003001320653001901350653001601369653002201385653001101407653001101418653003001429653000801459653000901467653001501476653003201491653003101523100001701554700001801571700002201589700001601611700001601627710004701643856003501690 2001 eng d a0895-435600aThe role of comorbidity in the assessment of intermittent claudication in older adults.0 arole of comorbidity in the assessment of intermittent claudicati c2001 Mar a294-3000 v543 aThe prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.
10aAged10aAngina Pectoris10aArterial Occlusive Diseases10aCerebrovascular Disorders10aCohort Studies10aComorbidity10aDiabetes Mellitus10aFemale10aHumans10aIntermittent Claudication10aLeg10aMale10aPrevalence10aSensitivity and Specificity10aSurveys and Questionnaires1 aNewman, A, B1 aNaydeck, B, L1 aSutton-Tyrrell, K1 aPolak, J, F1 aKuller, L H1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63802720nas a2200373 4500008004100000022001400041245008800055210006900143260001600212300001100228490000700239520168800246653000901934653002401943653001901967653001101986653002201997653001102019653001402030653003102044653000902075653003002084653001702114653001102131100001502142700001402157700001502171700002002186700001502206700001702221700001302238710006002251856003502311 2001 eng d a0028-387800aSilent MRI infarcts and the risk of future stroke: the cardiovascular health study.0 aSilent MRI infarcts and the risk of future stroke the cardiovasc c2001 Oct 09 a1222-90 v573 aBACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly.
OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors.
METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts.
RESULTS: Approximately 28% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes).
CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.
10aAged10aCerebral Infarction10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMagnetic Resonance Imaging10aMale10aPredictive Value of Tests10aRisk Factors10aStroke1 aBernick, C1 aKuller, L1 aDulberg, C1 aLongstreth, W T1 aManolio, T1 aBeauchamp, N1 aPrice, T1 aCardiovascular Health Study Collaborative Reseach Group uhttps://chs-nhlbi.org/node/66302622nas a2200361 4500008004100000022001400041245011600055210006900171260001300240300001000253490000800263520163200271653000901903653002801912653001901940653002801959653001101987653001101998653000902009653001602018653002602034100001402060700001802074700001502092700001402107700001702121700001602138700001902154700001702173700001902190700001602209856003502225 2001 eng d a1073-449X00aSleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.0 aSleepdisordered breathing and cardiovascular disease crosssectio c2001 Jan a19-250 v1633 aDisordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.
10aAged10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aMale10aMiddle Aged10aSleep Apnea Syndromes1 aShahar, E1 aWhitney, C, W1 aRedline, S1 aLee, E, T1 aNewman, A, B1 aNieto, F, J1 aO'Connor, G, T1 aBoland, L, L1 aSchwartz, J, E1 aSamet, J, M uhttps://chs-nhlbi.org/node/63602704nas a2200373 4500008004100000022001400041245010300055210006900158260001300227300001100240490000700251520168500258653000901943653003701952653001001989653002001999653001102019653001802030653001102048653002002059653002502079653000902104653002402113653002002137653001402157653003102171100001302202700001802215700001502233700001602248700001602264700001502280856003502295 2001 eng d a0025-707900aTransforming self-rated health and the SF-36 scales to include death and improve interpretability.0 aTransforming selfrated health and the SF36 scales to include dea c2001 Jul a670-800 v393 aBACKGROUND: Most measures of health-related quality of life are undefined for people who die. Longitudinal analyses are often limited to a healthier cohort (survivors) that cannot be identified prospectively, and that may have had little change in health.
OBJECTIVE: To develop and evaluate methods to transform a single self-rated health item (excellent to poor; EVGGFP) and the physical component score of the SF-36 (PCS) to new variables that include a defensible value for death.
METHODS: Using longitudinal data from two large studies of older adults, health variables were transformed to the probability of being healthy in the future, conditional on the current observed value; death then has the value of 0. For EVGGFP, the new transformations were compared with some that were published earlier, based on different data. For the PCS, how well three different transformations, based on different definitions of being healthy, discriminated among groups of patients, and detected change in time were assessed.
RESULTS: The new transformation for EVGGFP was similar to that published previously. Coding the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended. The three transformations of the PCS detected group differences and change at least as well as the standard PCS.
CONCLUSION: These easily interpretable transformed variables permit keeping persons who die in the analyses. Using the transformed variables for longitudinal analyses of health when deaths occur, either for secondary or primary analysis, is recommended. This approach can be applied to other measures of health.
10aAged10aData Interpretation, Statistical10aDeath10aDecision Making10aFemale10aHealth Status10aHumans10aLogistic Models10aLongitudinal Studies10aMale10aModels, Statistical10aQuality of Life10aROC Curve10aSurveys and Questionnaires1 aDiehr, P1 aPatrick, D, L1 aSpertus, J1 aKiefe, C, I1 aMcDonell, M1 aFihn, S, D uhttps://chs-nhlbi.org/node/65802702nas a2200421 4500008004100000022001400041245018700055210006900242260001600311300001100327490000700338520148600345653000901831653001501840653001901855653002101874653002401895653001101919653002201930653001101952653000901963653001501972653003201987653002402019653001702043653001102060653002202071100002102093700001702114700001802131700001602149700001502165700002002180700001702200700001502217700001302232856003502245 2001 eng d a0002-914900aUsefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (the Cardiovascular Health Study).0 aUsefulness of Taxis deviation as an independent risk indicator f c2001 Jul 15 a118-230 v883 aT-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (> or =45 degrees ) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.
10aAged10aAlgorithms10aCohort Studies10aCoronary Disease10aElectrocardiography10aFemale10aFollow-Up Studies10aHumans10aMale10aPrevalence10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke10aSurvival Analysis1 aRautaharju, P, M1 aNelson, J, C1 aKronmal, R, A1 aZhang, Z, M1 aRobbins, J1 aGottdiener, J S1 aFurberg, C D1 aManolio, T1 aFried, L uhttps://chs-nhlbi.org/node/65502974nas a2200397 4500008004100000022001400041245006500055210006400120260001300184300001200197490000700209520192800216653000902144653002502153653001602178653002802194653001102222653001802233653001102251653002502262653000902287653001402296653003202310653001702342653001802359653001602377653001602393100001702409700001302426700001402439700001502453700001802468700001502486710004002501856003502541 2001 eng d a0002-861400aWeight change in old age and its association with mortality.0 aWeight change in old age and its association with mortality c2001 Oct a1309-180 v493 aOBJECTIVES: Previous studies of weight change and mortality in older adults have relied on self-reported weight loss, have not evaluated weight gain, or have had limited information on health status. Our objective was to determine whether 5% weight gain or loss in 3 years was predictive of mortality in a large sample of older adults.
DESIGN: Longitudinal observational cohort study.
SETTING: Four U.S. communities.
PARTICIPANTS: Four thousand seven hundred fourteen community-dwelling older adults, age 65 and older.
MEASUREMENTS: Weight gain or loss of 5% in a 3-year period was examined in relationship to baseline health status and interim health events. Risk for subsequent mortality was estimated in those with weight loss or weight gain compared with the group whose weight was stable.
RESULTS: Weight changes occurred in 34.6% of women and 27.3% of men, with weight loss being more frequent than gain. Weight loss was associated with older age, black race, higher weight, lower waist circumference, current smoking, stroke, any hospitalization, death of a spouse, activities of daily living disability, lower grip strength, and slower gait speed. Weight loss but not weight gain of 5% or more was associated with an increased risk of mortality that persisted after multivariate adjustment (Hazard ratio (HR) = 1.67, 95% CI = 1.29-2.15) and was similar in those with no serious illness in the period of weight change. Those with weight loss and low baseline weight had the highest crude mortality rate, although the HR for weight loss was similar for all tertiles of baseline weight and for those with or without a special diet, compared with those whose weight was stable.
CONCLUSIONS: This study confirms that even modest decline in body weight is an important and independent marker of risk of mortality in older adults.
10aAged10aAnalysis of Variance10aBody Weight10aChi-Square Distribution10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aMortality10aProportional Hazards Models10aRisk Factors10aUnited States10aWeight Gain10aWeight Loss1 aNewman, A, B1 aYanez, D1 aHarris, T1 aDuxbury, A1 aEnright, P, L1 aFried, L P1 aCardiovascular Study Research Group uhttps://chs-nhlbi.org/node/68301903nas a2200301 4500008004100000022001400041245006600055210006100121260001300182300001100195490000700206520112000213653000901333653001001342653001001352653001101362653002901373653001101402653001801413653002501431653000901456653002101465100001701486700002101503700002201524700002001546856003501566 2002 eng d a0895-435600aThe aging and dying processes and the health of older adults.0 aaging and dying processes and the health of older adults c2002 Mar a269-780 v553 aIt is difficult to distinguish changes in health due to aging from those related to dying, because the two processes are highly related. Some potentially treatable conditions may mistakenly be dismissed as due to old age. The goal of this article was to examine the relationships of aging and of dying to changes in 10 health-related variables: self-rated health, depression, ADLs, IADLs, minimental state examination, body mass index, blocks walked per week, bed days, hospitalization, and walking speed (all coded so that higher values were better). We used longitudinal data from the Cardiovascular Health Study to estimate the changes in the variables associated with 5 years of aging and also in the 5 years before death, controlling for years from death and for age, respectively. All 10 health variables declined as death approached, and most of them also declined with age. The "effect" of the dying process was usually significantly larger than the effect of aging. Large declines in these health measures are probably not due to aging, and should be taken seriously by patients and their providers.
10aAged10aAging10aDeath10aFemale10aHealth Status Indicators10aHumans10aLinear Models10aLongitudinal Studies10aMale10aMuscular Atrophy1 aDiehr, Paula1 aWilliamson, Jeff1 aBurke, Gregory, L1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/68002960nas a2200409 4500008004100000022001400041245015100055210006900206260001300275300001100288490000700299520170300306653003902009653000902048653001902057653002802076653004002104653001102144653001902155653001102174653001702185653000902202653002602211653003402237653002702271653001802298100002302316700002302339700001902362700001902381700002002400700002202420700002402442700002402466700002502490856003502515 2002 eng d a0895-706100aAngiotensin II type 1 receptor polymorphisms in the cardiovascular health study: relation to blood pressure, ethnicity, and cardiovascular events.0 aAngiotensin II type 1 receptor polymorphisms in the cardiovascul c2002 Dec a1050-60 v153 aBACKGROUND: The angiotensin II type 1 receptor A1166C polymorphism has been associated with increased risks of hypertension and myocardial infarction in several small studies. We examined the association between this polymorphism and new-onset hypertension, blood pressure (BP) control, and incident cardiovascular events in a large population-based cohort of older adults.
METHODS: Eight hundred self-identified African Americans and 1,371 randomly selected white participants in the Cardiovascular Health Study were genotyped. The median duration of follow-up was 8.1 years.
RESULTS: The A1166C polymorphism was not associated with new-onset hypertension, with BP control, or with incident cardiovascular events in the overall population. In white participants, the CC genotype was associated with higher baseline systolic BP and pulse pressure, compared to the AC or AA genotype. In whites with treated hypertension at baseline, compared to the AA genotype, the CC genotype was associated with increased risks of incident congestive heart failure (hazard ratio = 2.5, 95% confidence interval [CI] 1.3-4.9) and incident ischemic stroke (hazard ratio = 2.6, 95% CI 1.1-6.0). These associations were not observed among white participants without treated hypertension, but the interaction of genotype with treated hypertension on ischemic stroke and heart failure was only marginally significant.
CONCLUSIONS: On the whole, in this large cohort of older adults, the A1166C polymorphism was not associated with BP control or incident cardiovascular events. The subgroup findings in treated hypertensives need to be confirmed in additional studies.
10aAfrican Continental Ancestry Group10aAged10aBlood Pressure10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aHumans10aHypertension10aMale10aPolymorphism, Genetic10aReceptor, Angiotensin, Type 110aReceptors, Angiotensin10aUnited States1 aHindorff, Lucia, A1 aHeckbert, Susan, R1 aTracy, Russell1 aTang, Zhonghua1 aPsaty, Bruce, M1 aEdwards, Karen, L1 aSiscovick, David, S1 aKronmal, Richard, A1 aNazar-Stewart, Valle uhttps://chs-nhlbi.org/node/71102303nas a2200397 4500008004100000022001400041245011600055210006900171260001300240300001200253490000800265520117100273653000901444653002201453653003201475653002501507653001101532653001101543653002101554653002101575653002501596653000901621653001601630653001501646653002401661653002101685653001701706653002001723653002201743100002301765700002101788700002101809700001801830700002201848856003501870 2002 eng d a0007-104800aAnticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study.0 aAnticardiolipin antibodies as a risk factor for venous thromboem c2002 Dec a1005-100 v1193 aAnticardiolipin antibodies, one of the family of 'antiphospholipid' antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.
10aAged10aAged, 80 and over10aAntibodies, Anticardiolipin10aCase-Control Studies10aFemale10aHumans10aImmunoglobulin G10aImmunoglobulin M10aLongitudinal Studies10aMale10aMiddle Aged10aOdds Ratio10aProspective Studies10aReference Values10aRisk Factors10aThromboembolism10aVenous Thrombosis1 aRunchey, Shauna, S1 aFolsom, Aaron, R1 aTsai, Michael, Y1 aCushman, Mary1 aMcGovern, Paul, D uhttps://chs-nhlbi.org/node/71203261nas a2200397 4500008004100000022001400041245008400055210006900139260001300208300001300221490000700234520216800241653002102409653000902430653002102439653002102460653002102481653001502502653002802517653001102545653001102556653002802567653000902595653001502604653002402619653001702643100002402660700002002684700001702704700002302721700002102744700002202765700002102787700002002808856003502828 2002 eng d a0085-253800aCardiovascular disease risk status in elderly persons with renal insufficiency.0 aCardiovascular disease risk status in elderly persons with renal c2002 Sep a997-10040 v623 aBACKGROUND: Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency.
METHODS: This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors.
RESULTS: Among the 5808 participants with creatinine levels measured at entry, 15.9% of men (N = 394), and 7.6% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64% in persons with renal insufficiency compared with 43% in those without it [odds ratio (OR) 2.34; 95% confidence interval (95% CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95% CI, 1.18, 1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk>20% by the Framingham equations, 78% of men and 61% of women with renal insufficiency had elevated cardiovascular risk status.
CONCLUSIONS: Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults.
10aAge Distribution10aAged10aCholesterol, HDL10aCholesterol, LDL10aCoronary Disease10aCreatinine10aCross-Sectional Studies10aFemale10aHumans10aKidney Failure, Chronic10aMale10aPrevalence10aProspective Studies10aRisk Factors1 aShlipak, Michael, G1 aFried, Linda, F1 aCrump, Casey1 aBleyer, Anthony, J1 aManolio, Teri, A1 aTracy, Russell, P1 aFurberg, Curt, D1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/69702765nas a2200373 4500008004100000022001400041245013000055210006900185260001600254300001100270490000800281520168800289653000901977653002101986653001102007653001102018653001402029653000902043653001602052653002602068653003202094653002402126653002302150653001702173653001802190653002202208100002002230700001802250700002302268700002302291700002102314700002102335856003502356 2002 eng d a0003-992600aCardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.0 aCardiovascular risk factors and venous thromboembolism incidence c2002 May 27 a1182-90 v1623 aBACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.
METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.
RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95% CI, 1.0-2.1]).
CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.
10aAged10aArteriosclerosis10aFemale10aHumans10aIncidence10aMale10aMiddle Aged10aMultivariate Analysis10aProportional Hazards Models10aProspective Studies10aPulmonary Embolism10aRisk Factors10aUnited States10aVenous Thrombosis1 aTsai, Albert, W1 aCushman, Mary1 aRosamond, Wayne, D1 aHeckbert, Susan, R1 aPolak, Joseph, F1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/69102775nas a2200409 4500008004100000022001400041245010100055210006900156260001300225300001200238490000700250520162100257653000901878653002201887653004201909653001001951653003001961653001901991653001602010653001502026653002402041653001102065653001902076653001102095653001402106653002002120653003102140653000902171653002902180653001502209653001802224100002302242700002602265700001702291700002202308856003502330 2002 eng d a1524-462800aCerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.0 aCerebrovascular disease and evolution of depressive symptoms in c2002 Jun a1636-440 v333 aBACKGROUND AND PURPOSE: Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms.
METHODS: The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently.
RESULTS: After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions.
CONCLUSIONS: These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.
10aAged10aAged, 80 and over10aBasal Ganglia Cerebrovascular Disease10aBrain10aCerebrovascular Disorders10aCohort Studies10aComorbidity10aDepression10aDisease Progression10aFemale10aHealth Surveys10aHumans10aIncidence10aLogistic Models10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aOdds Ratio10aUnited States1 aSteffens, David, C1 aKrishnan, Ranga, Rama1 aCrump, Casey1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/69203319nas a2200481 4500008004100000022001400041245014200055210006900197260001600266300001100282490000800293520191900301653000902220653001502229653003002244653002302274653001902297653002502316653001502341653001102356653001502367653001102382653002702393653002502420653000902445653001602454653002602470653002402496653002002520653001702540653003202557653002002589653002202609653002602631100002002657700001802677700002302695700002302718700002202741700001802763700002102781856003502802 2002 eng d a0002-934300aCoagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE).0 aCoagulation factors inflammation markers and venous thromboembol c2002 Dec 01 a636-420 v1133 aPURPOSE: We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism.
SUBJECTS AND METHODS: In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years).
RESULTS: A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count.
CONCLUSIONS: In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.
10aAged10aBiomarkers10aBlood Coagulation Factors10aC-Reactive Protein10aCohort Studies10aConfidence Intervals10aFactor VII10aFemale10aFibrinogen10aHumans10aInflammation Mediators10aLongitudinal Studies10aMale10aMiddle Aged10aMultivariate Analysis10aProspective Studies10aRisk Assessment10aRisk Factors10aSensitivity and Specificity10aThromboembolism10aVenous Thrombosis10avon Willebrand Factor1 aTsai, Albert, W1 aCushman, Mary1 aRosamond, Wayne, D1 aHeckbert, Susan, R1 aTracy, Russell, P1 aAleksic, Nena1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/71603000nas a2200397 4500008004100000022001400041245010600055210006900161260001300230300001000243490000700253520190400260653000902164653002202173653001002195653001002205653001102215653001502226653001102241653001702252653002302269653002502292653000902317653001902326653001702345653002102362100002202383700002402405700002702429700002402456700001902480700002402499700002302523700002102546856003502567 2002 eng d a0895-706100aCorrelates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study.0 aCorrelates of aortic stiffness in elderly individuals a subgroup c2002 Jan a16-230 v153 aBACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals.
METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998.
RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993.
CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.
10aAged10aAged, 80 and over10aAging10aAorta10aFemale10aHeart Rate10aHumans10aHypertension10aInsulin Resistance10aLongitudinal Studies10aMale10aPulsatile Flow10aRisk Factors10aSex Distribution1 aMackey, Rachel, H1 aSutton-Tyrrell, Kim1 aVaitkevicius, Peter, V1 aSakkinen, Pamela, A1 aLyles, Mary, F1 aSpurgeon, Harold, A1 aLakatta, Edward, G1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/67703016nas a2200397 4500008004100000022001400041245015200055210006900207260001600276300001100292490000800303520182700311653000902138653001802147653002802165653001202193653001102205653002702216653001102243653000902254653002602263653003002289653003202319653002002351653001102371100002302382700002402405700002102429700002102450700002302471700002102494700002402515700002402539700002002563856003502583 2002 eng d a0003-992600aFasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.0 aFasting and 2hour postchallenge serum glucose measures and risk c2002 Jan 28 a209-160 v1623 aBACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk.
METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk.
RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk.
CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.
10aAged10aBlood Glucose10aCardiovascular Diseases10aFasting10aFemale10aGlucose Tolerance Test10aHumans10aMale10aMyocardial Infarction10aPredictive Value of Tests10aProportional Hazards Models10aRisk Assessment10aStroke1 aSmith, Nicholas, L1 aBarzilay, Joshua, I1 aShaffer, Douglas1 aSavage, Peter, J1 aHeckbert, Susan, R1 aKuller, Lewis, H1 aKronmal, Richard, A1 aResnick, Helaine, E1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/67503092nas a2200409 4500008004100000022001400041245015800055210006900213260001600282300001200298490000800310520185700318653000902175653002202184653003202206653002802238653001902266653002702285653002202312653001102334653001802345653002502363653001102388653001702399653002502416653000902441100002002450700002402470700001702494700002202511700001902533700002202552700002102574700002002595710003202615856003502647 2002 eng d a0003-992600aFrailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study.0 aFrailty and activation of the inflammation and coagulation syste c2002 Nov 11 a2333-410 v1623 aBACKGROUND: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness.
OBJECTIVE: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus.
METHODS: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson chi2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures.
RESULTS: Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean +/- SD levels of C-reactive protein (5.5 +/- 9.8 vs 2.7 +/- 4.0 mg/L), factor VIII (13 790 +/- 4480 vs 11 860 +/- 3460 mg/dL), and, in a smaller subset, D dimer (647 +/- 1033 vs 224 +/- 258 ng/mL) (P< or =.001 for all, chi2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race.
CONCLUSIONS: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.
10aAged10aAged, 80 and over10aBlood Coagulation Disorders10aCardiovascular Diseases10aCohort Studies10aDiabetes Complications10aDiabetes Mellitus10aFemale10aFrail Elderly10aGeriatric Assessment10aHumans10aInflammation10aLongitudinal Studies10aMale1 aWalston, Jeremy1 aMcBurnie, Mary, Ann1 aNewman, Anne1 aTracy, Russell, P1 aKop, Willem, J1 aHirsch, Calvin, H1 aGottdiener, John1 aFried, Linda, P1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/70903238nas a2200397 4500008004100000022001400041245013200055210006900187260001300256300001100269490000700280520209000287653001602377653000902393653001802402653001902420653002802439653002102467653002802488653002702516653002202543653001102565653001102576653000902587653001502596653002402611653001702635100002302652700002102675700002302696700002402719700002102743700002102764700002002785856003502805 2002 eng d a0002-861400aGlucose, blood pressure, and lipid control in older people with and without diabetes mellitus: the Cardiovascular Health Study.0 aGlucose blood pressure and lipid control in older people with an c2002 Mar a416-230 v503 aOBJECTIVES: To determine the prevalence of cardiovascular risk-factor treatment and control in older adults with normal fasting glucose, impaired fasting glucose, and diabetes mellitus and whether those with diabetes mellitus had better risk factor control than older adults with normal fasting glucose.
DESIGN: Secondary analysis of data from population-based, prospective cohort study of risk factors for cardio-vascular and cerebrovascular disease in older people (Cardiovascular Health Study).
SETTING: Community-based.
PARTICIPANTS: Community-dwelling adults aged 65 and older.
MEASUREMENTS: Fasting plasma glucose, serum cholesterol and its subfractions, systolic and diastolic blood pressures, and body mass index.
RESULTS: There were 579 (18%) cohort members with diabetes mellitus (77% receiving antidiabetic medication, 23% with fasting glucose > or =126 mg/dL and no treatment), 213 (6%) with impaired fasting glucose, and 2,582 (77%)with normal fasting glucose. Of diabetic participants, 12% had recommended fasting glucose levels of less than 110 mg/dL. Of participants with hypertension, a larger proportion of diabetic participants than nondiabetic participants (89% versus 75%, P < .01) was treated with antihypertensive agents, but a smaller proportion of diabetic participants had recommended blood pressure levels of 129/85 mmHg or lower than nondiabetic participants had recommended blood pressure levels of 139/89 mmHg or lower (27% vs 48%, P < .01). Diabetic dyslipidemic participants were treated less often with lipid-lowering therapy (26% versus 55%, P < .01) and achieved recommended low-density lipoprotein goals less often (8%versus 54%, P < .01) than nondiabetic dyslipidemic participants.
CONCLUSIONS: Overall, treatment and control of cardiovascular risk factors were suboptimal in this older population, especially among those with diabetes mellitus. Optimizing risk-factor control can improve health outcomes in older adults with and without diabetes mellitus.
10aAge Factors10aAged10aBlood Glucose10aBlood Pressure10aCardiovascular Diseases10aCholesterol, LDL10aCross-Sectional Studies10aDiabetes Complications10aDiabetes Mellitus10aFemale10aHumans10aMale10aPrevalence10aProspective Studies10aRisk Factors1 aSmith, Nicholas, L1 aSavage, Peter, J1 aHeckbert, Susan, R1 aBarzilay, Joshua, I1 aBittner, Vera, A1 aKuller, Lewis, H1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/68502717nas a2200469 4500008004100000022001400041245014000055210006900195260001600264300001200280490000700292520136500299653001601664653000901680653001501689653002801704653002501732653001301757653001101770653002201781653003801803653001301841653001201854653001901866653001101885653001701896653001801913653001801931653000901949653002601958653003001984653003002014100002002044700002202064700002002086700001902106700002102125700002102146700002102167700002402188856003502212 2002 eng d a1524-463600aIn the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease.0 aIn the elderly interleukin6 plasma levels and the 174GC polymorp c2002 Dec 01 a2066-710 v223 aOBJECTIVE: Interleukin (IL)-6-mediated inflammation is involved in cardiovascular disease (CVD). We assessed IL-6 levels and the -174G>C genotype in a case-control study of men and women (average age 73 years) within the Cardiovascular Health Study.
METHODS AND RESULTS: Cases included incident angina, myocardial infarction (MI), and stroke (5-year follow-up), prevalent MI, and MRI-detectable infarcts. A control group and a group free of subclinical CVD were used for comparison. The -174C allele was associated with higher C-reactive protein (11% higher, P=0.02), fibrinogen (3% higher, P=0.02), and IL-6 (5% higher; P=0.16). IL-6 was associated with increased atherosclerosis when the control group was compared with the group free of subclinical CVD. No further association with CVD events was found when case groups were compared with the control group. Compared with its absence, presence of the -174C allele was associated with risk of MRI infarcts (odds ratio 1.5).
CONCLUSIONS: IL-6 levels differentiated those with subclinical CVD from those without. Although the -174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis.
10aAge Factors10aAged10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCytosine10aFemale10aFollow-Up Studies10aGenetic Predisposition to Disease10aGenotype10aGuanine10aHealth Surveys10aHumans10aInflammation10aInterleukin-610aLinear Models10aMale10aPolymorphism, Genetic10aPredictive Value of Tests10aPromoter Regions, Genetic1 aJenny, Nancy, S1 aTracy, Russell, P1 aOgg, Malcolm, S1 aLuong, Le, Ahn1 aKuller, Lewis, H1 aArnold, Alice, M1 aSharrett, Richey1 aHumphries, Steve, E uhttps://chs-nhlbi.org/node/71302839nas a2200361 4500008004100000022001400041245014300055210006900198260001600267300001100283490000700294520177600301653000902077653002802086653003002114653002802144653001502172653001102187653001102198653001702209653000902226653001702235100001902252700002402271700002502295700002002320700002402340700002002364700001702384700001902401700002202420856003502442 2002 eng d a0002-914900aInflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia.0 aInflammation and coagulation factors in persons 65 years of age c2002 Feb 15 a419-240 v893 aDepression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.
10aAged10aBlood Chemical Analysis10aBlood Coagulation Factors10aCardiovascular Diseases10aDepression10aFemale10aHumans10aInflammation10aMale10aRisk Factors1 aKop, Willem, J1 aGottdiener, John, S1 aTangen, Catherine, M1 aFried, Linda, P1 aMcBurnie, Mary, Ann1 aWalston, Jeremy1 aNewman, Anne1 aHirsch, Calvin1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/67802577nas a2200433 4500008004100000022001400041245014900055210006900204260001600273300001000289490000700299520121600306653003901522653001601561653000901577653002401586653001601610653002801626653002101654653002401675653004001699653002801739653001101767653001601778653002101794653001101815653000901826653002601835653002401861653001701885653002401902653003101926100002101957700002401978700002302002700002202025710006102047856003502108 2002 eng d a0002-914900aLeft atrial dimensions determined by M-mode echocardiography in black and white older (> or =65 years) adults (The Cardiovascular Health Study).0 aLeft atrial dimensions determined by Mmode echocardiography in b c2002 Nov 01 a983-70 v903 aStroke and atrial fibrillation are common and serious illnesses in the elderly, the risks of which are substantially increased by left atrial (LA) enlargement. Despite growing recognition of the importance of LA enlargement, the distribution and correlates of LA dimension in the elderly have not been well defined. A total of 3,882 women and men aged >65 years were studied. Increased LA dimension was independently associated with increased weight, mitral annular calcium, regional wall motion abnormalities, mitral early peak inflow velocity, and left ventricular (LV) fractional shortening. Increased LA dimension was negatively associated with aortic leaflet thickening. The relation with LV fractional shortening was curvilinear with a nadir at 35% to 40%. LA dimension in black men was approximately 1.9 mm less than in white men in multivariate analyses. Adjustment for spirometric lung volumes and chest dimensions appeared to diminish the race-LA dimension relation. Thus, LA dimension is strongly associated with weight and with several echocardiographic valvular abnormalities; its relation with LV fractional shortening is U-shaped with a nadir at the borderline of LV functional impairment.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aBlood Flow Velocity10aBody Weight10aCardiovascular Diseases10aEchocardiography10aElectrocardiography10aEuropean Continental Ancestry Group10aEvidence-Based Medicine10aFemale10aHeart Atria10aHeart Ventricles10aHumans10aMale10aMultivariate Analysis10aProspective Studies10aRisk Factors10aStatistics as Topic10aVentricular Function, Left1 aManolio, Teri, A1 aGottdiener, John, S1 aTsang, Teresa, S M1 aGardin, Julius, M1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/70702506nas a2200301 4500008004100000022001400041245012600055210006900181260001300250300001100263490000700274520165600281653001001937653000901947653002201956653002401978653001102002653001502013653001102028653000902039653001602048653001402064653002102078653002402099100002602123700002002149856003502169 2002 eng d a1045-387300aLinearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions.0 aLinearly scaled rateinvariant normal limits for QT interval eigh c2002 Dec a1211-80 v133 aINTRODUCTION: Normal limits for QT traditionally are derived as mean +/- 2*SD, with rate adjustment done by dividing QT values by power functions such as RR 1/2 (proportional scaling).
METHODS AND RESULTS: We evaluated procedures for deriving normal limits by comparing adjusted QT distributions versus heart rate using ECG data of 11,739 normal men and women aged > or = 40 years. QT decreased as predicted by many power functions with heart rate but its SD remained relatively unchanged. Consequently, proportional scaling induced rate-dependent distortion of normal limits. Furthermore, QT distributions by heart rate were variably skewed and non-normal. Therefore, normal limits expressed as mean +/- 2*SD were misleading. Omission of regression intercept was an additional reason for failure of Bazett's and Fridericia's formulas. Regularized normal limits for adjusted QT (Qta) were obtained with linear instead of proportional scaling of type QTa = QT + k1*(1 - RR(k2)), for instance, with k2 = 0.5, k1 = 0.360 for males and 0.353 for females, or with k2 = 0.42, k1 = 0.414 for males and 0.420 for females. With linear scaling, QTa = 460 msec was established as the upper 2% normal limit, with 32 msec as the limit for a significant QTa increase from reference ECG in serial comparison.
CONCLUSION: Traditional procedures for establishment of normal limits failed because of proportional scaling, assumption of normal QT distribution, or omission of regression intercept. Percentile distributions of linearly scaled adjusted QT produced regularized rate invariant normal limits within normal sinus rates.
10aAdult10aAged10aAged, 80 and over10aElectrocardiography10aFemale10aHeart Rate10aHumans10aMale10aMiddle Aged10aPrognosis10aReference Values10aSex Characteristics1 aRautaharju, Pentti, M1 aZhang, Zhu-Ming uhttps://chs-nhlbi.org/node/72002517nas a2200397 4500008004100000022001400041245012800055210006900183260001300252300001100265490000700276520138300283653000901666653002001675653001001695653002401705653001901729653001101748653001101759653001201770653000901782653001601791653002901807653001101836653002001847653003001867653002501897100002001922700001701942700001701959700002201976700001801998700001802016710005002034856003502084 2002 eng d a0962-110500aMeasures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study.0 aMeasures of cognitive function in persons with varying degrees o c2002 Sep a265-720 v113 aEpidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.
10aAged10aBody Mass Index10aBrain10aCognition Disorders10aCohort Studies10aFemale10aHumans10aHypoxia10aMale10aMiddle Aged10aNeuropsychological Tests10aOxygen10aPolysomnography10aSeverity of Illness Index10aSleep Apnea, Central1 aBoland, Lori, L1 aShahar, Eyal1 aIber, Conrad1 aKnopman, David, S1 aKuo, Tracy, F1 aNieto, Javier1 aSleep Heart Health Study (SHHS) Investigators uhttps://chs-nhlbi.org/node/70102711nas a2200505 4500008004100000022001400041245016300055210006900218260001300287300001100300490000700311520127900318653002801597653000901625653002201634653001201656653002001668653001901688653002801707653002501735653001601760653002201776653001101798653003801809653001101847653002001858653001701878653000901895653001301904653002601917653001201943653003001955653001601985653001702001653001202018653001102030653001202041100002002053700002002073700001902093700001802112700001802130700002202148856003502170 2002 eng d a0340-624500aNo association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study.0 aNo association of plasma prothrombin concentration or the G20210 c2002 Apr a614-210 v873 aProthrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n approximately 250 each). Population-based controls free of clinical cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical and subclinical CVD (n approximately 250) were used for comparison. The 20210 A allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.
10a3' Untranslated Regions10aAged10aAged, 80 and over10aAlleles10aAngina Pectoris10aBlood Proteins10aCardiovascular Diseases10aCase-Control Studies10aComorbidity10aDiabetes Mellitus10aFemale10aGenetic Predisposition to Disease10aHumans10aHyperlipidemias10aHypertension10aMale10aMutation10aMyocardial Infarction10aObesity10aPromoter Regions, Genetic10aProthrombin10aRisk Factors10aSmoking10aStroke10aVermont1 aSmiles, Adam, M1 aJenny, Nancy, S1 aTang, Zhonghua1 aArnold, Alice1 aCushman, Mary1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/69003032nas a2200445 4500008004100000022001400041245013100055210006900186260001600255300001200271490000700283520175100290653000902041653001002050653002602060653002502086653001902111653002102130653001102151653001802162653001102180653002202191653002202213653002302235653003602258653000902294653004502303653001702348653001602365100001802381700001802399700001902417700001702436700001602453700001702469700002102486700002302507700002102530856003502551 2002 eng d a1524-463600aNuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study.0 aNuclear magnetic resonance spectroscopy of lipoproteins and risk c2002 Jul 01 a1175-800 v223 aOBJECTIVES: Relationships between incident cardiovascular disease and lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy were evaluated in the Cardiovascular Health Study (CHS) in a nested case-cohort analysis.
METHODS AND RESULTS: The case group consisted of 434 participants with incident myocardial infarction (MI) and angina diagnosed after entry to the study (1990 to 1995) and the comparison group, 249 "healthy" participants with no prevalent clinical or subclinical disease. By univariate analysis, the median levels for healthy participants versus participants with incident MI and angina were 0 versus 7 mg% for small low density lipoprotein (LDL), 1501 versus 1680 nmol/L for the number of LDL particles, and 21.6 versus 21.3 for LDL size, and these values were significantly different between "healthy" participants and those with incident MI and angina for women but not men. The levels of less dense LDL, which is most of the total LDL cholesterol among women, was not related to incident MI and angina. For women, large high density lipoprotein cholesterol (HDLc), but not small HDLc, levels were significantly higher for healthy participants compared with levels for participants with MI and angina. For men and women, levels of total and very low density lipoprotein triglycerides were higher for the case group than for the healthy group. In multivariate models for women that included triglycerides and HDLc, the number of LDL particles (but not LDL size) remained significantly related to MI and angina.
CONCLUSIONS: Small LDL, the size of LDL particles, and the greater number of LDL particles are related to incident coronary heart disease among older women.
10aAged10aAging10aCardiovascular System10aCase-Control Studies10aCohort Studies10aCoronary Disease10aFemale10aHealth Status10aHumans10aLipoproteins, HDL10aLipoproteins, LDL10aLipoproteins, VLDL10aMagnetic Resonance Spectroscopy10aMale10aNuclear Magnetic Resonance, Biomolecular10aRisk Factors10aSex Factors1 aKuller, Lewis1 aArnold, Alice1 aTracy, Russell1 aOtvos, James1 aBurke, Greg1 aPsaty, Bruce1 aSiscovick, David1 aFreedman, David, S1 aKronmal, Richard uhttps://chs-nhlbi.org/node/69603533nas a2200457 4500008004100000022001400041245014200055210006900197260001600266300001000282490000800292520220800300653000902508653001902517653002102536653001102557653001802568653001102586653002502597653000902622653002602631653001502657653001402672653001702686653001102703653003502714653003102749100002402780700002502804700002102829700002002850700002102870700002302891700001802914700001802932700002202950700002202972700002502994700002103019856003503040 2002 eng d a1539-370400aOutcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.0 aOutcome of congestive heart failure in elderly persons influence c2002 Oct 15 a631-90 v1373 aBACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.
OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.
DESIGN: Population-based longitudinal study of coronary heart disease and stroke.
SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland.
PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community.
MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality.
RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category.
CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.
10aAged10aCause of Death10aEchocardiography10aFemale10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aPrevalence10aPrognosis10aRisk Factors10aStroke10aVentricular Dysfunction, Right10aVentricular Function, Left1 aGottdiener, John, S1 aMcClelland, Robyn, L1 aMarshall, Robert1 aShemanski, Lynn1 aFurberg, Curt, D1 aKitzman, Dalane, W1 aCushman, Mary1 aPolak, Joseph1 aGardin, Julius, M1 aGersh, Bernard, J1 aAurigemma, Gerard, P1 aManolio, Teri, A uhttps://chs-nhlbi.org/node/70503293nas a2200469 4500008004100000022001400041245010500055210006900160260001600229300001200245490000800257520198200265653001002247653001602257653000902273653002202282653001902304653003402323653001102357653001102368653000902379653001602388653001202404653003002416653003002446653001702476653001602493653002602509653001202535100001702547700001702564700001802581700001902599700002002618700002402638700002402662700001702686700001802703700002302721710004402744856003502788 2002 eng d a0003-992600aPredictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.0 aPredictors of sleepdisordered breathing in communitydwelling adu c2002 Apr 22 a893-9000 v1623 aBACKGROUND: Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis.
METHODS: The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater.
RESULTS: Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased.
CONCLUSIONS: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aCohort Studies10aContinental Population Groups10aFemale10aHumans10aMale10aMiddle Aged10aObesity10aPredictive Value of Tests10aResidence Characteristics10aRisk Factors10aSex Factors10aSleep Apnea Syndromes10aSnoring1 aYoung, Terry1 aShahar, Eyal1 aNieto, Javier1 aRedline, Susan1 aNewman, Anne, B1 aGottlieb, Daniel, J1 aWalsleben, Joyce, A1 aFinn, Laurel1 aEnright, Paul1 aSamet, Jonathan, M1 aSleep Heart Health Study Research Group uhttps://chs-nhlbi.org/node/68604046nas a2200421 4500008004100000022001400041245013300055210006900188260001600257300001200273490000800285520283600293653000903129653001503138653001203153653002403165653002403189653001603213653002803229653001403257653001303271653001503284653003303299653001103332653001103343653002503354653000903379653002903388653001503417653002503432100002903457700001703486700001903503700002803522700001903550700002003569856003503589 2002 eng d a0098-748400aPrevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.0 aPrevalence of neuropsychiatric symptoms in dementia and mild cog c2002 Sep 25 a1475-830 v2883 aCONTEXT: Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI.
OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study.
DESIGN: Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study.
SETTING AND PARTICIPANTS: A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia.
MAIN OUTCOME MEASURE: Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms.
RESULTS: Of the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P =.02).
CONCLUSIONS: Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.
10aAged10aAggression10aAnxiety10aBehavioral Symptoms10aCognition Disorders10aComorbidity10aCross-Sectional Studies10aDelusions10aDementia10aDepression10aFeeding and Eating Disorders10aFemale10aHumans10aLongitudinal Studies10aMale10aNeuropsychological Tests10aPrevalence10aSleep Wake Disorders1 aLyketsos, Constantine, G1 aLopez, Oscar1 aJones, Beverly1 aFitzpatrick, Annette, L1 aBreitner, John1 aDeKosky, Steven uhttps://chs-nhlbi.org/node/70204080nas a2200421 4500008004100000022001400041245008100055210006900136260001300205300001100218490000700229520291000236653001603146653000903162653002203171653001903193653001803212653001103230653001103241653002503252653000903277653001503286653002403301653001703325653002903342653001703371653001603388653003703404100002503441700002403466700002303490700002203513700002303535700002203558700002203580700002103602856003503623 2002 eng d a0741-521400aPrevalence of renovascular disease in the elderly: a population-based study.0 aPrevalence of renovascular disease in the elderly a populationba c2002 Sep a443-510 v363 aPURPOSE: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as > or = 60% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS).
METHODS: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with chi(2) and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis.
RESULTS: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 +/- 4.9 years and consisted of 63% women and 37% men. Participant race was 76% white and 23% African American. The overall prevalence rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral disease and seven (12%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1 +/- 4.9 years (P =.018). RVD was present in 5.5% of women and 9.1% of men (P =.053). RVD was present in 6.9% of white participants and 6.7% of African American participants (P =.933). Multivariate analysis revealed increasing participant age (P =.028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63; 95% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio, 1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD.
CONCLUSION: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure.
10aAge Factors10aAged10aAged, 80 and over10aCohort Studies10aEthnic Groups10aFemale10aHumans10aLongitudinal Studies10aMale10aPrevalence10aProspective Studies10aRenal Artery10aRenal Artery Obstruction10aRisk Factors10aSex Factors10aUltrasonography, Doppler, Duplex1 aHansen, Kimberley, J1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aCherr, Gregory, S1 aJackson, Sharon, A1 aAppel, Richard, G1 aBurke, Gregory, L1 aDean, Richard, H uhttps://chs-nhlbi.org/node/70002062nas a2200349 4500008004100000022001400041245007300055210006900128260001600197300001100213490000700224520111300231653001601344653000901360653001501369653001901384653002801403653001101431653001101442653002001453653000901473653001701482653001601499653003101515100002001546700002401566700001801590700002401608700002401632700002101656856003501677 2002 eng d a1524-463600aRacial differences in coronary artery calcification in older adults.0 aRacial differences in coronary artery calcification in older adu c2002 Mar 01 a424-300 v223 aReports on race-related differences in coronary artery calcium (CAC) are just beginning to emerge and have not been well studied in the elderly. This study was undertaken to assess whether such differences exist and the relationship between CAC and cardiovascular risk factors in a cohort of elderly community-dwelling adults. CAC was measured by using electron-beam tomography in 614 adults (aged 67 to 99 years), of whom 59% were women and 23% were black. The median CAC score was lower in blacks than in whites for men (159 versus 787, respectively; P<0.001) and for women (134 versus 233, respectively; P=0.02) after adjustment for age, cardiovascular disease, and risk factors for cardiovascular disease, although this difference was stronger and remained significant among men only. Lower CAC scores were also observed in the subgroup of blacks with a history of myocardial infarction. The lower CAC scores in blacks compared with whites observed in this study is consistent with either a lower prevalence of coronary artery disease or a lower extent of calcification of coronary artery disease.
10aAge Factors10aAged10aCalcinosis10aCohort Studies10aCoronary Artery Disease10aFemale10aHumans10aLogistic Models10aMale10aRisk Factors10aSex Factors10aTomography, X-Ray Computed1 aNewman, Anne, B1 aNaydeck, Barbara, L1 aWhittle, Jeff1 aSutton-Tyrrell, Kim1 aEdmundowicz, Daniel1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/68203590nas a2200469 4500008004100000022001400041245013400055210006900189260001300258300001000271490000700281520225800288653001702546653000902563653002202572653002102594653001702615653001902632653001902651653003002670653002502700653001102725653001102736653002502747653000902772653001502781653002402796653002402820653001702844653001702861653001702878100001802895700002102913700002102934700002102955700002202976700002402998700002203022700002203044700001903066856003503085 2002 eng d a0007-116100aThe relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.0 arelation of atherosclerotic cardiovascular disease to retinopath c2002 Jan a84-900 v863 aAIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes.
METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system.
RESULTS: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86).
CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.
10aAge of Onset10aAged10aAged, 80 and over10aArteriosclerosis10aBlack People10aBlood Pressure10aCohort Studies10aDiabetes Mellitus, Type 210aDiabetic Retinopathy10aFemale10aHumans10aLongitudinal Studies10aMale10aOdds Ratio10aProspective Studies10aRegression Analysis10aRisk Factors10aTime Factors10aWhite People1 aKlein, Ronald1 aMarino, Emily, K1 aKuller, Lewis, H1 aPolak, Joseph, F1 aTracy, Russell, P1 aGottdiener, John, S1 aBurke, Gregory, L1 aHubbard, Larry, D1 aBoineau, Robin uhttps://chs-nhlbi.org/node/67403104nas a2200421 4500008004100000022001400041245007700055210006900132260001600201300001100217490000700228520188500235653001002120653002002130653001902150653003002169653002802199653003802227653001102265653001802276653001102294653000902305653001602314653003802330653002002368653001502388653003002403653002902433653002202462100002202484700001902506700001802525700002002543700002002563700002602583710003802609856003502647 2002 eng d a0161-810500aThe relationship between chronically disrupted sleep and healthcare use.0 arelationship between chronically disrupted sleep and healthcare c2002 May 01 a289-960 v253 aSTUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population.
DESIGN: Cross-sectional study.
SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies.
INTERVENTIONS: N/A.
MEASUREMENTS: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data.
RESULTS: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS.
CONCLUSIONS: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.
10aAdult10aChronic Disease10aCohort Studies10aCommunity Health Services10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPatient Acceptance of Health Care10aPolysomnography10aPrevalence10aSeverity of Illness Index10aSleep Apnea, Obstructive10aSleep Deprivation1 aKapur, Vishesh, K1 aRedline, Susan1 aNieto, Javier1 aYoung, Terry, B1 aNewman, Anne, B1 aHenderson, Jeffrey, A1 aSleep Heart Health Research Group uhttps://chs-nhlbi.org/node/68802775nas a2200445 4500008004100000022001400041245012900055210006900184260001600253300001100269490000700280520149700287653000901784653002201793653001501815653002801830653002101858653001901879653002801898653001501926653001101941653001101952653000901963653001501972653001701987653003202004653001602036653003102052653001802083653001702101100002002118700002402138700002402162700002402186700002002210700002102230700002202251700002102273856003502294 2002 eng d a1524-463600aRelationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults.0 aRelationship between coronary artery calcification and other mea c2002 Oct 01 a1674-90 v223 aBACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown.
METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures.
CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.
10aAged10aAged, 80 and over10aCalcinosis10aCardiovascular Diseases10aCarotid Stenosis10aCohort Studies10aCoronary Artery Disease10aDemography10aFemale10aHumans10aMale10aPrevalence10aRisk Factors10aSensitivity and Specificity10aSex Factors10aTomography, X-Ray Computed10aTunica Intima10aTunica Media1 aNewman, Anne, B1 aNaydeck, Barbara, L1 aSutton-Tyrrell, Kim1 aEdmundowicz, Daniel1 aO'Leary, Daniel1 aKronmal, Richard1 aBurke, Gregory, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/70403202nas a2200397 4500008004100000022001400041245010900055210006900164260001300233300001200246490000700258520214600265653000902411653002202420653001902442653001902461653002502480653000802505653001102513653001102524653000902535653002102544653002402565653001102589653002102600100001502621700001802636700001302654700001702667700001502684700001902699700002002718700001302738700001802751856003502769 2002 eng d a0007-116100aRetinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study.0 aRetinal microvascular abnormalities and blood pressure in older c2002 Sep a1007-130 v863 aAIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people.
METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised.
RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes.
CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.
10aAged10aAged, 80 and over10aBlood Pressure10aCohort Studies10aDiabetic Retinopathy10aEye10aFemale10aHumans10aMale10aMicrocirculation10aProspective Studies10aRetina10aRetinal Diseases1 aWong, T, Y1 aHubbard, L, D1 aKlein, R1 aMarino, E, K1 aKronmal, R1 aSharrett, A, R1 aSiscovick, D, S1 aBurke, G1 aTielsch, J, M uhttps://chs-nhlbi.org/node/69903750nas a2200481 4500008004100000022001400041245014400055210006900199260001300268300001000281490000700291520238900298653001002687653000902697653002202706653001002728653001202738653002002750653002102770653002402791653002102815653002302836653001102859653001102870653000902881653001602890653002302906653002002929653001602949653002602965653001702991653001703008100002003025700002503045700001703070700001803087700002303105700001903128700001803147700001703165710005103182856003503233 2002 eng d a0161-810500aShort-term variability of respiration and sleep during unattended nonlaboratory polysomnography--the Sleep Heart Health Study. [corrected].0 aShortterm variability of respiration and sleep during unattended c2002 Dec a843-90 v253 aSTUDY OBJECTIVES: To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart.
DESIGN: Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3% (apnea or hypopnea events associated with > or = 3% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85% and > or = 85%). The RDI and sleep data from initial and repeated polysomnography were compared.
SETTING: NA.
PARTICIPANTS: A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study.
INTERVENTIONS: NA.
MEASUREMENTS AND RESULTS: Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3% and RDI4% (apnea or hypopnea events associated with > or = 4% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3% < 15, variability increased as a function of increasing RDI, but for those with a RDI3% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1%, 85.7%, and 87.9% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (% time in REM) to 0.76 (arousal index).
CONCLUSION: In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed.
10aAdult10aAged10aAged, 80 and over10aApnea10aArousal10aBody Mass Index10aCircadian Rhythm10aElectrocardiography10aElectromyography10aElectrooculography10aFemale10aHumans10aMale10aMiddle Aged10aOxygen Consumption10aPolysomnography10aRespiration10aSleep Apnea Syndromes10aSleep Stages10aTime Factors1 aQuan, Stuart, F1 aGriswold, Michael, E1 aIber, Conrad1 aNieto, Javier1 aRapoport, David, M1 aRedline, Susan1 aSanders, Mark1 aYoung, Terry1 aSleep Heart Health Study (SHHS) Research Group uhttps://chs-nhlbi.org/node/71402423nas a2200361 4500008004100000022001400041245008400055210006900139260001300208300001100221490000700232520144900239653000901688653002201697653001901719653001101738653002201749653001101771653001401782653000901796653002701805653003001832653001701862653001401879653001101893653001801904100001901922700002401941700001801965700002101983700002202004856003502026 2002 eng d a0895-435600aA stroke prediction score in the elderly: validation and Web-based application.0 astroke prediction score in the elderly validation and Webbased a c2002 Feb a129-360 v553 aThe objective of this study was to construct a prediction model for predicting stroke in an elderly U.S. population, and to assess the accuracy in this population of other previously published prediction models. The subjects were participants in the Cardiovascular Health Study: 2,495 men and 3,393 women age 65 years and older at baseline, and followed for 6.3 years. Among 5,711 participants free of baseline stroke, 399 strokes occurred. Sex-specific prediction equations were constructed using study variables that were most importantly related to incident stroke: age, systolic blood pressure, diabetes, ECG diagnosis of atrial fibrillation or left ventricular hypertrophy, confirmed history of cardiovascular disease, diabetes, time to walk 15 ft, and serum creatinine. The prediction rule was implemented as a risk score and in a Web-based interactive Java applet. Overall, the model predicted 5-year stroke risks ranging from less than 1 to 59%. The 20% of subjects in the highest predicted risk group had a 5-year actual stroke incidence rate of 15%, while the 20% lowest risk group had a 1% incidence. Risk scores from two other studies performed well in these study participants. Effective discrimination between low and high stroke risk in the elderly was possible in this cohort with data that are easy to obtain. Evaluation of the generalizability and clinical usefulness of this prediction model requires further research.
10aAged10aAged, 80 and over10aBlood Pressure10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aModels, Cardiovascular10aPredictive Value of Tests10aRisk Factors10aROC Curve10aStroke10aUnited States1 aLumley, Thomas1 aKronmal, Richard, A1 aCushman, Mary1 aManolio, Teri, A1 aGoldstein, Steven uhttps://chs-nhlbi.org/node/67603096nas a2200385 4500008004100000022001400041245019900055210006900254260001600323300001300339490000800352520187000360653000902230653002102239653002102260653001102281653002202292653001102314653005102325653002502376653002502401653001402426653000902440653002602449653003202475653001702507653001802524100002402542700002002566700002302586700002402609700002002633700002202653856003502675 2002 eng d a0003-992600aTherapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study.0 aTherapy with hydroxymethylglutaryl coenzyme a reductase inhibito c2002 Jun 24 a1395-4000 v1623 aBACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol.
METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years' follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding variables.
RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline.
CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.
10aAged10aCholesterol, LDL10aCoronary Disease10aFemale10aFollow-Up Studies10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aHypercholesterolemia10aHypolipidemic Agents10aIncidence10aMale10aMultivariate Analysis10aProportional Hazards Models10aRisk Factors10aUnited States1 aLemaitre, Rozenn, N1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aKronmal, Richard, A1 aNewman, Anne, B1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/69503826nas a2200433 4500008004100000022001400041245014100055210006900196260001600265300001200281490000800293520256400301653001602865653000902881653002802890653001402918653001902932653001702951653001102968653004202979653001103021653001703032653000903049653002403058653001703082100002003099700002103119700002303140700002303163700002403186700002203210700002003232700001803252700001903270700001503289700002103304710003203325856003503357 2002 eng d a0003-992600aTime trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study.0 aTime trends in high blood pressure control and the use of antihy c2002 Nov 11 a2325-320 v1623 aBACKGROUND: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention.
OBJECTIVE: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP.
METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications.
RESULTS: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37% at baseline to 49% in 1999. The 51% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5% in 1990 to 51.1% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased.
CONCLUSIONS: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers--the preferred agents since 1993 according to the recommendations of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure--remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure.
10aAge Factors10aAged10aAntihypertensive Agents10aAwareness10aCohort Studies10aDrug Therapy10aFemale10aHealth Knowledge, Attitudes, Practice10aHumans10aHypertension10aMale10aProspective Studies10aTime Factors1 aPsaty, Bruce, M1 aManolio, Teri, A1 aSmith, Nicholas, L1 aHeckbert, Susan, R1 aGottdiener, John, S1 aBurke, Gregory, L1 aWeissfeld, Joel1 aEnright, Paul1 aLumley, Thomas1 aPowe, Neil1 aFurberg, Curt, D1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/70802318nas a2200313 4500008004100000022001400041245006400055210006100119260001300180300001000193490000600203520148700209653002801696653002201724653001101746653001101757653000901768653001601777653001501793653002601808653001801834100001901852700002301871700001901894700001701913700002101930700001801951856003501969 2002 eng d a1520-951200aUnderdiagnosis of sleep apnea syndrome in U.S. communities.0 aUnderdiagnosis of sleep apnea syndrome in US communities c2002 Jun a49-540 v63 aWe hypothesize that clinical recognition rates for obstructive sleep apnea-hypoapnea syndrome (OSAHS) are influenced by comorbidity and demographic factors. Data on medical disorders, symptoms of sleep disorders, and cardiovascular risk factors gathered from 15,699 individuals in the Sleep Heart Health Study were compared. Participants were classified into three groups: those with a self-reported physician diagnosis of OSAHS, those with self-reported physician-diagnosed and -treated OSAHS, and those reporting both frequent snoring and daytime sleepiness (two-symptom group). Among all participants, 4.1% reported two symptoms (range across sites: 1.55 to 7.23%), whereas 1.6% reported a physician diagnosis of OSAHS (range: 0.66 to 2.88%) and 0.6% reported physician diagnosis and treatment (range: 0.11 to 0.88%). Recognized OSAHS groups were similar to the two-symptom group in age, having a sleeping partner, measured blood pressure, total cholesterol, and race. In a logistic model that included age along with characteristics found to vary significantly among the three groups (gender, body mass index [BMI], high-density lipoprotein cholesterol levels, hypertension), only male gender and BMI were increased in those with physician-diagnosed and -treated OSAHS. We conclude that disparities (especially in women and in those with lower BMI) exist between current recognition rates for OSAHS and the estimated prevalence by symptom report across the United States.
10aDiagnosis, Differential10aDiagnostic Errors10aFemale10aHumans10aMale10aMiddle Aged10aPrevalence10aSleep Apnea Syndromes10aUnited States1 aKapur, Vishesh1 aStrohl, Kingman, P1 aRedline, Susan1 aIber, Conrad1 aO'Connor, George1 aNieto, Javier uhttps://chs-nhlbi.org/node/69403196nas a2200457 4500008004100000022001400041245008100055210006900136260001300205300001100218490000800229520191200237653003102149653000902180653002202189653002802211653001902239653002102258653002802279653003002307653001802337653001102355653001102366653003102377653001802408653000902426653001902435653003202454653001102486653001802497653001202515100002102527700002402548700001802572700002202590700002102612700001802633700002002651710003202671856003502703 2003 eng d a0012-369200aThe 6-min walk test: a quick measure of functional status in elderly adults.0 a6min walk test a quick measure of functional status in elderly a c2003 Feb a387-980 v1233 aOBJECTIVES: To determine the correlates of the total 6-min walk distance (6MWD) in a population sample of adults > or = 68 years old.
METHODS: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular Health Study cohort during their seventh annual examination.
RESULTS: Of the 3,333 participants with a clinic visit, 2,281 subjects (68%) performed the 6MWT. There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general correlates of a shorter 6MWD in linear regression models in women and men included the following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression, and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV(1) in women; and the use of digitalis in men. Approximately 30% of the variance in 6MWD was explained by the linear regression models. Newly described bivariate associations of a shorter 6MWD included impaired activities of daily living; self-reported poor health; less education; nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes; and higher levels of C-reactive protein, fibrinogen, or WBC count.
CONCLUSIONS: Most community-dwelling elderly persons can quickly and safely perform this functional status test in the outpatient clinic setting. The test may be used clinically to measure the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis, diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older adults. Expected values should be adjusted for the patient's age, gender, height, and weight.
10aActivities of Daily Living10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aExercise Test10aFemale10aHumans10aIschemic Attack, Transient10aLinear Models10aMale10aMass Screening10aSensitivity and Specificity10aStroke10aUnited States10aWalking1 aEnright, Paul, L1 aMcBurnie, Mary, Ann1 aBittner, Vera1 aTracy, Russell, P1 aMcNamara, Robert1 aArnold, Alice1 aNewman, Anne, B1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/72502492nas a2200349 4500008004100000022001400041245010200055210006900157260001300226300001100239490000700250520147800257653000901735653002101744653002801765653002801793653002801821653001101849653001901860653001101879653002501890653000901915653002401924100002401948700002401972700002501996700002302021700002102044700001802065700002402083856003502107 2003 eng d a1524-463600aAlcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study.0 aAlcohol consumption and carotid atherosclerosis in older adults c2003 Dec a2252-90 v233 aOBJECTIVE: The association of alcohol use with atherosclerosis is inconsistent in previous studies.
METHODS AND RESULTS: For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07+/-0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07+/-0.05-mm higher IMT than abstainers (P quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24+/-0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22%.
CONCLUSIONS: Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.
10aAged10aAlcohol Drinking10aCardiovascular Diseases10aCarotid Artery Diseases10aCross-Sectional Studies10aFemale10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aProspective Studies1 aMukamal, Kenneth, J1 aKronmal, Richard, A1 aMittleman, Murray, A1 aO'Leary, Daniel, H1 aPolak, Joseph, F1 aCushman, Mary1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/75302738nas a2200361 4500008004100000022001400041245010800055210006900163260001600232300001100248490000800259520168900267653000901956653002501965653001901990653002102009653002402030653001102054653002202065653001502087653001102102653000902113653004202122653001702164653002402181653002202205653001802227100001802245700002802263700002602291700002402317856003502341 2003 eng d a0002-934300aThe association between the length of the QT interval and mortality in the Cardiovascular Health Study.0 aassociation between the length of the QT interval and mortality c2003 Dec 15 a689-940 v1153 aPURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain.
METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors.
RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7).
CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.
10aAged10aArrhythmias, Cardiac10aCause of Death10aCoronary Disease10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Rate10aHumans10aMale10aRandomized Controlled Trials as Topic10aRisk Factors10aStatistics as Topic10aSurvival Analysis10aUnited States1 aRobbins, John1 aNelson, Jennifer, Clark1 aRautaharju, Pentti, M1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/76102922nas a2200373 4500008004100000022001400041245011800055210006900173260001300242300001000255490000700265520188100272653000902153653001902162653002802181653001902209653001102228653001102239653001102250653001602261653000902277653002402286653002402310653001702334653001702351100002302368700002002391700001902411700001902430700001702449700002302466700002402489856003502513 2003 eng d a0002-861400aThe association between time since last meal and blood pressure in older adults: the cardiovascular health study.0 aassociation between time since last meal and blood pressure in o c2003 Jun a824-80 v513 aOBJECTIVES: To demonstrate a postprandial hypotensive (PPH) phenomenon in older adults.
DESIGN: Observational, prospective cohort study composed of baseline and nine follow-up visits.
SETTING: Cardiovascular Health Study, an epidemiological study of risk factors for cardiovascular disease in older adults.
PARTICIPANTS: Five thousand eight hundred eighty-eight community-dwelling adults aged 65 and older.
MEASUREMENTS: Blood pressure and time since last meal were recorded synchronously at baseline and at follow-up clinic visits. Generalized estimating equations were used to estimate associations between time since last meal and blood pressure and to adjust variance estimates to account for repeated blood pressure measures within subjects across fasting times.
RESULTS: Mean systolic and diastolic blood pressures were lower in the first hour after the last meal and were progressively higher through the fourth hour after the last meal than blood pressures measured immediately after the last meal (0 hour: 133.7/68.8 mmHg; 1st hour: 130.1/66.6 mmHg; 4th hour: 136.5/71.1 mmHg). Changes were significant for systolic and diastolic measures (P <.001 for both). Exploratory analyses suggested that the systolic PPH association was more pronounced in women. Little evidence was found that the degree of systolic or diastolic PPH varied by age, race, prevalent cardiovascular disease, heart rate, ejection fraction, treated hypertension or diabetes mellitus, or body mass index.
CONCLUSION: These data support previous observations that there is a significant drop in blood pressure within 1 hour after a meal in older adults. Time since last meal may be an important factor to consider when measuring blood pressure in older adults, and perhaps national standards need to be set.
10aAged10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aEating10aFemale10aHumans10aHypotension10aMale10aPostprandial Period10aProspective Studies10aRisk Factors10aTime Factors1 aSmith, Nicholas, L1 aPsaty, Bruce, M1 aRutan, Gale, H1 aLumley, Thomas1 aYanez, David1 aChaves, Paulo, H M1 aKronmal, Richard, A uhttps://chs-nhlbi.org/node/73802683nas a2200385 4500008004100000022001400041245009700055210006900152260000900221300001000230490000600240520166800246653002701914653000901941653002201950653001001972653002101982653001902003653002802022653000902050653002602059653001702085653002102102653001802123653001302141653001102154653001102165653000902176653001202185100001602197700001502213700002002228700001402248856003502262 2003 eng d a1279-770700aBody composition in the elderly: the influence of nutritional factors and physical activity.0 aBody composition in the elderly the influence of nutritional fac c2003 a130-90 v73 aBACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio.
OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue.
DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition.
RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes.
CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.
10aAbsorptiometry, Photon10aAged10aAged, 80 and over10aAging10aBody Composition10aCohort Studies10aCross-Sectional Studies10aDiet10aDietary Carbohydrates10aDietary Fats10aDietary Proteins10aEnergy Intake10aExercise10aFemale10aHumans10aMale10aWalking1 aMitchell, D1 aHaan, M, N1 aSteinberg, F, M1 aVisser, M uhttps://chs-nhlbi.org/node/73902818nas a2200397 4500008004100000022001400041245012000055210006900175260001600244300001100260490000800271520171100279653000901990653001201999653002502011653000902036653001102045653002502056653001102081653001102092653001102103653000902114653002602123653002402149653002402173653000902197653000902206100002502215700002402240700002102264700002202285700002202307700002402329710003202353856003502385 2003 eng d a1524-453900aCardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study.0 aCardiac benefits of fish consumption may depend on the type of f c2003 Mar 18 a1372-70 v1073 aBACKGROUND: Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk.
METHODS AND RESULTS: In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged > or =65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years' mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk.
CONCLUSIONS: Among adults aged > or =65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.
10aAged10aAnimals10aArrhythmias, Cardiac10aDiet10aEating10aFatty Acids, Omega-310aFemale10aFishes10aHumans10aMale10aMyocardial Infarction10aMyocardial Ischemia10aProspective Studies10aRisk10aTuna1 aMozaffarian, Dariush1 aLemaitre, Rozenn, N1 aKuller, Lewis, H1 aBurke, Gregory, L1 aTracy, Russell, P1 aSiscovick, David, S1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/73003409nas a2200349 4500008004100000022001400041245010900055210006900164260001600233300001200249490000800261520242900269653000902698653002802707653001802735653001702753653001102770653001002781653001102791653000902802653002502811653002402836653000902860653001502869100002502884700002602909700002402935700001902959700002202978700002403000856003503024 2003 eng d a0098-748400aCereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals.0 aCereal fruit and vegetable fiber intake and the risk of cardiova c2003 Apr 02 a1659-660 v2893 aCONTEXT: People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population.
OBJECTIVE: To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons.
DESIGN: Prospective cohort study conducted from 1989 to June 2000.
SETTING AND PARTICIPANTS: Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire.
MAIN OUTCOME MEASURE: Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction).
RESULTS: During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend =.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend =.98) nor vegetable fiber intake (P for trend =.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources.
CONCLUSIONS: Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber.
10aAged10aCardiovascular Diseases10aDietary Fiber10aEdible Grain10aFemale10aFruit10aHumans10aMale10aNutrition Assessment10aProspective Studies10aRisk10aVegetables1 aMozaffarian, Dariush1 aKumanyika, Shiriki, K1 aLemaitre, Rozenn, N1 aOlson, Jean, L1 aBurke, Gregory, L1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/73103113nas a2200553 4500008004100000022001400041245013800055210006900193260001600262300001100278490000800289520158800297653000901885653001901894653002301913653001501936653002101951653001901972653001601991653001102007653002202018653001102040653001402051653002502065653000902090653001302099653001902112653001502131653001702146653003202163653002002195653001702215653001102232653001802243653001702261653002002278100001602298700001602314700002102330700002002351700002102371700002302392700002102415700002402436700002502460700002102485700001802506856003502524 2003 eng d a1524-453900aC-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.0 aCreactive protein carotid intimamedia thickness and incidence of c2003 Jul 15 a166-700 v1083 aBACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT.
METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95% CI 0.92 to 1.53), 1.05 (95% CI 0.81 to 1.37), and 1.60 (95% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT.
CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.
10aAged10aBrain Ischemia10aC-Reactive Protein10aCalifornia10aCarotid Arteries10aCohort Studies10aComorbidity10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMaryland10aNorth Carolina10aOdds Ratio10aPennsylvania10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aStroke10aTunica Intima10aTunica Media10aUltrasonography1 aCao, Jie, J1 aThach, Chau1 aManolio, Teri, A1 aPsaty, Bruce, M1 aKuller, Lewis, H1 aChaves, Paulo, H M1 aPolak, Joseph, F1 aSutton-Tyrrell, Kim1 aHerrington, David, M1 aPrice, Thomas, R1 aCushman, Mary uhttps://chs-nhlbi.org/node/74103943nas a2200397 4500008004100000022001400041245008100055210006900136260001300205300001000218490000700228520285600235653000903091653002203100653001103122653001103133653002003144653000903164653001603173653002603189653001503215653001703230653002603247653002903273100002403302700001903326700001703345700001803362700001703380700001903397700001903416700002303435700002303458710002903481856003503510 2003 eng d a0149-599200aDiabetes and sleep disturbances: findings from the Sleep Heart Health Study.0 aDiabetes and sleep disturbances findings from the Sleep Heart He c2003 Mar a702-90 v263 aOBJECTIVE: To test the hypothesis that diabetes is independently associated with sleep-disordered breathing (SDB), and in particular that diabetes is associated with sleep abnormalities of a central, rather than obstructive, nature.
RESEARCH DESIGN AND METHODS: Using baseline data from the Sleep Heart Health Study (SHHS), we related diabetes to 1). the respiratory disturbance index (RDI; number of apneas plus hypopneas per h of sleep); 2). obstructive apnea index (OAI; >or=3 apneas/h of sleep associated with obstruction of the upper airway); 3). percent of sleep time < 90% O(2) saturation; 4). central apnea index (CAI; >or=3 apneas [without respiratory effort]/h sleep); 5). occurrence of a periodic breathing (Cheyne Stokes) pattern; and 6) sleep stages. Initial analyses excluding persons with prevalent cardiovascular disease (CVD) were repeated including these participants.
RESULTS: Of the 5874 participants included in this report, 692 (11.8%) reported diabetes or were taking oral hypoglycemic medications or insulin and 1002 had prevalent CVD. Among the 4872 persons without CVD, 470 (9.6%) had diabetes. Diabetic participants had worse CVD risk factor profiles than their nondiabetic counterparts, including higher BMI, waist and neck circumferences, triglycerides, higher prevalence of hypertension, and lower HDL cholesterol (P < 0.001, all). Descriptive analyses indicated differences between diabetic and nondiabetic participants in RDI, sleep stages, sleep time <90% O(2) saturation, CAI, and periodic breathing (P < 0.05, all). However, multivariable regression analyses that adjusted for age, sex, BMI, race, and neck circumference eliminated these differences for all sleep measures except percent time in rapid eye movement (REM) sleep (19.0% among diabetic vs. 20.1% among nondiabetic subjects, P < 0.001) and prevalence of periodic breathing (odds ratio [OR] for diabetic subjects versus nondiabetic subjects 1.80, 95% CI 1.02-3.15). Additionally, adjusted analyses showed diabetes was associated with nonstatistically significant elevations in the odds of an increased central breathing index (OR 1.42, 95% CI 0.80-2.55). Addition to the analysis of the 1002 persons with prevalent CVD (including 222 people with diabetes) did not materially change these results.
CONCLUSIONS: These data suggest that diabetes is associated with periodic breathing, a respiratory abnormality associated with abnormalities in the central control of ventilation. Some sleep disturbances may result from diabetes through the deleterious effects of diabetes on central control of respiration. The high prevalence of SDB in diabetes, although largely explained by obesity and other confounders, suggests the presence of a potentially treatable risk factor for CVD in the diabetic population.
10aAged10aDiabetes Mellitus10aFemale10aHumans10aLogistic Models10aMale10aMiddle Aged10aMultivariate Analysis10aPrevalence10aRisk Factors10aSleep Apnea Syndromes10aSleep Apnea, Obstructive1 aResnick, Helaine, E1 aRedline, Susan1 aShahar, Eyal1 aGilpin, Adele1 aNewman, Anne1 aWalter, Robert1 aEwy, Gordon, A1 aHoward, Barbara, V1 aPunjabi, Naresh, M1 aSleep Heart Health Study uhttps://chs-nhlbi.org/node/72703306nas a2200493 4500008004100000022001400041245007000055210006800125260001300193300001000206490000800216520195600224653003902180653000902219653002202228653002102250653001902271653002302290653001502313653001902328653000902347653004002356653001102396653001102407653001702418653002002435653002502455653002502480653000902505653002402514653001902538653001502557653002402572653001702596653001802613100001802631700002402649700002102673700002102694700001802715700002202733700002202755856003502777 2003 eng d a0161-642000aEarly age-related maculopathy in the cardiovascular health study.0 aEarly agerelated maculopathy in the cardiovascular health study c2003 Jan a25-330 v1103 aOBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes.
DESIGN: Population-based cohort study.
PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998.
METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System.
MAIN OUTCOME MEASURES: Early ARM.
RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites (18.2%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM.
CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aArteriosclerosis10aBlood Pressure10aC-Reactive Protein10aCalifornia10aCohort Studies10aDiet10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension10aLeukocyte Count10aLongitudinal Studies10aMacular Degeneration10aMale10aMid-Atlantic Region10aNorth Carolina10aPrevalence10aProspective Studies10aRisk Factors10aSerum Albumin1 aKlein, Ronald1 aKlein, Barbara, E K1 aMarino, Emily, K1 aKuller, Lewis, H1 aFurberg, Curt1 aBurke, Gregory, L1 aHubbard, Larry, D uhttps://chs-nhlbi.org/node/71803344nas a2200469 4500008004100000022001400041245010400055210006900159260001600228300001000244490000800254520201200262653000902274653002402283653001502307653003002322653002302352653002802375653001902403653001502422653002802437653001102465653004302476653001502519653001702534653001102551653001702562653001802579653000902597653002402606653002402630653001702654100002402671700002002695700001702715700002302732700002102755700002202776700002102798700002002819856003502839 2003 eng d a1524-453900aElevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.0 aElevations of inflammatory and procoagulant biomarkers in elderl c2003 Jan 07 a87-920 v1073 aBACKGROUND: Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease.
METHODS AND RESULTS: The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar.
CONCLUSION: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.
10aAged10aalpha-2-Antiplasmin10aBiomarkers10aBlood Coagulation Factors10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aCreatinine10aCross-Sectional Studies10aFemale10aFibrin Fibrinogen Degradation Products10aFibrinogen10aFibrinolysin10aHumans10aInflammation10aInterleukin-610aMale10aProspective Studies10aRenal Insufficiency10aRisk Factors1 aShlipak, Michael, G1 aFried, Linda, F1 aCrump, Casey1 aBleyer, Anthony, J1 aManolio, Teri, A1 aTracy, Russell, P1 aFurberg, Curt, D1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/71902725nas a2200397 4500008004100000022001400041245007300055210006900128260001700197300000900214490000700223520163300230653002101863653000901884653002201893653002801915653002401943653001901967653002801986653001302014653001102027653001102038653002502049653003102074653000902105653001502114653001702129653002102146100002002167700002102187700002502208700001602233700002102249700002202270856003502292 2003 eng d a0251-535000aEvaluation of dementia in the cardiovascular health cognition study.0 aEvaluation of dementia in the cardiovascular health cognition st c2003 Jan-Feb a1-120 v223 aOBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS).
METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists.
RESULTS: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer's disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women.
CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.
10aAge Distribution10aAged10aAged, 80 and over10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aCross-Sectional Studies10aDementia10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aPrevalence10aRisk Factors10aSex Distribution1 aLopez, Oscar, L1 aKuller, Lewis, H1 aFitzpatrick, Annette1 aIves, Diane1 aBecker, James, T1 aBeauchamp, Norman uhttps://chs-nhlbi.org/node/72302781nas a2200421 4500008004100000022001400041245007000055210006800125260001600193300001100209490000800220520163800228653000901866653002001875653001901895653003401914653001301948653001601961653001101977653004301988653001102031653002502042653000902067653001602076653001502092653002402107653001602131653001702147653002202164100001802186700002102204700001302225700001802238700002302256700002202279700002302301856003502324 2003 eng d a0006-497100aFibrin fragment D-dimer and the risk of future venous thrombosis.0 aFibrin fragment Ddimer and the risk of future venous thrombosis c2003 Feb 15 a1243-80 v1013 aPlasma D-dimer concentration rises more than 100-fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in 2 prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21 690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (P for trend <.0001). Following added adjustment for sex, race, body mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIII coagulant activity (factor VIII:c), these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (P for trend <.0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio, 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow-up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis.
10aAged10aBody Mass Index10aCohort Studies10aContinental Population Groups10aFactor V10aFactor VIII10aFemale10aFibrin Fibrinogen Degradation Products10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aOdds Ratio10aProspective Studies10aProthrombin10aRisk Factors10aVenous Thrombosis1 aCushman, Mary1 aFolsom, Aaron, R1 aWang, Lu1 aAleksic, Nena1 aRosamond, Wayne, D1 aTracy, Russell, P1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/70602735nas a2200493 4500008004100000022001400041245006400055210006200119260001600181300001200197490000800209520139200217653002101609653000901630653002001639653001401659653001901673653002501692653003301717653001101750653001101761653002001772653001601792653002601808653001501834653002001849653001801869653001501887653003201902653003001934653002601964653001701990653001802007100001702025700001902042700001702061700002002078700002202098700001802120700002402138700002302162700002102185856003502206 2003 eng d a1073-449X00aHormone replacement therapy and sleep-disordered breathing.0 aHormone replacement therapy and sleepdisordered breathing c2003 May 01 a1186-920 v1673 aDisordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant's home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.
10aAge Distribution10aAged10aBody Mass Index10aCausality10aCohort Studies10aConfidence Intervals10aEstrogen Replacement Therapy10aFemale10aHumans10aLogistic Models10aMiddle Aged10aMultivariate Analysis10aOdds Ratio10aPolysomnography10aPostmenopause10aPrevalence10aSensitivity and Specificity10aSeverity of Illness Index10aSleep Apnea Syndromes10aSleep Stages10aUnited States1 aShahar, Eyal1 aRedline, Susan1 aYoung, Terry1 aBoland, Lori, L1 aBaldwin, Carol, M1 aNieto, Javier1 aO'Connor, George, T1 aRapoport, David, M1 aRobbins, John, A uhttps://chs-nhlbi.org/node/72103151nas a2200493 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520176200271653000902033653002202042653002002064653001902084653003302103653001102136653001802147653001102165653001402176653001502190653001602205653002602221653001202247653003302259653003202292653002402324653000902348653001702357653001802374653001902392100001902411700002002430700002302450700001802473700002002491700001902511700002402530700002302554700002202577700002302599856003502622 2003 eng d a1540-999600aHormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.0 aHormone replacement therapy and the risk of incident congestive c2003 May a341-500 v123 aBACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.
METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).
RESULTS: At baseline, 62% were never users, 26% were past users, and 12% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).
CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.
10aAged10aAged, 80 and over10aBody Mass Index10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aHeart Failure10aHumans10aIncidence10aLife Style10aMiddle Aged10aMultivariate Analysis10aObesity10aOsteoporosis, Postmenopausal10aProportional Hazards Models10aProspective Studies10aRisk10aRisk Factors10aUnited States10aWomen's Health1 aRea, Thomas, D1 aPsaty, Bruce, M1 aHeckbert, Susan, R1 aCushman, Mary1 aMeilahn, Elaine1 aOlson, Jean, L1 aLemaitre, Rozenn, N1 aSmith, Nicholas, L1 aSotoodehnia, Nona1 aChaves, Paulo, H M uhttps://chs-nhlbi.org/node/74002504nas a2200337 4500008004100000022001400041245007000055210006800125260001300193300001100206490000700217520160800224653000901832653002501841653000901866653002101875653003701896653001501933653001101948653001801959653001101977653002501988653000902013653002002022653001702042653001102059653001802070100002602088700001702114856003502131 2003 eng d a0895-435600aImputation of missing longitudinal data: a comparison of methods.0 aImputation of missing longitudinal data a comparison of methods c2003 Oct a968-760 v563 aBACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal studies, and can result in biased estimates and a loss of power. One approach to this problem is to impute the missing data to yield a more complete data set. Our goal was to compare the performance of 14 methods of imputing missing data on depression, weight, cognitive functioning, and self-rated health in a longitudinal cohort of older adults.
METHODS: We identified situations where a person had a known value following one or more missing values, and treated the known value as a "missing value." This "missing value" was imputed using each method and compared to the observed value. Methods were compared on the root mean square error, mean absolute deviation, bias, and relative variance of the estimates.
RESULTS: Most imputation methods were biased toward estimating the "missing value" as too healthy, and most estimates had a variance that was too low. Imputed values based on a person's values before and after the "missing value" were superior to other methods, followed by imputations based on a person's values before the "missing value." Imputations that used no information specific to the person, such as using the sample mean, had the worst performance.
CONCLUSIONS: We conclude that, in longitudinal studies where the overall trend is for worse health over time and where missing data can be assumed to be primarily related to worse health, missing data in a longitudinal sequence should be imputed from the available longitudinal data for that person.
10aAged10aAnalysis of Variance10aBias10aCoronary Disease10aData Interpretation, Statistical10aDepression10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aResearch Design10aRisk Factors10aStroke10aUnited States1 aEngels, Jean, Mundahl1 aDiehr, Paula uhttps://chs-nhlbi.org/node/75402623nas a2200385 4500008004100000022001400041245005900055210005800114260001600172300001200188490000800200520156500208653000901773653002401782653002301806653002801829653001101857653001101868653001701879653002501896653000901921653001701930100002301947700002101970700002901991700002602020700002302046700002402069700002202093700002602115700002002141700002202161700001902183856003502202 2003 eng d a1524-453900aInflammation as a risk factor for atrial fibrillation.0 aInflammation as a risk factor for atrial fibrillation c2003 Dec 16 a3006-100 v1083 aBACKGROUND: The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort.
METHODS AND RESULTS: CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9+/-1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P=0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P=0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P<0.001).
CONCLUSIONS: CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.
10aAged10aAtrial Fibrillation10aC-Reactive Protein10aCross-Sectional Studies10aFemale10aHumans10aInflammation10aLongitudinal Studies10aMale10aRisk Factors1 aAviles, Ronnier, J1 aMartin, David, O1 aApperson-Hansen, Carolyn1 aHoughtaling, Penny, L1 aRautaharju, Pentti1 aKronmal, Richard, A1 aTracy, Russell, P1 aVan Wagoner, David, R1 aPsaty, Bruce, M1 aLauer, Michael, S1 aChung, Mina, K uhttps://chs-nhlbi.org/node/75802424nas a2200433 4500008004100000022001400041245013700055210006900192260001300261300001300274490000600287520117600293653003901469653000901508653001201517653002801529653002501557653001901582653004001601653001101641653001301652653001501665653001101680653000901691653002601700653003801726653002601764653003001790653000901820100001601829700001601845700001201861700001701873700001601890700001501906700001901921700001501940856003501955 2003 eng d a1538-793300aLack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.0 aLack of association of the plasminogen activator inhibitor1 4G5G c2003 Aug a1799-8040 v13 aElevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.
10aAfrican Continental Ancestry Group10aAged10aAlleles10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHomozygote10aHumans10aMale10aMyocardial Infarction10aPlasminogen Activator Inhibitor 110aPolymorphism, Genetic10aPromoter Regions, Genetic10aRisk1 aCrainich, P1 aJenny, N, S1 aTang, Z1 aArnold, A, M1 aKuller, L H1 aManolio, T1 aSharrett, A, R1 aTracy, R P uhttps://chs-nhlbi.org/node/74503326nas a2200373 4500008004100000022001400041245007100055210006600126260001600192300001200208490000800220520231600228653000902544653002102553653001102574653001102585653001402596653001902610653000902629653001402638653003202652653002402684653001702708653001602725653001102741653002202752653001802774653002202792100002202814700001602836700001902852710004602871856003502917 2003 eng d a1533-440600aLp(a) lipoprotein, vascular disease, and mortality in the elderly.0 aLpa lipoprotein vascular disease and mortality in the elderly c2003 Nov 27 a2108-150 v3493 aBACKGROUND: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults.
METHODS: In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line.
RESULTS: Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation.
CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.
10aAged10aCoronary Disease10aFemale10aHumans10aIncidence10aLipoprotein(a)10aMale10aMortality10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSex Factors10aStroke10aSurvival Analysis10aUnited States10aVascular Diseases1 aAriyo, Abraham, A1 aThach, Chau1 aTracy, Russell1 aCardiovascular Health Study Investigators uhttps://chs-nhlbi.org/node/75902460nas a2200433 4500008004100000022001400041245007700055210006900132260001600201300001000217490000800227520120800235653003901443653000901482653002201491653002501513653002801538653001901566653001901585653002001604653003701624653002601661653001101687653001101698653001801709653000901727653002701736653002401763653003001787653003201817653001701849653001301866653002201879653001801901653002701919100002101946700002401967856003501991 2003 eng d a0002-926200aMultiple imputation of baseline data in the cardiovascular health study.0 aMultiple imputation of baseline data in the cardiovascular healt c2003 Jan 01 a74-840 v1573 aMost epidemiologic studies will encounter missing covariate data. Software packages typically used for analyzing data delete any cases with a missing covariate to perform a complete case analysis. The deletion of cases complicates variable selection when different variables are missing on different cases, reduces power, and creates the potential for bias in the resulting estimates. Recently, software has become available for producing multiple imputations of missing data that account for the between-imputation variability. The implementation of the software to impute missing baseline data in the setting of the Cardiovascular Health Study, a large, observational study, is described. Results of exploratory analyses using the imputed data were largely consistent with results using only complete cases, even in a situation where one third of the cases were excluded from the complete case analysis. There were few differences in the exploratory results across three imputations, and the combined results from the multiple imputations were very similar to results from a single imputation. An increase in power was evident and variable selection simplified when using the imputed data sets.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aAnalysis of Variance10aCardiovascular Diseases10aCause of Death10aCohort Studies10aData Collection10aData Interpretation, Statistical10aEpidemiologic Studies10aFemale10aHumans10aLinear Models10aMale10aMathematical Computing10aModels, Statistical10aPredictive Value of Tests10aProportional Hazards Models10aRisk Factors10aSoftware10aSurvival Analysis10aUnited States10aVentricular Remodeling1 aArnold, Alice, M1 aKronmal, Richard, A uhttps://chs-nhlbi.org/node/71703213nas a2200457 4500008004100000022001400041245015200055210006900207260001300276300001100289490000700300520188900307653000902196653002502205653001502230653002502245653001902270653002102289653002402310653002602334653002602360653002502386653001102411653001402422653001102436653001402447653000902461653002602470653001502496653001802511653001502529653002402544653001702568100002402585700001902609700002502628700002102653700002202674700002402696856003502720 2003 eng d a0002-916500an-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study.0 an3 Polyunsaturated fatty acids fatal ischemic heart disease and c2003 Feb a319-250 v773 aBACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults.
OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults.
DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event.
RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction.
CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.
10aAged10aalpha-Linolenic Acid10aBiomarkers10aCase-Control Studies10aCohort Studies10aCoronary Disease10aDietary Supplements10aDocosahexaenoic Acids10aEicosapentaenoic Acid10aFatty Acids, Omega-310aFemale10aFish Oils10aHumans10aIncidence10aMale10aMyocardial Infarction10aOdds Ratio10aPhospholipids10aPrevalence10aProspective Studies10aRisk Factors1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aMozaffarian, Dariush1 aKuller, Lewis, H1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/72202076nas a2200349 4500008004100000022001400041245010900055210006900164260001300233300001200246490000700258520111000265653000901375653001501384653002001399653002101419653001801440653001101458653001801469653001101487653002501498653000901523653001801532653002701550653002001577653001201597100002101609700002001630700002001650700002101670856003501691 2003 eng d a0882-797400aPerceptions and implications of received spousal care: evidence from the Caregiver Health Effects Study.0 aPerceptions and implications of received spousal care evidence f c2003 Sep a593-6010 v183 aThe experiences of older care recipients have received far less theoretical and empirical attention than those of their family caregivers. In this study of 91 care recipients, the authors assessed perceptions of the amount, timing, and manner of spousal assistance; the amount of strain experienced from receiving care; and psychological well-being. Although female care recipients were more likely to report dissatisfaction with the manner in which assistance was provided, there were few gender differences in perceptions of care overall. In a stringent test of the hypothesis that perceived quality of spousal care affects recipient well-being, the authors found that poorer quality of care was related to increased depressive symptoms and a decreased sense of mastery 1 year later. These longitudinal effects were independent of the recipient's physical disability, marital quality, and care-receiving strain as well as the caregiver's well-being. These findings argue for a comprehensive assessment of the care-receiving experience that includes both care-recipient and caregiver perspectives.
10aAged10aCaregivers10aChronic Disease10aDisabled Persons10aFamily Health10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aMental Health10aQuality of Health Care10aResearch Design10aSpouses1 aMartire, Lynn, M1 aSchulz, Richard1 aWrosch, Carsten1 aNewsom, Jason, T uhttps://chs-nhlbi.org/node/75102997nas a2200469 4500008004100000022001400041245012300055210006900178260001300247300001100260490000700271520163400278653000901912653002201921653002801943653002401971653001901995653001302014653001102027653001102038653002502049653003102074653000902105653002102114653002902135653001702164653001502181653003702196100002002233700002302253700002302276700002102299700002502320700002102345700001902366700002602385700001902411700001902430700002202449700002102471856003502492 2003 eng d a0003-994200aPrevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.0 aPrevalence and classification of mild cognitive impairment in th c2003 Oct a1385-90 v603 aOBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study.
DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort.
SETTING: Multicenter population study.
PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI.
MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type.
RESULTS: The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%.
CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aDementia10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMemory Disorders10aNeuropsychological Tests10aPennsylvania10aPopulation10aPsychiatric Status Rating Scales1 aLopez, Oscar, L1 aJagust, William, J1 aDeKosky, Steven, T1 aBecker, James, T1 aFitzpatrick, Annette1 aDulberg, Corinne1 aBreitner, John1 aLyketsos, Constantine1 aJones, Beverly1 aKawas, Claudia1 aCarlson, Michelle1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/75503786nas a2200445 4500008004100000022001400041245012600055210006900181260001300250300001100263490000800274520252700282653000902809653002202818653001902840653002802859653002802887653001102915653001102926653001702937653000902954653001502963653002102978653002002999653001703019653001803036100002003054700001803074700002103092700002103113700002203134700002103156700001803177700001903195700002203214700002103236700002403257700002403281856003503305 2003 eng d a0161-642000aThe prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study.0 aprevalence and risk factors of retinal microvascular abnormaliti c2003 Apr a658-660 v1103 aPURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons.
DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities.
METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations.
MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis.
RESULTS: The prevalence of retinal microvascular abnormalities was 8.3% for retinopathy, 9.6% for focal arteriolar narrowing, and 7.7% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis.
CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.
10aAged10aAged, 80 and over10aBlood Pressure10aCoronary Artery Disease10aCross-Sectional Studies10aFemale10aHumans10aHypertension10aMale10aPrevalence10aRetinal Diseases10aRetinal Vessels10aRisk Factors10aUnited States1 aWong, Tien, Yin1 aKlein, Ronald1 aSharrett, Richey1 aManolio, Teri, A1 aHubbard, Larry, D1 aMarino, Emily, K1 aKuller, Lewis1 aBurke, Gregory1 aTracy, Russell, P1 aPolak, Joseph, F1 aGottdiener, John, S1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/73402971nas a2200409 4500008004100000022001400041245012000055210006900175260001700244300001100261490000700272520180300279653001602082653000902098653001902107653002102126653001502147653002802162653001102190653001502201653002902216653001102245653003102256653000902287653002402296653002402320653001702344653001202361100002002373700001802393700002502411700002002436700002102456700002902477700002002506856003502526 2003 eng d a0251-535000aA prospective analysis of risk factors for white matter disease in the brain stem: the Cardiovascular Health Study.0 aprospective analysis of risk factors for white matter disease in c2003 Sep-Oct a275-820 v223 aBACKGROUND AND PURPOSE: White matter disease (WMD) in the brain stem may be a predictor of poor clinical outcome, independent of WMD in the periventricular and subcortical areas of the brain. Many cardiovascular risk factors such as older age, hypertension, and smoking have been suggested as risk factors for WMD in the periventricular and subcortical areas of the brain. However, no epidemiologic study has examined the associations between cardiovascular risk factors and WMD in the brain stem.
METHODS: A total of 789 participants, aged 65 years or older, from the Cardiovascular Health Study constituted the present study population. WMD, defined as hyperintensive lesions on magnetic resonance imaging (MRI), in the brain stem was measured in 1992/1993 and 1997/1998.
RESULTS: Of the 789 participants, 212 (26.9%) had WMD in the brain stem in 1997/1998. In multivariate logistic regression analysis, the presence of WMD in the brain stem in 1997/1998 was significantly associated with several variables measured in 1992/1993: an increase by 5 years of age (OR = 1.51, 95% CI: 1.25-1.83), a 10-pack-years increase in smoking (OR = 1.12, 95% CI: 1.04-1.21), a 0.1-liter increase in first-second forced expiratory volume (OR = 0.95, 95% CI: 0.92-0.99), a 1 micromol/l increase in fibrinogen level (OR = 1.13, 95% CI: 1.03-1.23), and MRI infarction (OR = 2.58, 95% CI: 1.78-3.74). Excluding those (n = 167) with WMD in the brain stem in 1992/1993, the pattern remained. Hypertension was not associated with WMD in the brain stem.
CONCLUSIONS: Increased age, smoking, lower forced expiratory volume, increased fibrinogen level, and MRI infarction, but not hypertension, may be independent risk factors for WMD in the brain stem in older adults.
10aAge Factors10aAged10aBrain Diseases10aBrain Infarction10aBrain Stem10aCardiovascular Diseases10aFemale10aFibrinogen10aForced Expiratory Volume10aHumans10aMagnetic Resonance Imaging10aMale10aProspective Studies10aRegression Analysis10aRisk Factors10aSmoking1 aDing, Jingzhong1 aNieto, Javier1 aBeauchamp, Norman, J1 aLongstreth, W T1 aManolio, Teri, A1 aHetmanski, Jacqueline, B1 aFried, Linda, P uhttps://chs-nhlbi.org/node/74403022nas a2200373 4500008004100000022001400041245008300055210006900138260001600207300001200223490000800235520198200243653000902225653002102234653002202255653002202277653001002299653002502309653001302334653001102347653001102358653003102369653000902400653002902409653002402438653000902462100002402471700002102495700002802516700002002544700002502564700002402589856003502613 2003 eng d a0098-748400aProspective study of alcohol consumption and risk of dementia in older adults.0 aProspective study of alcohol consumption and risk of dementia in c2003 Mar 19 a1405-130 v2893 aCONTEXT: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear.
OBJECTIVE: To determine the prospective relationship of alcohol consumption and risk of dementia among older adults.
DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999.
MAIN OUTCOME MEASURES: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI.
RESULTS: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term =.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia.
CONCLUSIONS: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.
10aAged10aAlcohol Drinking10aApolipoprotein E410aApolipoproteins E10aBrain10aCase-Control Studies10aDementia10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aProspective Studies10aRisk1 aMukamal, Kenneth, J1 aKuller, Lewis, H1 aFitzpatrick, Annette, L1 aLongstreth, W T1 aMittleman, Murray, A1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/72902062nas a2200433 4500008004100000022001400041245007400055210006900129260001300198300001200211490000700223520086300230653000901093653002401102653002801126653001501154653003601169653002501205653001101230653001701241653001701258653001101275653000901286653001601295653001501311653003801326653001401364653002401378653002901402653001701431653002001448653002201468100002101490700001801511700002301529700002301552700001801575856003501593 2003 eng d a0895-435600aProspective study of fibrinolytic markers and venous thromboembolism.0 aProspective study of fibrinolytic markers and venous thromboembo c2003 Jun a598-6030 v563 aPrior research has conflicted on whether increased levels of plasma fibrinolytic factors may identify patients at risk of venous thromboembolism (VTE). We therefore performed a nested case-control study of VTE within two prospective population-based studies. In 308 participants who developed VTE and 640 controls, we measured PAI-1 antigen, tPA/PAI-1 complex, plasmin-alpha 2-antiplasmin (PAP), and the PAI-1 -675 4G/5G promoter polymorphism on pre-event blood samples. There was no overall association between any of these fibrinolytic variables and VTE, after adjustment for age or for multiple VTE risk factors. There was weak evidence for an interaction of PAP with elevated factor VIIIc and elevated D-dimer in augmenting VTE risk. We conclude that, for the most part, these fibrinolytic markers do not identify healthy subjects at risk for VTE.
10aAged10aalpha-2-Antiplasmin10aAntifibrinolytic Agents10aBiomarkers10aCaenorhabditis elegans Proteins10aCase-Control Studies10aFemale10aFibrinolysin10aFibrinolysis10aHumans10aMale10aMiddle Aged10aOdds Ratio10aPlasminogen Activator Inhibitor 110aPrognosis10aProspective Studies10aProtein-Tyrosine Kinases10aRisk Factors10aThromboembolism10aVenous Thrombosis1 aFolsom, Aaron, R1 aCushman, Mary1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aAleksic, Nena uhttps://chs-nhlbi.org/node/74302046nas a2200397 4500008004100000022001400041245015600055210006900211260001300280300001000293490000600303520093200309653001601241653000901257653002801266653002501294653001101319653001301330653001101343653001401354653000901368653002601377653001501403653002401418653001701442653002001459653001901479653002201498100001501520700001701535700001501552700001801567700001501585700001301600856003501613 2003 eng d a1538-793300aProspective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study.0 aProspective study of the A455V polymorphism in the thrombomoduli c2003 Jan a88-940 v13 aPlasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.
10aAge Factors10aAged10aAmino Acid Substitution10aCase-Control Studies10aFemale10aGenotype10aHumans10aIncidence10aMale10aPolymorphism, Genetic10aPrevalence10aProspective Studies10aRisk Factors10aThromboembolism10aThrombomodulin10aVenous Thrombosis1 aAleksic, N1 aFolsom, A, R1 aCushman, M1 aHeckbert, S R1 aTsai, M, Y1 aWu, K, K uhttps://chs-nhlbi.org/node/74202843nas a2200325 4500008004100000022001400041245011600055210006900171260001300240300001200253490000700265520188600272653003902158653000902197653002202206653002102228653004002249653001102289653001102300653000902311653001502320653001502335653001802350100001902368700002002387700002802407700002702435700002002462856003502482 2003 eng d a0885-318500aRegional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States.0 aRegional and racial differences in the prevalence of physiciandi c2003 Sep a1035-400 v183 aFor reasons that are unclear, prevalence estimates of essential tremor (ET) differ considerably across the United States. Separate communities have never been sampled within the framework of the same study to substantiate these differences. We estimated the prevalence of physician-diagnosed ET in the elderly in four communities in the United States in whom the same screening questions were used, and examined whether this prevalence differed between Caucasians and African Americans. The Cardiovascular Health Study recruited a sample of Medicare beneficiaries >/=65 years of age from four communities in different regions of the United States. In 1998 to 1999, 3,494 participants (mean age, 80.0 years; range, 70-103 years) answered a 12-question screen for ET, including the question, "has a doctor diagnosed you as having familial tremor or benign essential tremor?" Fifty-four participants reported that a doctor had diagnosed them as having ET (1.5%; 95% confidence interval, [CI], 1.1-2.0%). Prevalence was similar across the four communities (1.1-2.0%). A larger proportion of Caucasians than African Americans reported a diagnosis of ET (1.7% vs. 0.4%; odds ratio = 4.9; 95% CI, 1.2-20.2; P = 0.028). In a logistic regression analysis, physician-diagnosed ET was associated with Caucasian ethnicity (P = 0.038) but not with age, gender, education, mental status or depression scores, income, smoking status, or alcohol consumption. When a standardized screening question was used, the proportion of participants with physician-diagnosed ET was similar across four communities, suggesting that the prevalence of this condition may be less variable than is often reported. Caucasians were five times more likely to have physician-diagnosed ET than were African Americans. This study does not provide an explanation for this difference, which deserves further study.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aEssential Tremor10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aPhysicians10aPrevalence10aUnited States1 aLouis, Elan, D1 aFried, Linda, P1 aFitzpatrick, Annette, L1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/75002224nas a2200325 4500008004100000022001400041245010800055210006900163260001300232300001200245490000700257520130800264653000901572653002801581653002101609653000901630653001801639653001101657653002201668653001801690653001101708653001401719653001801733653000901751653004001760653001801800100001701818700002801835856003501863 2003 eng d a0895-435600aThe relation of dietary patterns to future survival, health, and cardiovascular events in older adults.0 arelation of dietary patterns to future survival health and cardi c2003 Dec a1224-350 v563 aBACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns.
METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later.
RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large.
CONCLUSIONS: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes.
10aAged10aCardiovascular Diseases10aCluster Analysis10aDiet10aEnergy Intake10aFemale10aFollow-Up Studies10aHealth Status10aHumans10aIncidence10aLinear Models10aMale10aNutritional Physiological Phenomena10aSurvival Rate1 aDiehr, Paula1 aBeresford, Shirley, A A uhttps://chs-nhlbi.org/node/76003244nas a2200349 4500008004100000022001400041245012500055210006900180260001300249300001000262490000700272520223000279653000902509653001902518653001102537653001102548653001702559653001102576653002002587653000902607653002402616653003702640653002202677100002402699700002502723700002302748700002202771700002302793700002202816700002102838856003502859 2003 eng d a1523-683800aRelationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study.0 aRelationships between renovascular disease blood pressure and re c2003 May a990-60 v413 aBACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS).
METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination.
RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041).
CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.
10aAged10aBlood Pressure10aFemale10aHumans10aHypertension10aKidney10aKidney Diseases10aMale10aProspective Studies10aUltrasonography, Doppler, Duplex10aVascular Diseases1 aEdwards, Matthew, S1 aHansen, Kimberley, J1 aCraven, Timothy, E1 aCherr, Gregory, S1 aBleyer, Anthony, J1 aBurke, Gregory, L1 aDean, Richard, H uhttps://chs-nhlbi.org/node/73703093nas a2200385 4500008004100000022001400041245010400055210006900159260001600228300001200244490000700256520198500263653000902248653002802257653002502285653001502310653001102325653001802336653001102354653003002365653002802395653000902423653001502432653003002447653002202477100002002499700002402519700001702543700002302560700002402583700002402607700002102631700002002652856003502672 2003 eng d a0735-109700aRenal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals.0 aRenal insufficiency as a predictor of cardiovascular outcomes an c2003 Apr 16 a1364-720 v413 aOBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.
BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.
METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women.
RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.
CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.
10aAged10aCardiovascular Diseases10aConfidence Intervals10aCreatinine10aFemale10aHeart Failure10aHumans10aIntermittent Claudication10aKidney Failure, Chronic10aMale10aOdds Ratio10aPredictive Value of Tests10aSurvival Analysis1 aFried, Linda, F1 aShlipak, Michael, G1 aCrump, Casey1 aBleyer, Anthony, J1 aGottdiener, John, S1 aKronmal, Richard, A1 aKuller, Lewis, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/73502708nas a2200421 4500008004100000022001400041245007600055210006900131260001700200300001000217490000700227520155000234653000901784653002201793653002201815653002801837653002401865653001301889653001101902653001301913653001101926653003101937653000901968653001501977653003001992653003202022653001702054100002102071700002002092700001702112700002502129700001602154700002102170700002502191700001702216700001802233856003502251 2003 eng d a0251-535000aRisk factors for dementia in the cardiovascular health cognition study.0 aRisk factors for dementia in the cardiovascular health cognition c2003 Jan-Feb a13-220 v223 aBACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999.
METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD).
RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes.
CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.
10aAged10aAged, 80 and over10aApolipoproteins E10aCardiovascular Diseases10aCognition Disorders10aDementia10aFemale10aGenotype10aHumans10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPredictive Value of Tests10aProportional Hazards Models10aRisk Factors1 aKuller, Lewis, H1 aLopez, Oscar, L1 aNewman, Anne1 aBeauchamp, Norman, J1 aBurke, Greg1 aDulberg, Corinne1 aFitzpatrick, Annette1 aFried, Linda1 aHaan, Mary, N uhttps://chs-nhlbi.org/node/72403994nas a2200493 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520261100262653000902873653002202882653002202904653001002926653002802936653002402964653001902988653002403007653001103031653001103042653002003053653002503073653003103098653000903129653001903138653001703157653001503174653001703189100002003206700002303226700002103249700002103270700002303291700002503314700001903339700002603358700001903384700001903403700002203422700002103444856003503465 2003 eng d a0003-994200aRisk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.0 aRisk factors for mild cognitive impairment in the Cardiovascular c2003 Oct a1394-90 v603 aOBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study.
DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type.
SETTING: Multicenter population study.
PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort.
MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease.
RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores.
CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.
10aAged10aApolipoprotein E410aApolipoproteins E10aBrain10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aDepressive Disorder10aFemale10aHumans10aLogistic Models10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMood Disorders10aPennsylvania10aPopulation10aRisk Factors1 aLopez, Oscar, L1 aJagust, William, J1 aDulberg, Corinne1 aBecker, James, T1 aDeKosky, Steven, T1 aFitzpatrick, Annette1 aBreitner, John1 aLyketsos, Constantine1 aJones, Beverly1 aKawas, Claudia1 aCarlson, Michelle1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/75602477nas a2200481 4500008004100000022001400041245018500055210006900240260001300309300001200322490000700334520104600341653000901387653001001396653001201406653002501418653001901443653001301462653001101475653001301486653001701499653001101516653002501527653000901552653004901561653001601610653001501626653004901641653002601690653002401716653001701740653002201757100002001779700001801799700002101817700002301838700002301861700001801884700001701902700002001919700002101939856003501960 2003 eng d a0361-860900aSerum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE).0 aSerum homocysteine thermolabile variant of methylene tetrahydrof c2003 Mar a192-2000 v723 aWe sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.
10aAged10aAging10aAnimals10aCase-Control Studies10aCohort Studies10aFactor V10aFemale10aGenotype10aHomocysteine10aHumans10aLongitudinal Studies10aMale10aMethylenetetrahydrofolate Reductase (NADPH2)10aMiddle Aged10aOdds Ratio10aOxidoreductases Acting on CH-NH Group Donors10aPolymorphism, Genetic10aProspective Studies10aRisk Factors10aVenous Thrombosis1 aTsai, Albert, W1 aCushman, Mary1 aTsai, Michael, Y1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aAleksic, Nena1 aYanez, David1 aPsaty, Bruce, M1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/72603188nas a2200433 4500008004100000022001400041245010300055210006900158260001600227300000900243490000800252520195400260653000902214653001902223653001102242653002902253653001102282653000902293653001602302653001902318653002002337653002402357653004302381653001002424653002902434653001502463653001902478100002102497700002002518700002702538700001902565700002202584700002002606700002402626700002302650700001702673710002902690856003502719 2003 eng d a1073-449X00aSleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease.0 aSleep and sleepdisordered breathing in adults with predominantly c2003 Jan 01 a7-140 v1673 aNeither the association between obstructive airways disease (OAD) and sleep apnea-hypopnea (SAH) nor the sleep consequences of each disorder alone and together have been characterized in an adult community setting. Our primary aims were (1) to determine if there is an association between OAD and SAH and (2) identify predictors of oxyhemoglobin desaturation during sleep in persons having OAD with and without SAH. Polysomnography and spirometry results from 5,954 participants in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC value less than 70%. Assessment of SAH prevalence in OAD was performed using thresholds of respiratory disturbance index (RDI) greater than 10 and greater than 15. A total of 1,132 participants had OAD that was predominantly mild (FEV1/FVC 63.81 +/- 6.56%, mean +/- SD). SAH was not more prevalent in participants with OAD than in those without OAD (22.32 versus 28.86%, with and without OAD, respectively, at RDI threshold values greater than 10; and 13.97 versus 18.63%, with and without OAD, respectively, at RDI threshold value greater than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation (> 5% total sleep time with saturation < 90%) was greater than 1.9 when FEV1/FVC was less than 65%. Participants with both OAD and SAH had greater sleep perturbation and desaturation than those with one disorder. Generally mild OAD alone was associated with minimally altered sleep quality. We conclude that (1) there is no association between generally mild OAD and SAH; (2) exclusive of SAH and after adjusting for demographic factors and awake oxyhemoglobin saturation, an FEV1/FVC value less than 65% is associated with increased risk of sleep desaturation; (3) desaturation is greater in persons with both OAD and SAH compared with each of these alone; and (4) individuals with generally mild OAD and without SAH in the community have minimally perturbed sleep.
10aAged10aCohort Studies10aFemale10aForced Expiratory Volume10aHumans10aMale10aMiddle Aged10aOxyhemoglobins10aPolysomnography10aProspective Studies10aPulmonary Disease, Chronic Obstructive10aSleep10aSleep Apnea, Obstructive10aSpirometry10aVital Capacity1 aSanders, Mark, H1 aNewman, Anne, B1 aHaggerty, Catherine, L1 aRedline, Susan1 aLebowitz, Michael1 aSamet, Jonathan1 aO'Connor, George, T1 aPunjabi, Naresh, M1 aShahar, Eyal1 aSleep Heart Health Study uhttps://chs-nhlbi.org/node/71503011nas a2200421 4500008004100000022001400041245007000055210006600125260001600191300001200207490000800219520184900227653000902076653002202085653001002107653002302117653002802140653001102168653001802179653001102197653002502208653000902233653002002242653002402262653001702286100002002303700002102323700002402344700002002368700002202388700001802410700002102428700001902449700002002468700001902488710004702507856003502554 2003 eng d a0003-992600a"Successful aging": effect of subclinical cardiovascular disease.0 aSuccessful aging effect of subclinical cardiovascular disease c2003 Oct 27 a2315-220 v1633 aBACKGROUND: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined.
METHODS: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning.
RESULTS: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself.
CONCLUSIONS: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.
10aAged10aAged, 80 and over10aAging10aC-Reactive Protein10aCardiovascular Diseases10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aQuality of Life10aRegression Analysis10aRisk Factors1 aNewman, Anne, B1 aArnold, Alice, M1 aNaydeck, Barbara, L1 aFried, Linda, P1 aBurke, Gregory, L1 aEnright, Paul1 aGottdiener, John1 aHirsch, Calvin1 aO'Leary, Daniel1 aTracy, Russell1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/75702151nas a2200361 4500008004100000022001400041245003900055210003800094260001300132300001100145490000700156520124200163653003001405653000901435653002201444653001501466653001101481653002001492653001801512653001101530653001901541653000901560653003001569653001201599653002601611653001701637100002101654700002001675700002001695700002001715700001901735856003501754 2003 eng d a0016-901300aTransitions in spousal caregiving.0 aTransitions in spousal caregiving c2003 Apr a230-410 v433 aPURPOSE: This study describes transitions over 5 years among community-dwelling elderly spouses into and within caregiving roles and associated health outcomes.
DESIGN AND METHODS: Participants in the Caregiver Health Effects Study (n = 818) were interviewed four times over 5 years with changes in their caregiving status described. Analyses of the effect on health outcomes of transitions were performed on those for whom four observations were available (n = 428).
RESULTS: Only half (49.5%) of noncaregivers at baseline remained noncaregivers at 5-year follow-up. The remainder experienced one or more transitions, including moving into the caregiving role, their own or their spouse's death, or placement of their spouse in a long-term care facility. The trajectory of health outcomes associated with caregiving was generally downward. Those who transitioned to heavy caregiving had more symptoms of depression, and poorer self-reported health and health behaviors.
IMPLICATIONS: Transitions into and within the caregiving role should be monitored for adverse health effects on the caregiver, with interventions tailored to the individual's location in the caregiving trajectory.
10aAdaptation, Psychological10aAged10aAged, 80 and over10aCaregivers10aFemale10aHealth Behavior10aHealth Status10aHumans10aLong-Term Care10aMale10aResidence Characteristics10aSpouses10aStress, Psychological10aTime Factors1 aBurton, Lynda, C1 aZdaniuk, Bozena1 aSchulz, Richard1 aJackson, Sharon1 aHirsch, Calvin uhttps://chs-nhlbi.org/node/73203293nas a2200421 4500008004100000022001400041245011100055210006900166260001600235300000900251490000700260520206600267653001002333653002802343653002702371653002302398653001802421653001102439653001502450653001102465653000902476653002002485653003002505653002602535653001202561653003102573100002402604700002002628700001802648700001802666700001902684700002302703700002002726700002402746700002302770710004302793856003502836 2003 eng d a0161-810500aVariation in symptoms of sleep-disordered breathing with race and ethnicity: the Sleep Heart Health Study.0 aVariation in symptoms of sleepdisordered breathing with race and c2003 Feb 01 a74-90 v263 aSTUDY OBJECTIVES: To examine the relation of sleep-related symptoms to race and ethnicity in a diverse sample of middle-aged and older men and women.
DESIGN: Cross-sectional questionnaire survey.
SETTING: In the initial phase of the Sleep Heart Health Study, men and women enrolled in participating epidemiologic cohort studies were surveyed.
PARTICIPANTS: 13,194 men and women 40 years of age and older, including 11,517 non-Hispanic white, 648 black, 643 American Indian, 296 Hispanic, and 90 Asian-Pacific Islander.
INTERVENTIONS: Not applicable.
MEASUREMENTS AND RESULTS: After adjustment for BMI and other factors, frequent snoring was more common among Hispanic women (odds ratio (OR) = 2.25, 95% confidence interval (CI) = 1.48, 3.42) and black women (OR = 1.55, 95% Ci = 1.13, 2.13) than among non-Hispanic white women. Hispanic men were significantly more likely to report frequent snoring than non-Hispanic white men (OR = 2.30, 95% CI = 1.43, 3.69). Black, American Indian, and Asian men did not differ significantly from white men in snoring prevalence. American Indian women were significantly more likely to report breathing pauses during sleep than their white, non-Hispanic counterparts (OR = 1.52, 95% CI 1.03, 2.24), although polysomnography data on a subset of the sample suggested that the association between this symptom reported on questionnaire and objective evidence of sleep-disordered breathing may be weaker among American Indians than among other groups. Mean Epworth Sleepiness Scale scores were slightly higher in black men and women than in their white, non-hispanic counterparts.
CONCLUSIONS: Frequent snoring was more common among black and Hispanic women and Hispanic men than among their white non-Hispanic counterparts, even after adjusting for BMI and other factors. Further research including polysomnography and objective measurements of sleepiness is needed to assess the physiologic and clinical significance of these findings.
10aAdult10aCross-Sectional Studies10aElectroencephalography10aElectrooculography10aEthnic Groups10aFemale10aHeart Rate10aHumans10aMale10aPolysomnography10aSeverity of Illness Index10aSleep Apnea Syndromes10aSnoring10aSurveys and Questionnaires1 aO'Connor, George, T1 aLind, Bonnie, K1 aLee, Elisa, T1 aNieto, Javier1 aRedline, Susan1 aSamet, Jonathan, M1 aBoland, Lori, L1 aWalsleben, Joyce, A1 aFoster, Gregory, L1 aSleep Heart Health Study Investigators uhttps://chs-nhlbi.org/node/72802505nas a2200433 4500008004100000022001400041245009900055210006900154260001300223300001000236490000800246520125900254653000901513653002201522653002101544653002201565653002301587653002801610653001101638653001501649653002501664653001101689653002701700653002001727653002001747653002501767653000901792653001601801653002401817653002001841653003201861653003001893100002401923700001801947700002501965700002201990700002402012856003502036 2004 eng d a0021-915000aAlcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study.0 aAlcohol consumption and inflammatory markers in older adults the c2004 Mar a79-870 v1733 aOBJECTIVE: We sought to determine the relation of alcohol intake and systemic inflammation in a population-based sample of older adults.
METHODS AND RESULTS: As part of the Cardiovascular Health Study (CHS), 5865 adults aged 65 years and older reported their intake of beer, wine, and liquor. We determined white blood cell count (WBC), factor VIII coagulant activity (factor VIIIc), and levels of C-reactive protein (CRP), fibrinogen, and albumin as markers of systemic inflammation. Among participants without confirmed cardiovascular disease, alcohol consumption was inversely associated with WBC, factor VIIIc, and fibrinogen level, and positively associated with albumin concentration in multivariate analyses. We found no consistent modification of these results by sex, obesity, or beverage type. The relation of alcohol use and CRP levels was significantly modified by apoE genotype (P interaction 0.03), with a positive association among participants with an apoE4 allele (P = 0.05), but a trend toward an inverse association among those without an apoE4 allele (P = 0.15).
CONCLUSIONS: Alcohol intake is associated with lower levels of inflammatory markers in older adults free of cardiovascular disease.
10aAged10aAged, 80 and over10aAlcohol Drinking10aApolipoproteins E10aC-Reactive Protein10aCoronary Artery Disease10aFemale10aFibrinogen10aGeriatric Assessment10aHumans10aInflammation Mediators10aLeukocyte Count10aLogistic Models10aLongitudinal Studies10aMale10aProbability10aProspective Studies10aRisk Assessment10aSensitivity and Specificity10aSeverity of Illness Index1 aMukamal, Kenneth, J1 aCushman, Mary1 aMittleman, Murray, A1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/78603280nas a2200481 4500008004100000022001400041245010100055210006900156260001600225300001000241490000700251520200000258653001002258653002102268653000902289653002202298653001202320653002202332653002202354653002802376653001902404653001602423653001102439653003802450653001302488653001102501653002002512653001702532653000902549653001602558653001202574653002002586653002902606653001202635100001902647700002002666700001602686700001402702700001502716700001902731700001302750856003502763 2004 eng d a1526-632X00aAPOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.0 aAPOE epsilon4 is associated with obstructive sleep apneahypopnea c2004 Aug 24 a664-80 v633 aBACKGROUND: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association.
METHODS: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship.
RESULTS: At least one APOE epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without.
CONCLUSION: The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.
10aAdult10aAge Distribution10aAged10aAged, 80 and over10aAlleles10aApolipoprotein E410aApolipoproteins E10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aGenetic Predisposition to Disease10aGenotype10aHumans10aHyperlipidemias10aHypertension10aMale10aMiddle Aged10aObesity10aPolysomnography10aSleep Apnea, Obstructive10aSmoking1 aGottlieb, D, J1 aDeStefano, A, L1 aFoley, D, J1 aMignot, E1 aRedline, S1 aGivelber, R, J1 aYoung, T uhttps://chs-nhlbi.org/node/79802144nas a2200313 4500008004100000022001400041245008300055210006900138260001600207300001200223490000700235520128900242653001001531653000901541653002201550653002501572653002401597653002401621653001101645653002101656653001101677653000901688653001601697100002601713700002001739700001701759700001901776856003501795 2004 eng d a0002-914900aAssessment of prolonged QT and JT intervals in ventricular conduction defects.0 aAssessment of prolonged QT and JT intervals in ventricular condu c2004 Apr 15 a1017-210 v933 aThe JT interval or Bazett's QTc - QRS has been advocated for detection of prolonged repolarization in ventricular conduction defects (VCDs). However, the use of neither JT nor QTc - QRS has been validated, and normal limits for rate-adjusted JT have not been established for VCDs or for normal ventricular conduction. Functional relations among RR, JT, and QT intervals were evaluated in 11,739 adult men and women with normal ventricular conduction and in 1,251 subjects with major VCD. The results showed that JT adjustment obtained as QTc - QRS retained a strong residual correlation with ventricular rate (r = 0.54), making its use ill-advised. In contrast, QT adjustment as a linear function of the RR interval for VCD as QT(RR,QRS) = QT - 155 x (60/heart rate - 1) - 0.93 x (QRS - 139) + k, with k = -22 ms for men and -34 ms for women, removed the rate dependence and produced upper 2% and 5% normal limits at 460 and 450 ms, respectively, which are identical to those in normal conduction. As an alternative, equally effective linear JT adjustment formulas were derived, including newly required normal standards. Thus, detection of prolonged repolarization in VCD requires the use of the JT interval or a bivariate model for QT with RR and QRS intervals as covariates.
10aAdult10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aBundle-Branch Block10aElectrocardiography10aFemale10aHeart Ventricles10aHumans10aMale10aMiddle Aged1 aRautaharju, Pentti, M1 aZhang, Zhu-Ming1 aPrineas, Ron1 aHeiss, Gerardo uhttps://chs-nhlbi.org/node/77402199nas a2200277 4500008004100000022001400041245006700055210006600122260001300188300001200201490000700213520147700220653000901697653001601706653001701722653002801739653001101767653001101778653000901789653001701798653001701815100001801832700001901850700001701869856003501886 2004 eng d a0027-968400aAssociates of bone mineral density in older African Americans.0 aAssociates of bone mineral density in older African Americans c2004 Dec a1609-150 v963 aOBJECTIVES: To assess correlates of bone mineral density (BMD) in older African Americans.
PARTICIPANTS: 189 women and 115 men over age 64.
METHODS: Variables investigated: BMD by dual X-ray absorptiometry (DXA), medications, cardiovascular disease risk factors, demographic, lifestyle factors and functional status. Variables showing univariate correlation with BMD (p < or = 0.1) were entered into sex-stratified linear regression models.
RESULTS: Age range 67-96 (mean 75). The mean BMD (gm/ cm2 +/- standard deviation) is reported for three sites. Total body: 1.03 (+/- 0.12) in women, 1.21 (+/- 0.11) in men. Spine: 1.05 (+/- 0.24) in women, 1.22 (+/- 0.26) in men. Total hip: 0.85 (+/- 0.15) in women, 1.04 (+/- 0.17) in men. Gender was significantly associated with BMD (t-test, p < 0.001). The R2 for tested variables were highly significant only for weight. Age was only significant for total hip in women (p < 0.05). Each kilogram of weight change was associated with a 5.3-6.8 mg/cm2 change in BMD.
CONCLUSIONS: In a population-based cohort of older African Americans, average BMD was significantly greater in men than women. Weight accounted for most of the explained variability (R2) in BMD; age added little to the overall R2. Lower-weight, older African-American men and women are at significantly increased risk for low BMD and, thus, likely to be at greater risk for osteoporotic fracture.
10aAged10aBody Weight10aBone Density10aCross-Sectional Studies10aFemale10aHumans10aMale10aOsteoporosis10aRisk Factors1 aRobbins, John1 aHirsch, Calvin1 aCauley, Jane uhttps://chs-nhlbi.org/node/81403017nas a2200457 4500008004100000022001400041245015200055210006900207260001300276300001200289490000700301520171100308653002202019653003902041653000902080653001102089653001902100653001102119653001402130653001102144653000902155653001402164653002602178653002802204653002402232653001702256653001102273653001802284100002002302700002202322700002402344700002202368700002002390700002002410700001902430700001802449700001602467700002002483700002102503856003502524 2004 eng d a0002-861400aThe association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study.0 aassociation between lipid levels and the risks of incident myoca c2004 Oct a1639-470 v523 aOBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults.
DESIGN: A prospective population-based study.
SETTING: Four field centers in U.S. communities.
PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later.
MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.
RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality.
CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.
10aAfrican Americans10aAfrican Continental Ancestry Group10aAged10aFemale10aHealth Surveys10aHumans10aIncidence10aLipids10aMale10aMortality10aMyocardial Infarction10aPopulation Surveillance10aProspective Studies10aRisk Factors10aStroke10aUnited States1 aPsaty, Bruce, M1 aAnderson, Melissa1 aKronmal, Richard, A1 aTracy, Russell, P1 aOrchard, Trevor1 aFried, Linda, P1 aLumley, Thomas1 aRobbins, John1 aBurke, Greg1 aNewman, Anne, B1 aFurberg, Curt, D uhttps://chs-nhlbi.org/node/80302863nas a2200457 4500008004100000022001400041245014400055210006900199260001600268300001200284490000700296520153900303653000901842653001501851653001801866653001901884653002101903653002201924653002601946653001201972653001101984653002201995653001802017653001102035653001402046653000902060653003202069653001702101653002402118653001802142653003102160100002402191700002402215700002402239700002302263700002202286700001902308700002102327700002202348856003502370 2004 eng d a0735-109700aThe association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study.0 aassociation of fasting glucose levels with congestive heart fail c2004 Jun 16 a2236-410 v433 aOBJECTIVES: The purpose of this study was to determine if fasting glucose levels are an independent risk factor for congestive heart failure (CHF) in elderly individuals with diabetes mellitus (DM) with or without coronary heart disease (CHD).
BACKGROUND: Diabetes mellitus and CHF frequently coexist in the elderly. It is not clear whether fasting glucose levels in the setting of DM are a risk factor for incident CHF in the elderly.
METHODS: A cohort of 829 diabetic participants, age > or =65 years, without prevalent CHF, was followed for five to eight years. The Cox proportional hazards modeling was used to determine the risk of CHF by fasting glucose levels. The cohort was categorized by the presence or absence of prevalent CHD.
RESULTS: For a 1 standard deviation (60.6 mg/dl) increase in fasting glucose, the adjusted hazard ratios for incident CHF among participants without CHD at baseline, with or without an incident myocardial infarction (MI) or CHD event on follow-up, was 1.41 (95% confidence interval 1.24 to 1.61; p < 0.0001). Among those with prevalent CHD at baseline, with or without another incident MI or CHD event on follow-up, the corresponding adjusted hazard ratio was 1.27 (95% confidence interval 1.02 to 1.58; p < 0.05).
CONCLUSIONS: Among older adults with DM, elevated fasting glucose levels are a risk factor for incident CHF. The relationship of fasting glucose to CHF differs somewhat by the presence or absence of prevalent CHD.
10aAged10aBiomarkers10aBlood Glucose10aBlood Pressure10aCoronary Disease10aDiabetes Mellitus10aDiabetic Angiopathies10aFasting10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aProportional Hazards Models10aRisk Factors10aStatistics as Topic10aStroke Volume10aVentricular Function, Left1 aBarzilay, Joshua, I1 aKronmal, Richard, A1 aGottdiener, John, S1 aSmith, Nicholas, L1 aBurke, Gregory, L1 aTracy, Russell1 aSavage, Peter, J1 aCarlson, Michelle uhttps://chs-nhlbi.org/node/79103482nas a2200397 4500008004100000022001400041245016900055210006900224260001300293300001200306490000700318520230100325653000902626653001502635653002802650653001902678653001102697653001402708653001102722653000902733653001302742653001302755653001902768653001702787653003002804653001702834653001702851653002602868653003102894100002502925700002202950700002302972700002202995710003203017856003503049 2004 eng d a0277-953600aThe association of personal and neighborhood socioeconomic indicators with subclinical cardiovascular disease in an elderly cohort. The cardiovascular health study.0 aassociation of personal and neighborhood socioeconomic indicator c2004 Nov a2139-470 v593 aThere has been recent interest in determining whether neighborhood characteristics are related to the cardiovascular health of residents. However, there are no data regarding the relationship between neighborhood socioeconomic status (SES) and prevalence of subclinical cardiovascular disease (CVD) in the elderly. We related personal SES (education, income, and occupation type) and neighborhood socioeconomic characteristics (a block-group score summing six variables reflecting neighborhood income and wealth, education, and occupation) to the prevalence of subclinical CVD (asymptomatic peripheral vascular disease or carotid atherosclerosis, electrocardiogram or echocardiogram abnormalities, and/or positive responses to Rose Questionnaire claudication or angina pectoris) among 3545 persons aged 65 and over, without prevalent CVD, in the Cardiovascular Health Study. Sixty percent of participants had at least one indicator of subclinical disease. Compared to those without, those with subclinical disease had significantly lower education, income, and neighborhood scores and were more likely to have blue-collar jobs. After adjustment for age, gender, and race, those in the lowest SES groups had increased prevalence of subclinical disease compared with those in the highest SES groups (OR = 1.50; 95% CI 1.21, 1.86 for income; OR = 1.41; 95% CI 1.18, 1.69 for education; OR = 1.39; 95% CI 1.16, 1.67 for block-group score). Those reporting a blue-collar lifetime occupation had greater prevalence of subclinical disease relative to those reporting a white-collar occupation (OR = 1.29; 95% CI 1.02-1.59). After adjustment for behavioral and biomedical risk factors, all of these associations were reduced. Neighborhood score tended to remain inversely associated with subclinical disease after adjustment for personal socioeconomic indicators but associations were not statistically significant. Personal income and blue-collar occupation remained significantly associated with subclinical disease after simultaneous adjustment for neighborhood score and education. Personal and neighborhood socioeconomic indicators were associated with subclinical disease prevalence in this elderly cohort. These relationships were reduced after controlling for traditional CVD risk factors.
10aAged10aCalifornia10aCardiovascular Diseases10aCohort Studies10aFemale10aGeography10aHumans10aMale10aMaryland10aMedicare10aNorth Carolina10aPennsylvania10aResidence Characteristics10aRisk Factors10aSocial Class10aSocioeconomic Factors10aSurveys and Questionnaires1 aNordstrom, Cheryl, K1 aRoux, Ana, V Diez1 aJackson, Sharon, A1 aGardin, Julius, M1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/79902672nas a2200373 4500008004100000022001400041245010000055210006900155260001600224300001100240490000700251520159500258653000901853653002801862653001901890653002801909653003801937653001101975653001801986653001102004653001702015653000902032653001602041653002002057653003002077653001602107100002202123700002202145700002602167700001702193700001802210710003502228856003502263 2004 eng d a0161-810500aAssociations between gender and measures of daytime somnolence in the Sleep Heart Health Study.0 aAssociations between gender and measures of daytime somnolence i c2004 Mar 15 a305-110 v273 aSTUDY OBJECTIVES: To examine the relationship of gender to subjective measures of sleepiness, including the Epworth Sleepiness Scale (ESS), in a community-based population.
DESIGN: A cross-sectional study.
SETTING/PARTICIPANTS: Multicenter Sleep Heart Health Study participants (N = 6.440, 52% women) recruited from ongoing cohort studies.
INTERVENTIONS: N/A.
MEASUREMENTS: Scores from the ESS, Sleep Heart Health Study daytime sleepiness and feeling unrested questions, polysomnography results (respiratory disturbance index at 4% desaturation), as well as data on difficulty initiating and maintaining sleep, insufficient sleep, sedative use, alcohol use, cardiovascular or respiratory disease, frequent awakening due to leg cramps.
RESULTS: Women reported feeling sleepy as often as men did (odds ratio [OR] = 1.06; confidence interval [CI], 0.86-1.32), but women were less likely to have an ESS score > 10 (adjusted OR = 0.77; CI, 0.66-0.90) and more likely to report feeling unrested (adjusted OR = 1.39; CI, 1.14-1.69) than men. In men, the ESS score was more strongly correlated with reports of feeling unrested or sleepy compared to women.
CONCLUSIONS: Men and women answer questions on sleepiness differently. Findings indicate that using the ESS to detect subjective sleepiness is more likely to identify men with sleepiness. Since the ESS is more strongly related to other subjective measures in men, the ESS may be a more sensitive measure of subjective sleepiness in men than in women.
10aAged10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHealth Status10aHumans10aHypertension10aMale10aMiddle Aged10aPolysomnography10aSeverity of Illness Index10aSex Factors1 aBaldwin, Carol, M1 aKapur, Vishesh, K1 aHolberg, Catharine, J1 aRosen, Carol1 aNieto, Javier1 aSleep Heart Health Study Group uhttps://chs-nhlbi.org/node/77701905nas a2200349 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520094000233653000901173653002201182653002801204653001101232653002001243653003401263653001101297653002001308653000901328653001301337653001301350653003101363653001801394100002801412700001801440700002201458700001901480700002101499856003501520 2004 eng d a0090-003600aBarriers to health care access among the elderly and who perceives them.0 aBarriers to health care access among the elderly and who perceiv c2004 Oct a1788-940 v943 aOBJECTIVES: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries.
METHODS: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study.
RESULTS: The questionnaires were completed by 4889 (91.1%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor's lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors.
CONCLUSIONS: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.
10aAged10aAged, 80 and over10aChi-Square Distribution10aFemale10aHealth Behavior10aHealth Services Accessibility10aHumans10aLogistic Models10aMale10aMedicare10aPatients10aSurveys and Questionnaires10aUnited States1 aFitzpatrick, Annette, L1 aPowe, Neil, R1 aCooper, Lawton, S1 aIves, Diane, G1 aRobbins, John, A uhttps://chs-nhlbi.org/node/80500699nas a2200229 4500008004100000022001400041245012500055210006900180260001700249300001000266490000700276653000900283653002800292653001100320653002500331653001100356653000900367653001700376100002000393700002100413856003500434 2004 eng d a1076-746000aThe Cardiovascular Health Study: risk factors, subclinical disease, and clinical cardiovascular disease in older adults.0 aCardiovascular Health Study risk factors subclinical disease and c2004 Mar-Apr a59-600 v1310aAged10aCardiovascular Diseases10aFemale10aGeriatric Assessment10aHumans10aMale10aRisk Factors1 aNewman, Anne, B1 aSiscovick, David uhttps://chs-nhlbi.org/node/77002554nas a2200385 4500008004100000022001400041245012100055210006900176260001700245300001000262490000700272520146800279653000901747653003001756653002801786653002001814653001501834653001501849653001401864653001101878653001501889653002501904653001101929653001401940653000901954653001501963653002401978653001702002100002402019700002002043700002902063700002102092700002002113856003502133 2004 eng d a1076-746000aChronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study.0 aChronic renal insufficiency and cardiovascular events in the eld c2004 Mar-Apr a81-900 v133 aIn the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community-dwelling elderly adults. Defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men, CRI was present in 647 (11%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64% in participants with CRI and 43% in those without CRI (odds ratio, 2.34; 95% confidence interval, 1.96-2.80). The incidence of cardiovascular disease events during follow-up was 3% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7% per year in those with creatinine > or =1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C-reactive protein, fibrinogen, and interleukin-6) and hemostatic (factor VII, factor VIII, plasmin-antiplasmin product, and D-dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.
10aAged10aBlood Coagulation Factors10aCardiovascular Diseases10aChronic Disease10aCreatinine10aCystatin C10aCystatins10aFemale10aFibrinogen10aGeriatric Assessment10aHumans10aIncidence10aMale10aPrevalence10aRenal Insufficiency10aRisk Factors1 aShlipak, Michael, G1 aFried, Linda, F1 aStehman-Breen, Catherine1 aSiscovick, David1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/77303477nas a2200385 4500008004100000022001400041245014400055210006900199260001600268300001100284490000800295520234400303653000902647653002102656653002402677653001902701653002802720653001102748653001102759653000902770653002902779653001502808653001702823653001802840100002402858700002202882700002102904700002102925700002302946700002202969700002502991700002003016700002003036856003503056 2004 eng d a1539-370400aCognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease.0 aCognitive impairment and decline are associated with carotid art c2004 Feb 17 a237-470 v1403 aBACKGROUND: Whether carotid artery disease is a cause of cognitive impairment in persons who have not had stroke is unknown. If this is the case, diminished performance on the Modified Mini-Mental State Examination should be more common in persons with left carotid artery disease than in those with right carotid artery disease.
OBJECTIVE: To determine whether left carotid artery disease is associated with cognitive impairment.
DESIGN: Cross-sectional and cohort study.
SETTING: Four U.S. communities participating in the Cardiovascular Health Study.
PATIENTS: 4006 right-handed men and women 65 years of age or older without history of stroke, transient ischemic attack, or carotid endarterectomy.
MEASUREMENTS: Internal carotid artery stenosis and intima-media thickness of the common carotid artery were assessed by using duplex ultrasonography. Cognitive impairment was defined as a score less than 80 on the Modified Mini-Mental State Examination, and cognitive decline was defined as an average decrease of more than 1 point annually in Modified Mini-Mental State Examination score during up to 5 years of follow-up. Multivariate logistic regression models were used to estimate the risk for cognitive impairment and decline associated with left internal carotid artery stenosis and intima-media thickness, after adjustment for measures of right-sided disease and risk factors for vascular disease.
RESULTS: After adjustment for right-sided stenosis, high-grade (> or =75% narrowing of diameter) stenosis of the left internal carotid artery (32 patients) was associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1] compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to 6.3]). Intima-media thickness of the left common carotid artery was associated with cognitive impairment and decline in univariate analysis, but this effect did not persist after adjustment.
CONCLUSIONS: Cognitive impairment and decline are associated with asymptomatic high-grade stenosis of the left internal carotid artery. The persistence of the association after adjustment for right-sided stenosis indicates that the association is not due to underlying vascular risk factors or atherosclerosis in general.
10aAged10aCarotid Stenosis10aCognition Disorders10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aMale10aNeuropsychological Tests10aOdds Ratio10aRisk Factors10aTunica Intima1 aJohnston, Claiborne1 aO'Meara, Ellen, S1 aManolio, Teri, A1 aLefkowitz, David1 aO'Leary, Daniel, H1 aGoldstein, Steven1 aCarlson, Michelle, C1 aFried, Linda, P1 aLongstreth, W T uhttps://chs-nhlbi.org/node/76602463nas a2200397 4500008004100000022001400041245007800055210006900133260001700202300000900219490000700228520137900235653000901614653002201623653003001645653001901675653002801694653001101722653002501733653001601758653001801774653001501792653001101807653001401818653000901832653001501841653001701856653001801873653001801891653003401909100002101943700002401964700002001988700002202008856003502030 2004 eng d a1076-746000aCongestive heart failure in the elderly: the Cardiovascular Health Study.0 aCongestive heart failure in the elderly the Cardiovascular Healt c2004 Mar-Apr a61-80 v133 aCongestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.
10aAged10aAged, 80 and over10aAtrial Natriuretic Factor10aBlood Pressure10aDiagnosis, Differential10aFemale10aGeriatric Assessment10aHeart Atria10aHeart Failure10aHeart Rate10aHumans10aIncidence10aMale10aPrevalence10aRisk Factors10aStroke Volume10aUnited States10aVentricular Dysfunction, Left1 aMathew, Sunil, T1 aGottdiener, John, S1 aKitzman, Dalane1 aAurigemma, Gerard uhttps://chs-nhlbi.org/node/77102878nas a2200409 4500008004100000022001400041245012400055210006900179260001600248300001000264490000800274520173300282653000902015653002502024653001902049653001102068653002202079653001102101653001402112653000902126653001602135653001402151653002802165653002302193653001502216653001702231653001802248653002202266100001802288700002002306700002202326700002302348700002302371700001802394700002102412856003502433 2004 eng d a0002-934300aDeep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.0 aDeep vein thrombosis and pulmonary embolism in two cohorts the l c2004 Jul 01 a19-250 v1173 aPURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States.
METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review.
RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48% (175/366) of events. The 28-day case-fatality rate was 11% (29/265) after a first venous thromboembolism and 25% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7% per year (95% confidence interval [CI]: 4.5% to 10.9% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95% CI: 2.0 to 41.7).
CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.
10aAged10aCase-Control Studies10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMiddle Aged10aNeoplasms10aPopulation Surveillance10aPulmonary Embolism10aRecurrence10aRisk Factors10aSurvival Rate10aVenous Thrombosis1 aCushman, Mary1 aTsai, Albert, W1 aWhite, Richard, H1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aEnright, Paul1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/79302785nas a2200373 4500008004100000022001400041245009400055210006900149260001600218300001100234490000800245520178500253653001002038653001602048653000902064653002202073653002002095653001602115653001102131653001102142653000902153653001602162653002602178653001602204653001002220653002602230100001902256700002102275700002002296700002402316700001902340700001702359856003502376 2004 eng d a0003-992600aThe effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture.0 aeffects of age sex ethnicity and sleepdisordered breathing on sl c2004 Feb 23 a406-180 v1643 aBACKGROUND: Polysomnography is used to assess sleep quality and to gauge the functional effect of sleep disorders. Few population-based data are available to estimate the variation in sleep architecture across the population and the extent to which sleep-disordered breathing (SDB), a common health condition, contributes to poor sleep independent of other factors. The objective of this study was to describe the population variability in sleep quality and to quantify the independent associations with SDB.
METHODS: Cross-sectional analyses were performed on data from 2685 participants, aged 37 to 92 years, in a community-based multicenter cohort study. Dependent measures included the percentage time in each sleep stage, the arousal index, and sleep efficiency. Independent measures were age, sex, ethnicity, comorbidity status, and the respiratory disturbance index.
RESULTS: Lighter sleep was found in men relative to women and in American Indians and blacks relative to other ethnic groups. Increasing age was associated with impaired sleep in men, with less consistent associations in women. Notably, women had, on average, 106% more slow wave sleep. Sleep-disordered breathing was associated with poorer sleep; however, these associations were generally smaller than associations with sex, ethnicity, and age. Current smokers had lighter sleep than ex-smokers or never smokers. Obesity had little effect on sleep.
CONCLUSIONS: Sleep architecture varies with sex, age, ethnicity, and SDB. Individual assessment of the effect of SDB on sleep quality needs to account for other host characteristics. Men, but not women, show evidence of poorer sleep with aging, suggesting important sex differences in sleep physiology.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aBody Mass Index10aComorbidity10aFemale10aHumans10aMale10aMiddle Aged10aMultivariate Analysis10aSex Factors10aSleep10aSleep Apnea Syndromes1 aRedline, Susan1 aKirchner, Lester1 aQuan, Stuart, F1 aGottlieb, Daniel, J1 aKapur, Vishesh1 aNewman, Anne uhttps://chs-nhlbi.org/node/76803779nas a2200481 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520245000233653002202683653002102705653000902726653002202735653002202757653002202779653001302801653002302814653001402837653004002851653001102891653001102902653001402913653002502927653000902952653001502961653003202976653001703008653002103025653001803046100002803064700002103092700001903113700002003132700002003152700002403172700001903196700002603215700002103241856003503262 2004 eng d a0002-861400aIncidence and prevalence of dementia in the Cardiovascular Health Study.0 aIncidence and prevalence of dementia in the Cardiovascular Healt c2004 Feb a195-2040 v523 aOBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort.
DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia.
SETTING: Four U.S. communities.
PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years.
MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD.
RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%).
CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.
10aAfrican Americans10aAge Distribution10aAged10aAged, 80 and over10aAlzheimer Disease10aApolipoproteins E10aDementia10aDementia, Vascular10aEducation10aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aPrevalence10aProportional Hazards Models10aRisk Factors10aSex Distribution10aUnited States1 aFitzpatrick, Annette, L1 aKuller, Lewis, H1 aIves, Diane, G1 aLopez, Oscar, L1 aJagust, William1 aBreitner, John, C S1 aJones, Beverly1 aLyketsos, Constantine1 aDulberg, Corinne uhttps://chs-nhlbi.org/node/76203282nas a2200481 4500008004100000022001400041245017500055210006900230260001600299300001200315490000700327520181100334653000902145653002202154653002802176653001302204653002102217653002402238653001102262653002202273653002102295653001102316653003402327653002502361653000902386653002602395653002402421653001702445653003202462653002402494653001802518653003402536100002102570700001802591700002102609700002402630700002302654700002202677700002102699700002102720700002402741856003502765 2004 eng d a0735-109700aIncreased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study.0 aIncreased left ventricular mass is a risk factor for the develop c2004 Jun 16 a2207-150 v433 aOBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF).
BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF.
METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF.
RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8% in quartile 1, 4.4% in quartile 2, 7.5% in quartile 3, and 14.1% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF.
CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.
10aAged10aBody Surface Area10aCoronary Artery Disease10aDiastole10aEchocardiography10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLongitudinal Studies10aMale10aMultivariate Analysis10aProspective Studies10aRisk Factors10aSensitivity and Specificity10aStatistics as Topic10aStroke Volume10aVentricular Dysfunction, Left1 aDrazner, Mark, H1 aRame, Eduardo1 aMarino, Emily, K1 aGottdiener, John, S1 aKitzman, Dalane, W1 aGardin, Julius, M1 aManolio, Teri, A1 aDries, Daniel, L1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/79003150nas a2200493 4500008004100000022001400041245010400055210006900159260001300228300001200241490000700253520179600260653000902056653001502065653002302080653001502103653001502118653001102133653001502144653002202159653003102181653001602212653001102228653002002239653001802259653002502277653000902302653003002311653002402341653002402365653001802389653001502407100001702422700001702439700002102456700002102477700002902498700002302527700001802550700001802568700001802586700001702604856003502621 2004 eng d a1046-667300aInflammatory and prothrombotic markers and the progression of renal disease in elderly individuals.0 aInflammatory and prothrombotic markers and the progression of re c2004 Dec a3184-910 v153 aInflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.
10aAged10aBiomarkers10aC-Reactive Protein10aCreatinine10aFactor VII10aFemale10aFibrinogen10aFollow-Up Studies10aGlomerular Filtration Rate10aHemoglobins10aHumans10aLeukocyte Count10aLinear Models10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProspective Studies10aRenal Insufficiency10aSerum Albumin10aThrombosis1 aFried, Linda1 aSolomon, Cam1 aShlipak, Michael1 aSeliger, Stephen1 aStehman-Breen, Catherine1 aBleyer, Anthony, J1 aChaves, Paolo1 aFurberg, Curt1 aKuller, Lewis1 aNewman, Anne uhttps://chs-nhlbi.org/node/81303920nas a2200409 4500008004100000022001400041245004600055210004500101260001300146300001000159490000700169520282600176653001603002653000903018653002203027653002103049653001803070653001903088653001103107653001103118653000903129653002403138653003203162653003403194653001503228653003703243653001603280100002503296700002103321700002303342700002303365700002403388700002403412700001703436700002203453856003503475 2004 eng d a0741-521400aMesenteric artery disease in the elderly.0 aMesenteric artery disease in the elderly c2004 Jul a45-520 v403 aPURPOSE: The purpose of this study was to estimate the population-based prevalence of mesenteric artery stenosis (MAS) and occlusion among independent elderly Americans.
METHOD: As part of an ancillary investigation to the Cardiovascular Health Study (CHS), participants in the Forsyth County, NC cohort had visceral duplex sonography of the celiac arteries and superior mesenteric arteries (SMAs). Critical MAS was defined by celiac peak systolic velocity >or=2.0 m/s and/or SMA peak systolic velocity >or=2.7 m/s. Occlusion of either vessel was defined by lack of a Doppler-shifted signal within the imaged artery. Demographic data, blood pressures, and blood lipid levels were collected as part of the baseline CHS examination. Participants' weights were measured at baseline and before the duplex exam. Univariate tests of association were performed with two-way contingency tables, Student t tests, and Fisher exact tests. Multivariate associations were examined with logistic regression analysis.
RESULTS: A total of 553 CHS participants had visceral duplex sonography technically adequate to define the presence or absence of MAS. The study group had a mean age of 77.2 +/- 4.9 years and comprised 63% women and 37% men. Participant race was 76% white and 23% African-American. Ninety-seven participants (17.5%) had MAS. There was no significant difference in age, race, gender, body mass index, blood pressure, cholesterol, or low-density lipoproteins for participants with or without MAS. Forward stepwise variable selection found renal artery stenosis (P =.008; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.31, 6.21) and high-density lipoprotein >40 (P =.02; OR, 3.03; 95% CI, 1.17, 7.81) significantly associated with MAS in a multivariate logistic regression model. Eighty-three of the 97 participants with MAS (15.0% of the cohort) had isolated celiac stenosis. Seven participants (1.3% of the cohort) had combined celiac and SMA stenosis. Five participants (0.9% of the cohort) had isolated SMA stenosis. Two participants (0.4% of the cohort) had celiac occlusion. Considering all participants with MAS, there was no association with weight change. However, SMA stenosis and celiac occlusion demonstrated an independent association with annualized weight loss (P =.028; OR, 1.54; 95% CI, 1.05, 2.26) and with renal artery stenosis (P =.001; OR, 9.48; 95% CI, 2.62, 34.47).
CONCLUSION: This investigation provides the first population-based estimate of the prevalence of MAS among independent elderly Americans. MAS existed in 17.5% of the study cohort. The majority had isolated celiac disease. SMA stenosis and celiac artery occlusion demonstrated a significant and independent association with weight loss and concurrent renal artery disease.
10aAge Factors10aAged10aAged, 80 and over10aArteriosclerosis10aCeliac Artery10aCohort Studies10aFemale10aHumans10aMale10aMesenteric Arteries10aMesenteric Artery, Superior10aMesenteric Vascular Occlusion10aPrevalence10aUltrasonography, Doppler, Duplex10aWeight Loss1 aHansen, Kimberley, J1 aWilson, David, B1 aCraven, Timothy, E1 aPearce, Jeffrey, D1 aEnglish, William, P1 aEdwards, Matthew, S1 aAyerdi, Juan1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/79602977nas a2200373 4500008004100000022001400041245011400055210006900169260001300238300001200251490000700263520191600270653000902186653002202195653002802217653001502245653001302260653002302273653001102296653001102307653001102318653002002329653000902349653001202358653003202370100002402402700002402426700003202450700002202482700002502504700002002529700001902549856003502568 2004 eng d a1046-667300aModerate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.0 aModerate renal impairment and risk of dementia among older adult c2004 Jul a1904-110 v153 aRenal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.
10aAged10aAlzheimer Disease10aCardiovascular Diseases10aCreatinine10aDementia10aDementia, Vascular10aFemale10aHumans10aKidney10aKidney Diseases10aMale10aMuscles10aProportional Hazards Models1 aSeliger, Stephen, L1 aSiscovick, David, S1 aStehman-Breen, Catherine, O1 aGillen, Daniel, L1 aFitzpatrick, Annette1 aBleyer, Anthony1 aKuller, Lew, H uhttps://chs-nhlbi.org/node/79503027nas a2200361 4500008004100000022001400041245011300055210006900168260001300237300001100250490000700261520198700268653002202255653000902277653002802286653004002314653001102354653002202365653001102387653001102398653000902409653001802418653003002436653001702466653002602483653001802509100002202527700002202549700001502571700002302586700002102609856003502630 2004 eng d a0143-005X00aNeighbourhood environments and mortality in an elderly cohort: results from the cardiovascular health study.0 aNeighbourhood environments and mortality in an elderly cohort re c2004 Nov a917-230 v583 aBACKGROUND: It has been postulated that neighbourhood conditions are related to the health of the elderly population but longitudinal studies are rare and confounding by individual level variables remains a possibility.
METHODS: Data were obtained from the cardiovascular health study, a population based study of adults aged 65 years and older. Census block groups were used as proxies for neighbourhoods. A summary score was used to characterise the neighbourhood socioeconomic environment. Information on personal socioeconomic indicators, cardiovascular disease prevalence, and cardiovascular risk factors was obtained from the baseline examination. Proportional hazards regression and propensity score matching were used to control for individual level variables.
RESULTS: Over the eight year follow up there were 1346 deaths among the 5074 participants, of which 43% were attributable to cardiovascular disease. Among white participants, living in the most disadvantaged neighbourhood group was associated with higher rates of cardiovascular death, after adjustment for income, education, and occupation (hazard ratio (HR) 1.5, 95% confidence intervals (CI) 1.2 to 1.9). No neighbourhood differences were observed for non-cardiovascular deaths. Estimates for black participants were 1.3 (95% CI 0.7 to 2.3) for cardiovascular deaths and 1.4 (95% CI 0.8 to 2.4) for non-cardiovascular deaths, but sample size was small. In white participants, associations of neighbourhood characteristics with cardiovascular mortality persisted after adjustment for prevalent baseline disease and cardiovascular risk factors. The use of propensity score matching led to similar results (HR for the lowest compared with the highest neighbourhood score group: 1.6 95% CI 1.1 to 2.5, controlling for personal socioeconomic indicators).
CONCLUSION: Neighbourhood disadvantage is related to rates of cardiovascular death in elderly white adults.
10aAfrican Americans10aAged10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aIncome10aMale10aPoverty Areas10aResidence Characteristics10aRisk Factors10aSocioeconomic Factors10aUnited States1 aRoux, Ana, V Diez1 aBorrell, Luisa, N1 aHaan, Mary1 aJackson, Sharon, A1 aSchultz, Richard uhttps://chs-nhlbi.org/node/80902815nas a2200385 4500008004100000022001400041245013800055210006900193260001300262300001000275490000700285520175300292653000902045653001002054653001002064653002102074653001102095653001702106653001102123653003102134653000902165653001502174653001602189653001702205100002002222700001602242700001602258700002102274700001802295700001902313700001902332700001802351700002502369856003502394 2004 eng d a0003-994200aPlasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons: the Cardiovascular Health Study.0 aPlasma total homocysteine levels and cranial magnetic resonance c2004 Jan a67-720 v613 aBACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI).
DESIGN: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype.
RESULTS: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P =.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P =.07 for linear trend).
CONCLUSION: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.
10aAged10aAging10aBrain10aBrain Infarction10aFemale10aHomocysteine10aHumans10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aRadiography10aRisk Factors1 aLongstreth, W T1 aKatz, Ronit1 aOlson, Jean1 aBernick, Charles1 aCarr, Jeffrey1 aMalinow, René1 aHess, David, L1 aCushman, Mary1 aSchwartz, Stephen, M uhttps://chs-nhlbi.org/node/76302657nas a2200469 4500008004100000022001400041245010200055210006900157260001600226300001100242490000700253520132800260653001701588653002201605653002801627653002401655653001901679653003901698653002401737653002001761653002301781653001101804653002201815653001101837653000901848653002101857653002901878653003001907653003201937653000901969653003201978653001702010100001402027700001602041700001602057700001502073700001502088700001802103700001702121700001402138856003502152 2004 eng d a1526-632X00aPreclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.0 aPreclinical Alzheimer disease neuropsychological test performanc c2004 Dec 28 a2341-70 v633 aOBJECTIVE: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset.
METHODS: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years).
RESULTS: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later.
CONCLUSIONS: Cognitive changes can be detected well before onset of Alzheimer disease.
10aAge of Onset10aAlzheimer Disease10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aConfounding Factors, Epidemiologic10aDisease Progression10aEarly Diagnosis10aEducational Status10aFemale10aFollow-Up Studies10aHumans10aMale10aMemory Disorders10aNeuropsychological Tests10aPredictive Value of Tests10aProportional Hazards Models10aRisk10aSensitivity and Specificity10aTime Factors1 aSaxton, J1 aLopez, O, L1 aRatcliff, G1 aDulberg, C1 aFried, L P1 aCarlson, M, C1 aNewman, A, B1 aKuller, L uhttps://chs-nhlbi.org/node/81502614nas a2200421 4500008004100000022001400041245009500055210006900150260001300219300001100232490000700243520144000250653002201690653001601712653000901728653002801737653001601765653004001781653001101821653001601832653001801848653001101866653000901877653001301886653002401899653001701923653002101940653001601961653001801977100002101995700001802016700002402034700001702058700002102075700002402096710003702120856003502157 2004 eng d a1047-279700aPredictors of falling cholesterol levels in older adults: the Cardiovascular Health Study.0 aPredictors of falling cholesterol levels in older adults the Car c2004 May a325-310 v143 aPURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline.
METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997.
RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change.
CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.
10aAfrican Americans10aAge Factors10aAged10aCardiovascular Diseases10aCholesterol10aEuropean Continental Ancestry Group10aFemale10aForecasting10aHealth Status10aHumans10aMale10aMedicare10aProspective Studies10aRisk Factors10aSex Distribution10aSex Factors10aUnited States1 aManolio, Teri, A1 aCushman, Mary1 aGottdiener, John, S1 aDobs, Adrian1 aKuller, Lewis, H1 aKronmal, Richard, A1 aCHS Collaborative Research Group uhttps://chs-nhlbi.org/node/78702816nas a2200337 4500008004100000022001400041245008100055210006900136260001300205300001000218490000700228520187600235653003102111653000902142653002802151653001102179653001802190653001102208653002802219653000902247653001802256100002402274700002902298700002002327700001502347700002102362700002002383700002002403700002002423856003502443 2004 eng d a1523-683800aThe presence of frailty in elderly persons with chronic renal insufficiency.0 apresence of frailty in elderly persons with chronic renal insuff c2004 May a861-70 v433 aBACKGROUND: Frailty has been defined as a tool to define individuals who lack functional reserve and are at risk for functional decline. We hypothesized that chronic renal insufficiency (CRI) would be associated with a greater prevalence of frailty and disability in the elderly.
METHODS: This cross-sectional analysis used baseline data collected from the Cardiovascular Health Study, which enrolled 5,888 community-dwelling adults aged 65 years or older from 4 clinical centers in the United States. Renal insufficiency is defined as a serum creatinine level of 1.3 mg/dL or greater (> or =115 micromol/L) in women and 1.5 mg/dL or greater (> or =133 micromol/L) in men. Frailty is defined by the presence of 3 of the following abnormalities: unintentional weight loss, self-reported exhaustion, measured weakness, slow walking speed, and low physical activity. Disability is defined as any self-reported difficulty with activities of daily living.
RESULTS: Among 5,808 participants with creatinine levels measured at entry, 15.9% of men (n = 394) and 7.6% of women (n = 254) had CRI. Prevalences of frailty (15% versus 6%; P < 0.001) and disability (12% versus 7%; P = 0.001) were greater in participants with CRI compared with those with normal renal function. After multivariate adjustment for comorbidity, CRI remained significantly associated with frailty (odds ratio, 1.76; 95% confidence interval, 1.28 to 2.41), but not disability (odds ratio, 1.26; 95% confidence interval, 0.94 to 1.69).
CONCLUSION: Elderly persons with CRI have a high prevalence of frailty, which may signal their risk for progression to adverse health outcomes. If confirmed in other studies, identification of frailty in patients with CRI may warrant special interventions to preserve their independence, quality of life, and survival.
10aActivities of Daily Living10aAged10aCross-Sectional Studies10aFemale10aFrail Elderly10aHumans10aKidney Failure, Chronic10aMale10aUnited States1 aShlipak, Michael, G1 aStehman-Breen, Catherine1 aFried, Linda, F1 aSong, Xiao1 aSiscovick, David1 aFried, Linda, P1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/77502879nas a2200337 4500008004100000022001400041245016400055210006900219260001600288300001100304490000700315520187000322653000902192653002802201653002102229653001102250653001102261653001602272653001402288653000902302653003002311653001502341653002402356653002002380100002002400700002102420700002102441700002102462700002302483856003502506 2004 eng d a0735-109700aPrevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131).0 aPrevalence of specific variant carotid geometric patterns and in c2004 Jan 21 a187-930 v433 aOBJECTIVES: We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT).
BACKGROUND: Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease.
METHOD: Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM).
RESULTS: Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95% confidence interval [CI] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95% CI 1.16 to 1.75) compared with CGP1 (normal).
CONCLUSIONS: Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT.
10aAged10aCardiovascular Diseases10aCarotid Arteries10aFemale10aHumans10aHypertrophy10aIncidence10aMale10aPredictive Value of Tests10aPrevalence10aProspective Studies10aUltrasonography1 aScuteri, Angelo1 aManolio, Teri, A1 aMarino, Emily, K1 aArnold, Alice, M1 aLakatta, Edward, G uhttps://chs-nhlbi.org/node/76402995nas a2200349 4500008004100000022001400041245007200055210006900127260001300196300001100209490000800220520199600228653003902224653000902263653002002272653001902292653002602311653004002337653001102377653001102388653002602399653001802425653001702443653001702460100002002477700002202497700002402519700002202543700002002565700002502585856003502610 2004 eng d a1097-674400aRacial differences in endothelial function in postmenopausal women.0 aRacial differences in endothelial function in postmenopausal wom c2004 Oct a606-110 v1483 aOBJECTIVE: Racial differences in cardiovascular mortality among women remain largely unexplained. Preliminary data suggest that African American and Caucasian differences in endothelial function may parallel differential cardiovascular disease (CVD) risk in women. To further study differences in endothelial function between African American and Caucasian women, we analyzed measures of brachial artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular Health Study (CHS).
METHODS AND RESULTS: Brachial artery FMD was measured in the fasting state using established ultrasound techniques in 1330 Caucasian and 297 African American female participants in CHS (mean age 78.4 +/- 4.4 years). General linear models were used to compare FMD between African American and Caucasian women after adjusting for baseline brachial diameter, hypertension, diabetes, smoking, cholesterol, systolic blood pressure, body mass index, waist/hip ratio, age, education, income level; use of angiotensin-converting enzyme inhibitors, beta-blockers, nitroglycerin, estrogens and lipid-lowering drugs; and presence of clinical or subclinical disease. Adjusted absolute change and percent change in brachial artery diameter was significantly reduced in African American women compared with Caucasian women (P <.0001 and P =.0002, respectively). Similar results were found when the women were stratified by history of CVD (- CVD, P =.02; + CVD, P =.001) and CVD or subclinical vascular disease (- disease, P =.01, + disease, P =.03).
CONCLUSIONS: In this cohort, brachial artery FMD was lower in African American women compared to Caucasian women, and this difference persisted after adjustment by multivariable analysis. The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health.
10aAfrican Continental Ancestry Group10aAged10aBrachial Artery10aCohort Studies10aEndothelium, Vascular10aEuropean Continental Ancestry Group10aFemale10aHumans10aMultivariate Analysis10aPostmenopause10aRisk Factors10aVasodilation1 aLoehr, Laura, R1 aEspeland, Mark, A1 aSutton-Tyrrell, Kim1 aBurke, Gregory, L1 aCrouse, John, R1 aHerrington, David, M uhttps://chs-nhlbi.org/node/80603224nas a2200493 4500008004100000022001400041245017200055210006900227260001300296300001000309490000700319520182100326653002102147653000902168653002202177653001602199653001502215653002002230653001602250653002102266653002802287653002202315653001102337653001102348653001702359653001702376653002002393653000902413653002602422653001502448653001702463653001202480653002002492100002402512700001702536700001802553700002302571700001602594700002002610700002202630700001802652700002502670856003502695 2004 eng d a1523-683800aThe relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the cardiovascular health study.0 arelationship of cardiovascular risk factors to microalbuminuria c2004 Jul a25-340 v443 aBACKGROUND: Microalbuminuria is a risk factor for coronary heart disease (CHD). It occurs most commonly in the settings of diabetes and hypertension. The mechanisms by which it increases CHD risk are uncertain.
METHODS: We examined the cross-sectional association of microalbuminuria with a broad range of CHD risk factors in 3 groups of adults aged 65 years or older with and without microalbuminuria: those with (1) no diabetes or hypertension (n = 1,098), (2) hypertension only (n = 1,450), and (3) diabetes with or without hypertension (n = 465).
RESULTS: Three factors were related to microalbuminuria in all 3 groups: age, elevated systolic blood pressure, and markers of systemic inflammation. In patients with neither diabetes nor hypertension, increasing C-reactive protein levels were associated with microalbuminuria (odds ratio per 1-mg/L increase, 1.46; 95% confidence interval [CI], 1.15 to 1.84). Among those with diabetes, an increase in white blood cell (WBC) count was associated with microalbuminuria (odds ratio per 1,000-cell/mL increase, 2.57; 95% CI, 1.12 to 5.89). Among those with hypertension, an increase in WBC count (odds ratio per 1,000-cell/mL increase, 1.83; 95% CI, 1.04 to 3.23) and fibrinogen level (odds ratio per 10-mg/dL increase, 1.02; 95% CI, 1.00 to 1.05) were significantly associated with microalbuminuria. In all 3 groups, prevalent CHD was related to an elevated WBC count. In none of the 3 groups was brachial artery reactivity to ischemia, an in vivo marker of endothelial function, related to microalbuminuria.
CONCLUSION: Microalbuminuria is associated with age, systolic blood pressure, and markers of inflammation. These associations reflect potential mechanisms by which microalbuminuria is related to CHD risk.
10aAge Distribution10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aBrachial Artery10aComorbidity10aCoronary Disease10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aHumans10aHypertension10aInflammation10aLogistic Models10aMale10aMultivariate Analysis10aOdds Ratio10aRisk Factors10aSmoking10aUltrasonography1 aBarzilay, Joshua, I1 aPeterson, Do1 aCushman, Mary1 aHeckbert, Susan, R1 aCao, Jie, J1 aBlaum, Caroline1 aTracy, Russell, P1 aKlein, Ronald1 aHerrington, David, M uhttps://chs-nhlbi.org/node/79402446nas a2200373 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520137500294653000901669653001901678653002101697653003001718653001201748653001101760653002201771653001101793653002401804653001401828653001201842653000901854653002101863653001701884100002401901700002401925700002201949700002101971700002301992700002202015856003502037 2004 eng d a0021-972X00aThe relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort.0 arelationship of fasting serum radioimmune insulin levels to inci c2004 Jun a2852-80 v893 aIt is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6-9 yr. All were free of CHD at baseline. There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43-150 microU/ml (258-900 pmol/liter)] had an adjusted 30% increased relative risk (95% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 microU/ml (<120 pmol/liter)]. Those in the fourth interval [151-400 microU/ml (906-2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3-13.1; P < 0.0001). Approximately 15% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels. Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.
10aAged10aCohort Studies10aCoronary Disease10aDiabetes Mellitus, Type 110aFasting10aFemale10aFollow-Up Studies10aHumans10aHypoglycemic Agents10aIncidence10aInsulin10aMale10aRadioimmunoassay10aRisk Factors1 aKronmal, Richard, A1 aBarzilay, Joshua, I1 aTracy, Russell, P1 aSavage, Peter, J1 aOrchard, Trevor, J1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/78902390nas a2200361 4500008004100000022001400041245008000055210006900135260001300204300001100217490000700228520139900235653002801634653001101662653002201673653002901695653001101724653000901735653003401744653002401778653002401802653001701826653001901843100002101862700001401883700001701897700001401914700001701928700001501945700001801960700001501978856003501993 2004 eng d a0040-637600aRespiratory muscle strength and the risk of incident cardiovascular events.0 aRespiratory muscle strength and the risk of incident cardiovascu c2004 Dec a1063-70 v593 aBACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained.
METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke.
RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly.
CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.
10aCardiovascular Diseases10aFemale10aFollow-Up Studies10aForced Expiratory Volume10aHumans10aMale10aMaximal Voluntary Ventilation10aProspective Studies10aRespiratory Muscles10aRisk Factors10aVital Capacity1 avan der Palen, J1 aRea, T, D1 aManolio, T A1 aLumley, T1 aNewman, A, B1 aTracy, R P1 aEnright, P, L1 aPsaty, B M uhttps://chs-nhlbi.org/node/81102896nas a2200421 4500008004100000022001400041245010700055210006900162260001300231300001200244490000700256520170000263653003301963653000901996653002802005653002202033653001902055653001902074653001402093653001102107653001802118653001102136653001702147653000902164653001702173653004102190653001802231100002102249700002302270700002102293700002302314700002102337700001902358700002102377700002102398700002002419856003502439 2004 eng d a0002-861400aRisk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.0 aRisk of congestive heart failure in an elderly population treate c2004 Oct a1648-540 v523 aOBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.
DESIGN: Prospective cohort study.
SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina.
PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.
MEASUREMENTS: Adjudicated incident CHF.
RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk.
CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.
10aAdrenergic alpha-Antagonists10aAged10aAntihypertensive Agents10aBenzothiadiazines10aBlood Pressure10aCohort Studies10aDiuretics10aFemale10aHeart Failure10aHumans10aHypertension10aMale10aRisk Factors10aSodium Chloride Symporter Inhibitors10aUnited States1 aBryson, Chris, L1 aSmith, Nicholas, L1 aKuller, Lewis, H1 aChaves, Paulo, H M1 aManolio, Teri, A1 aLewis, William1 aBoyko, Edward, J1 aFurberg, Curt, D1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/80402805nas a2200361 4500008004100000022001400041245014300055210006900198260001300267300001100280490000700291520173500298653002102033653000902054653002102063653002802084653002802112653001102140653001102151653002502162653000902187653002402196653001702220653002002237653001802257100002402275700002502299700002002324700002002344700002002364700002402384856003502408 2004 eng d a0002-861400aSelf-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study.0 aSelfreported alcohol consumption and falls in older adults cross c2004 Jul a1174-90 v523 aOBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults.
DESIGN: Cross-sectional and longitudinal analyses.
SETTING: Four U.S. communities.
PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated.
MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline.
RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25% higher risk in consumers of 14 or more drinks per week (95% CI=3-52%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity.
CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.
10aAccidental Falls10aAged10aAlcohol Drinking10aChi-Square Distribution10aCross-Sectional Studies10aFemale10aHumans10aLongitudinal Studies10aMale10aRegression Analysis10aRisk Factors10aSelf Disclosure10aUnited States1 aMukamal, Kenneth, J1 aMittleman, Murray, A1 aLongstreth, W T1 aNewman, Anne, B1 aFried, Linda, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/79202748nas a2200409 4500008004100000022001400041245009200055210006900147260001600216300001000232490000700242520160500249653000901854653002201863653002801885653002101913653001901934653003801953653001101991653001802002653001102020653000902031653001602040653002002056653001002076653001702086653003102103100002402134700002202158700002002180700001702200700002402217700002302241700002102264700001802285856003502303 2004 eng d a0161-810500aSleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study.0 aSleep and reported daytime sleepiness in normal subjects the Sle c2004 Mar 15 a293-80 v273 aSTUDY OBJECTIVES: To describe the distribution of nocturnal sleep characteristics and reports of daytime sleepiness in a large well-defined group of healthy adults.
DESIGN: The Sleep Heart Health Study is a multicenter study examining sleep and cardiopulmonary parameters through nocturnal polysomnography in adults enrolled in geographically distinct cardiovascular cohorts.
SETTING: Community setting.
PARTICIPANTS: 470 subjects enrolled in the Sleep Heart Health Study (n = 6440) were selected as a 'normative' group based on screening of health conditions and daily habits that could interfere with sleep.
MEASUREMENTS AND RESULTS: Home-based nocturnal polysomnography was obtained on all participants and centrally scored for sleep and respiratory parameters. Demographic and health-related data were obtained and updated at the time of the home visit. Sleep efficiency decreased by 1.6% for each 10 years of increased age. Sleep time decreased by 0.1 hours (6.0 minutes) for each 10-year age increase and was longer in women. The arousal index increased by 0.8 for each 10-year increase in age and was lower by 1.4 in women. Women had a lower mean percentage of stage 1 and stage 2 sleep. Mean percentage of slow-wave sleep was higher in women (by 6.7%). Percentage of slow-wave sleep decreased with increased age for men only (by 1.9% for each 10-year age change).
CONCLUSIONS: Data suggest a clear lessening in the quantity and quality of sleep with age that appears to be more rapid in males compared to females.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCircadian Rhythm10aCohort Studies10aDisorders of Excessive Somnolence10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPolysomnography10aSleep10aSleep Stages10aSurveys and Questionnaires1 aWalsleben, Joyce, A1 aKapur, Vishesh, K1 aNewman, Anne, B1 aShahar, Eyal1 aBootzin, Richard, R1 aRosenberg, Carl, E1 aO'Connor, George1 aNieto, Javier uhttps://chs-nhlbi.org/node/77602899nas a2200481 4500008004100000022001400041245010600055210006900161260001600230300001100246490000800257520154600265653001601811653000901827653002201836653001501858653002001873653002001893653002801913653001901941653001601960653002601976653001102002653001102013653001702024653001802041653000902059653002002068653001502088653001602103653003002119653002002149653002102169653003002190653002602220653002902246100001802275700002502293700001902318700002402337700002102361856003502382 2004 eng d a1073-449X00aSleep apnea and markers of vascular endothelial function in a large community sample of older adults.0 aSleep apnea and markers of vascular endothelial function in a la c2004 Feb 01 a354-600 v1693 aClinical studies have suggested that sleep apnea is associated with impaired brachial artery flow-mediated dilation, a surrogate of endothelial dysfunction. We examined this question among older participants in the baseline examination of the Sleep Heart Health/Cardiovascular Health Study cohort (n = 1,037, age 68 years or older, 56% female). Indices of sleep apnea, derived from 12-channel home polysomnography, were the apnea-hypopnea index (average number of apneas/hypopneas per hour) and the hypoxemia index (percentage of time below 90% O2 saturation). Baseline arterial diameter and percentage of flow-mediated dilation were measured by ultrasound. Sleep apnea measures were associated with baseline diameter and the percentage of flow-mediated dilation, although these associations were weakened after adjustment for other cardiovascular risk factors, particularly body mass index. However, a statistically significant linear association between the hypoxemia index and baseline diameter was observed even after adjustment for body mass index and other confounders (p < 0.01). The associations were stronger among participants who were younger than 80 years and among those who with hypertension. This study adds to the growing body of evidence linking sleep apnea with vascular dysfunction in older subjects. Whether these relationships are entirely independent of obesity is unclear. This association might be one of the mechanisms explaining the relationship between sleep apnea, hypertension, and cardiovascular disease.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aBody Mass Index10aBrachial Artery10aCardiovascular Diseases10aCohort Studies10aComorbidity10aEndothelium, Vascular10aFemale10aHumans10aHypertension10aLinear Models10aMale10aPolysomnography10aPrevalence10aProbability10aResidence Characteristics10aRisk Assessment10aSampling Studies10aSeverity of Illness Index10aSleep Apnea Syndromes10aUltrasonography, Doppler1 aNieto, Javier1 aHerrington, David, M1 aRedline, Susan1 aBenjamin, Emelia, J1 aRobbins, John, A uhttps://chs-nhlbi.org/node/75202954nas a2200505 4500008004100000022001400041245010700055210006900162260001600231300001100247490000800258520147700266653000901743653002301752653002201775653002001797653001901817653003901836653002801875653003001903653001201933653001101945653002401956653002701980653001102007653002302018653001802041653000902059653001602068653002602084653001902110653002002129653002002149653001702169653003002186653002602216100002302242700001702265700001902282700002402301700002102325700002402346710004302370856003502413 2004 eng d a0002-926200aSleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study.0 aSleepdisordered breathing glucose intolerance and insulin resist c2004 Sep 15 a521-300 v1603 aClinic-based studies suggest that sleep-disordered breathing (SDB) is associated with glucose intolerance and insulin resistance. However, in the available studies, researchers have not rigorously controlled for confounding variables to assess the independent relation between SDB and impaired glucose metabolism. The objective of this study was to determine whether SDB was associated with glucose intolerance and insulin resistance among community-dwelling subjects (n=2,656) participating in the Sleep Heart Health Study (1994-1999). SDB was characterized with the respiratory disturbance index and measurements of oxygen saturation during sleep. Fasting and 2-hour glucose levels measured during an oral glucose tolerance test were used to assess glycemic status. Relative to subjects with a respiratory disturbance index of less than 5.0 events/hour (the reference category), subjects with mild SDB (5.0-14.9 events/hour) and moderate to severe SDB (> or =15 events/hour) had adjusted odds ratios of 1.27 (95% confidence interval: 0.98, 1.64) and 1.46 (95% confidence interval: 1.09, 1.97), respectively, for fasting glucose intolerance (p for trend < 0.01). Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, body mass index, and waist circumference. The results of this study suggest that SDB is independently associated with glucose intolerance and insulin resistance and may lead to type 2 diabetes mellitus.
10aAged10aBlood Gas Analysis10aBody Constitution10aBody Mass Index10aCohort Studies10aConfounding Factors, Epidemiologic10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aFasting10aFemale10aGlucose Intolerance10aGlucose Tolerance Test10aHumans10aInsulin Resistance10aLinear Models10aMale10aMiddle Aged10aMultivariate Analysis10aOxyhemoglobins10aPolysomnography10aResearch Design10aRisk Factors10aSeverity of Illness Index10aSleep Apnea Syndromes1 aPunjabi, Naresh, M1 aShahar, Eyal1 aRedline, Susan1 aGottlieb, Daniel, J1 aGivelber, Rachel1 aResnick, Helaine, E1 aSleep Heart Health Study Investigators uhttps://chs-nhlbi.org/node/80003262nas a2200385 4500008004100000022001400041245013700055210006900192260001600261300001100277490000700288520215100295653000902446653002202455653002002477653002102497653002802518653001102546653001102557653001202568653001602580653002002596653003402616653001102650653002002661653002602681100002002707700001702727700001802744700001802762700002002780700002102800700002002821856003502841 2004 eng d a0161-810500aSleep-disordered breathing is not associated with the presence of retinal microvascular abnormalities: the Sleep Heart Health Study.0 aSleepdisordered breathing is not associated with the presence of c2004 May 01 a467-730 v273 aSTUDY OBJECTIVE: Sleep apnea and milder forms of sleep-disordered breathing (SDB) have been associated with overt clinical cardiovascular disease, but it is unknown whether SDB is associated with arterial microvascular pathology. We examined the relation between SDB and retinal microvascular abnormalities.
DESIGN: Cross-sectional study.
PARTICIPANTS: Subjects were 2,927 men and women, aged 51 to 97 years, who participated in the Sleep Heart Health Study and had retinal photographs taken within approximately 3 years of overnight, unattended, at-home polysomnography.
MEASUREMENTS AND RESULTS: A respiratory disturbance index (RDI), calculated as the average number of apneas and hypopneas per hour of sleep, was used as an indicator of SDB in analysis. The overall prevalence of retinopathy was slightly higher in people with higher RDI values (5.4%, 4.9%, 8.6%, and 7.6%, respectively, in increasing quartiles of RDI), but after adjustment for age, body-mass index, hypertension, diabetes, and other factors, the presence of retinopathy was not associated with SDB. With the possible exceptions of microaneurysms and generalized arteriolar narrowing, as measured by lower arteriole-to-venule ratio, specific retinal abnormalities were not associated consistently with the RDI. Relative to the first quartile of RDI, the adjusted odds ratios (95% confidence interval) for the presence of microaneurysm in the second, third, and fourth quartiles of RDI were 1.05 (0.44-2.55), 1.97 (0.89-4.37), and 1.79 (0.78-4.10), respectively. An increase of RDI from 0 to 10 was associated with a predicted decrease in arteriole-to-venule ratio of 0.01. Results were similar when analyses were conducted in normotensive and nondiabetic persons separately.
CONCLUSIONS: These data do not demonstrate a notable relation between SDB and retinal abnormalities. However, since this is the first investigation of a link between retinopathy and SDB, similar studies should be conducted in other population samples to demonstrate either consistency or inconsistency of our findings across studies.
10aAged10aAged, 80 and over10aBody Mass Index10aCoronary Disease10aCross-Sectional Studies10aFemale10aHumans10aHypoxia10aMiddle Aged10aPolysomnography10aPositive-Pressure Respiration10aRetina10aRetinal Vessels10aSleep Apnea Syndromes1 aBoland, Lori, L1 aShahar, Eyal1 aWong, Tien, Y1 aKlein, Ronald1 aPunjabi, Naresh1 aRobbins, John, A1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/78202832nas a2200433 4500008004100000022001400041245006100055210006000116260001600176300001000192490000700202520170100209653000901910653002201919653001001941653002401951653001901975653001601994653001102010653002202021653002802043653001102071653001402082653000902096653002002105653001702125653002102142653003202163653003002195653001102225653001802236100001702254700001802271700002002289700001802309700001702327700001902344856003502363 2004 eng d a1526-632X00aStroke risk factors and loss of high cognitive function.0 aStroke risk factors and loss of high cognitive function c2004 Sep 14 a793-90 v633 aBACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition.
METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS).
RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction).
CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.
10aAged10aAged, 80 and over10aAging10aCognition Disorders10aCohort Studies10aComorbidity10aFemale10aFollow-Up Studies10aHigher Nervous Activity10aHumans10aIncidence10aMale10aRisk Assessment10aRisk Factors10aSampling Studies10aSensitivity and Specificity10aSeverity of Illness Index10aStroke10aUnited States1 aElkins, J, S1 aO'Meara, E, S1 aLongstreth, W T1 aCarlson, M, C1 aManolio, T A1 aJohnston, S, C uhttps://chs-nhlbi.org/node/80102681nas a2200409 4500008004100000022001400041245009100055210006900146260001600215300001100231490000800242520154100250653000901791653002201800653001901822653002801841653001101869653002201880653001801902653001101920653001401931653000901945653001401954653003001968653002201998100002602020700001902046700002302065700002302088700001902111700002402130700002302154700002202177700001702199700002002216856003502236 2004 eng d a0002-926200aSurvival associated with two sets of diagnostic criteria for congestive heart failure.0 aSurvival associated with two sets of diagnostic criteria for con c2004 Oct 01 a628-350 v1603 aCongestive heart failure (CHF) definitions vary across epidemiologic studies. The Framingham Heart Study criteria include CHF signs and symptoms assessed by a physician panel. In the Cardiovascular Health Study, a committee of physicians adjudicated CHF diagnoses, confirmed by signs, symptoms, clinical tests, and/or medical therapy. The authors used data from the Cardiovascular Health Study, a population-based cohort study of 5,888 elderly US adults, to compare CHF incidence and survival patterns following onset of CHF as defined by Framingham and/or Cardiovascular Health Study criteria. They constructed an inception cohort of nonfatal, hospitalized CHF patients. Of 875 participants who had qualifying CHF hospitalizations between 1989 and 2000, 54% experienced a first CHF event that fulfilled both sets of diagnostic criteria (concordant), 31% fulfilled only the Framingham criteria (Framingham only), and 15% fulfilled only the Cardiovascular Health Study criteria (Cardiovascular Health Study only). No significant survival difference was found between the Framingham-only group (hazard ratio = 0.87, 95% confidence interval: 0.71, 1.07) or the Cardiovascular Health Study-only group (hazard ratio = 0.89, 95% confidence interval: 0.68, 1.15) and the concordant group (referent). Compared with Cardiovascular Health Study central adjudication, Framingham criteria for CHF identified a larger group of participants with incident CHF, but all-cause mortality rates were similar across these diagnostic classifications.
10aAged10aAged, 80 and over10aCohort Studies10aDiagnosis, Differential10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPrognosis10aSeverity of Illness Index10aSurvival Analysis1 aSchellenbaum, Gina, D1 aRea, Thomas, D1 aHeckbert, Susan, R1 aSmith, Nicholas, L1 aLumley, Thomas1 aRoger, Veronique, L1 aKitzman, Dalane, W1 aTaylor, Herman, A1 aLevy, Daniel1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/80202971nas a2200373 4500008004100000022001400041245011900055210006900174260001300243300001000256490000800266520185400274653003202128653000902160653004402169653004502213653001902258653001702277653003002294653001102324653001802335653001102353653000902364653002602373653001502399100002302414700002102437700001902458700002202477700002402499700001902523700002002542856003502562 2004 eng d a1097-674400aTime trends in the use of beta-blockers and other pharmacotherapies in older adults with congestive heart failure.0 aTime trends in the use of betablockers and other pharmacotherapi c2004 Oct a710-70 v1483 aBACKGROUND: Evidence supporting pharmacotherapy of congestive heart failure (CHF) has grown substantially over the past decade and includes large, placebo-controlled trials with mortality end points. We describe beta-blocker and other medication temporal treatment trends of CHF in the Cardiovascular Health Study, a community-based cohort study of 5888 adults > or =65 years of age.
METHODS: Prescription medication data were collected from hospital discharge summaries for incident CHF events and at in-study annual clinic visits for prevalent CHF cases from 1989 to 2000. Change in use of agents over time was estimated by using generalized estimating equations while adjusting for potential confounding factors of age, sex, race, and cardiovascular and pulmonary comorbidities.
RESULTS: Among 1033 incident CHF events, beta-blocker use after diagnosis increased an average of 2.4 percentage points annually (95% CI, 1.5 to 3.4 points) from 1989 to 2000. The increasing trend was consistent throughout follow-up. Among participants with coronary disease and/or hypertension and among those with low ejection fractions (<45%), beta-blocker use remained flat from 1989 to 1994 and increased 4.7 points annually (2.5 to 6.9) and 10.0 points annually (6.1 to 13.8), respectively, from 1995 to 2000. Among participants without coronary disease or hypertension, there was no overall increase in use. Use of renin-angiotensin system inhibitors increased 2.3 points annually (1.0 to 3.5), digoxin use decreased 2.4 points annually (-3.6 to -1.1), and loop diuretic use remained flat between 1989 and 2000. In general, treatment trends were similar for prevalent CHF.
CONCLUSIONS: Treatment of CHF has changed gradually in the 1990s and may in part reflect the influence of CHF clinical trial evidence.
10aAdrenergic beta-Antagonists10aAged10aAngiotensin II Type 1 Receptor Blockers10aAngiotensin-Converting Enzyme Inhibitors10aCohort Studies10aDrug Therapy10aDrug Therapy, Combination10aFemale10aHeart Failure10aHumans10aMale10aMultivariate Analysis10aPrevalence1 aSmith, Nicholas, L1 aChan, Jeannie, D1 aRea, Thomas, D1 aWiggins, Kerri, L1 aGottdiener, John, S1 aLumley, Thomas1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/80702841nas a2200421 4500008004100000022001400041245010100055210006900156260001700225300001000242490000700252520165700259653000901916653003001925653002801955653001901983653002702002653001102029653003802040653001102078653001702089653001502106653001702121653001102138653002502149653000902174653001202183653003002195653001702225653001202242653001802254100002402272700002402296700002202320700001802342700002402360856003502384 2004 eng d a1076-746000aTraditional and novel risk factors in older adults: cardiovascular risk assessment late in life.0 aTraditional and novel risk factors in older adults cardiovascula c2004 Mar-Apr a69-800 v133 aAs a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.
10aAged10aBlood Coagulation Factors10aCardiovascular Diseases10aCohort Studies10aDiabetes Complications10aFemale10aGenetic Predisposition to Disease10aHumans10aHypertension10aInfections10aInflammation10aLipids10aLongitudinal Studies10aMale10aObesity10aPredictive Value of Tests10aRisk Factors10aSmoking10aUnited States1 aMukamal, Kenneth, J1 aKronmal, Richard, A1 aTracy, Russell, P1 aCushman, Mary1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/77202407nas a2200337 4500008004100000022001400041245009400055210006900149260001300218300001100231490000700242520145700249653000901706653001001715653001101725653001101736653001801747653003101765653000901796653001601805653001701821653001101838100002101849700002001870700002101890700002101911700001601932700002501948710006101973856003502034 2004 eng d a1524-462800aWhite matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke.0 aWhite matter hyperintensity on cranial magnetic resonance imagin c2004 Aug a1821-50 v353 aBACKGROUND AND PURPOSE: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors.
METHODS: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.
10aAged10aBrain10aFemale10aHumans10aLeukoaraiosis10aMagnetic Resonance Imaging10aMale10aRadiography10aRisk Factors10aStroke1 aKuller, Lewis, H1 aLongstreth, W T1 aArnold, Alice, M1 aBernick, Charles1 aBryan, Nick1 aBeauchamp, Norman, J1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/78803206nas a2200409 4500008004100000022001400041245022100055210006900276260001600345300001100361490000800372520196600380653001002346653001602356653000902372653002802381653002802409653001302437653001102450653001102461653001702472653000902489653001602498653001702514653002602531653002502557653001202582100002002594700002302614700001802637700001902655700002402674700002102698700001702719700002502736856003502761 2005 eng d a1524-453900aAge-dependent associations between sleep-disordered breathing and hypertension: importance of discriminating between systolic/diastolic hypertension and isolated systolic hypertension in the Sleep Heart Health Study.0 aAgedependent associations between sleepdisordered breathing and c2005 Feb 08 a614-210 v1113 aBACKGROUND: Sleep-disordered breathing (SDB) is associated with hypertension in the middle-aged. The association is less clear in older persons. Most middle-aged hypertensives have systolic/diastolic hypertension, whereas isolated systolic hypertension (ISH) is common among persons over 60 years. Mechanistically, only systolic/diastolic hypertension is expected to be associated with SDB, but few studies of SDB and hypertension distinguish systolic/diastolic hypertension from ISH. Prior investigations may have underestimated an association between SDB and systolic/diastolic hypertension in the elderly by categorizing individuals with ISH as simply hypertensive.
METHODS AND RESULTS: We conducted cross-sectional analyses of 6120 participants in the Sleep Heart Health Study, stratified by age: 40 to 59 (n=2477) and > or =60 years. Outcome measures included apnea-hypopnea index (AHI; average number of apneas plus hypopneas per hour of sleep), systolic/diastolic hypertension (> or =140 and > or =90 mm Hg), and ISH (> or =140 and <90 mm Hg). With adjustment for covariates, ISH was not associated with SDB in either age category. In those aged<60 years, AHI was significantly associated with higher odds of systolic/diastolic hypertension (AHI 15 to 29.9, OR=2.38 [95% CI 1.30 to 4.38]; AHI > or =30, OR=2.24 [95% CI 1.10 to 4.54]). Among those aged > or =60 years, no adjusted association between AHI and systolic/diastolic hypertension was found.
CONCLUSIONS: SDB is associated with systolic/diastolic hypertension in those aged <60 years. No association was found between SDB and systolic/diastolic hypertension in those aged > or =60 years or between SDB and ISH in either age category. These findings have implications for SDB screening and treatment. Distinguishing between hypertensive subtypes reveals a stronger association between SDB and hypertension for those aged <60 years than previously reported.
10aAdult10aAge Factors10aAged10aAntihypertensive Agents10aCross-Sectional Studies10aDiastole10aFemale10aHumans10aHypertension10aMale10aMiddle Aged10aRisk Factors10aSleep Apnea Syndromes10aSleep Apnea, Central10aSystole1 aHaas, Donald, C1 aFoster, Gregory, L1 aNieto, Javier1 aRedline, Susan1 aResnick, Helaine, E1 aRobbins, John, A1 aYoung, Terry1 aPickering, Thomas, G uhttps://chs-nhlbi.org/node/82203344nas a2200577 4500008004100000022001400041245009700055210006900152260001300221300001100234490000700245520177500252653000902027653002102036653002202057653002102079653001902100653001902119653001102138653002202149653003802171653001302209653001102222653001702233653001702250653001302267653001102280653000902291653001602300653002602316653002602342653002402368653000902392653001702401653001102418653003202429653001502461653001702476653002202493100002402515700001702539700002002556700002102576700002002597700002502617700002202642700001802664700002502682700002402707856003502731 2005 eng d a1524-462800aAlcohol use and risk of ischemic stroke among older adults: the cardiovascular health study.0 aAlcohol use and risk of ischemic stroke among older adults the c c2005 Sep a1830-40 v363 aBACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype.
METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly.
RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors.
CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.
10aAged10aAlcohol Drinking10aApolipoproteins E10aBrain Infarction10aBrain Ischemia10aCohort Studies10aFemale10aFollow-Up Studies10aGenetic Predisposition to Disease10aGenotype10aHumans10aHypertension10aInflammation10aIschemia10aLipids10aMale10aMiddle Aged10aMultivariate Analysis10aMyocardial Infarction10aProspective Studies10aRisk10aRisk Factors10aStroke10aSubstance-Related Disorders10aThrombosis10aTime Factors10aVascular Diseases1 aMukamal, Kenneth, J1 aChung, Hyoju1 aJenny, Nancy, S1 aKuller, Lewis, H1 aLongstreth, W T1 aMittleman, Murray, A1 aBurke, Gregory, L1 aCushman, Mary1 aBeauchamp, Norman, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/85002976nas a2200373 4500008004100000022001400041245008600055210006900141260001600210300001100226490000800237520195000245653002702195653000902222653002202231653001902253653001102272653001802283653001102301653001402312653000902326653001902335653001702354653001702371653003202388100001802420700001802438700002302456700002802479700002202507700001802529700002002547856003502567 2005 eng d a1539-370400aAssociation between screening for osteoporosis and the incidence of hip fracture.0 aAssociation between screening for osteoporosis and the incidence c2005 Feb 01 a173-810 v1423 aBACKGROUND: Because direct evidence for the effectiveness of screening is lacking, guidelines disagree on whether people should be screened for osteoporosis.
OBJECTIVE: To determine whether population-based screening for osteoporosis in older adults is associated with fewer incident hip fractures than usual medical care.
DESIGN: Nonconcurrent cohort study.
SETTING: Population-based cohort enrolled in the Cardiovascular Health Study (CHS) from 4 states (California, Pennsylvania, Maryland, and North Carolina).
PATIENTS: 3107 adults 65 years of age and older who attended their CHS study visits in 1994-1995.
MEASUREMENTS: 31 participant characteristics (including demographic characteristics, medical histories, medications, and physical examination findings) and incident hip fractures over 6 years of follow-up.
INTERVENTION: Bone density scans (dual-energy x-ray absorptiometry [DEXA] at the hip) for participants in California and Pennsylvania (n = 1422) and usual care for participants in Maryland and North Carolina (n = 1685).
RESULTS: The incidence of hip fractures per 1000 person-years was 4.8 in the screened group and 8.2 in the usual care group. Screening was associated with a statistically significant lower hazard of hip fracture than usual care after adjustment for sex and propensity to be screened (Cox proportional hazard ratio, 0.64 [95% CI, 0.41 to 0.99]).
LIMITATIONS: The mechanism of the association was unclear. A small unmeasured confounder that decreased the hazard of hip fracture could diminish or erase the observed association.
CONCLUSIONS: Use of hip DEXA scans to screen for osteoporosis in older adults was associated with 36% fewer incident hip fractures over 6 years compared with usual medical care. Further research is needed to explore the mechanism of this association.
10aAbsorptiometry, Photon10aAged10aAged, 80 and over10aCohort Studies10aFemale10aHip Fractures10aHumans10aIncidence10aMale10aMass Screening10aOsteoporosis10aRisk Factors10aSensitivity and Specificity1 aKern, Lisa, M1 aPowe, Neil, R1 aLevine, Michael, A1 aFitzpatrick, Annette, L1 aHarris, Tamara, B1 aRobbins, John1 aFried, Linda, P uhttps://chs-nhlbi.org/node/82102860nas a2200361 4500008004100000022001400041245013800055210006900193260001300262300001100275490000800286520181600294653003202110653001602142653000902158653002202167653001102189653002202200653001802222653001102240653000902251100002102260700001902281700002302300700002102323700002302344700001902367700001802386700002102404700001802425700002002443856003502463 2005 eng d a1097-674400aAssociation of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS).0 aAssociation of betablocker use with mortality among patients wit c2005 Sep a464-700 v1503 aBACKGROUND: In clinical trials, beta-blocker therapy reduces all-cause mortality among people with congestive heart failure (CHF) characterized by depressed systolic function, but few trials included large numbers of elderly participants. This study assessed the association between beta-blocker therapy and mortality among community-dwelling older adults with CHF.
METHODS: The Cardiovascular Health Study (CHS) is a longitudinal, population-based study of adults aged > or = 65 years. Recruitment began in 1989 with follow-up extending through June 2000 or death. Cox proportional hazard regression models were used to assess the association between beta-blocker therapy and all-cause mortality among 950 participants who developed new-onset CHF.
RESULTS: beta-Blocker users (n = 157) were more likely than nonusers (n = 793) to have treated hypertension, clinical coronary artery disease, and valvular disease at the time of CHF diagnosis. Death occurred in 67 users and 446 nonusers during a median follow-up of 2.3 years. Compared with nonuse, use of beta-blockers was associated with a multivariable adjusted hazard ratio (HR) of 0.74 (95% CI 0.56-0.98) for all-cause mortality. Among the 520 participants who had left ventricular ejection fraction assessed within 90 days after CHF diagnosis, the risk for all cause mortality associated with beta-blocker use did not differ significantly between those with ejection fraction of < 40% and those with ejection fraction of > or = 40% (HR 0.56, 95% CI 0.27-1.13; HR 0.82, 95% CI 0.56-1.22, respectively; interaction P = .34).
CONCLUSIONS: This observational study suggests that beta-blocker treatment is associated with a reduced risk of all-cause mortality among community-dwelling older adults with CHF.
10aAdrenergic beta-Antagonists10aAge Factors10aAged10aAged, 80 and over10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aMale1 aChan, Jeannie, D1 aRea, Thomas, D1 aSmith, Nicholas, L1 aSiscovick, David1 aHeckbert, Susan, R1 aLumley, Thomas1 aChaves, Paulo1 aFurberg, Curt, D1 aKuller, Lewis1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/85603249nas a2200433 4500008004100000022001400041245008500055210006900140260001600209300001000225490000800235520207600243653001602319653000902335653002202344653001802366653002202384653002402406653001102430653002402441653001102465653000902476653001602485653001502501653001502516653002402531653001002555653003102565653001702596653001802613100002402631700002302655700001902678700002402697700001902721700002202740700001802762856003502780 2005 eng d a0003-992600aAssociation of sleep time with diabetes mellitus and impaired glucose tolerance.0 aAssociation of sleep time with diabetes mellitus and impaired gl c2005 Apr 25 a863-70 v1653 aBACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing.
METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index.
RESULTS: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded.
CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.
10aAge Factors10aAged10aAged, 80 and over10aBlood Glucose10aDiabetes Mellitus10aDisease Progression10aFemale10aGlucose Intolerance10aHumans10aMale10aMiddle Aged10aOdds Ratio10aPrevalence10aProspective Studies10aSleep10aSurveys and Questionnaires10aTime Factors10aUnited States1 aGottlieb, Daniel, J1 aPunjabi, Naresh, M1 aNewman, Ann, B1 aResnick, Helaine, E1 aRedline, Susan1 aBaldwin, Carol, M1 aNieto, Javier uhttps://chs-nhlbi.org/node/83404369nas a2200529 4500008004100000022001400041245015000055210006900205260001300274300001100287490000700298520286400305653002203169653000903191653002203200653001003222653002803232653001603260653001903276653001603295653001503311653002203326653002403348653004003372653001103412653003103423653001103454653001703465653001103482653000903493653001603502653002403518653001603542653001103558653002103569653002003590100002403610700002103634700002303655700002303678700002003701700001803721700001803739700002203757700002503779856003503804 2005 eng d a1523-683800aAssociations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study.0 aAssociations between retinal microvascular abnormalities and dec c2005 Aug a214-240 v463 aBACKGROUND: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals.
METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling.
RESULTS: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function.
CONCLUSION: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.
10aAfrican Americans10aAged10aAged, 80 and over10aAging10aAntihypertensive Agents10aCapillaries10aCohort Studies10aComorbidity10aCreatinine10aDiabetes Mellitus10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney10aMale10aPhotography10aProspective Studies10aProteinuria10aRetina10aRetinal Diseases10aRetinal Vessels1 aEdwards, Matthew, S1 aWilson, David, B1 aCraven, Timothy, E1 aStafford, Jeanette1 aFried, Linda, F1 aWong, Tien, Y1 aKlein, Ronald1 aBurke, Gregory, L1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/85402879nas a2200349 4500008004100000022001400041245007600055210006900131260001600200300001100216490000600227520190500233653000902138653001002147653002402157653003202181653001102213653001102224653003102235653000902266653002002275653003002295653002602325653002902351100001802380700001902398700001502417700002402432700002002456700001802476856003502494 2005 eng d a1550-938900aAssociations of sleep-disordered breathing and cerebral changes on MRI.0 aAssociations of sleepdisordered breathing and cerebral changes o c2005 Apr 15 a159-650 v13 aSTUDY OBJECTIVES: Population-based studies have demonstrated associations between sleep-disordered breathing (SDB), hypertension, and cardiovascular disease; few large-scale studies have examined associations of SDB with objective measures of cerebrovascular disease. This study tested the significance of associations of SDB with evidence of brain injury or ischemia determined by cerebral magnetic resonance imaging (MRI) studies.
DESIGN: Cross-sectional and longitudinal analyses in a nested sample of Cardiovascular Health Study participants in the Sleep Heart Health Study.
PARTICIPANTS: The 843 individuals (mean age 77, SD 4.3 years, 58% women) who had MRI studies as part of the Cardiovascular Health Study before and after polysomnography obtained as part of the Sleep Heart Health Study.
MEASUREMENTS: A 12-channel polysomnogram was used to derive indexes of sleep-disordered breathing. Repeated MRI measurements provided indexes of infarct (presence and size) and white matter disease. Logistic regression analyses were used to model MRI changes of infarct-like lesions and white matter disease as a function of age, baseline white matter grade, and indexes of central and obstructive sleep-disordered breathing.
RESULTS: Individuals who showed progression in white matter disease compared to those who did not were significantly more likely to show a Cheyne-Stokes respiration pattern and to have an increased number of central but not obstructive apneas.
CONCLUSIONS: An association between change in white matter grade and measures of central sleep apnea was demonstrated that was consistent with a causal pathway in which central sleep apnea contributes to the progression of white matter disease; alternatively, central sleep apnea may be a marker of subclinical cerebrovascular or cardiovascular disease.
10aAged10aBrain10aCerebral Infarction10aCerebrovascular Circulation10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aPolysomnography10aSeverity of Illness Index10aSleep Apnea Syndromes10aSleep Apnea, Obstructive1 aRobbins, John1 aRedline, Susan1 aErvin, Ann1 aWalsleben, Joyce, A1 aDing, Jingzhong1 aNieto, Javier uhttps://chs-nhlbi.org/node/96602672nas a2200469 4500008004100000022001400041245009000055210006900145260001600214300001200230490000700242520138900249653000901638653002201647653002201669653002201691653001901713653001301732653003001745653002501775653002101800653001101821653001401832653001801846653002101864653003801885653001101923653001401934653000901948653001701957653002601974653003102000100001602031700001602047700001702063700002202080700001602102700001502118700001602133700001802149856003502167 2005 eng d a1526-632X00aBenefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.0 aBenefits of fatty fish on dementia risk are stronger for those w c2005 Nov 08 a1409-140 v653 aOBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).
METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.
RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.
CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.
10aAged10aAlzheimer Disease10aApolipoprotein E410aApolipoproteins E10aCohort Studies10aDementia10aDietary Fats, Unsaturated10aFatty Acids, Omega-310aFeeding Behavior10aFemale10aFish Oils10aFish Products10aFood, Formulated10aGenetic Predisposition to Disease10aHumans10aIncidence10aMale10aRisk Factors10aSocioeconomic Factors10aSurveys and Questionnaires1 aHuang, T, L1 aZandi, P, P1 aTucker, K, L1 aFitzpatrick, A, L1 aKuller, L H1 aFried, L P1 aBurke, G, L1 aCarlson, M, C uhttps://chs-nhlbi.org/node/87003325nas a2200421 4500008004100000022001400041245012000055210006900175260001300244300001000257490000700267520209400274653002202368653002802390653002102418653002802439653004002467653001102507653001302518653001502531653001102546653001702557653001402574653000902588653001602597653002602613653003402639653001702673100002302690700002302713700002002736700001902756700002402775700002502799700002202824700002202846856003502868 2005 eng d a0895-706100abeta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.0 abeta2Adrenergic receptor polymorphisms and determinants of cardi c2005 Mar a392-70 v183 aBACKGROUND: Common Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) have been associated with hypertension and coronary disease. This analysis of older adults in the Cardiovascular Health Study examined whether these polymorphisms were associated with blood pressure (BP), subclinical atherosclerosis, and, among treated hypertensive individuals, differences in coronary disease risk according to antihypertensive drug class.
METHODS: Altogether, 5249 participants (4441 white and 808 African American, median follow-up time 10.2 years) were genotyped for both polymorphisms. Ankle-arm index (AAI), carotid intima-media thickness (IMT), and brachial flow-mediated dilation were measured cross-sectionally. All estimates were adjusted for ethnicity.
RESULTS: Relative to Gln27 homozygotes, carrying the Glu27 allele was not associated with new-onset hypertension (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.87 to 1.16), BP control (odds ratio [OR] = 0.97, 95% CI = 0.89 to 1.06), AAI (mean difference 0.0042 +/- 0.0052), carotid IMT (mean difference 0.0044 +/- 0.02 mm), or brachial flow-mediated dilation (mean difference in baseline diameter -0.028 +/- 0.036 mm; the most marked of three measures). Among treated hypertensive individuals, coronary disease risk was similar in Glu27 carriers relative to Gln27 homozygotes in subgroups defined by use of beta-blockers (HR = 1.09, 95% CI = 0.64 to 1.87) or other antihypertensive medications (HR = 1.00, 95% CI = 0.78 to 1.28). Results were similar for the Arg16Gly polymorphism.
CONCLUSIONS: The association of beta(2)AR genotype with coronary disease previously reported in this older adult population is not likely to be explained by BP levels, subclinical atherosclerosis, or antihypertensive treatment. Other measures of vascular response, gene-gene or gene-environment interactions, or characteristics developing earlier in life may mediate the association between beta(2)AR genotype and coronary disease and merit further research.
10aAfrican Americans10aAntihypertensive Agents10aArteriosclerosis10aCoronary Artery Disease10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHomozygote10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aPolymorphism, Genetic10aReceptors, Adrenergic, beta-210aRisk Factors1 aHindorff, Lucia, A1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aLumley, Thomas1 aSiscovick, David, S1 aHerrington, David, M1 aEdwards, Karen, L1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/82503855nas a2200481 4500008004100000022001400041245015500055210006900210260001300279300001000292490000800302520246000310653000902770653002202779653001502801653001902816653002802835653002102863653002802884653002802912653001302940653001102953653001502964653001102979653001702990653001903007653000903026653002703035653001603062653001903078653002703097653001703124100002003141700002803161700001803189700001903207700002103226700002403247700002203271700002403293700002103317856003503338 2005 eng d a1549-471300aCardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies.0 aCardiovascular risk factors for retinal vein occlusion and arter c2005 Apr a540-70 v1123 aOBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease.
DESIGN: Population-based cross-sectional study.
PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years).
METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography.
MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli.
RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3% (n = 39 cases) and 0.2% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95% CI, 2.60-12.16), body mass index (OR, 3.88; 95% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95% CI, 1.44-6.84), systolic BP (OR, 3.46; 95% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound.
CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.
10aAged10aAged, 80 and over10aArterioles10aBlood Pressure10aCardiovascular Diseases10aCarotid Stenosis10aCoronary Artery Disease10aCross-Sectional Studies10aEmbolism10aFemale10aFibrinogen10aHumans10aHypertension10aLipoprotein(a)10aMale10aMeta-Analysis as Topic10aMiddle Aged10aRetinal Artery10aRetinal Vein Occlusion10aRisk Factors1 aWong, Tien, Yin1 aLarsen, Emily, K Marino1 aKlein, Ronald1 aMitchell, Paul1 aCouper, David, J1 aKlein, Barbara, E K1 aHubbard, Larry, D1 aSiscovick, David, S1 aSharrett, Richey uhttps://chs-nhlbi.org/node/82603401nas a2200445 4500008004100000022001400041245009200055210006900147260001600216300001200232490000700244520220600251653000902457653002202466653002202488653001002510653002202520653001902542653002302561653002802584653002402612653001102636653001102647653003102658653000902689653003002698653001102728653001802739100001602757700001602773700001702789700001702806700001802823700001902841700001602860700001602876700001302892700001502905856003502920 2005 eng d a1526-632X00aClassification of vascular dementia in the Cardiovascular Health Study Cognition Study.0 aClassification of vascular dementia in the Cardiovascular Health c2005 May 10 a1539-470 v643 aOBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study.
METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI.
RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer's Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD).
CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.
10aAged10aAged, 80 and over10aAlzheimer Disease10aBrain10aCerebral Arteries10aCohort Studies10aDementia, Vascular10aDiagnosis, Differential10aDisease Progression10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aPredictive Value of Tests10aStroke10aUnited States1 aLopez, O, L1 aKuller, L H1 aBecker, J, T1 aJagust, W, J1 aDeKosky, S, T1 aFitzpatrick, A1 aBreitner, J1 aLyketsos, C1 aKawas, C1 aCarlson, M uhttps://chs-nhlbi.org/node/83702760nas a2200505 4500008004100000022001400041245013500055210006900190260001300259300001100272490000800283520133700291653000901628653001001637653002401647653001901671653001901690653001101709653001301720653001801733653001101751653001701762653001401779653000901793653001601802653003801818653002601856653003001882653002401912653001701936653001501953100002501968700001701993700002302010700002602033700002002059700001802079700002202097700002002119700001902139700002002158700002102178700002002199856003502219 2005 eng d a0021-915000aCommon promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.0 aCommon promoter polymorphisms of inflammation and thrombosis gen c2005 Jul a175-830 v1813 aInflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.
10aAged10aAging10aCarboxypeptidase B210aCause of Death10aCohort Studies10aFemale10aGenotype10aHealth Status10aHumans10aInflammation10aLongevity10aMale10aMiddle Aged10aPlasminogen Activator Inhibitor 110aPolymorphism, Genetic10aPromoter Regions, Genetic10aProspective Studies10aRisk Factors10aThrombosis1 aReiner, Alexander, P1 aDiehr, Paula1 aBrowner, Warren, S1 aHumphries, Stephen, E1 aJenny, Nancy, S1 aCushman, Mary1 aTracy, Russell, P1 aWalston, Jeremy1 aLumley, Thomas1 aNewman, Anne, B1 aKuller, Lewis, H1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/84202889nas a2200361 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520186700271653000902138653001002147653001502157653002402172653002802196653002802224653001302252653001102265653001102276653002002287653003102307653000902338653001702347653001802364100002102382700002102403700002102424700002702445700002002472856003502492 2005 eng d a0002-861400aCoronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status.0 aCoronary artery calcium associations with brain magnetic resonan c2005 Apr a609-150 v533 aOBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment).
DESIGN: Cross-sectional.
SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults.
PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS.
MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status.
RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status.
CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.
10aAged10aBrain10aCalcinosis10aCognition Disorders10aCoronary Artery Disease10aCross-Sectional Studies10aDementia10aFemale10aHumans10aLogistic Models10aMagnetic Resonance Imaging10aMale10aRisk Factors10aUnited States1 aRosano, Caterina1 aNaydeck, Barbara1 aKuller, Lewis, H1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/82903506nas a2200373 4500008004100000022001400041245016100055210006900216260001300285300001100298490000700309520239700316653003102713653000902744653002502753653002402778653002102802653001102823653001102834653002502845653000902870653002602879653000902905653001802914100001902932700002002951700002102971700002002992700001803012700001903030700002303049700002503072856003503097 2005 eng d a0002-861400aThe course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study.0 acourse of functional decline in older people with persistently e c2005 Apr a569-750 v533 aOBJECTIVES: To examine the relationship between persistently high depressive symptoms and long-term changes in functional disability in elderly persons.
DESIGN: A community-based, prospective, observational study.
SETTING: Participant data from the Cardiovascular Health Study.
PARTICIPANTS: From the overall sample of 5,888 subjects, three types of participants were identified for this study: (1) persistently depressed individuals, who experienced an onset of depressive symptoms that persisted over 4 years (n=119); (2) temporarily depressed individuals, who experienced an onset of depressive symptoms that resolved over time (n=259); and (3) nondepressed individuals, with persistently low depressive symptoms throughout the follow-up period who were matched on baseline activity of daily living (ADL) scores, sex, and age to the previous two groups combined (n=378).
MEASUREMENTS: Four consecutive years of data were assessed: validated measures of depression (10-item CES-D), functional disability (10-item ADL/instrumental ADL measure), physical performance, medical illness, and cognition.
RESULTS: The persistently depressed group showed a greater linear increase in functional disability ratings than the temporarily depressed and nondepressed groups. This association between persistent depression and functional disability was robust even when controlling for baseline demographic and clinical/performance measures, including cognition. The persistently depressed group had an adjusted odds ratio (OR) of 5.27 (95% confidence interval (CI) 3.03-9.16) for increased functional disability compared with the nondepressed group over 3 years of follow-up, whereas the temporarily depressed group had an adjusted OR of 2.39 (95% CI=1.55-3.69) compared with the nondepressed group.
CONCLUSION: Persistently elevated depressive symptoms in elderly persons are associated with a steep trajectory of worsening functional disability, generating the hypothesis that treatments for late-life depression need to be assessed on their efficacy in maintaining long-term functional status as well as remission of depressive symptoms. These results also demonstrate the need for studies to differentiate between persistent and temporary depressive symptoms when examining their relationship to disability.
10aActivities of Daily Living10aAged10aCase-Control Studies10aDepressive Disorder10aDisabled Persons10aFemale10aHumans10aLongitudinal Studies10aMale10aMultivariate Analysis10aRisk10aUnited States1 aLenze, Eric, J1 aSchulz, Richard1 aMartire, Lynn, M1 aZdaniuk, Bozena1 aGlass, Thomas1 aKop, Willem, J1 aJackson, Sharon, A1 aReynolds, Charles, F uhttps://chs-nhlbi.org/node/82802779nas a2200397 4500008004100000022001400041245013200055210006900187260001600256300001000272490000800282520164900290653001601939653000901955653002201964653001501986653002302001653002102024653001102045653001102056653001402067653001702081653000902098653002602107653003002133653001702163100001802180700002102198700002002219700002102239700002102260700002202281700002102303700002202324856003502346 2005 eng d a1524-453900aC-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study.0 aCreactive protein and the 10year incidence of coronary heart dis c2005 Jul 05 a25-310 v1123 aBACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available.
METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33% in men and 17% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20%; the incidences were 31% and 10% for elevated and normal CRP levels, respectively.
CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCoronary Disease10aFemale10aHumans10aIncidence10aInflammation10aMale10aMyocardial Infarction10aPredictive Value of Tests10aRisk Factors1 aCushman, Mary1 aArnold, Alice, M1 aPsaty, Bruce, M1 aManolio, Teri, A1 aKuller, Lewis, H1 aBurke, Gregory, L1 aPolak, Joseph, F1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/84502721nas a2200397 4500008004100000022001400041245012500055210006900180260001900249300001200268490000800280520157700288653000901865653001901874653001501893653001401908653001101922653001901933653001101952653002501963653000901988653003301997653003002030653001702060653001402077653001802091100001902109700002002128700001602148700002002164700003202184700002402216700002402240700002402264856003502288 2005 eng d a0003-992600aCystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study.0 aCystatin C and incident peripheral arterial disease events in th c2005 Dec 12-26 a2666-700 v1653 aBACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined.
METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR).
RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses.
CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.
10aAged10aCohort Studies10aCystatin C10aCystatins10aFemale10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aPeripheral Vascular Diseases10aPredictive Value of Tests10aRisk Factors10aROC Curve10aUnited States1 aO'Hare, Ann, M1 aNewman, Anne, B1 aKatz, Ronit1 aFried, Linda, F1 aStehman-Breen, Catherine, O1 aSeliger, Stephen, L1 aSiscovick, David, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/87303275nas a2200589 4500008004100000022001400041245004900055210004800104260001300152300001100165490000700176520170100183653001601884653000901900653002201909653001501931653002101946653002501967653001501992653002802007653001502035653001402050653002402064653001102088653002502099653001102124653001402135653003102149653003102180653000902211653001502220653003002235653001402265653002002279653003202299653003002331653001602361653002202377100002402399700002002423700001602443700001802459700002002477700002102497700003202518700001702550700001702567700002202584700002002606700002402626856003502650 2005 eng d a1046-667300aCystatin C and subclinical brain infarction.0 aCystatin C and subclinical brain infarction c2005 Dec a3721-70 v163 aSubclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aBrain Infarction10aConfidence Intervals10aCreatinine10aCross-Sectional Studies10aCystatin C10aCystatins10aDisease Progression10aFemale10aGeriatric Assessment10aHumans10aIncidence10aIschemic Attack, Transient10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPredictive Value of Tests10aPrognosis10aRisk Assessment10aSensitivity and Specificity10aSeverity of Illness Index10aSex Factors10aSurvival Analysis1 aSeliger, Stephen, L1 aLongstreth, W T1 aKatz, Ronit1 aManolio, Teri1 aFried, Linda, F1 aShlipak, Michael1 aStehman-Breen, Catherine, O1 aNewman, Anne1 aSarnak, Mark1 aGillen, Daniel, L1 aBleyer, Anthony1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/86203216nas a2200445 4500008004100000022001400041245008600055210006900141260001600210300001200226490000800238520200500246653000902251653001502260653002802275653003302303653001502336653001502351653001402366653001102380653002202391653003102413653001102444653001102455653002002466653000902486653001402495653002602509653001402535653000902549100002402558700002002582700001602602700002002618700002402638700002002662700002402682700002902706856003502735 2005 eng d a1533-440600aCystatin C and the risk of death and cardiovascular events among elderly persons.0 aCystatin C and the risk of death and cardiovascular events among c2005 May 19 a2049-600 v3523 aBACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community.
METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c).
RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes.
CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.
10aAged10aBiomarkers10aCardiovascular Diseases10aCerebrospinal Fluid Proteins10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMortality10aMultivariate Analysis10aPrognosis10aRisk1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSeliger, Stephen, L1 aNewman, Anne, B1 aSiscovick, David, S1 aStehman-Breen, Catherine uhttps://chs-nhlbi.org/node/84003555nas a2200445 4500008004100000022001400041245008100055210006900136260001600205300001200221490000800233520234700241653000902588653001502597653001502612653001502627653001402642653001102656653002202667653003102689653001802720653001102738653001402749653001102763653002602774653000902800653001702809653001802826100002002844700001602864700003202880700002002912700002502932700002002957700002002977700002102997700002403018710003203042856003503074 2005 eng d a1539-370400aCystatin C concentration as a risk factor for heart failure in older adults.0 aCystatin C concentration as a risk factor for heart failure in o c2005 Apr 05 a497-5050 v1423 aBACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.
OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.
DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.
SETTING: Adults 65 years of age or older from 4 communities in the United States.
PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.
MEASUREMENTS: Incident heart failure.
RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).
LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.
CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.
10aAged10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney10aKidney Function Tests10aMale10aRisk Factors10aUnited States1 aSarnak, Mark, J1 aKatz, Ronit1 aStehman-Breen, Catherine, O1 aFried, Linda, F1 aJenny, Nancy, Swords1 aPsaty, Bruce, M1 aNewman, Anne, B1 aSiscovick, David1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/82702928nas a2200433 4500008004100000022001400041245006700055210006500122260001300187300000900200490000800209520175900217653001601976653000901992653001502001653002302016653002802039653001502067653001402082653001102096653001502107653003102122653001102153653002002164653000902184653003002193653003202223100002402255700001602279700001802295700002002313700002902333700002002362700002102382700002202403700001702425700001702442856003502459 2005 eng d a1555-716200aCystatin-C and inflammatory markers in the ambulatory elderly.0 aCystatinC and inflammatory markers in the ambulatory elderly c2005 Dec a14160 v1183 aPURPOSE: Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels.
METHODS: This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes.
RESULTS: After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5.
CONCLUSIONS: The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.
10aAge Factors10aAged10aBiomarkers10aC-Reactive Protein10aCross-Sectional Studies10aCystatin C10aCystatins10aFemale10aFibrinogen10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aPredictive Value of Tests10aSensitivity and Specificity1 aShlipak, Michael, G1 aKatz, Ronit1 aCushman, Mary1 aSarnak, Mark, J1 aStehman-Breen, Catherine1 aPsaty, Bruce, M1 aSiscovick, David1 aTracy, Russell, P1 aNewman, Anne1 aFried, Linda uhttps://chs-nhlbi.org/node/87602720nas a2200433 4500008004100000022001400041245006800055210006600123260001600189300001100205490000700216520154600223653001601769653000901785653002201794653001501816653001501831653001401846653001101860653002201871653003101893653001801924653001101942653000901953653001901962653003001981653002002011653002202031100002402053700001602077700002002093700002502113700003202138700002002170700002102190700002002211700002002231856003502251 2005 eng d a0735-109700aCystatin-C and mortality in elderly persons with heart failure.0 aCystatinC and mortality in elderly persons with heart failure c2005 Jan 18 a268-710 v453 aOBJECTIVES: We sought to evaluate cystatin-C, a novel measure of renal function, as a predictor of mortality in elderly persons with heart failure (HF) and to compare it with creatinine.
BACKGROUND: Renal function is an important prognostic factor in patients with HF, but creatinine levels, which partly reflect muscle mass, may be insensitive for detecting renal insufficiency.
METHODS: A total of 279 Cardiovascular Health Study participants with prevalent HF and measures of serum cystatin-C and creatinine were followed for mortality outcomes over a median of 6.5 years.
RESULTS: Median creatinine and cystatin-C levels were 1.05 mg/dl and 1.26 mg/l. Each standard deviation increase in cystatin-C (0.35 mg/l) was associated with a 31% greater adjusted mortality risk (95% confidence interval [CI] 20% to 43%, p < 0.001), whereas each standard deviation increase in creatinine (0.39 mg/dl) was associated with a 17% greater adjusted mortality risk (95% CI 1% to 36%, p = 0.04). When both measures were combined in a single adjusted model, cystatin-C remained associated with elevated mortality risk (hazard ratio 1.60, 95% CI 1.32 to 1.94), whereas creatinine levels appeared associated with lower risk (hazard ratio 0.73, 95% CI 0.57 to 0.95).
CONCLUSIONS: Cystatin-C is a stronger predictor of mortality than creatinine in elderly persons with HF. If confirmed in future studies, this new marker of renal function could improve risk stratification in patients with HF.
10aAge Factors10aAged10aAged, 80 and over10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aMale10aPilot Projects10aPredictive Value of Tests10aRisk Assessment10aSurvival Analysis1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aJenny, Nancy, Swords1 aStehman-Breen, Catherine, O1 aNewman, Anne, B1 aSiscovick, David1 aPsaty, Bruce, M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/81603025nas a2200409 4500008004100000022001400041245013200055210006900187260001300256300001100269490000700280520183100287653000902118653002202127653002202149653002802171653001902199653002102218653001302239653001102252653001102263653002502274653003102299653000902330653003302339653001702372100002002389700002802409700001702437700002002454700002602474700002002500700001602520700002302536700002102559856003502580 2005 eng d a0002-861400aDementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.0 aDementia and Alzheimers disease incidence in relationship to car c2005 Jul a1101-70 v533 aOBJECTIVES: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD).
DESIGN: Longitudinal cohort study.
SETTING: Four U.S. communities.
PARTICIPANTS: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded.
MEASUREMENTS: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders.
RESULTS: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4-4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease.
CONCLUSION: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.
10aAged10aAged, 80 and over10aAlzheimer Disease10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aDementia10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aPeripheral Vascular Diseases10aRisk Factors1 aNewman, Anne, B1 aFitzpatrick, Annette, L1 aLopez, Oscar1 aJackson, Sharon1 aLyketsos, Constantine1 aJagust, William1 aIves, Diane1 aDeKosky, Steven, T1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/85202989nas a2200517 4500008004100000022001400041245008400055210006900139260001600208300001200224490000700236520159200243653001601835653000901851653002201860653002201882653001201904653001001916653002801926653002201954653002401976653001902000653001602019653003402035653002302069653001102092653001102103653002302114653003102137653000902168653002902177653002902206653001702235653001602252100001602268700001602284700001702300700001702317700001802334700001602352700001302368700002102381700001902402700001502421856003502436 2005 eng d a1526-632X00aDeterminants of vascular dementia in the Cardiovascular Health Cognition Study.0 aDeterminants of vascular dementia in the Cardiovascular Health C c2005 May 10 a1548-520 v643 aOBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia.
METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
RESULTS: Approximately 44% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke.
CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.
10aAge Factors10aAged10aAged, 80 and over10aAlzheimer Disease10aAtrophy10aBrain10aCardiovascular Diseases10aCerebral Arteries10aCerebral Infarction10aCohort Studies10aComorbidity10aContinental Population Groups10aDementia, Vascular10aFemale10aHumans10aLateral Ventricles10aMagnetic Resonance Imaging10aMale10aNerve Fibers, Myelinated10aNeuropsychological Tests10aRisk Factors10aSex Factors1 aKuller, L H1 aLopez, O, L1 aJagust, W, J1 aBecker, J, T1 aDeKosky, S, T1 aLyketsos, C1 aKawas, C1 aBreitner, J, C S1 aFitzpatrick, A1 aDulberg, C uhttps://chs-nhlbi.org/node/83802819nas a2200409 4500008004100000022001400041245014000055210006900195260001300264300001100277490000800288520165500296653000901951653002801960653001901988653001502007653001102022653001802033653001102051653001402062653002002076653000902096653001502105653001502120653001702135653001602152653004702168653003102215100002002246700001602266700001602282700002102298700002102319700001702340700001702357856003502374 2005 eng d a0002-962900aFactors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study.0 aFactors associated with incidence and persistence of symptoms of c2005 Apr a163-720 v3293 aBACKGROUND: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well.
METHODS: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination 1 to 4 years later.
RESULTS: Annualized incidence and nonremission rates were the following: TFA (2.8% and 15.4%), FA (12.3% and 22.7%), and EDS (4.4% and 13.4%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining nonremission was much more limited.
CONCLUSIONS: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression.
10aAged10aCardiovascular Diseases10aCohort Studies10aDepression10aFemale10aHealth Status10aHumans10aIncidence10aLogistic Models10aMale10aOdds Ratio10aPrevalence10aRisk Factors10aSex Factors10aSleep Initiation and Maintenance Disorders10aSurveys and Questionnaires1 aQuan, Stuart, F1 aKatz, Ronit1 aOlson, Jean1 aBonekat, William1 aEnright, Paul, L1 aYoung, Terry1 aNewman, Anne uhttps://chs-nhlbi.org/node/83303506nas a2200517 4500008004100000022001400041245009400055210006900149260001600218300001000234490000800244520209500252653002102347653000902368653002202377653001202399653001902411653002502430653000902455653002502464653001102489653001402500653001102514653001102525653001402536653000902550653002602559653001602585653003202601653002002633653001202653653003202665653002102697653001102718653003102729653001802760653001802778100002502796700002002821700002402841700002102865700002102886700002202907700002402929856003502953 2005 eng d a0003-992600aFish consumption and stroke risk in elderly individuals: the cardiovascular health study.0 aFish consumption and stroke risk in elderly individuals the card c2005 Jan 24 a200-60 v1653 aBACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential.
METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained.
RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke.
CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.
10aAge Distribution10aAged10aAged, 80 and over10aAnimals10aCohort Studies10aConfidence Intervals10aDiet10aFatty Acids, Omega-310aFemale10aFish Oils10aFishes10aHumans10aIncidence10aMale10aMultivariate Analysis10aProbability10aProportional Hazards Models10aRisk Assessment10aSeafood10aSensitivity and Specificity10aSex Distribution10aStroke10aSurveys and Questionnaires10aSurvival Rate10aUnited States1 aMozaffarian, Dariush1 aLongstreth, W T1 aLemaitre, Rozenn, N1 aManolio, Teri, A1 aKuller, Lewis, H1 aBurke, Gregory, L1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/81802802nas a2200373 4500008004100000022001400041245005200055210005100107260001600158300001200174490000700186520187100193653000902064653001202073653001902085653001202104653000902116653001702125653002602142653001102168653001102179653001802190653001102208653001402219653000902233653001702242653001802259100002502277700002102302700002402323700002202347700002402369856003502393 2005 eng d a0735-109700aFish intake and risk of incident heart failure.0 aFish intake and risk of incident heart failure c2005 Jun 21 a2015-210 v453 aOBJECTIVES: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF).
BACKGROUND: The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown.
METHODS: Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated.
RESULTS: During 12 years' follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to 0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% CI = 0.52 to 0.91), and 32% lower risk with intake > or =5 times/week (HR = 0.68, 95% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37% lower risk in the highest quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest.
CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.
10aAged10aAnimals10aCohort Studies10aCooking10aDiet10aDiet Surveys10aDisease-Free Survival10aFemale10aFishes10aHeart Failure10aHumans10aIncidence10aMale10aRisk Factors10aUnited States1 aMozaffarian, Dariush1 aBryson, Chris, L1 aLemaitre, Rozenn, N1 aBurke, Gregory, L1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/84303245nas a2200397 4500008004100000022001400041245013100055210006900186260001300255300001100268490000700279520209400286653000902380653003502389653002702424653002802451653001102479653001702490653001102507653000902518653001602527653002602543653002102569653001402590653002002604653001502624653002602639100002002665700001502685700002502700700001902725700002402744700002002768700002402788856003502812 2005 eng d a0161-810500aHaptoglobin phenotype, sleep-disordered breathing, and the prevalence of cardiovascular disease: the Sleep Heart Health Study.0 aHaptoglobin phenotype sleepdisordered breathing and the prevalen c2005 Feb a207-130 v283 aBACKGROUND: Diabetes is an independent risk factor for cardiovascular disease, and there is growing evidence that sleep-disordered breathing also may increase the risk of cardiovascular disease. The mechanism responsible for increased susceptibility of people with diabetes to cardiovascular disease is thought to share several features with sleep-disordered breathing, notably increased oxidative stress. We recently demonstrated that a particular haptoglobin phenotype that is associated with differential antioxidant activity is an independent risk factor for cardiovascular disease in individuals with diabetes. We therefore sought to determine whether sleep-disordered breathing and cardiovascular disease are more strongly associated among people with the unfavorable haptoglobin phenotype.
METHODS: We tested this hypothesis in 2612 middle-aged and older participants from the Sleep Heart Health Study. Haptoglobin phenotyping was performed by gel electrophoresis. Respiratory disturbance index was assessed by standard methods. Logistic regression analysis was performed to estimate the association between haptoglobin phenotype and cardiovascular disease, adjusting for known cardiovascular risk factors (age, sex, diabetes, smoking, lipid levels, and hypertension). Possible modification by haptoglobin phenotype of the association of sleep-disordered breathing with cardiovascular disease prevalence was explored by examining interaction terms.
RESULTS: We found no significant association between haptoglobin phenotype and prevalent cardiovascular disease in this cohort, nor were significant interactions found between haptoglobin phenotype and sleep-disordered breathing on the prevalence of cardiovascular disease.
CONCLUSIONS: Sleep-disordered breathing did not appear to interact with haptoglobin phenotype in modifying the association with prevalent cardiovascular disease in the Sleep Heart Health Study. These findings could be due to the absence of association or to survivor bias in these cross-sectional analyses.
10aAged10aAngioplasty, Balloon, Coronary10aCoronary Artery Bypass10aCross-Sectional Studies10aFemale10aHaptoglobins10aHumans10aMale10aMiddle Aged10aMyocardial Infarction10aOxidative Stress10aPhenotype10aPolysomnography10aPrevalence10aSleep Apnea Syndromes1 aLevy, Andrew, P1 aZhang, Lin1 aMiller-Lotan, Rachel1 aRedline, Susan1 aO'Connor, George, T1 aQuan, Stuart, F1 aResnick, Helaine, E uhttps://chs-nhlbi.org/node/85702906nas a2200373 4500008004100000022001400041245013100055210006900186260001300255300001200268490000700280520184800287653000902135653002202144653001402166653001602180653002702196653001102223653002002234653001102254653000902265653001402274653001402288653002402302653004002326653001702366653001202383100002202395700001602417700002402433700001902457700002102476856003502497 2005 eng d a0002-861400aHospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival.0 aHospitalization for pneumonia in the Cardiovascular Health Study c2005 Jul a1108-160 v533 aOBJECTIVES: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality.
DESIGN: Prospective observational study.
SETTING: The Cardiovascular Health Study (CHS) in four U.S. communities.
PARTICIPANTS: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years.
MEASUREMENTS: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death.
RESULTS: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2-12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1-6.0) during the first year after hospitalization and 2.6 (95% CI=2.2-3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1-4.8) and 2.0 (95% CI=1.6-2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function.
CONCLUSION: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.
10aAged10aAged, 80 and over10aCognition10aComorbidity10aDiabetes Complications10aFemale10aHospitalization10aHumans10aMale10aMortality10aPneumonia10aProspective Studies10aRespiratory Physiological Phenomena10aRisk Factors10aSmoking1 aO'Meara, Ellen, S1 aWhite, Mark1 aSiscovick, David, S1 aLyles, Mary, F1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/85303094nas a2200397 4500008004100000022001400041245016600055210006900221260001300290300001000303490000700313520192700320653000902247653001002256653002802266653002402294653001102318653001102329653001402340653001802354653002502372653003102397653000902428653001702437653001102454100002002465700002102485700002502506700002102531700002102552700002202573700002202595700002302617700002102640856003502661 2005 eng d a1524-462800aIncidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.0 aIncidence manifestations and predictors of worsening white matte c2005 Jan a56-610 v363 aBACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.
METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.
RESULTS: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.
CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.
10aAged10aBrain10aCardiovascular Diseases10aCognition Disorders10aFemale10aHumans10aIncidence10aLeukoaraiosis10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRisk Factors10aStroke1 aLongstreth, W T1 aArnold, Alice, M1 aBeauchamp, Norman, J1 aManolio, Teri, A1 aLefkowitz, David1 aJungreis, Charles1 aHirsch, Calvin, H1 aO'Leary, Daniel, H1 aFurberg, Curt, D uhttps://chs-nhlbi.org/node/81202904nas a2200409 4500008004100000022001400041245009300055210006900148260001300217300001000230490000700240520174800247653002201995653002102017653000902038653002202047653002802069653004002097653001102137653002502148653001102173653001402184653002502198653000902223653002102232653001802253653001802271100002102289700002002310700002102330700002202351700002102373700002002394700002102414700002402435856003502459 2005 eng d a0002-861400aIncidence of cardiovascular disease in older Americans: the cardiovascular health study.0 aIncidence of cardiovascular disease in older Americans the cardi c2005 Feb a211-80 v533 aOBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans.
DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events.
SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS).
PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American).
MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD.
RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95% confidence interval (CI)=36.4-43.1) in men and 22.3 (95% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95% CI=13.0-16.6) and 13.7 (95% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9% with each year of age over 65 and was greater than 6% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians.
CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.
10aAfrican Americans10aAge Distribution10aAged10aAged, 80 and over10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aGeriatric Assessment10aHumans10aIncidence10aLongitudinal Studies10aMale10aSex Distribution10aSurvival Rate10aUnited States1 aArnold, Alice, M1 aPsaty, Bruce, M1 aKuller, Lewis, H1 aBurke, Gregory, L1 aManolio, Teri, A1 aFried, Linda, P1 aRobbins, John, A1 aKronmal, Richard, A uhttps://chs-nhlbi.org/node/82003317nas a2200553 4500008004100000022001400041245006700055210006600122260001300188300001200201490000700213520179100220653001602011653000902027653002202036653002802058653001902086653001902105653002502124653001502149653001502164653001402179653001102193653003102204653001102235653002802246653002602274653002502300653000902325653001602334653003202350653002002382653003002402653002202432653001802454100002002472700001602492700002002508700002402528700002302552700002502575700002902600700001602629700002302645700001902668700002102687700002002708856003502728 2005 eng d a1046-667300aKidney function as a predictor of noncardiovascular mortality.0 aKidney function as a predictor of noncardiovascular mortality c2005 Dec a3728-350 v163 aChronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.
10aAge Factors10aAged10aAged, 80 and over10aCardiovascular Diseases10aCause of Death10aCohort Studies10aConfidence Intervals10aCreatinine10aCystatin C10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aKidney Function Tests10aLongitudinal Studies10aMale10aProbability10aProportional Hazards Models10aRisk Assessment10aSeverity of Illness Index10aSurvival Analysis10aUnited States1 aFried, Linda, F1 aKatz, Ronit1 aSarnak, Mark, J1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aJenny, Nancy, Swords1 aStehman-Breen, Catherine1 aGillen, Dan1 aBleyer, Anthony, J1 aHirsch, Calvin1 aSiscovick, David1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/86502928nas a2200385 4500008004100000022001400041245015000055210006900205260000900274300001000283490000700293520182500300653000902125653002202134653001002156653001302166653002302179653002402202653001102226653001802237653001102255653004002266653003102306653001502337653003102352100001402383700001402397700001302411700002002424700001702444700001402461700001402475700001802489856003502507 2005 eng d a0251-535000aMorphometric analysis of gray matter volume in demented older adults: exploratory analysis of the cardiovascular health study brain MRI database.0 aMorphometric analysis of gray matter volume in demented older ad c2005 a221-90 v243 aWe tested the feasibility of a fully automated brain MRI voxel count technique--automated labeling pathway (ALP)--in a sample of 15 demented and 13 cognitively normal women (age 75-85 years) participating to the Cardiovascular Health Study (CHS). We hypothesized that ALP would replicate well-established findings of the anatomical correlates of dementia. In particular, we hypothesized that ALP volumetric measures would: (1) significantly differ between cognitively normal and demented women in those brain areas that are established markers for diagnosis of dementia (temporal and medial temporal lobes, hippocampus, amygdala and parahippocampus) but not in other brain areas (e.g., occipital lobe, visual cortex, motor cortex) and (2) correlate with visual ratings of brain disease which have been previously collected as part of the CHS. ALP required minimal operator intervention (input of brain images and verification of misalignments) and employed computer time of about 1 h per brain. ALP detected significant focal volumetric differences in the limbic system (p values between groups for hippocampus and parahippocampus: 0.002 and 0.005, respectively), temporal lobe (p < 0.0001) and caudate (p = 0.009), but not in other brain areas (e.g. occipital lobe, visual or motor cortex). Furthermore, ALP measures of medial temporal lobe atrophy strongly correlated with CHS visual ratings of ventricular enlargement (r(2) = 0.6, p = 0.002 for medial temporal lobe). In conclusion, ALP-detected focal brain atrophy was strongly associated with dementia. Because of its fully automated design, ALP technique is an ideal candidate to assess whether volumetric measures of specific areas can discriminate dementia better than currently available measures of global brain atrophy in large epidemiological studies.
10aAged10aAged, 80 and over10aBrain10aDementia10aEducational Status10aFeasibility Studies10aFemale10aHealth Status10aHumans10aImage Processing, Computer-Assisted10aMagnetic Resonance Imaging10aOrgan Size10aReproducibility of Results1 aRosano, C1 aBecker, J1 aLopez, O1 aLopez-Garcia, P1 aCarter, C, S1 aNewman, A1 aKuller, L1 aAizenstein, H uhttps://chs-nhlbi.org/node/83202544nas a2200397 4500008004100000022001400041245011400055210006900169260001600238300001100254490000800265520141500273653000901688653002201697653002201719653002201741653001301763653002301776653001101799653001301810653001101823653000901834653001901843653003201862653002401894653001701918653001801935100002601953700002001979700002101999700002002020700002002040700002202060700002902082856003502111 2005 eng d a0002-926200aPhysical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.0 aPhysical activity APOE genotype and dementia risk findings from c2005 Apr 01 a639-510 v1613 aPhysical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.
10aAged10aAged, 80 and over10aAlzheimer Disease10aApolipoproteins E10aDementia10aDementia, Vascular10aFemale10aGenotype10aHumans10aMale10aMotor Activity10aProportional Hazards Models10aProspective Studies10aRisk Factors10aUnited States1 aPodewils, Laura, Jean1 aGuallar, Eliseo1 aKuller, Lewis, H1 aFried, Linda, P1 aLopez, Oscar, L1 aCarlson, Michelle1 aLyketsos, Constantine, G uhttps://chs-nhlbi.org/node/82403006nas a2200337 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520204400243653001902287653002802306653001102334653001102345653001702356653000902373653001602382653002002398653003002418653003102448653003002479653002902509100001902538700001802557700001702575700002002592700002102612856003502633 2005 eng d a0161-810500aPolysomnographic predictors of blood pressure and hypertension: is one index best?0 aPolysomnographic predictors of blood pressure and hypertension i c2005 Sep a1122-300 v283 aSTUDY OBJECTIVES: Numerous indexes derived from polysomnography are available to characterize sleep-disordered breathing, with no consensus over which measures best predict clinical outcomes. This study addresses the relative merits of using alternative polysomnography indexes by characterizing the consistency and strength of the association of each index with blood pressure and hypertension.
DESIGN: Cross-sectional analyses of the association of alternative polysomnography indexes with blood pressure and hypertension were performed in construction and validation data sets. Linear and logistic regression models were used to identify the best variable sets.
PATIENTS: Data were obtained from 6433 men and women (age 62.9 +/- 11.0 years, 52.8% women) who participated in the Sleep Heart Health Study.
RESULTS: In multivariable models, most indexes showed weak linear associations with systolic, with slightly stronger associations for diastolic blood pressure, and the log odds of hypertension. No single index showed consistent superiority over others. Systolic blood pressure, diastolic blood pressure, and hypertension each were associated with distinct sets of polysomnography variables. Slightly more-consistent associations were demonstrated for indexes that included hypopneas that were linked with either a 3% or 4% desaturation level than indexes that did not require hypopneas to have linked desaturation. For indexes that combined apneas and hypopneas, there was no evidence that linking obstructive apneas to desaturation or arousal altered prediction compared with counting all apneas.
CONCLUSION: In summary, using a rigorous cross-validation assessment, we did not identify a clear superiority of any single index for blood pressure or hypertension prediction. Detailed analyses of alternative definitions of the respiratory disturbance index support current scoring guidelines, where desaturation criteria are recommended for hypopneas but not apneas.
10aBlood Pressure10aCross-Sectional Studies10aFemale10aHumans10aHypertension10aMale10aMiddle Aged10aPolysomnography10aPredictive Value of Tests10aReproducibility of Results10aSeverity of Illness Index10aSleep Apnea, Obstructive1 aRedline, Susan1 aMin, Nancy, I1 aShahar, Eyal1 aRapoport, David1 aO'Connor, George uhttps://chs-nhlbi.org/node/86703543nas a2200469 4500008004100000022001400041245012700055210006900182260001300251300001100264490000700275520219900282653002202481653000902503653001002512653001502522653002802537653001902565653001102584653002502595653001302620653001102633653000902644653002002653653001402673653003602687653002802723653001702751653002602768100002502794700001402819700002002833700002802853700002402881700002402905700001702929700003202946700002202978700002003000700001803020856003503038 2005 eng d a0002-929700aPopulation structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study.0 aPopulation structure admixture and agingrelated phenotypes in Af c2005 Mar a463-770 v763 aU.S. populations are genetically admixed, but surprisingly little empirical data exists documenting the impact of such heterogeneity on type I and type II error in genetic-association studies of unrelated individuals. By applying several complementary analytical techniques, we characterize genetic background heterogeneity among 810 self-identified African American subjects sampled as part of a multisite cohort study of cardiovascular disease in older adults. On the basis of the typing of 24 ancestry-informative biallelic single-nucleotide-polymorphism markers, there was evidence of substantial population substructure and admixture. We used an allele-sharing-based clustering algorithm to infer evidence for four genetically distinct subpopulations. Using multivariable regression models, we demonstrate the complex interplay of genetic and socioeconomic factors on quantitative phenotypes related to cardiovascular disease and aging. Blood glucose level correlated with individual African ancestry, whereas body mass index was associated more strongly with genetic similarity. Blood pressure, HDL cholesterol level, C-reactive protein level, and carotid wall thickness were not associated with genetic background. Blood pressure and HDL cholesterol level varied by geographic site, whereas C-reactive protein level differed by occupation. Both ancestry and genetic similarity predicted the number and quality of years lived during follow-up, but socioeconomic factors largely accounted for these associations. When the 24 genetic markers were tested individually, there were an excess number of marker-trait associations, most of which were attenuated by adjustment for genetic ancestry. We conclude that the genetic demography underlying older individuals who self identify as African American is complex, and that controlling for both genetic admixture and socioeconomic characteristics will be required in assessing genetic associations with chronic-disease-related traits in African Americans. Complementary methods that identify discrete subgroups on the basis of genetic similarity may help to further characterize the complex biodemographic structure of human populations.
10aAfrican Americans10aAged10aAging10aAlgorithms10aCardiovascular Diseases10aCohort Studies10aFemale10aGenetics, Population10aGenotype10aHumans10aMale10aModels, Genetic10aPhenotype10aPolymorphism, Single Nucleotide10aQuantitative Trait Loci10aRisk Factors10aSocioeconomic Factors1 aReiner, Alexander, P1 aZiv, Elad1 aLind, Denise, L1 aNievergelt, Caroline, M1 aSchork, Nicholas, J1 aCummings, Steven, R1 aPhong, Angie1 aBurchard, Esteban González1 aHarris, Tamara, B1 aPsaty, Bruce, M1 aKwok, Pui-Yan uhttps://chs-nhlbi.org/node/81703101nas a2200373 4500008004100000022001400041245007800055210006900133260001300202300001200215490000800227520208800235653000902323653002002332653002502352653001902377653002302396653001102419653002802430653001402458653001102472653000902483653001602492653002602508653002402534653001002558653003102568100001702599700002002616700002402636700001502660700001702675856003502692 2005 eng d a0012-369200aPredictors of heartburn during sleep in a large prospective cohort study.0 aPredictors of heartburn during sleep in a large prospective coho c2005 May a1658-660 v1273 aBACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study.
METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable
RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep.
CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.
10aAged10aBody Mass Index10aCarbonated Beverages10aCohort Studies10aEducational Status10aFemale10aGastroesophageal Reflux10aHeartburn10aHumans10aMale10aMiddle Aged10aMultivariate Analysis10aProspective Studies10aSleep10aSurveys and Questionnaires1 aFass, Ronnie1 aQuan, Stuart, F1 aO'Connor, George, T1 aErvin, Ann1 aIber, Conrad uhttps://chs-nhlbi.org/node/83902475nas a2200409 4500008004100000022001400041245011500055210006900170260001600239300001200255490000800267520135300275653003001628653001401658653001901672653001601691653001101707653002201718653001101740653001801751653000901769653001601778653001201794653001501806653002101821653002601842653001801868653001601886653001601902100002001918700001701938700002101955700001801976700001901994700001702013856003502030 2005 eng d a0003-992600aProgression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study.0 aProgression and regression of sleepdisordered breathing with cha c2005 Nov 14 a2408-130 v1653 aBACKGROUND: The relationship of weight changes to the incidence, progression, and remission of sleep-disordered breathing (SDB) is not well defined. This study aims to determine the relationship between change in weight and progression or remission of SDB by polysomnography.
METHODS: We performed a longitudinal cohort study of the cardiovascular consequences of sleep apnea in diverse US communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5 years apart.
RESULTS: A total of 2968 men and women (mean age, 62 years) participated in the study. Men were more likely to have an increase in Respiratory Disturbance Index (RDI) with a given increase in weight than were women, and this was not explained by differences in starting weight, waist circumference, age, or ethnicity. In a linear regression analysis, both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss. In a categorical analysis of larger degrees of change, this sex difference was also evident. Associations were similar in diverse ethnic groups. However, SDB progressed over time, even in those with stable weight.
CONCLUSION: Modest changes in weight were related to an increase or decrease in SDB, and this association was stronger in men than in women.
10aBody Weights and Measures10aCausality10aCohort Studies10aComorbidity10aFemale10aFollow-Up Studies10aHumans10aLinear Models10aMale10aMiddle Aged10aObesity10aOdds Ratio10aSex Distribution10aSleep Apnea Syndromes10aUnited States10aWeight Gain10aWeight Loss1 aNewman, Anne, B1 aFoster, Greg1 aGivelber, Rachel1 aNieto, Javier1 aRedline, Susan1 aYoung, Terry uhttps://chs-nhlbi.org/node/87103036nas a2200445 4500008004100000022001400041245013700055210006900192260001600261300001200277490000800289520180100297653001602098653000902114653001102123653001502134653001102149653002202160653001802182653001602200653001102216653000902227653001302236653002602249653001902275653001602294653001702310653002402327653001702351653003002368653001802398100001902416700001602435700001902451700002402470700002302494700002002517700001802537856003502555 2005 eng d a0003-992600aA prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study.0 aprospective study of anemia status hemoglobin concentration and c2005 Oct 24 a2214-200 v1653 aBACKGROUND: Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear.
METHODS: Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities.
RESULTS: A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95% CI, 1.25-1.62) and 1.24 (95% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95% CI, 1.15-1.54) and 1.17 (95% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95% CI, 1.38-1.78) and 1.38 (95% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations.
CONCLUSIONS: Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations.
10aAge Factors10aAged10aAnemia10aCalifornia10aFemale10aFollow-Up Studies10aHealth Status10aHemoglobins10aHumans10aMale10aMaryland10aMultivariate Analysis10aNorth Carolina10aObservation10aPennsylvania10aProspective Studies10aRisk Factors10aSeverity of Illness Index10aSurvival Rate1 aZakai, Neil, A1 aKatz, Ronit1 aHirsch, Calvin1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aNewman, Anne, B1 aCushman, Mary uhttps://chs-nhlbi.org/node/86403279nas a2200541 4500008004100000022001400041245008300055210006900138260001300207300001100220490000700231520176200238653002202000653000902022653001002031653002102041653001902062653002802081653001902109653001502128653002802143653001302171653002402184653004002208653001102248653001102259653003102270653001102301653002002312653002602332653000902358653001702367653002902384653002202413653001702435653002102452653001202473653003702485653001802522100002302540700002402563700002302587700002402610700002202634700002102656700002502677856003502702 2005 eng d a1523-683800aRenal duplex parameters, blood pressure, and renal function in elderly people.0 aRenal duplex parameters blood pressure and renal function in eld c2005 May a842-500 v453 aBACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans.
METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques.
RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine.
CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.
10aAfrican Americans10aAged10aAging10aArteriosclerosis10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aCreatinine10aCross-Sectional Studies10aDiastole10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension, Renovascular10aKidney10aKidney Diseases10aKidney Function Tests10aMale10aRenal Artery10aRenal Artery Obstruction10aRenal Circulation10aRisk Factors10aSampling Studies10aSystole10aUltrasonography, Doppler, Duplex10aUnited States1 aPearce, Jeffrey, D1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aEnglish, William, P1 aMondi, Matthew, M1 aReavis, Scott, W1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/83603313nas a2200493 4500008004100000022001400041245012000055210006900175260001600244300001100260490000800271520188900279653002102168653000902189653002202198653002502220653001902245653001602264653002102280653001102301653002502312653002502337653001102362653003102373653001402404653002602418653000902444653002602453653001602479653001402495653002402509653002002533653003002553653002102583653001802604653002902622653001802651100002402669700002302693700002202716700002102738700002502759856003502784 2005 eng d a0003-992600aRenovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.0 aRenovascular disease and the risk of adverse coronary events in c2005 Jan 24 a207-130 v1653 aBACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans.
METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization.
RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure.
CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.
10aAge Distribution10aAged10aAged, 80 and over10aAnalysis of Variance10aCohort Studies10aComorbidity10aCoronary Disease10aFemale10aGeriatric Assessment10aHeart Function Tests10aHumans10aHypertension, Renovascular10aIncidence10aKidney Function Tests10aMale10aMultivariate Analysis10aProbability10aPrognosis10aProspective Studies10aRisk Assessment10aSeverity of Illness Index10aSex Distribution10aSurvival Rate10aUltrasonography, Doppler10aUnited States1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aBurke, Gregory, L1 aDean, Richard, H1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/81902852nas a2200373 4500008004100000022001400041245012100055210006900176260001600245300001300261490000800274520178900282653000902071653002202080653001002102653002002112653002802132653001102160653001102171653000902182653003302191653002002224653001702244100002202261700001702283700002102300700002302321700002002344700002102364700002202385700001802407700001802425856003502443 2005 eng d a0003-992600aRisk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study.0 aRisk factors for declining anklebrachial index in men and women c2005 Sep 12 a1896-9020 v1653 aBACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population.
METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI.
RESULTS: The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89).
CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.
10aAged10aAged, 80 and over10aAnkle10aBrachial Artery10aCardiovascular Diseases10aFemale10aHumans10aMale10aPeripheral Vascular Diseases10aRisk Assessment10aRisk Factors1 aKennedy, Margaret1 aSolomon, Cam1 aManolio, Teri, A1 aCriqui, Michael, H1 aNewman, Anne, B1 aPolak, Joseph, F1 aBurke, Gregory, L1 aEnright, Paul1 aCushman, Mary uhttps://chs-nhlbi.org/node/85502830nas a2200409 4500008004100000022001400041245007900055210006900134260001300203300001000216490000700226520168600233653000901919653002001928653001901948653002801967653003801995653001102033653001102044653000902055653001602064653001102080653002002091653001502111653001702126653003002143653002602173653002802199653001702227653003102244100002202275700002202297700002402319700002402343700001802367856003502385 2005 eng d a0161-810500aSleepiness in patients with moderate to severe sleep-disordered breathing.0 aSleepiness in patients with moderate to severe sleepdisordered b c2005 Apr a472-70 v283 aBACKGROUND: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15).
DESIGN: Cross-sectional study.
SETTING: The Sleep Heart Health Study.
PARTICIPANTS: Sleep Heart Health Study participants (N = 6440).
MEASUREMENTS AND RESULTS: Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not.
CONCLUSIONS: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.
10aAged10aBody Mass Index10aCohort Studies10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHumans10aMale10aMiddle Aged10aOxygen10aPolysomnography10aPrevalence10aRisk Factors10aSeverity of Illness Index10aSleep Apnea Syndromes10aSleep Arousal Disorders10aSleep Stages10aSurveys and Questionnaires1 aKapur, Vishesh, K1 aBaldwin, Carol, M1 aResnick, Helaine, E1 aGottlieb, Daniel, J1 aNieto, Javier uhttps://chs-nhlbi.org/node/85803216nas a2200445 4500008004100000022001400041245012700055210006900182260001300251300001000264490000700274520189900281653000902180653002202189653001502211653002202226653001902248653003302267653002402300653001102324653001502335653001102350653000902361653002702370653002302397653004202420653001502462653003202477653003102509653002002540653001702560653003202577653001802609100002202627700002602649700001602675700002302691700002102714856003502735 2005 eng d a1045-387300aSometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses.0 aSometimes higher heart rate variability is not better heart rate c2005 Sep a954-90 v163 aOBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly.
METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality.
RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04).
CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.
10aAged10aAged, 80 and over10aAlgorithms10aArrhythmia, Sinus10aCohort Studies10aDiagnosis, Computer-Assisted10aElectrocardiography10aFemale10aHeart Rate10aHumans10aMale10aModels, Cardiovascular10aNonlinear Dynamics10aNumerical Analysis, Computer-Assisted10aPrevalence10aProportional Hazards Models10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSensitivity and Specificity10aUnited States1 aStein, Phyllis, K1 aDomitrovich, Peter, P1 aHui, Nelson1 aRautaharju, Pentti1 aGottdiener, John uhttps://chs-nhlbi.org/node/85903069nas a2200397 4500008004100000022001400041245008300055210006900138260001300207300001200220490000700232520193800239653000902177653002202186653002802208653001902236653001302255653001102268653001102279653005102290653002002341653000902361100001902370700002202389700002002411700002802431700002002459700002002479700002402499700002002523700002202543700002902565700002102594700002102615856003502636 2005 eng d a0003-994200aStatin use and the risk of incident dementia: the Cardiovascular Health Study.0 aStatin use and the risk of incident dementia the Cardiovascular c2005 Jul a1047-510 v623 aBACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia.
OBJECTIVE: To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs).
DESIGN: Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 participants free of dementia at baseline.
MAIN OUTCOME MEASURES: Using Cox proportional hazards regression analysis, we estimated the risk of incident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses included the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach.
RESULTS: Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia and 0.56 (95% CI, 0.35-0.92) for any Alzheimer disease.
CONCLUSIONS: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aDementia10aFemale10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aHyperlipidemias10aMale1 aRea, Thomas, D1 aBreitner, John, C1 aPsaty, Bruce, M1 aFitzpatrick, Annette, L1 aLopez, Oscar, L1 aNewman, Anne, B1 aHazzard, William, R1 aZandi, Peter, P1 aBurke, Gregory, L1 aLyketsos, Constantine, G1 aBernick, Charles1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/84603276nas a2200445 4500008004100000022001400041245008400055210006900139260001600208300001200224490000700236520205700243653000902300653002202309653001002331653002902341653001202370653001002382653001602392653002402408653001902432653001302451653001102464653001102475653005102486653002502537653000902562653002102571653002102592653002202613100001502635700001202650700001502662700001202677700001602689700001502705700001402720710006102734856003502795 2005 eng d a1526-632X00aStatins and cognitive function in the elderly: the Cardiovascular Health Study.0 aStatins and cognitive function in the elderly the Cardiovascular c2005 Nov 08 a1388-940 v653 aOBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults.
METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy.
RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups.
CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.
10aAged10aAged, 80 and over10aAging10aAnticholesteremic Agents10aAtrophy10aBrain10aCholesterol10aCognition Disorders10aCohort Studies10aDementia10aFemale10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aLongitudinal Studies10aMale10aMemory Disorders10aNootropic Agents10aTreatment Outcome1 aBernick, C1 aKatz, R1 aSmith, N L1 aRapp, S1 aBhadelia, R1 aCarlson, M1 aKuller, L1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/86903089nas a2200385 4500008004100000022001400041245013300055210006900188260001300257300001100270490000700281520198100288653003102269653000902300653002202309653001002331653001102341653002202352653000902374653001102383653001402394653003102408653000902439653003202448653002602480653001702506653001802523100002102541700002102562700001702583700002102600700002702621700002002648856003502668 2005 eng d a0002-861400aSubclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.0 aSubclinical brain magnetic resonance imaging abnormalities predi c2005 Apr a649-540 v533 aOBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance.
DESIGN: Longitudinal analysis, average follow-up time: 4.0 years.
SETTING: Cardiovascular Health Study (CHS).
PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4).
MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand).
RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed.
CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.
10aActivities of Daily Living10aAged10aAged, 80 and over10aBrain10aFemale10aFollow-Up Studies10aGait10aHumans10aIncidence10aMagnetic Resonance Imaging10aMale10aProportional Hazards Models10aPsychomotor Disorders10aRisk Factors10aUnited States1 aRosano, Caterina1 aKuller, Lewis, H1 aChung, Hyoju1 aArnold, Alice, M1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/83002297nas a2200361 4500008004100000022001400041245008200055210006900137260001600206300000900222490001200231520128500243653000901528653002201537653002201559653001001581653001601591653003201607653003201639653003001671653001101701653001701712653001101729653000901740653001601749653002401765100002801789700002101817700002001838700002201858700002001880856003501900 2005 eng d a0022-510X00aSurvival following dementia onset: Alzheimer's disease and vascular dementia.0 aSurvival following dementia onset Alzheimers disease and vascula c2005 Mar 15 a43-90 v229-2303 aSurvival following the onset of dementia has been reported to vary from 3 to over 9 years. We examined mortality in 3602 participants of the Cardiovascular Health (CHS) Cognition Study in four US communities evaluated for dementia incidence between 1992 and 1999 and followed for 6.5 years. By June 2000, 33 of 62 (53.2%) participants who developed vascular dementia (VaD) had died compared to 79 of 245 (32.2%) with Alzheimer's disease (AD), 66 of 151 (43.7%) with both AD and VaD, and 429 of 2318 (18.5%) with normal cognition. Using Cox proportional hazards regression with a time-dependent covariate for dementia status adjusted for age, gender and race, individuals with VaD were more than four times as likely to die during follow-up than those with normal cognition (HR: 4.4, 95% CI: 3.1-6.3). The hazard ratios were 2.1 (95% CI: 1.6-2.7) for AD and 2.5 (95% CI: 1.9-3.3) for both types. Adjusted accelerated life models estimated median survival from dementia onset to death as 3.9 years for those with VaD, 7.1 years for AD, 5.4 years for mixed dementia, and 11.0 years for matched controls with normal cognition. While persons with VaD died primarily from cerebrovascular disease, those with AD/mixed dementia died more frequently from dementia/failure to thrive.
10aAged10aAged, 80 and over10aAlzheimer Disease10aBrain10aCapillaries10aCerebral Amyloid Angiopathy10aCerebrovascular Circulation10aCerebrovascular Disorders10aFemale10aFrontal Lobe10aHumans10aMale10aMiddle Aged10aProspective Studies1 aFitzpatrick, Annette, L1 aKuller, Lewis, H1 aLopez, Oscar, L1 aKawas, Claudia, H1 aJagust, William uhttps://chs-nhlbi.org/node/82303211nas a2200505 4500008004100000022001400041245009700055210006900152260001600221300001100237490000700248520187300255653001602128653000902144653002202153653001002175653001902185653002802204653001902232653001902251653001602270653002802286653002102314653001102335653001102346653002002357653001702377653002502394653000902419653001402428653002402442653001502466653001602481653001102497653002202508100001702530700002102547700002002568700001702588700001802605700001702623700001502640700001502655856003502670 2005 eng d a1526-632X00aVascular events, mortality, and preventive therapy following ischemic stroke in the elderly.0 aVascular events mortality and preventive therapy following ische c2005 Sep 27 a835-420 v653 aBACKGROUND: The authors studied mortality, vascular events, and preventive therapies following ischemic stroke among adults aged > or =65 years.
METHODS: The authors identified 546 subjects with first ischemic stroke during 1989 to 2001 among Cardiovascular Health Study participants. Deaths, recurrent strokes, and coronary heart disease (CHD) events were identified over 3.2 years (median) follow-up.
RESULTS: During the first year of follow-up, rates were 105.4/1,000 for recurrent stroke and 59.3/1,000 for CHD. After the first year, the stroke rate was 52.0/1,000 and the CHD rate was 46.5/1,000. Cardioembolic strokes had the highest mortality (185.4/1,000) and recurrence rates (86.6/1,000). Lacunar strokes had the lowest mortality (119.3/1,000) and recurrence rates (43.0/1,000). Age and male sex predicted death and CHD, but not recurrence. Outcomes did not differ by race. Following stroke, 47.8% used aspirin and 13.5% used other antiplatelet agents; 52.6% of patients with atrial fibrillation used warfarin; 31.3% of hyperlipidemic subjects, 57.0% of diabetic patients, and 81.5% of hypertensive patients were drug-treated; and 40.0% of hypertensive patients had blood pressure (BP) <140/90 mm Hg. Older subjects were less likely to use lipid-lowering therapy, women were less likely to have BP <140/90 mm Hg, and low-income subjects were less likely to use diabetes medications.
CONCLUSIONS: Recurrent strokes were nearly twice as frequent as coronary heart disease (CHD) events during the first year after initial stroke, but stroke and CHD rates were similar after the first year. Preventive drug therapies were underused, which may reflect clinical uncertainty due to the lack of clinical trials among the elderly. Utilization was lower among the oldest patients, women, and low-income individuals.
10aAge Factors10aAged10aAged, 80 and over10aAging10aAnticoagulants10aAntihypertensive Agents10aBrain Ischemia10aCohort Studies10aComorbidity10aCoronary Artery Disease10aDrug Utilization10aFemale10aHumans10aHyperlipidemias10aHypertension10aHypolipidemic Agents10aMale10aMortality10aProspective Studies10aRecurrence10aSex Factors10aStroke10aTreatment Outcome1 aKaplan, R, C1 aTirschwell, D, L1 aLongstreth, W T1 aManolio, T A1 aHeckbert, S R1 aLefkowitz, D1 aEl-Saed, A1 aPsaty, B M uhttps://chs-nhlbi.org/node/86002874nas a2200409 4500008004100000022001400041245014200055210006900197260001300266300001400279490000700293520165500300653000901955653002201964653004501986653001102031653001802042653001802060653001102078653001702089653000902106653002602115653003602141653002402177653002402201653001802225653001602243100002602259700002302285700002302308700001902331700001902350700002102369700001902390700002002409856003502429 2005 eng d a0002-861400aWeight loss, muscle strength, and angiotensin-converting enzyme inhibitors in older adults with congestive heart failure or hypertension.0 aWeight loss muscle strength and angiotensinconverting enzyme inh c2005 Nov a1996-20000 v533 aOBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor use may be associated with weight maintenance and sustained muscle strength (measured by grip strength) in older adults.
DESIGN: Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used.
SETTING: Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001.
PARTICIPANTS: CHS participants with congestive heart failure (CHF) or treated hypertension.
MEASUREMENTS: The exposure, current ACE inhibitor use, was ascertained by medication inventory at annual clinic visits; the outcomes were weight change and grip-strength change during the following year. Multivariate linear regression was used, accounting for correlations between observations on the same participant over time.
RESULTS: The average annual weight change was -0.38 kg in 2,834 participants (14,443 person-years) with treated hypertension and -0.62 kg in 342 participants (980 person-years) with CHF. ACE inhibitor use was associated with less annual weight loss after adjustment for potential confounders: a difference of 0.17 kg (95% confidence interval (CI)=0.05-0.29) in those with treated hypertension and 0.29 kg (95% CI=-0.25-0.83) in those with CHF. There was no evidence of association between ACE inhibitor use and grip-strength change.
CONCLUSION: ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.
10aAged10aAged, 80 and over10aAngiotensin-Converting Enzyme Inhibitors10aFemale10aHand Strength10aHeart Failure10aHumans10aHypertension10aMale10aMultivariate Analysis10aOutcome Assessment, Health Care10aProspective Studies10aStatistics as Topic10aUnited States10aWeight Loss1 aSchellenbaum, Gina, D1 aSmith, Nicholas, L1 aHeckbert, Susan, R1 aLumley, Thomas1 aRea, Thomas, D1 aFurberg, Curt, D1 aLyles, Mary, F1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/86803299nas a2200481 4500008004100000022001400041245013100055210006900186260001600255300000900271490000800280520187800288653003902166653000902205653002802214653002802242653001602270653002102286653002102307653004002328653001102368653002202379653001102401653001402412653000902426653002602435653001502461653003202476653002402508653001702532653002102549653001802570100002102588700002102609700002002630700002102650700002302671700002202694700002202716700002102738700002302759856003502782 2006 eng d a0003-992600a10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study.0 a10year followup of subclinical cardiovascular disease and risk o c2006 Jan 09 a71-80 v1663 aBACKGROUND: The incidence of coronary heart disease (CHD) is very high among individuals 65 years or older.
METHODS: We evaluated the relationships between measurements of subclinical disease at baseline (1989-1990) and at the third-year follow-up examination (1992-1993) and subsequent incidence of cardiovascular disease and total mortality as of June 2001. Approximately 61% of the participants without clinical cardiovascular disease at baseline had subclinical disease based on our previously described criteria from the Cardiovascular Health Study.
RESULTS: The incidence of CHD was substantially increased for participants with subclinical disease compared with those who had no subclinical disease: 30.5 per 1000 person-years with and 16.3 per 1000 person-years without for white individuals, and 31.2 per 1000 person-years with and 12.5 per 1000 person-years without for black individuals. The risk persisted over the entire follow-up period. Incidence rates were higher for men than for women with or without subclinical disease, but there was little difference in rates for black individuals and white individuals.
CONCLUSIONS: In multivariable models, subclinical disease at baseline remained a significant predictor of CHD in both men and women; the hazard ratios (95% confidence intervals) of their relative risks were 1.64 (1.30-2.06) and 1.49 (1.21-1.84), respectively. The presence of subclinical disease substantially increased the risk of subsequent CHD for participants with hypertension, diabetes mellitus, or elevated C-reactive protein. In summary, subclinical disease is very prevalent among older individuals, is independently associated with risk of CHD even over a 10-year follow-up period, and substantially increases the risk of CHD among participants with hypertension or diabetes mellitus.
10aAfrican Continental Ancestry Group10aAged10aBlood Chemical Analysis10aCardiovascular Diseases10aComorbidity10aCoronary Disease10aEchocardiography10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMultivariate Analysis10aPrevalence10aProportional Hazards Models10aRegression Analysis10aRisk Factors10aSex Distribution10aUnited States1 aKuller, Lewis, H1 aArnold, Alice, M1 aPsaty, Bruce, M1 aRobbins, John, A1 aO'Leary, Daniel, H1 aTracy, Russell, P1 aBurke, Gregory, L1 aManolio, Teri, A1 aChaves, Paolo, H M uhttps://chs-nhlbi.org/node/87802707nas a2200337 4500008004100000022001400041245008100055210006900136260001300205300001200218490000700230520179100237653000902028653001902037653001102056653001802067653001902085653001802104653001102122653000902133653001402142653003302156653003202189653002102221653001702242653001802259100002102277700001902298700001702317856003502334 2006 eng d a0002-861400aAdjusted mortality after hip fracture: From the cardiovascular health study.0 aAdjusted mortality after hip fracture From the cardiovascular he c2006 Dec a1885-910 v543 aOBJECTIVES: To estimate the risk of death associated with hip fracture (HFx), stratifying by sex and time since fracture.
DESIGN: Prospective cohort study compared participants with and without hip fracture, matched on sex, age, race, recruitment period, and time since enrollment.
SETTING: The Cardiovascular Health Study, a more-than-15-year longitudinal study of 5,888 older individuals from four U.S. sites.
PARTICIPANTS: Three hundred seventy-nine individuals with HFx were compared with 1,134 without HFx.
MEASUREMENTS: Extended Cox models were used to estimate mortality hazard ratios (HRs) for different periods after fracture, adjusting for prefracture health.
RESULTS: Age- and race-adjusted excess mortality was 9% in women and 24% in men 1 year after fracture, and 24% in women and 26% men 5 years postfracture. Multivariable-adjusted HRs of mortality associated with HFx in women were 7.1 (95% confidence interval (CI) = 2.3-21.5), 2.1 (95% CI = 1.0-4.1), 1.4 (95% CI = 1.1-2.0), and 1.0 (95% CI = 0.6-1.5) for 0 to 1 months, 2 to 6 months, 7 months to 4 years, and 5 to 8 years, respectively, after index date. In men, respective HRs for the same time periods were 39.9 (95% CI = 5.2-308.7), 3.8 (95% CI = 1.4-10.3), 1.1 (95% CI = 0.7-1.8), and 1.0 (95% CI = 0.3-2.7). HRs adjusted for age and race were 20% to 40% higher.
CONCLUSION: The risk of mortality was highest in the first 6 months after HFx. In men, the risk of death approximated that of men without HFx after 6 months; in women, a moderately greater risk persisted through the fourth year. Although the mortality pattern was different in women and men, excess mortality 5 years postfracture was similar for both sexes.
10aAged10aCohort Studies10aFemale10aHealth Status10aHealth Surveys10aHip Fractures10aHumans10aMale10aMortality10aMulticenter Studies as Topic10aProportional Hazards Models10aSex Distribution10aTime Factors10aUnited States1 aRobbins, John, A1 aBiggs, Mary, L1 aCauley, Jane uhttps://chs-nhlbi.org/node/93403443nas a2200421 4500008004100000022001400041245012400055210006900179260001300248300001100261490000700272520226300279653002202542653000902564653001502573653002802588653001502616653001402631653002402645653001102669653003102680653001102711653002002722653001802742653002502760653000902785653001702794100002302811700001402834700001602848700001702864700003202881700001702913700001802930700001702948700002102965856003502986 2006 eng d a1046-667300aAfrican ancestry, socioeconomic status, and kidney function in elderly African Americans: a genetic admixture analysis.0 aAfrican ancestry socioeconomic status and kidney function in eld c2006 Dec a3491-60 v173 aKidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged >65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine > or =0.05 mg/dl per yr (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.06) or with change in eGFR > or =3 ml/min per 1.73 m(2) per yr (OR 1.02; 95% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95% CI 2.54 to 4.06). Among self-identified African Americans, low income (< US dollars 8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C >1.29 g/dl (adjusted OR 2.7; 95% CI 1.0 to 7.5) or by eGFR <60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95% CI 1.1 to 9.4) compared with those with incomes >US dollars 35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors.
10aAfrican Americans10aAged10aCreatinine10aCross-Sectional Studies10aCystatin C10aCystatins10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLinear Models10aLongitudinal Studies10aMale10aSocial Class1 aPeralta, Carmen, A1 aZiv, Elad1 aKatz, Ronit1 aReiner, Alex1 aBurchard, Esteban González1 aFried, Linda1 aKwok, Pui-Yan1 aPsaty, Bruce1 aShlipak, Michael uhttps://chs-nhlbi.org/node/92703137nas a2200457 4500008004100000022001400041245010900055210006900164260001300233300000900246490000700255520188900262653000902151653002102160653002202181653000902203653001902212653002102231653001102252653001302263653002002276653001102296653001402307653000902321653003002330653002002360653002602380653001802406653000902424100002402433700001702457700002002474700002102494700002002515700002502535700002202560700001802582700002002600700002402620856003502644 2006 eng d a0002-861400aAlcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study.0 aAlcohol consumption and risk of coronary heart disease in older c2006 Jan a30-70 v543 aOBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome.
DESIGN: Prospective cohort study.
SETTING: Four U.S. communities.
PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline.
MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly.
RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76 (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele.
CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.
10aAged10aAlcohol Drinking10aApolipoproteins E10aBeer10aCohort Studies10aCoronary Disease10aFemale10aGenotype10aHealth Behavior10aHumans10aIncidence10aMale10aResidence Characteristics10aRisk Assessment10aSocioeconomic Factors10aUnited States10aWine1 aMukamal, Kenneth, J1 aChung, Hyoju1 aJenny, Nancy, S1 aKuller, Lewis, H1 aLongstreth, W T1 aMittleman, Murray, A1 aBurke, Gregory, L1 aCushman, Mary1 aPsaty, Bruce, M1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/88101665nas a2200361 4500008004100000022001400041245006000055210005900115260001600174300001000190490000700200520069800207653000900905653002100914653002800935653001100963653002400974653002000998653001101018653002501029653000901054653001301063653001801076100002401094700001901118700002401137700001901161700002501180700002101205700001801226700002401244856003501268 2006 eng d a0195-863100aAlcohol consumption in older adults and Medicare costs.0 aAlcohol consumption in older adults and Medicare costs c2006 Spring a49-610 v273 aWe determined the relationship of alcohol consumption and Medicare costs among 4,392 participants in the Cardiovascular Health Study (CHS), a longitudinal, population-based cohort study of adults age 65 or over in four U.S. communities. We assessed 5-year Parts A and B costs and self-reported intake of beer, wine, and liquor at baseline. Among both sexes, total costs were approximately $2,000 lower among consumers of > 1-6 drinks per week than abstainers. The lower costs associated with moderate drinking were most apparent among participants with cardiovascular disease (CVD) and for hospitalization costs for CVD among healthy participants. Former drinkers had the highest costs.
10aAged10aAlcohol Drinking10aCardiovascular Diseases10aFemale10aHealth Expenditures10aHospitalization10aHumans10aLongitudinal Studies10aMale10aMedicare10aUnited States1 aMukamal, Kenneth, J1 aLumley, Thomas1 aLuepker, Russell, V1 aLapin, Pauline1 aMittleman, Murray, A1 aMcBean, Marshall1 aCrum, Rosa, M1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/94102707nas a2200385 4500008004100000022001400041245010400055210006900159260001600228300001100244490000700255520160700262653000901869653002101878653002801899653001601927653001101943653001801954653001101972653001501983653000901998653003302007653002602040653003202066653001702098653001202115100002102127700002402148700002502172700002002197700002202217700002302239700002402262856003502286 2006 eng d a1558-359700aThe association of alcohol consumption and incident heart failure: the Cardiovascular Health Study.0 aassociation of alcohol consumption and incident heart failure th c2006 Jul 18 a305-110 v483 aOBJECTIVES: We investigated the association between alcohol consumption and incident congestive heart failure (CHF) both overall and after adjusting for incident myocardial infarction (MI).
BACKGROUND: Moderate alcohol consumption has been associated with lower risk of CHF and MI.
METHODS: The Cardiovascular Health study, a prospective cohort study of cardiovascular disease risk factors and outcomes, followed 5,888 subjects > or =65 years old for 7 to 10 years. Cox models were used to estimate the adjusted risk of CHF by reported alcohol consumption.
RESULTS: There were 5,595 subjects at baseline at risk for incident CHF with alcohol data and 1,056 events during follow-up. Compared with abstainers, the adjusted risk of CHF was lower among subjects who reported consuming 1 to 6 drinks per week (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67 to 1.00, p = 0.05) and 7 to 13 drinks per week (HR 0.66, 95% CI 0.47 to 0.91, p = 0.01). Time-dependent adjustment for incident MI altered only slightly the association between moderate alcohol consumption and CHF (for 1 to 6 drinks per week, HR 0.84, 95% CI 0.65 to 1.04; for 7 to 13 drinks per week, HR 0.69, 95% CI 0.49 to 0.99). Baseline former drinkers had a higher risk of CHF than abstainers (HR 1.51, p < 0.01), but those who quit during the study did not have a higher risk (HR 0.83, 95% CI 0.66 to 1.03).
CONCLUSIONS: Moderate alcohol use is associated with a lower risk of incident CHF among older adults, even after accounting for incident MI and other factors.
10aAged10aAlcohol Drinking10aChi-Square Distribution10aComorbidity10aFemale10aHeart Failure10aHumans10aLife Style10aMale10aMulticenter Studies as Topic10aMyocardial Infarction10aProportional Hazards Models10aRisk Factors10aSmoking1 aBryson, Chris, L1 aMukamal, Kenneth, J1 aMittleman, Murray, A1 aFried, Linda, P1 aHirsch, Calvin, H1 aKitzman, Dalane, W1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/90502437nas a2200373 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520142900271653000901700653001501709653002301724653002801747653001601775653001101791653001501802653001101817653001701828653001801845653002001863653000901883653001901892653001601911653001601927100001901943700001601962700001801978700001501996700001702011856003502028 2006 eng d a0307-056500aThe association of markers of inflammation with weight change in older adults: the Cardiovascular Health Study.0 aassociation of markers of inflammation with weight change in old c2006 Sep a1362-70 v303 aOBJECTIVE: Elevated levels of inflammation factors often precede weight loss and may be causally related to it. Newer studies suggest that elevated levels of inflammation factors also precede weight gain. In this study, we examined whether inflammation factors are elevated in individuals, age >or=65 years, who lost or gained >5% weight over a 3 year follow-up period compared to those with stable weight.
SUBJECTS: In total, 3254 participants in the Cardiovascular Health Study whose weight was stable; 661 who gained >5% weight; and 842 who lost >5% weight.
MEASUREMENTS: C-reactive protein (CRP), fibrinogen, factor VIIIc, white blood cell (WBC) and platelet counts, and interleukin-6 (IL-6) levels.
RESULTS: As compared to participants whose weight was stable, those who lost >5% weight had higher baseline CRP concentration (1.05 (95% CI, 1.02, 1.08) per interquartile increase) and WBC count (1.10 (1.01, 1.19) per interquartile increase) on adjusted analyses. Those who gained >5% weight had higher baseline CRP (1.05 (1.01, 1.08)), fibrinogen (1.13 (1.01, 1.27)), and factor VIIIc (1.15 (1.03, 1.30)).
CONCLUSIONS: Inflammation factors are associated with weight gain and weight loss in older individuals. These findings suggest that subclinical inflammation, or unknown factors associated with subclinical inflammation, contribute to weight change.
10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aFactor VIII10aFemale10aFibrinogen10aHumans10aInflammation10aInterleukin-610aLeukocyte Count10aMale10aPlatelet Count10aWeight Gain10aWeight Loss1 aBarzilay, J, I1 aForsberg, C1 aHeckbert, S R1 aCushman, M1 aNewman, A, B uhttps://chs-nhlbi.org/node/89203064nas a2200433 4500008004100000022001400041245015800055210006900213260001300282300001000295490000800305520182700313653000902140653002202149653001602171653002002187653002802207653002102235653002202256653001102278653001102289653001702300653000902317653003302326653001502359653001702374653001102391653001802402100001602420700002402436700001702460700002102477700002002498700001802518700001802536700002302554700001802577856003502595 2006 eng d a0021-915000aThe association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study.0 aassociation of microalbuminuria with clinical cardiovascular dis c2006 Aug a372-70 v1873 aPURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events.
METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass.
RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]).
CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.
10aAged10aAged, 80 and over10aAlbuminuria10aAtherosclerosis10aCardiovascular Diseases10aCoronary Disease10aDiabetes Mellitus10aFemale10aHumans10aHypertension10aMale10aPeripheral Vascular Diseases10aPrevalence10aRisk Factors10aStroke10aUnited States1 aCao, Jie, J1 aBarzilay, Joshua, I1 aPeterson, Do1 aManolio, Teri, A1 aPsaty, Bruce, M1 aKuller, Lewis1 aWexler, Jason1 aBleyer, Anthony, J1 aCushman, Mary uhttps://chs-nhlbi.org/node/86303356nas a2200457 4500008004100000022001400041245010400055210006900159260001600228300001000244490000800254520207400262653000902336653002202345653002502367653002102392653002402413653001102437653002202448653001102470653000902481653001602490653001502506653002002521653001502541653002602556653001702582653003002599653001002629653002902639100001702668700002402685700001702709700002402726700001902750700002102769700002502790700001902815710002902834856003502863 2006 eng d a1073-449X00aAssociation of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study.0 aAssociation of nocturnal arrhythmias with sleepdisordered breath c2006 Apr 15 a910-60 v1733 aRATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development.
OBJECTIVE: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing.
METHODS: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5).
RESULTS: Atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome.
CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.
10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aCircadian Rhythm10aElectrocardiography10aFemale10aFollow-Up Studies10aHumans10aMale10aMiddle Aged10aOdds Ratio10aPolysomnography10aPrevalence10aRetrospective Studies10aRisk Factors10aSeverity of Illness Index10aSleep10aSleep Apnea, Obstructive1 aMehra, Reena1 aBenjamin, Emelia, J1 aShahar, Eyal1 aGottlieb, Daniel, J1 aNawabit, Rawan1 aKirchner, Lester1 aSahadevan, Jayakumar1 aRedline, Susan1 aSleep Heart Health Study uhttps://chs-nhlbi.org/node/88203674nas a2200505 4500008004100000022001400041245011900055210006900174260001600243300001200259490000800271520220500279653003902484653000902523653002302532653002802555653002102583653004002604653001102644653001302655653001102668653000902679653002602688653003602714653003202750653000902782653001102791653001802802100002102820700002802841700002302869700002002892700002002912700001702932700001802949700001902967700001802986700001503004700002103019700002603040700002003066700002203086700002503108856003503133 2006 eng d a1538-359800aAssociation of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events.0 aAssociation of polymorphisms in the CRP gene with circulating Cr c2006 Dec 13 a2703-110 v2963 aCONTEXT: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD).
OBJECTIVE: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events.
DESIGN, SETTING, AND PARTICIPANTS: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003).
MAIN OUTCOME MEASURES: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up.
RESULTS: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality.
CONCLUSIONS: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.
10aAfrican Continental Ancestry Group10aAged10aC-Reactive Protein10aCardiovascular Diseases10aCarotid Arteries10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHumans10aMale10aMyocardial Infarction10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aRisk10aStroke10aTunica Intima1 aLange, Leslie, A1 aCarlson, Christopher, S1 aHindorff, Lucia, A1 aLange, Ethan, M1 aWalston, Jeremy1 aDurda, Peter1 aCushman, Mary1 aBis, Joshua, C1 aZeng, Donglin1 aLin, Danyu1 aKuller, Lewis, H1 aNickerson, Deborah, A1 aPsaty, Bruce, M1 aTracy, Russell, P1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/93202615nas a2200445 4500008004100000022001400041245007500055210006900130260001300199300001100212490000700223520139000230653002201620653000901642653001301651653002801664653001901692653002801711653004001739653001101779653001801790653001801808653001101826653000901837653001601846653001901862653001501881653001801896653001601914100001901930700002501949700001701974700001601991700002002007700002102027700001902048700002002067710004702087856003502134 2006 eng d a1047-279700aThe association of race with frailty: the cardiovascular health study.0 aassociation of race with frailty the cardiovascular health study c2006 Jul a545-530 v163 aPURPOSE: Frailty, which has been conceptualized as a state of decreased physiologic reserve contributing to functional decline, has a prevalence among older African Americans that is twice that in older whites. This study assesses the independent contribution of race to frailty.
METHODS: We evaluated 786 African-American and 4491 white participants of the Cardiovascular Health Study (CHS). Frailty is defined as meeting three or more of five criteria derived from CHS measures: lowest quintile for grip strength, self-reported exhaustion, unintentional weight loss of 10 lbs or greater in 1 year, slowest quintile for gait speed, and lowest quintile for physical activity. Controlling for age, sex, comorbidity, socioeconomic factors, and race, multinomial logistic regression estimated the odds ratio (OR) of prefrail (one or two criteria) to not frail and frail to not frail.
RESULTS: Among African Americans, 8.7% of men and 15.0% of women were frail compared with 4.6% and 6.8% of white men and women, respectively. In adjusted models, nonobese African Americans had a fourfold greater odds of frailty compared with whites. The increased OR of frailty associated with African-American race was less pronounced among those who were obese or disabled.
CONCLUSION: African-American race is associated independently with frailty.
10aAfrican Americans10aAged10aAsthenia10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aEuropean Continental Ancestry Group10aFemale10aFrail Elderly10aHealth Status10aHumans10aMale10aMiddle Aged10aMotor Activity10aOdds Ratio10aUnited States10aWeight Loss1 aHirsch, Calvin1 aAnderson, Melissa, L1 aNewman, Anne1 aKop, Willem1 aJackson, Sharon1 aGottdiener, John1 aTracy, Russell1 aFried, Linda, P1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/87703456nas a2200445 4500008004100000022001400041245008900055210006900144260001300213300001200226490000700238520224900245653001002494653000902504653002202513653002002535653001902555653001602574653002802590653001102618653001902629653001102648653001702659653000902676653001602685653001502701653002402716653001002740653002902750653002202779653002402801100002402825700001902849700001802868700002202886700002002908700002402928700002302952856003502975 2006 eng d a0161-810500aAssociation of usual sleep duration with hypertension: the Sleep Heart Health Study.0 aAssociation of usual sleep duration with hypertension the Sleep c2006 Aug a1009-140 v293 aSTUDY OBJECTIVES: Limited experimental data suggest that sleep restriction acutely elevates blood pressure; however, little is known about the relationship between usual sleep duration and hypertension. This study assesses the relationship between usual sleep duration and hypertension in a community-based cohort.
DESIGN: Cross-sectional observational study.
SETTING: The Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing.
PARTICIPANTS: Two thousand eight hundred thirteen men and 3097 women, aged 40 to 100 years.
INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: Usual weekday and weekend sleep durations were obtained by questionnaire, and their weighted average were categorized as less than 6, 6 to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication to treat hypertension. The relationship between sleep duration and hypertension was examined using categorical logistic regression with adjustment for age, sex, race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7 to less than 8 hours per night, those sleeping less than 6 and between 6 and 7 hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping between 8 and 9 and 9 or more hours per night had adjusted odds ratios for hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p < .0001 for association of sleep duration with hypertension). These associations persisted when analyses were further adjusted for caffeine and alcohol consumption, current smoking, insomnia symptoms, depression symptoms, sleep efficiency, and prevalent diabetes mellitus or cardiovascular disease.
CONCLUSIONS: Usual sleep duration above or below the median of 7 to less than 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night.
10aAdult10aAged10aAged, 80 and over10aBody Mass Index10aCohort Studies10aComorbidity10aCross-Sectional Studies10aFemale10aHealth Surveys10aHumans10aHypertension10aMale10aMiddle Aged10aOdds Ratio10aProspective Studies10aSleep10aSleep Apnea, Obstructive10aSleep Deprivation10aStatistics as Topic1 aGottlieb, Daniel, J1 aRedline, Susan1 aNieto, Javier1 aBaldwin, Carol, M1 aNewman, Anne, B1 aResnick, Helaine, E1 aPunjabi, Naresh, M uhttps://chs-nhlbi.org/node/91503303nas a2200505 4500008004100000022001400041245008100055210006900136260001600205300001100221490000800232520183100240653003902071653000902110653002502119653002702144653004002171653001102211653001902222653003802241653002202279653001402301653001502315653001502330653001102345653000902356653003602365653003402401653003102435100002202466700002402488700001802512700002002530700002202550700002302572700002402595700001902619700001702638700001902655700002202674700002102696700002202717700002302739856003502762 2006 eng d a1524-453900aBeta2-adrenergic receptor genetic variants and risk of sudden cardiac death.0 aBeta2adrenergic receptor genetic variants and risk of sudden car c2006 Apr 18 a1842-80 v1133 aBACKGROUND: Sympathetic activation influences the risk of ventricular arrhythmias and sudden cardiac death (SCD), mediated in part by the beta2-adrenergic receptor (B2AR). We investigated whether variation in the B2AR gene is associated with SCD risk.
METHODS AND RESULTS: In this study, 4441 white and 808 black Cardiovascular Health Study (CHS) participants were followed up prospectively for SCD and genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated in 155 case and 144 control white subjects in a population-based case-control study of SCD, the Cardiac Arrest Blood Study (CABS). In CHS, Gly16 and Gln27 allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events occurred in white and black participants, respectively. The Gln27Glu variant was associated with SCD risk (P=0.008 for general model). SCD risk was higher in Gln27 homozygous participants than in Glu27 carriers (ethnicity-adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P=0.003). The increased risk did not differ significantly between white (HR, 1.62; 95% CI, 1.18 to 2.23) and black (HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the confidence interval was wide in blacks. In the CABS replication study, Gln27 homozygous participants similarly had higher SCD risk than Glu27 carriers (odds ratio, 1.64; 95% CI, 1.02 to 2.63; P=0.040). Gly16Arg was not associated with SCD risk in either study.
CONCLUSIONS: Gln27 homozygous individuals have an increased risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role in SCD in humans. Study of genetic variation within the B2AR gene may help identify those at increased SCD risk.
10aAfrican Continental Ancestry Group10aAged10aCase-Control Studies10aDeath, Sudden, Cardiac10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenetic Predisposition to Disease10aGenetic Variation10aGlutamine10aHaplotypes10aHomozygote10aHumans10aMale10aPolymorphism, Single Nucleotide10aReceptors, Adrenergic, beta-210aReproducibility of Results1 aSotoodehnia, Nona1 aSiscovick, David, S1 aVatta, Matteo1 aPsaty, Bruce, M1 aTracy, Russell, P1 aTowbin, Jeffrey, A1 aLemaitre, Rozenn, N1 aRea, Thomas, D1 aDurda, Peter1 aChang, Joel, M1 aLumley, Thomas, S1 aKuller, Lewis, H1 aBurke, Gregory, L1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/89302904nas a2200397 4500008004100000022001400041245009400055210006900149260001300218300001200231490000700243520180100250653000902051653002202060653001902082653001902101653001102120653002202131653001102153653000902164653003602173653002402209653001502233653001102248653001802259100002202277700002502299700002002324700002102344700002302365700002302388700002102411700001902432700002002451856003502471 2006 eng d a0002-861400aBlood pressure level and outcomes in adults aged 65 and older with prior ischemic stroke.0 aBlood pressure level and outcomes in adults aged 65 and older wi c2006 Sep a1309-160 v543 aOBJECTIVES: To examine the association between blood pressure (BP) levels and long-term stroke outcomes in elderly stroke survivors.
DESIGN: Observational study.
SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling adults.
PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age 78.6) who sustained a nonfatal first ischemic stroke.
MEASUREMENTS: BP levels assessed at prestroke and poststroke CHS visits were examined as predictors of stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs), and mortality.
RESULTS: Higher poststroke BP level, assessed 261.6 days (mean) after stroke, was associated with higher risk of stroke recurrence over 5.4 years (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence was 1.42 (95% confidence interval (CI) = 1.03-1.99) per standard deviation (SD) of systolic BP (P = .04) and 1.39 (95% CI = 1.01-1.91) per SD of diastolic BP (P = .04). Mortality was significantly greater in patients with low or high poststroke BP than in those with intermediate BP. Poststroke BP was not associated with risk of CHD or CVE, although further analyses suggested that high systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP did not predict poststroke outcomes.
CONCLUSION: In this observational study of adults aged 65 and older assessed approximately 8 months after stroke, low BP was associated with favorable risk of recurrent stroke, although high and low poststroke BP levels were associated with greater mortality. Long-term antihypertensive trials in older stroke survivors would increase knowledge about the benefits of lowering BP in this population.
10aAged10aAged, 80 and over10aBlood Pressure10aBrain Ischemia10aFemale10aFollow-Up Studies10aHumans10aMale10aOutcome Assessment, Health Care10aProspective Studies10aRecurrence10aStroke10aSurvival Rate1 aKaplan, Robert, C1 aTirschwell, David, L1 aLongstreth, W T1 aManolio, Teri, A1 aHeckbert, Susan, R1 aLeValley, Aaron, J1 aLefkowitz, David1 aEl-Saed, Aiman1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/91702539nas a2200337 4500008004100000022001400041245009600055210006900151260001700220300001100237490000600248520163200254653002701886653000901913653002201922653001301944653001601957653002001973653001601993653001702009653001102026653001102037653001102048653000902059653001802068100001802086700002302104700001802127700002102145856003502166 2006 eng d a1094-695000aBody mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS.0 aBody mass index is not a good predictor of bone density results c2006 Jul-Sep a329-340 v93 aBody mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women's Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.
10aAbsorptiometry, Photon10aAged10aAged, 80 and over10aBiometry10aBody Height10aBody Mass Index10aBody Weight10aBone Density10aFemale10aFrance10aHumans10aMale10aUnited States1 aRobbins, John1 aSchott, Anne-Marie1 aAzari, Rahman1 aKronmal, Richard uhttps://chs-nhlbi.org/node/91302821nas a2200385 4500008004100000022001400041245020700055210006900262260001600331300001100347490000700358520164400365653000902009653001702018653001502035653002102050653001102071653002202082653001802104653002502122653001102147653000902158653001702167653002402184653001702208653001402225653003002239653001802269100001802287700002402305700002802329700002302357700002002380856003502400 2006 eng d a0002-914900aCardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).0 aCardiovascular morbidity and mortality in communitydwelling elde c2006 May 01 a1281-60 v973 aIn the elderly, mitral annular calcification (MAC) and aortic valve sclerosis (AVS) are associated with increased cardiovascular morbidity and mortality. Aortic annular calcification (AAC) commonly occurs with MAC. However, the prognostic value of AAC, singly or in combination with MAC and AVS, for incident cardiovascular disease and mortality is unknown. From the Cardiovascular Health Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60% women) who had an echocardiogram at the 1994 to 1995 examination and who were prospectively followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification categories were associated with incident congestive heart failure (MAC: hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95% CI 1.28 to 2.06, and AVS: HR 1.50, 95% CI 1.19 to 1.89) and death. A stronger association with incident cardiovascular disease and mortality was observed with a larger number of calcification categories and with increased MAC severity. Moreover, in the participants with prevalent cardiovascular disease at echocardiographic examination (n = 1,054), MAC and AAC were still associated with cardiovascular mortality (MAC: HR 1.91, 95% CI 1.04 to 3.50; AAC: HR 2.11, 95% CI 1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are associated with a significant risk of incident congestive heart failure, cardiovascular and all-cause mortalities, and worse outcome in older patients with preexisting cardiovascular disease. Elderly patients with these findings represent a high-risk group and may require close medical attention.
10aAged10aAortic Valve10aCalcinosis10aEchocardiography10aFemale10aFollow-Up Studies10aHeart Failure10aHeart Valve Diseases10aHumans10aMale10aMitral Valve10aProspective Studies10aRisk Factors10aSclerosis10aSeverity of Illness Index10aUnited States1 aBarasch, Eddy1 aGottdiener, John, S1 aLarsen, Emily, K Marino1 aChaves, Paulo, H M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/89503066nas a2200397 4500008004100000022001400041245013300055210006900188260001600257300001200273490000700285520188100292653000902173653002202182653002502204653001902229653002402248653001702272653001102289653003802300653001102338653005002349653002502399653000902424653002202433653001302455100002202468700002602490700001502516700002102531700001802552700001802570700002302588700002202611856003502633 2006 eng d a0964-690600aCFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses.0 aCFH ELOVL4 PLEKHA1 and LOC387715 genes and susceptibility to age c2006 Nov 01 a3206-180 v153 aAge-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P=0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P=0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.
10aAged10aAged, 80 and over10aCase-Control Studies10aCohort Studies10aComplement Factor H10aEye Proteins10aFemale10aGenetic Predisposition to Disease10aHumans10aIntracellular Signaling Peptides and Proteins10aMacular Degeneration10aMale10aMembrane Proteins10aProteins1 aConley, Yvette, P1 aJakobsdottir, Johanna1 aMah, Tammy1 aWeeks, Daniel, E1 aKlein, Ronald1 aKuller, Lewis1 aFerrell, Robert, E1 aGorin, Michael, B uhttps://chs-nhlbi.org/node/92004109nas a2200553 4500008004100000022001400041245016500055210006900220260001600289300001200305490000800317520252600325653001602851653000902867653002202876653002702898653001902925653001602944653002102960653002202981653002403003653001103027653002203038653001603060653001803076653002103094653002003115653001103135653002003146653001703166653000903183653002603192653002603218653001503244653003003259653001703289653002103306653001803327653001703345653001803362100002303380700002103403700002203424700002003446700001803466700001803484700001803502856003503520 2006 eng d a1524-453900aCharacteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study.0 aCharacteristics and baseline clinical predictors of future fatal c2006 May 09 a2177-850 v1133 aBACKGROUND: Although >80% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described.
METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups.
CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.
10aAge Factors10aAged10aAged, 80 and over10aCarotid Artery, Common10aCohort Studies10aComorbidity10aCoronary Disease10aDiabetes Mellitus10aElectrocardiography10aFemale10aFollow-Up Studies10aForecasting10aHeart Failure10aHeart Ventricles10aHospitalization10aHumans10aHyperlipidemias10aHypertension10aMale10aMultivariate Analysis10aMyocardial Infarction10aOrgan Size10aPredictive Value of Tests10aRisk Factors10aSampling Studies10aTunica Intima10aTunica Media10aUnited States1 aPearte, Camille, A1 aFurberg, Curt, D1 aO'Meara, Ellen, S1 aPsaty, Bruce, M1 aKuller, Lewis1 aPowe, Neil, R1 aManolio, Teri uhttps://chs-nhlbi.org/node/89602391nas a2200361 4500008004100000022001400041245005600055210005500111260001600166300001100182490000800193520147400201653000901675653001201684653002801696653001101724653001101735653000901746653001601755653002001771653001501791653002401806653001701830653001701847653002501864653001201889653001801901100001501919700002001934700001701954700002301971856003501994 2006 eng d a0002-926200aCigarette smoking and nocturnal sleep architecture.0 aCigarette smoking and nocturnal sleep architecture c2006 Sep 15 a529-370 v1643 aCigarette smoking has been associated with a high prevalence of sleep-related complaints. However, its effects on sleep architecture have not been fully examined. The primary objective of this investigation was to assess the impact of cigarette smoking on sleep architecture. Polysomnography was used to characterize sleep architecture among 6,400 participants of the Sleep Heart Health Study (United States, 1994-1999). Sleep parameters included total sleep time, latency to sleep onset, sleep efficiency, and percentage of time in each sleep stage. The study sample consisted of 2,916 never smokers, 2,705 former smokers, and 779 current smokers. Compared with never smokers, current smokers had a longer initial sleep latency (5.4 minutes, 95% confidence interval (CI): 2.9, 7.9) and less total sleep time (14.0 minutes, 95% CI: 6.4, 21.7). Furthermore, relative to never smokers, current smokers also had more stage 1 sleep (relative proportion = 1.24, 95% CI: 1.14, 1.33) and less slow wave sleep (relative proportion = 0.86, 95% CI: 0.78, 0.95). Finally, no differences in sleep architecture were noted between former and never smokers. The results of this study show that cigarette smoking is independently associated with disturbances in sleep architecture, including a longer latency to sleep onset and a shift toward lighter stages of sleep. Nicotine in cigarette smoke and acute withdrawal from it may contribute to disturbances in sleep architecture.
10aAged10aArousal10aChi-Square Distribution10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aPrevalence10aRegression Analysis10aRisk Factors10aSleep Stages10aSleep Wake Disorders10aSmoking10aUnited States1 aZhang, Lin1 aSamet, Jonathan1 aCaffo, Brian1 aPunjabi, Naresh, M uhttps://chs-nhlbi.org/node/90403089nas a2200385 4500008004100000022001400041245007200055210006900127260001600196300001300212490000800225520201000233653000902243653002202252653001902274653001602293653001102309653001102320653000902331653002402340653003402364653003202398653002402430653001602454653001702470653003102487653002002518100002102538700002002559700002302579700001702602700002402619700002502643856003502668 2006 eng d a0003-992600aClinical course of mesenteric artery stenosis in elderly americans.0 aClinical course of mesenteric artery stenosis in elderly america c2006 Oct 23 a2095-1000 v1663 aBACKGROUND: To examine prospectively the relationship between stenosis or occlusion of the celiac and superior mesenteric arteries and symptoms of chronic intestinal ischemia in free-living elderly patients in the United States.
METHODS: As part of an ancillary study to the Cardiovascular Health Study, participants in the Forsyth County (North Carolina) cohort underwent visceral duplex ultrasonography of the celiac and superior mesenteric arteries. Critical mesenteric artery stenosis (MAS) or occlusion was defined by Doppler flow ultrasound-derived criteria. Clinical outcomes were assessed at annual follow-up examinations and review of death certificates. Multivariate associations between the presence of MAS and all-cause mortality and adverse cardiovascular events were analyzed. Participants with MAS were contacted to determine the presence of symptoms consistent with chronic intestinal ischemia.
RESULTS: Of 553 participants who underwent visceral duplex ultrasonography, 97 (17.5%) had disease of the celiac or superior mesenteric artery. At a mean follow-up of 6(1/2) years, 20 participants with MAS (20.6%) and 93 without MAS (20.4%) had died (relative risk, 1.01; 95% confidence interval, 0.66-1.55). No deaths were attributed to intestinal infarction. No association existed between the presence of MAS and prevalent cardiovascular disease, all-cause mortality, or adverse cardiovascular events. A questionnaire was completed by 71% of the surviving participants with MAS. No participant reported symptoms or weight loss consistent with chronic intestinal ischemia.
CONCLUSIONS: Mesenteric artery stenosis was a common finding in free-living elderly patients. At long-term follow-up, the presence of asymptomatic MAS was not associated with death or adverse cardiovascular events. Participants with asymptomatic MAS by duplex ultrasonographic criteria did not experience intestinal infarction or develop chronic intestinal ischemia.
10aAged10aAged, 80 and over10aCohort Studies10aComorbidity10aFemale10aHumans10aMale10aMesenteric Arteries10aMesenteric Vascular Occlusion10aProportional Hazards Models10aProspective Studies10aRadiography10aRisk Factors10aSurveys and Questionnaires10aUltrasonography1 aWilson, David, B1 aMostafavi, Kian1 aCraven, Timothy, E1 aAyerdi, Juan1 aEdwards, Matthew, S1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/92402729nas a2200361 4500008004100000022001400041245016900055210006900224260001300293300001000306490000800316520167000324653000901994653001702003653001502020653001102035653002502046653001102071653000902082653001702091653001502108653002402123653001702147653001402164653002002178100001802198700002402216700002802240700002302268700002002291700002102311856003502332 2006 eng d a1097-674400aClinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS).0 aClinical significance of calcification of the fibrous skeleton o c2006 Jan a39-470 v1513 aBACKGROUND: Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population.
METHODS: We used 2-dimensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons.
RESULTS: Mitral annular calcification was found in 1640 (42 %) subjects, AAC in 1710 (44 %), AVS in 2114 (54 %), and all 3 combined in 662 (17 %). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC.
CONCLUSIONS: In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile.
10aAged10aAortic Valve10aCalcinosis10aFemale10aHeart Valve Diseases10aHumans10aMale10aMitral Valve10aPrevalence10aProspective Studies10aRisk Factors10aSclerosis10aUltrasonography1 aBarasch, Eddy1 aGottdiener, John, S1 aLarsen, Emily, K Marino1 aChaves, Paulo, H M1 aNewman, Anne, B1 aManolio, Teri, A uhttps://chs-nhlbi.org/node/87402705nas a2200337 4500008004100000022001400041245016900055210006900224260001600293300001100309490000700320520169200327653000902019653002102028653002402049653001102073653001102084653000902095653000902104100002602113700001502139700002402154700002802178700002002206700002102226700002002247700001802267700002402285700002302309856003502332 2006 eng d a0002-914900aComparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study).0 aComparison of mortality risk for electrocardiographic abnormalit c2006 Feb 01 a309-150 v973 aMortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.
10aAged10aCoronary Disease10aElectrocardiography10aFemale10aHumans10aMale10aRisk1 aRautaharju, Pentti, M1 aGe, Sijian1 aNelson, Jennifer, C1 aLarsen, Emily, K Marino1 aPsaty, Bruce, M1 aFurberg, Curt, D1 aZhang, Zhu-Ming1 aRobbins, John1 aGottdiener, John, S1 aChaves, Paulo, H M uhttps://chs-nhlbi.org/node/88702489nas a2200361 4500008004100000022001400041245013800055210006900193260001300262300001100275490000700286520145100293653000901744653002201753653001901775653001101794653001801805653001101823653001401834653000901848653002201857653001401879100002601893700002301919700002301942700001901965700001901984700002302003700002402026700002202050700002002072856003502092 2006 eng d a1047-279700aCongestive heart failure incidence and prognosis: case identification using central adjudication versus hospital discharge diagnoses.0 aCongestive heart failure incidence and prognosis case identifica c2006 Feb a115-220 v163 aPURPOSE: We compared hospitalized congestive heart failure (CHF) incidence and prognosis estimates using hospital discharge diagnoses or central adjudication.
METHODS: We used the Cardiovascular Health Study (CHS), a population-based cohort study of 5888 elderly adults. A physician committee adjudicated potential CHF events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A CHF discharge diagnosis included any of these ICD-9 codes in any position: 428, 425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by discharge diagnosis, adjudication, or both.
RESULTS: Incidence rates for hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and 17.1 per 1000 person-years using central adjudication. Compared to the group identified as having CHF by both methods, the group with only a discharge diagnosis (hazard ratio=0.77, 95% confidence interval=0.65-0.91) and the group with central adjudication only (hazard ratio=0.72, 95% confidence interval=0.55-0.94) had lower mortality rates.
CONCLUSIONS: In the elderly, studies using only discharge diagnoses, as compared to central adjudication, may estimate higher rates of incident hospitalized CHF. Mortality following CHF onset may be similar for these methods and higher if both methods are used together.
10aAged10aAged, 80 and over10aCohort Studies10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aPatient Discharge10aPrognosis1 aSchellenbaum, Gina, D1 aHeckbert, Susan, R1 aSmith, Nicholas, L1 aRea, Thomas, D1 aLumley, Thomas1 aKitzman, Dalane, W1 aRoger, Veronique, L1 aTaylor, Herman, A1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/84402491nas a2200385 4500008004100000022001400041245011700055210006900172260001700241300001000258490000700268520143000275653000901705653001001714653001801724653001401742653002801756653000901784653001101793653001901804653001101823653000901834653002701843653002201870653002901892653001601921653003101937100001201968700002101980700001902001700001802020700001702038700001502055856003502070 2006 eng d a1279-770700aA cross-sectional study of vitamin C and cognitive function in older adults: the differential effects of gender.0 acrosssectional study of vitamin C and cognitive function in olde c2006 Jan-Feb a37-440 v103 aPrevious studies have suggested that vitamin C status may be associated with cognitive function in community-dwelling populations. However, this has not been consistent across all studies due to methodological differences. This cross-sectional study assessed the association between vitamin C and cognitive function in 544 community-dwelling older adults aged 65 or older who participated in both the Cardiovascular Health Study (CHS) and the CLUE II study in 1989. Three percent of the subjects had low plasma vitamin C concentrations (< 40 mg/dL) and 15% had low total vitamin C intake (< 60 mg/day). Most participants (96.7 percent) had normal cognitive function. In the unadjusted analyses, the highest fifth of plasma vitamin C concentration was associated with better Digit Symbol Substitution Test (DSST) scores and marginally associated with Mini-Mental State Examination (MMSE) compared to the lowest fifth. Total vitamin C intake, measured by Block's food frequency questionnaire, was generally associated with higher MMSE scores, though it was not significant. Adjusting for numerous factors did not substantially change results. In a stratified analysis by gender, higher plasma concentrations or intake were associated with higher MMSE scores for men but not for women. These mixed results do not provide strong evidence of an association between vitamin C concentrations or intake and cognitive function.
10aAged10aAging10aAscorbic Acid10aCognition10aCross-Sectional Studies10aDiet10aFemale10aHealth Surveys10aHumans10aMale10aMental Status Schedule10aNutrition Surveys10aNutritional Requirements10aSex Factors10aSurveys and Questionnaires1 aSato, R1 aHelzlsouer, K, J1 aComstock, G, W1 aHoffman, S, C1 aNorkus, E, P1 aFried, L P uhttps://chs-nhlbi.org/node/88803476nas a2200409 4500008004100000022001400041245012100055210006900176260001300245300001000258490000700268520227900275653000902554653003002563653002402593653001602617653001302633653002302646653002402669653001102693653002202704653002502726653001102751653002502762653000902787653002402796653003702820653001702857653002102874653002202895100002302917700002702940700002002967700002402987700002003011856003503031 2006 eng d a0003-990X00aDepressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study.0 aDepressive symptoms vascular disease and mild cognitive impairme c2006 Mar a273-90 v633 aCONTEXT: Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons.
OBJECTIVES: To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease.
DESIGN: Prospective, population-based, longitudinal study.
SETTING: Random sample of adults 65 years or older recruited from 4 US communities.
PARTICIPANTS: Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria.
MAIN OUTCOME MEASURE: Diagnosis of MCI.
RESULTS: Depressive symptoms at baseline were associated with increased risk of MCI (10.0%, 13.3%, and 19.7% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics.
CONCLUSION: Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.
10aAged10aCerebrovascular Disorders10aCognition Disorders10aComorbidity10aDementia10aDementia, Vascular10aDepressive Disorder10aFemale10aFollow-Up Studies10aGeriatric Assessment10aHumans10aLongitudinal Studies10aMale10aProspective Studies10aPsychiatric Status Rating Scales10aRisk Factors10aSampling Studies10aVascular Diseases1 aBarnes, Deborah, E1 aAlexopoulos, George, S1 aLopez, Oscar, L1 aWilliamson, Jeff, D1 aYaffe, Kristine uhttps://chs-nhlbi.org/node/89102997nas a2200349 4500008004100000022001400041245009800055210006900153260001600222300001100238490000700249520203700256653000902293653001202302653002602314653002802340653000902368653002402377653002502401653001102426653001102437653001002448653001502458653001102473653000902484653002502493100002502518700002302543700002202566700002402588856003502612 2006 eng d a1558-359700aDietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans.0 aDietary fish and n3 fatty acid intake and cardiac electrocardiog c2006 Aug 01 a478-840 v483 aOBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk.
BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects.
METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories.
RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88).
CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.
10aAged10aAnimals10aAtrioventricular Node10aCross-Sectional Studies10aDiet10aElectrocardiography10aFatty Acids, Omega-310aFemale10aFishes10aHeart10aHeart Rate10aHumans10aMale10aVentricular Function1 aMozaffarian, Dariush1 aPrineas, Ronald, J1 aStein, Phyllis, K1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/91003067nas a2200385 4500008004100000022001400041245008400055210006900139260001300208300001200221490000700233520197700240653003902217653000902256653001402265653001302279653002302292653004002315653001102355653002202366653001102388653001402399653000902413653002402422653002602446653001702472653001802489100002802507700002102535700002802556700002102584700002102605700002002626856003502646 2006 eng d a0002-861400aEducation, cognitive test scores, and black-white differences in dementia risk.0 aEducation cognitive test scores and blackwhite differences in de c2006 Jun a898-9050 v543 aOBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups.
DESIGN: Longitudinal, 6-year follow-up.
PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study.
MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes.
RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5-2.4 and 95% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE.
CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.
10aAfrican Continental Ancestry Group10aAged10aCognition10aDementia10aEducational Status10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aPsychological Tests10aRetrospective Studies10aRisk Factors10aUnited States1 aShadlen, Marie-Florence1 aSiscovick, David1 aFitzpatrick, Annette, L1 aDulberg, Corinne1 aKuller, Lewis, H1 aJackson, Sharon uhttps://chs-nhlbi.org/node/89902929nas a2200409 4500008004100000022001400041245011800055210006900173260001300242300001100255490000700266520181100273653000902084653001002093653001502103653001102118653001102129653001402140653003102154653000902185653001302194653001902207653001702226653003202243653002002275653001702295653001102312100001902323700002102342700002002363700001702383700002302400700002202423700001802445700002102463856003502484 2006 eng d a1524-462800aFactors associated with geographic variations in stroke incidence among older populations in four US communities.0 aFactors associated with geographic variations in stroke incidenc c2006 Aug a1980-50 v373 aBACKGROUND AND PURPOSE: In the Cardiovascular Health Study (CHS), we previously observed lower stroke incidence in Allegheny County, PA compared with the other 3 study sites. The purpose of this study was to study possible reasons for the lower stroke incidence in Allegheny County.
METHODS: CHS participants 65 years or older who were stroke-free at baseline (n=5639) were followed between 1989 to 1990 and 2000 for the development of stroke. Risk factors at baseline and their subsequent control were compared among both groups. Site-specific hazard ratios for stroke incidence were calculated using Cox regression models.
RESULTS: The unadjusted hazard ratio for total stroke incidence in Forsyth County, NC; Sacramento County, CA; and Washington County, MD combined compared with Allegheny County, PA was 1.74 (95% CI: 1.42, 2.14). After adjustment for age and other traditional risk factors, there was modest reduction of the excess hazard in non-Allegheny sites compared with Allegheny County (hazard ratio=1.52, 95% CI: 1.17, 1.98). Between baseline and the seventh-year visits, control of hypertension, diabetes, lipids, smoking, atrial fibrillation and transient ischemic attack were similar across sites. White matter grade > or = 3 on the baseline brain MRI was less common in Allegheny County (25.8% versus 36.3%, respectively; P<0.001) and accounted for 25% of the excess hazard in non-Allegheny sites compared with Allegheny County.
CONCLUSIONS: Site differences in stroke risk factors at baseline and subsequent control only partially explain site differences in stroke incidence. White matter grade as a possible integrated measure of exposure and control of risk factors may help in explaining geographic variations in stroke incidence.
10aAged10aBrain10aCalifornia10aFemale10aHumans10aIncidence10aMagnetic Resonance Imaging10aMale10aMaryland10aNorth Carolina10aPennsylvania10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aStroke1 aEl-Saed, Aiman1 aKuller, Lewis, H1 aNewman, Anne, B1 aLopez, Oscar1 aCostantino, Joseph1 aMcTigue, Kathleen1 aCushman, Mary1 aKronmal, Richard uhttps://chs-nhlbi.org/node/90002702nas a2200361 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520173000263653000901993653002202002653001502024653001102039653001102050653001402061653000902075653001302084653001902097653001702116653001102133100001902144700002102163700002002184700001702204700002302221700002202244700001802266700002102284856003502305 2006 eng d a1524-462800aGeographic variations in stroke incidence and mortality among older populations in four US communities.0 aGeographic variations in stroke incidence and mortality among ol c2006 Aug a1975-90 v373 aBACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability in the US. There is limited data on geographic variations in stroke incidence among older US populations who experience the majority of stroke burden. The purpose of this study was to compare stroke incidence and mortality rates in 4 US communities.
METHODS: Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n=5639) were followed for 10 or 7 years in predominantly white (n=5002) and black (n=637) participants, respectively. Incident stroke was validated by a stroke adjudication committee after ascertainment at annual visits, interim telephone contacts, and review of Medicare hospitalization data.
RESULTS: The 2000 US population age and sex standardized total stroke incidence rate for all CHS participants was 17.7 per 1000 person-years (95% CI: 15.9, 19.5). The rate was significantly lower in Allegheny County, Pennsylvania 9.6/1000 person-years (95% CI: 7.7, 11.5) than Forsyth County, North Carolina 19.2/1000 person-years (95% CI: 15.6, 22.8), Sacramento County, California 20.7/1000 person-years (95% CI: 16.9, 24.5), and Washington County, Maryland 19.8/1000 person-years (95% CI: 16.1, 23.5). The lower stroke incidence rate in Allegheny County was consistent in gender, race, and age groups. Though not statistically significant, stroke mortality was also lower in Allegheny County than other 3 sites. The 1-month case fatality rate was similar in the 4 sites for all strokes, and by stroke types.
CONCLUSIONS: Understanding geographic variations in stroke incidence may be an important step in improving preventive practices of stroke.
10aAged10aAged, 80 and over10aCalifornia10aFemale10aHumans10aIncidence10aMale10aMaryland10aNorth Carolina10aPennsylvania10aStroke1 aEl-Saed, Aiman1 aKuller, Lewis, H1 aNewman, Anne, B1 aLopez, Oscar1 aCostantino, Joseph1 aMcTigue, Kathleen1 aCushman, Mary1 aKronmal, Richard uhttps://chs-nhlbi.org/node/90101769nas a2200289 4500008004100000022001400041245011100055210006900166260001700235300001100252490000700263520094900270653003101219653000901250653001601259653002101275653001101296653001801307653001801325653001701343653001101360653000901371653002001380100002201400700002201422856003501444 2006 eng d a1076-746000aHeart failure at the end of life: symptoms, function, and medical care in the Cardiovascular Health Study.0 aHeart failure at the end of life symptoms function and medical c c2006 Jul-Aug a217-250 v153 aAmong Cardiovascular Health Study participants who died from coronary heart disease, the authors compared those with incident and definite congestive heart failure (CHF) (n=60; 15%) and those with prevalent or probable CHF (n=70; 17.5%) to those with no history of CHF (n=198; 50%) concerning health status at the end of life. Both CHF groups had worse health status before death than the group without CHF. Patients in the CHF groups were more likely to use benzodiazepines (20% and 19% vs. 6%; p=0.001) and to rate their health as fair or poor (68% and 63% vs. 41%; p<0.001). They were more likely to be hospitalized (33% and 28% vs. 11%; p<0.001), to have activity restrictions (79% and 62% vs. 38%; p<0.001), and to report a wide array of physical symptoms. These data suggest that patients who die from coronary heart disease in the presence of CHF have greater need for hospice or palliative care than those with no history of CHF.
10aActivities of Daily Living10aAged10aComorbidity10aCoronary Disease10aFemale10aHealth Status10aHeart Failure10aHospice Care10aHumans10aMale10aPalliative Care1 aSullivan, Mark, D1 aO'Meara, Ellen, S uhttps://chs-nhlbi.org/node/90602953nas a2200457 4500008004100000022001400041245010600055210006900161260001300230300001000243490000700253520169200260653002701952653000901979653001701988653001502005653001502020653001402035653001102049653000802060653001102068653002002079653002602099653001802125653002502143653000902168653001702177653003002194100002002224700002402244700002902268700002402297700002102321700001702342700001802359700002102377700002202398700002002420700002002440856003502460 2006 eng d a1079-500600aKidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study.0 aKidney function predicts the rate of bone loss in older individu c2006 Jul a743-80 v613 aBACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old.
METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women.
RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women.
CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.
10aAbsorptiometry, Photon10aAged10aBone Density10aCreatinine10aCystatin C10aCystatins10aFemale10aHip10aHumans10aKidney Diseases10aKidney Function Tests10aLinear Models10aLongitudinal Studies10aMale10aOsteoporosis10aPredictive Value of Tests1 aFried, Linda, F1 aShlipak, Michael, G1 aStehman-Breen, Catherine1 aMittalhenkle, Anuja1 aSeliger, Stephen1 aSarnak, Mark1 aRobbins, John1 aSiscovick, David1 aHarris, Tamara, B1 aNewman, Anne, B1 aCauley, Jane, A uhttps://chs-nhlbi.org/node/90802308nas a2200337 4500008004100000022001400041245015500055210006900210260001600279300000900295490000700304520131300311653000901624653002601633653002501659653001301684653002101697653001101718653001601729653001801745653001101763653000901774653002601783653001201809100002401821700002301845700002501868700002101893700002101914856003501935 2006 eng d a0002-914900aLeft atrial volume, geometry, and function in systolic and diastolic heart failure of persons > or =65 years of age (the cardiovascular health study).0 aLeft atrial volume geometry and function in systolic and diastol c2006 Jan 01 a83-90 v973 aThe left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects > or =65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction.
10aAged10aAtrial Function, Left10aCase-Control Studies10aDiastole10aEchocardiography10aFemale10aHeart Atria10aHeart Failure10aHumans10aMale10aMultivariate Analysis10aSystole1 aGottdiener, John, S1 aKitzman, Dalane, W1 aAurigemma, Gerard, P1 aArnold, Alice, M1 aManolio, Teri, A uhttps://chs-nhlbi.org/node/87503809nas a2200433 4500008004100000022001400041245010000055210006900155260001300224300001200237490000700249520259500256653002202851653001602873653000902889653002202898653001802920653002802938653001902966653004002985653001203025653001103037653001103048653001403059653000903073653002303082653001703105653001603122100002403138700001603162700002303178700002303201700002603224700002403250700002203274700002103296700002303317856003503340 2006 eng d a0002-861400aMetabolic syndrome and cardiovascular disease in older people: The cardiovascular health study.0 aMetabolic syndrome and cardiovascular disease in older people Th c2006 Sep a1317-240 v543 aOBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD.
DESIGN: Prospective cohort study.
SETTING: Four field centers in U.S. communities.
PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62% female, 14% black).
MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L).
RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95% confidence interval (CI) = 1.07-1.57), 0.94 (95% CI = 0.73-1.21), and 1.40 (95% CI = 1.12-1.76) for women and 1.35 (95% CI = 1.10-1.66), 1.51 (95% CI = 1.08-2.12), and 1.47 (95% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20% to 30% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16% to 46%) and an additional 9% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD.
CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.
10aAfrican Americans10aAge Factors10aAged10aAged, 80 and over10aBlood Glucose10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFasting10aFemale10aHumans10aIncidence10aMale10aMetabolic Syndrome10aRisk Factors10aSex Factors1 aMcNeill, Ann, Marie1 aKatz, Ronit1 aGirman, Cynthia, J1 aRosamond, Wayne, D1 aWagenknecht, Lynne, E1 aBarzilay, Joshua, I1 aTracy, Russell, P1 aSavage, Peter, J1 aJackson, Sharon, A uhttps://chs-nhlbi.org/node/91802956nas a2200361 4500008004100000022001400041245012100055210006900176260001600245300001100261490000800272520195500280653000902235653001002244653000802254653001902262653002002281653002102301653001102322653002202333653001102355653002502366653000902391653003302400653001702433653001202450100001902462700001602481700002402497700001802521700002002539856003502559 2006 eng d a1524-453900aMortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study.0 aMortality and cardiovascular risk across the anklearm index spec c2006 Jan 24 a388-930 v1133 aBACKGROUND: A low ankle-arm index (AAI) is a strong predictor of mortality and cardiovascular events. A high AAI also appears to be associated with higher mortality risk in select populations. However, mortality and cardiovascular risk across the AAI spectrum have not been described in a more broadly defined population.
METHODS AND RESULTS: We examined total and cardiovascular mortality and cardiovascular events across the AAI spectrum among 5748 participants in the Cardiovascular Health Study (CHS). The mean age of the sample population was 73+/-6 years, and the sample included 3289 women (57%) and 883 blacks (15%). The median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6 (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of which were cardiovascular) and 1491 cardiovascular events during follow-up. After adjustment for potential confounders, AAI measurements < or =0.60 (hazard ratio [HR] 1.82, 95% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95% CI 1.61 to 2.69), 0.71 to 0.8 (HR 1.80, 95% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95% CI 1.43 to 2.11), 0.91 to 1.0 (HR 1.40, 95% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95% CI 1.07 to 2.31) were associated with higher mortality risk from all causes compared with the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular mortality. For cardiovascular events, risk was higher at all AAI levels <1 but not for AAI levels >1.4 (HR 1.00, 95% CI 0.57 to 1.74). The association of a high AAI with mortality was stronger in men than in women and in younger than in older cohort members.
CONCLUSIONS: In a cohort of community-dwelling elders, mortality risk was higher than the referent category of 1.11 to 1.2 among participants with AAI values above the traditional cutpoint of 0.9 (ie, 0.91 to 1.0 and >1.4), and the specific association of AAI with mortality varied by age and gender.
10aAged10aAnkle10aArm10aBlood Pressure10aBody Mass Index10aCholesterol, LDL10aFemale10aFollow-Up Studies10aHumans10aLongitudinal Studies10aMale10aPeripheral Vascular Diseases10aRisk Factors10aSmoking1 aO'Hare, Ann, M1 aKatz, Ronit1 aShlipak, Michael, G1 aCushman, Mary1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/88402947nas a2200385 4500008004100000022001400041245011500055210006900170260001300239300000900252490000600261520183800267653002502105653000902130653002802139653002102167653002202188653001102210653001102221653002402232653001202256653000902268653003202277653002402309653002002333653002102353100002402374700002402398700002302422700002002445700002102465700002202486700001802508856003502526 2006 eng d a1549-167600aMortality in pharmacologically treated older adults with diabetes: the Cardiovascular Health Study, 1989-2001.0 aMortality in pharmacologically treated older adults with diabete c2006 Oct ae4000 v33 aBACKGROUND: Diabetes mellitus (DM) confers an increased risk of mortality in young and middle-aged individuals and in women. It is uncertain, however, whether excess DM mortality continues beyond age 75 years, is related to type of hypoglycemic therapy, and whether women continue to be disproportionately affected by DM into older age.
METHODS AND FINDINGS: From the Cardiovascular Health Study, a prospective study of 5,888 adults, we examined 5,372 participants aged 65 y or above without DM (91.2%), 322 with DM treated with oral hypoglycemic agents (OHGAs) (5.5%), and 194 with DM treated with insulin (3.3%). Participants were followed (1989-2001) for total, cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD/noncancer mortality. Compared with non-DM participants, those treated with OHGAs or insulin had adjusted hazard ratios (HRs) for total mortality of 1.33 (95% confidence interval [CI], 1.10 to 1.62) and 2.04 (95% CI, 1.62 to 2.57); CVD mortality, 1.99 (95% CI, 1.54 to 2.57) and 2.16 (95% CI, 1.54 to 3.03); CHD mortality, 2.47 (95% CI, 1.89 to 3.24) and 2.75 (95% CI, 1.95 to 3.87); and infectious and renal mortality, 1.35 (95% CI, 0.70 to 2.59) and 6.55 (95% CI, 4.18 to 10.26), respectively. The interaction of age (65-74 y versus > or =75 y) with DM was not significant. Women treated with OHGAs had a similar HR for total mortality to men, but a higher HR when treated with insulin.
CONCLUSIONS: DM mortality risk remains high among older adults in the current era of medical care. Mortality risk and type of mortality differ between OHGA and insulin treatment. Women treated with insulin therapy have an especially high mortality risk. Given the high absolute CVD mortality in older people, those with DM warrant aggressive CVD risk factor reduction.
10aAdministration, Oral10aAged10aCardiovascular Diseases10aCoronary Disease10aDiabetes Mellitus10aFemale10aHumans10aHypoglycemic Agents10aInsulin10aMale10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aSex Distribution1 aKronmal, Richard, A1 aBarzilay, Joshua, I1 aSmith, Nicholas, L1 aPsaty, Bruce, M1 aKuller, Lewis, H1 aBurke, Gregory, L1 aFurberg, Curt uhttps://chs-nhlbi.org/node/92302803nas a2200397 4500008004100000022001400041245007900055210006900134260001300203300001100216490000700227520176600234653000902000653002202009653002202031653001202053653002402065653001102089653001102100653000902111653002902120653001802149653002102167100001602188700001702204700001702221700001902238700001802257700001802275700001602293700001902309700001302328700001302341700001602354856003502370 2006 eng d a0022-305000aNeuropsychological characteristics of mild cognitive impairment subgroups.0 aNeuropsychological characteristics of mild cognitive impairment c2006 Feb a159-650 v773 aOBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.
METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.
RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits.
CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.
10aAged10aAged, 80 and over10aAlzheimer Disease10aAmnesia10aCognition Disorders10aFemale10aHumans10aMale10aNeuropsychological Tests10aPsychometrics10aReference Values1 aLopez, O, L1 aBecker, J, T1 aJagust, W, J1 aFitzpatrick, A1 aCarlson, M, C1 aDeKosky, S, T1 aBreitner, J1 aLyketsos, C, G1 aJones, B1 aKawas, C1 aKuller, L H uhttps://chs-nhlbi.org/node/85103146nas a2200433 4500008004100000022001400041245009500055210006900150260001300219300001100232490000700243520191200250653002402162653002002186653001902206653001102225653001102236653001702247653000902264653001602273653002602289653002502315653001202340653002002352653001502372653003002387653003002417653002902447100002602476700002202502700001702524700002402541700001802565700002302583700002002606700002402626700002702650856003502677 2006 eng d a0161-810500aObstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample.0 aObstructive sleep apnea and plasma natriuretic peptide levels in c2006 Oct a1301-60 v293 aSTUDY OBJECTIVES: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample.
DESIGN: Cross-sectional, retrospective, observational study.
SETTING: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study.
PARTICIPANTS: Community-based sample of 623 individuals.
MEASUREMENTS: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates.
RESULTS: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed forAHI categories 5-15, 15-30, >30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0.93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index.
CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels.
10aAtrial Fibrillation10aBody Mass Index10aCohort Studies10aFemale10aHumans10aHypertension10aMale10aMiddle Aged10aMyocardial Infarction10aNatriuretic Peptides10aObesity10aPolysomnography10aPrevalence10aResidence Characteristics10aSeverity of Illness Index10aSleep Apnea, Obstructive1 aPatwardhan, Anjali, A1 aLarson, Martin, G1 aLevy, Daniel1 aBenjamin, Emelia, J1 aLeip, Eric, P1 aKeyes, Michelle, J1 aWang, Thomas, J1 aGottlieb, Daniel, J1 aVasan, Ramachandran, S uhttps://chs-nhlbi.org/node/92503437nas a2200481 4500008004100000022001400041245010100055210006900156260001300225300001200238490000600250520205500256653001002311653002402321653004002345653001502385653003802400653002102438653002302459653001102482653001802493653001102511653001202522653000902534653001602543653002902559653001102588653002002599653003002619653002902649653003102678100002002709700001602729700002202745700002602767700002202793700001802815700002102833700002002854700002202874700002402896856003502920 2006 eng d a1389-945700aObstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep Heart Health Study.0 aObstructive sleep apneahypopnea and neurocognitive functioning i c2006 Sep a498-5070 v73 aBACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients with OSAH frequently are found to have deficits in neuropsychological function. However, the nature and severity of these abnormalities in non-clinical populations is less well defined.
PATIENTS AND METHODS: One hundred and forty-one participants from the Tucson, AZ and New York, NY field centers of the Sleep Heart Health Study completed a battery of neuropsychological tests for 9-40 months (mean=24 months, SD=7 months) after an unattended home polysomnogram. Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests, composite variables representing attention, executive function, MotorSpeed and processing speed were constructed from the neuropsychological test battery.
RESULTS: There were no significant differences in any individual neuropsychological test or composite variable between the OSAH and CTL groups. However, when time spent with O(2) saturations less than 85% was dichotomized into those participants in the top quartile of the distribution and those in the lower three quartiles, motor speed was significantly impaired in those who were more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242, P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001) were associated with more severe oxygen desaturation even after controlling for degree of daytime sleepiness, age, gender and educational level.
CONCLUSIONS: Mild to moderate OSAH has little impact on the selected measures of attention, executive function, motor speed and processing speed. However, hypoxemia adversely affects both motor and processing speed. These results suggest that in middle-aged to elderly adults the neuropsychological effects of clinically unrecognized mild to moderate OSAH are neither global nor large.
10aBrain10aCognition Disorders10aContinuous Positive Airway Pressure10aDemography10aDisorders of Excessive Somnolence10aElectromyography10aElectrooculography10aFemale10aHealth Status10aHumans10aHypoxia10aMale10aMiddle Aged10aNeuropsychological Tests10aOxygen10aPolysomnography10aSeverity of Illness Index10aSleep Apnea, Obstructive10aSurveys and Questionnaires1 aQuan, Stuart, F1 aWright, Ron1 aBaldwin, Carol, M1 aKaemingk, Kristine, L1 aGoodwin, James, L1 aKuo, Tracy, F1 aKaszniak, Alfred1 aBoland, Lori, L1 aCaccappolo, Elise1 aBootzin, Richard, R uhttps://chs-nhlbi.org/node/90203003nas a2200385 4500008004100000022001400041245014800055210006900203260001600272300001100288490000800299520186800307653000902175653002202184653001502206653002502221653002102246653002702267653001102294653001102305653000902316653002402325653001802349653002202367653001802389100002402407700001902431700002502450700002202475700001902497700002102516700002102537700002402558856003502582 2006 eng d a1524-453900aPlasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: the cardiovascular health study.0 aPlasma phospholipid trans fatty acids fatal ischemic heart disea c2006 Jul 18 a209-150 v1143 aBACKGROUND: Intake of trans fatty acids is associated with increased risk of coronary heart disease. Whether different classes of trans fatty acids show similar associations is unclear. We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids. To extend these findings, we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease (IHD) and sudden cardiac death.
METHODS AND RESULTS: We conducted a case-control study nested in the Cardiovascular Health Study. We identified 214 cases of fatal IHD (fatal myocardial infarction and coronary heart disease death) between 1992 and 1998. We randomly selected 214 controls, matched to cases on demographics, prevalent cardiovascular disease, and timing of blood draw. Plasma phospholipid fatty acids were assessed in blood samples collected earlier. Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD (odds ratio [OR] for interquintile range 1.68, 95% confidence interval [CI] 1.21 to 2.33) after adjustment for risk factors and trans-18:1 levels. Trans-18:1 levels above the 20th percentile were associated with lower risk (OR 0.34, 95% CI 0.18 to 0.63). In analyses limited to cases of sudden cardiac death (n=95), higher levels of trans-18:2 fatty acids were associated with higher risk (OR 2.34, 95% CI 1.27 to 4.31) and higher trans-18:1 with lower risk (OR 0.18, 95% CI 0.06 to 0.54).
CONCLUSIONS: Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death. If confirmed, these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content.
10aAged10aAged, 80 and over10aBiomarkers10aCase-Control Studies10aCoronary Disease10aDeath, Sudden, Cardiac10aFemale10aHumans10aMale10aMyocardial Ischemia10aPhospholipids10aTrans Fatty Acids10aUnited States1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aMozaffarian, Dariush1 aSotoodehnia, Nona1 aRea, Thomas, D1 aKuller, Lewis, H1 aTracy, Russel, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/90303255nas a2200433 4500008004100000022001400041245018000055210006900235260001300304300001100317490000700328520198600335653000902321653001002330653001902340653001802359653001902377653002802396653001902424653003002443653001202473653001102485653002402496653002802520653001102548653001202559653001502571653001102586653002002597653000902617653002202626100002702648700002102675700002302696700002102719700002102740700002502761856003502786 2006 eng d a0021-972X00aThe prevalence of the 65-kilodalton isoform of glutamic acid decarboxylase autoantibodies by glucose tolerance status in elderly patients from the cardiovascular health study.0 aprevalence of the 65kilodalton isoform of glutamic acid decarbox c2006 Aug a2871-70 v913 aCONTEXT: Autoantibodies (AA) to glutamic acid decarboxylase (GAD65), a determinant of risk for autoimmune diabetes, have been found in up to 10% of patients with type 2 diabetes. In older adults, this marker may also serve as a determinant of risk for autoimmune diabetes and enhance diabetes classification.
OBJECTIVE: The objective of this study was to evaluate the relationship between GAD65AA and glucose tolerance status, current diabetes treatment, and clinical measures in older adults.
DESIGN: GAD65AA were measured at baseline in 3318 participants from the Cardiovascular Health Study, a cohort study of 5888 individuals 65 or older.
SETTING: The population-based cohort was recruited from four U.S. sites.
PATIENTS: Patients included all Cardiovascular Health Study participants with known diabetes, newly diagnosed diabetes, impaired fasting glucose, impaired glucose tolerance, and a sample of normal glucose-tolerant participants.
MAIN OUTCOME MEASURES: GAD65AA, body mass index, fasting glucose and insulin levels, blood pressure, lipid levels, and diabetes treatment at baseline were measured.
RESULTS: The prevalence of GAD65AA increased with decreasing glucose tolerance in both Blacks (n = 560) and Whites (n = 2730), being more pronounced in known diabetic individuals. GAD65AA were found in 2.3, 5.8, 7.8, and 8.3% of diabetic participants, reporting use of no diabetes medication, oral hypoglycemic agents, insulin only, and both oral hypoglycemic agents and insulin, respectively (P = 0.02, linear trend). Among diabetic participants, GAD65AA positivity was associated with diabetes treatment, higher fasting glucose, and lower body mass index.
CONCLUSIONS: Even among older individuals with diabetes, GAD65AA may be a useful marker in identifying a subgroup of autoimmune diabetes, serve as a marker of insulin requirement, and remain stable over years.
10aAged10aAging10aAutoantibodies10aBlood Glucose10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus, Type 210aFasting10aFemale10aGlucose Intolerance10aGlutamate Decarboxylase10aHumans10aInsulin10aIsoenzymes10aLipids10aLogistic Models10aMale10aNutrition Surveys1 aBarinas-Mitchell, Emma1 aKuller, Lewis, H1 aPietropaolo, Susan1 aZhang, Ying-Jian1 aHenderson, Tyona1 aPietropaolo, Massimo uhttps://chs-nhlbi.org/node/89804012nas a2200445 4500008004100000022001400041245009500055210006900150260001300219300002900232490000700261520271900268653000902987653002202996653002003018653002403038653001903062653002403081653001103105653002203116653001103138653001403149653000903163653001903172653002803191653001403219653002403233653002903257653003003286653001703316653003703333100002303370700002303393700002303416700001703439700002603456700002403482700002503506856003503531 2006 eng d a0741-521400aProgression of atherosclerotic renovascular disease: A prospective population-based study.0 aProgression of atherosclerotic renovascular disease A prospectiv c2006 Nov a955-62; discussion 962-30 v443 aOBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS).
METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion.
RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95% CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD.
CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0% of kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and no prevalent RVD progressed to occlusion.
10aAged10aAged, 80 and over10aAtherosclerosis10aBlood Flow Velocity10aBlood Pressure10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aNorth Carolina10aPopulation Surveillance10aPrognosis10aProspective Studies10aRenal Artery Obstruction10aSeverity of Illness Index10aTime Factors10aUltrasonography, Doppler, Duplex1 aPearce, Jeffrey, D1 aCraven, Brandon, L1 aCraven, Timothy, E1 aPiercy, Todd1 aStafford, Jeanette, M1 aEdwards, Matthew, S1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/91903292nas a2200385 4500008004100000022001400041245016100055210006900216260000900285300001000294490000700304520216600311653000902477653001002486653002402496653002402520653003002544653001902574653001302593653001102606653000902617653003102626653001102657653001702668653003102685653000902716653002902725653001102754653001802765100002102783700002002804700002702824700002002851856003502871 2006 eng d a0251-535000aQuantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults.0 aQuantitative measures of gait characteristics indicate prevalenc c2006 a52-600 v263 aAbnormal gait in high-functioning older adults may indicate underlying subtle structural brain abnormalities. We tested the hypothesis that temporal and spatial parameters of gait, including speed, stride length and double support time, are cross-sectionally associated with white matter hyperintensity, subcortical infarcts or brain atrophy on brain MRI. We examined 321 men and women (mean age = 78.3) participating to the Cardiovascular Health Study who were free of dementia or stroke at the time of the gait assessment. Analyses were set with gait as independent variable and brain MRIs as dependent variables. Gait measures were determined from the footfalls recorded on a 4-meter-long instrumented walking surface, the GaitMat II. Brain MRIs were examined for the presence of white matter hyperintensity (WMG, graded from 0 to 9), brain infarcts (predominantly subcortical) and ventricular enlargement (graded from 0 to 9). Slower gait, shorter stride length and longer double support times were associated with greater prevalence of white matter grade > or =3 (p = 0.02), and at least 1 brain infarct (p = 0.04) independent of age. In multivariate logistic regression models adjusted for demographics and clinical cardiovascular diseases, those with gait speed <1.02 m/s were more likely to have WMG > or =3 and at least 1 brain infarct, compared with those with faster gait - odds ratio (OR): 2.85, 95% confidence interval (95% CI): 1.35, 6.02, and OR: 2.09, 95% CI: 1.04, 4.19. Shorter stride length was also associated with greater probability of having at least 1 brain infarct (gait stride <0.88 vs. >1.10 m: OR: 3.20, 95% CI: 1.49, 6.88), while longer double support times were associated with a greater probability of having WMG > or =3 (double support time >0.19 vs. <0.14 s: OR: 2.3, 95% CI: 1.1, 4.7) independent of demographics and clinical cardiovascular diseases. Gait parameters were not significantly associated with ventricular grade. In summary, in this group of high-functioning older adults, poorer gait speed, shorter stride and longer double support time are associated with high white matter disease and subclinical strokes.
10aAged10aBrain10aCerebral Infarction10aCerebral Ventricles10aCerebrovascular Disorders10aCohort Studies10aDementia10aFemale10aGait10aGait Disorders, Neurologic10aHumans10aHypertension10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aStroke10aUnited States1 aRosano, Caterina1 aBrach, Jennifer1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/86603298nas a2200445 4500008004100000022001400041245012700055210006900182260001600251300001200267490000800279520204400287653000902331653002202340653001502362653002802377653001902405653001102424653001102435653004002446653001402486653000902500653001602509653002402525653002102549653001702570653002002587653001702607653001102624653001802635100002002653700002002673700001802693700002102711700002202732700002402754700001802778700002102796856003502817 2006 eng d a0003-992600aQuantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.0 aQuantitative retinal venular caliber and risk of cardiovascular c2006 Nov 27 a2388-940 v1663 aBACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons.
METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods.
RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73).
CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.
10aAged10aAged, 80 and over10aAlgorithms10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aImage Processing, Computer-Assisted10aIncidence10aMale10aPhotography10aProspective Studies10aRetinal Diseases10aRetinal Vein10aRetinal Vessels10aRisk Factors10aStroke10aUnited States1 aWong, Tien, Yin1 aKamineni, Aruna1 aKlein, Ronald1 aSharrett, Richey1 aKlein, Barbara, E1 aSiscovick, David, S1 aCushman, Mary1 aDuncan, Bruce, B uhttps://chs-nhlbi.org/node/92902656nas a2200385 4500008004100000022001400041245015100055210006900206260001300275300001100288490000700299520155000306653001001856653001601866653000901882653002801891653001101919653001501930653001101945653000901956653002701965653002401992653002402016653001702040653001602057653001202073653001702085110003702102700002002139700001502159700002302174700002102197700001702218856003502235 2006 eng d a0300-577100aRegression dilution methods for meta-analysis: assessing long-term variability in plasma fibrinogen among 27,247 adults in 15 prospective studies.0 aRegression dilution methods for metaanalysis assessing longterm c2006 Dec a1570-80 v353 aBACKGROUND: Within-person variability in measured values of a risk factor can bias its association with disease. The extent of this regression dilution bias for plasma fibrinogen was investigated using repeat measurement data collected at varying time intervals on 27 247 adults in 15 prospective studies.
METHODS: Regression dilution ratios (RDRs) were estimated from a linear regression of repeat measurements on baseline values in each study and for each time interval, and pooled allowing for within- and between-study heterogeneity. RDRs were estimated both without and with adjustment for confounders, and factors were investigated that might influence the RDRs.
RESULTS: The unadjusted overall RDR was 0.51 (95% CI: 0.47, 0.55), which decreased to 0.46 (95% CI: 0.42, 0.49) after adjustment for age, sex and measured values of other established vascular risk factors. The RDR did not vary materially by assay method, age, sex or smoking status, but decreased at higher levels of baseline fibrinogen.
CONCLUSION: It is appropriate to use an RDR of 0.5 to correct approximately for regression dilution bias in plasma fibrinogen values; however, this correction factor may produce somewhat conservative hazard ratios in adjusted analyses, at higher fibrinogen concentrations and in follow-up beyond a decade. More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies.
10aAdult10aAge Factors10aBias10aCardiovascular Diseases10aFemale10aFibrinogen10aHumans10aMale10aMeta-Analysis as Topic10aProspective Studies10aRegression Analysis10aRisk Factors10aSex Factors10aSmoking10aTime Factors1 aFibrinogen Studies Collaboration1 aWood, Angela, M1 aWhite, Ian1 aThompson, Simon, G1 aLewington, Sarah1 aDanesh, John uhttps://chs-nhlbi.org/node/93102509nas a2200349 4500008004100000022001400041245006400055210005900119260001300178300001100191490000600202520158700208653000901795653002201804653001501826653001301841653002801854653001101882653001101893653000901904653002401913653001701937653001401954653003201968653001702000100001602017700002902033700001802062700001902080700002502099856003502124 2006 eng d a1465-464400aThe sensitivity and specificity of markers for event times.0 asensitivity and specificity of markers for event times c2006 Apr a182-970 v73 aThe statistical literature on assessing the accuracy of risk factors or disease markers as diagnostic tests deals almost exclusively with settings where the test, Y, is measured concurrently with disease status D. In practice, however, disease status may vary over time and there is often a time lag between when the marker is measured and the occurrence of disease. One example concerns the Framingham risk score (FR-score) as a marker for the future risk of cardiovascular events, events that occur after the score is ascertained. To evaluate such a marker, one needs to take the time lag into account since the predictive accuracy may be higher when the marker is measured closer to the time of disease occurrence. We therefore consider inference for sensitivity and specificity functions that are defined as functions of time. Semiparametric regression models are proposed. Data from a cohort study are used to estimate model parameters. One issue that arises in practice is that event times may be censored. In this research, we extend in several respects the work by Leisenring et al. (1997) that dealt only with parametric models for binary tests and uncensored data. We propose semiparametric models that accommodate continuous tests and censoring. Asymptotic distribution theory for parameter estimates is developed and procedures for making statistical inference are evaluated with simulation studies. We illustrate our methods with data from the Cardiovascular Health Study, relating the FR-score measured at enrollment to subsequent risk of cardiovascular events.
10aAged10aAged, 80 and over10aBiomarkers10aBiometry10aCardiovascular Diseases10aFemale10aHumans10aMale10aModels, Statistical10aRisk Factors10aROC Curve10aSensitivity and Specificity10aTime Factors1 aCai, Tianxi1 aPepe, Margaret, Sullivan1 aZheng, Yingye1 aLumley, Thomas1 aJenny, Nancy, Swords uhttps://chs-nhlbi.org/node/84902915nas a2200421 4500008004100000022001400041245014000055210006900195260001300264300001100277490000700288520167100295653001901966653002001985653002802005653002502033653002802058653002202086653001102108653001102119653002802130653000902158653001602167653001502183653001902198653003002217653002602247100001902273700002102292700001902313700002102332700002002353700002302373700001902396700002302415700002002438856003502458 2006 eng d a1046-667300aSleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study.0 aSleep apnea in patients on conventional thriceweekly hemodialysi c2006 Dec a3503-90 v173 aSleep-disordered breathing (SDB) has been noted commonly in hemodialysis (HD) patients, but it is not known whether this is related directly to the treatment of kidney failure with HD or to the higher prevalence of obesity and older age. Forty-six HD patients were compared with 137 participants from the Sleep Heart Health Study (SHHS) who were matched for age, gender, body mass index (BMI), and race. Home unattended polysomnography was performed and scored using similar protocols. The study sample was 62.7 +/- 10.1 yr, was predominantly male (72%) and white (63%), and had an average BMI of 28 +/- 5.3 kg/m(2). The HD sample had a higher systolic BP (137 versus 121 mmHg; P < 0.01) and a higher prevalence of diabetes (33 versus 9%; P < 0.01) and cardiovascular disease (33 versus 13%; P < 0.01) compared with the SHHS sample. The HD group had significantly less sleep time (320 versus 379 min; P < 0.0001) but similar sleep efficiency. HD patients had a higher frequency of arousals per hour (25.1 versus 17.1; P < 0.0001) and apnea-hypopneas per hour (27.2 versus 15.2; P < 0.0001) and greater percentage of the total sleep time below an oxygen saturation of 90% (7.2 versus 1.8; P < 0.0001). HD patients were more likely to have severe SDB (>30 respiratory events per hour) compared with the SHHS sample (odds ratio 4.07; 95% confidence interval 1.83 to 9.07). There was a strong association of HD with severe SDB and nocturnal hypoxemia independent of age, BMI, and the higher prevalence of chronic disease. The potential mechanisms for the higher likelihood of SDB in the HD population must be identified to provide specific prevention and therapy.
10aBlood Pressure10aBody Mass Index10aCardiovascular Diseases10aCase-Control Studies10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aPrevalence10aRenal Dialysis10aSeverity of Illness Index10aSleep Apnea Syndromes1 aUnruh, Mark, L1 aSanders, Mark, H1 aRedline, Susan1 aPiraino, Beth, M1 aUmans, Jason, G1 aHammond, Terese, C1 aSharief, Imran1 aPunjabi, Naresh, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/92602758nas a2200421 4500008004100000022001400041245012400055210006900179260001300248300001100261490000600272520161000278653000901888653002201897653002001919653001501939653002801954653001101982653001101993653001402004653003802018653000902056653001402065653002602079653002402105653001702129653001602146653001502162653001102177100001602188700001702204700001602221700001902237700001502256700001502271700001502286856003502301 2006 eng d a1538-793300aSoluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.0 aSoluble intracellular adhesion molecule1 is associated with card c2006 Jan a107-130 v43 aBACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression.
OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study.
METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up.
RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events.
CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.
10aAged10aAged, 80 and over10aAngina Pectoris10aBiomarkers10aCardiovascular Diseases10aFemale10aHumans10aIncidence10aIntercellular Adhesion Molecule-110aMale10aMortality10aMyocardial Infarction10aRegression Analysis10aRisk Factors10aSex Factors10aSolubility10aStroke1 aJenny, N, S1 aArnold, A, M1 aKuller, L H1 aSharrett, A, R1 aFried, L P1 aPsaty, B M1 aTracy, R P uhttps://chs-nhlbi.org/node/88002728nas a2200373 4500008004100000022001400041245010900055210006900164260001300233300001100246490000600257520169000263653000901953653002201962653002001984653003002004653001902034653001102053653001102064653000902075653003202084653001702116653002002133653002202153100002402175700001702199700001602216700001802232700001802250700001602268700002002284700001502304856003502319 2006 eng d a1538-793300aSubclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study.0 aSubclinical atherosclerosis and the risk of future venous thromb c2006 Sep a1903-80 v43 aBACKGROUND: Recent reports have suggested an association of atherosclerosis with risk of venous thrombosis.
OBJECTIVE: To confirm whether subclinical atherosclerosis is a risk factor for venous thrombosis (VT) among men and women age 65 and older.
METHODS: Participants of the Cardiovascular Health Study (n = 4,108) without baseline clinical cardiovascular disease, anticoagulant use or previous VT were followed for a median of 11.7 years after non-invasive assessment of subclinical atherosclerosis using carotid ultrasound (intima-media thickness and presence of plaques), ankle-brachial blood pressure index and electrocardiogram. Each event was classified as idiopathic or secondary. We used Cox proportional hazards regression to estimate the relative risk of overall and idiopathic VT for individuals with and without baseline subclinical atherosclerosis.
RESULTS: There were 133 first time VT events. No subclinical atherosclerosis measures were associated with increased risk of overall or idiopathic VT. The adjusted relative risks of overall and idiopathic VT for presence of any type of subclinical disease were 0.60 (95% confidence interval 0.39-0.91) and 0.32 (0.18-0.59), respectively. Most of this association was explained by an inverse association of high-risk carotid plaques (prevalent in 54% of those at risk) with VT.
CONCLUSION: Non-invasively measured subclinical atherosclerosis was not associated with increased risk of overall or idiopathic VT in this observational study. Carotid plaques and arterial events during follow up were inversely associated, a finding that requires further study.
10aAged10aAged, 80 and over10aAtherosclerosis10aCarotid Artery Thrombosis10aCohort Studies10aFemale10aHumans10aMale10aProportional Hazards Models10aRisk Factors10aUltrasonography10aVenous Thrombosis1 avan der Hagen, P, B1 aFolsom, A, R1 aJenny, N, S1 aHeckbert, S R1 aO'Meara, E, S1 aReich, L, M1 aRosendaal, F, R1 aCushman, M uhttps://chs-nhlbi.org/node/91603566nas a2200373 4500008004100000022001400041245007200055210006900127260001600196300001200212490000800224520254200232653000902774653002402783653002802807653001102835653001102846653002002857653001902877653000902896653003202905653001702937653001802954653001602972100002102988700002003009700002103029700002003050700002103070700002203091700002203113700002203135856003503157 2006 eng d a1538-359800aThyroid status, cardiovascular risk, and mortality in older adults.0 aThyroid status cardiovascular risk and mortality in older adults c2006 Mar 01 a1033-410 v2953 aCONTEXT: Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system.
OBJECTIVE: To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication.
DESIGN, SETTING, AND PARTICIPANTS: A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study.
MAIN OUTCOME MEASURES: Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism.
RESULTS: Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease.
CONCLUSION: Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.
10aAged10aAtrial Fibrillation10aCardiovascular Diseases10aFemale10aHumans10aHyperthyroidism10aHypothyroidism10aMale10aProportional Hazards Models10aRisk Factors10aThyroid Gland10aThyrotropin1 aCappola, Anne, R1 aFried, Linda, P1 aArnold, Alice, M1 aDanese, Mark, D1 aKuller, Lewis, H1 aBurke, Gregory, L1 aTracy, Russell, P1 aLadenson, Paul, W uhttps://chs-nhlbi.org/node/89003370nas a2200409 4500008004100000022001400041245022900055210006900284260001600353300001000369490000700379520208600386653001602472653000902488653002202497653001002519653002802529653003002557653001102587653001802598653001102616653003402627653000902661653003302670653002602703653003002729653001702759653001602776653001102792100002202803700002102825700001802846700002002864700002002884700002102904856003502925 2006 eng d a0002-914900aUsefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study).0 aUsefulness of aortic root dimension in persons or 65 years of ag c2006 Jan 15 a270-50 v973 aEchocardiographic measures of left ventricular (LV) function and structure as well as left atrial size have been reported to predict adverse cardiovascular disease (CVD) outcomes. Although anatomic changes of the aortic root are likely to reflect effects of hypertension and atherosclerosis, few data are available on the predictive value of aortic root dimension (ARD) for outcome in free-living populations. The purpose of this investigation was to determine whether in a cohort of patients aged > or = 65 years ARD was associated with traditional coronary heart disease (CHD) risk factors and with 10-year incident CVD outcomes. In the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Health Study, 3,933 free-living black and white men and women > or = 65 years of age without prevalent CVD had 2-dimensional directed M-mode echocardiographic measurements of ARD as part of a comprehensive evaluation. ARD was associated with age and gender (greater in men) but not race. ARD was also positively associated with diastolic blood pressure, LV hypertrophy, major electrocardiographic abnormalities, and other echocardiographic measures, including LV mass, ventricular septal and posterior wall thickness, and LV dimension. After adjustment for other known risk factors, high ARD was associated with an increased risk for incident congestive heart failure (CHF) in men (hazard ratio for upper compared with all other quintiles 1.47, p = 0.014), stroke in men and women (hazard ratio 1.39 per cm, p = 0.015), CVD mortality in men and women (hazard ratio 1.48 per cm, p = 0.007), and total mortality in men and women taking antihypertensive medications (hazard ratio 1.46 per cm, p = 0.007), but not with incident myocardial infarction (MI) (hazard ratio 0.89, p = 0.39). In conclusion, in a cohort of patients aged > or = 65 years without clinical CVD at baseline, ARD was associated with several CHD risk factors and measures of subclinical disease and was predictive of incident CHF, stroke, CVD mortality, and all-cause mortality, but not of incident MI.
10aAge Factors10aAged10aAged, 80 and over10aAorta10aCardiovascular Diseases10aEchocardiography, Doppler10aFemale10aHeart Failure10aHumans10aHypertrophy, Left Ventricular10aMale10aMulticenter Studies as Topic10aMyocardial Infarction10aPredictive Value of Tests10aRisk Factors10aSex Factors10aStroke1 aGardin, Julius, M1 aArnold, Alice, M1 aPolak, Joseph1 aJackson, Sharon1 aSmith, Vivienne1 aGottdiener, John uhttps://chs-nhlbi.org/node/88602648nas a2200409 4500008004100000022001400041245014800055210006900203260001300272300001200285490000600297520150000303653002701803653000901830653002501839653002701864653001301891653001601904653001101920653001101931653002501942653000901967653001601976653001701992653002002009653002202029653002602051100001302077700001502090700001502105700001302120700001802133700001602151700001902167700001702186856003502203 2007 eng d a1538-793300aABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).0 aABO blood group other risk factors and incidence of venous throm c2007 Jul a1455-610 v53 aBACKGROUND: Numerous case-control studies have reported higher prevalence of non-O blood type among venous thromboembolism (VTE) patients than controls, but potential mechanisms or effect modifiers for the association are not fully established.
PATIENTS/METHODS: Using a nested case-control design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, ABO blood type and other VTE risk factors were measured on pre-event blood samples of 492 participants who subsequently developed VTE and 1008 participants who remained free of VTE.
RESULTS: A total of 64.4% of cases and 52.5% of controls had non-O blood type. Among controls, mean values of factor VIIIc (FVIIIc) and von Willebrand factor among the non-O blood type group were higher than among the O group. Compared with O blood type, the age-adjusted odds ratio (OR) of VTE for non-O blood type was 1.64 (95% CI, 1.32-2.05) and was similar for the two parent studies and race groups. Further adjustment for sex, race, body mass index, diabetes mellitus and FVIIIc reduced the OR: 1.31 (95% CI, 1.02-1.68). Factor V Leiden (FV Leiden) appeared to modify the non-O blood type association with VTE in a supra-additive fashion, with an age-, sex- and race-adjusted OR of 6.77 (95% CI, 3.65-12.6) for having both risk factors.
CONCLUSIONS: Non-O blood type was independently associated with risk of VTE, and added to the risk associated with FV Leiden.
10aABO Blood-Group System10aAged10aCase-Control Studies10aDiabetes Complications10aFactor V10aFactor VIII10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aRisk Factors10aThromboembolism10aVenous Thrombosis10avon Willebrand Factor1 aOhira, T1 aCushman, M1 aTsai, M, Y1 aZhang, Y1 aHeckbert, S R1 aZakai, N, A1 aRosamond, W, D1 aFolsom, A, R uhttps://chs-nhlbi.org/node/95602331nas a2200445 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520114200243653000901385653002501394653002801419653002401447653001101471653001101482653002501493653003101518653000901549653002101558653002601579653001601605653001701621100002401638700001601662700001601678700001901694700001701713700001001730700001401740700001401754700002101768700001801789700001101807700001501818700001701833856003501850 2007 eng d a1558-149700aAcceleration of cerebral ventricular expansion in the Cardiovascular Health Study.0 aAcceleration of cerebral ventricular expansion in the Cardiovasc c2007 Sep a1316-210 v283 aInteractions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.
10aAged10aAnalysis of Variance10aCardiovascular Diseases10aCerebral Ventricles10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aReference Values10aRetrospective Studies10aSex Factors10aTime Factors1 aCarmichael, Owen, T1 aKuller, L H1 aLopez, O, L1 aThompson, P, M1 aDutton, R, A1 aLu, A1 aLee, S, E1 aLee, J, Y1 aAizenstein, H, J1 aMeltzer, C, C1 aLiu, Y1 aToga, A, W1 aBecker, J, T uhttps://chs-nhlbi.org/node/90902882nas a2200385 4500008004100000022001400041245006800055210006700123260001300190300001200203490000700215520181900222653000902041653002102050653001602071653002102087653002102108653002202129653002102151653002802172653001102200653001102211653003602222653000902258653001502267653001702282100002402299700002202323700002102345700002202366700002402388700002502412700002402437856003502461 2007 eng d a0021-972X00aAlcohol consumption and lipoprotein subclasses in older adults.0 aAlcohol consumption and lipoprotein subclasses in older adults c2007 Jul a2559-660 v923 aCONTEXT: Limited evidence suggests that alcohol intake may be associated with lipoprotein subclass distribution, which could mediate its relationship with coronary heart disease.
OBJECTIVES: The objective was to determine the relationship of alcohol intake with lipoprotein particle subclasses.
DESIGN, SETTING, AND PARTICIPANTS: The study included a cross-sectional analysis of 1850 participants of the Cardiovascular Health Study aged 65 yr and older and free of clinical cardiovascular disease.
MAIN OUTCOME MEASURE: Lipoprotein subclass distribution was measured with nuclear magnetic resonance spectroscopy, according to self-reported alcohol intake.
RESULTS: Alcohol intake was associated with total low-density lipoprotein (LDL) particles in a U-shaped manner. Consumers of one or more drinks per week had the highest number of large LDL particles, whereas consumers of 7-13 drinks per week had the lowest number of small LDL particles. Alcohol intake was strongly positively associated with large- and medium-sized high-density lipoprotein (HDL) particles but had an inverse relationship with concentrations of small HDL particles and small- and medium-sized very-low-density lipoprotein particles. Average particle sizes of all three lipoproteins were positively associated with alcohol intake. Associations were generally stronger among women than men but in similar directions. Beverage type did not consistently modify these findings.
CONCLUSIONS: Alcohol intake is associated with less total LDL particles, lower levels of small LDL, HDL, and very-low-density lipoprotein particles, and higher levels of large LDL and medium- and large-sized HDL particles in older adults free of prevalent clinical cardiovascular disease.
10aAged10aAlcohol Drinking10aCholesterol10aCholesterol, HDL10aCholesterol, LDL10aCholesterol, VLDL10aCoronary Disease10aCross-Sectional Studies10aFemale10aHumans10aMagnetic Resonance Spectroscopy10aMale10aPrevalence10aRisk Factors1 aMukamal, Kenneth, J1 aMackey, Rachel, H1 aKuller, Lewis, H1 aTracy, Russell, P1 aKronmal, Richard, A1 aMittleman, Murray, A1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/95902744nas a2200361 4500008004100000022001400041245012300055210006900178260001300247300001000260490000800270520170700278653000901985653002101994653002402015653001102039653002202050653001102072653001402083653002502097653000902122653001402131653001702145100002402162700002002186700002602206700002102232700002102253700002502274700002402299700002402323856003502347 2007 eng d a1097-674400aAlcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.0 aAlcohol consumption and risk and prognosis of atrial fibrillatio c2007 Feb a260-60 v1533 aBACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined.
METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations.
RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95% CI, 1.02-1.54) among former drinkers, 1.09 (95% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95% CI, 1.06-1.52) among former drinkers, 0.94 (95% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12).
CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.
10aAged10aAlcohol Drinking10aAtrial Fibrillation10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aPrognosis10aRisk Factors1 aMukamal, Kenneth, J1 aPsaty, Bruce, M1 aRautaharju, Pentti, M1 aFurberg, Curt, D1 aKuller, Lewis, H1 aMittleman, Murray, A1 aGottdiener, John, S1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/93902567nas a2200373 4500008004100000022001400041245009700055210006900152260001300221300001200234490000700246520156300253653000901816653002201825653002101847653003001868653001101898653002201909653001101931653001401942653002501956653000901981653001301990653001602003653000902019653001202028653001502040653001802055100001802073700001902091700002402110700002402134856003502158 2007 eng d a1930-738100aAlcohol consumption and type 2 diabetes among older adults: the Cardiovascular Health Study.0 aAlcohol consumption and type 2 diabetes among older adults the C c2007 Jul a1758-650 v153 aOBJECTIVE: The objective was to examine the role of total and beverage-specific alcohol consumption on the incidence of type 2 diabetes mellitus (DM) among elderly men and women.
RESEARCH METHODS AND PROCEDURES: We studied prospectively 4655 participants of the Cardiovascular Health Study who were free of DM at baseline. Alcohol consumption was obtained at baseline and during follow-up examinations. DM was defined using fasting glucose and/or use of hypoglycemic medications. We used Cox proportional hazard models to estimate adjusted relative risks of diabetes across alcohol categories.
RESULTS: During a mean follow-up of 6.3 years, 234 incident cases of DM were documented. Compared with never drinkers, hazard ratios [95% confidence interval (CI)] for DM were 0.7 (0.3 to 1.4), 0.5 (0.3 to 0.9), 0.6 (0.4 to 1.1), and 0.8 (0.4 to 1.3) for former drinkers and current drinkers of <1, 1 to 6, and 7+ drinks per week, respectively, for men after adjustment for age, BMI, education, and smoking. Corresponding values for women were 1.2 (0.6 to 2.3), 0.7 (0.4 to 1.1), 0.6 (0.3 to 1.1), and 0.4 (0.2 to 1.0), respectively. A reduced risk of DM was observed with all types of beverage consumed. Similar findings were observed when we repeated the above analyses using simple or weighted cumulative alcohol update and covariates over time.
DISCUSSION: Light to moderate alcohol consumption was associated with a lower incidence of DM among elderly people, irrespective of the type of beverage consumed.
10aAged10aAged, 80 and over10aAlcohol Drinking10aDiabetes Mellitus, Type 210aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMedicare10aMiddle Aged10aRisk10aSmoking10aTemperance10aUnited States1 aDjoussé, Luc1 aBiggs, Mary, L1 aMukamal, Kenneth, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/97102833nas a2200409 4500008004100000022001400041245010900055210006900164260001300233300001200246490000700258520172900265653002701994653000902021653002102030653002402051653002202075653001702097653001102114653001502125653001302140653000802153653001802161653001102179653002502190653000902215653002002224653001702244653002102261653001802282100001802300700001802318700001702336700001502353700002002368856003502388 2007 eng d a0937-941X00aAlcohol consumption, bone density, and hip fracture among older adults: the cardiovascular health study.0 aAlcohol consumption bone density and hip fracture among older ad c2007 May a593-6020 v183 aINTRODUCTION: Previous studies have found inconsistent relationships of alcohol consumption with risk of hip fracture, and the importance of bone mineral density and risk of falls in mediating such a relationship has not been determined.
METHODS: As part of the Cardiovascular Health Study, a population-based cohort study of adults aged 65 years and older from four U.S. communities, 5,865 participants reported their use of beer, wine, and liquor yearly. We identified cases of hip fracture unrelated to malignancy or motor vehicle accidents using hospitalization discharge diagnoses. A subgroup of 1,567 participants in two communities underwent dual-energy x-ray absorptiometry scans to assess bone mineral density.
RESULTS: A total of 412 cases of hip fracture occurred during an average of 12 years of follow-up. There was a significant U-shaped relationship between alcohol intake and risk of hip fracture (p quadratic 0.02). Compared with long-term abstainers, the adjusted hazard ratios for hip fracture were 0.78 (95% confidence interval [CI], 0.61-1.00) among consumers of up to 14 drinks per week and 1.18 (95% CI, 0.77-1.81) among consumers of 14 or more drinks per week. Alcohol intake was associated with bone mineral density of the total hip and femoral neck in a stepwise manner, with approximately 5% (95% CI, 1%-9%) higher bone density among consumers of 14 or more drinks per week than among abstainers. These relationships were all similar among men and women.
CONCLUSIONS: Among older adults, moderate alcohol consumption has a U-shaped relationship with risk of hip fracture, but a graded positive relationship with bone mineral density at the hip.
10aAbsorptiometry, Photon10aAged10aAlcohol Drinking10aAlcoholic Beverages10aApolipoproteins E10aBone Density10aFemale10aFemur Neck10aGenotype10aHip10aHip Fractures10aHumans10aLongitudinal Studies10aMale10aRisk Assessment10aRisk Factors10aSex Distribution10aUnited States1 aMukamal, K, J1 aRobbins, J, A1 aCauley, J, A1 aKern, L, M1 aSiscovick, D, S uhttps://chs-nhlbi.org/node/94402232nas a2200349 4500008004100000022001400041245014400055210006900199260001300268300001100281490000700292520120200299653000901501653002101510653002201531653002201553653001801575653002301593653001901616653001101635653001301646653001101659653001801670653000901688653003001697653003001727100002401757700002001781700002201801700002401823856003501847 2007 eng d a0002-916500aAlcohol consumption, interleukin-6 and apolipoprotein E genotypes, and concentrations of interleukin-6 and serum amyloid P in older adults.0 aAlcohol consumption interleukin6 and apolipoprotein E genotypes c2007 Aug a444-500 v863 aBACKGROUND: Whether alcohol intake is associated with concentrations of interleukin-6 (IL-6) and serum amyloid P (SAP) is uncertain.
OBJECTIVE: We determined how alcohol intake and apolipoprotein E (apo E) and IL-6 promoter (IL-6 -174G-->C) polymorphisms interact for concentrations of IL-6 and SAP.
DESIGN: In the Cardiovascular Health Study, 2454 older adults reported their intake of beer, wine, and liquor and underwent measurements of circulating IL-6 and SAP.
RESULTS: Alcohol intake was not associated with IL-6 concentrations among apo E4-negative or IL-6C-positive participants but was positively associated among both apo E4-positive and IL-6C-negative participants (P for trend = 0.02 for both). The corresponding interactions on SAP were not significant for alcohol overall but were similar for liquor intake.
CONCLUSIONS: Among older adults free of clinical cardiovascular disease, specific IL-6 promoter and apo E alleles appeared to confer positive associations of alcohol consumption with IL-6 concentrations. Genetic heterogeneity should be considered in understanding the cardiovascular effects of alcohol intake.
10aAged10aAlcohol Drinking10aApolipoprotein E410aApolipoproteins E10aBlood Glucose10aC-Reactive Protein10aCohort Studies10aFemale10aGenotype10aHumans10aInterleukin-610aMale10aPromoter Regions, Genetic10aSerum Amyloid P-Component1 aMukamal, Kenneth, J1 aJenny, Nancy, S1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/97402454nas a2200445 4500008004100000022001400041245010900055210006900164260001300233300001000246490000800256520118900264653002201453653000901475653002201484653001201506653002201518653002201540653002201562653002801584653004001612653001101652653001301663653001101676653002501687653000901712653001501721653002601736653001701762100002401779700001401803700002201817700001801839700002401857700002801881700002401909700002201933700001801955856003501973 2007 eng d a0003-995000aApolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study.0 aApolipoprotein e gene and agerelated maculopathy in older indivi c2007 Jan a68-730 v1253 aOBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and age-related maculopathy (ARM) in an older population.
METHODS: Two thousand one hundred seventy persons 65 years and older sampled from 4 US communities had ARM signs assessed from retinal photographs using a modified Wisconsin Age-Related Maculopathy Grading System. DNA extracted from blood samples was analyzed for common APOE alleles.
RESULTS: After controlling for age, sex, cigarette smoking, and other factors, white participants carrying the epsilon2 allele had an increased risk of late ARM (odds ratio, 2.53 [95% confidence interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too few late ARM cases in African American individuals for analysis.
CONCLUSION: APOE polymorphism is associated with late ARM in older white persons 65 years and older. Consistent with previous studies, the APOE epsilon2 allele is associated with a significant increased risk of late ARM development, whereas the epsilon4 allele may confer some protection.
10aAfrican Americans10aAged10aAged, 80 and over10aAlleles10aApolipoprotein E210aApolipoprotein E310aApolipoprotein E410aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aGenotype10aHumans10aMacular Degeneration10aMale10aOdds Ratio10aPolymorphism, Genetic10aRisk Factors1 aTikellis, Gabriella1 aSun, Cong1 aGorin, Michael, B1 aKlein, Ronald1 aKlein, Barbara, E K1 aLarsen, Emily, K Marino1 aSiscovick, David, S1 aHubbard, Larry, D1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/93503354nas a2200409 4500008004100000022001400041245010800055210006900163260001600232300001200248490000700260520220200267653000902469653002202478653002202500653002202522653002202544653004002566653001102606653001902617653001302636653001702649653001502666653001102681653000902692653002102701653002602722653002102748653002002769100001402789700002402803700001702827700001802844700002802862700001802890856003602908 2007 eng d a1090-053500aApolipoprotein E gene and retinal microvascular signs in older people: the Cardiovascular Health Study.0 aApolipoprotein E gene and retinal microvascular signs in older p c2007 Nov 12 a2105-110 v133 aPURPOSE: To examine the association between apolipoprotein E (APOE) gene polymorphism and retinal microvascular signs in an older population.
METHODS: Retinal photographs were taken of 2,152 participants (1,831 whites, and 321 African-Americans), aged 69-96 years, who were participating in a population-based study of four United States communities. We used standardized protocols to assess photographs for the presence of retinal microvascular signs (retinopathy, arterio-venous nicking, and focal arteriolar narrowing) and a computer-assisted method to measure retinal vessel diameters. We analyzed DNA extracted from blood samples of participants for common allelic variants of the APOE gene.
RESULTS: After adjusting for age, gender, systolic blood pressure, smoking, total serum cholesterol, and other risk factors, we found white participants carrying the epsilon2 and epsilon4 alleles were more likely to have arterio-venous nicking than the epsilon3/epsilon3 homozygotes, with odds ratio (OR) of 1.70 and confidence interval (CI) 95% (1.03-2.83) for the epsilon2 carriers and OR 1.74 (95% CI 1.06-2.84) for the epsilon4 carriers. Among white participants without hypertension, the associations remained significant for the epsilon4 carriers (OR 2.32, 95% CI 1.18-4.57). Whites, normotensive carriers of the epsilon2 allele had significantly narrower retinal arteriolar diameters (adjusted mean arteriolar diameter of 163.5 mum, 95% CI 160.1-167.0, p=0.03) compared to the epsilon3/epsilon3 homozygotes (167.8 mum, 95% CI 166.0-169.6). APOE gene polymorphism was not associated with retinopathy, focal narrowing, or retinal venular diameters in white participants. There were insufficient numbers of African-Americans for separate multivariate analysis.
CONCLUSIONS: This study provides little evidence that the APOE gene polymorphism plays a significant role in the pathogenesis of retinal microvascular changes in the general population. In the older white population, APOE epsilon2 and epsilon4 allele carriers were more likely to have arterio-venous nicking. Other retinal signs, however, were not related to APOE gene polymorphism.
10aAged10aAged, 80 and over10aApolipoprotein E210aApolipoprotein E410aApolipoproteins E10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenotype10aHeterozygote10aHomozygote10aHumans10aMale10aMicrocirculation10aPolymorphism, Genetic10aRetinal Diseases10aRetinal Vessels1 aSun, Cong1 aTikellis, Gabriella1 aLiew, Gerald1 aKlein, Ronald1 aLarsen, Emily, K Marino1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/100303099nas a2200469 4500008004100000022001400041245012000055210006900175260001300244300001100257490000700268520174700275653000902022653002202031653002002053653002802073653001902101653001602120653002802136653001502164653001102179653002802190653001102218653000902229653002102238653002602259653002902285653002102314653002702335653001702362653002402379653001802403100001402421700002402435700001802459700002302477700002802500700002402528700002402552700001802576856003502594 2007 eng d a1064-748100aAre microvascular abnormalities in the retina associated with depression symptoms? The Cardiovascular Health Study.0 aAre microvascular abnormalities in the retina associated with de c2007 Apr a335-430 v153 aOBJECTIVE: Depression has been linked with vascular risk factors and stroke. The authors examined the relationship between retinal microvascular abnormalities and depression symptoms in an elderly population.
METHODS: The Cardiovascular Health Study is a population-based study conducted in four U.S. communities initiated in 1989-1990. A total of 2,420 persons aged 65 years and older were included in the current analyses. During the 1997-1998 examination, retinal photographs were performed and assessed for retinal microvascular abnormalities (retinopathy, focal arteriolar narrowing, arteriovenous nicking, generalized retinal arteriolar narrowing, and generalized retinal venular dilation) according to standardized methods. Depression symptoms were assessed by a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989 through 1997-1998 and was defined as a CES-D score of >9.
RESULTS: Participants with retinal microvascular abnormalities were not more likely to have depression symptoms, with adjusted odds ratio (OR) (95% confidence intervals) of 1.08 (0.71-1.65) for retinopathy, OR 1.09 (0.71-1.68) for focal arteriolar narrowing, OR 0.85 (0.52-1.40) for arteriovenous nicking, OR 0.97 (0.70-1.34) for generalized arteriolar narrowing, and OR 0.79 (0.56-1.12) for generalized venular dilation. Retinal microvascular abnormalities were not related to depression symptoms in multinomial logistic regression comparing the three top quartiles of the depression CES-D scores with the lowest quartile.
CONCLUSIONS: Our study did not find an association between retinal microvascular abnormalities and depression symptoms in older people.
10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aComorbidity10aCross-Sectional Studies10aDepression10aFemale10aFluorescein Angiography10aHumans10aMale10aMicrocirculation10aPersonality Inventory10aRetinal Artery Occlusion10aRetinal Diseases10aRetinal Vein Occlusion10aRisk Factors10aStatistics as Topic10aUnited States1 aSun, Cong1 aTikellis, Gabriella1 aKlein, Ronald1 aSteffens, David, C1 aLarsen, Emily, K Marino1 aSiscovick, David, S1 aKlein, Barbara, E K1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/94902663nas a2200385 4500008004100000022001400041245010900055210006900164260000900233300000800242490000800250520154800258653003901806653000901845653002501854653004001879653001101919653001501930653001301945653001101958653002001969653000901989653001601998653002302014653002602037653002702063100003102090700001802121700002102139700001502160700002302175700002302198700002102221856003502242 2007 eng d a0049-384800aThe association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study.0 aassociation of alphafibrinogen Thr312Ala polymorphism and venous c2007 a1-70 v1213 aINTRODUCTION: The alpha-fibrinogen Thr312Ala variant has been shown to influence clot structure through increased factor XIII cross-linking and formation of thicker fibrin fibers. However, the effect of this common variant on risk of venous thromboembolism (VTE) is unclear. This paper reports the association between the Thr312Ala variant and VTE in the LITE study.
MATERIALS AND METHODS: 506 cases and 1014 controls frequency matched on age, sex, race, and study were drawn from two prospective studies and included in the analysis. Logistic regression was used to examine the association between Thr312Ala and VTE.
RESULTS: In a logistic regression model minimally adjusted for the matching variables, the Thr312Ala TA and AA genotypes were associated with a significantly higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27 [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE and DVT considered separately and across racial and study subgroups. The association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected by an additive or multiplicative model of individual risk factors.
CONCLUSIONS: These results suggest that alpha-fibrinogen Thr312Ala is involved in the pathogenesis of VTE and that its action may be modified by other VTE risk factors.
10aAfrican Continental Ancestry Group10aAged10aCase-Control Studies10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aGenotype10aHumans10aLogistic Models10aMale10aMiddle Aged10aMutation, Missense10aPolymorphism, Genetic10aVenous Thromboembolism1 aRasmussen-Torvik, Laura, J1 aCushman, Mary1 aTsai, Michael, Y1 aZhang, Yan1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/95803594nas a2200661 4500008004100000022001400041245018300055210006900238260001600307300000900323490000800332520170200340653002202042653000902064653001502073653002302088653002802111653002802139653001902167653001602186653002202202653004002224653001102264653002202275653001102297653002002308653001702328653001402345653001702359653002602376653000902402653001902411653001402430653002602444653001202470653003002482653003202512653002402544653002002568653001702588653001402605653001202619653001102631653002202642653001802664653001702682653002002699653001802719100001602737700002102753700002102774700002102795700002002816700002202836700002102858700001802879856003502897 2007 eng d a1524-453900aAssociation of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.0 aAssociation of carotid artery intimamedia thickness plaques and c2007 Jul 03 a32-80 v1163 aBACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.
METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.
CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.
10aAfrican Americans10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCarotid Artery Diseases10aCohort Studies10aComorbidity10aDiabetes Mellitus10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aHyperlipidemias10aHypertension10aIncidence10aInflammation10aKaplan-Meier Estimate10aMale10aMass Screening10aMortality10aMyocardial Infarction10aObesity10aPredictive Value of Tests10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aROC Curve10aSmoking10aStroke10aSurvival Analysis10aTunica Intima10aTunica Media10aUltrasonography10aUnited States1 aCao, Jie, J1 aArnold, Alice, M1 aManolio, Teri, A1 aPolak, Joseph, F1 aPsaty, Bruce, M1 aHirsch, Calvin, H1 aKuller, Lewis, H1 aCushman, Mary uhttps://chs-nhlbi.org/node/96702943nas a2200457 4500008004100000022001400041245007900055210006900134260001300203300001000216490000700226520171800233653000901951653002201960653001501982653001401997653001102011653001802022653001102040653001102051653002802062653002502090653000902115653001702124653002402141653001702165653001602182100002002198700002402218700002402242700002102266700002202287700002902309700001702338700002102355700001902376700001702395700002002412700001802432856003502450 2007 eng d a1046-667300aAssociation of kidney function with incident hip fracture in older adults.0 aAssociation of kidney function with incident hip fracture in old c2007 Jan a282-60 v183 aKidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95% CI 1.01, 1.33) but not in men (HR 1.14; 95% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk.
10aAged10aAged, 80 and over10aCystatin C10aCystatins10aFemale10aHip Fractures10aHumans10aKidney10aKidney Failure, Chronic10aLongitudinal Studies10aMale10aOsteoporosis10aProspective Studies10aRisk Factors10aSex Factors1 aFried, Linda, F1 aBiggs, Mary, Louise1 aShlipak, Michael, G1 aSeliger, Stephen1 aKestenbaum, Bryan1 aStehman-Breen, Catherine1 aSarnak, Mark1 aSiscovick, David1 aHarris, Tamara1 aCauley, Jane1 aNewman, Anne, B1 aRobbins, John uhttps://chs-nhlbi.org/node/93303135nas a2200469 4500008004100000022001400041245007000055210006800125260001300193300001100206490000700217520184800224653001002072653002702082653002802109653001902137653001302156653001102169653001102180653002502191653000902216653001602225653001202241653002002253653004302273653002602316653001702342653001602359653002602375653002902401653001702430653001602447100002002463700002402483700001902507700001902526700002402545700001702569700002102586700002302607856003502630 2007 eng d a1520-951200aAssociation of physical activity with sleep-disordered breathing.0 aAssociation of physical activity with sleepdisordered breathing c2007 Sep a149-570 v113 aThis study was performed to determine whether there is a protective association between participation in vigorous or vigorous/moderately vigorous physical activity and the prevalence of sleep-disordered breathing (SDB). Polysomnographic and questionnaire data from the baseline examination of 4,275 participants in the Sleep Heart Health Study (SHHS) were analyzed in relation to information on amount of physical activity and other potentially relevant factors collected from five SHHS parent cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, Strong Heart Study, and Tucson Epidemiologic Study of Airways Obstructive Diseases). Logistic regression models were fitted to determine if amount and strenuousness of physical activity was associated with the presence of SDB. At least 3 h per week of vigorous physical activity reduced the odds of SDB, defined as a respiratory disturbance index (RDI) of at least 15 apneas/hypopneas per hour (Adjusted OR, 0.68; 95%CI, 0.51-0.91). A qualitatively similar but slightly weaker association was observed when SDB was defined as a RDI > or = 10 per hour (Adjusted OR, 0.81; 95%CI, 0.64-1.02). These findings remained after adjustment for sleepiness and restricting analyses to participants with good health. Three or more hours of moderately vigorous or vigorous physical activity also appeared to confer some protection against SDB, but these associations were weaker. Gender- and obesity-stratified analyses suggested that the protective association between physical activity and SDB occurred primarily in men and those who were obese. A program of regular vigorous physical activity of at least 3 h per week may be a useful adjunctive treatment modality for SDB, but this association needs confirmation with a prospective clinical trial.
10aAdult10aCardiac Rehabilitation10aCardiovascular Diseases10aCohort Studies10aExercise10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aObesity10aPolysomnography10aPulmonary Disease, Chronic Obstructive10aPulmonary Ventilation10aRisk Factors10aSex Factors10aSleep Apnea Syndromes10aSleep Apnea, Obstructive10aSleep Stages10aWeight Loss1 aQuan, Stuart, F1 aO'Connor, George, T1 aQuan, Jason, S1 aRedline, Susan1 aResnick, Helaine, E1 aShahar, Eyal1 aSiscovick, David1 aSherrill, Duane, L uhttps://chs-nhlbi.org/node/93703188nas a2200409 4500008004100000022001400041245018100055210006900236260001300305300001200318490000700330520189900337653000902236653002802245653002502273653001902298653002102317653001102338653001102349653004902360653004902409653003302458653000902491653002602500653001702526653001102543100002202554700002202576700002302598700002102621700002502642700001802667700002102685700001702706700002002723856003502743 2007 eng d a0021-972X00aAssociation of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke.0 aAssociation of total insulinlike growth factorI insulinlike grow c2007 Apr a1319-250 v923 aCONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.
OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.
DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.
MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.
RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.
CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.
10aAged10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCoronary Disease10aFemale10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aMultivariate Analysis10aRisk Factors10aStroke1 aKaplan, Robert, C1 aMcGinn, Aileen, P1 aPollak, Michael, N1 aKuller, Lewis, H1 aStrickler, Howard, D1 aRohan, Tom, E1 aCappola, Anne, R1 aXue, XiaoNan1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/94002775nas a2200433 4500008004100000022001400041245014500055210006900200260001600269300001000285490000800295520153200303653001601835653000901851653002201860653002101882653002401903653001101927653001101938653001801949653002501967653003101992653000902023653002102032653001602053653001102069653002102080653002002101653002002121653001702141100001902158700002802177700001802205700002002223700002102243700002102264700002102285856003502306 2007 eng d a0002-926200aAssociations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study.0 aAssociations between findings on cranial magnetic resonance imag c2007 Jan 01 a78-840 v1653 aAssociations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.
10aAge Factors10aAged10aAged, 80 and over10aArteriosclerosis10aCerebral Infarction10aFemale10aHumans10aLeukoaraiosis10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMicrocirculation10aPhotography10aRetina10aRetinal Diseases10aRetinal Vessels10aRisk Assessment10aRisk Factors1 aLongstreth, Wt1 aLarsen, Emily, K Marino1 aKlein, Ronald1 aWong, Tien, Yin1 aSharrett, Richey1 aLefkowitz, David1 aManolio, Teri, A uhttps://chs-nhlbi.org/node/92102953nas a2200457 4500008004100000022001400041245026000055210006900315260001600384300001100400490000800411520157000419653001001989653002201999653001602021653001502037653002002052653002302072653002802095653001902123653001102142653001502153653001102168653001802179653000902197653002402206653001702230653001602247653001202263653001702275653001802292110003702310700001502347700001602362700001902378700001502397700001702412700001702429700001402446856003502460 2007 eng d a0002-926200aAssociations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collab0 aAssociations of plasma fibrinogen levels with established cardio c2007 Oct 15 a867-790 v1663 aLong-term increases in plasma fibrinogen levels of 1 g/liter are associated with an approximate doubling of risk of major cardiovascular disease outcomes, but causality remains uncertain. To quantify cross-sectional associations of fibrinogen levels with established risk factors and other characteristics, the investigators combined individual data on 154,211 apparently healthy adults from 31 prospective studies conducted between 1967 and 2003, using a linear mixed model that included random effects at the cohort level. Fibrinogen levels increased with age and showed continuous, approximately linear relations with several risk markers and slightly curvilinear associations with log triglycerides, albumin, and tobacco and alcohol consumption. Female sex, Black ethnicity, lower socioeconomic status, and alcohol abstinence were each associated with modestly higher fibrinogen levels. Approximately one third of the variation in fibrinogen levels was explained by cohort, age, and sex. An additional 7% was explained by established risk factors (notably, positive associations with smoking and body mass index and an inverse association with high density lipoprotein cholesterol), and a further 10% was explained by inflammatory markers (notably, a positive association with C-reactive protein). The association with body mass index was twice as strong in women as in men, whereas the association with smoking was much stronger in men. These findings substantially advance understanding of the correlates and possible determinants of fibrinogen levels.
10aAdult10aAfrican Americans10aAge Factors10aBiomarkers10aBody Mass Index10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aFemale10aFibrinogen10aHumans10aLinear Models10aMale10aProspective Studies10aRisk Factors10aSex Factors10aSmoking10aSocial Class10aUnited States1 aFibrinogen Studies Collaboration1 aKaptoge, S1 aWhite, I, R1 aThompson, S, G1 aWood, A, M1 aLewington, S1 aLowe, G, D O1 aDanesh, J uhttps://chs-nhlbi.org/node/97903381nas a2200493 4500008004100000022001400041245012600055210006900181260001600250300001100266490000800277520197400285653000902259653002202268653002002290653001502310653002002325653002802345653001902373653002602392653002602418653001102444653001702455653001102472653001402483653000902497653003002506653001402536653003202550653002402582653003102606653001702637653002302654653001602677653002002693653001802713653001702731100001902748700002002767700001802787700002202805700002502827856003502852 2007 eng d a1524-453900aBrachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study.0 aBrachial flowmediated dilation predicts incident cardiovascular c2007 May 08 a2390-70 v1153 aBACKGROUND: The relationship between impaired brachial flow-mediated dilation (FMD) and subsequent clinical cardiovascular events is not well established, especially in older adults whose FMD is often diminished. We assessed the hypothesis that FMD predicts incident cardiovascular events in a population-based cohort of older adults.
METHODS AND RESULTS: FMD was measured at the 1997 to 1998 Cardiovascular Health Study clinic visit in 2792 adults aged 72 to 98 years (82.7% white, 58.6% women) recruited at 4 clinic sites in the United States. Log-rank test and Cox proportional hazard models were used to examine the association between FMD and adjudicated cardiovascular events. A total of 674 subjects (24.1%) had an adjudicated event over the 5-year follow-up period. Event-free survival rates for cardiovascular events were significantly higher in subjects with FMD greater than the sex-specific medians than in subjects with FMD less than or equal to the sex-specific medians (78.3% versus 73.6%, log-rank P=0.006). FMD remained a significant predictor of cardiovascular events after adjustment for age, gender, diabetes mellitus, cigarette smoking, systolic and diastolic blood pressure, baseline cardiovascular disease status, and total cholesterol (hazard ratio, 0.91 [95% CI, 0.83 to 0.99], P=0.02 per unit SD of FMD) but added only approximately 1% to the prognostic accuracy of the best Cox model. Brachial artery diameter was also predictive of CV events in the adjusted Cox proportional hazard model (hazard ratio, 1.12 [95% CI, 1.02 to 1.28], P=0.025) and also added approximately 1% to the accuracy of our best Cox model.
CONCLUSIONS: FMD is a predictor of future cardiovascular events but adds very little to the prognostic accuracy of traditional cardiovascular risk scores/factors in older adults. FMD and brachial artery diameter may have similar predictive values for cardiovascular events in older adults.
10aAged10aAged, 80 and over10aAtherosclerosis10aBiomarkers10aBrachial Artery10aCardiovascular Diseases10aCohort Studies10aDisease-Free Survival10aEndothelium, Vascular10aFemale10aHemorheology10aHumans10aHyperemia10aMale10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aProspective Studies10aReproducibility of Results10aRisk Factors10aStress, Mechanical10aTourniquets10aUltrasonography10aUnited States10aVasodilation1 aYeboah, Joseph1 aCrouse, John, R1 aHsu, Fang-Chi1 aBurke, Gregory, L1 aHerrington, David, M uhttps://chs-nhlbi.org/node/96202728nas a2200481 4500008004100000022001400041245013700055210006900192260001700261300001000278490000700288520131500295653000901610653002201619653002501641653002401666653002401690653001301714653002401727653001101751653001101762653004001773653002501813653003101838653000901869653001701878653003001895653001701925100002401942700002101966700002001987700002202007700002302029700001402052700001902066700002002085700002602105700002402131700001502155700002002170700002102190856003502211 2007 eng d a0893-034100aCerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia.0 aCerebral ventricular changes associated with transitions between c2007 Jan-Mar a14-240 v213 aExpansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.
10aAged10aAged, 80 and over10aCase-Control Studies10aCerebral Ventricles10aCognition Disorders10aDementia10aDisease Progression10aFemale10aHumans10aImage Processing, Computer-Assisted10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRisk Factors10aSeverity of Illness Index10aTime Factors1 aCarmichael, Owen, T1 aKuller, Lewis, H1 aLopez, Oscar, L1 aThompson, Paul, M1 aDutton, Rebecca, A1 aLu, Allen1 aLee, Sharon, E1 aLee, Jessica, Y1 aAizenstein, Howard, J1 aMeltzer, Carolyn, C1 aLiu, Yanxi1 aToga, Arthur, W1 aBecker, James, T uhttps://chs-nhlbi.org/node/94503097nas a2200409 4500008004100000022001400041245013700055210006900192260001600261300001100277490000700288520191300295653000902208653002202217653001702239653002602256653002302282653001502305653002802320653001902348653002402367653001102391653002202402653002502424653001102449653000902460653001702469100002002486700001602506700002302522700002402545700001802569700002002587700002302607700002202630856003502652 2007 eng d a1558-359700aClinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study.0 aClinical factors but not Creactive protein predict progression o c2007 Nov 13 a1992-80 v503 aOBJECTIVES: The purpose of this study was to examine the relationship between C-reactive protein (CRP) and calcific aortic valve disease in a large, randomly selected, population-based cohort.
BACKGROUND: The pathobiology of calcific aortic stenosis involves an active inflammatory, atheromatous, osteogenic process. Elevations in CRP, a measure of systemic inflammation, have been associated with aortic stenosis.
METHODS: Two-dimensional and Doppler echocardiography and CRP measurement were performed at baseline in 5,621 participants in the Cardiovascular Health Study. Multivariable analysis was used to identify CRP as a predictor of baseline and incident aortic stenosis.
RESULTS: At a mean echocardiographic follow-up of 5 years, 9% of subjects with aortic sclerosis progressed to some degree of aortic stenosis. Increasing age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.16; p < 0.001) and male gender (OR 3.05, 95% CI 1.76 to 5.27; p < 0.001) were related to risk of incident aortic stenosis, whereas increasing height (OR 0.96, 95% CI 0.94 to 0.99; p = 0.013) and African-American ethnicity conveyed a lower risk (OR 0.49, 95% CI 0.25 to 0.95; p = 0.035). C-reactive protein, treated as a continuous variable, was not associated with baseline aortic stenosis, progression to aortic sclerosis (adjusted OR 0.93, 95% CI 0.85 to 1.02; p = 0.107), or progression to aortic stenosis (adjusted OR 0.85, 95% CI 0.70 to 1.03; p = 0.092).
CONCLUSIONS: In this large population-based cohort, approximately 9% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year follow-up period. There was no association between CRP levels and the presence of calcific aortic-valve disease or incident aortic stenosis. C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease.
10aAged10aAged, 80 and over10aAortic Valve10aAortic Valve Stenosis10aC-Reactive Protein10aCalcinosis10aCardiovascular Diseases10aCohort Studies10aDisease Progression10aFemale10aFollow-Up Studies10aHeart Valve Diseases10aHumans10aMale10aRisk Factors1 aNovaro, Gian, M1 aKatz, Ronit1 aAviles, Ronnier, J1 aGottdiener, John, S1 aCushman, Mary1 aPsaty, Bruce, M1 aOtto, Catherine, M1 aGriffin, Brian, P uhttps://chs-nhlbi.org/node/99702656nas a2200433 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520141500262653000901677653002201686653002101708653003401729653002001763653002601783653001101809653001101820653001701831653002401848653000901872653001301881653002301894653002601917653001201943653003101955653002401986653002402010653001802034100002202052700002402074700002002098700002202118700002402140700002302164856003502187 2007 eng d a1935-554800aCosts of the metabolic syndrome in elderly individuals: findings from the Cardiovascular Health Study.0 aCosts of the metabolic syndrome in elderly individuals findings c2007 Oct a2553-80 v303 aOBJECTIVE: The cardiovascular consequences of the metabolic syndrome and its component risk factors have been documented in elderly individuals. Little is known about how the metabolic syndrome and its individual components translate into long-term medical costs.
RESEARCH DESIGN AND METHODS: We used log-linear regression models to assess the independent contributions of the metabolic syndrome and its individual components to 10-year medical costs among 3,789 individuals aged > or = 65 years in the Cardiovascular Health Study.
RESULTS: As defined by the National Cholesterol Education Program Third Adult Treatment Panel report, the metabolic syndrome was present in 47% of the sample. Total costs to Medicare were 20% higher among participants with the metabolic syndrome ($40,873 vs. $33,010; P < 0.001). Controlling for age, sex, race/ethnicity, and other covariates, we found that abdominal obesity, low HDL cholesterol, and elevated blood pressure were associated with 15% (95% CI 4.3-26.7), 16% (1.7-31.8), and 20% (10.1-31.7) higher costs, respectively. When added to the model, the metabolic syndrome composite variable did not contribute significantly (P = 0.32).
CONCLUSIONS: Abdominal obesity, low HDL cholesterol, and hypertension but not the metabolic syndrome per se are important predictors of long-term costs in the Medicare population.
10aAged10aAged, 80 and over10aCholesterol, HDL10aContinental Population Groups10aCost of Illness10aDiabetic Angiopathies10aFemale10aHumans10aHypertension10aInterviews as Topic10aMale10aMedicare10aMetabolic Syndrome10aMultivariate Analysis10aObesity10aPatient Education as Topic10aProspective Studies10aRegression Analysis10aUnited States1 aCurtis, Lesley, H1 aHammill, Bradley, G1 aBethel, Angelyn1 aAnstrom, Kevin, J1 aGottdiener, John, S1 aSchulman, Kevin, A uhttps://chs-nhlbi.org/node/96902577nas a2200361 4500008004100000022001400041245011100055210006900166260001700235300001100252490000700263520154200270653000901812653002201821653002801843653002801871653002401899653001101923653001901934653001101953653002301964653002501987653000902012653001602021653001802037100001402055700002402069700001802093700002302111700002802134700001802162856003502180 2007 eng d a0928-658600aDepressive symptoms and age-related macular degeneration in older people: the cardiovascular health study.0 aDepressive symptoms and agerelated macular degeneration in older c2007 May-Jun a127-330 v143 aPURPOSE: To examine the association between age-related macular degeneration (AMD) and depressive symptoms.
METHODS: Population-based, cross-sectional study. A total of 2,194 persons aged 69-97 years were included in the current analyses. During the 1997-1998 examination, retinal photography from one randomly selected eye was graded for presence of early and late AMD using a modified Wisconsin AMD by Grading System. Depressive symptoms were assessed via a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989 through 1997-1998. Depressive symptoms were defined as a CES-D score of >9 (top quartile of CES-D score) at the 1997-1998 examination.
RESULTS: There were 338 (15.6%) individuals with early AMD and 29 (1.3%) with late AMD. Among them, 368 (16.8%) persons had depressive symptoms at the 1997-1998 examination. Depressive symptoms were not associated with early AMD (multivariable adjusted odds ratio [OR]: 0.97; 95% confidence intervals [CI]: 0.69-1.36) or late AMD (OR: 1.15; 95% CI: 0.38-3.46). Including persons using anti-depressive medications did not alter these associations (OR: 0.98; 95% CI: 0.74-1.32 for early AMD and OR: 0.97; 95% CI: 0.35-2.67 for late AMD). There was no association in multinomial logistic regression models of increasing quartiles of the CES-D scores with early or late AMD status.
CONCLUSIONS: Our study did not find an association between early AMD and depressive symptoms in older people.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCross-Sectional Studies10aDepressive Disorder10aFemale10aHealth Surveys10aHumans10aIntelligence Tests10aMacular Degeneration10aMale10aPhotography10aUnited States1 aSun, Cong1 aTikellis, Gabriella1 aKlein, Ronald1 aSteffens, David, C1 aLarsen, Emily, K Marino1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/96803074nas a2200457 4500008004100000022001400041245013500055210006900190260001300259300001200272490000700284520172600291653000902017653002302026653002802049653002402077653001902101653001502120653001102135653002502146653001102171653001702182653002602199653002502225653000902250653002602259653002702285653003202312653002402344653002602368653001702394653002602411653002402437653001802461100002202479700002202501700001802523700002002541700002002561856003502581 2007 eng d a1532-541500aDepressive symptoms, inflammation, and ischemic stroke in older adults: a prospective analysis in the cardiovascular health study.0 aDepressive symptoms inflammation and ischemic stroke in older ad c2007 Nov a1825-300 v553 aOBJECTIVES: To investigate the mediator role of inflammation in any relationship between depressive symptoms and ischemic stroke.
DESIGN: Longitudinal prospective study.
SETTING: Review of medical records, death certificates, and the Medicare healthcare utilization database for hospitalizations.
PARTICIPANTS: Total of 5,525 elderly men and women aged 65 and older who were prospectively followed from 1989 to 2000 as participants in the Cardiovascular Health Study.
MEASUREMENTS: Depression symptom scores, inflammatory markers.
RESULTS: Greater depressive symptoms were associated with risk of ischemic stroke (unadjusted hazard ratio (HR)=1.32, 95% confidence interval (CI)=1.09-1.59; HR=1.26, 95% CI=1.03-1.54, adjusted for traditional risk factors). When a term for inflammation (C-reactive protein (CRP)) was introduced in the model, the HRs were not appreciably altered (unadjusted HR=1.31, 95% CI=1.08-1.58; adjusted HR=1.25, 95% CI=1.02-1.53), indicating that CRP at baseline was not a mediator in this relationship. In analyses stratified according to CRP levels, a J-shaped relationship between depressive symptoms and stroke was evident in the unadjusted analyses; in the fully adjusted model, only CRP in the highest tertile was associated with a higher risk for stroke in the presence of higher depressive symptoms scores.
CONCLUSION: The analyses from this prospective study provide evidence of a positive association between depressive symptoms and risk of incident stroke. Inflammation, as measured according to CRP at baseline, did not appear to mediate the relationship between depressive symptoms and stroke.
10aAged10aC-Reactive Protein10aCardiovascular Diseases10aCerebral Infarction10aCohort Studies10aDepression10aFemale10aGeriatric Assessment10aHumans10aInflammation10aKaplan-Meier Estimate10aLongitudinal Studies10aMale10aMultivariate Analysis10aPersonality Assessment10aProportional Hazards Models10aProspective Studies10aPsychoneuroimmunology10aRisk Factors10aSocioeconomic Factors10aStatistics as Topic10aUnited States1 aArbelaez, Jose, J1 aAriyo, Abraham, A1 aCrum, Rosa, M1 aFried, Linda, P1 aFord, Daniel, E uhttps://chs-nhlbi.org/node/99202902nas a2200481 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520158400251653002101835653000901856653002201865653001001887653002001897653002801917653003301945653001101978653001101989653001702000653002602017653002302043653001202066653001602078653001002094653001802104653003002122653001502152653001702167653001702184100002102201700002402222700002202246700002202268700001702290700001802307700002102325700001902346700002002365856003502385 2007 eng d a0021-972X00aDeterminants of serum total and free testosterone levels in women over the age of 65 years.0 aDeterminants of serum total and free testosterone levels in wome c2007 Feb a509-160 v923 aCONTEXT: Little is known about testosterone (T) levels and their determinants in women of late postmenopausal age.
OBJECTIVE: We describe levels of total and free T and selected factors that influence these levels in a random sample of older women.
DESIGN: Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to define factors associated with total and free T levels.
RESULTS: In adjusted models: 1) total T levels declined with age until 80, whereas free T levels did not vary by age; 2) women with bilateral oophorectomy had 23% lower total T and 16% lower free T levels than those with at least one intact ovary; 3) oral estrogen users had total and free T levels that were 47% lower than never users; 4) obese women had 47% higher total T and 20% higher free T levels, and overweight women had 24% higher total T and 14% higher free T levels, than normal weight women; and 5) free T levels were 51% higher in black women. Corticosteroid users had 75% lower total T and 43% lower free T levels than nonusers.
CONCLUSIONS: Bilateral oophorectomy, estrogen use, corticosteroid use, and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over. Although highly prevalent in women of this age, the physiological significance of low T levels in late postmenopausal women requires further investigation.
10aAge Distribution10aAged10aAged, 80 and over10aAging10aBody Mass Index10aCross-Sectional Studies10aEstrogen Replacement Therapy10aFemale10aHumans10aHypogonadism10aMultivariate Analysis10aNonlinear Dynamics10aObesity10aOvariectomy10aOvary10aPostmenopause10aPredictive Value of Tests10aPrevalence10aRisk Factors10aTestosterone1 aCappola, Anne, R1 aRatcliffe, Sarah, J1 aBhasin, Shalender1 aBlackman, Marc, R1 aCauley, Jane1 aRobbins, John1 aZmuda, Joseph, M1 aHarris, Tamara1 aFried, Linda, P uhttps://chs-nhlbi.org/node/92802394nas a2200337 4500008004100000022001400041245008400055210006900139260001300208300001100221490000700232520146900239653001001708653000901718653002201727653002301749653001101772653001101783653000901794653001601803653003301819653001801852100002401870700001401894700002401908700002201932700002001954700002401974700002301998856003502021 2007 eng d a0749-379700aEthnic-specific prevalence of peripheral arterial disease in the United States.0 aEthnicspecific prevalence of peripheral arterial disease in the c2007 Apr a328-330 v323 aBACKGROUND: Individuals diagnosed with peripheral arterial disease (PAD) are at increased risk for future functional limitations as well as cardiovascular morbidity and mortality. The aim of this study was to estimate the age-, gender-, and ethnic-specific burden of PAD in the United States for the year 2000.
METHODS: Data were collected from seven community-based studies that assessed subjects for the presence of PAD using the ankle-brachial index (ABI). Using standardized weighting criteria, age-, gender-, and ethnic-specific prevalence rates were computed and then multiplied by the corresponding 2000 Census population totals to estimate the burden of PAD in the United States for that year. Evidence-based adjustments for studies which did not consider possible subclavian stenosis, prior revascularization for PAD, or both were employed.
RESULTS: In 2000, it is conservatively estimated that at least 6.8 million (5.8%) individuals aged 40 years or older had PAD based on an ABI of less than 0.9 or previous revascularization for PAD, and that that there are an additional 1.7 million Americans with PAD but "normal" ABIs. Including this group gives a total of 8.5 million (7.2%) individuals with PAD.
CONCLUSIONS: Roughly one in 16 individuals residing in the United States in 2000 who were aged 40 years and older had PAD. Clinicians are encouraged to screen for the presence of PAD using the ABI.
10aAdult10aAged10aAged, 80 and over10aDatabases as Topic10aFemale10aHumans10aMale10aMiddle Aged10aPeripheral Vascular Diseases10aUnited States1 aAllison, Matthew, A1 aHo, Elena1 aDenenberg, Julie, O1 aLanger, Robert, D1 aNewman, Anne, B1 aFabsitz, Richard, R1 aCriqui, Michael, H uhttps://chs-nhlbi.org/node/94802449nas a2200361 4500008004100000022001400041245011700055210006900172260001300241300001100254490000600265520147100271653001201742653001301754653001501767653001501782653001101797653001301808653001101821653000901832653002601841653002401867653001701891653002001908653002201928100001701950700001501967700001801982700001302000700002402013700001502037856003502052 2007 eng d a1538-793300aFactor VII coagulant activity, factor VII -670A/C and -402G/A polymorphisms, and risk of venous thromboembolism.0 aFactor VII coagulant activity factor VII 670AC and 402GA polymor c2007 Aug a1674-80 v53 aBACKGROUND: Most epidemiological studies have found no association between levels of factor (F) VII:C and venous thromboembolism (VTE). Our Longitudinal Investigation of Thromboembolism Etiology (LITE) had, in contrast, reported an independent, increased risk of VTE after 7.8 years of follow-up for those with high baseline levels of FVII:C.
OBJECTIVE: To confirm whether FVII:C is associated with VTE after 12.6 years of follow-up and to examine whether two FVII gene polymorphisms (-670A/C and -402G/A) are related to VTE occurrence.
METHODS: In 19 091 LITE participants with no prior history of VTE or cancer, we measured FVII:C at baseline and identified 404 new VTEs. We also performed a nested case-control study to relate the polymorphisms to VTE (n = 490 without exclusion for cancer or prior VTE).
RESULTS: FVII:C was not independently associated with VTE occurrence after extended follow-up. Multivariable-adjusted rate ratios for VTE were 1.00, 1.00, 0.94, 1.00, and 1.38 (P-trend = 0.48) for the <25th, 25th-49th, 50th-74th, 75th-94th, and >or=95th percentiles of FVII:C, respectively. The -670C and -402A alleles were in high linkage disequilibrium, and both were associated with greater FVII:C levels. However, neither polymorphism was associated with VTE occurrence.
CONCLUSION: After extended follow-up, LITE offers little evidence that a greater FVII level is a risk factor for VTE.
10aAlleles10aAntigens10aCoagulants10aFactor VII10aFemale10aGenotype10aHumans10aMale10aPolymorphism, Genetic10aProspective Studies10aRisk Factors10aThromboembolism10aVenous Thrombosis1 aFolsom, A, R1 aCushman, M1 aHeckbert, S R1 aOhira, T1 aRasmussen-Torvik, L1 aTsai, M, Y uhttps://chs-nhlbi.org/node/97302479nas a2200397 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520136700263653000901630653002201639653002501661653001201686653003001698653001401728653001101742653001101753653002001764653002501784653003101809653000901840653001701849653001801866653001801884100002101902700002601923700001501949700002001964700002101984700002002005700002102025856003502046 2007 eng d a1051-228400aFocal atrophy and cerebrovascular disease increase dementia risk among cognitively normal older adults.0 aFocal atrophy and cerebrovascular disease increase dementia risk c2007 Apr a148-550 v173 aBACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults.
METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD.
RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions.
CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.
10aAged10aAlzheimer Disease10aAnalysis of Variance10aAtrophy10aCerebrovascular Disorders10aCognition10aFemale10aHumans10aLogistic Models10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRisk Factors10aTemporal Lobe10aUnited States1 aRosano, Caterina1 aAizenstein, Howard, J1 aWu, Minjie1 aNewman, Anne, B1 aBecker, James, T1 aLopez, Oscar, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/96002475nas a2200385 4500008004100000022001400041245006400055210006300119260001300182300001000195490000700205520146200212653001601674653000901690653002201699653001101721653002201732653001801754653001101772653000901783653001401792653001901806653002401825653001701849653002001866653001801886653002201904100002101926700002001947700001801967700002301985700002302008700002302031856003502054 2007 eng d a1079-500600aFrailty and risk of venous thromboembolism in older adults.0 aFrailty and risk of venous thromboembolism in older adults c2007 Jan a79-820 v623 aBACKGROUND: Frailty is a common risk factor for morbidity and mortality in elderly persons. Recent evidence links frailty to activation of coagulation and inflammatory pathways. We aimed to determine whether frailty in community-dwelling older adults is a risk factor for venous thromboembolism (VTE).
METHODS: We conducted a prospective cohort study in four U.S. communities involving 4859 participants 65 years old and older. At baseline, in 1989-1993, we assessed frailty based on weight loss, grip strength, feelings of exhaustion, walk time, and physical activity. Incident VTE (deep vein thrombosis or pulmonary embolus) through 2002 was identified by review of hospital records.
RESULTS: Fifty-two percent of the sample was classified as having intermediate or definite frailty. After adjustment for age, race, sex, body mass index, and diabetes, the relative risk of total VTE (n = 150) for people who were frail compared with no frailty was 1.31 (95% confidence interval [CI], 0.93-1.84). The comparably adjusted relative risk for idiopathic VTE (n = 58) was 1.79 (95% CI, 1.02-3.13).
CONCLUSIONS: The incidence rates of idiopathic VTE was higher in community-dwelling older adults with baseline frailty compared with no frailty. Further studies of the clotting process in frailty may allow the development of an improved strategy to determine VTE risk in this vulnerable subset of older adults.
10aAge Factors10aAged10aAged, 80 and over10aFemale10aFollow-Up Studies10aFrail Elderly10aHumans10aMale10aMorbidity10aMotor Activity10aProspective Studies10aRisk Factors10aThromboembolism10aUnited States10aVenous Thrombosis1 aFolsom, Aaron, R1 aBoland, Lori, L1 aCushman, Mary1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aWalston, Jeremy, D uhttps://chs-nhlbi.org/node/94202748nas a2200349 4500008004100000022001400041245010200055210006900157260001300226300001000239490000700249520177800256653000902034653002202043653001002065653001902075653001102094653000902105653003102114653001102145653000902156653002402165653002402189653001702213653001202230100002302242700002802265700002102293700002902314700002002343856003502363 2007 eng d a1079-500600aGait variability and the risk of incident mobility disability in community-dwelling older adults.0 aGait variability and the risk of incident mobility disability in c2007 Sep a983-80 v623 aBACKGROUND: Gait speed is a strong predictor of incident walking disability. The objective was to determine if gait variability adds to the prediction of incident mobility disability independent of gait speed.
METHODS: Participants included 379 older adults (mean age = 79 years; 78% Caucasian, and 40% men) in the Cardiovascular Health Study at the Pittsburgh site. All could ambulate independently and reported no difficulty walking a half mile. Gait characteristics were determined from a 4-meter computerized walkway. For each gait parameter, variability was defined as the standard deviation from the individual steps from two passes. Incident walking disability was obtained by phone interview every 6 months for 54 months and was defined as new difficulty walking a half mile or inability to walk a half mile.
RESULTS: Of the 379 participants, 222 (58.6%) developed incident mobility disability. In unadjusted Cox proportional hazards models gait speed, mean step length, mean stance time, and stance time variability were associated with incident mobility disability. After adjusting for gait speed, demographics, chronic conditions, prescription medications, health status, and physical activity level, only stance time variability remained an important indicator of disability. In the adjusted model, an increase in stance time variability of 0.01 seconds was associated with a 13% higher incidence of mobility disability (hazard ratio 1.13, 95% confidence interval, 1.01-1.27).
CONCLUSIONS: Stance time variability is an independent predictor of future mobility disability. Future efforts are needed to determine whether interventions that decrease stance time variability will also delay mobility disability.
10aAged10aAged, 80 and over10aAging10aCohort Studies10aFemale10aGait10aGait Disorders, Neurologic10aHumans10aMale10aMobility Limitation10aProspective Studies10aRisk Factors10aWalking1 aBrach, Jennifer, S1 aStudenski, Stephanie, A1 aPerera, Subashan1 aVanSwearingen, Jessie, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/98702786nas a2200445 4500008004100000022001400041245011500055210006900170260000900239300001200248490000700260520147700267653002101744653003101765653000901796653002201805653004201827653001001869653002401879653001601903653001101919653003101930653002501961653001901986653001102005653002502016653003102041653000902072653002402081653003102105653002702136653001702163653001802180100002102198700002002219700002502239700002002264700002002284856003602304 2007 eng d a1423-020800aGait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults.0 aGait variability is associated with subclinical brain vascular a c2007 a193-2000 v293 aBACKGROUND: Gait variability is an index of how much gait parameters, such as step length, change from one step to the next. Gait variability increases with age and in individuals affected by cortical and subcortical neurodegenerative conditions, and it is associated with falls and incident mobility disability. The brain anatomical correlates of gait variability have not been studied in high-functioning community-dwelling older adults.
METHODS: Gait variability and brain MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free from stroke, dementia or Parkinson's disease. Gait variability was computed for spatial parameters (step length and step width) and for temporal parameters (stance time). Subclinical brain vascular abnormalities were measured on brain MRIs as infarcts and white matter hyperintensities.
RESULTS: Greater variability of step length was associated with greater prevalence of infarcts, including infarcts in the basal ganglia, and with greater white matter hyperintensities severity, independent of age, gender, cognitive function and cardiovascular disease. Weaker associations were found between the other variability measures and the MRI measures.
CONCLUSION: In this group of older adults free from neurodegenerative diseases, a greater variability of step length was associated with greater burden of subclinical brain vascular abnormalities as defined by MRI.
10aAccidental Falls10aActivities of Daily Living10aAged10aAged, 80 and over10aBasal Ganglia Cerebrovascular Disease10aBrain10aCerebral Infarction10aComorbidity10aFemale10aGait Disorders, Neurologic10aGeriatric Assessment10aHealth Surveys10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMobility Limitation10aNeurodegenerative Diseases10aNeurologic Examination10aRisk Factors10aUnited States1 aRosano, Caterina1 aBrach, Jennifer1 aStudenski, Stephanie1 aLongstreth, W T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/100203584nas a2200373 4500008004100000022001400041245006300055210006100118260001600179300000700195490001400202520259400216653001002810653001202820653002802832653002102860653001902881653001102900653001902911653002002930653001802950653001302968653001102981653000902992653001603001653001403017653003603031653001003067653003103077100002403108700002403132700001903156856003503175 2007 eng d a1471-235000aGenome-wide association of sleep and circadian phenotypes.0 aGenomewide association of sleep and circadian phenotypes c2007 Sep 19 aS90 v8 Suppl 13 aBACKGROUND: Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits.
METHODS: Sleepiness (defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency > or =10%, call rate > or =80%, and no significant deviation from Hardy-Weinberg equilibrium (p > or = 0.001).
RESULTS: Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD >2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.
CONCLUSION: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.
10aAdult10aAlleles10aCardiovascular Diseases10aCircadian Rhythm10aCohort Studies10aFemale10aGene Frequency10aGenetic Linkage10aGenome, Human10aGenotype10aHumans10aMale10aMiddle Aged10aPhenotype10aPolymorphism, Single Nucleotide10aSleep10aSurveys and Questionnaires1 aGottlieb, Daniel, J1 aO'Connor, George, T1 aWilk, Jemma, B uhttps://chs-nhlbi.org/node/98902708nas a2200469 4500008004100000022001400041245014600055210006900201260001300270300001100283490000800294520133100302653002201633653000901655653001201664653002301676653002801699653001901727653004001746653001101786653001901797653003801816653002201854653001101876653001801887653001201905653002501917653000901942653003601951653003001987100002302017700002002040700001802060700001802078700001702096700001702113700002002130700001902150700001702169700001702186856003502203 2007 eng d a1432-120300aIL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study.0 aIL6 gene variation is associated with IL6 and Creactive protein c2007 Dec a485-940 v1223 aInterleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05-1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.
10aAfrican Americans10aAged10aAlleles10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenetic Predisposition to Disease10aGenetic Variation10aHumans10aInterleukin-610aIntrons10aLongitudinal Studies10aMale10aPolymorphism, Single Nucleotide10aPromoter Regions, Genetic1 aWalston, Jeremy, D1 aFallin, Daniele1 aCushman, Mary1 aLange, Leslie1 aPsaty, Bruce1 aJenny, Nancy1 aBrowner, Warren1 aTracy, Russell1 aDurda, Peter1 aReiner, Alex uhttps://chs-nhlbi.org/node/98203305nas a2200349 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520232400262653000902586653002202595653002602617653002402643653001302667653002402680653001102704653001102715653001402726653000902740653002602749100002002775700002102795700002102816700002102837700002102858700001802879700002302897856003502920 2007 eng d a0003-994200aIncidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study.0 aIncidence of dementia in mild cognitive impairment in the cardio c2007 Mar a416-200 v643 aOBJECTIVES: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study.
DESIGN: Prospective epidemiological study.
SETTING: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999. Subjects There were 136 subjects with MCI. Mild cognitive impairment was subclassified as MCI amnestic type and MCI multiple cognitive deficits type (MCI-MCDT); subjects with MCI-MCDT were also grouped based on the presence of a memory impairment. Subjects with MCI were classified as possible when there were comorbidities that could explain the subjects' cognitive deficits and as probable when there were none. Main Outcome Measure Dementia.
RESULTS: The incidence of all dementias in the subjects with MCI was 147 per 1000 person-years (mean follow-up overall, 4.3 years). Of the 136 subjects with MCI, 69 (51%) in 1998 through 1999 progressed to dementia (57 [83%] to Alzheimer disease [AD]), but 25 (18%) returned to normal. Of the 10 subjects with probable MCI amnestic type, 7 (70%) progressed to dementia (all of them to AD) and none returned to normal, whereas 7 (41%) of the 17 subjects with possible MCI amnestic type became demented (6 [86%] to AD) and 3 (18%) returned to normal. Of the 40 subjects with probable MCI-MCDT, 21 (52%) progressed to dementia (17 [81%] to AD) and 2 (5%) returned to normal. Of the 69 subjects with possible MCI-MCDT, 34 (49%) progressed to dementia (28 [82%] to AD) and 20 (29%) returned to normal. Among the subjects with probable MCI-MCDT, 15 (54%) of 28 with and 6 (50%) of 12 without memory deficits progressed to dementia.
CONCLUSIONS: Subjects with MCI are at high risk for dementia. The probable MCI diagnosis identified individuals in the earliest stages of dementia, usually AD, whereas the possible MCI diagnosis identified a more heterogeneous group. However, this latter group had only a slightly lower rate of conversion to dementia than the group with probable MCI, suggesting that even with comorbid conditions, there is a high likelihood of the presence of a progressive dementing disorder.
10aAged10aAged, 80 and over10aCardiovascular System10aCognition Disorders10aDementia10aDisease Progression10aFemale10aHumans10aIncidence10aMale10aRetrospective Studies1 aLopez, Oscar, L1 aKuller, Lewis, H1 aBecker, James, T1 aDulberg, Corinne1 aSweet, Robert, A1 aGach, Michael1 aDeKosky, Steven, T uhttps://chs-nhlbi.org/node/94702561nas a2200373 4500008004100000022001400041245015100055210006900206260001300275300001100288490000700299520147200306653001601778653000901794653001901803653001101822653001101833653001401844653002801858653000901886653003201895653003001927653001701957653001601974653001701990653001802007100002602025700002202051700001802073700002002091700002302111700001802134856003502152 2007 eng d a0277-953600aIndividual and neighborhood socioeconomic status and progressive chronic kidney disease in an elderly population: The Cardiovascular Health Study.0 aIndividual and neighborhood socioeconomic status and progressive c2007 Aug a809-210 v653 aFew studies have focused on the association between socioeconomic status (SES) and progressive chronic kidney disease (pCKD) in an elderly population. We conducted a cohort study of 4735 Cardiovascular Health Study participants, ages 65 and older and living in 4 US communities, to examine the independent risk of pCKD associated with income, education and living in a low SES area. pCKD was defined as creatinine elevation 0.4 mg/dL (35 micromol/L) over a 4-7 year follow-up or CKD hospitalization. Area SES was characterized using measures of income, wealth, education and occupation for 1990 (corresponding to time of enrollment) US Census block groups of residence. Age and study site-adjusted incidence rates (per 1000 person years) of pCKD by quartiles of area-level SES score, income and education showed decreasing rates with increasing SES. Cox proportional hazards models showed that living in the lowest SES area quartile, as opposed to the highest, was associated with 50% greater risk of pCKD, after adjusting for age, gender, study site, baseline creatinine, and individual-level SES. This increased risk and trend persisted after adjusting for lifestyle risk factors, diabetes and hypertension. We found no significant independent associations between pCKD and individual-level income or education (after adjusting for all other SES factors). As such, living in a low SES area is associated with greater risk of pCKD in an elderly US population.
10aAge Factors10aAged10aCohort Studies10aFemale10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aProportional Hazards Models10aResidence Characteristics10aRisk Factors10aSex Factors10aSocial Class10aUnited States1 aMerkin, Sharon, Stein1 aRoux, Ana, V Diez1 aCoresh, Josef1 aFried, Linda, F1 aJackson, Sharon, A1 aPowe, Neil, R uhttps://chs-nhlbi.org/node/96403065nas a2200457 4500008004100000022001400041245011600055210006900171260001300240300001200253490000600265520185200271653000902123653001002132653001502142653002302157653002802180653001602208653001902224653001602243653001102259653001502270653001502285653001702300653001102317653002702328653001802355653002002373653001902393653000902412653002402421653001702445100001602462700001202478700001602490700001502506700001702521700001902538700001502557856003502572 2007 eng d a1538-793300aInflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study.0 aInflammation and hemostasis biomarkers and cardiovascular risk i c2007 Jun a1128-350 v53 aBACKGROUND: There are few studies of inflammation and hemostasis biomarkers and cardiovascular disease risk (CVD) in older adults.
OBJECTIVES: To assess multiple biomarkers simultaneously and in combinations for CVD risk assessment in older individuals.
PATIENTS/METHODS: Thirteen biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, fibrinogen, factor VII, factor VIII, leukocyte count (WBC), platelet count, lipoprotein(a), soluble intercellular adhesion molecule-1 (sICAM-1), albumin, homocysteine and uric acid, were correlated with incident CVD in 4510 individuals in the Cardiovascular Health Study. Baseline biomarkers were analyzed as gender-specific SD increments and quintiles in proportional hazards models adjusted for demographics, CVD risk factors and medications.
RESULTS: Over 9 years with 1700 CVD events, seven biomarkers were associated with CVD. Adjusted hazard ratios (HRs, 95% CI) per SD increment were 1.16 (1.09, 1.23) for IL-6, 1.16 (1.09, 1.23) for CRP, 1.13 (1.05, 1.21) for D-dimer, 1.17 (1.09, 1.25) for homocysteine, 1.06 (1.00, 1.12) for WBC, 1.06 (1.00, 1.12) for factor VIII, and 1.07 (1.00, 1.13) for lipoprotein(a). Fibrinogen was associated with CVD in men only (HR 1.12, 95% CI 1.04, 1.22) and sICAM-1 in women only (HR 1.16, 95% CI 1.05, 1.27). IL-6 and CRP remained associated with CVD when modeled with WBC. Participants were classified by all combinations of two biomarkers being high or low (IL-6, CRP, WBC, factor VIII, cholesterol/HDL). All were associated with CVD when cholesterol/HDL was low and none when CRP was low.
CONCLUSIONS: Seven biomarkers were associated with CVD in older adults, with CRP having some advantages compared with others. Even larger studies are needed to better characterize these associations.
10aAged10aAging10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol10aCohort Studies10aFactor VIII10aFemale10aFibrinogen10aHemostasis10aHomocysteine10aHumans10aInflammation Mediators10aInterleukin-610aLeukocyte Count10aLipoprotein(a)10aMale10aProspective Studies10aRisk Factors1 aZakai, N, A1 aKatz, R1 aJenny, N, S1 aPsaty, B M1 aReiner, A, P1 aSchwartz, S, M1 aCushman, M uhttps://chs-nhlbi.org/node/95002766nas a2200517 4500008004100000022001400041245006200055210006000117260001600177300001100193490000800204520138100212653002101593653000901614653001501623653002301638653002801661653002701689653002601716653001101742653001501753653002201768653001101790653002501801653001701826653001701843653000901860653001601869653001201885653002801897653003001925653001401955653003201969653001702001653002102018653001202039653001702051653001802068100002502086700001702111700002002128700002102148700002202169700002202191856003502213 2007 eng d a0002-926200aInflammation biomarkers and near-term death in older men.0 aInflammation biomarkers and nearterm death in older men c2007 Mar 15 a684-950 v1653 aAssociations of C-reactive protein (CRP) and fibrinogen with death may weaken over time. Combining both markers may improve prediction of death in older adults. In 5,828 Cardiovascular Health Study participants (United States, 1989-2000), 383 deaths (183 cardiovascular disease (CVD)) in years 1-3 (early) and 914 deaths (396 CVD) in years 4-8 (late) occurred. For men, when comparing highest to lowest quartiles, hazard ratios for early death were 4.1 (95% confidence interval (CI): 2.7, 6.3) for CRP and 4.1 (95% CI: 2.7, 6.4) for fibrinogen in models adjusted for CVD risk. For early CVD death, hazard ratios were 4.3 (95% CI: 2.2, 8.4) and 3.4 (95% CI: 1.8, 6.3), respectively. When comparing men in the highest quartiles of both biomarkers with those in the lowest, hazard ratios were 9.6 (95% CI: 4.3, 21.1) for early death and 13.5 (95% CI: 3.2, 56.5) for early CVD death. Associations were weaker for late deaths. For women, CRP (hazard ratio = 2.3, 95% CI: 1.4, 3.9), but not fibrinogen (hazard ratio = 1.3, 95% CI: 0.8, 2.2), was associated with early death. Results were similar for CVD death. Neither was associated with late deaths. CRP and fibrinogen were more strongly associated with death in older men than women and more strongly associated with early than late death. Combining both markers may identify older men at greatest risk of near-term death.
10aAge Distribution10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aDiabetes Complications10aEpidemiologic Studies10aFemale10aFibrinogen10aFollow-Up Studies10aHumans10aHypercholesterolemia10aHypertension10aInflammation10aMale10aMiddle Aged10aObesity10aPopulation Surveillance10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aRisk Factors10aSex Distribution10aSmoking10aTime Factors10aUnited States1 aJenny, Nancy, Swords1 aYanez, David1 aPsaty, Bruce, M1 aKuller, Lewis, H1 aHirsch, Calvin, H1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/93602827nas a2200349 4500008004100000022001400041245009900055210006900154260001600223300001100239490000800250520185800258653000902116653002202125653001102147653001802158653001502176653001102191653001702202653002302219653000902242653002302251653002402274100002402298700002002322700001702342700001802359700002202377700002302399700002002422856003502442 2007 eng d a0003-992600aInsulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study.0 aInsulin resistance and inflammation as precursors of frailty the c2007 Apr 09 a635-410 v1673 aBACKGROUND: Our research group has previously shown that the geriatric syndrome of frailty is associated with features of the metabolic syndrome (MetS) on cross-sectional analysis.
METHODS: To test whether MetS and its physiologic determinants-insulin resistance as measured by homeostasis model assessment score (IR-HOMA), increased inflammation and coagulation factor levels, and elevated blood pressure-are associated with incident frailty, we studied a subcohort of participants from the Cardiovascular Health Study observed from 1989/1990 through 1998/1999: 3141 community-dwelling adults, aged 69 to 74 years, without frailty and illnesses that increase inflammation markers or mimic frailty. The association of baseline MetS, IR-HOMA, levels of inflammation and coagulation factors, and systolic blood pressure (SBP) with time to onset of frailty was adjusted for demographic and psychosocial factors and incident events. Our main outcome measure was incident frailty.
RESULTS: Metabolic syndrome was not significantly associated with incident frailty (hazard ratio, 1.16 (95% confidence interval [CI], 0.85-1.57). On the other hand, IR-HOMA and C-reactive protein levels were associated with incident frailty: for every standard deviation increment the hazard ratio for frailty was 1.15 (95% CI, 1.02-1.31) and 1.16 (95% CI, 1.02-1.32), respectively. The white blood cell count and factor VIIIc levels had a borderline association. Elevated systolic blood pressure had no association. Similar trends were found for incident prefrailty, a condition that precedes frailty.
CONCLUSIONS: Two physiologic components of MetS- IR-HOMA and inflammation-are associated with incident frailty. Based on these results, IR-HOMA can be considered part of a larger process that leads to generalized decline.
10aAged10aAged, 80 and over10aFemale10aFrail Elderly10aGeriatrics10aHumans10aInflammation10aInsulin Resistance10aMale10aMetabolic Syndrome10aProspective Studies1 aBarzilay, Joshua, I1 aBlaum, Caroline1 aMoore, Tisha1 aXue, Qian, Li1 aHirsch, Calvin, H1 aWalston, Jeremy, D1 aFried, Linda, P uhttps://chs-nhlbi.org/node/95502852nas a2200421 4500008004100000022001400041245009800055210006900153260001300222300001000235490000600245520167800251653000901929653002201938653002401960653002801984653002002012653002102032653002402053653001102077653001102088653001102099653002002110653000902130653002002139100002202159700002002181700002402201700002002225700002002245700001602265700002002281700002102301700002902322700002002351700002402371856003502395 2007 eng d a1555-905X00aKidney function, electrocardiographic findings, and cardiovascular events among older adults.0 aKidney function electrocardiographic findings and cardiovascular c2007 May a501-80 v23 aChronic kidney disease (CKD) is associated with cardiovascular (CV) disease and mortality. It is not known whether cardiac rhythm disturbances are more prevalent among individuals with CKD or whether resting electrocardiogram findings predict future CV events in the CKD setting. Data were obtained from the Cardiovascular Health Study, a community-based study of adults aged >/=65 yr. After exclusions for prevalent heart disease, atrial fibrillation, implantable pacemaker, or antiarrhythmic medication use, 3238 participants were analyzed. CKD was defined by an estimated GFR <60 ml/min per 1.73 m(2). Outcomes were adjudicated incident heart failure (HF), incident coronary heart disease (CHD), and mortality. Participants with CKD had longer PR and corrected QT intervals compared with those without CKD; however, differences in electrocardiographic markers were explained by traditional CV risk factors and CV medication use. After adjustment for known risk factors, each 10-ms increase in the QRS interval was associated with a 15% greater risk for incident HF (95% confidence interval [CI] 1.04 to 1.27), a 13% greater risk for CHD (95% CI 1.04 to 1.24), and a 17% greater risk for mortality (95% CI 1.09, 1.25) among CKD participants. Each 5% increase in QTI was associated with a 42% (95% CI 1.23 to 1.65), 22% (95% CI 1.07 to 1.40), and 10% (95% CI 0.98 to 1.22) greater risk for HF, CHD, and mortality, respectively. Associations seemed stronger for participants with CKD; however, no significant interactions were detected. Resting electrocardiographic abnormalities are common in CKD and independently predict future clinical CV events in this setting.
10aAged10aAged, 80 and over10aCardiac Output, Low10aCardiovascular Diseases10aChronic Disease10aCoronary Disease10aElectrocardiography10aFemale10aHumans10aKidney10aKidney Diseases10aMale10aRisk Assessment1 aKestenbaum, Bryan1 aRudser, Kyle, D1 aShlipak, Michael, G1 aFried, Linda, F1 aNewman, Anne, B1 aKatz, Ronit1 aSarnak, Mark, J1 aSeliger, Stephen1 aStehman-Breen, Catherine1 aPrineas, Ronald1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/97502795nas a2200433 4500008004100000022001400041245009300055210006900148260001600217300001000233490000800243520160000251653000901851653002801860653000801888653001101896653001101907653001701918653001501935653000901950653002601959653002101985653001902006653004602025653000902071653002002080653001702100653001302117100002802130700002402158700002402182700002002206700002002226700002202246700002002268700002002288700001802308856003502326 2007 eng d a0002-926200aLeukocyte telomere length and cardiovascular disease in the cardiovascular health study.0 aLeukocyte telomere length and cardiovascular disease in the card c2007 Jan 01 a14-210 v1653 aThe telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD). Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities. The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002). In these participants (average age = 74.2 years (standard deviation, 5.2)), mean TRF length was 6.3 kilobase pairs (standard deviation, 0.62). Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6. Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger. In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio = 3.08, 95% confidence interval: 1.22, 7.73) and stroke (hazard ratio = 3.22, 95% confidence interval: 1.29, 8.02). These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD.
10aAged10aCardiovascular Diseases10aDNA10aFemale10aHumans10aInflammation10aLeukocytes10aMale10aMyocardial Infarction10aOxidative Stress10aPilot Projects10aPolymorphism, Restriction Fragment Length10aRisk10aRisk Assessment10aRisk Factors10aTelomere1 aFitzpatrick, Annette, L1 aKronmal, Richard, A1 aGardner, Jeffrey, P1 aPsaty, Bruce, M1 aJenny, Nancy, S1 aTracy, Russell, P1 aWalston, Jeremy1 aKimura, Masyuki1 aAviv, Abraham uhttps://chs-nhlbi.org/node/92202878nas a2200361 4500008004100000022001400041245014500055210006900200260001600269300001000285490000800295520182500303653000902128653002002137653002302157653001502180653003002195653001302225653001102238653001102249653002502260653000902285653001202294100002702306700001902333700002402352700002302376700002102399700002202420700001802442700002102460856003502481 2007 eng d a0003-992600aLongitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study.0 aLongitudinal association between depressive symptoms and inciden c2007 Apr 23 a802-70 v1673 aBACKGROUND: Prospective studies indicate that a single self-report of high depressive symptoms is associated with an increased risk of developing type 2 diabetes mellitus.
METHODS: We tested whether a single report of high depressive symptoms, an increase in depressive symptoms, or persistently high depressive symptoms over time were associated with the development of diabetes in adults 65 years and older. Participants from the Cardiovascular Health Study completed the 10-item Center for Epidemiological Studies-Depression Scale (CES-D) annually from 1989 to 1999. A single report of high depressive symptoms (CES-D score, >/=8), an increase in symptoms during follow-up (>/=5 from baseline), and persistently high symptoms (2 consecutive scores >/=8) were each studied in relation to incident diabetes, defined by initiation of diabetes control medications among participants who were free from diabetes at baseline (n = 4681).
RESULTS: The mean CES-D score at baseline was 4.5 (SD, 4.5). The incidence rate of diabetes was 4.4 per 1000 person-years. Following adjustment for baseline demographic characteristics and measures of physical activity, smoking, alcohol intake, body mass index, and C-reactive protein during follow-up, each measure of depressive symptoms was significantly associated with incident diabetes (high baseline CES-D score: hazard ratio, 1.6 [95% confidence interval, 1.1-2.3]; CES-D score increase: hazard ratio, 1.5 [95% confidence interval, 1.1-2.2]; and persistently high symptoms: hazard ratio, 1.5 [95% confidence interval, 1.1-2.3]).
CONCLUSION: Older adults who reported higher depressive symptoms were more likely to develop diabetes than their counterparts; this association was not fully explained by risk factors for diabetes.
10aAged10aBody Mass Index10aC-Reactive Protein10aDepression10aDiabetes Mellitus, Type 210aDrinking10aFemale10aHumans10aLongitudinal Studies10aMale10aSmoking1 aCarnethon, Mercedes, R1 aBiggs, Mary, L1 aBarzilay, Joshua, I1 aSmith, Nicholas, L1 aVaccarino, Viola1 aBertoni, Alain, G1 aArnold, Alice1 aSiscovick, David uhttps://chs-nhlbi.org/node/96102996nas a2200373 4500008004100000022001400041245012700055210006900182260001300251300001100264490000800275520192400283653000902207653002802216653001102244653002102255653001802276653001102294653000902305653001302314653002402327653001702351100001902368700002202387700002402409700002002433700002202453700002302475700002502498700002002523700002302543700002102566856003502587 2007 eng d a1097-674400aLong-term costs and resource use in elderly participants with congestive heart failure in the Cardiovascular Health Study.0 aLongterm costs and resource use in elderly participants with con c2007 Feb a245-520 v1533 aBACKGROUND: Although heart failure (HF) afflicts nearly 5 million Americans, the long-term cost of HF care has not been described previously. In a prospective, longitudinal cohort of community-dwelling elderly from 4 regions, we examined the long-term costs and resource use of elderly patients with HF.
METHODS: We linked 4860 elderly participants in the National Heart, Lung, and Blood Institute Cardiovascular Health Study to Medicare part A and part B claims from 1992 to 2003. Costs were calculated from Medicare payments and discounted at 3% annually. We applied nonparametric estimators to calculate mean costs and resource use per patient for a 10-year period. To describe the relationship between patient characteristics and long-term costs, we constructed censoring-adjusted regression models.
RESULTS: There were 343 participants (84.8% white; 50.1% men; mean age, 78.2 years) with prevalent HF and 4517 participants without HF at study entry. Mean follow-up was 6.7 years (median, 6.4 years). The 10-year survival rates were 33% and 63% for the prevalent HF and nonprevalent HF groups (P < .001), respectively. The mean 10-year medical costs were significantly higher for the prevalent HF cohort (54,704 dollars vs 41 dollars,780, P < .001). The higher costs associated with HF were also reflected in greater resource use with more hospitalizations (P < .05) and more intensive care unit days (P < .05). Participants with HF had more physician visits (P < .05), with most of these encounters involving noncardiology physicians. However, in multivariate models, prevalent HF was not an independent predictor of higher costs.
CONCLUSION: Patients with HF consume substantially more health care resources than their elderly peers, and these higher costs persist through 10 years of follow-up. Many of these costs may be related to other comorbid conditions.
10aAged10aCosts and Cost Analysis10aFemale10aHealth Resources10aHeart Failure10aHumans10aMale10aMedicare10aProspective Studies10aTime Factors1 aLiao, Lawrence1 aAnstrom, Kevin, J1 aGottdiener, John, S1 aPappas, Paul, A1 aWhellan, David, J1 aKitzman, Dalane, W1 aAurigemma, Gerard, P1 aMark, Daniel, B1 aSchulman, Kevin, A1 aJollis, James, G uhttps://chs-nhlbi.org/node/93801432nas a2200361 4500008004100000022001400041245008100055210006900136260001600205300001100221490000700232520043800239653003100677653000900708653002200717653002400739653001900763653002700782653002400809653001100833653001100844653003100855653000900886653001900895653001800914100001900932700001500951700001700966700001900983700001601002700001701018856003501035 2007 eng d a1526-632X00aPhysical activity and white matter lesion progression: assessment using MRI.0 aPhysical activity and white matter lesion progression assessment c2007 Apr 10 a1223-60 v683 aWe evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.
10aActivities of Daily Living10aAged10aAlzheimer Disease10aCognition Disorders10aCohort Studies10aDemyelinating Diseases10aDisease Progression10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aMotor Activity10aUnited States1 aPodewils, L, J1 aGuallar, E1 aBeauchamp, N1 aLyketsos, C, G1 aKuller, L H1 aScheltens, P uhttps://chs-nhlbi.org/node/95402965nas a2200385 4500008004100000022001400041245012300055210006900178260001300247300001200260490000700272520183300279653000902112653002802121653002202149653005202171653001102223653001502234653002702249653001102276653000902287653001302296653003202309653001702341653001902358653002302377653002602400653001702426653001502443100001902458700002502477700002202502700002002524856003502544 2007 eng d a1542-627000aPotential interactions between complementary/alternative products and conventional medicines in a Medicare population.0 aPotential interactions between complementaryalternative products c2007 Oct a1617-240 v413 aBACKGROUND: Despite the high prevalence of complementary and alternative medicine (CAM) product use among the elderly, little is known about the extent of concurrent CAM-conventional medicine use and the potential for adverse reactions.
OBJECTIVE: To determine the prevalence of CAM product use concurrent with conventional medications, prescription and nonprescription, in a Medicare population and assess the risk for adverse interactions.
METHODS: Retrospective analysis was performed on Cardiovascular Health Study interview data from 1994, 1995, 1997, and 1999. The prevalence of concurrent combinations of CAM products and conventional drugs was tabulated. The adverse interaction risks were categorized as unknown, theoretical, and significant.
RESULTS: Of 5052 participants, the median age was 75, 60.2% were female, 16.6% were African American, and 83.4% were white. The percent using CAM products during the 4 time periods was 6.3%, 6.7%, 12.8%, and 15.1%. The percent using both CAM products and conventional drugs was 6.0%, 6.2%, 11.7%, and 14.4%. Of these, 294 (5.8%) individuals took combinations considered to have a significant risk for an adverse interaction. Combinations with risk were observed on 393 separate interviews. Most (379) involved a risk of bleeding due to use of ginkgo, garlic, or ginseng together with aspirin, warfarin, ticlopidine, or pentoxifylline. An additional 786 observations of combinations were considered to have some, albeit theoretical or uncertain, risk for an adverse interaction.
CONCLUSIONS: Concurrent use of CAM products and conventional medicines in a Medicare population was found to be common. Research to define the risks of combining ginkgo and garlic supplements with aspirin should be of high priority.
10aAged10aComplementary Therapies10aDrug Interactions10aDrug-Related Side Effects and Adverse Reactions10aFemale10aHemorrhage10aHerb-Drug Interactions10aHumans10aMale10aMedicare10aPharmaceutical Preparations10aPhytotherapy10aPlant Extracts10aPlant Preparations10aRetrospective Studies10aRisk Factors10aWashington1 aElmer, Gary, W1 aLafferty, William, E1 aTyree, Patrick, T1 aLind, Bonnie, K uhttps://chs-nhlbi.org/node/97802624nas a2200313 4500008004100000022001400041245010600055210006900161260001300230300001200243490000700255520175400262653000902016653002202025653001002047653001002057653001102067653000902078653001102087653003102098653000902129653002402138653002102162100002102183700002602204700002502230700002002255856003502275 2007 eng d a1079-500600aA regions-of-interest volumetric analysis of mobility limitations in community-dwelling older adults.0 aregionsofinterest volumetric analysis of mobility limitations in c2007 Sep a1048-550 v623 aBACKGROUND: In community-dwelling older adults, greater mobility impairment is associated with greater burden of diffuse brain structural abnormalities, such as higher white matter hyperintensities. This study examined the association between gray matter volumes of regions related to motor control, gait, and balance and whether this association is independent of burden of white matter hyperintensities.
METHODS: A random sample of 327 participants of the Cardiovascular Health Study (78.3 +/- 4.1 years old, 57% women) contributed brain magnetic resonance imaging (MRI) and mobility data. A brain imaging automated method measured gray matter volume in cerebellum, basal ganglia, and prefrontal and parietal cortex in both hemispheres. Gait speed was measured while walking 15 feet at usual pace. Standing balance was assessed by timing tandem stance. Associations between each region's volume and gait speed or balance were measured before and after adjustment for demographics, head size, cardiovascular risk factors, and 0-9 grading scores of white matter hyperintensities.
RESULTS: Smaller left cerebellum and left prefrontal regions were associated with slower gait, independently of covariates and of white matter hyperintensities. Smaller right putamen, right posterior superior parietal cortex, and both left and right cerebellum were associated with balance difficulty, independently of covariates and white matter hyperintensities.
CONCLUSIONS: Smaller gray matter volumes in regions crucial for motor control are associated with slower gait and poorer balance, and the association appears to be independent of other diffuse brain abnormalities such as white matter hyperintensities.
10aAged10aAged, 80 and over10aAging10aBrain10aFemale10aGait10aHumans10aMagnetic Resonance Imaging10aMale10aMobility Limitation10aPostural Balance1 aRosano, Caterina1 aAizenstein, Howard, J1 aStudenski, Stephanie1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/98802785nas a2200409 4500008004100000022001400041245009700055210006900152260001600221300001100237490000600248520162700254653001001881653002301891653001101914653001801925653001101943653000901954653001601963653002001979653001801999653004702017653001702064653003102081653001702112653001602129100002302145700002202168700002302190700002002213700002402233700001702257700002402274700002202298700002002320856003502340 2007 eng d a1550-938900aRelationship between reported and measured sleep times: the sleep heart health study (SHHS).0 aRelationship between reported and measured sleep times the sleep c2007 Oct 15 a622-300 v33 aSTUDY OBJECTIVE: Subjective and objective assessments of sleep may be discrepant due to sleep misperception and measurement effects, the latter of which may change the quality and quantity of a person's usual sleep. This study compared sleep times from polysomnography (PSG) with self-reports of habitual sleep and sleep estimated on the morning after a PSG in adults.
DESIGN: Total sleep time and sleep onset latency obtained from unattended home PSGs were compared to sleep times obtained from a questionnaire completed before the PSG and a Morning Survey completed the morning after the PSG.
PARTICIPANTS: A total of 2,113 subjects who were > or = 40 years of age were included in this analysis.
MEASURES AND RESULTS: Subjects were 53% female, 75% Caucasian, and 38% obese. The mean habitual sleep time (HABTST), morning estimated sleep time (AMTST), and PSG total sleep times (PSGTST) were 422 min, 379 min, and 363 min, respectively. The mean habitual sleep onset latency, morning estimated sleep onset latency, and PSG sleep onset latency were 17.0 min, 21.8 min, and 16.9 min, respectively. Models adjusting for related demographic factors showed that HABTST and AMTST differ significantly from PSGTST by 61 and 18 minutes, respectively. Obese and higher educated people reported less sleep time than their counterparts. Similarly, small but significant differences were seen for sleep latency.
CONCLUSIONS: In a community population, self-reported total sleep times and sleep latencies are overestimated even on the morning following overnight PSG.
10aAdult10aAttitude to Health10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPolysomnography10aPsychometrics10aSleep Initiation and Maintenance Disorders10aSleep Stages10aSurveys and Questionnaires10aTime Factors10aWakefulness1 aSilva, Graciela, E1 aGoodwin, James, L1 aSherrill, Duane, L1 aArnold, Jean, L1 aBootzin, Richard, R1 aSmith, Terry1 aWalsleben, Joyce, A1 aBaldwin, Carol, M1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/99602730nas a2200361 4500008004100000022001400041245016200055210006900217260001300286300001100299490000700310520169000317653000902007653002202016653002502038653001802063653001202081653001102093653002402104653001502128653001102143653000902154653002302163653001702186100001602203700001902219700002202238700001702260700002002277700001802297700001802315856003502333 2007 eng d a0742-307100aThe relationship of heart rate and heart rate variability to non-diabetic fasting glucose levels and the metabolic syndrome: the Cardiovascular Health Study.0 arelationship of heart rate and heart rate variability to nondiab c2007 Aug a855-630 v243 aBACKGROUND: Increased heart rate (HR) and diminished heart rate variability (HRV) are signs of early cardiovascular autonomic neuropathy. We tested the hypotheses that increased HR and diminished HRV are present in people: (i) with increased fasting glucose (FG) levels not in the range of diabetes mellitus (DM), and (ii) in people with the metabolic syndrome (MetS) independent of elevated FG levels.
METHODS: HR and HRV were determined in 1267 adults (mean age 72 years) who had Holter monitoring and FG measures: 536 had normal FG levels (NORM, FG 4.5-5.5 mmol/l), 363 had mildly impaired FG (IFG-1, FG 5.6-6.0 mmol/l), 182 had significantly impaired FG (IFG-2, FG 6.1-6.9 mmol/l) and 178 had DM (FG > 6.9 mmol/l or use of glucose-lowering agents/insulin). HR and HRV in NORM/IFG-1 was further compared by the number of components of the MetS and compared by the presence or absence of MetS in IFG-2/DM.
RESULTS: HRV indices were more impaired in IFG-2 and DM than in NORM or IFG-1. There were few differences in HRV indices between NORM and IFG-1 or between IFG-2 and DM. In NORM/IFG-1 participants, having > or = 2 components of the MetS was associated with a greater decrease in HRV compared with having no or one components. In IFG-2/DM participants, MetS was associated with decreased HRV compared with no MetS.
CONCLUSIONS: Increased HR and diminished HRV occur in the non-diabetic FG range. Diminished HRV is associated with the MetS, independent of FG levels. Both these results suggest that factors associated with increasing non-diabetic FG levels and the MetS play a role in the onset of cardiac autonomic impairment.
10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aBlood Glucose10aFasting10aFemale10aGlucose Intolerance10aHeart Rate10aHumans10aMale10aMetabolic Syndrome10aRisk Factors1 aStein, P, K1 aBarzilay, J, I1 aDomitrovich, P, P1 aChaves, P, M1 aGottdiener, J S1 aHeckbert, S R1 aKronmal, R, A uhttps://chs-nhlbi.org/node/95202989nas a2200385 4500008004100000022001400041245006600055210006500121260001300186300001100199490000700210520194000217653000902157653002202166653001902188653002802207653002402235653001102259653003102270653001102301653002002312653000902332653002402341653001402365100002102379700002402400700001602424700002002440700002002460700002402480700002202504700002202526700002002548856003502568 2007 eng d a1523-683800aRelationship of uric acid with progression of kidney disease.0 aRelationship of uric acid with progression of kidney disease c2007 Aug a239-470 v503 aBACKGROUND: Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,808 participants of the Cardiovascular Health Study.
PREDICTOR: Uric acid levels.
OUTCOMES & MEASUREMENTS: Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m(2) per year or greater (>or=0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation.
RESULTS: Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m(2) (<1.00 mL/s) of 7%, 14%, 12%, 25%, and 42% for quintiles 1 (
LIMITATIONS: Measurements of albuminuria were not available.
CONCLUSIONS: Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.
10aAged10aAged, 80 and over10aCohort Studies10aCross-Sectional Studies10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aMale10aProspective Studies10aUric Acid1 aChonchol, Michel1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aNewman, Anne, B1 aSiscovick, David, S1 aKestenbaum, Bryan1 aCarney, Jan, Kirk1 aFried, Linda, F uhttps://chs-nhlbi.org/node/97203109nas a2200409 4500008004100000022001400041245011700055210006900172260001300241300001100254490000700265520193500272653000902207653002202216653002802238653001402266653002802280653001302308653001102321653001102332653002502343653000902368653002102377653002902398653002002427653001702447100002302464700002802487700002102515700001802536700002402554700002402578700002102602700002102623700002002644856003502664 2007 eng d a1524-462800aRetinal microvascular signs, cognitive function, and dementia in older persons: the Cardiovascular Health Study.0 aRetinal microvascular signs cognitive function and dementia in o c2007 Jul a2041-70 v383 aBACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals.
METHODS: In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded.
RESULTS: After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension.
CONCLUSIONS: In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCognition10aCross-Sectional Studies10aDementia10aFemale10aHumans10aLongitudinal Studies10aMale10aMicrocirculation10aNeuropsychological Tests10aRetinal Vessels10aRisk Factors1 aBaker, Michelle, L1 aLarsen, Emily, K Marino1 aKuller, Lewis, H1 aKlein, Ronald1 aKlein, Barbara, E K1 aSiscovick, David, S1 aBernick, Charles1 aManolio, Teri, A1 aWong, Tien, Yin uhttps://chs-nhlbi.org/node/96502680nas a2200421 4500008004100000022001400041245007700055210006900132260001300201300001200214490000700226520153900233653002201772653002101794653002401815653002101839653001101860653002201871653001101893653001701904653001401921653000901935653001601944653002601960653003001986653001502016653002402031653001702055653001102072653001802083100002302101700002102124700002002145700001702165700002302182700001802205856003502223 2007 eng d a1524-462800aRisk factors for intracerebral hemorrhage in a pooled prospective study.0 aRisk factors for intracerebral hemorrhage in a pooled prospectiv c2007 Oct a2718-250 v383 aBACKGROUND AND PURPOSE: Few prospective studies have reported risk factors for intracerebral hemorrhage (ICH), and results are inconsistent. We studied risk factors for ICH in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).
METHODS: The ARIC cohort was recruited in 1987 to 1989 and involves 15 792 men and women, aged 45 to 64 years at baseline, sampled from 4 US communities. The CHS cohort was recruited in 1989 to 1993 and involves 5888 men and women, aged 65 or over at baseline, sampled from 4 US communities. Baseline measurements included many potential vascular risk factors. The cohorts were followed for incident stroke events.
RESULTS: Over 263 489 person-years of follow-up, 135 incident ICH events occurred. In a multivariable model, age, African-American ethnicity (versus Whites), and hypertension were positively associated with incident ICH, whereas low-density lipoprotein cholesterol and triglycerides were inversely related to incident ICH. Participants with systolic blood pressure >or=160 mm Hg or diastolic blood pressure >/=110 mm Hg had 5.55 (95% CI 3.07 to 10.0) times the rate of ICH as nonhypertensives. Sex, smoking, alcohol intake, body mass index, waist-to-hip ratio, waist circumference, and diabetes were not related to ICH.
CONCLUSIONS: In this pooled cohort the risk factors for ICH were older age, African-American ethnicity, hypertension, lower LDL-C, and lower triglycerides.
10aAfrican Americans10aAge Distribution10aCerebral Hemorrhage10aCholesterol, LDL10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aMultivariate Analysis10aPredictive Value of Tests10aPrevalence10aProspective Studies10aRisk Factors10aStroke10aTriglycerides1 aSturgeon, Jared, D1 aFolsom, Aaron, R1 aLongstreth, W T1 aShahar, Eyal1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/97702586nas a2200421 4500008004100000022001400041245011700055210006900172260001300241300001000254490000700264520139000271653000901661653002201670653001001692653002101702653002001723653002301743653002801766653002501794653001101819653001101830653001701841653002101858653000901879653002601888653001201914653001501926653003201941653001701973653003001990100002502020700002102045700002102066700002202087700002002109856003502129 2007 eng d a1524-463600aSerum amyloid P and cardiovascular disease in older men and women: results from the Cardiovascular Health Study.0 aSerum amyloid P and cardiovascular disease in older men and wome c2007 Feb a352-80 v273 aOBJECTIVE: Serum amyloid P (SAP), a pentraxin like C-reactive protein (CRP), functions in innate immunity. However, associations of SAP with cardiovascular disease (CVD) are unknown.
METHODS AND RESULTS: We examined these associations in the Cardiovascular Health Study using a case-cohort design. Nonexclusive case groups were incident angina (n=523), myocardial infarction (MI; n=308), stroke (n=323), and CVD death (n=288). 786 participants had no events. SAP was correlated with CRP, CVD risk factors (obesity, blood pressure, lipids), common and internal carotid wall thickness, and ankle-brachial index (all P<0.02). In Cox regression models adjusted for age, sex, and ethnicity, a standard deviation increase in SAP (9.8 mg/L) was associated with angina (hazard ratio; 95% confidence interval 1.3; 1.2 to 1.5) and MI (1.3; 1.1 to 1.5), but not stroke (1.1; 0.9 to 1.3) or CVD death (1.1; 0.9 to 1.3). Adding CRP to the models had no significant effect on associations. Adjusting for CVD risk factors slightly attenuated SAP associations with CVD events; however, associations with angina and MI remained significant.
CONCLUSIONS: Although both are pentraxins, SAP and CRP may represent different facets of inflammation. The association of SAP with CVD in these older adults further supports the role of innate immunity in atherosclerosis.
10aAged10aAged, 80 and over10aAging10aAngina, Unstable10aAtherosclerosis10aC-Reactive Protein10aCardiovascular Diseases10aCase-Control Studies10aFemale10aHumans10aHypertension10aImmunity, Innate10aMale10aMyocardial Infarction10aObesity10aPrevalence10aProportional Hazards Models10aRisk Factors10aSerum Amyloid P-Component1 aJenny, Nancy, Swords1 aArnold, Alice, M1 aKuller, Lewis, H1 aTracy, Russell, P1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/93002093nas a2200397 4500008004100000022001400041245009600055210006900151260001600220300000700236490000600243520099900249653000901248653002201257653002101279653002101300653001401321653001101335653002201346653001101368653001401379653002501393653000901418653002401427653003001451653001701481653001101498653001801509100002501527700002201552700002001574700001801594700002301612700002501635856003501660 2007 eng d a1471-231800aSocioeconomic position and incident mobility impairment in the Cardiovascular Health Study.0 aSocioeconomic position and incident mobility impairment in the C c2007 May 10 a110 v73 aBACKGROUND: We investigated if personal socioeconomic position (SEP) factors and neighborhood characteristics were associated with incident mobility impairment in the elderly.
METHODS: We used data from the Cardiovascular Health Study, a longitudinal, population-based examination of coronary heart disease and stroke among persons aged 65 and older in the United States.
RESULTS: Among 3,684 persons without baseline mobility impairment, lower baseline SEP was associated with increased risk of incident mobility disability during the 10-year follow-up period, although the strengths of these associations varied by socioeconomic indicator and race/sex group.
CONCLUSION: Among independent-living elderly, SEP affected development of mobility impairment into later life. Particular effort should be made to prevent or delay its onset among the elderly with low income, education, and/or who live in economically disadvantaged neighborhoods.
10aAged10aAged, 80 and over10aCoronary Disease10aDisabled Persons10aEducation10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMobility Limitation10aResidence Characteristics10aSocial Class10aStroke10aUnited States1 aNordstrom, Cheryl, K1 aRoux, Ana, V Diez1 aSchulz, Richard1 aHaan, Mary, N1 aJackson, Sharon, A1 aBalfour, Jennifer, L uhttps://chs-nhlbi.org/node/96303388nas a2200613 4500008004100000022001400041245011700055210006900172260001300241300001200254490000700266520163000273653001001903653001601913653000901929653002201938653001001960653001801970653002301988653001202011653002802023653002702051653001902078653002802097653002102125653004002146653001102186653002202197653003802219653001102257653003802268653001202306653001802318653002702336653001102363653000902374653001502383653001402398653003602412653002402448653002002472653001702492653001702509653001802526653003302544100002502577700002802602700002002630700001702650700002402667700002602691700002202717856003502739 2007 eng d a1524-463600aUSF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies.0 aUSF1 gene variants cardiovascular risk and mortality in European c2007 Dec a2736-420 v273 aOBJECTIVE: A common haplotype of the upstream transcription factor 1 gene (USF1) has been associated with decreased susceptibility to familial combined hyperlipidemia (FCHL) and, paradoxically, with increased risk of cardiovascular disease (CVD) and all-cause mortality.
METHODS AND RESULTS: We assessed associations between USF1 tagSNPs, CVD risk factors, and aging-related phenotypes using data from 2 large population-based cohorts, Coronary Artery Risk Development in Young Adults (CARDIA) and the Cardiovascular Health Study (CHS), comprising younger and older adults, respectively. In CARDIA, each additional copy of the FCHL low-risk allele was associated with 2.4 mg/dL lower levels of LDL cholesterol (P=0.01) and decreased risk of subclinical atherosclerosis as assessed by coronary artery calcium (odds ratio 0.79; 95%CI 0.63 to 0.98). Whereas there was little association between USF1 genotype and metabolic or CVD traits in older adults from CHS, the USF1 low-risk dyslipidemia allele was associated with higher plasma C-reactive protein and interleukin (IL)-6 levels and with increased risk of mortality, particularly attributable to noncardiovascular causes.
CONCLUSIONS: There appears to be a complex and possibly age-dependent relationship between USF1 genotype, atherosclerosis phenotypes, and CVD risk. USF1 may influence mortality through pathways distinct from atherosclerosis. Alternatively, linkage disequilibrium with neighboring polymorphisms in other genes such as F11R may be responsible for the observed USF1 genotype-phenotype associations in older adults.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aAging10aBlood Glucose10aC-Reactive Protein10aCalcium10aCardiovascular Diseases10aCarotid Artery, Common10aCohort Studies10aCoronary Artery Disease10aCoronary Vessels10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aGenetic Predisposition to Disease10aHumans10aHyperlipidemia, Familial Combined10aInsulin10aInterleukin-610aLinkage Disequilibrium10aLipids10aMale10aOdds Ratio10aPhenotype10aPolymorphism, Single Nucleotide10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States10aUpstream Stimulatory Factors1 aReiner, Alexander, P1 aCarlson, Christopher, S1 aJenny, Nancy, S1 aDurda, Peter1 aSiscovick, David, S1 aNickerson, Deborah, A1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/98503277nas a2200469 4500008004100000022001400041245015200055210006900207260001600276300001100292490000700303520192500310653002102235653000902256653001402265653002502279653001902304653001602323653003402339653002102373653001102394653001802405653002102423653001102444653001702455653002502472653000902497653002602506653001502532653002402547653001702571653002102588653001802609653001802627100002202645700002102667700002002688700002102708700002002729700002302749856003502772 2007 eng d a1558-359700aVentricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.0 aVentricular structure and function in hypertensive participants c2007 Mar 06 a972-810 v493 aOBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample.
BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures.
METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167).
RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively.
CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly.
10aAge Distribution10aAged10aBody Size10aCase-Control Studies10aCohort Studies10aComorbidity10aContinental Population Groups10aEchocardiography10aFemale10aHeart Failure10aHeart Ventricles10aHumans10aHypertension10aLongitudinal Studies10aMale10aMultivariate Analysis10aPrevalence10aRegression Analysis10aRisk Factors10aSex Distribution10aStroke Volume10aUnited States1 aMaurer, Mathew, S1 aBurkhoff, Daniel1 aFried, Linda, P1 aGottdiener, John1 aKing, Donald, L1 aKitzman, Dalane, W uhttps://chs-nhlbi.org/node/94602632nas a2200505 4500008004100000022001400041245008400055210006900139260001300208300001100221490000700232520122700239653000901466653002201475653001001497653002401507653002801531653001301559653002401572653001101596653002201607653001101629653002301640653001801663653003101681653000901712653003001721653002401751653002601775653001701801100002401818700002101842700002001863700002201883700002301905700001401928700001901942700002001961700002601981700002802007700001502035700002002050700002102070856003502091 2007 eng d a1558-149700aVentricular volume and dementia progression in the Cardiovascular Health Study.0 aVentricular volume and dementia progression in the Cardiovascula c2007 Mar a389-970 v283 aElevated cerebral ventricular volume may be associated with dementia risk and progression. A fully-automated technique that agreed highly with radiological readings was used to estimate lateral ventricle volume on MR scans done at baseline in 1997-99 of 377 subjects in the Cardiovascular Health Study (CHS) from the Pittsburgh Center. 327 subjects were normal or diagnosed with mild cognitive impairment (MCI) at baseline and were evaluated 4 years later. Baseline ventricular volume was analyzed in multivariate models with age, gender, education level, presence and incidence of cerebral infarcts, and dementia category (normal, MCI, or dementia) at baseline and follow-up as fixed effects. Ventricular volume at baseline was significantly higher among subjects normal at baseline and demented 4 years later. Age, gender, education level, and dementia progression were significant factors affecting ventricular volume. Ventricular volume was higher in dementia compared to MCI, higher in MCI compared to controls, and higher in Possible-Alzheimer's-disease (AD) dementia compared to Probable-AD. Larger ventricles in healthy subjects may indicate susceptibility to, or progression of, dementia-related pathology.
10aAged10aAged, 80 and over10aAging10aCognition Disorders10aCross-Sectional Studies10aDementia10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aLateral Ventricles10aLinear Models10aMagnetic Resonance Imaging10aMale10aPredictive Value of Tests10aProspective Studies10aRetrospective Studies10aTime Factors1 aCarmichael, Owen, T1 aKuller, Lewis, H1 aLopez, Oscar, L1 aThompson, Paul, M1 aDutton, Rebecca, A1 aLu, Allen1 aLee, Sharon, E1 aLee, Jessica, Y1 aAizenstein, Howard, J1 aMeltzer, Carolyn, Cidis1 aLiu, Yanxi1 aToga, Arthur, W1 aBecker, James, T uhttps://chs-nhlbi.org/node/88902245nas a2200445 4500008004100000022001400041245011900055210006900174260001300243300001200256490000700268520094500275653003901220653000901259653002201268653001501290653001001305653002801315653002401343653004001367653001101407653002501418653001801443653001101461653002501472653003101497653000901528653002601537653001701563653001601580100002101596700002101617700002001638700002101658700002301679700002201702700002001724700002001744856003501764 2007 eng d a1558-149700aWhite matter grade and ventricular volume on brain MRI as markers of longevity in the cardiovascular health study.0 aWhite matter grade and ventricular volume on brain MRI as marker c2007 Sep a1307-150 v283 aHigh white matter grade (WMG) on magnetic resonance imaging (MRI) is a risk factor for dementia, stroke and disability. Higher ventricular size is a marker of brain "atrophy." In the Cardiovascular Health Study (CHS) (n=3245) mean age 75 years, 50% black and 40% men, we evaluated WM and ventricular grade (VG), total, cardiovascular and noncardiovascular mortality and longevity before and after adjusting for numerous determinants of longevity over an approximate 10-12 years of follow-up. A low WMG and VG was a marker for low total, cardiovascular and noncardiovascular mortality and for increased longevity over 10+ years of follow-up. We estimated that a 75-year-old with WMG below median would have about a 5-6 years greater longevity and for VG about 3 years, than above the median even after adjustment for numerous risk factors. Low WMG and VG on MRI is a powerful determinant of long-term survival among older individuals.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aBiomarkers10aBrain10aCardiovascular Diseases10aCerebral Ventricles10aEuropean Continental Ancestry Group10aFemale10aGeriatric Assessment10aHealth Status10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aRetrospective Studies10aRisk Factors10aSex Factors1 aKuller, Lewis, H1 aArnold, Alice, M1 aLongstreth, W T1 aManolio, Teri, A1 aO'Leary, Daniel, H1 aBurke, Gregory, L1 aFried, Linda, P1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/90702911nas a2200397 4500008004100000022001400041245020400055210006900259260001600328300001100344490000800355520168900363653000902052653002202061653002102083653003102104653001902135653001102154653002202165653001102187653001402198653003002212653001102242653000902253653002402262653001702286653002102303653002002324100002502344700002102369700002002390700002402410700002202434700002102456856003602477 2008 eng d a1524-453900aAbdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.0 aAbdominal aortic aneurysms increasing infrarenal aortic diameter c2008 Feb 26 a1010-70 v1173 aBACKGROUND: Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse.
METHODS AND RESULTS: In 1992 to 1993, 4734 Cardiovascular Health Study participants > or = 65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter > or = 3.0 cm or an infrarenal/suprarenal ratio > or = 1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation > or = 3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a > or = 2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters < 2.0 cm, infrarenal aortic diameters 2.0 to < 3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men.
CONCLUSIONS: This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters > 2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.
10aAged10aAged, 80 and over10aAorta, Abdominal10aAortic Aneurysm, Abdominal10aCause of Death10aFemale10aFollow-Up Studies10aHumans10aIncidence10aIntermittent Claudication10aKidney10aMale10aProspective Studies10aRisk Factors10aSex Distribution10aUltrasonography1 aFreiberg, Matthew, S1 aArnold, Alice, M1 aNewman, Anne, B1 aEdwards, Matthew, S1 aKraemer, Kevin, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/101703092nas a2200385 4500008004100000022001400041245010000055210006900155260001300224300001100237490000700248520202800255653000902283653002202292653002002314653003202334653001402366653002402380653001102404653002002415653001802435653001102453653001702464653003102481653000902512653001202521653001602533100001702549700002002566700002402586700002102610700002102631700001802652856003602670 2008 eng d a1524-462800aAbnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension.0 aAbnormal regional cerebral blood flow in cognitively normal elde c2008 Feb a349-540 v393 aBACKGROUND AND PURPOSE: The purpose of this study was to examine regional cerebral blood flow (rCBF) in normal cognitive-performing subjects with hypertension (HTN) using continuous arterial spin-labeled MRI. The most common explanation for the effect of blood pressure on cognition is that HTN increases the risk of cerebrovascular disease, and it may increase the risk for Alzheimer disease possibly through small vessel disease, ischemia, oxidative stress, and inflammation. However, few studies to date have examined the rCBF of cognitively normal subjects with HTN in population-based cohorts, and none have used continuous arterial spin-labeled MRI. This is a noninvasive technique that does not require either injections or ionizing radiation and can measure absolute rCBF rates over the entire brain.
METHODS: rCBF was measured at 1.5 T using continuous arterial spin-labeled MRI in 41 cognitively normal subjects who were participating in the Cardiovascular Health Study Cognition Study. A deformable atrophy-corrected registration method was used to warp the rCBF maps to the standard colin27 brain space. Image and cluster-based statistical analyses were performed between subject groups.
RESULTS: Cognitively normal subjects with HTN (n=19) had decreased rCBF in the putamen, globus pallidus, bilaterally, and in the left hippocampus compared with normotensives (n=22). In addition, decreased rCBF was observed in the right and left anterior cingulate gyrus with extension to the subcallosal region, left posterior cingulate gyrus and medial precuneus, left lateral inferior and superior frontal, and inferior parietal, left orbitofrontal, and left superior temporal cortices.
CONCLUSIONS: rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.
10aAged10aAged, 80 and over10aCerebral Cortex10aCerebrovascular Circulation10aCognition10aCognition Disorders10aFemale10aGlobus Pallidus10aGyrus Cinguli10aHumans10aHypertension10aMagnetic Resonance Imaging10aMale10aPutamen10aSpin Labels1 aDai, Weiying1 aLopez, Oscar, L1 aCarmichael, Owen, T1 aBecker, James, T1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/100502997nas a2200349 4500008004100000022001400041245007500055210006900130260001300199300001200212490000700224520205900231653001602290653001602306653000902322653002202331653001602353653002502369653001902394653002102413653001102434653001102445653002502456653000902481653001502490653001702505100002002522700002402542700002102566700002402587856003602611 2008 eng d a0021-972X00aAdiponectin and risk of coronary heart disease in older men and women.0 aAdiponectin and risk of coronary heart disease in older men and c2008 Sep a3357-640 v933 aCONTEXT: Despite established insulin-sensitizing and antiatherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain.
OBJECTIVE: Our objective was to investigate the relationship between adiponectin and CHD in older adults.
DESIGN, SETTING, AND PARTICIPANTS: This was a case-control study (n = 1386) nested within the population-based Cardiovascular Health Study from 1992--2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease, and center.
MAIN OUTCOME MEASURES: Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, nonfatal myocardial infarction (MI), or CHD death. A more restrictive CHD endpoint was limited to nonfatal MI and CHD death.
RESULTS: Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist to hip ratio, hypertension, smoking, alcohol, low-density lipoprotein cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end [odds ratio = 1.37 (quintile 5 vs. 1-4), 95% confidence interval 1.02-1.84]. This association was stronger when the outcome was limited to nonfatal MI and fatal CHD (odds ratio = 1.69, 95% confidence interval 1.23-2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators.
CONCLUSIONS: This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.
10aAdiponectin10aAge Factors10aAged10aAged, 80 and over10aBody Weight10aCase-Control Studies10aCohort Studies10aCoronary Disease10aFemale10aHumans10aLongitudinal Studies10aMale10aOdds Ratio10aRisk Factors1 aKizer, Jorge, R1 aBarzilay, Joshua, I1 aKuller, Lewis, H1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/103803056nas a2200433 4500008004100000022001400041245006400055210006200119260001300181300001100194490000700205520191800212653001602130653000902146653002202155653001602177653001002193653001402203653002802217653001302245653001102258653001102269653001402280653003102294653000902325653001502334653002802349653001402377653002602391653001702417100002402434700002802458700002102486700001702507700002102524700002002545700002102565856003602586 2008 eng d a1523-683800aAlbuminuria and dementia in the elderly: a community study.0 aAlbuminuria and dementia in the elderly a community study c2008 Aug a216-260 v523 aBACKGROUND: Dementia is associated with microvascular disease of the retina. In this study, we examine whether cognitive status (normal cognition, mild cognitive impairment, and dementia) is associated with albuminuria, a microvascular disorder of the kidney.
STUDY DESIGN: Cross-sectional analysis.
SETTING & PARTICIPANTS: 2,316 participants from the Cardiovascular Health Cognition Study who underwent brain magnetic resonance imaging and testing for albuminuria.
PREDICTOR: Doubling of albuminuria.
OUTCOME: Dementia defined according to neuropsychological and clinical evaluation.
MEASUREMENTS: Multinomial logistic modeling was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of dementia and mild cognitive impairment with doubling of albuminuria compared with the odds with normal cognition.
RESULTS: 283 participants (12.2%) had dementia, 344 (14.9%) had mild cognitive impairment, and 1,689 (72.9%) had normal cognition. Compared with participants with normal cognition, doubling of albuminuria was associated with increased odds of dementia (OR, 1.22; 95% CI, 1.15 to 1.29). Adjustment for prevalent cardiovascular disease and cardiovascular risk factors, lipid levels, C-reactive protein level, estimated glomerular filtration rate, and apolipoprotein E-4 genotype attenuated this association, but it remained statistically significant (OR, 1.12; 95% CI, 1.03 to 1.22). Mild cognitive impairment was associated with albuminuria on unadjusted analysis, but not with adjustment for other factors.
LIMITATIONS: Results are cross-sectional; causality cannot be imputed.
CONCLUSIONS: The odds of dementia increased in the presence of albuminuria. These findings suggest a role of shared susceptibility for microvascular disease in the brain and kidney in older adults.
10aAge Factors10aAged10aAged, 80 and over10aAlbuminuria10aBrain10aCognition10aCross-Sectional Studies10aDementia10aFemale10aHumans10aIncidence10aMagnetic Resonance Imaging10aMale10aOdds Ratio10aPopulation Surveillance10aPrognosis10aRetrospective Studies10aRisk Factors1 aBarzilay, Joshua, I1 aFitzpatrick, Annette, L1 aLuchsinger, Jose1 aYasar, Sevil1 aBernick, Charles1 aJenny, Nancy, S1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/103202445nas a2200397 4500008004100000022001400041245011400055210006900169260001600238300001000254490000800264520131600272653000901588653002101597653001101618653002201629653001901651653001101670653003001681653000901711653001501720653002401735653001701759653003101776653001701807653001801824100002401842700002201866700001801888700002101906700002001927700001801947700002301965700002401988856003502012 2008 eng d a1476-625600aAlcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.0 aAlcohol consumption and lower extremity arterial disease among o c2008 Jan 01 a34-410 v1673 aFew studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.
10aAged10aAlcohol Drinking10aFemale10aFollow-Up Studies10aHealth Surveys10aHumans10aIntermittent Claudication10aMale10aPrevalence10aProspective Studies10aRisk Factors10aSurveys and Questionnaires10aTime Factors10aUnited States1 aMukamal, Kenneth, J1 aKennedy, Margaret1 aCushman, Mary1 aKuller, Lewis, H1 aNewman, Anne, B1 aPolak, Joseph1 aCriqui, Michael, H1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/99402703nas a2200349 4500008004100000022001400041245014500055210006900200260001300269300001200282490000700294520168700301653000901988653001101997653001002008653002802018653002402046653001102070653001102081653001702092653001802109653003102127653000902158100002002167700002502187700002102212700001902233700002702252700001802279700002002297856003602317 2008 eng d a1532-541500aAnemia is associated with the progression of white matter disease in older adults with high blood pressure: the cardiovascular health study.0 aAnemia is associated with the progression of white matter diseas c2008 Oct a1867-720 v563 aOBJECTIVES: To investigate whether anemia predicts worsening white matter hyperintensities (WMHs) in older community-dwellers.
DESIGN: Prospective cohort study.
SETTING: Older community-dwellers.
PARTICIPANTS: One thousand eight hundred forty-six Cardiovascular Health Study (CHS) participants (mean age 73.7 +/- 4.4, 41% male, 15.6% African American).
MEASUREMENTS: Participants had hemoglobin measured and brain magnetic resonance imaging (MRI) in 1992/93 and a second brain MRI in 1997/98. Anemia was defined according to World Health Organization criteria (hemoglobin <12 g/dL in women and <13 g/dL in men). Worsening WMHs were determined according to standardized side-by-side readings.
RESULTS: After 5 years, WMHs worsened in 517 participants (28%). Progression was not associated with anemia in the whole sample, in sex or race strata, or in other prespecified subgroups (participants with renal dysfunction or diabetes mellitus), except in participants with high blood pressure (>or=140/90 mmHg). Of the 678 participants with high blood pressure, those with anemia (10.5%) had a 1.79 times greater risk of WMHs worsening (95% confidence interval=1.06-2.98; P for interaction between anemia and high blood pressure=.01) independent of demographics, baseline WMHs, cardiovascular risk factors and comorbidities, medications, renal function, inflammation, and incident stroke (logistic regression models). There was no greater risk in participants with anemia with normal blood pressure.
CONCLUSION: Anemia may contribute to worsening of WMHs in older adults with high blood pressure.
10aAged10aAnemia10aBrain10aCardiovascular Diseases10aDisease Progression10aFemale10aHumans10aHypertension10aLeukoaraiosis10aMagnetic Resonance Imaging10aMale1 aInzitari, Marco1 aStudenski, Stephanie1 aRosano, Caterina1 aZakai, Neil, A1 aLongstreth, William, T1 aCushman, Mary1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/105405258nas a2200985 4500008004100000022001400041245012600055210006900181260001600250300001200266490000800278520269500286653001002981653001602991653000903007653002203016653001003038653002003048653001903068653002003087653002803107653001903135653002503154653001103179653001803190653001103208653000903219653001603228653001503244653003003259653002003289653001703309653003003326110003903356700001903395700001703414700001503431700001603446700001403462700002003476700001703496700001703513700001503530700001603545700001903561700001703580700001703597700001503614700002203629700001903651700001403670700001603684700002103700700001903721700001703740700001603757700001503773700001703788700002103805700001703826700001703843700001603860700001503876700002203891700001603913700002003929700001903949700001503968700002103983700001304004700001504017700001804032700002104050700001904071700001404090700001704104700001704121700001404138700001604152700001404168700001804182700001604200700002004216856003604236 2008 eng d a1538-359800aAnkle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.0 aAnkle brachial index combined with Framingham Risk Score to pred c2008 Jul 09 a197-2080 v3003 aCONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.
OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.
DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.
STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.
DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.
RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women.
CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.
10aAdult10aAge Factors10aAged10aAged, 80 and over10aAnkle10aAtherosclerosis10aBlood Pressure10aBrachial Artery10aCardiovascular Diseases10aCohort Studies10aConfidence Intervals10aFemale10aGlobal Health10aHumans10aMale10aMiddle Aged10aOdds Ratio10aPredictive Value of Tests10aRisk Assessment10aRisk Factors10aSeverity of Illness Index1 aAnkle Brachial Index Collaboration1 aFowkes, F, G R1 aMurray, G, D1 aButcher, I1 aHeald, C, L1 aLee, R, J1 aChambless, L, E1 aFolsom, A, R1 aHirsch, A, T1 aDramaix, M1 adeBacker, G1 aWautrecht, J-C1 aKornitzer, M1 aNewman, A, B1 aCushman, M1 aSutton-Tyrrell, K1 aFowkes, F, G R1 aLee, A, J1 aPrice, J, F1 aD'Agostino, R, B1 aMurabito, J, M1 aNorman, P, E1 aJamrozik, K1 aCurb, J, D1 aMasaki, K, H1 aRodríguez, B, L1 aDekker, J, M1 aBouter, L, M1 aHeine, R, J1 aNijpels, G1 aStehouwer, C, D A1 aFerrucci, L1 aMcDermott, M, M1 aStoffers, H, E1 aHooi, J, D1 aKnottnerus, J, A1 aOgren, M1 aHedblad, B1 aWitteman, J C1 aBreteler, M, M B1 aHunink, M, G M1 aHofman, A1 aCriqui, M, H1 aLanger, R, D1 aFronek, A1 aHiatt, W, R1 aHamman, R1 aResnick, H, E1 aGuralnik, J1 aMcDermott, M, M uhttps://chs-nhlbi.org/node/103902669nas a2200373 4500008004100000022001400041245015000055210006900205260001300274300001100287490000700298520153200305653000901837653002601846653003701872653001901909653002401928653001101952653002201963653001101985653001801996653003102014653000902045653002602054653002002080653003202100100002302132700001702155700002302172700002002195700002202215700002202237856003602259 2008 eng d a1524-462800aAntidepressant treatment and worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.0 aAntidepressant treatment and worsening white matter on serial cr c2008 Mar a857-620 v393 aBACKGROUND AND PURPOSE: In some studies, late life depression is associated with white matter lesions on MRI. The effect of different classes of antidepressants on progression of white matter lesions is unknown. Selective serotonergic reuptake inhibitors (SSRIs) may decrease platelet aggregation. We hypothesized that Cardiovascular Health Study participants taking SSRIs would less often have worsening white matter on serial MRI than participants not on antidepressants.
METHODS: Among 1826 participants who were not using an antidepressant at initial MRI scan, we examined the association of worsening in white matter grade from initial to follow-up MRI scans, 5 years apart on average, and antidepressant use between the scans. Logistic regression models were used, controlling for a variety of potential confounding variables.
RESULTS: Use of any antidepressant during the period of study was associated with worsening white matter. In a multivariable model, risk was slightly increased, not reduced, with use of serotonergic agents (OR 1.36, 95% CI 0.87 to 2.12) and was significantly increased with the use of tricyclic antidepressants (OR 1.77, 95% CI 1.07 to 2.94).
CONCLUSIONS: The association between worsening white matter and use of tricyclic antidepressants was an unexpected finding that may relate to indications for use other than depression or to side effects such as hypotension. Protection against worsening was not seen with use of serotonergic agents.
10aAged10aAntidepressive Agents10aAntidepressive Agents, Tricyclic10aCohort Studies10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aLeukoaraiosis10aMagnetic Resonance Imaging10aMale10aMultivariate Analysis10aRisk Assessment10aSerotonin Uptake Inhibitors1 aSteffens, David, C1 aChung, Hyoju1 aKrishnan, Ranga, R1 aLongstreth, W T1 aCarlson, Michelle1 aBurke, Gregory, L uhttps://chs-nhlbi.org/node/101402837nas a2200373 4500008004100000022001400041245014000055210006900195260001300264300001100277490000800288520175300296653000902049653002202058653001502080653002002095653002802115653001902143653001102162653001702173653001102190653000902201653003302210653001402243653002002257653001702277100001902294700002402313700002402337700002202361700002502383700002002408856003502428 2008 eng d a1879-148400aAssociation between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study.0 aAssociation between brachial artery reactivity and cardiovascula c2008 Apr a768-760 v1973 aBACKGROUND AND OBJECTIVES: The association of brachial flow-mediated dilation (FMD) and cardiovascular disease (CVD) status is unclear especially in older adults whose FMD is greatly diminished. We assessed the association of FMD and the presence or absence of subclinical and clinical CVD in a population based cohort of older adults.
METHODS AND RESULTS: FMD was measured in 2971 adults aged 72-98 years (mean age 78.6 years) who participated in the Cardiovascular Health Study. Multiple linear regression analysis was used to examine the association between FMD and CVD status (clinical, subclinical and free of CVD). Out of 2791 with complete data, 82.7% were Caucasians and 59% females. Seven hundred and forty-three were classified as having clinical CVD, 607 as subclinical CVD and 1441 as neither clinical CVD nor subclinical CVD (CVD free). FMD was higher in the CVD free group compared with either the clinical (3.13+/-0.05% vs 2.93+/-0.07%, p=0.025) or the subclinical CVD group (3.13+/-0.05% vs 2.95+/-0.08%, p=0.05) after adjusting for covariates. There was no significant difference between the FMD of subjects with clinical and subclinical CVD (2.93+/-0.07% vs 2.95+/-0.08%, p=0.84). Similar but inverted associations were observed between height adjusted brachial artery diameter (BAD) and CVD status. However, FMD and BAD had poor diagnostic accuracies for identifying older adults with subclinical CVD.
CONCLUSION: Among older adults, those with either clinical or subclinical CVD have lower FMD than CVD free subjects. BAD showed similar but inverted associations with CVD status in this cohort. FMD and BAD had poor diagnostic accuracies for identifying older adults with subclinical CVD.
10aAged10aAged, 80 and over10aBiomarkers10aBrachial Artery10aCardiovascular Diseases10aCohort Studies10aFemale10aHemorheology10aHumans10aMale10aPeripheral Vascular Diseases10aROC Curve10aUltrasonography10aVasodilation1 aYeboah, Joseph1 aSutton-Tyrrell, Kim1 aMcBurnie, Mary, Ann1 aBurke, Gregory, L1 aHerrington, David, M1 aCrouse, John, R uhttps://chs-nhlbi.org/node/97603518nas a2200457 4500008004100000022001400041245018500055210006900240260001300309300001200322490000700334520215200341653003102493653000902524653002202533653002502555653001202580653001002592653001902602653001902621653001902640653002602659653002802685653001102713653000902724653001102733653000902744653002302753653002402776653002902800653003202829653001802861653002802879653001702907100002102924700002002945700001602965700002202981700002103003856003603024 2008 eng d a1532-541500aAssociation between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.0 aAssociation between lower digit symbol substitution test score a c2008 Sep a1618-250 v563 aOBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.
DESIGN: Observational cohort study.
SETTING: Community.
PARTICIPANTS: Three thousand one hundred fifty-six (43% men, 29% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher.
MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years.
RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively).
CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.
10aActivities of Daily Living10aAged10aAged, 80 and over10aAnalysis of Variance10aAtrophy10aBrain10aBrain Diseases10aCause of Death10aCohort Studies10aDisability Evaluation10aDiscrimination Learning10aFemale10aGait10aHumans10aMale10aMemory, Short-Term10aMobility Limitation10aNeuropsychological Tests10aPattern Recognition, Visual10aPsychometrics10aPsychomotor Performance10aRisk Factors1 aRosano, Caterina1 aNewman, Anne, B1 aKatz, Ronit1 aHirsch, Calvin, H1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/104902878nas a2200517 4500008004100000022001400041245010500055210006900160260001300229300001000242490000700252520134800259653002201607653000901629653002201638653002101660653004001681653001101721653003801732653001101770653002501781653000901806653002601815653005301841653003601894653003201930653001801962100001801980700002201998700001902020700002402039700001902063700002302082700001902105700001802124700002002142700001702162700002302179700002002202700001802222700002202240700002202262700002102284700002002305856003502325 2008 eng d a1524-463600aAssociation of gene variants with incident myocardial infarction in the Cardiovascular Health Study.0 aAssociation of gene variants with incident myocardial infarction c2008 Jan a173-90 v283 aOBJECTIVE: We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.
METHODS AND RESULTS: Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided P<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HR=1.29; 90%CI 1.1 to 1.52), VAMP8 (HR=1.2; 90%CI 1.02 to 1.41), TAS2R50 (HR=1.13; 90%CI 1 to 1.27), and LPA (HR=1.62; 90%CI 1.09 to 2.42).
CONCLUSIONS: Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.
10aAfrican Americans10aAged10aAged, 80 and over10aCoronary Disease10aEuropean Continental Ancestry Group10aFemale10aGenetic Predisposition to Disease10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aNational Heart, Lung, and Blood Institute (U.S.)10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aUnited States1 aShiffman, Dov1 aO'Meara, Ellen, S1 aBare, Lance, A1 aRowland, Charles, M1 aLouie, Judy, Z1 aArellano, Andre, R1 aLumley, Thomas1 aRice, Kenneth1 aIakoubova, Olga1 aLuke, May, M1 aYoung, Bradford, A1 aMalloy, Mary, J1 aKane, John, P1 aEllis, Stephen, G1 aTracy, Russell, P1 aDevlin, James, J1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/99502927nas a2200361 4500008004100000022001400041245010200055210006900157260001600226300001000242490000700252520189600259653000902155653002002164653002802184653002802212653003202240653001102272653001902283653001102302653002002313653000902333653001602342653001502358653001502373653002702388653003102415100002302446700001702469700001902486700002402505856003602529 2008 eng d a1526-632X00aAssociation of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study.0 aAssociation of restless legs syndrome and cardiovascular disease c2008 Jan 01 a35-420 v703 aOBJECTIVE: We evaluated the cross-sectional association between restless legs syndrome (RLS) and prevalent cardiovascular disease (CVD) in a large community-based sample of middle-aged and elderly subjects.
METHODS: This is a cross-sectional observational study of 1,559 men and 1,874 women (mean age of 67.9 years) who were enrolled in the Sleep Heart Health Study, a community-based study of the cardiovascular consequences of sleep-disordered breathing. RLS was defined by positive responses on a self-administered questionnaire to the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Coronary artery disease (CAD) was determined by self-report of doctor-diagnosed angina, myocardial infarction, or coronary revascularization procedure. Total CVD included CAD or history of physician-diagnosed stroke or heart failure. The relation of RLS to prevalent CAD and CVD was examined by multivariable logistic regression models
RESULTS: RLS was present in 6.8% of women (n = 128) and 3.3% of men (n = 51). After adjustment for age, sex, race, body mass index, diabetes mellitus, systolic blood pressure, antihypertensive medication use, total:high-density lipoprotein cholesterol ratio, and smoking history, the ORs for CAD were 2.05 (95% CI 1.38 to 3.04) and for CVD were 2.07 (1.43 to 3.00) for subjects with RLS compared to those without RLS. The associations of RLS with CAD and CVD were stronger in those with RLS symptoms at least 16 times per month and were stronger in those with severe than in those with moderately bothersome symptoms.
CONCLUSIONS: Restless legs syndrome (RLS) is associated with prevalent coronary artery disease and cardiovascular disease. This association appears stronger in those with greater frequency or severity of RLS symptoms.
10aAged10aBody Mass Index10aCardiovascular Diseases10aCross-Sectional Studies10aEvaluation Studies as Topic10aFemale10aHealth Surveys10aHumans10aLogistic Models10aMale10aMiddle Aged10aOdds Ratio10aPrevalence10aRestless Legs Syndrome10aSurveys and Questionnaires1 aWinkelman, John, W1 aShahar, Eyal1 aSharief, Imran1 aGottlieb, Daniel, J uhttps://chs-nhlbi.org/node/100403467nas a2200589 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520174200294653002202036653001602058653000902074653001902083653002802102653002802130653004002158653001102198653001502209653001902224653003802243653001502281653001102296653000902307653002602316653003602342653002802378653003202406653002402438653003102462653002002493653001702513653001602530653001102546653001802557100001902575700001802594700001802612700002102630700002302651700001802674700002002692700001702712700002002729700002802749700002202777700002202799700002002821856003602841 2008 eng d a0340-624500aAssociations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study.0 aAssociations between common fibrinogen gene polymorphisms and ca c2008 Feb a388-950 v993 aElevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European- (EA) and African-descent (AA) adults (> or = 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807, FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437; each additional copy of the minor allele was associated with 13 mg/dl (95%CI: 9-16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR = 1.9 (95%CI: 1.3-2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.
10aAfrican Americans10aAge Factors10aAged10aBrain Ischemia10aCardiovascular Diseases10aCarotid Artery Diseases10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aGene Frequency10aGenetic Predisposition to Disease10aHaplotypes10aHumans10aMale10aMyocardial Infarction10aPolymorphism, Single Nucleotide10aPopulation Surveillance10aProportional Hazards Models10aProspective Studies10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSex Factors10aStroke10aUnited States1 aCarty, Cara, L1 aCushman, Mary1 aJones, Daniel1 aLange, Leslie, A1 aHindorff, Lucia, A1 aRice, Kenneth1 aJenny, Nancy, S1 aDurda, Peter1 aWalston, Jeremy1 aCarlson, Christopher, S1 aNickerson, Debbie1 aTracy, Russell, P1 aReiner, Alex, P uhttps://chs-nhlbi.org/node/101902936nas a2200409 4500008004100000022001400041245011500055210006900170260001300239300001100252490000700263520173600270653003902006653000902045653001502054653002102069653002302090653001902113653004002132653001102172653001502183653001102198653001702209653001802226653003102244653000902275653003602284100002002320700001702340700002202357700002002379700002502399700002402424700002202448700002002470856003602490 2008 eng d a1524-462800aBiomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain: The Cardiovascular Health Study.0 aBiomarkers of Inflammation and MRIDefined Small Vessel Disease o c2008 Jul a1952-90 v393 aBACKGROUND AND PURPOSE: To clarify the role of inflammation in the pathogenesis of small vessel disease of the brain, we investigated the association between common variation in the C-reactive protein (CRP) and interleukin (IL)-6 genes, plasma CRP and IL6 levels, and presence of MRI-defined white matter lesions (WML) and brain infarcts (BI) in elderly participants of the Cardiovascular Health Study.
METHODS: Tag single nucleotide polymorphisms (SNPs) in the CRP and IL6 genes were selected from the SeattleSNPs database. In cross-sectional analyses, logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of plasma CRP and IL6 levels and common CRP and IL6 gene haplotypes with presence of WML or BI in Blacks (n=532) and Whites (n=2905).
RESULTS: Plasma IL6 and CRP levels were associated with presence of WML and BI in both races. In Whites, common haplotypes of the IL6 gene were significantly associated with WML and BI. The common haplotype tagged by the -174G/C promoter polymorphism was associated with an increased risk of WML (OR=1.14; 95% CI: [1.02; 1.28]). The common haplotype tagged by the -572G/C promoter polymorphism was associated with an increased risk of BI (OR=1.57; 95% CI: [1.15; 2.14]). Significant associations were lacking for WML or BI with IL6 gene variation in Blacks, or with CRP gene variation in either race.
CONCLUSIONS: This study provides evidence of a genetic basis underlying the relationship between plasma biomarkers of inflammation and small vessel disease of the brain. Further studies to elucidate the specific role of IL6 in disease pathogenesis are warranted.
10aAfrican Continental Ancestry Group10aAged10aBiomarkers10aBrain Infarction10aC-Reactive Protein10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHaplotypes10aHumans10aInflammation10aInterleukin-610aMagnetic Resonance Imaging10aMale10aPolymorphism, Single Nucleotide1 aFornage, Myriam1 aChiang, Aron1 aO'Meara, Ellen, S1 aPsaty, Bruce, M1 aReiner, Alexander, P1 aSiscovick, David, S1 aTracy, Russell, P1 aLongstreth, W T uhttps://chs-nhlbi.org/node/102703258nas a2200421 4500008004100000022001400041245016200055210006900217260001300286300001100299490000800310520205700318653000902375653002202384653001602406653001502422653001902437653002102456653002802477653001102505653001902516653001102535653000902546653003002555653000902585100001602594700001902610700002102629700001802650700002002668700001802688700002302706700001602729700001802745700002002763700001802783856003502801 2008 eng d a1879-148400aCardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68-102: the Cardiovascular Health Study.0 aCardiovascular and mortality risk prediction and stratification c2008 Apr a806-130 v1973 aBACKGROUND: Elevated urinary albumin excretion (UAE) is associated with the risk of cardiovascular disease (CVD) and all-cause mortality. We tested the hypothesis that elevated UAE improves cardiovascular risk stratification in an elderly cohort aged 68-102 years.
METHODS: We evaluated UAE in 3112 participants of the Cardiovascular Health Study who attended the 1996-1997 examination and had median follow up of 5.4 years. Elevated UAE was defined as urinary albumin to creatinine ratio > or =30 microg/mg. Microalbuminuria and macroalbuminuria were defined as urinary albumin to creatinine ratio 30-300 microg/mg and >300 microg/mg, respectively. Outcomes included CVD (myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox proportional hazards models were used to assess the risk of outcomes associated with elevated UAE.
RESULTS: The prevalence of elevated UAE was 14.3%, 17.1% and 26.9% in those aged 68-74, 75-84 and 85-102 years, respectively. CVD incidence and all-cause mortality were doubled (7.2% and 8.1% per year) in those with microalbuminuria and tripled (11.1% and 12.3% per year) in those with macroalbuminuria compared to those with normal UAE (3.3% and 3.8% per year). The increased CVD and mortality risks were observed in all age groups after adjustment for conventional risk factors. The adjusted population attributable risk percent of CVD and all-cause mortality for elevated UAE was 11% and 12%, respectively. When participants were cross-classified by UAE and Framingham Risk Score categories, the 5-year cumulative incidence of coronary heart disease among participants with elevated UAE and a 5-year predicted risk of 5-10% was 20%, substantially higher than 6.3% in those with UAE <30m microg/mg.
CONCLUSION: Elevated UAE was associated with an increased risk of CVD and all-cause mortality in all age groups from 68 to 102 years. Combining elevated UAE with the Framingham risk scores may improve risk stratification for CVD in the elderly.
10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCohort Studies10aCoronary Disease10aCross-Sectional Studies10aFemale10aHealth Surveys10aHumans10aMale10aPredictive Value of Tests10aRisk1 aCao, Jie, J1 aBiggs, Mary, L1 aBarzilay, Joshua1 aKonen, Joseph1 aPsaty, Bruce, M1 aKuller, Lewis1 aBleyer, Anthony, J1 aOlson, Jean1 aWexler, Jason1 aSummerson, John1 aCushman, Mary uhttps://chs-nhlbi.org/node/98302746nas a2200373 4500008004100000022001400041245011500055210006900170260001300239300001000252490000600262520167500268653002401943653000901967653002801976653001102004653002202015653001102037653000902048653002402057653001702081100002402098700003202122700002402154700002002178700001602198700002102214700002102235700001902256700002002275700002002295700002102315856003602336 2008 eng d a1555-905X00aCardiovascular risk factors and incident acute renal failure in older adults: the cardiovascular health study.0 aCardiovascular risk factors and incident acute renal failure in c2008 Mar a450-60 v33 aBACKGROUND AND OBJECTIVES: Although the elderly are at increased risk for acute renal failure, few prospective studies have identified risk factors for acute renal failure in the elderly.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The associations of cardiovascular disease risk factors, subclinical cardiovascular disease, and clinical coronary heart disease with the risk for development of acute renal failure were examined in older adults in the Cardiovascular Health Study, a prospective cohort study of community-dwelling older adults. Incident hospitalized cases of acute renal failure were identified through hospital discharge International Classification of Diseases, Ninth Revision codes and confirmed through physician diagnoses of acute renal failure in discharge summaries.
RESULTS: Acute renal failure developed in 225 (3.9%) of the 5731 patients during a median follow-up period of 10.2 yr. In multivariate analyses, diabetes, current smoking, hypertension, C-reactive protein, and fibrinogen were associated with acute renal failure. Prevalent coronary heart disease was associated with incident acute renal failure, and among patients without prevalent coronary heart disease, subclinical vascular disease measures were also associated with acute renal failure: Low ankle-arm index (< or =0.9), common carotid intima-media thickness, and internal carotid intima-media thickness.
CONCLUSIONS: In this large, population-based, prospective cohort study, cardiovascular risk factors and both subclinical and clinical vascular disease were associated with incident acute renal failure in the elderly.
10aAcute Kidney Injury10aAged10aCardiovascular Diseases10aFemale10aFollow-Up Studies10aHumans10aMale10aProspective Studies10aRisk Factors1 aMittalhenkle, Anuja1 aStehman-Breen, Catherine, O1 aShlipak, Michael, G1 aFried, Linda, F1 aKatz, Ronit1 aYoung, Bessie, A1 aSeliger, Stephen1 aGillen, Daniel1 aNewman, Anne, B1 aPsaty, Bruce, M1 aSiscovick, David uhttps://chs-nhlbi.org/node/101502459nas a2200385 4500008004100000022001400041245007000055210006900125260001300194300001100207490000700218520139300225653000901618653002201627653002001649653002701669653001601696653001101712653003101723653001101754653001701765653002801782653002501810653000901835653001601844653001701860653002001877653002201897100002701919700001801946700002901964700002301993700002102016856003602037 2008 eng d a1533-345000aChronic kidney disease increases risk for venous thromboembolism.0 aChronic kidney disease increases risk for venous thromboembolism c2008 Jan a135-400 v193 aChronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.
10aAged10aAged, 80 and over10aBody Mass Index10aDiabetic Nephropathies10aFactor VIII10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney Failure, Chronic10aLongitudinal Studies10aMale10aMiddle Aged10aRisk Factors10aThromboembolism10aVenous Thrombosis1 aWattanakit, Keattiyoat1 aCushman, Mary1 aStehman-Breen, Catherine1 aHeckbert, Susan, R1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/100103152nas a2200445 4500008004100000022001400041245012800055210006900183260001300252300001000265490000600275520186400281653001102145653002202156653000902178653002202187653002202209653001102231653004002242653001102282653004302293653001502336653001702351653001302368653001102381653000902392653001602401653003802417653003602455653002402491653001802515653004102533100001602574700001702590700001602607700001602623700001502639700001602654856003602670 2008 eng d a1538-783600aCommon genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults.0 aCommon genetic variants associated with plasma fibrin Ddimer con c2008 Apr a654-90 v63 aBACKGROUND AND OBJECTIVES: D-dimer is a hemostasis marker that reflects ongoing fibrin formation and degradation. There is significant inter-individual and inter-population variability in D-dimer concentration, but whether genetic factors underlie these differences is largely unknown. We hypothesized that common coagulation gene variants contribute to differences in circulating D-dimer concentration.
METHODS: The setting was European-American (EA; n = 1858) and African-American (AA; n = 327) unrelated older adults from the Cardiovascular Health Study (CHS), in which we genotyped SNPs in 42 genes related to blood coagulation and fibrinolysis.
RESULTS: Several fibrinogen gene polymorphisms, including the Thr312Ala Aalpha chain variant and the FGG-10034 C/T variant, were associated with approximately 20% higher plasma D-dimer levels in EA (false discovery rate < 5% for covariate-adjusted model). There was also some evidence that a Pro41Leu variant of the PLAU gene encoding urinary plasminogen activator and non-coding polymorphism of the plasminogen activator inhibitor type 1 gene (SERPINE1) were associated with higher plasma D-dimer in EA. There were no significant associations between the studied coagulation or fibrinolysis gene SNPs and plasma D-dimer levels in the smaller AA sample. However, each standard deviation increase in European ancestry assessed by ancestry-informative gene markers was associated with approximately 10% lower mean D-dimer levels in AA.
CONCLUSIONS: Together, common coagulation/fibrinolysis gene SNPs explained only approximately 2% of the variance in plasma D-dimer levels in EA. These findings suggest that the association of D-dimer with risk of vascular outcomes may be mediated largely by environmental factors, other genes, and/or genetic interactions.
10aAfrica10aAfrican Americans10aAged10aAged, 80 and over10aBlood Coagulation10aEurope10aEuropean Continental Ancestry Group10aFemale10aFibrin Fibrinogen Degradation Products10aFibrinogen10aFibrinolysis10aGenotype10aHumans10aMale10aMiddle Aged10aPlasminogen Activator Inhibitor 110aPolymorphism, Single Nucleotide10aProspective Studies10aUnited States10aUrokinase-Type Plasminogen Activator1 aLange, L, A1 aReiner, A, P1 aCarty, C, L1 aJenny, N, S1 aCushman, M1 aLange, E, M uhttps://chs-nhlbi.org/node/101102806nas a2200493 4500008004100000022001400041245014000055210006900195260001300264300001100277490000800288520137300296653002201669653000901691653002301700653002801723653001901751653001901770653001101789653003801800653001501838653001101853653001801864653001401882653000901896653003601905653003201941653001801973100002301991700002102014700002102035700001702056700002002073700002002093700001402113700001402127700002502141700002402166700002002190700002202210700002002232700002502252856003502277 2008 eng d a1879-148400aCommon variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study.0 aCommon variants in the CRP gene in relation to longevity and cau c2008 Apr a922-300 v1973 aCommon polymorphisms in the CRP gene are associated with plasma CRP levels in population-based studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, noncardiovascular (non-CV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality. CRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of non-CV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and non-CV mortality in older adults, particularly in self-identified blacks.
10aAfrican Americans10aAged10aC-Reactive Protein10aCardiovascular Diseases10aCause of Death10aCohort Studies10aFemale10aGenetic Predisposition to Disease10aHaplotypes10aHumans10aLinear Models10aLongevity10aMale10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aUnited States1 aHindorff, Lucia, A1 aRice, Kenneth, M1 aLange, Leslie, A1 aDiehr, Paula1 aHalder, Indrani1 aWalston, Jeremy1 aKwok, Pui1 aZiv, Elad1 aNievergelt, Caroline1 aCummings, Steven, R1 aNewman, Anne, B1 aTracy, Russell, P1 aPsaty, Bruce, M1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/98602759nas a2200325 4500008004100000022001400041245010000055210006900155260001300224300001100237490000700248520183900255653000902094653002202103653002502125653001502150653002802165653001102193653002502204653001102229653000902240653002402249653001702273653003102290653001202321100002002333700002402353700002002377856003602397 2008 eng d a1079-500600aCoronary artery calcium and physical function in older adults: the Cardiovascular Health Study.0 aCoronary artery calcium and physical function in older adults th c2008 Oct a1112-80 v633 aBACKGROUND: In older adults without clinical cardiovascular disease, coronary artery calcium (CAC) is associated with other subclinical vascular diseases, which, in turn, predict physical dysfunction. However, the association between CAC and physical function is unstudied.
METHODS: In 387 older community-dwellers from the Cardiovascular Health Study without clinical cardiovascular diseases (mean age +/- standard deviation = 78.7 +/- 3.7, 35% men, 22% African Americans), CAC was measured using electron beam tomography, and physical performance was assessed by usual pace gait speed, chair stand, and tandem stand. Differences in physical performance across CAC quartiles were investigated in the whole cohort and by gender. Associations with gait speed (m/s) were assessed in multivariable models using both the continuous form of CAC score (log(CAC)) and quartiles of CAC, adjusting for demographics and comorbidities.
RESULTS: No differences in physical performance were observed across CAC quartiles in the whole group. In gender-stratified analyses, a significant association was shown among women, who had progressively lower gait speed across CAC quartiles: Those with CAC > 220 walked more than 0.1 m/s slower than those with CAC < 35 (age-adjusted ptrend =.017). After multivariable adjustment, the association remained statistically significant for women in both linear (log(CAC) and gait speed, p =.025) and logistic models: Each of the top three CAC quartiles (35-220, 221-659, and > or = 660) had a more than twofold odds of walking slower than 1 m/s, compared to the lowest CAC quartile (< 35; p =.021).
CONCLUSIONS: In this sample of older community-dwellers without overt cardiovascular disease, CAC was inversely related to gait speed in women, but not in men.
10aAged10aAged, 80 and over10aAnalysis of Variance10aCalcinosis10aCoronary Artery Disease10aFemale10aGeriatric Assessment10aHumans10aMale10aRegression Analysis10aRisk Factors10aTomography, X-Ray Computed10aWalking1 aInzitari, Marco1 aNaydeck, Barbara, L1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/106002894nas a2200397 4500008004100000022001400041245012600055210006900181260001600250300001100266490000800277520172100285653000902006653002202015653002802037653002702065653002902092653002802121653002102149653001102170653001102181653000902192653001402201653003002215653002202245653002002267653001802287100002002305700002402325700001902349700002402368700002402392700002302416700002102439856003602460 2008 eng d a0002-914900aCoronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old.0 aCoronary artery calcium carotid artery wall thickness and cardio c2008 Jan 15 a186-920 v1013 aFew population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.
10aAged10aAged, 80 and over10aCarotid Artery Diseases10aCarotid Artery, Common10aCarotid Artery, Internal10aCoronary Artery Disease10aCoronary Vessels10aFemale10aHumans10aMale10aROC Curve10aSeverity of Illness Index10aSurvival Analysis10aUltrasonography10aUnited States1 aNewman, Anne, B1 aNaydeck, Barbara, L1 aIves, Diane, G1 aBoudreau, Robert, M1 aSutton-Tyrrell, Kim1 aO'Leary, Daniel, H1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/100602997nas a2200409 4500008004100000022001400041245003400055210003300089260001600122300001100138490000800149520198900157653000902146653001002155653001502165653001502180653001502195653001402210653001102224653002202235653003102257653001102288653001102299653000902310100002002319700001602339700002002355700002102375700002202396700002102418700001702439700001902456700002002475700002402495710003202519856003602551 2008 eng d a0003-992600aCystatin C and aging success.0 aCystatin C and aging success c2008 Jan 28 a147-530 v1683 aBACKGROUND: To our knowledge, the effect of kidney function on successful aging has not been examined.
METHODS: We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged >or= 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.
RESULTS: A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m(2), respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).
CONCLUSION: A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.
10aAged10aAging10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aMale1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aKestenbaum, Brian1 aSeliger, Stephen1 aRifkin, Dena1 aTracy, Russell1 aNewman, Anne, B1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/101302801nas a2200505 4500008004100000022001400041245008500055210006900140260001300209300001000222490000700232520138800239653000901627653002201636653001501658653001901673653002501692653001501717653001401732653002101746653001101767653002901778653002801807653001101835653002501846653000901871653003001880653001601910653003201926653002001958653003201978653001802010653002202028100001802050700001602068700002202084700002002106700002002126700002402146700001702170700002402187700002402211700002402235856003602259 2008 eng d a1532-841400aCystatin C concentration as a predictor of systolic and diastolic heart failure.0 aCystatin C concentration as a predictor of systolic and diastoli c2008 Feb a19-260 v143 aBACKGROUND: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study.
METHODS AND RESULTS: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF > or = 50%) or SHF (EF < 50%). We compared the association of cystatin C with the risk for DHF and SHF, after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHF. After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]).
CONCLUSIONS: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF.
10aAged10aAged, 80 and over10aBiomarkers10aCohort Studies10aConfidence Intervals10aCystatin C10aCystatins10aEchocardiography10aFemale10aHeart Failure, Diastolic10aHeart Failure, Systolic10aHumans10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProbability10aProportional Hazards Models10aRisk Assessment10aSensitivity and Specificity10aStroke Volume10aSurvival Analysis1 aMoran, Andrew1 aKatz, Ronit1 aSmith, Nicolas, L1 aFried, Linda, F1 aSarnak, Mark, J1 aSeliger, Stephen, L1 aPsaty, Bruce1 aSiscovick, David, S1 aGottdiener, John, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/101202954nas a2200361 4500008004100000022001400041245007400055210006900129260001300198300001200211490000700223520196300230653000902193653002002202653001402222653002802236653002202264653001102286653000902297653002502306653001802331653001102349653001802360653002502378653000902403653003302412653002002445100002302465700002402488700002402512700002002536856003602556 2008 eng d a1538-672400aDiabetes mellitus and gait dysfunction: possible explanatory factors.0 aDiabetes mellitus and gait dysfunction possible explanatory fact c2008 Nov a1365-740 v883 aBACKGROUND AND OBJECTIVE: Gait characteristics differ in individuals with diabetes compared with those without diabetes. Limited information regarding potential explanatory factors for this association exists. This study examined the association between diabetes and gait characteristics in older adults and explored potential explanatory factors.
DESIGN: A cross-sectional, observational study design was used.
METHODS: At the 1998-1999 clinic visit, 558 ambulatory older adults (mean age=79 years) from the Pittsburgh site of the Cardiovascular Health Study had an assessment of their gait characteristics, diabetes, health status, cognition, mood, lower-extremity circulation and sensation, vision, lower-extremity strength (force-producing capacity), physical activity, and body mass index (BMI). A series of linear regression models were developed to examine the association between diabetes and gait characteristics and to examine potential explanatory factors for the associations.
RESULTS: Diabetes was related to gait speed (beta=-.06 m/s); however, the association was partially explained by health status variables, cognition, mood, lower-extremity circulation and sensation, visual impairment, lower-extremity strength, physical activity, and BMI. Health status and lower-extremity strength each explained the greatest proportion of the association (beta reduced 66% by each). Diabetes was related to step width (beta=.02 m), and the association could not be explained by the examined factors.
CONCLUSIONS: Diabetes was associated with gait alterations in older adults. Slowed gait speed appears to be secondary to the peripheral effect of the disease on other body systems. The effect of diabetes on step width was not explained in the analyses and may be related to peripheral motor nerve function or central influences of the disease, which could not be assessed in this study.
10aAged10aBody Mass Index10aCognition10aCross-Sectional Studies10aDiabetes Mellitus10aFemale10aGait10aGeriatric Assessment10aHealth Status10aHumans10aLinear Models10aLongitudinal Studies10aMale10aMulticenter Studies as Topic10aMuscle Strength1 aBrach, Jennifer, S1 aTalkowski, Jaime, B1 aStrotmeyer, Elsa, S1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/105203226nas a2200385 4500008004100000022001400041245009300055210006900148260001600217300001100233490000800244520217800252653000902430653002202439653001202461653002802473653001902501653002802520653002402548653002502572653001102597653001102608653001502619653001102634653000902645653001702654653001202671653000902683653001802692100002502710700002202735700002302757700002402780856003602804 2008 eng d a1524-453900aDietary fish and omega-3 fatty acid consumption and heart rate variability in US adults.0 aDietary fish and omega3 fatty acid consumption and heart rate va c2008 Mar 04 a1130-70 v1173 aBACKGROUND: Fish and omega-3 fatty acid consumption reduce risk of cardiac death, but mechanisms are not well established. Heart rate variability (HRV) predicts cardiac death and reflects specific electrophysiological pathways and influences. We hypothesized that habitual consumption of fish and marine omega-3 fatty acids would be associated with more favorable HRV, elucidating electrophysiological influences and supporting effects on clinical risk.
METHODS AND RESULTS: In a population-based cohort of older US adults, we evaluated cross-sectional associations of usual dietary fish and omega-3 consumption during the prior year and ECG-derived (n=4263) and 24-hour Holter monitor-derived (n=1152) HRV. After multivariable adjustment, consumption of tuna or other broiled/baked fish was associated with specific HRV components, including indices suggesting greater vagal predominance and moderated baroreceptor responses (eg, higher root mean square successive differences of normal-to-normal intervals [P=0.001]; higher normalized high-frequency power [P=0.008]; and lower low-frequency/high-frequency ratio [P=0.03]) and less erratic sinoatrial node firing (eg, lower Poincaré ratio [P=0.02] and higher short-term fractal scaling exponent [P=0.005]) but not measures of circadian fluctuations (eg, 24-hour standard deviation of normal-to-normal intervals). Findings were similar for estimated dietary consumption of marine omega-3 fatty acids. For magnitudes of observed differences in HRV comparing the highest to lowest category of fish intake, differences in relative risk of cardiac death during 10.8 years of follow-up ranged from 1.1% (for difference in standard deviation of normal-to-normal intervals) to 5.9% and 8.4% (for differences in Poincaré ratio and short-term fractal scaling exponent) lower risk.
CONCLUSIONS: Habitual tuna/other fish and marine omega-3 consumption are associated with specific HRV components in older adults, particularly indices of vagal activity, baroreceptor responses, and sinoatrial node function. Cellular mechanisms and implications for clinical risk deserve further investigation.
10aAged10aAged, 80 and over10aAnimals10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aElectrocardiography10aFatty Acids, Omega-310aFemale10aFishes10aHeart Rate10aHumans10aMale10aRisk Factors10aSeafood10aTuna10aUnited States1 aMozaffarian, Dariush1 aStein, Phyllis, K1 aPrineas, Ronald, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/102003297nas a2200469 4500008004100000022001400041245013000055210006900185260001300254300001000267490000700277520190900284653005102193653000902244653002002253653002002273653002402293653002802317653002102345653002102366653001902387653002802406653002402434653001102458653001802469653001102487653003402498653002102532653000902553653002102562653002402583653001702607653002402624653001802648100002102666700002402687700001702711700001802728700002502746700002002771856003602791 2008 eng d a1532-541500aDistribution and correlates of lipoprotein-associated phospholipase A2 in an elderly cohort: the Cardiovascular Health Study.0 aDistribution and correlates of lipoproteinassociated phospholipa c2008 May a792-90 v563 aOBJECTIVES: To determine whether high levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with prevalent cardiovascular disease (CVD) and to evaluate factors most influencing Lp-PLA(2) levels in a community-based cohort of older adults.
DESIGN: Cross-sectional.
SETTING: The Cardiovascular Health Study (CHS), a population-based cohort study of men and women aged 65 and older.
PARTICIPANTS: Five thousand five hundred thirty-one CHS participants.
MEASUREMENTS: Levels of Lp-PLA(2) activity were determined using stored blood samples from the baseline examination.
RESULTS: Mean Lp-PLA(2) was higher in participants with electrocardiographically determined ventricular conduction defect and major Q-wave abnormality and was positively correlated with left ventricular (LV) mass. It was high in those with echocardiographically determined abnormal LV ejection fraction, which persisted after adjustment. Mean Lp-PLA(2) was also higher in participants with mild renal insufficiency and kidney disease. After multivariable adjustment, there was a modest but significant 27% greater risk of prevalent CHF per standard deviation increment of Lp-PLA(2) and a modest but significant 12% greater risk of prevalent myocardial infarction. Lp-PLA(2) was weakly but mainly most strongly correlated with cholesterol and lipoproteins, but those correlations were not especially strong. Lp-PLA(2) was weakly positively correlated with soluble intercellular adhesion molecule-1 but not interleukin-6. In total, all factors considered could explain only 29% of Lp-PLA(2) activity.
CONCLUSION: Novel findings in the study are the associations, in those aged 65 and older, between Lp-PLA(2) activity and LV dysfunction, CHF, and renal disease. CVD risk factors only minimally explain levels of Lp-PLA(2).
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aAtherosclerosis10aBody Mass Index10aCardiac Output, Low10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aCross-Sectional Studies10aElectrocardiography10aFemale10aHeart Failure10aHumans10aHypertrophy, Left Ventricular10aLong QT Syndrome10aMale10aReference Values10aRenal Insufficiency10aRisk Factors10aStatistics as Topic10aTriglycerides1 aFurberg, Curt, D1 aNelson, Jeanenne, J1 aSolomon, Cam1 aCushman, Mary1 aJenny, Nancy, Swords1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/102202691nas a2200325 4500008004100000022001400041245010300055210006900158260001300227300001200240490000700252520180600259653000902065653001202074653001902086653001102105653001102116653000902127653001602136653002002152653002002172653002902192653001202221653001202233100001902245700002302264700002202287700002002309856003602329 2008 eng d a0161-810500aEffect of sleep disordered breathing on the sleep of bed partners in the Sleep Heart Health Study.0 aEffect of sleep disordered breathing on the sleep of bed partner c2008 Oct a1449-560 v313 aOBJECTIVE: To study the sleep quality of bed partners of persons with sleep disordered breathing in a non-clinical population based sample in a home environment.
DESIGN: Cross-sectional study in a community sample.
METHODS: 110 pairs of subjects living in the same household from the Tucson, Minnesota, and Pittsburgh sites of the Sleep Heart Health Study (SHHS) were included if both partners had an in-home, unattended polysomnogram (PSG) performed as a part of SHHS exam cycle 2. Sleep disordered breathing (SDB) was considered present if the respiratory disturbance index (RDI) was > or =10 events/h and no SDB if RDI was <5 events/h. Pairs were classified according to their SDB status and assigned to one of 3 groups: 1) NoSDB-NoSDB (n = 46), 2) NoSDB-SDB (n = 42), and 3) SDB-SDB (n = 22).
RESULTS: There were no differences between the NoSDB-NoSDB and the SDB-SDB partners in their demographic, PSG, or quality of life variables. However, within the NoSDB-SDB group, NoSDB in comparison to their SDB partners weighed less (mean BMI: 26 vs. 29 kg/m2, P < 0.0003), had decreased stage 2% (55 vs. 64, P < 0.0001), increased stage 3 and 4% (21 vs. 11, P <0.0005) and a lower arousal index (13.8 vs. 20 events/h, P < 0.0001). When comparing the NoSDB subjects from the NoSDB-SDB group to subjects in the NoSDB-NoSDB group and to subjects in the SDB-SDB group, significant differences were seen for RDI and BMI but not for any other parameter.
CONCLUSION: In a non-clinical population based sample, the sleep quality of bed partners of SDB subjects without SDB is better than their SDB bed partner. However, their sleep quality was not different in comparison to the sleep of those without SDB who also had a bed partner without SDB.
10aAged10aArousal10aCohort Studies10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aQuality of Life10aSleep Apnea, Obstructive10aSnoring10aSpouses1 aSharief, Imran1 aSilva, Graciela, E1 aGoodwin, James, L1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/105902839nas a2200469 4500008004100000022001400041245014000055210006900195260001300264300001000277490000700287520146600294653002201760653001601782653000901798653002201807653002201829653001401851653001901865653002501884653002301909653003001932653004001962653001102002653001302013653001102026653002502037653000902062653002902071653003202100653002402132653001702156653001602173100001702189700002802206700002002234700002102254700001602275700002002291700002202311856003602333 2008 eng d a0003-994200aEnhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study.0 aEnhanced risk for Alzheimer disease in persons with type 2 diabe c2008 Jan a89-930 v653 aBACKGROUND: Diabetes and the apolipoprotein E epsilon4 allele (APOE epsilon4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE epsilon4 may modify the risk for AD in individuals with diabetes.
OBJECTIVE: To examine the joint effect of type 2 diabetes and APOE epsilon4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD.
DESIGN: The Cardiovascular Health Study (CHS) Cognition Study (1992-2000) is a prospective study designed to identify all existing and new cases of dementia among study participants. Diagnoses were made according to international criteria for dementia and subtypes. There were 2547 dementia-free participants in the CHS Cognition Study cohort with complete information on APOE epsilon4 and type 2 diabetes status; among these, 411 new cases of dementia developed. Risk of dementia was estimated with a Cox proportional hazard model adjusted for age and other demographic and cardiovascular risk factors.
RESULTS: Compared with those who had neither type 2 diabetes nor APOE epsilon4, those with both factors had a significantly higher risk of AD (hazard ratio, 4.58; 95% confidence interval, 2.18-9.65) and mixed AD (hazard ratio, 3.89; 95% confidence interval, 1.46-10.40).
CONCLUSION: These data suggest that having both diabetes and APOE epsilon4 increases the risk of dementia, especially for AD and mixed AD.
10aAfrican Americans10aAge Factors10aAged10aAlzheimer Disease10aApolipoprotein E410aCognition10aCohort Studies10aConfidence Intervals10aDementia, Vascular10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aFemale10aGenotype10aHumans10aLongitudinal Studies10aMale10aNeuropsychological Tests10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSex Factors1 aIrie, Fumiko1 aFitzpatrick, Annette, L1 aLopez, Oscar, L1 aKuller, Lewis, H1 aPeila, Rita1 aNewman, Anne, B1 aLauner, Lenore, J uhttps://chs-nhlbi.org/node/100901807nas a2200385 4500008004100000022001400041245014600055210006900201260001600270300001200286490000700298520065000305653003100955653000900986653002200995653002801017653002601045653003701071653002401108653001101132653001101143653002501154653000901179653001801188653002401206653002501230653001701255100001601272700002401288700001801312700001701330700001801347700002001365856003601385 2008 eng d a0277-671500aEvaluation of a method for fitting a semi-Markov process model in the presence of left-censored spells using the Cardiovascular Health Study.0 aEvaluation of a method for fitting a semiMarkov process model in c2008 Nov 20 a5509-240 v273 aWe used a longitudinal data set covering 13 years from the Cardiovascular Health Study to evaluate the properties of a recently developed approach to deal with left censoring that fits a semi-Markov process (SMP) model by using an analog to the stochastic EM algorithm--the SMP-EM approach. It appears that the SMP-EM approach gives estimates of duration-dependent probabilities of health changes similar to those obtained by using SMP models that have the advantage of actual duration data. SMP-EM estimates of duration-dependent transition probabilities also appear more accurate and less variable than multi-state life table estimates.
10aActivities of Daily Living10aAged10aAged, 80 and over10aCardiovascular Diseases10aCardiovascular System10aData Interpretation, Statistical10aDisease Progression10aFemale10aHumans10aLongitudinal Studies10aMale10aMarkov Chains10aModels, Statistical10aStochastic Processes10aTime Factors1 aCai, Liming1 aSchenker, Nathaniel1 aLubitz, James1 aDiehr, Paula1 aArnold, Alice1 aFried, Linda, P uhttps://chs-nhlbi.org/node/105003455nas a2200421 4500008004100000022001400041245010600055210006900161260001300230300001200243490000700255520228800262653000902550653001802559653002002577653001902597653002802616653003002644653001202674653001102686653001102697653000902708653001602717653001502733653001102748653001902759653002002778653002102798653002902819100002602848700002102874700001702895700002402912700002102936700001702957700002302974856003602997 2008 eng d a0161-810500aFasting glycemia in sleep disordered breathing: lowering the threshold on oxyhemoglobin desaturation.0 aFasting glycemia in sleep disordered breathing lowering the thre c2008 Jul a1018-240 v313 aSTUDY OBJECTIVES: Commonly used definitions of sleep-disordered breathing (SDB) are based on identifying discrete events of breathing abnormalities during sleep that are accompanied by an oxyhemoglobin desaturation (delta SaO2) of at least 4%. However, it is not known whether disordered breathing events with oxyhemoglobin desaturation less than 4% are associated with clinical sequelae such as abnormalities in fasting glycemia.
DESIGN: Cross-sectional study.
SUBJECTS AND SETTING: Participants from the Sleep Heart Health Study (SHHS) with a fasting glucose measurement made within a year of the baseline polysomnogram.
MEASUREMENTS AND RESULTS: SDB severity was defined using the apnea-hypopnea index (AHI) and the hypopnea index (HI) by counting events with different levels of oxyhemoglobin desaturation (0.0%-1.9%, 2.0%-2.9%, 3.0%-3.9%, > or = 4.0%). Fasting glucose levels were used to classify individuals into normal (<100 mg/dL), impaired (100-125 mg/dL), and diabetic (> or = 126 mg/dL) groups. Ordinal logistic regression was used to determine the adjusted relative odds of an abnormal glucose value across quartiles of the hypopnea index, independent of factors such as age, body mass index, waist circumference, and usual sleep duration. The prevalence of impaired and diabetic fasting glucose in the analytical sample was 32.9% and 5.8%, respectively. The covariate-adjusted relative odds of impaired or diabetic fasting glucose in the highest versus the lowest AHI quartile was 1.35 (95% CI: 1.04-1.76) for events with a delta SaO2 > or = 4.0%, 1.72 (95% CI: 1.20-2.48) for events with a delta SaO2 between 3.0%-3.9%, 1.41 (95% CI: 1.07-1.86) for events with a delta SaO2 between 2.0%-2.9%, and 1.07 (95% CI: 0.84-1.37) for events with a delta SaO2 between 0.0%-1.9%. The corresponding odds ratios for the HI were 1.47 (95% CI: 1.13-1.92), 2.25 (95% CI: 1.59-3.19), 1.44 (95% CI: 1.09-1.90), and 1.15 (95% CI: 0.90-1.47), respectively.
CONCLUSIONS: The results of this study indicate that SDB events accompanied by oxyhemoglobin desaturation of between 2% to 4% are associated with fasting hyperglycemia. These findings suggest that milder degrees of SDB may predispose to adverse metabolic outcomes.
10aAged10aBlood Glucose10aBody Mass Index10aCohort Studies10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aFasting10aFemale10aHumans10aMale10aMiddle Aged10aOdds Ratio10aOxygen10aOxyhemoglobins10aPolysomnography10aReference Values10aSleep Apnea, Obstructive1 aStamatakis, Katherine1 aSanders, Mark, H1 aCaffo, Brian1 aResnick, Helaine, E1 aGottlieb, Dan, J1 aMehra, Reena1 aPunjabi, Naresh, M uhttps://chs-nhlbi.org/node/104302595nas a2200373 4500008004100000022001400041245008900055210006900144260001600213300001100229490000700240520161900247653000901866653001201875653001001887653002101897653001201918653002801930653000901958653001101967653001801978653001101996653001102007653003102018653000902049653002402058653000902082100001902091700002002110700002002130700001602150700001902166856003602185 2008 eng d a1526-632X00aFish consumption and risk of subclinical brain abnormalities on MRI in older adults.0 aFish consumption and risk of subclinical brain abnormalities on c2008 Aug 05 a439-460 v713 aOBJECTIVE: To investigate the association between fish consumption and subclinical brain abnormalities.
METHODS: In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses.
RESULTS: After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities.
CONCLUSIONS: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.
10aAged10aAnimals10aBrain10aBrain Infarction10aCooking10aCross-Sectional Studies10aDiet10aFemale10aFish Products10aFishes10aHumans10aMagnetic Resonance Imaging10aMale10aProspective Studies10aRisk1 aVirtanen, J, K1 aSiscovick, D, S1 aLongstreth, W T1 aKuller, L H1 aMozaffarian, D uhttps://chs-nhlbi.org/node/104602653nas a2200469 4500008004100000022001400041245009400055210006900149260001300218300001200231490000700243520139700250653002101647653000901668653001501677653002301692653002401715653001901739653001601758653001101774653001501785653002201800653001101822653002001833653001901853653000901872653001601881653002601897653001501923653001701938653001101955653001801966653001501984653002601999100002302025700002102048700002002069700001702089700002302106700001802129856003602147 2008 eng d a1524-462800aHemostatic and inflammatory risk factors for intracerebral hemorrhage in a pooled cohort.0 aHemostatic and inflammatory risk factors for intracerebral hemor c2008 Aug a2268-730 v393 aBACKGROUND AND PURPOSE: The purpose of this study was to identify novel risk factors for intracerebral hemorrhagic stroke (ICH).
METHODS: Risk factors were assessed at baseline in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) involving 21,680 adults aged 45 or over. Over 263,489 person-years of follow-up, we identified 135 incident ICH events.
RESULTS: In multivariable models, for each SD higher baseline level of fibrinogen, the relative rate of incident ICH increased 35% (95% CI, 17% to 55%). Fibrinogen was more strongly related to ICH in ARIC than in CHS. In multivariable models, those with von Willebrand factor levels above the median were 1.72 (95% CI, 0.97 to 3.03) times more likely to have an incident ICH as those below the median. Factor VIII was significantly positively related to ICH in ARIC (relative rate per standard deviation of 1.31; 95% CI, 1.07 to 1.62), but not in CHS. There was no relation in multivariable models between lipoprotein (a), Factor VII, white blood cell count, or C-reactive protein and ICH.
CONCLUSIONS: Greater plasma fibrinogen and, to some degree, von Willebrand factor were associated with increased rates of ICH in these prospective studies, whereas Factor VIII was related to ICH in younger ARIC study participants only.
10aAge Distribution10aAged10aBiomarkers10aC-Reactive Protein10aCerebral Hemorrhage10aCohort Studies10aFactor VIII10aFemale10aFibrinogen10aFollow-Up Studies10aHumans10aLeukocyte Count10aLipoprotein(a)10aMale10aMiddle Aged10aMultivariate Analysis10aPrevalence10aRisk Factors10aStroke10aUnited States10aVasculitis10avon Willebrand Factor1 aSturgeon, Jared, D1 aFolsom, Aaron, R1 aLongstreth, W T1 aShahar, Eyal1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/103603025nas a2200397 4500008004100000022001400041245011800055210006900173260001300242300001200255490000800267520183100275653000902106653002202115653001102137653001802148653001102166653001402177653004902191653004902240653003302289653000902322653003002331653002402361653001702385100002202402700002202424700002302446700001802469700002502487700002102512700002102533700001702554700002002571856003602591 2008 eng d a1097-674400aHigh insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly.0 aHigh insulinlike growth factor binding protein 1 level predicts c2008 Jun a1006-120 v1553 aBACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.
METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.
RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.
CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.
10aAged10aAged, 80 and over10aFemale10aHeart Failure10aHumans10aIncidence10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aPredictive Value of Tests10aProspective Studies10aRisk Factors1 aKaplan, Robert, C1 aMcGinn, Aileen, P1 aPollak, Michael, N1 aKuller, Lewis1 aStrickler, Howard, D1 aRohan, Thomas, E1 aCappola, Anne, R1 aXue, XiaoNan1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/103502289nas a2200337 4500008004100000022001400041245013800055210006900193260001600262300001200278490000800290520128900298653000901587653002301596653002101619653001101640653001101651653001401662653002501676653000901701653001601710653003201726653001801758653002701776100002701803700002101830700002301851700002301874700001801897856003601915 2008 eng d a1528-002000aHigh-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).0 aHighdensity lipoprotein cholesterol and venous thromboembolism i c2008 Oct 01 a2675-800 v1123 aWe determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL(2), HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.
10aAged10aApolipoprotein A-I10aCholesterol, HDL10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aMiddle Aged10aProportional Hazards Models10aUnited States10aVenous Thromboembolism1 aChamberlain, Alanna, M1 aFolsom, Aaron, R1 aHeckbert, Susan, R1 aRosamond, Wayne, D1 aCushman, Mary uhttps://chs-nhlbi.org/node/104002896nas a2200385 4500008004100000022001400041245022700055210006900282260001300351300001100364490000700375520165900382653000902041653002302050653002802073653002802101653003602129653001102165653001502176653001502191653001102206653002702217653002302244653001802267653000902285653001702294100002202311700002402333700002302357700002102380700002602401700002302427700002402450856003602474 2008 eng d a1532-541500aHigher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: the Cardiovascular Health Study.0 aHigher levels of inflammation factors and greater insulin resist c2008 Feb a315-210 v563 aOBJECTIVES: To explore the relationship between (1) insulin resistance and inflammation factors with (2) higher heart rate (HR) and lower heart rate variability (HRV) in normoglycemic older adults.
DESIGN: Cross-sectional population-based study.
PARTICIPANTS: Five hundred forty-five adults aged 65 and older with normoglycemia (fasting glucose <100 mg/dL) who participated in the Cardiovascular Health Study.
MEASUREMENTS: Serum levels of three inflammation proteins (C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen); insulin resistance, quantified according to the homeostasis assessment model (HOMA-IR); HR; and four representative measures of HRV (the standard deviation of normal beat to beat intervals (SDNN), the root mean square of successive differences (rMSSD), very low frequency power (VLF), and the low- to high-frequency power ratio (LF/HF)) derived from 24-hour Holter recordings.
RESULTS: High CRP and IL-6 levels were associated with higher HR and lower SDNN and VLF after adjustment for multiple covariates, including HOMA-IR and clinical cardiovascular disease. High IL-6 was also associated with lower LF/HF. Significant univariate inverse relationships between HOMA-IR and HR and HRV were also found, but the strengths of these relationships were attenuated after adjustment for inflammation factors.
CONCLUSION: Increased levels of inflammation markers and HOMA-IR are associated with higher HR and lower HRV. These findings suggest that inflammation may contribute to the pathogenesis of cardiovascular autonomic decline in older adults.
10aAged10aC-Reactive Protein10aCardiovascular Diseases10aCross-Sectional Studies10aElectrocardiography, Ambulatory10aFemale10aFibrinogen10aHeart Rate10aHumans10aInflammation Mediators10aInsulin Resistance10aInterleukin-610aMale10aRisk Factors1 aStein, Phyllis, K1 aBarzilay, Joshua, I1 aChaves, Paulo, H M1 aTraber, Jennifer1 aDomitrovich, Peter, P1 aHeckbert, Susan, R1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/100802841nas a2200385 4500008004100000022001400041245014000055210006900195260001300264300001200277490000700289520173200296653002102028653000902049653002202058653002302080653002802103653001102131653000902142653002502151653001802176653001102194653000902205653001902214653002602233653001502259653002102274653002002295653001202315100002402327700002302351700002502374700002002399856003602419 2008 eng d a1538-672400aImpact of health perception, balance perception, fall history, balance performance, and gait speed on walking activity in older adults.0 aImpact of health perception balance perception fall history bala c2008 Dec a1474-810 v883 aBACKGROUND AND PURPOSE: Disagreement currently exists regarding the contributions of various factors to physical activity in older adults. The purpose of this cross-sectional study was to investigate the simultaneous impact of psychological (health perception and balance perception) and physiological (gait speed, fall history, and balance performance) factors on walking activity in older adults.
SUBJECTS AND METHODS: This cross-sectional secondary data analysis included 2,269 community-dwelling older adults from the Cardiovascular Health Study. A series of simultaneous linear regression models were constructed to examine the association of walking activity with health and balance perception, gait speed, fall history, and balance performance after controlling for potential confounding factors.
RESULTS: Health and balance perception and gait speed were significantly related to walking activity after controlling for potential confounding factors. Participants who perceived both their health and their balance to be good walked more blocks per week than those who reported a discordant perception, who walked more than those who perceived both their health and their balance to be poor. Participants who walked at a normal speed walked more blocks per week than those who walked at a slow speed.
DISCUSSION AND CONCLUSION: The measure of physical activity used in this study included only walking, not other low- to moderate-intensity activities that are common in older adults. Health and balance perception and gait speed were associated with walking activity more so than fall history or balance performance after controlling for potential confounding factors.
10aAccidental Falls10aAged10aAged, 80 and over10aAttitude to Health10aCross-Sectional Studies10aFemale10aGait10aGeriatric Assessment10aHealth Status10aHumans10aMale10aMotor Activity10aMultivariate Analysis10aPerception10aPostural Balance10aRisk Assessment10aWalking1 aTalkowski, Jaime, B1 aBrach, Jennifer, S1 aStudenski, Stephanie1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/105803343nas a2200457 4500008004100000022001400041245012900055210006900184260001300253300001200266490000700278520198400285653003102269653000902300653002802309653001902337653001602356653002602372653001102398653000902409653002502418653001102443653002002454653000902474653002402483653003302507653003202540653002002572653001702592653001802609100002302627700001702650700002402667700002402691700002102715700002502736700002102761700002002782710004702802856003602849 2008 eng d a1532-541500aIncident physical disability in people with lower extremity peripheral arterial disease: the role of cardiovascular disease.0 aIncident physical disability in people with lower extremity peri c2008 Jun a1037-440 v563 aOBJECTIVES: To evaluate the risk of incident physical disability and the decline in gait speed over a 6-year follow-up associated with a low ankle-arm index (AAI) in older adults.
DESIGN: Observational cohort study.
SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.
PARTICIPANTS: Four thousand seven hundred five older adults, 58% women and 17.6% black, participating in the Cardiovascular Health Study.
MEASUREMENTS: AAI was measured in 1992/93 (baseline). Self-reported mobility, activity of daily living (ADL), and instrumental activity of daily living (IADL) disability and gait speed were recorded at baseline and at 1-year intervals over 6 years of follow-up. Mobility disability was defined as any difficulty walking half a mile and ADL and IADL disability was defined as any difficulty with 11 specific ADL and IADL tasks. Individuals with mobility, ADL, or IADL disability at baseline were excluded from the respective incident disability analyses.
RESULTS: Lower baseline AAI values were associated with increased risk of mobility disability and ADL/IADL disability. Clinical cardiovascular disease (CVD), diabetes mellitus, and interim CVD events partially explained these associations for mobility disability and clinical CVD and diabetes mellitus partially explained these associations for ADL and IADL disability. Individuals with an AAI less than 0.9 had on average a mean decrease in gait speed of 0.02 m/s per year, or a decline of 0.12 m/s over the 6-year follow-up. Prevalent CVD partly explained this decrease but interim CVD events did not further attenuate it.
CONCLUSION: Low AAI serves as marker of future disability risk. Reduction of disability risk in patients with a low AAI should consider cardiovascular comorbidity and the prevention of additional disabling CVD events.
10aActivities of Daily Living10aAged10aCardiovascular Diseases10aCohort Studies10aComorbidity10aDisability Evaluation10aFemale10aGait10aGeriatric Assessment10aHumans10aLower Extremity10aMale10aMobility Limitation10aPeripheral Vascular Diseases10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aUnited States1 aBrach, Jennifer, S1 aSolomon, Cam1 aNaydeck, Barbara, L1 aSutton-Tyrrell, Kim1 aEnright, Paul, L1 aJenny, Nancy, Swords1 aChaves, Paulo, M1 aNewman, Anne, B1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/102402756nas a2200433 4500008004100000022001400041245008000055210006900135260001600204300001100220490000800231520152100239653000901760653002301769653002801792653001101820653001501831653002901846653002501875653001101900653002001911653002501931653002901956653000901985653003301994653004302027653001502070100001502085700002202100700002102122700002002143700002402163700001802187700002202205700001802227700002402245700001702269856003602286 2008 eng d a1476-625600aInflammatory markers and longitudinal lung function decline in the elderly.0 aInflammatory markers and longitudinal lung function decline in t c2008 Sep 15 a602-100 v1683 aLongitudinal studies examining associations of the inflammatory markers fibrinogen and C-reactive protein (CRP) with lung function decline are sparse. The authors examined whether elevated fibrinogen and CRP levels were associated with greater longitudinal lung function decline in the elderly. The Cardiovascular Health Study measured fibrinogen and CRP in 5,790 Whites and African Americans from four US communities aged 65 years or older in 1989-1990 or 1992-1993. Spirometry was performed in 1989-1990 and 4, 7, and 16 years later. Fibrinogen and CRP were inversely associated with lung function at baseline after adjustment for multiple potential confounders. In mixed models, the rate of decline in forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) ratio with increasing age was faster among those with higher baseline fibrinogen (-0.032%/year per standard deviation higher fibrinogen (95% confidence interval: -0.057, -0.0074)) but not among those with higher CRP (-0.0037%/year per standard deviation higher CRP (95% confidence interval: -0.013, 0.0056)). Longitudinal analyses for FEV(1) and FVC yielded results in the direction opposite of that hypothesized, possibly because of the high mortality rate and strong inverse association of FEV(1) and FVC but not FEV(1)/FVC with mortality. An alternative approach to missing data yielded similar results. In conclusion, higher levels of fibrinogen, but not CRP, independently predicted greater FEV(1)/FVC decline in the elderly.
10aAged10aC-Reactive Protein10aCross-Sectional Studies10aFemale10aFibrinogen10aForced Expiratory Volume10aGeriatric Assessment10aHumans10aLogistic Models10aLongitudinal Studies10aLung Volume Measurements10aMale10aMulticenter Studies as Topic10aPulmonary Disease, Chronic Obstructive10aSpirometry1 aJiang, Rui1 aBurke, Gregory, L1 aEnright, Paul, L1 aNewman, Anne, B1 aMargolis, Helene, G1 aCushman, Mary1 aTracy, Russell, P1 aWang, Yuanjia1 aKronmal, Richard, A1 aBarr, Graham uhttps://chs-nhlbi.org/node/104802753nas a2200421 4500008004100000022001400041245010100055210006900156260001300225300001100238490000700249520154500256653000901801653002201810653001901832653002801851653001101879653002401890653001101914653001701925653004801942653000901990653002401999653001702023100002602040700002202066700002502088700002102113700002002134700002102154700001802175700001702193700002002210700002402230700002002254700002202274856003502296 2008 eng d a1096-637400aInsulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults.0 aInsulinlike growth factorIGFaxis inflammation and glucose intole c2008 Apr a166-730 v183 aIncreasing evidence suggests that the insulin-like growth factor (IGF)-axis may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women > or = 65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95% CI: 0.26, 0.64; p-trend: <0.01) for IFG. We did not find any significant association between IGF-I and glucose intolerance in this study and the association for IGFBP-3 was less clear. However, low levels of IGF-I and IGFBP-3 were associated with increased levels of markers of inflammation including C-reactive protein and interleukin-6 levels. We conclude that among adults > or = 65 years, low IGFBP-1 levels are associated with increased prevalence of glucose intolerance. We did not confirm prior associations of low IGF-I with glucose intolerance in this cohort of older individuals.
10aAged10aAged, 80 and over10aCohort Studies10aCross-Sectional Studies10aFemale10aGlucose Intolerance10aHumans10aInflammation10aInsulin-Like Growth Factor Binding Proteins10aMale10aSignal Transduction10aSomatomedins1 aRajpathak, Swapnil, N1 aMcGinn, Aileen, P1 aStrickler, Howard, D1 aRohan, Thomas, E1 aPollak, Michael1 aCappola, Anne, R1 aKuller, Lewis1 aXue, XiaoNan1 aNewman, Anne, B1 aStrotmeyer, Elsa, S1 aPsaty, Bruce, M1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/99102542nas a2200373 4500008004100000022001400041245011500055210006900170260001300239300001500252490000700267520147600274653000901750653002201759653002401781653001301805653002401818653002601842653001101868653001101879653000901890653002901899653001801928100001901946700002401965700002201989700001902011700002302030700002002053700001802073700001902091700002202110856003602132 2008 eng d a1878-592100aItem response theory facilitated cocalibrating cognitive tests and reduced bias in estimated rates of decline.0 aItem response theory facilitated cocalibrating cognitive tests a c2008 Oct a1018-27.e90 v613 aOBJECTIVE: To cocalibrate the Mini-Mental State Examination, the Modified Mini-Mental State, the Cognitive Abilities Screening Instrument, and the Community Screening Instrument for Dementia using item response theory (IRT) to compare screening cut points used to identify cases of dementia from different studies, to compare measurement properties of the tests, and to explore the implications of these measurement properties on longitudinal studies of cognitive functioning over time.
STUDY DESIGN AND SETTING: We used cross-sectional data from three large (n>1000) community-based studies of cognitive functioning in the elderly. We used IRT to cocalibrate the scales and performed simulations of longitudinal studies.
RESULTS: Screening cut points varied quite widely across studies. The four tests have curvilinear scaling and varied levels of measurement precision, with more measurement error at higher levels of cognitive functioning. In longitudinal simulations, IRT scores always performed better than standard scoring, whereas a strategy to account for varying measurement precision had mixed results.
CONCLUSION: Cocalibration allows direct comparison of cognitive functioning in studies using any of these four tests. Standard scoring appears to be a poor choice for analysis of longitudinal cognitive testing data. More research is needed into the implications of varying levels of measurement precision.
10aAged10aAged, 80 and over10aCognition Disorders10aDementia10aDisease Progression10aEpidemiologic Methods10aFemale10aHumans10aMale10aNeuropsychological Tests10aPsychometrics1 aCrane, Paul, K1 aNarasimhalu, Kaavya1 aGibbons, Laura, E1 aMungas, Dan, M1 aHaneuse, Sebastien1 aLarson, Eric, B1 aKuller, Lewis1 aHall, Kathleen1 avan Belle, Gerald uhttps://chs-nhlbi.org/node/102902835nas a2200481 4500008004100000022001400041245009100055210006900146260001600215300001200231490000700243520162400250653000901874653002201883653001001905653001801915653000801933653001601941653001001957653001001967653002101977653001301998653001602011653001102027653002202038653001102060653001102071653002002082653000902102653000902111653001602120653002402136653001702160653002402177653001302201100001602214700001802230700002202248700001602270700001502286700001602301856003602317 2008 eng d a1526-632X00aKnee height and arm span: a reflection of early life environment and risk of dementia.0 aKnee height and arm span a reflection of early life environment c2008 May 06 a1818-260 v703 aOBJECTIVES: To determine if anthropometric measures, as markers of early life environment, are associated with risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).
METHODS: A total of 2,798 subjects were followed as part of the Cardiovascular Health Cognition Study for an average of 5.4 years; 480 developed dementia. Knee height was measured 3 years prior to and arm span 4 years after the study's baseline. Cox proportional hazard models were used to examine their association with subsequent risk of dementia, AD, and VaD.
RESULTS: Among women, greater knee height and arm span were associated with lower risks of dementia (knee height: HR per 1-inch increase 0.84; 95% CI 0.74-0.96; arm span: HR per 1-inch increase 0.93; 95% CI 0.88-0.98) and AD (knee height: HR per 1-inch increase 0.78; 95% CI 0.65-0.93; arm span: HR per 1-inch increase 0.90; 95% CI 0.85-0.96). Women in the lowest quartile of arm span had approximately 1.5 times greater risk of dementia (HR 1.45; 95% CI 1.03-2.05) and AD (HR 1.70; 95% CI 1.10-2.62) than other women. Among men, only arm span was associated with lower risks of dementia (HR per 1-inch increase 0.94; 95% CI 0.89-1.00) and AD (HR per 1-inch increase 0.92; 95% CI 0.84-1.00). For each gender, knee height was not associated with VaD, while arm span was associated with a nonsignificant lower risk of VaD.
CONCLUSIONS: Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk.
10aAged10aAged, 80 and over10aAging10aAnthropometry10aArm10aBody Height10aBrain10aChild10aChild, Preschool10aDementia10aEnvironment10aFemale10aFollow-Up Studies10aHumans10aInfant10aInfant, Newborn10aKnee10aMale10aMiddle Aged10aProspective Studies10aRisk Factors10aSex Characteristics10aSkeleton1 aHuang, T, L1 aCarlson, M, C1 aFitzpatrick, A, L1 aKuller, L H1 aFried, L P1 aZandi, P, P uhttps://chs-nhlbi.org/node/103102395nas a2200337 4500008004100000022001400041245012900055210006900184260001300253300001000266490000700276520141300283653000901696653002201705653002601727653002101753653001101774653001801785653001101803653001701814653003401831653000901865653002601874653001201900653001701912100002401929700002401953700002201977700002201999856003602021 2008 eng d a0195-668X00aLeft ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study.0 aLeft ventricular mass predicts heart failure not related to prev c2008 Mar a741-70 v293 aAIMS: The relationship of left ventricular hypertrophy (LVH) to incident heart failure (HF) not attributable to myocardial infarction (MI) has not been defined. We assessed whether LVH is an independent predictor of MI-independent HF.
METHODS AND RESULTS: LVH was assessed by echocardiographic LV mass index (in g/m2.7) and excess of LV mass (eLVM, in % of the observed value) relative to the amount predicted by sex, stroke work, and height, using a prognostically validated equation in 2078 participants of Cardiovascular Health Study without prevalent MI and normal systolic function. Increasing eLVM was associated with progressively increasing left atrial dimension and concentric geometry, decreasing systolic (P < 0.0001), and diastolic function (P < 0.04). After adjustment for age, sex, obesity, diabetes, hypertension, and antihypertensive therapy, and accounting for by incident MI, hazard of HF increased by 1% for each 1% increase in eLVM and by 3% for each g/m2.7 increase in LV mass index (both P < 0.0001). The results were confirmed when also C-reactive protein and measures of systolic (endocardial shortening) and diastolic function (categories of E/A ratio) were added to the Cox models.
CONCLUSION: In an elderly population, LVH, measured as LV mass index or eLVM is an independent predictor of incident HF not related to prevalent or incident MI.
10aAged10aAged, 80 and over10aDiabetic Angiopathies10aEchocardiography10aFemale10aHeart Failure10aHumans10aHypertension10aHypertrophy, Left Ventricular10aMale10aMyocardial Infarction10aObesity10aRisk Factors1 ade Simone, Giovanni1 aGottdiener, John, S1 aChinali, Marcello1 aMaurer, Mathew, S uhttps://chs-nhlbi.org/node/101002889nas a2200361 4500008004100000022001400041245011500055210006900170260001600239300001300255490000800268520185100276653000902127653002102136653001102157653001102168653003402179653001202213653000902225653001602234653001502250653002602265653001202291653003402303100002102337700002502358700002402383700001702407700001902424700002402443700002402467856003602491 2008 eng d a1524-453900aLeft ventricular morphology and systolic function in sleep-disordered breathing: the Sleep Heart Health Study.0 aLeft ventricular morphology and systolic function in sleepdisord c2008 May 20 a2599-6070 v1173 aBACKGROUND: Whether sleep-disordered breathing (SDB) is a risk factor for left ventricular (LV) hypertrophy and dysfunction is controversial. We assessed the relation of SDB to LV morphology and systolic function in a community-based sample of middle-aged and older adults.
METHODS AND RESULTS: The present study was a cross-sectional observational study of 2058 Sleep Heart Health Study participants (mean age 65+/-12 years; 58% women; 44% ethnic minorities) who had technically adequate echocardiograms. A polysomnographically derived apnea-hypopnea index (AHI) and hypoxemia index (percent of sleep time with oxyhemoglobin saturation < 90%) were used to quantify SDB severity. LV mass index was significantly associated with both AHI and hypoxemia index after adjustment for age, sex, ethnicity, study site, body mass index, current and prior smoking, alcohol consumption, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and prevalent myocardial infarction. Adjusted LV mass index was 41.3 (SD 9.90) g/m(2.7) in participants with AHI < 5 (n=957) and 44.1 (SD 9.90) g/m(2.7) in participants with AHI > or = 30 (n=84) events per hour. Compared with participants with AHI < 5, those with AHI > or = 30 had an adjusted odds ratio of 1.78 (95% confidence interval 1.14 to 2.79) for LV hypertrophy. A higher AHI and higher hypoxemia index were also associated with larger LV diastolic dimension and lower LV ejection fraction, with a trend toward lower LV fractional shortening. LV wall thickness was significantly associated with the hypoxemia index but not with AHI. Left atrial diameter was not associated with either SDB measure.
CONCLUSIONS: In a community-based cohort, SDB is associated with echocardiographic evidence of increased LV mass and reduced LV systolic function.
10aAged10aEchocardiography10aFemale10aHumans10aHypertrophy, Left Ventricular10aHypoxia10aMale10aMiddle Aged10aOdds Ratio10aSleep Apnea Syndromes10aSystole10aVentricular Dysfunction, Left1 aChami, Hassan, A1 aDevereux, Richard, B1 aGottdiener, John, S1 aMehra, Reena1 aRoman, Mary, J1 aBenjamin, Emelia, J1 aGottlieb, Daniel, J uhttps://chs-nhlbi.org/node/103002223nas a2200325 4500008004100000022001400041245009100055210006900146260001300215300001000228490000700238520130400245653005101549653000901600653001101609653001101620653000901631653001701640653002201657100001601679700002201695700002001717700002101737700002101758700002101779700002301800700002001823700001801843856003601861 2008 eng d a1096-865200aLipoprotein-associated phospholipase A2 and risk of venous thrombosis in older adults.0 aLipoproteinassociated phospholipase A2 and risk of venous thromb c2008 Jul a524-70 v833 aLipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in inflammation and platelet function. Inherited deficiency and elevated levels are associated with atherosclerosis. Given potential common etiologies of atherosclerosis and venous thrombosis (VT), we hypothesized that low and high Lp-PLA2 would be associated with VT risk. Lp-PLA(2) mass and activity were measured in baseline samples of Cardiovascular Health Study participants (5,888 men and women age > or =65), excluding 354 reporting pre-baseline VT. The study endpoint was VT unrelated to cancer after 11.6 years follow-up. Hazard ratios were estimated using Cox proportional hazard models, adjusting for age, race, sex, and body-mass index. With 129 cases of VT, there was no association of Lp-PLA2 activity with risk. Adjusted hazard ratios were 1.19 (CI 0.62, 2.29) and 0.87 (CI 0.43, 1.76) for the lowest and highest decile, respectively, compared to the 10-25th percentile. Corresponding hazard ratios for Lp-PLA2 mass were 1.63 (CI 0.79, 3.34) and 1.33 (CI 0.61, 2.87). Results were robust to several definitions of low or high Lp-PLA2. While the association of Lp-PLA(2) levels with arterial disease events implies a role for this enzyme in atherogenesis, our findings suggest that it is not prothrombotic.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aFemale10aHumans10aMale10aRisk Factors10aVenous Thrombosis1 aOlson, Nels1 aO'Meara, Ellen, S1 aJenny, Nancy, S1 aFolsom, Aaron, R1 aBovill, Edwin, G1 aFurberg, Curt, D1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aCushman, Mary uhttps://chs-nhlbi.org/node/102303487nas a2200361 4500008004100000022001400041245008700055210006900142260001600211300001100227490000800238520247700246653000902723653002202732653001802754653001202772653001102784653002202795653001102817653001702828653000902845653002302854653002602877653003202903653002402935653002002959653001802979100002502997700002003022700002303042700002403065856003603089 2008 eng d a1538-367900aMetabolic syndrome and mortality in older adults: the Cardiovascular Health Study.0 aMetabolic syndrome and mortality in older adults the Cardiovascu c2008 May 12 a969-780 v1683 aBACKGROUND: The utility of metabolic syndrome (MetS) for predicting mortality among older adults, the highest-risk population, is not well established. In addition, few studies have compared the predictive utility of MetS to that of its individual risk factors.
METHODS: We evaluated relationships of MetS (as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III (ATPIII)], International Diabetes Foundation [IDF], and World Health Organization [WHO]) and individual MetS criteria with mortality between 1989 and 2004 among 4258 US adults 65 years or older and free of prevalent cardiovascular disease (CVD) in the Cardiovascular Health Study, a multicenter, population-based, prospective cohort. Total, CVD, and non-CVD mortality were evaluated. Cox proportional hazards models were used to estimate the mortality hazard ratio (relative risk [RR]) predicted by MetS.
RESULTS: At baseline (mean age, 73 years), 31% of men and 38% of women had MetS (ATPIII). During 15 years of follow-up, 2116 deaths occurred. After multivariable adjustment, compared with persons without MetS, those with MetS had a 22% higher mortality (RR, 1.22; 95% confidence interval [CI], 1.11-1.34). Higher risk with MetS was confined to persons having elevated fasting glucose level (EFG) (defined as > or = 110 mg/dL [> or = 6.1 mmol/L] or treated diabetes mellitus) (RR, 1.41; 95% CI, 1.27-1.57) or hypertension (RR, 1.26; 95% CI, 1.15-1.39) as one of the criteria; persons having MetS without EFG (RR, 0.97; 95% CI, 0.85-1.11) or MetS without hypertension (RR, 0.92; 95% CI, 0.71-1.19) did not have higher risk. Evaluating MetS criteria individually, we found that only hypertension and EFG predicted higher mortality; persons having both hypertension and EFG had 82% higher mortality (RR, 1.82; 95% CI, 1.58-109). Substantially higher proportions of deaths were attributable to EFG and hypertension (population attributable risk fraction [PAR%], 22.2%) than to MetS (PAR%, 6.3%). Results were similar when we used WHO or IDF criteria, when we evaluated different cut points of each individual criterion, and when we evaluated CVD mortality.
CONCLUSION: These findings suggest limited utility of MetS for predicting total or CVD mortality in older adults compared with assessment of fasting glucose and blood pressure alone.
10aAged10aAged, 80 and over10aBlood Glucose10aFasting10aFemale10aFollow-Up Studies10aHumans10aHypertension10aMale10aMetabolic Syndrome10aMultivariate Analysis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aUnited States1 aMozaffarian, Dariush1 aKamineni, Aruna1 aPrineas, Ronald, J1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/103302898nas a2200433 4500008004100000022001400041245012200055210006900177260001300246300001100259490000800270520169300278653001001971653000901981653002001990653002602010653001102036653001102047653002602058653000902084653002302093653001602116653001402132653002402146653001702170653001102187653002202198100001902220700001902239700002602258700001702284700001802301700001902319700002902338700002402367700001702391700002002408856003602428 2008 eng d a1097-674400aMetabolic syndrome, endothelial dysfunction, and risk of cardiovascular events: the Northern Manhattan Study (NOMAS).0 aMetabolic syndrome endothelial dysfunction and risk of cardiovas c2008 Aug a405-100 v1563 aBACKGROUND: Metabolic syndrome (MetS) predisposes to cardiovascular disease. Endothelial dysfunction is thought to be an important factor in the pathogenesis of atherosclerosis. We tested the hypothesis that both MetS and endothelial dysfunction are vascular risk factors and provide additive prognostic values in predicting cardiovascular events in a multiethnic community sample.
METHODS: The study population consisted of 819 subjects (467 female, mean age 66.5 +/- 8.8 years, 66% Hispanic) enrolled in the NOMAS. Metabolic syndrome was defined using the revised Adult Treatment Panel III criteria. Brachial artery flow-mediated dilation (FMD) was measured using high-resolution ultrasound. Endothelial dysfunction was defined as FMD <8.44% (lower 3 quartiles). Cox proportional hazards models were used to assess the effect of MetS and endothelial dysfunction on risk of cardiovascular events.
RESULTS: During 81 +/- 21 months of follow-up, events occurred in 84 subjects. Metabolic syndrome was independently associated with cardiovascular events in a multivariate model, including cardiovascular risk factors (adjusted hazard ratio 2.08, 95% CI 1.27-3.40). Subjects with both MetS and endothelial dysfunction were at higher risk for cardiovascular events than those with either one of them alone (adjusted hazard ratio 2.60, 95% CI 1.14-5.92).
CONCLUSIONS: Metabolic syndrome is associated with incident cardiovascular events. Combined use of MetS and FMD identifies those who are at higher risk of cardiovascular events. Metabolic syndrome and noninvasive FMD testing can be used concurrently for cardiovascular risk prediction.
10aAdult10aAged10aBrachial Artery10aEndothelium, Vascular10aFemale10aHumans10aKaplan-Meier Estimate10aMale10aMetabolic Syndrome10aMiddle Aged10aPrognosis10aProspective Studies10aRisk Factors10aStroke10aVascular Diseases1 aSuzuki, Takeki1 aHirata, Kumiko1 aElkind, Mitchell, S V1 aJin, Zhezhen1 aRundek, Tanja1 aMiyake, Yumiko1 aBoden-Albala, Bernadette1 aDi Tullio, Marco, R1 aSacco, Ralph1 aHomma, Shunichi uhttps://chs-nhlbi.org/node/104403257nas a2200565 4500008004100000022001400041245011300055210006900168260001600237300001100253490000700264520171200271653001801983653001502001653001002016653000902026653002202035653002202057653002602079653002902105653004402134653001202178653001902190653001102209653001102220653000902231653001602240653002702256653002202283653003202305653002402337653001702361100001802378700001602396700002102412700001702433700001702450700001802467700001602485700001502501700001602516700001602532700001502548700001802563700001502581700002002596700002302616700001602639856003602655 2008 eng d a1526-632X00aNo advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.0 aNo advantage of A beta 42lowering NSAIDs for prevention of Alzhe c2008 Jun 10 a2291-80 v703 aINTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.
METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.
RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).
CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.
10aAcetaminophen10aAdolescent10aAdult10aAged10aAged, 80 and over10aAlzheimer Disease10aAmyloid beta-Peptides10aAnalgesics, Non-Narcotic10aAnti-Inflammatory Agents, Non-Steroidal10aAspirin10aCohort Studies10aFemale10aHumans10aMale10aMiddle Aged10aNeuroprotective Agents10aPeptide Fragments10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aSzekely, C, A1 aGreen, R, C1 aBreitner, J, C S1 astbye, T, Ø1 aBeiser, A, S1 aCorrada, M, M1 aDodge, H, H1 aGanguli, M1 aKawas, C, H1 aKuller, L H1 aPsaty, B M1 aResnick, S, M1 aWolf, P, A1 aZonderman, A, B1 aWelsh-Bohmer, K, A1 aZandi, P, P uhttps://chs-nhlbi.org/node/103403075nas a2200421 4500008004100000022001400041245018900055210006900244260001300313300001200326490000700338520176300345653000902108653002202117653002502139653002702164653003602191653001102227653001502238653001102253653000902264653001302273653003102286653002002317653001702337653003202354653002202386653001802408100002202426700002402448700002302472700002802495700002602523700002402549700002102573700002302594856003602617 2008 eng d a1540-816700aNovel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS).0 aNovel measures of heart rate variability predict cardiovascular c2008 Nov a1169-740 v193 aUNLABELLED: Novel HRV Predicts CV Mortality in the Elderly.
BACKGROUND: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth).
METHODS: Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people >or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (
RESULTS: CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2).
CONCLUSIONS: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.
10aAged10aAged, 80 and over10aArrhythmias, Cardiac10aDeath, Sudden, Cardiac10aElectrocardiography, Ambulatory10aFemale10aHeart Rate10aHumans10aMale10aMaryland10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSensitivity and Specificity10aSurvival Analysis10aSurvival Rate1 aStein, Phyllis, K1 aBarzilay, Joshua, I1 aChaves, Paulo, H M1 aMistretta, Stephanie, Q1 aDomitrovich, Peter, P1 aGottdiener, John, S1 aRich, Michael, W1 aKleiger, Robert, E uhttps://chs-nhlbi.org/node/104202815nas a2200385 4500008004100000022001400041245009700055210006900152260001600221300001000237490000700247520174200254653000901996653002202005653002202027653004402049653002202093653002602115653001302141653001102154653001102165653001402176653000902190653003202199653002402231653001702255100001802272700002102290700002202311700001402333700001502347700001602362700001602378856003502394 2008 eng d a1526-632X00aNSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type.0 aNSAID use and dementia risk in the Cardiovascular Health Study r c2008 Jan 01 a17-240 v703 aBACKGROUND: Epidemiologic and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce risk of Alzheimer disease (AD). We therefore investigated the association between use of NSAIDs, aspirin, and the non-NSAID analgesic acetaminophen with incidence of dementia and AD.
METHODS: Participants in the Cardiovascular Health Cognition Study included 3,229 individuals aged 65 or older, free of dementia at baseline, with information on medication use. We used Cox proportional hazards regression to estimate the association of medication use with incident all-cause dementia, AD, and vascular dementia (VaD). Additional analyses considered the NSAID-AD relationship as a function of age, presence of at least one epsilon 4 allele at APOE, race, and individual NSAIDs' reported ability to reduce production of the amyloid-beta peptide variant A beta(42).
RESULTS: Use of NSAIDs was associated with a lower risk of dementia (adjusted hazard ratio or aHR 0.76, 95% CI or CI 0.60-0.96) and, in particular, AD (aHR 0.63, CI 0.45-0.88), but not VaD (aHR 0.92, CI 0.65-1.28). No similar trends were observed with acetaminophen (aHR 0.99, CI 0.79-1.24). Closer examination suggested AD risk reduction with NSAIDs only in participants having an APOE epsilon 4 allele (aHR 0.34, CI 0.18-0.65; aHR for others 0.88, CI 0.59-1.32). There was no advantage in AD risk reduction with NSAIDs reported to selectively reduce A beta(42).
CONCLUSIONS: Results were consistent with previous cohort studies showing reduced risk of AD in NSAID users, but this association was found only in those with an APOE epsilon 4 allele, and there was no advantage for A beta(42)-lowering NSAIDs.
10aAged10aAged, 80 and over10aAlzheimer Disease10aAnti-Inflammatory Agents, Non-Steroidal10aApolipoproteins E10aCardiovascular System10aDementia10aFemale10aHumans10aIncidence10aMale10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aSzekely, C, A1 aBreitner, J, C S1 aFitzpatrick, A, L1 aRea, T, D1 aPsaty, B M1 aKuller, L H1 aZandi, P, P uhttps://chs-nhlbi.org/node/99803196nas a2200421 4500008004100000022001400041245013400055210006900189260001300258300001000271490000700281520196600288653000902254653002202263653002802285653001902313653002102332653001102353653002202364653002202386653001802408653001102426653002802437653000902465653002602474653003602500653001402536653002402550653001102574100002202585700002402607700002002631700002202651700001902673700002402692700002302716856003502739 2008 eng d a1473-487700aPancreatic beta-cell function as a predictor of cardiovascular outcomes and costs: findings from the Cardiovascular Health Study.0 aPancreatic betacell function as a predictor of cardiovascular ou c2008 Jan a41-500 v243 aOBJECTIVE: To explore relationships between beta-cell function and incident cardiovascular events, death, and medical costs among elderly individuals.
RESEARCH DESIGN AND METHODS: In a prospective, population-based cohort of 4555 elderly individuals, we examined the effect of beta-cell function on incident cardiovascular events and mortality. We also examined costs for 3715 of these individuals. We used the computer-based homeostasis model assessment (HOMA) to calculate indices of beta-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S) using baseline fasting glucose and insulin levels. All subjects were followed from 1992/1993 for 6 years or until death.
MAIN OUTCOME MEASURES: Discrete-time survival model of the effects of beta-cell function on incident cardiovascular events and all-cause mortality; and semiparametric estimators for calculations of mean 6-year costs.
RESULTS: Controlling for HOMA-%S, a 20% decrease in HOMA-%B was associated with increased odds of incident cardiovascular events (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.14) and death (OR, 1.10; 95% CI, 1.07-1.14). The relationships persisted after controlling for clinical and sociodemographic confounders. A 20% decrease in HOMA-%B was also associated with increased costs (cost ratio, 1.03; 95% CI, 1.01-1.05). The significant association did not persist after controlling for confounders.
LIMITATIONS: The sample comprises relatively healthy elderly individuals and is based on data from 1992 through 1999, which may not reflect current experience. The measure of beta-cell function is an estimate generated from single measures of glucose and insulin.
CONCLUSIONS: Beta-cell function as measured by HOMA-%B is a significant predictor of incident cardiovascular events and mortality but not of costs, controlling for HOMA-%S and sociodemographic and clinical confounders.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aFemale10aFollow-Up Studies10aHealth Care Costs10aHeart Failure10aHumans10aInsulin-Secreting Cells10aMale10aMyocardial Infarction10aOutcome Assessment, Health Care10aPrognosis10aProspective Studies10aStroke1 aCurtis, Lesley, H1 aHammill, Bradley, G1 aBethel, Angelyn1 aAnstrom, Kevin, J1 aLiao, Lawrence1 aGottdiener, John, S1 aSchulman, Kevin, A uhttps://chs-nhlbi.org/node/99903085nas a2200325 4500008004100000022001400041245010900055210006900164260001600233300001000249490000800259520217800267653000902445653002202454653002402476653001302500653001102513653001102524653001402535653002302549653000902572653001902581653002402600653001202624100002502636700002102661700002002682700002102702856003602723 2008 eng d a1524-453900aPhysical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study.0 aPhysical activity and incidence of atrial fibrillation in older c2008 Aug 19 a800-70 v1183 aBACKGROUND: Vigorous exertion and endurance training have been reported to increase atrial fibrillation (AF). Associations of habitual light or moderate activity with AF incidence have not been evaluated.
METHODS AND RESULTS: We prospectively investigated associations of leisure-time activity, exercise intensity, and walking habits, assessed at baseline and updated during follow-up visits, with incident AF, diagnosed by annual 12-lead ECGs and hospital discharge records, from 1989 to 2001 among 5446 adults > or =65 years of age in the Cardiovascular Health Study. During 47 280 person-years of follow-up, 1061 new AF cases occurred (incidence 22.4/1000 person-years). In multivariable-adjusted analyses, leisure-time activity was associated with lower AF incidence in a graded manner, with 25% (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.61 to 0.90), 22% (HR 0.78, 95% CI 0.65 to 0.95), and 36% (HR 0.64, 95% CI 0.52 to 0.79) lower risk in quintiles 3, 4, and 5 versus quintile 1 (P for trend <0.001). Exercise intensity had a U-shaped relationship with AF (quadratic P=0.02): Versus no exercise, AF incidence was lower with moderate-intensity exercise (HR 0.72, 95% CI 0.58 to 0.89) but not with high-intensity exercise (HR 0.87, 95% CI 0.64 to 1.19). Walking distance and pace were each associated with lower AF risk in a graded manner (P for trend <0.001); when we assessed the combined effects of distance and pace, individuals in quartiles 2, 3, and 4 had 25% (HR 0.75, 95% CI 0.56 to 0.99), 32% (HR 0.68, 95% CI 0.50 to 0.92), and 44% (HR 0.56, 95% CI 0.38 to 0.82) lower AF incidence than individuals in quartile 1. Findings appeared unrelated to confounding by comorbidity or indication. After evaluation of cut points of moderate leisure-time activity (approximately 600 kcal/week), walking distance (12 blocks per week), and pace (2 mph), 26% of all new AF cases (95% CI 7% to 43%) appeared attributable to absence of these activities.
CONCLUSIONS: Light to moderate physical activities, particularly leisure-time activity and walking, are associated with significantly lower AF incidence in older adults.
10aAged10aAged, 80 and over10aAtrial Fibrillation10aExercise10aFemale10aHumans10aIncidence10aLeisure Activities10aMale10aMotor Activity10aProspective Studies10aWalking1 aMozaffarian, Dariush1 aFurberg, Curt, D1 aPsaty, Bruce, M1 aSiscovick, David uhttps://chs-nhlbi.org/node/104502685nas a2200337 4500008004100000022001400041245008200055210006900137260001300206300001000219490000700229520173900236653003101975653000902006653001602015653002102031653001102052653001802063653001102081653000902092653002402101653001402125653003002139653003202169100002002201700002402221700002402245700002002269700002202289856003602311 2008 eng d a1079-500600aA physiologic index of comorbidity: relationship to mortality and disability.0 aphysiologic index of comorbidity relationship to mortality and d c2008 Jun a603-90 v633 aBACKGROUND: In older adults, there is often substantial undiagnosed chronic disease detectable on noninvasive testing, not accounted for by most comorbidity indices. We developed a simple physiologic index of comorbidity by scoring five noninvasive tests across the full range of values. We examined the predictive validity of this index for mortality and disability.
METHODS: There were 2928 (mean age 74.5 years, 60% women, 85% white, and 15% black) participants in the Cardiovascular Health Study (1992-1993) who had carotid ultrasound, pulmonary function testing, brain magnetic resonance scan, serum cystatin-C, and fasting glucose. These were combined into a single physiologic index of comorbid chronic disease on a scale of 0-10. Cox proportional hazard models were used to predict mortality, mobility limitation, and activities of daily living (ADL) difficulty after a maximum of 9 years.
RESULTS: The range of the physiologic index was quite broad, with very few individuals having total scores of either 0 or 10. Those with an index of 7-10 had a hazard ratio of 3.80 (95% confidence interval, 2.82-5.13) for mortality compared to those with scores of 0-2, after adjustment for demographics, behavioral risk factors, and clinically diagnosed conditions. Associations with mobility limitation and ADL difficulty were also significant. The index explained about 40% of the age effect on mortality risk.
CONCLUSION: Older adults with low levels of markers of chronic disease are rather rare but have remarkably good health outcomes. The ability of such an index to distinguish usual from low risk might provide an opportunity to better understand optimal health in old age.
10aActivities of Daily Living10aAged10aComorbidity10aDisabled Persons10aFemale10aHealth Status10aHumans10aMale10aMobility Limitation10aMortality10aPredictive Value of Tests10aProportional Hazards Models1 aNewman, Anne, B1 aBoudreau, Robert, M1 aNaydeck, Barbara, L1 aFried, Linda, F1 aHarris, Tamara, B uhttps://chs-nhlbi.org/node/103703386nas a2200553 4500008004100000022001400041245010000055210006900155260001600224300001200240490000700252520188100259653001602140653000902156653002202165653002202187653002602209653002202235653001502257653001002272653003002282653001602312653002802328653001502356653001402371653001102385653001102396653001402407653002502421653003102446653000902477653002402486653002902510653002202539653003002561653002402591653002102615653001702636100001602653700001602669700001602685700001702701700001502718700001602733700001602749700001302765700001802778856003602796 2008 eng d a1526-632X00aPlasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.0 aPlasma amyloid levels and the risk of AD in normal subjects in t c2008 May 06 a1664-710 v703 aOBJECTIVES: To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study.
METHODS: We determined the plasma A beta 1-40 and A beta 1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 +/- 3.6 years. We examined the association between A beta levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts.
RESULTS: In an unadjusted prospective model in normal subjects, both A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD.
CONCLUSIONS: Plasma A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of A beta do not seem to be useful biomarkers for AD.
10aAge Factors10aAged10aAged, 80 and over10aAlzheimer Disease10aAmyloid beta-Peptides10aApolipoprotein E410aBiomarkers10aBrain10aCerebrovascular Disorders10aComorbidity10aCross-Sectional Studies10aCystatin C10aCystatins10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aModels, Statistical10aNeuropsychological Tests10aPeptide Fragments10aPredictive Value of Tests10aProspective Studies10aReference Values10aRisk Factors1 aLopez, O, L1 aKuller, L H1 aMehta, P, D1 aBecker, J, T1 aGach, H, M1 aSweet, R, A1 aChang, Y, F1 aTracy, R1 aDeKosky, S, T uhttps://chs-nhlbi.org/node/102502050nas a2200493 4500008004100000022001400041245011900055210006900174260001300243300001300256490000700269520060400276653000900880653001800889653002300907653001100930653003800941653001100979653005100990653000901041653001601050653003601066653001601102653001601118100002501134700002201159700001801181700002001199700002101219700002301240700002301263700002301286700002001309700002001329700001701349700002101366700001901387700002201406700002201428700002201450700002601472700002201498856003601520 2008 eng d a1537-660500aPolymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein.0 aPolymorphisms of the HNF1A gene encoding hepatocyte nuclear fact c2008 May a1193-2010 v823 aData from the Pharmacogenomics and Risk of Cardiovascular Disease (PARC) study and the Cardiovascular Health Study (CHS) provide independent and confirmatory evidence for association between common polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha and plasma C-reactive protein (CRP) concentration. Analyses with the use of imputation-based methods to combine genotype data from both studies and to test untyped SNPs from the HapMap database identified several SNPs within a 5 kb region of HNF1A intron 1 with the strongest evidence of association with CRP phenotype.
10aAged10aBayes Theorem10aC-Reactive Protein10aFemale10aHepatocyte Nuclear Factor 1-alpha10aHumans10aHydroxymethylglutaryl-CoA Reductase Inhibitors10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aPravastatin10aSimvastatin1 aReiner, Alexander, P1 aBarber, Mathew, J1 aGuan, Yongtao1 aRidker, Paul, M1 aLange, Leslie, A1 aChasman, Daniel, I1 aWalston, Jeremy, D1 aCooper, Gregory, M1 aJenny, Nancy, S1 aRieder, Mark, J1 aDurda, Peter1 aSmith, Joshua, D1 aNovembre, John1 aTracy, Russell, P1 aRotter, Jerome, I1 aStephens, Matthew1 aNickerson, Deborah, A1 aKrauss, Ronald, M uhttps://chs-nhlbi.org/node/102802728nas a2200313 4500008004100000022001400041245007900055210006900134260001300203300001100216490000800227520186900235653002702104653001102131653001102142653002002153653000902173653001602182653002002198653001002218653001202228653004502240100001502285700002002300700001702320700001902337700002302356856003502379 2008 eng d a0012-369200aPower spectral analysis of EEG activity during sleep in cigarette smokers.0 aPower spectral analysis of EEG activity during sleep in cigarett c2008 Feb a427-320 v1333 aBACKGROUND: Research on the effects of cigarette smoking on sleep architecture is limited. The objective of this investigation was to examine differences in sleep EEG between smokers and nonsmokers.
METHODS: Smokers and nonsmokers who were free of all medical comorbidities were matched on different factors, including age, gender, race, body mass index, and anthropometric measures. Home polysomnography was conducted using a standard recording montage. Sleep architecture was assessed using visual sleep-stage scoring. The discrete fast Fourier transform was used to calculate the EEG power spectrum for the entire night within contiguous 30-s epochs of sleep for the following frequency bandwidths: delta (0.8 to 4.0 Hz); theta (4.1 to 8.0 Hz); alpha (8.1 to 13.0 Hz); and beta (13.1 to 20.0 Hz).
RESULTS: Conventional sleep stages were similar between the two groups. However, spectral analysis of the sleep EEG showed that, compared to nonsmokers, smokers had a lower percentage of EEG power in the delta-bandwidth (59.7% vs 62.6%, respectively; p < 0.04) and higher percentage of EEG power in alpha-bandwidth (15.6% vs 12.5%, respectively; p < 0.001). Differences in the EEG power spectrum between smokers and nonsmokers were greatest in the early part of the sleep period and decreased toward the end. Subjective complaints of lack of restful sleep were also more prevalent in smokers than in nonsmokers (22.5% vs 5.0%, respectively; p < 0.02) and were explained, in part, by the differences in EEG spectral power.
CONCLUSIONS: Cigarette smokers manifest disturbances in the sleep EEG that are not evident in conventional measures of sleep architecture. Nicotine in cigarette smoke and withdrawal from it during sleep may contribute to these changes and the subjective experience of nonrestorative sleep.
10aElectroencephalography10aFemale10aHumans10aLogistic Models10aMale10aMiddle Aged10aPolysomnography10aSleep10aSmoking10aSpectroscopy, Fourier Transform Infrared1 aZhang, Lin1 aSamet, Jonathan1 aCaffo, Brian1 aBankman, Isaac1 aPunjabi, Naresh, M uhttps://chs-nhlbi.org/node/99303076nas a2200385 4500008004100000022001400041245015600055210006900211260001600280300001100296490000800307520195300315653001602268653000902284653002502293653002802318653001902346653002402365653001102389653001802400653001102418653000902429653001602438653001502454653001402469653002402483100001702507700002302524700002102547700002002568700002102588700001802609700002702627856003602654 2008 eng d a1524-453900aPrevalence, prognosis, and implications of isolated minor nonspecific ST-segment and T-wave abnormalities in older adults: Cardiovascular Health Study.0 aPrevalence prognosis and implications of isolated minor nonspeci c2008 Dec 16 a2790-60 v1183 aBACKGROUND: The prevalence and prognostic significance of isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTTAs) in older adults are poorly understood.
METHODS AND RESULTS: Cardiovascular Health Study participants free of both clinical cardiovascular disease and major ECG abnormalities were included. We examined the prospective association of isolated minor NSSTTAs (defined by Minnesota Codes 4-3, 4-4, 5-3, and 5-4) with total, cardiovascular, and coronary mortality and incident nonfatal myocardial infarction. Among 3224 participants (61.9% women; mean age, 72 years), 233 (7.2%) had isolated NSSTTAs at baseline. Covariates associated with isolated NSSTTAs included older age, nonwhite race (20.5% of blacks versus 4.8% of whites; P<0.001), diabetes, and higher blood pressure and body mass index but not the presence of subclinical cardiovascular disease. After 39 518 person-years of follow-up, the presence of isolated NSSTTAs was associated with significantly increased risk for coronary heart disease mortality (multivariable-adjusted hazards ratio, 1.76; 95% CI, 1.18 to 2.61) but not with incident nonfatal myocardial infarction (multivariable-adjusted hazards ratio, 0.71; 95% CI, 0.43 to 1.17). The association of isolated NSSTTAs with coronary death was independent of subclinical atherosclerosis and left ventricular mass measures. In secondary analyses, among those with cardiac death, there was a significantly higher rate of primary arrhythmic death (32.3% versus 15.4%; P=0.02) in participants with isolated NSSTTAs versus those without NSSTTAs.
CONCLUSIONS: Isolated NSSTTAs are common in older Americans and are associated with significantly increased risk for coronary death. However, isolated NSSTTAs are not associated with incident nonfatal myocardial infarction, suggesting that they are associated particularly with increased risk for primary arrhythmic death.
10aAge Factors10aAged10aArrhythmias, Cardiac10aCardiovascular Diseases10aCohort Studies10aElectrocardiography10aFemale10aHealth Status10aHumans10aMale10aMiddle Aged10aPrevalence10aPrognosis10aProspective Studies1 aKumar, Anita1 aPrineas, Ronald, J1 aArnold, Alice, M1 aPsaty, Bruce, M1 aFurberg, Curt, D1 aRobbins, John1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/106603208nas a2200493 4500008004100000022001400041245017300055210006900228260001300297300001200310490000600322520181600328653000902144653002202153653001002175653001702185653004002202653002802242653002102270653003502291653001102326653001102337653001702348653000902365653001602374653001402390653002602404653001402430653001402444653002802458653000902486653001102495653001502506100001702521700001602538700001602554700001802570700001502588700002702603700001602630700001602646700001602662856003602678 2008 eng d a1538-783600aPROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study.0 aPROC PROCR and PROS1 polymorphisms plasma anticoagulant phenotyp c2008 Oct a1625-320 v63 aBACKGROUND AND OBJECTIVES: Genes encoding protein C anticoagulant pathways are candidates for atherothrombotic and other aging-related disorders.
METHODS: Using a tagSNP approach, and data from the Cardiovascular Health Study (CHS), we assessed associations of common polymorphisms of PROC, PROS1 and PROCR with: (i) plasma protein C, soluble protein C endothelial receptor (sEPCR) and protein S levels measured in a subsample of 336 participants at study entry; and (ii) risk of incident clinical outcomes [coronary heart disease (CHD), stroke, and mortality] in 4547 participants during follow-up. Secondarily, we explored associations between plasma protein C, protein S and sEPCR levels and other candidate genes involved in thrombosis, inflammation, and aging.
RESULTS: The PROCR Ser219Gly polymorphism (rs867186) was strongly associated with higher sEPCR levels, explaining 75% of the phenotypic variation. The PROCR Ser219Gly variant was also associated with higher levels of circulating protein C antigen. An IL10 polymorphism was associated with higher free protein S levels. The minor alleles of PROC rs2069901 and PROS1 rs4857343 were weakly associated with lower protein C and free protein S levels, respectively. There was no association between PROCR Ser219Gly and risk of CHD, stroke, or mortality. The minor allele of another common PROCR tagSNP, rs2069948, was associated with lymphoid PROCR mRNA expression and with increased risk of incident stroke and all-cause mortality, and decreased healthy survival during follow-up.
CONCLUSIONS: A common PROCR variant may be associated with decreased healthy survival in older adults. Additional studies are warranted to establish the role of PROCR variants in ischemic and aging-related disorders.
10aAged10aAged, 80 and over10aAging10aAntigens, CD10aBlood Coagulation Factor Inhibitors10aCardiovascular Diseases10aCoronary Disease10aEndothelial Protein C Receptor10aFemale10aHumans10aInflammation10aMale10aMiddle Aged10aMortality10aPolymorphism, Genetic10aProtein C10aProtein S10aReceptors, Cell Surface10aRisk10aStroke10aThrombosis1 aReiner, A, P1 aCarty, C, L1 aJenny, N, S1 aNievergelt, C1 aCushman, M1 aStearns-Kurosawa, D, J1 aKurosawa, S1 aKuller, L H1 aLange, L, A uhttps://chs-nhlbi.org/node/104702916nas a2200349 4500008004100000022001400041245007000055210006900125260001600194300001100210490000800221520198600229653000902215653002802224653001502252653001402267653001102281653003102292653001102323653001102334653000902345653001402354100002002368700002402388700001602412700002002428700002102448700002102469700002002490700002002510856003602530 2008 eng d a1538-367900aRapid kidney function decline and mortality risk in older adults.0 aRapid kidney function decline and mortality risk in older adults c2008 Nov 10 a2212-80 v1683 aBACKGROUND: Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults.
METHODS: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR(creat)) and cystatin C (eGFR(cys)) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m(2) per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up.
RESULTS: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR(creat) and eGFR(cys) were 79 (23) mL/min/1.73 m(2) and 79 (19) mL/min/1.73 m(2), respectively. Individuals with rapid decline measured by eGFR(creat) (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR(cys) (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease.
CONCLUSION: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aMortality1 aRifkin, Dena, E1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aChonchol, Michel1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/106202453nas a2200337 4500008004100000022001400041245008900055210006900144260001300213300001100226490000800237520153300245653000901778653002101787653002801808653001101836653001101847653000901858653001601867653001501883653001701898653002601915653001801941653001701959653002001976100002701996700001702023700002302040700001702063856003502080 2008 eng d a1879-148400aRelation of sleep-disordered breathing to carotid plaque and intima-media thickness.0 aRelation of sleepdisordered breathing to carotid plaque and inti c2008 Mar a125-310 v1973 aBACKGROUND: Sleep-disordered breathing (SDB) is associated with clinical cardiovascular disease (CVD), but its relation to subclinical atherosclerosis remains to be determined.
METHODS: We analyzed the cross-sectional associations of SDB, measured by the respiratory disturbance index (RDI), a hypoxemia index, and an arousal index, with carotid plaque and carotid intima-media thickness (IMT), measured by ultrasound. The sample included 985 participants in the Sleep Heart Health Study (mean age-62, median RDI-8.7) with no history of coronary heart disease and stroke, of whom 396 had evidence of a carotid plaque.
RESULTS: As compared with the first quartile of the RDI (0-1.2), the crude odds ratio for carotid plaque was 1.14, 1.27, and 1.48 for the second (1.3-4.1), third (4.2-10.7), and fourth (>10.7) quartile, respectively. After adjustment for CVD risk factors, the corresponding odds ratios were reduced (1.00, 1.04, 1.07, and 1.25). Similarly, the unadjusted mean carotid IMT increased with RDI, but adjusted means (mm) were similar (0.84, 0.85, 0.84, 0.85). Spline regression models did not show monotonicity of the dose-response functions at the right end of the RDI distribution. Neither the hypoxemia index nor the arousal index was associated with carotid plaque or carotid IMT.
CONCLUSION: The results of this study suggest that crude, positive associations between SDB and subclinical atherosclerosis can be attributed to confounding by CVD risk factors.
10aAged10aCarotid Arteries10aCarotid Artery Diseases10aFemale10aHumans10aMale10aMiddle Aged10aOdds Ratio10aRisk Factors10aSleep Apnea Syndromes10aTunica Intima10aTunica Media10aUltrasonography1 aWattanakit, Keattiyoat1 aBoland, Lori1 aPunjabi, Naresh, M1 aShahar, Eyal uhttps://chs-nhlbi.org/node/95702762nas a2200361 4500008004100000022001400041245014700055210006900202260001300271300001000284490000800294520172200302653001602024653000902040653002202049653002002071653002102091653002802112653001902140653001102159653001702170653001102187653000902198653001802207653001702225653002002242653001702262100001902279700002202298700002002320700002502340856003502365 2008 eng d a1879-148400aRelationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the Cardiovascular Health Study.0 aRelationship between brachial flowmediated dilation and carotid c2008 Apr a840-50 v1973 aOBJECTIVE: The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort.
BACKGROUND: Brachial flow-mediated dilation (FMD) is a physiologic measure and carotid IMT is an anatomic structural measure of subclinical atherosclerosis. Both brachial FMD and carotid IMT have been associated with cardiovascular risk factors and cardiovascular events. The relationship between brachial FMD and carotid IMT is less clear especially in older adults.
METHODS: Brachial FMD, carotid IMT and traditional cardiovascular risk factors were measured in 2338 adults, age 72-98 years who were participants in the Cardiovascular Health Study. The relationship between FMD and IMT was assessed both unadjusted and also after adjusting for age, gender and race/ethnicity, BMI, HDL, LDL, systolic and diastolic blood pressure, serum creatinine, current smoking, diabetes mellitus, hormone therapy and prior CVD.
RESULTS: Both brachial FMD and carotid IMT correlated significantly with age, HDL levels, waist/hip ratio, serum cholesterol and number of CV risk factors. Brachial FMD was not associated with CCA IMT in this elderly cohort (Pearson partial correlation coefficient=-0.0252, p=0.222). In the adjusted linear regression model with CCA IMT as the dependent variable, brachial FMD was also not associated with CCA IMT (beta coefficient=-0.006, p=0.470).
CONCLUSION: Brachial FMD and CCA IMT are not related in population-based older adults. Brachial FMD and CCA IMT may be distinct and independent stages in the complex atherosclerotic process.
10aAge Factors10aAged10aAged, 80 and over10aBrachial Artery10aCarotid Arteries10aCarotid Artery Diseases10aCohort Studies10aFemale10aHemorheology10aHumans10aMale10aTunica Intima10aTunica Media10aUltrasonography10aVasodilation1 aYeboah, Joseph1 aBurke, Gregory, L1 aCrouse, John, R1 aHerrington, David, M uhttps://chs-nhlbi.org/node/98002767nas a2200397 4500008004100000022001400041245008700055210006900142260001300211300001100224490000700235520168000242653000901922653002201931653002501953653001901978653002201997653001302019653001102032653001102043653000902054653001502063653001702078653001802095653002202113100002802135700002402163700001902187700001802206700002102224700002002245700002102265700002402286700002302310856003602333 2008 eng d a1532-541500aThe relationship between exercise and risk of venous thrombosis in elderly people.0 arelationship between exercise and risk of venous thrombosis in e c2008 Mar a517-220 v563 aOBJECTIVES: To study whether exercise is associated with the risk of venous thrombosis in elderly people.
DESIGN: Observational study with a median follow-up of 11.6 years.
SETTING: The Cardiovascular Health Study in four U.S. communities.
PARTICIPANTS: People aged 65 and older without prior venous thrombosis (deep venous thrombosis or pulmonary embolism).
MEASUREMENTS: Self-reported exercise was measured two or three times during follow-up and was defined as expending more than 500 kcal/wk on exercise, including walking for exercise. Venous thrombosis cases were verified using medical record review.
RESULTS: Of 5,534 participants, 171 developed a first venous thrombosis. Self-reported exercise at baseline was not related to the risk of venous thrombosis after adjustment for sex, age, race, self-reported health, and body mass index (adjusted hazard ratio (HR(adj))=1.16, 95% confidence interval (CI)=0.84-1.61), although with exercise modeled as a time-varying exposure, overall results were in the direction of greater risk of venous thrombosis (HR(adj)=1.38, 95% CI=0.99-1.91). For mild-intensity exercise, such as walking, there was a nonsignificant finding in the direction of benefit (HR(adj)=0.75, 95% CI=0.49-1.16), but strenuous exercise, such as jogging, was associated with greater risk of venous thrombosis (HR(adj)=1.75, 95% CI=1.08-2.83) than no exercise at all.
CONCLUSION: In elderly people, strenuous exercise was associated with a higher risk of venous thrombosis than no exercise at all. Future studies are needed to explain this unexpected higher risk.
10aAged10aAged, 80 and over10aCase-Control Studies10aCohort Studies10aEnergy Metabolism10aExercise10aFemale10aHumans10aMale10aPrevalence10aRisk Factors10aUnited States10aVenous Thrombosis1 avan Stralen, Karlijn, J1 aDoggen, Carine, J M1 aLumley, Thomas1 aCushman, Mary1 aFolsom, Aaron, R1 aPsaty, Bruce, M1 aSiscovick, David1 aRosendaal, Frits, R1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/100702434nas a2200337 4500008004100000022001400041245010100055210006900156260001300225300001100238490000700249520148300256653003101739653000901770653002801779653002601807653001301833653001101846653000901857653001801866653001101884653000901895653001701904653001901921653003101940100002301971700002101994700002502015700002002040856003602060 2008 eng d a1532-821X00aThe reliability and validity of measures of gait variability in community-dwelling older adults.0 areliability and validity of measures of gait variability in comm c2008 Dec a2293-60 v893 aOBJECTIVE: To examine the test-retest reliability and concurrent validity of variability of gait characteristics.
DESIGN: Cross-sectional study.
SETTING: Research laboratory.
PARTICIPANTS: Older adults (N=558) from the Cardiovascular Health Study.
INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: Gait characteristics were measured using a 4-m computerized walkway. SD determined from the steps recorded were used as the measures of variability. Intraclass correlation coefficients (ICC) were calculated to examine test-retest reliability of a 4-m walk and two 4-m walks. To establish concurrent validity, the measures of gait variability were compared across levels of health, functional status, and physical activity using independent t tests and analysis of variances.
RESULTS: Gait variability measures from the two 4-m walks demonstrated greater test-retest reliability than those from the single 4-m walk (ICC=.22-.48 and ICC=.40-.63, respectively). Greater step length and stance time variability were associated with poorer health, functional status and physical activity (P<.05).
CONCLUSIONS: Gait variability calculated from a limited number of steps has fair to good test-retest reliability and concurrent validity. Reliability of gait variability calculated from a greater number of steps should be assessed to determine if the consistency can be improved.
10aActivities of Daily Living10aAged10aCross-Sectional Studies10aDisability Evaluation10aExercise10aFemale10aGait10aHealth Status10aHumans10aMale10aPennsylvania10aRehabilitation10aReproducibility of Results1 aBrach, Jennifer, S1 aPerera, Subashan1 aStudenski, Stephanie1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/106503055nas a2200373 4500008004100000022001400041245010300055210006900158260001300227300001200240490000700252520198600259653000902245653002802254653001602282653002802298653003802326653001102364653001902375653001102394653001702405653000902422653001602431653001502447653001102462653002002473653002902493653001802522100002202540700002402562700002402586710003502610856003602645 2008 eng d a0161-810500aSleep disordered breathing and hypertension: does self-reported sleepiness modify the association?0 aSleep disordered breathing and hypertension does selfreported sl c2008 Aug a1127-320 v313 aSTUDY OBJECTIVES: Epidemiologic studies that demonstrate increased risk of hypertension in persons with sleep disordered breathing indicate that only a minority of these persons report significant subjective sleepiness. Studies also suggest that presence of self-reported sleepiness may identify a subset of persons with sleep disordered breathing who are at greatest risk of cardiovascular sequelae, including hypertension. We explore whether self-reported sleepiness modifies the relationship between sleep disordered breathing and prevalent hypertension.
DESIGN: Cross-sectional.
SETTING: Multicenter study.
PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study.
MEASUREMENTS: Polysomnography, systolic and diastolic blood pressure, antihypertensive medication use, questionnaire determined excessive sleepiness and Epworth Sleepiness Scale, and covariates.
RESULTS: The odds of hypertension at higher apnea hypopnea index categories were larger in participants identified as sleepy based on responses to a frequency of sleepiness question or the Epworth score. For example, for those with AHI > or =30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or =5 days per month, but only 1.22 (0.89-1.68) among those reporting less frequent daytime sleepiness. In adjusted logistic regression models, there was statistical evidence for effect modification by frequency of sleepiness (P = 0.033) of the association between apnea hypopnea index and hypertension. In adjusted models that included the Epworth score as a continuous variable, the interaction term fell slightly short of statistical significance (beta = 0.010, P = 0.07).
CONCLUSION: This study finds that the association of sleep disordered breathing with hypertension is stronger in individuals who report daytime sleepiness than in those who do not.
10aAged10aAntihypertensive Agents10aComorbidity10aCross-Sectional Studies10aDisorders of Excessive Somnolence10aFemale10aHealth Surveys10aHumans10aHypertension10aMale10aMiddle Aged10aOdds Ratio10aOxygen10aPolysomnography10aSleep Apnea, Obstructive10aUnited States1 aKapur, Vishesh, K1 aResnick, Helaine, E1 aGottlieb, Daniel, J1 aSleep Heart Health Study Group uhttps://chs-nhlbi.org/node/105103134nas a2200349 4500008004100000022001400041245010100055210006900156260001600225300001100241490000800252520216200260653000902422653001002431653002802441653001902469653001102488653001102499653000902510653001602519653001502535653001902550653002002569653002602589653002502615100002302640700002002663700002002683700002402703700002102727856003602748 2008 eng d a1535-497000aSleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas.0 aSleepdisordered breathing and cardiovascular disease an outcomeb c2008 May 15 a1150-50 v1773 aRATIONALE: Epidemiologic studies on the consequences of sleep-disordered breathing invariably use the apnea-hypopnea index as the primary measure of disease severity. Although hypopneas constitute a majority of disordered breathing events, significant controversy remains about the best criteria used to define these events.
OBJECTIVES: The current investigation sought to assess the most appropriate definition for hypopneas that would be best correlated with cardiovascular disease.
METHODS: A community sample of middle-aged and older adults was recruited as part of the Sleep Heart Health Study. Full-montage polysomnography was conducted and hypopneas were defined using different thresholds of oxyhemoglobin desaturation with and without arousals. Prevalent cardiovascular disease was assessed based on self-report. Logistic regression analysis was used to characterize the independent association between the hypopnea index and prevalent cardiovascular disease.
MEASUREMENTS AND MAIN RESULTS: Using a sample of 6,106 adults with complete data on cardiovascular disease status and polysomnography, the current study found that hypopneas associated with an oxyhemoglobin desaturation of 4% or more were associated with prevalent cardiovascular disease independent of confounding covariates. The adjusted prevalent odds ratios for quartiles of the hypopnea index using a 4% desaturation criterion were as follows: 1.00 (<1.10 events/h), 1.10 (1.01-3.20 events/h), 1.33 (3.21-7.69 events/h), and 1.41 (>7.69 events/h). Hypopnea measures based on less than 4% oxyhemoglobin desaturation or presence of arousals showed no association with cardiovascular disease.
CONCLUSIONS: Hypopneas comprise a significant component of sleep-disordered breathing in the general community. By varying the criteria for defining hypopneas, this study demonstrates that hypopneas with a desaturation of at least 4% are independently associated with cardiovascular disease. In contrast, no association was observed between cardiovascular disease and hypopneas associated with milder desaturations or arousals.
10aAged10aApnea10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aMale10aMiddle Aged10aOdds Ratio10aOxyhemoglobins10aPolysomnography10aSleep Apnea Syndromes10aTerminology as Topic1 aPunjabi, Naresh, M1 aNewman, Anne, B1 aYoung, Terry, B1 aResnick, Helaine, E1 aSanders, Mark, H uhttps://chs-nhlbi.org/node/101802979nas a2200433 4500008004100000022001400041245014400055210006900199260001300268300001100281490000700292520172800299653000902027653002202036653001602058653002802074653002802102653001102130653002402141653002702165653001102192653000902203653001602212653001202228653001502240653002002255653002102275653002502296100002202321700002102343700002402364700002302388700002102411700001802432700002102450700001902471700001902490856003602509 2008 eng d a1935-554800aSleep-disordered breathing and impaired glucose metabolism in normal-weight and overweight/obese individuals: the Sleep Heart Health Study.0 aSleepdisordered breathing and impaired glucose metabolism in nor c2008 May a1001-60 v313 aOBJECTIVE: To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus.
RESEARCH DESIGN AND METHODS: Cross-sectional analysis of 2,588 participants (aged 52-96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index >or=10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference.
RESULTS: SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% CI 1.1-1.6) for IFG, 1.2 (1.0-1.4) for IGT, 1.4 (1.1-2.7) for IFG plus IGT, and 1.7 (1.1-2.7) for occult diabetes.
CONCLUSIONS: SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and overweight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction.
10aAged10aAged, 80 and over10aBody Weight10aCardiovascular Diseases10aCross-Sectional Studies10aFemale10aGlucose Intolerance10aGlucose Tolerance Test10aHumans10aMale10aMiddle Aged10aObesity10aOverweight10aPolysomnography10aReference Values10aSleep Wake Disorders1 aSeicean, Sinziana1 aKirchner, Lester1 aGottlieb, Daniel, J1 aPunjabi, Naresh, M1 aResnick, Helaine1 aSanders, Mark1 aBudhiraja, Rohit1 aSinger, Mendel1 aRedline, Susan uhttps://chs-nhlbi.org/node/101602899nas a2200361 4500008004100000022001400041245009800055210006900153260001300222300001000235490000700245520182900252653000902081653002202090653002802112653001102140653003102151653001102182653001802193653002502211653000902236653002902245653002102274653003102295653001702326653004102343100002302384700002502407700002102432700002902453700002002482856003502502 2008 eng d a0966-636200aStance time and step width variability have unique contributing impairments in older persons.0 aStance time and step width variability have unique contributing c2008 Apr a431-90 v273 aGait variability may have multiple causes. We hypothesized that central nervous system (CNS) impairments would affect motor control and be manifested as increased stance time and step length variability, while sensory impairments would affect balance and be manifested as increased step width variability. Older adults (mean+/-standard deviation (S.D.) age=79.4+/-4.1, n=558) from the Pittsburgh site of the Cardiovascular Health Study participated. The S.D. across steps was the indicator of gait variability, determined for three gait measures, step length, stance time and step width, using a computerized walkway. Impairment measures included CNS function (modified mini-mental state examination, Trails A and B, Digit Symbol Substitution, finger tapping), sensory function (lower extremity (LE) vibration, vision), strength (grip strength, repeated chair stands), mood, and LE pain. Linear regression models were fit for the three gait variability characteristics using impairment measures as independent variables, adjusted for age, race, gender, and height. Analyses were repeated stratified by gait speed. All measures of CNS impairment were directly related to stance time variability (p<0.01), with increased CNS impairment associated with increased stance time variability. CNS impairments were not related to step length or width variability. Both sensory impairments were inversely related to step width (p<0.01) but not step length or stance time variability. CNS impairments affected stance time variability especially in slow walkers while sensory impairments affected step width variability in fast walkers. Specific patterns of gait variability may imply different underlying causes. Types of gait variability should be specified. Interventions may be targeted at specific types of gait variability.
10aAged10aAged, 80 and over10aBiomechanical Phenomena10aFemale10aGait Disorders, Neurologic10aHumans10aLinear Models10aLongitudinal Studies10aMale10aNeuropsychological Tests10aPostural Balance10aRange of Motion, Articular10aRisk Factors10aSignal Processing, Computer-Assisted1 aBrach, Jennifer, S1 aStudenski, Stephanie1 aPerera, Subashan1 aVanSwearingen, Jessie, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/97003214nas a2200433 4500008004100000022001400041245011900055210006900174260001600243300001100259490000700270520199500277653000902272653002202281653001902303653002102322653001102343653001002354653001802364653002502382653001102407653002002418653003402438653001902472653000902491653001702500653001702517100002102534700002202555700002102577700002002598700001802618700002002636700002202656700002202678700002402700700002002724856003602744 2008 eng d a1558-359700aSubclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.0 aSubclinical thyroid dysfunction cardiac function and the risk of c2008 Sep 30 a1152-90 v523 aOBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities.
BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited.
METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism.
RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF.
CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.
10aAged10aAged, 80 and over10aCohort Studies10aEchocardiography10aFemale10aHeart10aHeart Failure10aHeart Function Tests10aHumans10aHyperthyroidism10aHypertrophy, Left Ventricular10aHypothyroidism10aMale10aRisk Factors10aTime Factors1 aRodondi, Nicolas1 aBauer, Douglas, C1 aCappola, Anne, R1 aCornuz, Jacques1 aRobbins, John1 aFried, Linda, P1 aLadenson, Paul, W1 aVittinghoff, Eric1 aGottdiener, John, S1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/105303469nas a2200541 4500008004100000022001400041245016700055210006900222260001300291300001100304490000700315520191400322653000902236653002202245653002002267653002802287653002402315653001102339653002202350653001502372653001102387653001402398653002802412653000902440653001602449653001502465653001702480653002002497653001402517653001902531653002602550653001702576653003002593653001002623653002602633653003102659100001902690700002102709700001902730700002102749700002002770700001802790700002102808700002302829700001902852700002002871856003602891 2008 eng d a1523-683800aSubjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study.0 aSubjective and objective sleep quality in patients on convention c2008 Aug a305-130 v523 aBACKGROUND: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy.
STUDY DESIGN: Cross-sectional matched-group study.
SETTING & PARTICIPANTS: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race.
PREDICTOR: HD patients compared with community-dwelling non-HD participants.
OUTCOMES & MEASUREMENTS: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale.
RESULTS: Average age of study samples was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population.
LIMITATIONS: The study was limited to participants older than 45 years.
CONCLUSIONS: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality.
10aAged10aAged, 80 and over10aBody Mass Index10aCross-Sectional Studies10aDisease Progression10aFemale10aFollow-Up Studies10aHeart Rate10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aMiddle Aged10aOdds Ratio10aPennsylvania10aPolysomnography10aPrognosis10aRenal Dialysis10aRetrospective Studies10aRisk Factors10aSeverity of Illness Index10aSleep10aSleep Apnea Syndromes10aSurveys and Questionnaires1 aUnruh, Mark, L1 aSanders, Mark, H1 aRedline, Susan1 aPiraino, Beth, M1 aUmans, Jason, G1 aChami, Hassan1 aBudhiraja, Rohit1 aPunjabi, Naresh, M1 aBuysse, Daniel1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/104103435nas a2200529 4500008004100000022001400041245014200055210006900197260001300266300001100279490000700290520186600297653003102163653000902194653002202203653001502225653002802240653003802268653001202306653001102318653002202329653001802351653001102369653001402380653004902394653004902443653003302492653000902525653001602534653001402550653002402564653001702588653001802605653001802623653001202641100002202653700002202675700002302697700001802720700002502738700002102763700001702784700002802801700002002829700002002849856003602869 2008 eng d a1532-541500aTotal insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults.0 aTotal insulinlike growth factor 1 and insulinlike growth factor c2008 Apr a652-600 v563 aOBJECTIVES: To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults.
DESIGN: Cohort study.
SETTING/PARTICIPANTS: One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study.
MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality.
RESULTS: Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties.
CONCLUSION: In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.
10aActivities of Daily Living10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aEnzyme-Linked Immunosorbent Assay10aFasting10aFemale10aFollow-Up Studies10aHand Strength10aHumans10aIncidence10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aMiddle Aged10aPrognosis10aProspective Studies10aRisk Factors10aSurvival Rate10aUnited States10aWalking1 aKaplan, Robert, C1 aMcGinn, Aileen, P1 aPollak, Michael, N1 aKuller, Lewis1 aStrickler, Howard, D1 aRohan, Thomas, E1 aXue, XiaoNan1 aKritchevsky, Stephen, B1 aNewman, Anne, B1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/102102836nas a2200397 4500008004100000022001400041245009000055210006900145260001300214300001000227490000700237520176100244653003102005653000902036653002202045653002002067653001602087653001102103653002902114653001102143653002002154653001502174653000902189653001402198653001702212653001602229653001802245653001802263100001702281700002202298700002502320700002002345700001802365700001902383856003602402 2008 eng d a1532-541500aWeight, mortality, years of healthy life, and active life expectancy in older adults.0 aWeight mortality years of healthy life and active life expectanc c2008 Jan a76-830 v563 aOBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults.
DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults.
SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.
PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline.
MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated.
RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes.
CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a "healthy" weight may be much higher than currently believed.
10aActivities of Daily Living10aAged10aAged, 80 and over10aBody Mass Index10aBody Weight10aFemale10aHealth Status Indicators10aHumans10aLife Expectancy10aLife Style10aMale10aPrognosis10aRisk Factors10aSex Factors10aSurvival Rate10aUnited States1 aDiehr, Paula1 aO'Meara, Ellen, S1 aFitzpatrick, Annette1 aNewman, Anne, B1 aKuller, Lewis1 aBurke, Gregory uhttps://chs-nhlbi.org/node/100002717nas a2200373 4500008004100000022001400041245004900055210004600104260001600150300001300166490000700179520174600186653000901932653002201941653001001963653002201973653001001995653001802005653002402023653001102047653001102058653004002069653001802109653003102127653000902158653002902167653002602196100001502222700001602237700001602253700002102269700001702290856003602307 2009 eng d a1526-632X00aAge, Alzheimer disease, and brain structure.0 aAge Alzheimer disease and brain structure c2009 Dec 01 a1899-9050 v733 aBACKGROUND: Lack of clear understanding remains on the overlapping atrophy patterns of aging and early Alzheimer disease (AD) pathology in gray matter (GM) of the brain in vivo.
OBJECTIVE: To evaluate the independent and overlapping patterns of GM atrophy in normal aging and AD.
METHODS: A total of 169 cognitively normal subjects and 33 persons with probable AD enrolled in the longitudinal Cardiovascular Health Study-Cognition Study underwent 3-dimensional volumetric MRI scans. Controls remained cognitively normal for at least 5 years after their MRI scans and the probable AD subjects were relatively early in their clinical course with an average modified Mini-Mental State Examination score of 76/100. The scans were analyzed using voxel-based morphometry adjusting for total intracranial volume, gender, education, and race.
RESULTS: With older age, GM volume was lower in the sensorimotor and heteromodal association areas in frontal, temporal, occipital, and parietal lobes, as well as in the cerebellum (false discovery rate p = 0.05). Additional atrophy was observed in the posterior hippocampus, thalamus, and middle cingulate gyrus. By contrast, atrophy was seen in subjects with AD in the anterior hippocampal/parahippocampal regions and the precuneus. Normal aging and AD overlapped in the hippocampal body and the entorhinal cortex.
CONCLUSION: Brain atrophy with aging was observed in supratentorial and infratentorial areas, as well in primary motor, sensory, and heteromodal association regions. Age and Alzheimer disease exert independent gray matter atrophy patterns but these effects overlapped substantially in the hippocampus and entorhinal cortex.
10aAged10aAged, 80 and over10aAging10aAlzheimer Disease10aBrain10aBrain Mapping10aCognition Disorders10aFemale10aHumans10aImage Processing, Computer-Assisted10aLinear Models10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aRetrospective Studies1 aRaji, C, A1 aLopez, O, L1 aKuller, L H1 aCarmichael, O, T1 aBecker, J, T uhttps://chs-nhlbi.org/node/114002772nas a2200397 4500008004100000022001400041245011700055210006900172260001300241300001100254490000800265520167100273653002201944653001601966653000901982653002201991653001902013653002102032653002102053653004002074653001102114653001102125653001402136653002502150653000902175653002402184653001702208653001602225653001102241653001802252653001802270100001402288700001802302700001802320856003602338 2009 eng d a1549-471300aAge-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study.0 aAgerelated macular degeneration and risk of coronary heart disea c2009 Oct a1913-90 v1163 aPURPOSE: To examine the associations of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and stroke in the Cardiovascular Health Study.
DESIGN: Population-based prospective cohort study.
PARTICIPANTS: A total of 1786 white and African-American participants free of CHD or 2228 participants free of stroke, aged 69 to 97 years.
METHODS: AMD was evaluated from photographs taken in 1997 and 1998.
MAIN OUTCOME MEASURES: Incident CHD and stroke ascertained using standardized methods.
RESULTS: Of the 1786 persons free of CHD, 303 developed incident CHD over 7 years. Participants with early AMD (n = 277) had a higher cumulative incidence of CHD than participants without early AMD (25.8% vs. 18.9%, P = 0.001). By adjusting for age, gender, race, systolic and diastolic blood pressure, hypertension status, fasting glucose, triglyceride, low-density lipoprotein cholesterol, cigarette smoking, pack years of smoking, and C-reactive protein, the presence of early AMD was associated with an increased risk of incident CHD (hazard ratio 1.57; 95% confidence interval, 1.17-2.22). Late AMD (n = 25) was not associated with incident CHD (hazard ratio 0.78; 95% confidence interval, 0.25-2.48). Among 2228 persons at risk, 198 developed incident stroke; neither early nor late AMD was associated with incident stroke.
CONCLUSIONS: This study suggests persons with early AMD have a higher risk of CHD but not stroke in a population aged 69 to 97 years. This provides further support that AMD is associated with underlying systemic vascular disease.
10aAfrican Americans10aAge Factors10aAged10aAged, 80 and over10aBlood Pressure10aCholesterol, LDL10aCoronary Disease10aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aMacular Degeneration10aMale10aProspective Studies10aRisk Factors10aSex Factors10aStroke10aTriglycerides10aUnited States1 aSun, Cong1 aKlein, Ronald1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/111102973nas a2200313 4500008004100000022001400041245011900055210006900174260001300243300001000256490000700266520207900273653000902352653002202361653001902383653002102402653002302423653001102446653003002457653001102487653002502498653000902523653001102532100001902543700002002562700002002582700002102602856003602623 2009 eng d a1532-541500aAgreement between nosologist and cardiovascular health study review of deaths: implications of coding differences.0 aAgreement between nosologist and cardiovascular health study rev c2009 Jan a133-90 v573 aOBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS).
DESIGN: Observational.
SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh).
PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004.
MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only.
RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95% confidence interval (CI)=0.89-0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95% CI=0.58-0.64; stroke, kappa=0.59, 95% CI=0.54-0.64; chronic obstructive pulmonary disease, kappa=0.58, 95% CI=0.51-0.65; dementia, kappa=0.40, 95% CI=0.34-0.45; and pneumonia, kappa=0.35, 95% CI=0.29-0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5%) to dementia as the underlying cause.
CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.
10aAged10aAged, 80 and over10aCause of Death10aCoronary Disease10aDeath Certificates10aFemale10aForms and Records Control10aHumans10aLongitudinal Studies10aMale10aStroke1 aIves, Diane, G1 aSamuel, Paulraj1 aPsaty, Bruce, M1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/106303350nas a2200421 4500008004100000022001400041245014800055210006900203260001600272300001300288490000800301520213900309653000902448653004502457653002402502653001402526653001302540653001102553653002202564653001102586653001702597653001402614653000902628653002402637653001702661100002002678700001802698700002102716700002802737700002002765700001802785700001702803700001802820700001802838700001702856700001902873856003602892 2009 eng d a1538-367900aAngiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study.0 aAngiotensinconverting enzyme inhibitors and cognitive decline in c2009 Jul 13 a1195-2020 v1693 aBACKGROUND: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control.
METHODS: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs).
RESULTS: Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs.
CONCLUSIONS: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.
10aAged10aAngiotensin-Converting Enzyme Inhibitors10aBlood-Brain Barrier10aCognition10aDementia10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aMale10aProspective Studies10aRisk Factors1 aSink, Kaycee, M1 aLeng, Xiaoyan1 aWilliamson, Jeff1 aKritchevsky, Stephen, B1 aYaffe, Kristine1 aKuller, Lewis1 aYasar, Sevil1 aAtkinson, Hal1 aRobbins, Mike1 aPsaty, Bruce1 aGoff, David, C uhttps://chs-nhlbi.org/node/111203286nas a2200325 4500008004100000022001400041245011700055210006900172260001300241300001100254490000600265520238300271653000902654653002202663653001102685653001302696653001802709653001102727653000902738653001502747653002002762100001802782700002402800700002202824700002302846700001402869700001902883700002202902856003602924 2009 eng d a1941-329700aAssociation between elevated fibrosis markers and heart failure in the elderly: the cardiovascular health study.0 aAssociation between elevated fibrosis markers and heart failure c2009 Jul a303-100 v23 aBACKGROUND: Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly.
METHODS AND RESULTS: Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77+/-6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction > or =55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001).
CONCLUSIONS: Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.
10aAged10aAged, 80 and over10aFemale10aFibrosis10aHeart Failure10aHumans10aMale10aMyocardium10aUltrasonography1 aBarasch, Eddy1 aGottdiener, John, S1 aAurigemma, Gerard1 aKitzman, Dalane, W1 aHan, Jing1 aKop, Willem, J1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/113403049nas a2200433 4500008004100000022001400041245012300055210006900178260001600247300001200263490000700275520179800282653000902080653002202089653002502111653002302136653002802159653002002187653001902207653002802226653001102254653003102265653001102296653002002307653001102327653000902338653001702347100001902364700001602383700002002399700002502419700002402444700002402468700002002492700002002512700002402532700002302556856003602579 2009 eng d a1558-359700aAssociation of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).0 aAssociation of chronic kidney disease with the spectrum of ankle c2009 Sep 22 a1176-840 v543 aOBJECTIVES: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.
BACKGROUND: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.
METHODS: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.
RESULTS: Among 4,513 participants, 23% had CKD, 13% had a low ABI, and 3% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.
CONCLUSIONS: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.
10aAged10aAged, 80 and over10aAnkle Brachial Index10aC-Reactive Protein10aCardiovascular Diseases10aChronic Disease10aCohort Studies10aCross-Sectional Studies10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLipids10aMale10aRisk Factors1 aIx, Joachim, H1 aKatz, Ronit1 ade Boer, Ian, H1 aKestenbaum, Brian, R1 aAllison, Matthew, A1 aSiscovick, David, S1 aNewman, Anne, B1 aSarnak, Mark, J1 aShlipak, Michael, G1 aCriqui, Michael, H uhttps://chs-nhlbi.org/node/113003039nas a2200553 4500008004100000022001400041245010400055210006900159260001300228300001100241490000600252520146700258653000901725653002201734653001101756653002201767653002801789653003501817653001801852653001301870653001101883653001201894653003301906653001401939653000901953653001701962653003601979653003402015653002402049100002502073700001602098700002002114700001702134700001902151700001702170700002502187700002402212700001902236700002502255700002002280700001602300700001802316700002402334700002302358700001802381700001402399710003602413856003602449 2009 eng d a1474-972600aAssociation of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.0 aAssociation of common genetic variation in the insulinIGF1 signa c2009 Aug a460-720 v83 aThe insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) = 95.3 +/- 2.2y) and 603 average-lifespan controls (lifespan < or = 79y, mean = 75.7 +/- 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68-0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15-1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.
10aAged10aAged, 80 and over10aFemale10aFollow-Up Studies10aForkhead Box Protein O310aForkhead Transcription Factors10aGenome, Human10aGenotype10aHumans10aInsulin10aInsulin-Like Growth Factor I10aLongevity10aMale10aOsteoporosis10aPolymorphism, Single Nucleotide10aProto-Oncogene Proteins c-akt10aSignal Transduction1 aPawlikowska, Ludmila1 aHu, Donglei1 aHuntsman, Scott1 aSung, Andrew1 aChu, Catherine1 aChen, Justin1 aJoyner, Alexander, H1 aSchork, Nicholas, J1 aHsueh, Wen-Chi1 aReiner, Alexander, P1 aPsaty, Bruce, M1 aAtzmon, Gil1 aBarzilai, Nir1 aCummings, Steven, R1 aBrowner, Warren, S1 aKwok, Pui-Yan1 aZiv, Elad1 aStudy of Osteoporotic Fractures uhttps://chs-nhlbi.org/node/110403161nas a2200433 4500008004100000022001400041245017600055210006900231260001300300300001100313490000700324520179400331653000902125653002802134653002102162653001402183653001102197653002902208653001102237653002702248653004602275653002202321653001802343653000902361653003602370653003202406653002802438653003202466653001802498100001902516700002202535700002302557700002702580700002002607700001702627700002202644700002502666856003602691 2009 eng d a1880-387300aAssociation of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study.0 aAssociation of genetic variation in serum amyloidA with cardiova c2009 Aug a419-300 v163 aAIM: Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-alpha in influencing CVD was also explored.
METHODS: SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during 14 years of follow-up.
RESULTS: No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.981.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.80.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests.
CONCLUSION: Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.
10aAged10aCardiovascular Diseases10aCholesterol, HDL10aCytokines10aFemale10aGene Regulatory Networks10aHumans10aInflammation Mediators10aInterleukin 1 Receptor Antagonist Protein10aInterleukin-1beta10aInterleukin-610aMale10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aSerum Amyloid A Protein10aTumor Necrosis Factor-alpha10aTunica Intima1 aCarty, Cara, L1 aHeagerty, Patrick1 aHeckbert, Susan, R1 aEnquobahrie, Daniel, A1 aJarvik, Gail, P1 aDavis, Scott1 aTracy, Russell, P1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/112603838nas a2200829 4500008004100000022001400041245013700055210006900192260001300261300001100274490000600285520145100291653001001742653000901752653002201761653002801783653001901811653004001830653001101870653001501881653001701896653003401913653001101947653000901958653001601967653001301983653003601996653001602032100001902048700001602067700002002083700001702103700001902120700002402139700002002163700002002183700001802203700002202221700002202243700001802265700002002283700002202303700002302325700002202348700001902370700002102389700001902410700002302429700002602452700001802478700002002496700002302516700002202539700001802561700002402579700002102603700002302624700002802647700002402675700002202699700002002721700002102741700002102762700002102783700003002804700002802834700002302862700002302885700002102908710004302929856003602972 2009 eng d a1942-326800aAssociation of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.0 aAssociation of novel genetic Loci with circulating fibrinogen le c2009 Apr a125-330 v23 aBACKGROUND: Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.
METHODS AND RESULTS: We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg Study, and the British 1958 Birth Cohort Study, including 22 096 participants of European ancestry. Four loci were marked by 1 or more single-nucleotide polymorphisms that demonstrated genome-wide significance (P<5.0 x 10(-8)). These included a single-nucleotide polymorphism located in the fibrinogen beta chain (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of FGB (P=1.8 x 10(-30)), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3 x 10(-15)), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9 x 10(-10)), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04 x 10(-8)).
CONCLUSIONS: Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.
10aAdult10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aPedigree10aPolymorphism, Single Nucleotide10aYoung Adult1 aDehghan, Abbas1 aYang, Qiong1 aPeters, Annette1 aBasu, Saonli1 aBis, Joshua, C1 aRudnicka, Alicja, R1 aKavousi, Maryam1 aChen, Ming-Huei1 aBaumert, Jens1 aLowe, Gordon, D O1 aMcKnight, Barbara1 aTang, Weihong1 ade Maat, Moniek1 aLarson, Martin, G1 aEyhermendy, Susana1 aMcArdle, Wendy, L1 aLumley, Thomas1 aPankow, James, S1 aHofman, Albert1 aMassaro, Joseph, M1 aRivadeneira, Fernando1 aKolz, Melanie1 aTaylor, Kent, D1 aDuijn, Cornelia, M1 aKathiresan, Sekar1 aIllig, Thomas1 aAulchenko, Yurii, S1 aVolcik, Kelly, A1 aJohnson, Andrew, D1 aUitterlinden, André, G1 aTofler, Geoffrey, H1 aGieger, Christian1 aPsaty, Bruce, M1 aCouper, David, J1 aBoerwinkle, Eric1 aKoenig, Wolfgang1 aO'Donnell, Christopher, J1 aWitteman, Jacqueline, C1 aStrachan, David, P1 aSmith, Nicholas, L1 aFolsom, Aaron, R1 aWellcome Trust Case Control Consortium uhttps://chs-nhlbi.org/node/115303448nas a2200409 4500008004100000022001400041245011200055210006900167260001300236300001100249490000700260520229700267653000902564653001702573653001502590653002502605653001902630653001502649653001502664653001102679653003102690653002502721653001102746653002002757653000902777653001702786653001702803100002702820700002502847700001602872700002202888700002002910700002402930700002402954700002402978856003603002 2009 eng d a1460-238500aAssociation of renal function with cardiac calcifications in older adults: the cardiovascular health study.0 aAssociation of renal function with cardiac calcifications in old c2009 Mar a834-400 v243 aBACKGROUND: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function and MAC, aortic annular calcification (AAC) and AVS in the elderly.
METHODS: From the Cardiovascular Health Study, a community-based cohort of ambulatory adults >or= age 65, a total of 3929 individuals (mean +/- SD age 74 +/- 5 years, 60% women) were evaluated with two-dimensional echocardiography. Renal function was assessed by means of creatinine-based estimated glomerular filtration rate (eGFR) and cystatin C.
RESULTS: The prevalences of MAC and AAC were significantly higher in individuals with an eGFR < 45 mL/ min/1.73 m(2) (P < 0.01 for each), and cystatin C levels were significantly higher in individuals with MAC or AAC compared to individuals without these cardiac calcifications (P < 0.001 for each). After multivariate-adjustment, an eGFR <45 mL/min/1.73 m(2) was significantly associated with MAC [odds ratio 1.54 (95% CI 1.16-2.06), P = 0.003] and not associated with AAC [1.30 (0.97-1.74), P = 0.085] and AVS [1.15 (0.86-1.53), P = 0.355]. In addition, cystatin C levels were independently associated with MAC [odds ratio per SD 1.12 (1.05-1.21), P = 0.001] and not associated with AAC [1.07 (1.00-1.15), P = 0.054] and AVS [0.99 (0.93-1.06), P = 0.82]. Furthermore, the prevalence of multiple cardiac calcifications was higher in subjects with an eGFR < 45 mL/ min/1.73 m(2) and increased per quartile of cystatin C (P-values < 0.001). In addition, a significant trend was observed between an eGFR < 45 mL/min/1.73 m(2), increasing levels of cystatin C and the number of cardiac calcifications (P < 0.05).
CONCLUSIONS: In a community-based cohort of the elderly, moderate kidney disease as defined by an eGFR <45 mL/min/1.73m(2) and elevated levels of cystatin C was associated with prevalent MAC. In addition, a significant trend was observed between an eGFR <45 mL/min/1.73m(2), increasing levels of cystatin C and the number of cardiac calcifications. No associations were found between renal function and AAC or AVS.
10aAged10aAortic Valve10aCalcinosis10aCase-Control Studies10aCohort Studies10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Valve Diseases10aHumans10aKidney Diseases10aMale10aMitral Valve10aRisk Factors1 aAsselbergs, Folkert, W1 aMozaffarian, Dariush1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aGottdiener, John, S1 aShlipak, Michael, G1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/105602610nas a2200433 4500008004100000022001400041245011400055210006900169260001300238300001000251490000700261520136200268653000901630653001501639653002301654653002801677653002501705653001101730653001901741653001101760653002701771653001801798653000901816653003001825653003201855653002401887653002001911653001701931653003001948653001701978653001801995653001802013100002502031700002102056700002102077700002202098700002002120856003602140 2009 eng d a1524-463600aAssociations of pentraxin 3 with cardiovascular disease and all-cause death: the Cardiovascular Health Study.0 aAssociations of pentraxin 3 with cardiovascular disease and allc c2009 Apr a594-90 v293 aOBJECTIVE: We examined associations of pentraxin 3 (PTX3), a vascular inflammation marker, with incident cardiovascular disease (CVD) and all-cause death.
METHODS AND RESULTS: 1583 Cardiovascular Health Study participants free of prevalent CVD were included. Nonexclusive case groups were angina (n=476), myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282), and all-cause death (n=772). 535 participants had no events. PTX3 levels were higher in those with subclinical CVD (1.90+/-1.89 ng/mL) than those without (1.71+/-1.88 ng/mL; P=0.001). Using Cox regression adjusted for age, sex, and ethnicity, a standard deviation increase in PTX3 (1.89 ng/mL) was associated with CVD death (hazard ratio 1.11; 95% confidence interval 1.02 to 1.21) and all-cause death (1.08; 1.02 to 1.15). PTX3 was not associated with angina (1.09; 0.98 to 1.20), MI (0.96; 0.81 to 1.12), or stroke (1.06; 0.95 to 1.18). Adding C-reactive protein (CRP) or CVD risk factors to the models had no significant effects on associations.
CONCLUSIONS: In these older adults, PTX3 was associated with CVD and all-cause death independent of CRP and CVD risk factors. PTX3 likely reflects different aspects of inflammation than CRP and may provide insight into vascular health in aging and chronic diseases of aging that lead to death.
10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCase-Control Studies10aFemale10aHealth Surveys10aHumans10aInflammation Mediators10aLinear Models10aMale10aPredictive Value of Tests10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aSerum Amyloid P-Component10aTime Factors10aUnited States10aUp-Regulation1 aJenny, Nancy, Swords1 aArnold, Alice, M1 aKuller, Lewis, H1 aTracy, Russell, P1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/107203160nas a2200481 4500008004100000022001400041245009900055210006900154260001300223300001100236490000700247520181400254653001002068653000902078653002202087653002402109653002002133653002802153653001102181653001102192653001402203653001202217653002802229653000902257653001602266653002002282653002402302653003002326653002602356653002002382653001702402100002102419700002302440700002002463700002202483700002202505700001602527700002702543700002402570700002402594700002402618856003602642 2009 eng d a1358-863X00aBrachial artery diameter, blood flow and flow-mediated dilation in sleep-disordered breathing.0 aBrachial artery diameter blood flow and flowmediated dilation in c2009 Nov a351-600 v143 aClinic-based, case-control studies linked sleep-disordered breathing (SDB) to markers of endothelial dysfunction. We attempted to validate this association in a large community-based sample, and evaluate the relation of SDB to arterial diameter and peripheral blood flow. This community-based, cross-sectional observational study included 327 men and 355 women, aged 42-83 years, from the Framingham Heart Study site of the Sleep Heart Health Study. The polysomnographically derived apnea-hypopnea index and the hypoxemia index (percent sleep time with oxyhemoglobin saturation below 90%) were used to quantify the severity of SDB. Brachial artery ultrasound measurements included baseline diameter, percent flow-mediated dilation, and baseline and hyperemic flow velocity and volume. The baseline brachial artery diameter was significantly associated with both the apnea-hypopnea index and the hypoxemia index. The association was diminished by adjustment for body mass index, but remained significant for the apnea-hypopnea index. Age-, sex-, race- and body mass index-adjusted mean diameters were 4.32, 4.33, 4.33, 4.56, 4.53 mm for those with apnea-hypopnea index < 1.5, 1.5-4.9, 5-14.9, 15-29.9, >/= 30, respectively; p = 0.03. Baseline flow measures were associated with the apnea-hypopnea index but this association was non-significant after adjusting for body mass index. No significant association was observed between measures of SDB and percent flow-mediated dilation or hyperemic flow in any model. In conclusion, this study supports a moderate association of SDB and larger baseline brachial artery diameter, which may reflect SDB-induced vascular remodeling. This study does not support a link between SDB and endothelial dysfunction as measured by brachial artery flow-mediated dilation.
10aAdult10aAged10aAged, 80 and over10aBlood Flow Velocity10aBrachial Artery10aCross-Sectional Studies10aFemale10aHumans10aHyperemia10aHypoxia10aLaser-Doppler Flowmetry10aMale10aMiddle Aged10aPolysomnography10aRegional Blood Flow10aSeverity of Illness Index10aSleep Apnea Syndromes10aUltrasonography10aVasodilation1 aChami, Hassan, A1 aKeyes, Michelle, J1 aVita, Joseph, A1 aMitchell, Gary, F1 aLarson, Martin, G1 aFan, Shuxia1 aVasan, Ramachandran, S1 aO'Connor, George, T1 aBenjamin, Emelia, J1 aGottlieb, Daniel, J uhttps://chs-nhlbi.org/node/113702609nas a2200445 4500008004100000022001400041245007800055210006900133260000900202300001100211490000700222520142700229653000901656653002201665653001501687653002301702653002101725653001501746653002201761653001601783653001101799653002201810653001101832653002401843653001801867653002001885653000901905653001501914653003301929653001701962653001501979100002001994700001602014700001802030700001702048700002402065700001802089700002002107856003602127 2009 eng d a1421-967000aChange in cardiovascular risk factors with progression of kidney disease.0 aChange in cardiovascular risk factors with progression of kidney c2009 a334-410 v293 aBACKGROUND: Prior studies evaluating the relationship of kidney disease with cardiovascular risk factors have been limited by their cross-sectional design. We evaluated the change in lipids, inflammatory and procoagulant biomarkers with decline in kidney function in a nested case-cohort study in the Cardiovascular Health Study, a community-based study of adults aged >65 years.
METHODS: Individuals with an increase in serum creatinine >or=0.3 mg/dl (baseline to 3 years later, n = 207) were matched to controls of similar age, race, gender, diabetes and baseline serum creatinine, but whose change in creatinine was <0.3 mg/dl. Baseline and change in risk factors were analyzed with conditional logistic regression.
RESULTS: Changes in C-reactive protein were similar. In contrast, cases had larger increases in fibrinogen (OR 1.38 per standard deviation, 95% confidence interval 1.08-1.76) and factor VIII [1.38 (1.10-1.72)] and larger decreases in HDL [OR 0.80 (0.64, 1.00)]. Change in interleukin-6 was greater in cases than controls, but this did not persist after multivariate adjustment. However, in linear regression, change in interleukin-6 was correlated with change in creatinine.
CONCLUSION: Cardiovascular risk factors and kidney function may change concurrently. This could lead to an increased risk of cardiovascular disease as kidney function worsens.
10aAged10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCholesterol, HDL10aCreatinine10aDiabetes Mellitus10aFactor VIII10aFemale10aFollow-Up Studies10aHumans10aHypertension, Renal10aInterleukin-610aLogistic Models10aMale10aPrevalence10aRenal Insufficiency, Chronic10aRisk Factors10aVasculitis1 aFried, Linda, F1 aKatz, Ronit1 aCushman, Mary1 aSarnak, Mark1 aShlipak, Michael, G1 aKuller, Lewis1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/106103044nas a2200445 4500008004100000022001400041245009600055210006900151260001300220300001200233490000800245520184200253653001602095653000902111653002002120653002802140653001502168653001502183653001102198653003102209653001802240653001102258653001102269653002002280653001802300653002502318653000902343653001502352653002002367653001702387653001702404653001802421100002402439700001602463700002202479700002002501700002102521700002002542856003602562 2009 eng d a1879-148400aClinical and subclinical cardiovascular disease and kidney function decline in the elderly.0 aClinical and subclinical cardiovascular disease and kidney funct c2009 May a298-3030 v2043 aOBJECTIVE: Kidney function decline in elderly persons may be the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline.
METHODS: This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >or=65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration rate (eGFR(creat)) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m(2). Predictors of rapid kidney decline included prevalent and subclinical measures of CVD.
RESULTS: Mean decline in eGFR(creat) was 0.4+/-2.6/year; 714 (16%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95% CI: 1.55, 1.16-2.08) and heart failure (OR, 95% CI: 1.80, 1.40-2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle-arm index <0.9 (OR, 95% CI: 1.67, 1.25-2.24), common carotid intima-media thickness (>or=1.14 mm) (OR, 95% CI: 1.52, 1.12-2.06) and internal carotid intima-media thickness (>1.82 mm) (OR, 95% CI: 1.50, 1.12-2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C.
CONCLUSION: Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis.
10aAge Factors10aAged10aAtherosclerosis10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aKidney10aKidney Diseases10aLinear Models10aLongitudinal Studies10aMale10aOdds Ratio10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aSiscovick, David1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/105702378nas a2200385 4500008004100000022001400041245014200055210006900197260001600266300001200282490000800294520128700302653000901589653002201598653002501620653001401645653001301659653001401672653001501686653001601701653001101717653001101728653002501739653000901764653001601773653001501789653002401804653001701828653002701845100001801872700002201890700002101912700002301933856003601956 2009 eng d a1528-002000aCoagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology.0 aCoagulation factors IX through XIII and the risk of future venou c2009 Oct 01 a2878-830 v1143 aHigher levels of procoagulant factors and factor XII deficiency may be risk factors for first venous thromboembolism (VTE). We studied associations of coagulation factors IX through XIII with risk of future VTE in 2 general population samples. Using a nested case-control study combining the 21 860 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study, we determined antigenic levels of these coagulation factors in primarily pre-event blood samples from 462 participants who subsequently developed VTE and 1047 participants who remained free of VTE. Only elevated levels of factors IX and XI were associated with increased risk of VTE after adjustment for age, sex, race, and study. For factor IX, the odds ratio (OR) was 1.4 (95% confidence interval [CI], 1.0-2.0) comparing the top to bottom quintile. The OR for factor XI was higher: 2.0 (95% CI, 1.4-2.9). With further adjustment for body mass index and diabetes, only elevated factor XI remained associated with VTE risk: OR 1.8 (95% CI, 1.3-2.7). Associations were similar by study and whether the thrombosis was idiopathic or secondary. Factor XII deficiency was not related to VTE risk. Among these procoagulant factors, only elevated factor XI was a risk factor for VTE.
10aAged10aAged, 80 and over10aCase-Control Studies10aFactor IX10aFactor X10aFactor XI10aFactor XII10aFactor XIII10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aOdds Ratio10aProspective Studies10aRisk Factors10aVenous Thromboembolism1 aCushman, Mary1 aO'Meara, Ellen, S1 aFolsom, Aaron, R1 aHeckbert, Susan, R uhttps://chs-nhlbi.org/node/111503253nas a2200457 4500008004100000022001400041245017300055210006900228260001300297300001000310490000600320520189200326653001002218653000902228653001002237653001902247653001102266653003802277653003402315653001302349653001902362653001102381653000902392653002702401653001602428653001402444653002002458653001702478100002002495700003002515700002402545700002402569700002102593700002202614700002802636700002202664700003002686700002102716710002202737856003602759 2009 eng d a1942-326800aCohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts.0 aCohorts for Heart and Aging Research in Genomic Epidemiology CHA c2009 Feb a73-800 v23 aBACKGROUND: The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration. Methods- The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci.
CONCLUSIONS: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.
10aAdult10aAged10aAging10aCohort Studies10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHeart Diseases10aHumans10aMale10aMeta-Analysis as Topic10aMiddle Aged10aPhenotype10aResearch Design10aRisk Factors1 aPsaty, Bruce, M1 aO'Donnell, Christopher, J1 aGudnason, Vilmundur1 aLunetta, Kathryn, L1 aFolsom, Aaron, R1 aRotter, Jerome, I1 aUitterlinden, André, G1 aHarris, Tamara, B1 aWitteman, Jacqueline, C M1 aBoerwinkle, Eric1 aCHARGE Consortium uhttps://chs-nhlbi.org/node/115203764nas a2200541 4500008004100000022001400041245026000055210006900315260001300384300001100397490000600408520204700414653001502461653001002476653002202486653000902508653002202517653002302539653002802562653002102590653001902611653004002630653001102670653001502681653003002696653003802726653001302764653003802777653001102815653000902826653001602835653001402851653003602865653001702901100002502918700002002943700002802963700002602991700002103017700002003038700002003058700002003078700002203098700001903120700002103139700002603160856003603186 2009 eng d a1942-326800aCommon coding variants of the HNF1A gene are associated with multiple cardiovascular risk phenotypes in community-based samples of younger and older European-American adults: the Coronary Artery Risk Development in Young Adults Study and The Cardiovascula0 aCommon coding variants of the HNF1A gene are associated with mul c2009 Jun a244-540 v23 aBACKGROUND: The transcription factor hepatocyte nuclear factor (HNF)-1 alpha regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1 alpha gene (HNF1A) were recently associated with plasma C-reactive protein and gamma-glutamyl transferase concentration in middle-aged to older European Americans (EA).
METHODS AND RESULTS: We assessed whether common variants of HNF1A are associated with C-reactive protein, gamma-glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and gamma-glutamyl transferase levels in EA. The same HNF1A coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between HNF1A coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between HNF1A genotype and atherosclerosis-related phenotypes in AA.
CONCLUSIONS: Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.
10aAdolescent10aAdult10aAfrican Americans10aAged10aAged, 80 and over10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, LDL10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10agamma-Glutamyltransferase10aGenetic Predisposition to Disease10aGenotype10aHepatocyte Nuclear Factor 1-alpha10aHumans10aMale10aMiddle Aged10aPhenotype10aPolymorphism, Single Nucleotide10aRisk Factors1 aReiner, Alexander, P1 aGross, Myron, D1 aCarlson, Christopher, S1 aBielinski, Suzette, J1 aLange, Leslie, A1 aFornage, Myriam1 aJenny, Nancy, S1 aWalston, Jeremy1 aTracy, Russell, P1 aWilliams, Dale1 aJacobs, David, R1 aNickerson, Deborah, A uhttps://chs-nhlbi.org/node/115403056nas a2200397 4500008004100000022001400041245012900055210006900184260001300253300001300266490000600279520200300285653000902288653001202297653001302309653001602322653001102338653001502349653001102364653001702375653000902392653001602401653002002417653001602437653001602453653000902469653002602478653002202504100001702526700001602543700001502559700001602574700001502590700001702605856003602622 2009 eng d a1538-783600aCommon hemostasis and inflammation gene variants and venous thrombosis in older adults from the Cardiovascular Health Study.0 aCommon hemostasis and inflammation gene variants and venous thro c2009 Sep a1499-5050 v73 aBACKGROUND/OBJECTIVES: Age-related changes in blood coagulation and fibrinolysis are associated with increased risk of thrombotic events. Inherited deficiencies of coagulation proteins, such as factor V (FV) Leiden and prothrombin G20210A, explain a small fraction of venous thromboembolic disease (VTE). Additional genetic factors are likely to underlie the etiology of VTE, some of which may become manifest at older ages.
METHODS: We tested 290 common SNPs within 51 thrombosis and inflammation genes for association with VTE in the Cardiovascular Health Study, a large, prospective cohort of older adults followed for up to 12 years.
RESULTS: There were 184 VTE events that occurred at mean age of 78 years. TagSNPs within four genes encoding FXIII subunit A (F13A), FVII activating protease (HABP2), protease activated receptor-1 (F2R) and the urokinase receptor (PLAUR) showed the strongest evidence for association with VTE, with each gene having a global P-value < 0.05 and at least one tagSNP false discovery rate (FDR) q-value < 0.05. The rs3024409 variant allele of F13A1 was associated with 1.66-fold increased risk of VTE, while the minor alleles of HABP2 rs6585234 and rs3862019, F2R rs253061 and rs153311, and PLAUR rs344782 were each associated with lower risk of VTE (hazard ratios in the range of 0.49-0.66). Consistent with the observed protective association for VTE risk, the HABP2 rs3862019 variant allele was also associated with lower activity levels of coagulation factors FVIII, FIX, FX and plasminogen. We also confirm previously reported associations between common variants of the coagulation FII, FV, FVIII, FXI, alpha-fibrinogen and protein C genes and risk of VTE.
CONCLUSIONS: These findings suggest that several novel common coagulation gene variants may be related to risk of VTE in older adults. Further studies in older adults are needed to validate these findings and assess functional molecular mechanisms.
10aAged10aAlleles10aFactor V10aFactor VIII10aFemale10aHemostasis10aHumans10aInflammation10aMale10aMiddle Aged10aModels, Genetic10aPlasminogen10aProthrombin10aRisk10aSerine Endopeptidases10aVenous Thrombosis1 aReiner, A, P1 aLange, L, A1 aSmith, N L1 aZakai, N, A1 aCushman, M1 aFolsom, A, R uhttps://chs-nhlbi.org/node/110602856nas a2200397 4500008004100000022001400041245007700055210006900132260001300201300001100214490000700225520178700232653000902019653002202028653001602050653001502066653001502081653002202096653001102118653003102129653001102160653002602171653000902197653001702206100002002223700001602243700001602259700002002275700002202295700001702317700002002334700002002354700002402374700002402398856003602422 2009 eng d a1935-554800aCystatin C, albuminuria, and mortality among older adults with diabetes.0 aCystatin C albuminuria and mortality among older adults with dia c2009 Oct a1833-80 v323 aOBJECTIVE: Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population.
RESEARCH DESIGN AND METHODS: This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.
RESULTS: Of 691 participants, 378 died over 10 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR.
CONCLUSIONS: Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.
10aAged10aAged, 80 and over10aAlbuminuria10aCreatinine10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Function Tests10aMale10aRisk Factors1 ade Boer, Ian, H1 aKatz, Ronit1 aCao, Jie, J1 aFried, Linda, F1 aKestenbaum, Bryan1 aMukamal, Ken1 aRifkin, Dena, E1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/111003445nas a2200469 4500008004100000022001400041245009100055210006900146260001300215300001100228490000700239520212400246653000902370653002202379653002202401653002402423653001302447653001502460653001102475653002202486653001102508653001402519653002502533653003102558653000902589653002702598653002402625653003702649653003002686653001702716100002102733700002002754700002002774700002202794700002102816700002002837700002002857700001902877700001802896700002502914856003602939 2009 eng d a1545-721400aDepressed mood is not a risk factor for incident dementia in a community-based cohort.0 aDepressed mood is not a risk factor for incident dementia in a c c2009 Aug a653-630 v173 aOBJECTIVES: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals.
DESIGN: Longitudinal and observational.
SETTING: Community-based cohort study.
PARTICIPANTS: A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years).
MEASUREMENTS: The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams.
RESULTS: The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood.
CONCLUSION: Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.
10aAged10aAged, 80 and over10aAlzheimer Disease10aCognition Disorders10aDementia10aDepression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aProspective Studies10aPsychiatric Status Rating Scales10aResidence Characteristics10aRisk Factors1 aBecker, James, T1 aChang, Yue-Fang1 aLopez, Oscar, L1 aDew, Mary, Amanda1 aSweet, Robert, A1 aBarnes, Deborah1 aYaffe, Kristine1 aYoung, Jeffrey1 aKuller, Lewis1 aReynolds, Charles, F uhttps://chs-nhlbi.org/node/111802544nas a2200397 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520142400267653000901691653002201700653002801722653002401750653001301774653001101787653001101798653002301809653002501832653000901857653002901866653001501895653002401910653001701934653001801951100002301969700001901992700001902011700001802030700002102048700002102069700002002090856003602110 2009 eng d a1538-360100aEarly age-related macular degeneration, cognitive function, and dementia: the Cardiovascular Health Study.0 aEarly agerelated macular degeneration cognitive function and dem c2009 May a667-730 v1273 aOBJECTIVE: To describe the association of cognitive function and dementia with early age-related macular degeneration (AMD) in older individuals.
METHODS: This population-based study included 2,088 persons aged 69 to 97 years who participated in the Cardiovascular Health Study. The AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and the Modified Mini-Mental State Examination. Participants were also evaluated for dementia using detailed neuropsychological testing.
RESULTS: After controlling for age, sex, race, and study center, persons with low DSST scores (lowest quartile of scores, < or =30) were more likely to have early AMD (odds ratio, 1.38; 95% confidence interval, 1.03-1.85) than were persons with higher DSST scores. In analyses further controlling for education, systolic blood pressure, total cholesterol level, diabetes mellitus, smoking status, and apolipoprotein E genotype, this association was stronger (odds ratio, 2.00; 95% confidence interval, 1.29-3.10). There was no association of low Modified Mini-Mental State Examination scores, dementia, or Alzheimer disease with early AMD.
CONCLUSIONS: In this older population, cognitive impairment may share common age-related pathogenesis and risk factors with early AMD.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCognition Disorders10aDementia10aFemale10aHumans10aIntelligence Tests10aMacular Degeneration10aMale10aNeuropsychological Tests10aOdds Ratio10aProspective Studies10aRisk Factors10aUnited States1 aBaker, Michelle, L1 aWang, Jie, Jin1 aRogers, Sophie1 aKlein, Ronald1 aKuller, Lewis, H1 aLarsen, Emily, K1 aWong, Tien, Yin uhttps://chs-nhlbi.org/node/110002807nas a2200361 4500008004100000022001400041245010100055210006900156260001300225300001100238490000700249520176500256653000902021653002802030653001902058653001602077653001102093653001102104653000902115653001302124653004202137653003102179653002602210653001802236100002302254700002402277700002202301700002402323700002102347700001802368700002302386856003602409 2009 eng d a1537-194800aExternal validity of the cardiovascular health study: a comparison with the Medicare population.0 aExternal validity of the cardiovascular health study a compariso c2009 Aug a916-230 v473 aBACKGROUND: The Cardiovascular Health Study (CHS), a population-based prospective cohort study, has been used to identify major risk factors associated with cardiovascular disease and stroke in the elderly.
OBJECTIVE: To assess the external validity of the CHS.
RESEARCH DESIGN: Comparison of the CHS cohort to a national cohort of Medicare beneficiaries and to Medicare beneficiaries residing in the CHS geographic regions.
SUBJECTS: CHS participants and a 5% sample of Medicare beneficiaries.
MEASURES: Demographic and administrative characteristics, comorbid conditions, resource use, and mortality.
RESULTS: Compared with both Medicare cohorts, the CHS cohort was older and included more men and African American participants. CHS participants were more likely to be enrolled in Medicare managed care than beneficiaries in the national Medicare cohort. Compared with the Medicare cohorts, mortality in the CHS was more than 40% lower at 1 year, approximately 25% lower at 5 years, and approximately 15% lower at 10 years. There were minimal differences in comorbid conditions and health care resource use.
CONCLUSION: The CHS cohort is comparable with the Medicare population, particularly with regard to comorbid conditions and resource use, but had lower mortality. The difference in mortality may reflect the CHS recruitment strategy or volunteer bias. These findings suggest it may not be appropriate to project absolute rates of disease and outcomes based on CHS data to the entire Medicare population. However, there is no reason to expect that the relative risks associated with physiologic processes identified by CHS data would differ for nonparticipants.
10aAged10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aHumans10aMale10aMedicare10aRandomized Controlled Trials as Topic10aReproducibility of Results10aSocioeconomic Factors10aUnited States1 aDiMartino, Lisa, D1 aHammill, Bradley, G1 aCurtis, Lesley, H1 aGottdiener, John, S1 aManolio, Teri, A1 aPowe, Neil, R1 aSchulman, Kevin, A uhttps://chs-nhlbi.org/node/111303092nas a2200505 4500008004100000022001400041245008400055210006900139260001300208300001000221490000700231520167900238653003901917653000901956653001201965653001901977653002801996653002102024653001802045653004002063653001102103653001902114653002202133653001102155653002602166653000902192653003602201653002402237653001702261653001102278653001802289100001702307700002202324700002402346700001802370700001902388700002302407700002002430700001902450700001802469700002202487700002102509700002002530856003602550 2009 eng d a1524-462800aGene variants associated with ischemic stroke: the cardiovascular health study.0 aGene variants associated with ischemic stroke the cardiovascular c2009 Feb a363-80 v403 aBACKGROUND AND PURPOSE: The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.
METHODS: Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).
RESULTS: In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS.
CONCLUSIONS: The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.
10aAfrican Continental Ancestry Group10aAged10aAlleles10aBrain Ischemia10aCardiovascular Diseases10aCoronary Disease10aEthnic Groups10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenetic Variation10aHumans10aKaplan-Meier Estimate10aMale10aPolymorphism, Single Nucleotide10aProspective Studies10aRisk Factors10aStroke10aUnited States1 aLuke, May, M1 aO'Meara, Ellen, S1 aRowland, Charles, M1 aShiffman, Dov1 aBare, Lance, A1 aArellano, Andre, R1 aLongstreth, W T1 aLumley, Thomas1 aRice, Kenneth1 aTracy, Russell, P1 aDevlin, James, J1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/106405728nas a2201213 4500008004100000022001400041245013400055210006900189260001600258300001100274490000800285520227000293653001002563653000902573653002202582653001002604653002802614653002102642653004002663653001102703653003402714653001302748653001602761653002102777653001102798653000902809653001602818653001502834653001402849653003602863653001702899653003402916653003102950100002702981700002203008700002103030700001903051700002103070700002203091700002303113700002203136700002303158700001903181700002303200700002003223700002203243700002203265700002203287700001903309700002403328700002003352700001803372700001803390700002303408700002103431700001903452700002603471700002203497700002403519700001803543700002003561700001503581700002703596700002703623700001703650700002303667700002103690700001803711700002103729700001703750700002003767700002003787700002303807700003003830700002303860700002303883700002103906700002503927700002603952700001703978700002203995700001804017700002104035700001904056700002404075700002804099700002204127700002004149700002004169700002004189700002004209700002304229700002204252700002204274700002104296700002404317700002204341700002804363700002404391700002004415700001904435700002404454856003604478 2009 eng d a1538-359800aGenetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.0 aGenetic variants associated with cardiac structure and function c2009 Jul 08 a168-780 v3023 aCONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.
OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.
DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort.
MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.
RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance).
CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
10aAdult10aAged10aAged, 80 and over10aAorta10aCardiovascular Diseases10aEchocardiography10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aGenotype10aHeart Atria10aHeart Ventricles10aHumans10aMale10aMiddle Aged10aOrgan Size10aPhenotype10aPolymorphism, Single Nucleotide10aRisk Factors10aVentricular Dysfunction, Left10aVentricular Function, Left1 aVasan, Ramachandran, S1 aGlazer, Nicole, L1 aFelix, Janine, F1 aLieb, Wolfgang1 aWild, Philipp, S1 aFelix, Stephan, B1 aWatzinger, Norbert1 aLarson, Martin, G1 aSmith, Nicholas, L1 aDehghan, Abbas1 aGrosshennig, Anika1 aSchillert, Arne1 aTeumer, Alexander1 aSchmidt, Reinhold1 aKathiresan, Sekar1 aLumley, Thomas1 aAulchenko, Yurii, S1 aKönig, Inke, R1 aZeller, Tanja1 aHomuth, Georg1 aStruchalin, Maksim1 aAragam, Jayashri1 aBis, Joshua, C1 aRivadeneira, Fernando1 aErdmann, Jeanette1 aSchnabel, Renate, B1 aDörr, Marcus1 aZweiker, Robert1 aLind, Lars1 aRodeheffer, Richard, J1 aGreiser, Karin, Halina1 aLevy, Daniel1 aHaritunians, Talin1 aDeckers, Jaap, W1 aStritzke, Jan1 aLackner, Karl, J1 aVölker, Uwe1 aIngelsson, Erik1 aKullo, Iftikhar1 aHaerting, Johannes1 aO'Donnell, Christopher, J1 aHeckbert, Susan, R1 aStricker, Bruno, H1 aZiegler, Andreas1 aReffelmann, Thorsten1 aRedfield, Margaret, M1 aWerdan, Karl1 aMitchell, Gary, F1 aRice, Kenneth1 aArnett, Donna, K1 aHofman, Albert1 aGottdiener, John, S1 aUitterlinden, André, G1 aMeitinger, Thomas1 aBlettner, Maria1 aFriedrich, Nele1 aWang, Thomas, J1 aPsaty, Bruce, M1 aDuijn, Cornelia, M1 aWichmann, H-Erich1 aMunzel, Thomas, F1 aKroemer, Heyo, K1 aBenjamin, Emelia, J1 aRotter, Jerome, I1 aWitteman, Jacqueline, C1 aSchunkert, Heribert1 aSchmidt, Helena1 aVölzke, Henry1 aBlankenberg, Stefan uhttps://chs-nhlbi.org/node/110804313nas a2200889 4500008004100000022001400041245004600055210004500101260001600146300001200162490000800174520183800182653003902020653000902059653003202068653001902100653004002119653001102159653002002170653003802190653003402228653001302262653001102275653000902286653001602295653003602311653003202347653001702379653001102396100002002407700002002427700001902447700002002466700002402486700002402510700002302534700001902557700002102576700002802597700002002625700001802645700001802663700002202681700001702703700002302720700001702743700002202760700002302782700002602805700002602831700002002857700001802877700001902895700002102914700002302935700002402958700001602982700002302998700002003021700001803041700002303059700001703082700002303099700002003122700002303142700001903165700002803184700002203212700002103234700002003255700002203275700002303297700002703320700002003347700002003367856003603387 2009 eng d a1533-440600aGenomewide association studies of stroke.0 aGenomewide association studies of stroke c2009 Apr 23 a1718-280 v3603 aBACKGROUND: The genes underlying the risk of stroke in the general population remain undetermined.
METHODS: We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/-SD] age, 63+/-8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons.
RESULTS: Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5x10(-8)). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P=0.04) and 1.42 (95% CI, 1.06 to 1.91; P=0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P=0.03) and 1.19 (95% CI, 1.01 to 1.41; P=0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant.
CONCLUSIONS: A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.
10aAfrican Continental Ancestry Group10aAged10aChromosomes, Human, Pair 1210aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGenetic Markers10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aRisk Factors10aStroke1 aIkram, Arfan, M1 aSeshadri, Sudha1 aBis, Joshua, C1 aFornage, Myriam1 aDeStefano, Anita, L1 aAulchenko, Yurii, S1 aDebette, Stephanie1 aLumley, Thomas1 aFolsom, Aaron, R1 avan den Herik, Evita, G1 aBos, Michiel, J1 aBeiser, Alexa1 aCushman, Mary1 aLauner, Lenore, J1 aShahar, Eyal1 aStruchalin, Maksim1 aDu, Yangchun1 aGlazer, Nicole, L1 aRosamond, Wayne, D1 aRivadeneira, Fernando1 aKelly-Hayes, Margaret1 aLopez, Oscar, L1 aCoresh, Josef1 aHofman, Albert1 aDeCarli, Charles1 aHeckbert, Susan, R1 aKoudstaal, Peter, J1 aYang, Qiong1 aSmith, Nicholas, L1 aKase, Carlos, S1 aRice, Kenneth1 aHaritunians, Talin1 aRoks, Gerwin1 ade Kort, Paul, L M1 aTaylor, Kent, D1 ade Lau, Lonneke, M1 aOostra, Ben, A1 aUitterlinden, André, G1 aRotter, Jerome, I1 aBoerwinkle, Eric1 aPsaty, Bruce, M1 aMosley, Thomas, H1 aDuijn, Cornelia, M1 aBreteler, Monique, M B1 aLongstreth, W T1 aWolf, Philip, A uhttps://chs-nhlbi.org/node/109202540nas a2200409 4500008004100000022001400041245007300055210006900128260001300197300001000210490000700220520137800227653002101605653000901626653001001635653003101645653002901676653002801705653002801733653003601761653001101797653001501808653001101823653001701834653000901851653002301860653001501883653002401898653001701922653003601939100002201975700002401997700002302021700002602044700002402070856003602094 2009 eng d a1468-283400aHeart rate variability and its changes over 5 years in older adults.0 aHeart rate variability and its changes over 5 years in older adu c2009 Mar a212-80 v383 aPURPOSE: to characterise the association between age, ageing and heart rate variability (HRV) in older individuals, 585 adults age >65 years with two 24-h Holter recordings in the Cardiovascular Health Study were studied.
METHODS: heart rate (HR), ventricular premature contractions (VPCs), atrial premature contractions (APCs), frequency-domain, ratio-based and non-linear HRV and heart rate turbulence (HRT) were examined cross-sectionally by 5-year age groups and prospectively over 5 years. Analyses adjusted for gender, lower versus elevated cardiovascular (CV) risk and for the change in CV risk.
RESULTS: HR declined, and VPCs and APCs increased per 5-year increase in age. Frequency-domain HRV decreased more at 65-69, less at 70-74 and minimally at > or =75 years, independent of CVD risk or change in CVD risk. Ratio and non-linear HRV continued to decline to > or =75 years old. Ratio HRV and HRT slope were more strongly related to CVD risk than frequency-domain HRV.
CONCLUSIONS: cardiac autonomic function, assessed by frequency-domain HRV, declines most at 65-70 and levels off at age >75. The decline is independent of CVD risk or change in CVD risk. Ratio-based and non-linear HRV and HRT slope continued to change with increasing age and were more closely related to CVD risk than frequency-domain HRV.
10aAge Distribution10aAged10aAging10aAtrial Premature Complexes10aAutonomic Nervous System10aCardiovascular Diseases10aCross-Sectional Studies10aElectrocardiography, Ambulatory10aFemale10aHeart Rate10aHumans10aHypertension10aMale10aNonlinear Dynamics10aPrevalence10aProspective Studies10aRisk Factors10aVentricular Premature Complexes1 aStein, Phyllis, K1 aBarzilay, Joshua, I1 aChaves, Paulo, H M1 aDomitrovich, Peter, P1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/106902837nas a2200409 4500008004100000022001400041245014000055210006900195260001300264300001100277490000700288520164000295653000901935653002001944653001601964653002201980653003702002653003002039653001102069653003202080653001102112653000902123653002602132653002402158653001702182653002102199653002102220653001602241653001402257653002102271100002102292700002102313700001602334700002002350700002102370856003602391 2009 eng d a1945-719700aHigh frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over.0 aHigh frequency of and factors associated with thyroid hormone ov c2009 Apr a1342-50 v943 aCONTEXT: Thyroid hormone use is common in older populations, but the frequency of over- or under-replacement is debated.
OBJECTIVE: We sought to describe the frequency of and factors associated with thyroid hormone over- or under-replacement in a population of older men and women.
DESIGN: Participants were 3678 U.S. community dwelling individuals aged 65 yr or older enrolled in the Cardiovascular Health Study who had thyroid function tests in 1989-1990. Thyroid hormone users (n = 339) were identified and classified into low TSH (<0.45 mU/liter), euthyroid (0.45-4.5 mU/liter), and high TSH (>4.5 mU/liter).
RESULTS: Of the 339 thyroid hormone users, 41% had a low TSH, 16% had a high TSH, and 43% were in the euthyroid range. In multivariable analyses, lower weight (P < 0.001) was independently associated with low TSH status. For every 10 kg lower weight, the likelihood of having low TSH increased by 65% [odd ratio (OR) 1.65; 95% confidence interval (CI) 1.31-2.07]. Those with renal insufficiency were less likely to have low TSH levels (P = 0.02). The presence of diabetes was independently associated with having low (OR 3.35; 95% CI 1.46-7.65) and high TSH levels (OR 2.66; 95% CI 1.14-6.21).
CONCLUSIONS: There is a very high prevalence of thyroid function testing abnormalities in older people taking thyroid hormone preparations, particularly in those of low weight or with diabetes. Because of potential adverse cardiovascular and skeletal effects from over-replacement, older people represent a key population for increased TSH monitoring on therapy.
10aAged10aBody Mass Index10aBody Weight10aDiabetes Mellitus10aDose-Response Relationship, Drug10aDrug Therapy, Combination10aFemale10aHormone Replacement Therapy10aHumans10aMale10aMultivariate Analysis10aRenal Insufficiency10aRisk Factors10aThyroid Diseases10aThyroid Hormones10aThyrotropin10aThyroxine10aTriiodothyronine1 aSomwaru, Lily, L1 aArnold, Alice, M1 aJoshi, Neha1 aFried, Linda, P1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/106703110nas a2200445 4500008004100000022001400041245014600055210006900201260001300270300001200283490000700295520180900302653000902111653002202120653001802142653002802160653002102188653001102209653001102220653001202231653002302243653002302266653001502289653002102304653002602325653001702351653002202368100002102390700002402411700002402435700002202459700002202481700002202503700002002525700002402545700001802569700002002587700002102607856003602628 2009 eng d a1945-719700aHigher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease.0 aHigher serum testosterone concentration in older women is associ c2009 Dec a4776-840 v943 aCONTEXT: Early postmenopausal women with higher testosterone (T) levels have increased insulin resistance (IR) and cardiovascular risk factors, but whether this translates into increased cardiovascular disease later in life is unknown.
OBJECTIVE: The objective of the study was to determine whether higher T levels are associated with IR, the metabolic syndrome (MetSyn), and coronary heart disease (CHD) in elderly women.
DESIGN: Total T and free T by equilibrium dialysis were measured using ultrasensitive assays in 344 women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to examine the associations between total and free T and IR, MetSyn, and CHD.
RESULTS: There was a stepwise increase in the homeostasis model assessment of insulin resistance with increasing total (P = 0.0.003) and free T (P = 0.02) level and a corresponding decrease in Quantitative Insulin Sensitivity Check Index (P < 0.001 and P = 0.002, respectively). In adjusted models, higher levels of both total and free T were strongly associated with abdominal obesity and high fasting glucose, the two MetSyn components most strongly linked to IR. After adjustment, women in the top quartile of total T levels had a 3-fold greater odds of MetSyn (odds ratio 3.15, 95% confidence interval 1.57-6.35) than those in the bottom quartile and a 3-fold greater odds of CHD (odds ratio 2.95, 95% confidence interval 1.2-7.3) than those in second quartile, whereas free T was not significantly associated with MetSyn or CHD.
CONCLUSIONS: Higher levels of T are associated with IR, MetSyn, and CHD in elderly women. Whether T is a marker or mediator of cardiovascular disease in this population merits further investigation.
10aAged10aAged, 80 and over10aBlood Glucose10aCardiovascular Diseases10aCoronary Disease10aFemale10aHumans10aInsulin10aInsulin Resistance10aMetabolic Syndrome10aOdds Ratio10aRadioimmunoassay10aSocioeconomic Factors10aTestosterone10aTreatment Outcome1 aPatel, Shrita, M1 aRatcliffe, Sarah, J1 aReilly, Muredach, P1 aWeinstein, Rachel1 aBhasin, Shalender1 aBlackman, Marc, R1 aCauley, Jane, A1 aSutton-Tyrrell, Kim1 aRobbins, John1 aFried, Linda, P1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/113902893nas a2200361 4500008004100000022001400041245015400055210006900209260001300278300001100291490000700302520181400309653002202123653001002145653001002155653001802165653003202183653001102215653001102226653003102237653000902268653003102277653004102308653001602349100001702365700002002382700002102402700001602423700001702439700002102456700001802477856003602495 2009 eng d a1552-656900aImaging cerebral blood flow in the cognitively normal aging brain with arterial spin labeling: implications for imaging of neurodegenerative disease.0 aImaging cerebral blood flow in the cognitively normal aging brai c2009 Oct a344-520 v193 aINTRODUCTION: Arterial spin labeling (ASL) is a safe, noninvasive imaging method for evaluating cerebral blood flow (rCBF). The purpose of this article is to present ASL imaging features of 38 elderly cognitively normals (CN) with their rCBF values and an averaged profile of targeted anatomic regions rCBF values.
METHODS: Thirty-eight CN underwent MR imaging especially ASL with voxel morphometric techniques fusing the MR anatomical and ASL images to a standard reference brain (colin27). The ASL images were fused to echo planar images, which were then coregistered to high-resolution anatomical SPGR images. rCBF was calculated per region of interest using a modified continuous arterial spin labeling (CASL) convolutional method. Anatomical regions were selected and identified by the Talairach atlas in SPM2.
RESULTS: We identified areas of decreased and increased perfusion (compared to the averaged rCBF of all 38 CN) corresponding to decreased and increased quantified rCBF. The most common sites for decreased perfusion were precuneus (53%), superior temporal (48%), and orbitofrontal (37%), and for increased perfusion the caudate (39%), posterior cingulate (34%), anterior cingulate (32%), and amygdala (32%).
CONCLUSION: There are regional variations in rCBF both increased and decreased with the posterior cingulate and precuneus cortex showing the highest averaged values and signal intensity (bright spots). These variations represent the normal profile of a CN elderly brain, with higher perfusion in areas associated with cognition, memory, and behavior. It is necessary to understand these normal variations in order to determine if there are perfusion changes in ASL detected in neurodegenerative disorders such as Alzheimer's disease.
10aAged, 80 and over10aAging10aBrain10aBrain Mapping10aCerebrovascular Circulation10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aNeurodegenerative Diseases10aSignal Processing, Computer-Assisted10aSpin Labels1 aLee, Charles1 aLopez, Oscar, L1 aBecker, James, T1 aRaji, Cyrus1 aDai, Weiying1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/108602825nas a2200529 4500008004100000022001400041245011300055210006900168260001300237300001000250490000700260520135800267653000901625653002201634653001001656653002801666653002501694653001101719653002201730653001301752653001101765653001701776653001801793653001401811653000901825653001401834653003501848653003301883653001701916100002301933700002101956700002501977700002102002700002002023700001802043700001402061700002502075700001402100700002302114700002402137700002002161700002202181700001602203700002002219700002002239856003602259 2009 eng d a1873-681500aInflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.0 aInflammation and stressrelated candidate genes plasma interleuki c2009 May a350-50 v443 aInterleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%-20% higher baseline IL-6 concentration per copy among CHS European-American (EA) participants (all p<10(-4)). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p=0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415--longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the "risk" of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62-1.02; p=0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.
10aAged10aAged, 80 and over10aAging10aCardiovascular Diseases10aCase-Control Studies10aFemale10aGenetic Variation10aGenotype10aHumans10aInflammation10aInterleukin-610aLongevity10aMale10aPhenotype10aPoly (ADP-Ribose) Polymerase-110aPoly(ADP-ribose) Polymerases10aRisk Factors1 aWalston, Jeremy, D1 aMatteini, Amy, M1 aNievergelt, Caroline1 aLange, Leslie, A1 aFallin, Dani, M1 aBarzilai, Nir1 aZiv, Elad1 aPawlikowska, Ludmila1 aKwok, Pui1 aCummings, Steve, R1 aKooperberg, Charles1 aLaCroix, Andrea1 aTracy, Russell, P1 aAtzmon, Gil1 aLange, Ethan, M1 aReiner, Alex, P uhttps://chs-nhlbi.org/node/108102796nas a2200361 4500008004100000022001400041245010300055210006900158260001300227300001000240490000700250520173200257653002201989653000902011653001902020653001602039653004002055653001102095653002202106653001902128653001102147653001702158653000902175653002402184653001702208653004702225653001802272100002202290700002102312700001802333710004702351856003602398 2009 eng d a0161-810500aInsomnia did not predict incident hypertension in older adults in the cardiovascular health study.0 aInsomnia did not predict incident hypertension in older adults i c2009 Jan a65-720 v323 aSTUDY OBJECTIVE: We hypothesized that the sleep complaints of insomnia predict incident hypertension, particularly in African Americans. The purpose of this study was to analyze insomnia complaints as predictors of incident hypertension in the Cardiovascular Health Study (CHS), stratifying by gender and allowing for race and sleep variable interaction.
DESIGN: This is a prospective cohort study over a 6-year period of follow-up.
SETTING: This is a community-based study of participants in Forsyth County, North Carolina; Pittsburgh, Pennsylvania; Sacramento County, California; and Washington County, Maryland.
PARTICIPANTS: The study analyzed data from 1419 older individuals (baseline mean age 73.4 +/- 4.4 years) from the Cardiovascular Health Study who were not hypertensive at baseline.
INTERVENTIONS: none.
MEASUREMENTS: We constructed relative risks of incident hypertension over a 6-year period for insomnia complaints singly and in combination.
RESULTS: Difficulty falling asleep, singly or in combination with other sleep complaints, predicted a statistically significant reduction of risk for incident hypertension for non-African American men in 6 years of follow-up. Insomnia complaints did not predict incident hypertension in 6 years of follow-up in women or in African Americans, although there may not have been enough power to show a significant association for African Americans.
CONCLUSIONS: Insomnia did not predict hypertension in this older cohort which was free of hypertension at baseline. Difficulty falling asleep was associated with reduced risk of hypertension in non-African American men.
10aAfrican Americans10aAged10aCohort Studies10aComorbidity10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHealth Surveys10aHumans10aHypertension10aMale10aProspective Studies10aRisk Factors10aSleep Initiation and Maintenance Disorders10aUnited States1 aPhillips, Barbara1 aBůzková, Petra1 aEnright, Paul1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/107602317nas a2200433 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520102500251653000901276653001001285653002801295653001101323653001101334653004901345653004901394653004801443653003301491653001501524653001801539653000901557653002401566653001301590100002201603700002801625700002301653700002401676700002001700700002201720700002101742700002501763700002101788700002001809700001801829856003601847 2009 eng d a1758-535X00aInsulin-like growth factors and leukocyte telomere length: the cardiovascular health study.0 aInsulinlike growth factors and leukocyte telomere length the car c2009 Nov a1103-60 v643 aThe insulin-like growth factor (IGF) axis may affect immune cell replicative potential and telomere dynamics. Among 551 adults 65 years and older, leukocyte telomere length (LTL), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1, IGFBP-3) were measured. Multivariate linear regression was used to model the association of LTL with IGF-1 and IGFBPs, while controlling for confounding and increasing precision by adjusting for covariates. We observed a significant association between higher IGF-1 and longer LTL after adjustment for age, sex, race, smoking status, body mass index, hypertension, diabetes, and serum lipids. The results suggested an increase of .08 kb in LTL for each standard deviation increase of IGF-1 (p = .04). IGFBP-1 and IGFBP-3 were not significantly associated with LTL. High IGF-1 may be an independent predictor of longer LTL, consistent with prior evidence suggesting a role for IGF-1 in mechanisms relating to telomere maintenance.
10aAged10aAging10aCross-Sectional Studies10aFemale10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor Binding Proteins10aInsulin-Like Growth Factor I10aLeukocytes10aLinear Models10aMale10aSex Characteristics10aTelomere1 aKaplan, Robert, C1 aFitzpatrick, Annette, L1 aPollak, Michael, N1 aGardner, Jeffrey, P1 aJenny, Nancy, S1 aMcGinn, Aileen, P1 aKuller, Lewis, H1 aStrickler, Howard, D1 aKimura, Masayuki1 aPsaty, Bruce, M1 aAviv, Abraham uhttps://chs-nhlbi.org/node/108802372nas a2200373 4500008004100000022001400041245016100055210006900216260001300285300001000298490000800308520125300316653001701569653002501586653003501611653001101646653001301657653001101670653002001681653000901701653001601710653001501726653002601741653002401767653002801791653000901819653002701828100002401855700001801879700002301897700002101920700002101941856003601962 2009 eng d a1365-214100aLack of association of soluble endothelial protein C receptor and PROCR 6936A/G polymorphism with the risk of venous thromboembolism in a prospective study.0 aLack of association of soluble endothelial protein C receptor an c2009 Apr a221-60 v1453 aPrior case-control studies reported that levels of the soluble form of the endothelial protein C receptor (sEPCR) were strongly controlled by the PROCR 6963A/G polymorphism and higher levels were a risk factor for venous thromboembolism (VTE). We sought to prospectively examine the association of sEPCR and the 6963A/G polymorphism with the incidence of VTE. The Longitudinal Investigation of Thromboembolism Etiology (LITE) pooled data from the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study on men and women aged > or =45 years. A nested case-control study of 458 incident VTE and 1038 controls was performed. sEPCR levels were distributed trimodally according to 6963A/G polymorphism. Adjusting for age, sex and race, there was no overall association between sEPCR level and VTE: odds ratio (OR) [95% confidence interval] for highest versus lowest quartile = 1.17[0.86-1.59]. However, higher sEPCR was associated with VTE in non-whites (OR = 1.84[1.05-3.22]) and women (OR = 1.51[1.01-2.26]). The 6963A/G polymorphism was not associated with VTE risk (OR = 0.93[0.70-1.25]). In conclusion, sEPCR levels and the PROCR 6963A/G polymorphism were not associated overall with increased risk of VTE.
10aAntigens, CD10aCase-Control Studies10aEndothelial Protein C Receptor10aFemale10aGenotype10aHumans10aLogistic Models10aMale10aMiddle Aged10aOdds Ratio10aPolymorphism, Genetic10aProspective Studies10aReceptors, Cell Surface10aRisk10aVenous Thromboembolism1 aYamagishi, Kazumasa1 aCushman, Mary1 aHeckbert, Susan, R1 aTsai, Michael, Y1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/108002960nas a2200445 4500008004100000022001400041245008700055210006900142260001300211300001000224490000600234520173600240653001601976653000901992653002202001653001002023653002602033653001402059653002202073653004002095653001102135653001602146653001102162653001802173653000902191653002302200653001502223653002802238653002402266653002102290653001602311653001802327100002502345700002402370700002102394700002202415700002102437700002002458856003602478 2009 eng d a1942-008000aLeft atrial volume and geometry in healthy aging: the Cardiovascular Health Study.0 aLeft atrial volume and geometry in healthy aging the Cardiovascu c2009 Jul a282-90 v23 aBACKGROUND: The left atrium is a validated marker of clinical and subclinical cardiovascular disease. Left atrial enlargement is often seen among older individuals; however, there are few population-based data regarding normal left atrial size among older persons, especially from those who are healthy, and from women. Furthermore, because the left atrium is a 3D structure, the commonly used parasternal long-axis diastolic diameter often underdiagnoses left atrial enlargement.
METHODS AND RESULTS: We evaluated left atrial size in 230 healthy participants (mean age, 76+/-5 years) free of prevalent cardiac disease, rhythm abnormality, hypertension, and diabetes selected from the Cardiovascular Health Study, a prospective community-based study of risk factors for cardiovascular disease in 5888 elderly participants. In addition to the standard long-axis measurement, we obtained left atrial superoinferior and lateral diameters and used these dimensions to estimate left atrial volume. These measurements were used to generate reference ranges for determining left atrial enlargement in older men and women, based on the 95% percentiles of the left atrial dimensions in healthy participants, both unadjusted, and after adjustment for age, height, and weight. In healthy elderly subjects, indices of left atrial size do not correlate with age or height but with weight and other measures of body build.
CONCLUSIONS: These data provide normative reference values for left atrial size in healthy older women and men. The results should be useful for refining diagnostic criteria for left atrial dilation in the older population and may be relevant for cardiovascular risk stratification.
10aAge Factors10aAged10aAged, 80 and over10aAging10aAtrial Function, Left10aBody Size10aBody Surface Area10aEchocardiography, Three-Dimensional10aFemale10aHeart Atria10aHumans10aLinear Models10aMale10aModels, Biological10aOrgan Size10aPopulation Surveillance10aProspective Studies10aReference Values10aSex Factors10aUnited States1 aAurigemma, Gerard, P1 aGottdiener, John, S1 aArnold, Alice, M1 aChinali, Marcello1 aHill, Jeffrey, C1 aKitzman, Dalane uhttps://chs-nhlbi.org/node/113603823nas a2200361 4500008004100000022001400041245010900055210006900164260001600233300001200249490000800261520277400269653001703043653000903060653002203069653003003091653001103121653001103132653001403143653001503157653000903172653005303181653002403234653001703258653001803275100002503293700002003318700002403338700001803362700002403380700002103404856003603425 2009 eng d a1538-367900aLifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study.0 aLifestyle risk factors and newonset diabetes mellitus in older a c2009 Apr 27 a798-8070 v1693 aBACKGROUND: The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults.
METHODS: We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989-1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73 [6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels.
RESULTS: During 34,539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35% lower (relative risk, 0.65; 95% confidence interval, 0.59-0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes (relative risk, 0.18; 95% confidence interval, 0.06-0.56) compared with all other participants. When absence of adiposity (either body mass index <25 or waist circumference < or =88/92 cm for women/men) was added to the other 4 low-risk lifestyle factors, incidence of diabetes was 89% lower (relative risk, 0.11; 95% confidence interval, 0.01-0.76). Overall, 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors. Associations were slightly attenuated, but still highly significant, for incident diabetes defined by medication use or glucose level.
CONCLUSION: Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus.
10aAge of Onset10aAged10aAged, 80 and over10aDiabetes Mellitus, Type 210aFemale10aHumans10aIncidence10aLife Style10aMale10aNational Heart, Lung, and Blood Institute (U.S.)10aProspective Studies10aRisk Factors10aUnited States1 aMozaffarian, Dariush1 aKamineni, Aruna1 aCarnethon, Mercedes1 aDjoussé, Luc1 aMukamal, Kenneth, J1 aSiscovick, David uhttps://chs-nhlbi.org/node/109503185nas a2200469 4500008004100000022001400041245013300055210006900188260001300257300001100270490000600281520182900287653005102116653000902167653001502176653002302191653001102214653001502225653001802240653001102258653001402269653002702283653001802310653002602328653000902354653002802363653003202391653002402423653002002447653001702467653001702484653001802501100001902519700001702538700002502555700001902580700002402599700002002623700001802643700001802661856003602679 2009 eng d a1941-329700aLipoprotein-associated phospholipase A(2) and risk of congestive heart failure in older adults: the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 and risk of congestive he c2009 Sep a429-360 v23 aBACKGROUND: Inflammation may be a causative factor in congestive heart failure (CHF). Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammation marker associated with vascular risk. One previous study showed an association of Lp-PLA(2) activity with CHF risk, but there were only 94 CHF cases and Lp-PLA(2) antigen, which is available clinically in the United States, was not measured.
METHODS AND RESULTS: We measured baseline Lp-PLA(2) antigen and activity in 3991 men and women without baseline CHF or cardiovascular disease who were participating in the Cardiovascular Health Study, a prospective observational study of adults 65 years or older. Cox proportional hazards models adjusted for age, sex, clinic site, race, low-density and high-density lipoprotein cholesterol, body mass index, systolic and diastolic blood pressure, hypertension, smoking status, pack-years, and diabetes were used to calculate hazard ratios and 95% CIs for incident CHF. Further models adjusted for coronary disease events during follow-up and C-reactive protein. Eight hundred twenty-nine participants developed CHF during 12.1 years. Adjusted hazard ratios for CHF with Lp-PLA(2) in the fourth compared with the first quartile were 1.44 (95% CI, 1.16 to 1.79) for Lp-PLA(2) antigen and 1.06 (95% CI, 0.84 to 1.32) for activity. Adjustment for incident coronary disease attenuated the hazard ratio for Lp-PLA(2) antigen to 1.26 (95% CI, 1.02 to 1.57), adjustment for C-reactive protein had minimal impact.
CONCLUSIONS: Lp-PLA(2) antigen was associated with risk of future CHF in older people, independent of CHF and coronary risk factors, and partly mediated by coronary disease events. Further clinical and basic research is needed to better understand the role of Lp-PLA(2) in CHF.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aBiomarkers10aC-Reactive Protein10aFemale10aFibrinogen10aHeart Failure10aHumans10aIncidence10aInflammation Mediators10aInterleukin-610aKaplan-Meier Estimate10aMale10aPopulation Surveillance10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aSuzuki, Takeki1 aSolomon, Cam1 aJenny, Nancy, Swords1 aTracy, Russell1 aNelson, Jeanenne, J1 aPsaty, Bruce, M1 aFurberg, Curt1 aCushman, Mary uhttps://chs-nhlbi.org/node/113503228nas a2200409 4500008004100000022001400041245014600055210006900201260001300270300001200283490000700295520200200302653000902304653002302313653001902336653001602355653002402371653003802395653001102433653001102444653002502455653000902480653001602489653002002505653002002525653002902545653004702574100002302621700001702644700002202661700001702683700001902700700002102719700002202740700002002762856003602782 2009 eng d a0161-810500aLongitudinal evaluation of sleep-disordered breathing and sleep symptoms with change in quality of life: the Sleep Heart Health Study (SHHS).0 aLongitudinal evaluation of sleepdisordered breathing and sleep s c2009 Aug a1049-570 v323 aSTUDY OBJECTIVES: Findings from population studies evaluating the progression and incidence of sleep disordered breathing have shown evidence of a longitudinal increase in the severity of sleep disordered breathing. The present study evaluates the association among changes in sleep disordered breathing, sleep symptoms, and quality of life over time.
DESIGN: Prospective cohort study. Data were from the Sleep Heart Health Study.
SETTING: Multicenter study.
PARTICIPANTS: Three thousand seventy-eight subjects aged 40 years and older from the baseline and follow-up examination cycles were included.
MEASUREMENTS: The primary outcomes were changes in the Physical Component Summary and Mental Component Summary scales obtained from the Medical Outcomes Study Short-Form Health Survey. The primary exposure was change in the respiratory disturbance index obtained from unattended overnight polysomnograms performed approximately 5 years apart. Other covariates included measures of excessive daytime sleepiness and difficulty initiating and maintaining sleep.
RESULTS: Mean respiratory disturbance index increased from 8.1 +/- 11 SD at baseline to 10.9 +/- 14 (P < 0.0001) at follow-up. The mean Physical Component Summary and Mental Component Summary scores were 48.5 and 54.1 at baseline and 46.3 and 54.8 at follow-up. No associations between change in respiratory disturbance index and changes in Physical Component Summary or Mental Component Summary scores were seen. However, worsening of difficulty initiating and maintaining sleep and excessive daytime sleepiness were significantly associated with lower quality of life.
CONCLUSIONS: A slight increase in severity of sleep disordered breathing was seen over 5 years; this was not associated with worsening of quality of life. However, subjective symptoms of quality of sleep and daytime sleepiness were associated with declining quality of life.
10aAged10aAttitude to Health10aCohort Studies10aComorbidity10aDisease Progression10aDisorders of Excessive Somnolence10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aPolysomnography10aQuality of Life10aSleep Apnea, Obstructive10aSleep Initiation and Maintenance Disorders1 aSilva, Graciela, E1 aAn, Ming-Wen1 aGoodwin, James, L1 aShahar, Eyal1 aRedline, Susan1 aResnick, Helaine1 aBaldwin, Carol, M1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/112503520nas a2200565 4500008004100000022001400041245009200055210006900147260001300216300001100229490000700240520195400247653003102201653001602232653000902248653002202257653002202279653001402301653002802315653002002343653001902363653001602382653002802398653001102426653002202437653000902459653002502468653001802493653001902511653001102530653000902541653002302550653002702573653003202600653001802632653001702650653001802667100002002685700002102705700002202726700001902748700001802767700002402785700002002809700002802829700002302857700002002880700001802900856003602918 2009 eng d a1532-541500aLong-term function in an older cohort--the cardiovascular health study all stars study.0 aLongterm function in an older cohortthe cardiovascular health st c2009 Mar a432-400 v573 aOBJECTIVES: To evaluate shared and unique risk factors for maintaining physical and cognitive function into the ninth decade and beyond.
DESIGN: Longitudinal cohort study.
SETTING: Four U.S. communities.
PARTICIPANTS: One thousand six hundred seventy-seven participants in the Cardiovascular Health Study All Stars Study, assessed in 2005/06. Median age was 85 (range 77-102), 66.5% were women, and 16.6% were black.
MEASUREMENTS: Intact function was defined as no difficulty with any activities of daily living and a score of 80 or higher on the Modified Mini-Mental State Examination. Baseline characteristics assessed in 1992/93 included demographics, behavioral health factors, chronic disease history, subclinical disease markers, cardiovascular risk factors, and inflammatory markers. Multinomial logistic regression was used to compare risk for physical disability, cognitive impairment,and combined impairments with no functional impairment.
RESULTS: Of the 1,677 participants evaluated in both domains, 891 (53%) were functionally intact. Continuous measures of function, including the Digit Symbol Substitution Test and gait speed, showed that all groups, including the most functional, had declined over time. The functional group had less decline but also tended to have higher starting values. Functional individuals had a higher baseline health profile than those with either or cognitive impairment or both impairments combined. Women and individuals with greater weight had higher rates of physical impairment but not cognitive impairment. Risk factors common to both types of impairment included cardiovascular disease and hypertension.
CONCLUSION: Intact function was found in only approximately half of these older adults in the ninth decade and beyond. High baseline function and low vascular disease risk characterized functional aging.
10aActivities of Daily Living10aAge Factors10aAged10aAged, 80 and over10aAlzheimer Disease10aAttention10aCardiovascular Diseases10aChronic Disease10aCohort Studies10aComorbidity10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aGait10aGeriatric Assessment10aHand Strength10aHealth Surveys10aHumans10aMale10aMemory, Short-Term10aMental Status Schedule10aProportional Hazards Models10aPsychometrics10aRisk Factors10aUnited States1 aNewman, Anne, B1 aArnold, Alice, M1 aSachs, Michael, C1 aIves, Diane, G1 aCushman, Mary1 aStrotmeyer, Elsa, S1 aDing, Jingzhong1 aKritchevsky, Stephen, B1 aChaves, Paulo, H M1 aFried, Linda, P1 aRobbins, John uhttps://chs-nhlbi.org/node/107503237nas a2200481 4500008004100000022001400041245007900055210006900134260001600203300001100219490000800230520194800238653001002186653000902196653001502205653001502220653002102235653001102256653001102267653000902278653001602287653003202303653002002335653001702355653001602372653001202388100002102400700001702421700002102438700001502459700001802474700002402492700001902516700001902535700002802554700002602582700003002608700002702638700001902665700001702684700001802701856003602719 2009 eng d a1539-370400aMeta-analysis: retinal vessel caliber and risk for coronary heart disease.0 aMetaanalysis retinal vessel caliber and risk for coronary heart c2009 Sep 15 a404-130 v1513 aBACKGROUND: Retinal vessel caliber may be a novel marker of coronary heart disease (CHD) risk. However, the sex-specific effect, magnitude of association, and effect independent of traditional CHD disease risk factors remain unclear.
PURPOSE: To determine the association between retinal vessel caliber and risk for CHD.
DATA SOURCES: Relevant studies in any language identified through MEDLINE (1950 to June 2009) and EMBASE (1950 to June 2009) databases.
STUDY SELECTION: Studies were included if they examined a general population, measured retinal vessel caliber from retinal photographs, and documented CHD risk factors and incident CHD events.
DATA EXTRACTION: 6 population-based prospective cohort studies provided data for individual participant meta-analysis.
DATA SYNTHESIS: Proportional hazards models, adjusted for traditional CHD risk factors, were constructed for retinal vessel caliber and incident CHD in women and men. Among 22,159 participants who were free of CHD and followed for 5 to 14 years, 2219 (10.0%) incident CHD events occurred. Retinal vessel caliber changes (wider venules and narrower arterioles) were each associated with an increased risk for CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95% CI, 1.06 to 1.26] per 20-microm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per 20-microm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10] per 20-microm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20-microm decrease in arteriolar caliber). Women without hypertension or diabetes had higher hazard ratios.
LIMITATION: Error in the measurement of retinal vessel caliber and Framingham variables was not taken into account.
CONCLUSION: Retinal vessel caliber changes were independently associated with an increased risk for CHD events in women.
10aAdult10aAged10aArterioles10aBiomarkers10aCoronary Disease10aFemale10aHumans10aMale10aMiddle Aged10aProportional Hazards Models10aRetinal Vessels10aRisk Factors10aSex Factors10aVenules1 aMcGeechan, Kevin1 aLiew, Gerald1 aMacaskill, Petra1 aIrwig, Les1 aKlein, Ronald1 aKlein, Barbara, E K1 aWang, Jie, Jin1 aMitchell, Paul1 aVingerling, Johannes, R1 aDejong, Paulus, T V M1 aWitteman, Jacqueline, C M1 aBreteler, Monique, M B1 aShaw, Jonathan1 aZimmet, Paul1 aWong, Tien, Y uhttps://chs-nhlbi.org/node/112902923nas a2200397 4500008004100000022001400041245011500055210006900170260001300239300001100252490000600263520181100269653003002080653001802110653001902128653002002147653001902167653001102186653001502197653001102212653001102223653002502234653000902259653002302268653003202291653001702323653002702340100001802367700001502385700001802400700001802418700001702436700001902453700001702472856003602489 2009 eng d a1538-783600aMetabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology.0 aMetabolic syndrome and risk of venous thromboembolism Longitudin c2009 May a746-510 v73 aSUMMARY BACKGROUND: In a recent case-control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among controls. We tested the hypothesis that the incidence of non-cancer-related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE.
METHODS: A total of 20 374 middle-aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Investigation of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined using ATP III guidelines, including >or=3 of the following components: abdominal obesity, elevated blood pressure, low HDL-cholesterol, high triglycerides and high glucose. Because sex modified the relation between MetSyn and VTE (p(interaction) = 0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non-cancer-related VTE, adjusting for potential confounders.
RESULTS: Incident VTE (n = 358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR) = 1.84, 95% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95% CI = 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95% CI = 1.24, 2.34, in women), with no additional contribution by the other MetSyn components.
CONCLUSION: Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.
10aBlood Coagulation Factors10aBlood Glucose10aBlood Pressure10aBody Mass Index10aCohort Studies10aFemale10aFibrinogen10aHumans10aLipids10aLongitudinal Studies10aMale10aMetabolic Syndrome10aProportional Hazards Models10aRisk Factors10aVenous Thromboembolism1 aSteffen, L, M1 aCushman, M1 aPeacock, J, M1 aHeckbert, S R1 aJacobs, D, R1 aRosamond, W, D1 aFolsom, A, R uhttps://chs-nhlbi.org/node/107303301nas a2200433 4500008004100000022001400041245008900055210006900144260001300213300001100226490000700237520210800244653000902352653002202361653001002383653002202393653001802415653002002433653002302453653003202476653001102508653001102519653002502530653003102555653000902586653001602595653001202611653002402623653000902647653002202656100002802678700002102706700002002727700001702747700002202764700002002786700002502806856003602831 2009 eng d a1538-368700aMidlife and late-life obesity and the risk of dementia: cardiovascular health study.0 aMidlife and latelife obesity and the risk of dementia cardiovasc c2009 Mar a336-420 v663 aBACKGROUND: While high adiposity in middle age appears to be related to greater dementia risk, studies exploring this association in the elderly are conflicting.
OBJECTIVE: To evaluate associations between midlife and late-life obesity and risk of dementia.
DESIGN: Prospective study with mean follow-up of 5.4 years (1992-1994 through 1999).
SETTING: Community-dwelling sample in 4 US sites recruited from Medicare eligibility files.
PARTICIPANTS: A total of 2798 adults without dementia (mean age, 74.7 years; 59.1% women) participating in the Cardiovascular Health Study who underwent magnetic resonance imaging were measured for height and weight at baseline at age 65 years or older (late life), and self-reported weight at age 50 years (midlife). Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was calculated at both times.
MAIN OUTCOME MEASURES: Dementia, Alzheimer disease, and vascular dementia classified by a multidisciplinary committee using standardized criteria.
RESULTS: Classification resulted in 480 persons with incident dementia, 245 with Alzheimer disease (no vascular dementia), and 213 with vascular dementia (with or without Alzheimer disease). In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI.
CONCLUSION: These results help explain the "obesity paradox" as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability.
10aAged10aAged, 80 and over10aAging10aAlzheimer Disease10aAnthropometry10aBody Mass Index10aDementia, Vascular10aEvaluation Studies as Topic10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMiddle Aged10aObesity10aProspective Studies10aRisk10aSurvival Analysis1 aFitzpatrick, Annette, L1 aKuller, Lewis, H1 aLopez, Oscar, L1 aDiehr, Paula1 aO'Meara, Ellen, S1 aLongstreth, W T1 aLuchsinger, José, A uhttps://chs-nhlbi.org/node/108503130nas a2200325 4500008004100000022001400041245010800055210006900163260001300232300001100245490000800256520220200264653000902466653002202475653002202497653001002519653003202529653002402561653001102585653001102596653003102607653000902638100001702647700002002664700002402684700002102708700002102729700001802750856003602768 2009 eng d a1527-131500aMild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging.0 aMild cognitive impairment and alzheimer disease patterns of alte c2009 Mar a856-660 v2503 aPURPOSE: To examine regional cerebral blood flow (rCBF) in incident mild cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous arterial spin-labeling (CASL) magnetic resonance (MR) imaging.
MATERIALS AND METHODS: This study was approved by the local institutional review board and was compliant with HIPAA regulations. Informed consent was obtained. rCBF was measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were participating in a longitudinal epidemiologic study. Multisection CASL MR imaging with alternating single and double adiabatic inversion pulses and ramp-sampled echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel-level rCBF was compared among groups by using an analysis of variance design; clusters of voxels with significant group differences were identified. Multiple regression models controlled for age, sex, and presence of hypertension and related the mean rCBF in those clusters to the presence of MCI and AD.
RESULTS: MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P = .01) with extension to the medial precuneus compared with that in control subjects. MCI patients had increased rCBF in the left hippocampus (P < .001), right amygdala (P = .007), and rostral head of the right caudate nucleus and ventral putamen and globus pallidus (P = .003) compared with that in control subjects. AD patients had decreased rCBF relative to that in control subjects and MCI patients in the left inferior parietal (P = .005), left lateral frontal (P < .001), left superior temporal (P = .001), and left orbitofrontal (P = .003) cortices. AD patients had increased rCBF in the right anterior cingulate gyrus (P = .02) compared with that in control subjects.
CONCLUSION: The transition from normal cognition to AD is associated with dynamic pathologic processes in the brain, and this is reflected by both decreases and increases in rCBF. Increases in rCBF suggest a cellular and vascular compensatory process associated with incipient AD.
SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2503080751/DC1.
10aAged10aAged, 80 and over10aAlzheimer Disease10aBrain10aCerebrovascular Circulation10aCognition Disorders10aFemale10aHumans10aMagnetic Resonance Imaging10aMale1 aDai, Weiying1 aLopez, Oscar, L1 aCarmichael, Owen, T1 aBecker, James, T1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/107103239nas a2200481 4500008004100000022001400041245010600055210006900161260000900230300001000239490000600249520187600255653004102131653001502172653001002187653002202197653000902219653002702228653002402255653001802279653004002297653001102337653003402348653001902382653001502401653002302416653001102439653001802450653002702468653000902495653001602504653003602520653001602556653001602572100001902588700001602607700001502623700002002638700001602658700002102674700002602695856003602721 2009 eng d a1932-620300aMultiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.0 aMultiple independent genetic factors at NOS1AP modulate the QT i c2009 ae43330 v43 aExtremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.
10aAdaptor Proteins, Signal Transducing10aAdolescent10aAdult10aAfrican Americans10aAged10aDeath, Sudden, Cardiac10aElectrocardiography10aEthnic Groups10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHeart Diseases10aHeart Rate10aHispanic Americans10aHumans10aLinear Models10aLinkage Disequilibrium10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aSex Factors10aYoung Adult1 aArking, Dan, E1 aKhera, Amit1 aXing, Chao1 aKao, Linda, W H1 aPost, Wendy1 aBoerwinkle, Eric1 aChakravarti, Aravinda uhttps://chs-nhlbi.org/node/107404323nas a2201033 4500008004100000022001400041245011200055210006900167260001300236300001300249490000600262520134000268653000901608653002001617653001901637653004001656653001101696653003801707653003401745653001101779653000901790653001601799653002601815653001201841653003601853653002401889100002601913700002501939700001901964700001901983700002202002700001202024700002302036700002102059700001902080700002402099700002002123700002202143700002102165700002502186700002402211700002302235700002602258700002102284700001902305700002302324700002102347700002102368700002202389700002202411700002202433700002002455700002202475700001602497700002002513700002002533700002202553700002602575700001602601700002302617700002202640700001602662700001602678700002502694700001902719700002102738700001902759700002402778700002402802700003002826700002702856700002202883700002402905700001902929700001902948700002602967700002802993700003003021700001903051700002203070700002403092700002603116700002303142700002303165700002503188700002103213700001903234856003603253 2009 eng d a1553-740400aNRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.0 aNRXN3 is a novel locus for waist circumference a genomewide asso c2009 Jun ae10005390 v53 aCentral abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance. In stage 1, 31,373 individuals of Caucasian descent from eight cohort studies confirmed the role of FTO and MC4R and identified one novel locus associated with WC in the neurexin 3 gene [NRXN3 (rs10146997, p = 6.4x10(-7))]. The association with NRXN3 was confirmed in stage 2 by combining stage 1 results with those from 38,641 participants in the GIANT consortium (p = 0.009 in GIANT only, p = 5.3x10(-8) for combined analysis, n = 70,014). Mean WC increase per copy of the G allele was 0.0498 z-score units (0.65 cm). This SNP was also associated with body mass index (BMI) [p = 7.4x10(-6), 0.024 z-score units (0.10 kg/m(2)) per copy of the G allele] and the risk of obesity (odds ratio 1.13, 95% CI 1.07-1.19; p = 3.2x10(-5) per copy of the G allele). The NRXN3 gene has been previously implicated in addiction and reward behavior, lending further evidence that common forms of obesity may be a central nervous system-mediated disorder. Our findings establish that common variants in NRXN3 are associated with WC, BMI, and obesity.
10aAged10aBody Mass Index10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aNerve Tissue Proteins10aObesity10aPolymorphism, Single Nucleotide10aWaist Circumference1 aHeard-Costa, Nancy, L1 aZillikens, Carola, M1 aMonda, Keri, L1 aJohansson, Asa1 aHarris, Tamara, B1 aFu, Mao1 aHaritunians, Talin1 aFeitosa, Mary, F1 aAspelund, Thor1 aEiriksdottir, Gudny1 aGarcia, Melissa1 aLauner, Lenore, J1 aSmith, Albert, V1 aMitchell, Braxton, D1 aMcArdle, Patrick, F1 aShuldiner, Alan, R1 aBielinski, Suzette, J1 aBoerwinkle, Eric1 aBrancati, Fred1 aDemerath, Ellen, W1 aPankow, James, S1 aArnold, Alice, M1 aChen, Yii-Der Ida1 aGlazer, Nicole, L1 aMcKnight, Barbara1 aPsaty, Bruce, M1 aRotter, Jerome, I1 aAmin, Najaf1 aCampbell, Harry1 aGyllensten, Ulf1 aPattaro, Cristian1 aPramstaller, Peter, P1 aRudan, Igor1 aStruchalin, Maksim1 aVitart, Veronique1 aGao, Xiaoyi1 aKraja, Aldi1 aProvince, Michael, A1 aZhang, Qunyuan1 aAtwood, Larry, D1 aDupuis, Josée1 aHirschhorn, Joel, N1 aJaquish, Cashell, E1 aO'Donnell, Christopher, J1 aVasan, Ramachandran, S1 aWhite, Charles, C1 aAulchenko, Yurii, S1 aEstrada, Karol1 aHofman, Albert1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aWitteman, Jacqueline, C M1 aOostra, Ben, A1 aKaplan, Robert, C1 aGudnason, Vilmundur1 aO'Connell, Jeffrey, R1 aBorecki, Ingrid, B1 aDuijn, Cornelia, M1 aCupples, Adrienne, L1 aFox, Caroline, S1 aNorth, Kari, E uhttps://chs-nhlbi.org/node/110702964nas a2200385 4500008004100000022001400041245014300055210006900198260001600267300001200283490000800295520179300303653000902096653002202105653002402127653001102151653001102162653001602173653002502189653000902214653003102223653002202254653003002276653001502306653003202321653001702353100002302370700002402393700002302417700002702440700002702467700002402494700002402518856003602542 2009 eng d a1524-453900aN-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study.0 aNterminal proBtype natriuretic peptide is a major predictor of t c2009 Nov 03 a1768-740 v1203 aBACKGROUND: Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and healthcare expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, AF, and mortality.
METHODS AND RESULTS: The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5445 Cardiovascular Health Study participants with the use of relative risk regression for predicting prevalent AF and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95% confidence interval, 17.9 to 913.3; P<0.001) and adjusted prevalence ratio of 147 for the highest quintile (95% confidence interval, 20.4 to 1064.3; P<0.001) compared with the lowest. After a median follow-up of 10 years (maximum of 16 years), there were 1126 cases of incident AF (a rate of 2.2 per 100 person-years). NT-proBNP was highly predictive of incident AF, with an unadjusted hazard ratio of 5.2 (95% confidence interval, 4.3 to 6.4; P<0.001) for the development of AF for the highest quintile compared with the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes mellitus, and heart failure, with an adjusted hazard ratio of 4.0 (95% confidence interval, 3.2 to 5.0; P<0.001).
CONCLUSIONS: In a community-based population of older adults, NT-proBNP was a remarkable predictor of incident AF, independent of any other previously described risk factor.
10aAged10aAged, 80 and over10aAtrial Fibrillation10aFemale10aHumans10aImmunoassay10aLongitudinal Studies10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aPredictive Value of Tests10aPrevalence10aProportional Hazards Models10aRisk Factors1 aPatton, Kristen, K1 aEllinor, Patrick, T1 aHeckbert, Susan, R1 aChristenson, Robert, H1 aDeFilippi, Christopher1 aGottdiener, John, S1 aKronmal, Richard, A uhttps://chs-nhlbi.org/node/113803050nas a2200445 4500008004100000022001400041245006000055210005900115260001300174300001200187490000700199520190000206653000902106653001002115653002102125653002002146653002002166653001902186653001502205653001502220653001102235653003102246653001102277653001102288653002002299653002502319653000902344653001202353653001702365100002002382700001602402700002002418700001902438700002102457700002002478700002402498700002402522700002202546856003602568 2009 eng d a1523-683800aObesity and change in estimated GFR among older adults.0 aObesity and change in estimated GFR among older adults c2009 Dec a1043-510 v543 aBACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.
PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.
OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.
MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.
RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95% CI, 1.16-1.36) per 12 cm, and 1.14 (95% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.
LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.
CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.
10aAged10aAging10aBody Composition10aBody Mass Index10aChronic Disease10aCohort Studies10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLongitudinal Studies10aMale10aObesity10aRisk Factors1 ade Boer, Ian, H1 aKatz, Ronit1 aFried, Linda, F1 aIx, Joachim, H1 aLuchsinger, Jose1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/113102859nas a2200397 4500008004100000022001400041245014100055210006900196260001300265300001200278490000600290520171800296653001002014653000902024653001502033653003002048653002502078653001802103653001602121653001102137653004302148653001102191653000902202653001602211653003202227653002402259653001702283653001302300653001802313653002702331100001702358700001702375700001802392700001502410856003602425 2009 eng d a1538-783600aPeak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study.0 aPeak thrombin generation and subsequent venous thromboembolism t c2009 Oct a1639-480 v73 aBACKGROUND: Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin.
OBJECTIVES: We evaluated the relationship of basal peak thrombin generation with the risk of future venous thromboembolism (VTE), and determined whether associations were independent of other coagulation markers.
METHODS: The Longitudinal Investigation of Thromboembolism Etiology (LITE) study investigated VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case-control sample (434 cases and 1004 controls). Logistic regression was used to estimate the relationship of peak thrombin generation with VTE, adjusted for age, sex, race, center, and body mass index. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer.
RESULTS: Relative to the first quartile of peak thrombin generation, the odds ratio (OR) of VTE for those above the median was 1.74 [95% confidence interval (CI) 1.28-2.37]. The association was modestly attenuated by adjustment for FVIII and D-dimer (OR 1.47, 95% CI 1.05-2.05). Associations appeared to be stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with FV Leiden or low activated partial thromboplastin time.
CONCLUSIONS: In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independently of established VTE risk factors.
10aAdult10aAged10aBiomarkers10aBlood Coagulation Factors10aCase-Control Studies10aEthnic Groups10aFactor VIII10aFemale10aFibrin Fibrinogen Degradation Products10aHumans10aMale10aMiddle Aged10aPartial Thromboplastin Time10aProspective Studies10aRisk Factors10aThrombin10aUnited States10aVenous Thromboembolism1 aLutsey, P, L1 aFolsom, A, R1 aHeckbert, S R1 aCushman, M uhttps://chs-nhlbi.org/node/111902654nas a2200373 4500008004100000022001400041245007900055210006900134260001600203300001200219490000800231520161700239653000901856653001501865653001101880653003101891653001101922653002601933653002501959653000901984653001901993653002402012653001702036100003002053700001602083700002502099700002502124700001702149700001702166700001802183700002102201700002202222856003602244 2009 eng d a1538-367900aPhysical activity and rapid decline in kidney function among older adults.0 aPhysical activity and rapid decline in kidney function among old c2009 Dec 14 a2116-230 v1693 aBACKGROUND: Habitual physical activity (PA) has both physiologic and metabolic effects that may moderate the risk of kidney function decline. We tested the hypothesis that higher levels of PA are associated with a lower risk of kidney function decline using longitudinal data from a large cohort of older adults.
METHODS: We studied 4011 ambulatory participants aged 65 or older from the Cardiovascular Health Study (CHS) who completed at least 2 measurements of kidney function over 7 years. We calculated a PA score (range, 2-8) by summing kilocalories expended per week (ordinal score of 1-5 from quintiles of kilocalories per week) and walking pace (ordinal score for categories of <2, 2-3, and >3 mph). Rapid decline in kidney function decline (RDKF) was defined by loss of more than 3.0 mL/min/1.73 m(2) per year in glomerular filtration rate, which we estimated by using longitudinal measurements of cystatin C levels.
RESULTS: A total of 958 participants had RDKF (23.9%; 4.1 events per 100 person-years). The estimated risk of RDKF was 16% in the highest PA group (score of 8) and 30% in the lowest PA group (score of 2). After multivariate adjustment, we found that the 2 highest PA groups (scores of 7-8) were associated with a 28% lower risk of RDKF (95% confidence interval, 21%-41% lower risk) than the 2 lowest PA groups (score of 2-3). Greater kilocalories of leisure-time PA and walking pace were also each associated with a lower incidence of RDKF.
CONCLUSION: Higher levels of PA are associated with a lower risk of RDKF among older adults.
10aAged10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Function Tests10aLongitudinal Studies10aMale10aMotor Activity10aRenal Insufficiency10aTime Factors1 aRobinson-Cohen, Cassianne1 aKatz, Ronit1 aMozaffarian, Dariush1 aDalrymple, Lorien, S1 ade Boer, Ian1 aSarnak, Mark1 aShlipak, Mike1 aSiscovick, David1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/114802476nas a2200397 4500008004100000022001400041245007300055210006900128260001300197300001200210490000600222520144700228653000901675653002201684653001901706653002401725653001101749653001101760653000901771653002601780653001901806653000901825653001101834653002201845653001501867653002201882100002201904700001801926700001401944700001701958700001501975700001701990700002002007700001502027856003602042 2009 eng d a1538-783600aPlatelet count and the risk for thrombosis and death in the elderly.0 aPlatelet count and the risk for thrombosis and death in the elde c2009 Mar a399-4050 v73 aAIM: Our aim was to examine the association between platelet count and the incidence of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thrombosis, and mortality.
METHODS AND RESULTS: Platelet count was measured at baseline in 1989-1990 and at 3 years follow-up, or at baseline (for a newly recruited group) in 1992-1993 in 5766 community-dwelling individuals aged 65 years and older (mean age at baseline, 73 years). During 12-15 years of follow-up, there were 821 incident myocardial infarctions, 807 ischemic strokes, 161 hemorrhagic strokes, 159 venous thrombotic events, and 3413 participants died. Platelet count was not associated with the occurrence of myocardial infarction, ischemic or hemorrhagic stroke, venous thrombosis, or cardiovascular mortality. Non-cardiovascular mortality was higher among both participants with low and with high platelet count. Adjusted non-cardiovascular mortality rates for platelet counts below 100, 100-199, 300-399, and above 400 x 10(9) L(-1) relative to the reference mortality rate in participants with platelet count values between 200 and 299 x 10(9) L(-1) were 1.89 (1.21-2.96), 1.08 (0.98-1.20), 1.20 (1.06-1.37), and 1.47 (1.14-1.90), respectively.
CONCLUSION: Platelet counts were not associated with vascular outcomes but low and high platelet counts were associated with non-cardiovascular mortality, including cancer mortality.
10aAged10aAged, 80 and over10aCause of Death10aCerebral Hemorrhage10aFemale10aHumans10aMale10aMyocardial Infarction10aPlatelet Count10aRisk10aStroke10aSurvival Analysis10aThrombosis10aVenous Thrombosis1 avan der Bom, J, G1 aHeckbert, S R1 aLumley, T1 aHolmes, C, E1 aCushman, M1 aFolsom, A, R1 aRosendaal, F, R1 aPsaty, B M uhttps://chs-nhlbi.org/node/106802897nas a2200385 4500008004100000022001400041245012600055210006900181260001300250300001000263490000700273520177200280653001002052653000902062653001902071653001602090653002802106653001102134653001102145653000902156653001602165653002002181653002402201653002002225653002702245653004702272653002402319100002302343700001902366700002202385700002402407700002002431700002402451856003602475 2009 eng d a0161-810500aPolysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study.0 aPolysomnographic and healthrelated quality of life correlates of c2009 Jun a772-80 v323 aSTUDY OBJECTIVES: Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS.
DESIGN: Cross-sectional observational study.
SETTING: Community-based.
PARTICIPANTS: 3433 older men and women.
INTERVENTIONS: None.
MEASUREMENTS AND RESULTS: RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring > or = five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5-15 days per month to 6-7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains.
CONCLUSIONS: These novel PSG data from a nonclinical, community-based sample of individuals with RLS document sleep disturbance in the home even in individuals with intermittent symptoms.
10aAdult10aAged10aCohort Studies10aComorbidity10aCross-Sectional Studies10aFemale10aHumans10aMale10aMiddle Aged10aPolysomnography10aProspective Studies10aQuality of Life10aRestless Legs Syndrome10aSleep Initiation and Maintenance Disorders10aStatistics as Topic1 aWinkelman, John, W1 aRedline, Susan1 aBaldwin, Carol, M1 aResnick, Helaine, E1 aNewman, Anne, B1 aGottlieb, Daniel, J uhttps://chs-nhlbi.org/node/110502976nas a2200469 4500008004100000022001400041245008400055210006900139260001600208300001000224490000700234520170800241653001601949653000901965653002201974653002101996653002202017653002002039653002102059653001302080653002402093653001902117653002702136653001302163653001102176653002002187653002902207653001102236653002002247653000902267653003002276653002002306653001702326653002802343100001702371700001902388700001802407700001602425700001602441700001302457856003602470 2009 eng d a1526-632X00aPredicting risk of dementia in older adults: The late-life dementia risk index.0 aPredicting risk of dementia in older adults The latelife dementi c2009 Jul 21 a173-90 v733 aOBJECTIVE: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.
METHODS: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.
RESULTS: Subjects had a mean age of 76 years at baseline; 59% were women and 15% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23% of subjects with moderate scores and 56% of subjects with high scores.
CONCLUSIONS: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.
10aAge Factors10aAged10aAged, 80 and over10aAlcohol Drinking10aApolipoprotein E410aBody Mass Index10aCarotid Stenosis10aCerebrum10aCognition Disorders10aCohort Studies10aCoronary Artery Bypass10aDementia10aFemale10aGenetic Markers10aHealth Status Indicators10aHumans10aLogistic Models10aMale10aPredictive Value of Tests10aRisk Assessment10aRisk Factors10aRisk Reduction Behavior1 aBarnes, D, E1 aCovinsky, K, E1 aWhitmer, R, A1 aKuller, L H1 aLopez, O, L1 aYaffe, K uhttps://chs-nhlbi.org/node/110102919nas a2200445 4500008004100000022001400041245010200055210006900157260001300226300001100239490000700250520167600257653002201933653000901955653002201964653001001986653002301996653002802019653001902047653002802066653004002094653001102134653001702145653001802162653001102180653000902191653001602200653001502216653002402231653001202255653002602267653001802293100002102311700001802332700002302350700002602373700002202399700001602421856003602437 2009 eng d a1092-438800aPrevalence of hearing loss in Black and White elders: results of the Cardiovascular Health Study.0 aPrevalence of hearing loss in Black and White elders results of c2009 Aug a973-890 v523 aPURPOSE: The goal of this study was to determine the impact of age, gender, and race on the prevalence and severity of hearing loss in elder adults, aged 72-96 years, after accounting for income, education, smoking, and clinical and subclinical cardiovascular disease. Methods Air-conduction thresholds for standard and extended high-frequency pure-tones were obtained from a cohort of 548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and cardiovascular disease histories were obtained from the CHS database and were included as factors.
RESULTS: Hearing loss was more common and more severe for the participants in their 80s than for those in their 70s-the men more than the women and the White participants more than the Black participants. The inclusion of education, income, smoking, and cardiovascular disease (clinical and subclinical) histories as factors did not substantively impact the overall results.
CONCLUSION: Although the data reported in this article were cross-sectional and a cohort phenomenon might have been operational, they suggested that hearing loss is more substantive in the 8th than the 7th decade of life and that race and gender influence this decline in audition. Given the high prevalence in the aging population and the differences across groups, there is a clear need to understand the nature and causes of hearing loss across various groups in order to improve prevention and develop appropriate interventions.
10aAfrican Americans10aAged10aAged, 80 and over10aAging10aAuditory Threshold10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aEuropean Continental Ancestry Group10aFemale10aHearing Loss10aHearing Tests10aHumans10aMale10aOccupations10aPrevalence10aSex Characteristics10aSmoking10aSocioeconomic Factors10aUnited States1 aPratt, Sheila, R1 aKuller, Lewis1 aTalbott, Evelyn, O1 aMcHugh-Pemu, Kathleen1 aBuhari, Alhaji, M1 aXu, Xiaohui uhttps://chs-nhlbi.org/node/109303032nas a2200469 4500008004100000022001400041245010000055210006900155260001600224300001200240490000800252520174900260653001002009653001902019653002502038653002802063653001102091653002202102653001102124653001702135653001402152653000902166653001602175653001502191653002002206653001402226653002402240653001702264653002602281653001702307653001802324100002402342700001702366700002002383700002002403700002302423700001902446700002402465700002002489700001702509856003602526 2009 eng d a1535-497000aProspective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study.0 aProspective study of sleepdisordered breathing and hypertension c2009 Jun 15 a1159-640 v1793 aRATIONALE: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.
OBJECTIVES: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.
METHODS: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.
MEASUREMENTS AND MAIN RESULTS: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95% confidence interval, 0.93-2.47) does not exclude the possibility of a modest association.
CONCLUSIONS: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded.
10aAdult10aBlood Pressure10aConfidence Intervals10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aOdds Ratio10aPolysomnography10aPrognosis10aProspective Studies10aRisk Factors10aSleep Apnea Syndromes10aTime Factors10aUnited States1 aO'Connor, George, T1 aCaffo, Brian1 aNewman, Anne, B1 aQuan, Stuart, F1 aRapoport, David, M1 aRedline, Susan1 aResnick, Helaine, E1 aSamet, Jonathan1 aShahar, Eyal uhttps://chs-nhlbi.org/node/108302978nas a2200397 4500008004100000022001400041245013200055210006900187260001600256300001100272490000800283520181200291653002202103653001602125653000902141653002202150653001902172653003402191653004002225653001102265653001802276653001102294653001402305653000902319653003202328653001602360653001802376100002202394700001602416700002302432700002102455700002102476700002302497700002402520856003602544 2009 eng d a1879-191300aRace, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study).0 aRace gender and mortality in adults or 65 years of age with inci c2009 Apr 15 a1120-70 v1033 aIn patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults > or =65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15% to 20% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.
10aAfrican Americans10aAge Factors10aAged10aAged, 80 and over10aCohort Studies10aContinental Population Groups10aEuropean Continental Ancestry Group10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aProportional Hazards Models10aSex Factors10aUnited States1 aParashar, Susmita1 aKatz, Ronit1 aSmith, Nicholas, L1 aArnold, Alice, M1 aVaccarino, Viola1 aWenger, Nanette, K1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/109002675nas a2200445 4500008004100000022001400041245008300055210006900138260001300207300001200220490000700232520145100239653000901690653002201699653002801721653001501749653001501764653001101779653003101790653001801821653001101839653002501850653000901875653002601884653003301910653003301943653001701976653001101993653001702004653001802021100002402039700001602063700002202079700002102101700001702122700001702139700001702156700002002173856003602193 2009 eng d a1533-345000aRapid decline of kidney function increases cardiovascular risk in the elderly.0 aRapid decline of kidney function increases cardiovascular risk i c2009 Dec a2625-300 v203 aChronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C-based estimated GFR as >3 ml/min per 1.73 m(2)/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aPeripheral Vascular Diseases10aRenal Insufficiency, Chronic10aRisk Factors10aStroke10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aSiscovick, David1 aFried, Linda1 aNewman, Anne1 aRifkin, Dena1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/114402550nas a2200373 4500008004100000022001400041245009900055210006900154260000900223300001000232490000700242520153600249653001601785653000901801653001501810653001501825653002401840653001101864653003101875653001101906653001101917653002001928653000901948653001701957100002401974700001601998700002202014700002002036700002002056700002402076700002002100700002002120856003602140 2009 eng d a1421-967000aRate of kidney function decline in older adults: a comparison using creatinine and cystatin C.0 aRate of kidney function decline in older adults a comparison usi c2009 a171-80 v303 aBACKGROUND/AIMS: The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
METHODS: In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 +/- 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m(2)).
RESULTS: Mean annual eGFR loss as estimated from creatinine was 0.4 +/- 3.6 ml/min/1.73 m(2), with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 +/- 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16-1.65), 1.62 (1.31-1.99) and 2.96 (2.28-3.84) for participants aged 70-74, 75-79 and 80+ at baseline, compared with those aged 65-69.
CONCLUSION: In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
10aAge Factors10aAged10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aNewman, Anne, B1 aSiscovick, David, S1 aStevens, Lesley1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/108901428nas a2200517 4500008004100000022001400041245013100055210006900186260001300255300001100268490000600279653001500285653001000300653000900310653002200319653002500341653001900366653001100385653003200396653003800428653002200466653001500488653001500503653001100518653001400529653000900543653001400552653001600566653003600582653003100618653000900649653001800658653002200676653001600698100001500714700001800729700001700747700001600764700001500780700001800795700001400813700001500827700001700842700001500859856003600874 2009 eng d a1538-783600aReplication of findings on the association of genetic variation in 24 hemostasis genes and risk of incident venous thrombosis.0 aReplication of findings on the association of genetic variation c2009 Oct a1743-60 v710aAdolescent10aAdult10aAged10aAged, 80 and over10aCase-Control Studies10aCohort Studies10aFemale10aGenetic Association Studies10aGenetic Predisposition to Disease10aGenetic Variation10aHaplotypes10aHemostasis10aHumans10aIncidence10aMale10aMenopause10aMiddle Aged10aPolymorphism, Single Nucleotide10aReproducibility of Results10aRisk10aThrombophilia10aVenous Thrombosis10aYoung Adult1 aSmith, N L1 aWiggins, K, L1 aReiner, A, P1 aLange, L, A1 aCushman, M1 aHeckbert, S R1 aLumley, T1 aRice, K, M1 aFolsom, A, R1 aPsaty, B M uhttps://chs-nhlbi.org/node/112102551nas a2200385 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520145000294653000901744653002001753653001101773653003801784653001101822653001401833653000901847653002601856653001501882653001501897653002401912653001701936653001301953653001101966653001801977100001701995700002202012700001802034700002202052700001802074710003702092856003602129 2009 eng d a1873-258500aSibling history of myocardial infarction or stroke and risk of cardiovascular disease in the elderly: the Cardiovascular Health Study.0 aSibling history of myocardial infarction or stroke and risk of c c2009 Dec a858-660 v193 aPURPOSE: To assess the relationship between sibling history of myocardial infarction (MI) or stroke with cardiovascular disease (CVD) and risk factors in older adults.
METHODS: Prospective cohort study of 5,888 older adults participating in the Cardiovascular Health Study (CHS). History of MI and stroke in siblings was obtained by self-report. Participants with positive sibling histories were compared to those with negative histories to determine if prevalent or incident disease (coronary heart disease [CHD], MI, stroke, angina), subclinical CVD (carotid wall thickness, left ventricular mass, hypertension, diabetes, ankle-brachial index), CVD risk factors differed between groups.
RESULTS: More than 91% (n = 5,383) of CHS participants reported at least one sibling. Sibling history of MI was associated with increased disease prevalence (CHD, MI, angina) and incidence (CHD, angina). Sibling history of stroke was associated with increased disease prevalence (CHD, angina). Sibling history of either MI or stroke was associated with increased disease prevalence and incidence for CHD, MI and angina, more subclinical disease, and a higher CVD risk profile.
CONCLUSIONS: Sibling history of MI and stroke were markers of higher CVD risk status even in older adults. Of clinical importance, participants with positive sibling history have numerous risk factors amenable to intervention.
10aAged10aAtherosclerosis10aFemale10aGenetic Predisposition to Disease10aHumans10aIncidence10aMale10aMyocardial Infarction10aOdds Ratio10aPrevalence10aProspective Studies10aRisk Factors10aSiblings10aStroke10aUnited States1 aYanez, David1 aBurke, Gregory, L1 aManolio, Teri1 aGardin, Julius, M1 aPolak, Joseph1 aCHS Collaborative Research Group uhttps://chs-nhlbi.org/node/114602624nas a2200469 4500008004100000022001400041245008600055210006900141260001600210300001200226490000800238520131400246653003101560653000901591653002801600653002601628653001901654653002501673653002301698653001101721653001801732653001801750653001101768653002001779653000901799653002401808653002401832653001901856653002001875653001501895653002001910653001801930653001701948653002901965653001601994100002602010700001902036700002002055700002002075700002302095856003602118 2009 eng d a1476-625600aSleep-disordered breathing and frailty in the Cardiovascular Health Study Cohort.0 aSleepdisordered breathing and frailty in the Cardiovascular Heal c2009 Jul 15 a193-2020 v1703 aSleep-disordered breathing (SDB) is associated with pathophysiology that may influence the development and progression of frailty. Using data collected in 1995-1996, the authors explored the relation between SDB and components of frailty among 1,042 participants of the Cardiovascular Health Study. Diagnosis of SDB was based on the results of overnight polysomnography, and severe SDB was defined as an apnea-hypopnea index of >30 per hour of sleep. Slow walking speed, low grip strength, exhaustion, low physical activity, and unexplained weight loss were referred to as frailty indicator variables. There were 584 (56%) female and 458 (44%) male participants, and the mean age was 77 (standard deviation, 4) years. There was independent association between severe SDB and 1 or more frailty indicator variables (adjusted odds ratio = 4.85, 95% confidence interval: 1.40, 16.78), slow walking speed (adjusted odds ratio = 2.67, 95% confidence interval: 1.04, 6.84), and low grip strength (adjusted odds ratio = 3.29, 95% confidence interval: 1.36, 7.96) among female study participants. The finding of an independent association between SDB and frailty indicator variables among older women could have important implications in interventions aimed at preventing or delaying the progression of frailty.
10aActivities of Daily Living10aAged10aCardiovascular Diseases10aCardiovascular System10aCohort Studies10aConfidence Intervals10aExercise Tolerance10aFemale10aFrail Elderly10aHand Strength10aHumans10aLogistic Models10aMale10aMobility Limitation10aModels, Statistical10aMotor Activity10aMuscle Strength10aOdds Ratio10aPolysomnography10aPsychometrics10aRisk Factors10aSleep Apnea, Obstructive10aWeight Loss1 aEndeshaw, Yohannes, W1 aUnruh, Mark, L1 aKutner, Michael1 aNewman, Anne, B1 aBliwise, Donald, L uhttps://chs-nhlbi.org/node/110303483nas a2200457 4500008004100000022001400041245007400055210006900129260001300198300001300211490000600224520223200230653000902462653002802471653001102499653001102510653001202521653000902533653001602542653001502558653003202573653002402605653001702629653001602646653002602662653002202688100002302710700002002733700002202753700002402775700002002799700002402819700002302843700001902866700002402885700002102909700001702930700001902947700002302966856003602989 2009 eng d a1549-167600aSleep-disordered breathing and mortality: a prospective cohort study.0 aSleepdisordered breathing and mortality a prospective cohort stu c2009 Aug ae10001320 v63 aBACKGROUND: Sleep-disordered breathing is a common condition associated with adverse health outcomes including hypertension and cardiovascular disease. The overall objective of this study was to determine whether sleep-disordered breathing and its sequelae of intermittent hypoxemia and recurrent arousals are associated with mortality in a community sample of adults aged 40 years or older.
METHODS AND FINDINGS: We prospectively examined whether sleep-disordered breathing was associated with an increased risk of death from any cause in 6,441 men and women participating in the Sleep Heart Health Study. Sleep-disordered breathing was assessed with the apnea-hypopnea index (AHI) based on an in-home polysomnogram. Survival analysis and proportional hazards regression models were used to calculate hazard ratios for mortality after adjusting for age, sex, race, smoking status, body mass index, and prevalent medical conditions. The average follow-up period for the cohort was 8.2 y during which 1,047 participants (587 men and 460 women) died. Compared to those without sleep-disordered breathing (AHI: <5 events/h), the fully adjusted hazard ratios for all-cause mortality in those with mild (AHI: 5.0-14.9 events/h), moderate (AHI: 15.0-29.9 events/h), and severe (AHI: >or=30.0 events/h) sleep-disordered breathing were 0.93 (95% CI: 0.80-1.08), 1.17 (95% CI: 0.97-1.42), and 1.46 (95% CI: 1.14-1.86), respectively. Stratified analyses by sex and age showed that the increased risk of death associated with severe sleep-disordered breathing was statistically significant in men aged 40-70 y (hazard ratio: 2.09; 95% CI: 1.31-3.33). Measures of sleep-related intermittent hypoxemia, but not sleep fragmentation, were independently associated with all-cause mortality. Coronary artery disease-related mortality associated with sleep-disordered breathing showed a pattern of association similar to all-cause mortality.
CONCLUSIONS: Sleep-disordered breathing is associated with all-cause mortality and specifically that due to coronary artery disease, particularly in men aged 40-70 y with severe sleep-disordered breathing. Please see later in the article for the Editors' Summary.
10aAged10aCoronary Artery Disease10aFemale10aHumans10aHypoxia10aMale10aMiddle Aged10aOdds Ratio10aProportional Hazards Models10aProspective Studies10aRisk Factors10aSex Factors10aSleep Apnea Syndromes10aSurvival Analysis1 aPunjabi, Naresh, M1 aCaffo, Brian, S1 aGoodwin, James, L1 aGottlieb, Daniel, J1 aNewman, Anne, B1 aO'Connor, George, T1 aRapoport, David, M1 aRedline, Susan1 aResnick, Helaine, E1 aRobbins, John, A1 aShahar, Eyal1 aUnruh, Mark, L1 aSamet, Jonathan, M uhttps://chs-nhlbi.org/node/112202827nas a2200433 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520161000263653003101873653000901904653002801913653001501941653001501956653001101971653002201982653001102004653001402015653002002029653002502049653000902074653001502083653001702098653002602115653001202141653002602153653003102179100002002210700002002230700002102250700002102271700001902292700002402311700002202335856003602357 2009 eng d a1545-721400aSpousal suffering and partner's depression and cardiovascular disease: the Cardiovascular Health Study.0 aSpousal suffering and partners depression and cardiovascular dis c2009 Mar a246-540 v173 aOBJECTIVES: To assess the effects of suffering in a spouse on prevalent and incident psychiatric (depression) and physical morbidity (cardiovascular disease [CVD]) in their partner, controlling for known risk factors for depression and CVD.
DESIGN: Descriptive longitudinal study.
PARTICIPANTS: A total of 1,330 older married couples enrolled in the Cardiovascular Health Study, a large epidemiologic study of the elderly.
MEASUREMENTS: Predictor variables were physical, psychological, and existential/spiritual indicators of suffering. Primary outcomes were prevalent and incident depression and CVD.
RESULTS: Controlling for known risk factors for depression, the authors found a dose-response relationship between suffering in a spouse and concurrent depression in their partner as well as a relationship between suffering and the partner's future risk for depression. With respect to CVD, and controlling for subclinical CVD at baseline, husbands whose wives reported high levels of suffering also had higher rates of prevalent CVD, but there were no significant associations between wives suffering and husbands incident CVD. There were no associations between husbands' suffering and wives' prevalent or incident CVD.
CONCLUSION: Exposure to spousal suffering is an independent and unique source of distress in married couples that contributes to psychiatric and physical morbidity. More attention should be paid to the interpersonal effects of suffering in married couples and to its role in contributing to morbidity.
10aActivities of Daily Living10aAged10aCardiovascular Diseases10aCaregivers10aDepression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLogistic Models10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors10aSocioeconomic Factors10aSpouses10aStress, Psychological10aSurveys and Questionnaires1 aSchulz, Richard1 aBeach, Scott, R1 aHebert, Randy, S1 aMartire, Lynn, M1 aMonin, Joan, K1 aTompkins, Connie, A1 aAlbert, Steven, M uhttps://chs-nhlbi.org/node/110205120nas a2201681 4500008004100000022001400041245011700055210006900172260001600241300001200257490000700269520098300276653001901259653002401278653002101302653003701323653001101360653001501371653001101386653000901397653002701406653002401433110003701457700001701494700001501511700001701526700001701543700001701560700001001577700001701587700001601604700001701620700001501637700001401652700002001666700001901686700001701705700001501722700001501737700001501752700002301767700001701790700002001807700001901827700001901846700001401865700001601879700001501895700001401910700001201924700001501936700001801951700001801969700001701987700001902004700001402023700001202037700001702049700001702066700001702083700001802100700001402118700001602132700001402148700001302162700001502175700001702190700001202207700001802219700001802237700001902255700001502274700001602289700001602305700001402321700001402335700001602349700001602365700001702381700001802398700001902416700001702435700001702452700001602469700002002485700001202505700001602517700001302533700001102546700001502557700001402572700001202586700001502598700001802613700001502631700001902646700001502665700001602680700001602696700001702712700001902729700001502748700001502763700001502778700001402793700001602807700001802823700001902841700002202860700001702882700001602899700001802915700001902933700001602952700001402968700001602982700001602998700001503014700001903029700001703048700001403065700001803079700001503097700001603112700001703128700001203145700001703157700001503174700001503189700002003204700002303224700001503247700001703262700001703279700001403296700001903310700001403329700001403343700001603357700001503373700001403388856003603402 2009 eng d a0277-671500aSystematically missing confounders in individual participant data meta-analysis of observational cohort studies.0 aSystematically missing confounders in individual participant dat c2009 Apr 15 a1218-370 v283 aOne difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts
10aCohort Studies10aComputer Simulation10aCoronary Disease10aData Interpretation, Statistical10aFemale10aFibrinogen10aHumans10aMale10aMeta-Analysis as Topic10aModels, Statistical1 aFibrinogen Studies Collaboration1 aJackson, Dan1 aWhite, Ian1 aKostis, J, B1 aWilson, A, C1 aFolsom, A, R1 aWu, K1 aChambless, L1 aBenderly, M1 aGoldbourt, U1 aWilleit, J1 aKiechl, S1 aYarnell, J, W G1 aSweetnam, P, M1 aElwood, P, C1 aCushman, M1 aPsaty, B M1 aTracy, R P1 aTybjaerg-Hansen, A1 aHaverkate, F1 ade Maat, M, P M1 aThompson, S, G1 aFowkes, F, G R1 aLee, A, J1 aSmith, F, B1 aSalomaa, V1 aHarald, K1 aRasi, V1 aVahtera, E1 aJousilahti, P1 aD'Agostino, R1 aKannel, W, B1 aWilson, P, W F1 aTofler, G1 aLevy, D1 aMarchioli, R1 aValagussa, F1 aRosengren, A1 aWilhelmsen, L1 aLappas, G1 aEriksson, H1 aCremer, P1 aNagel, D1 aCurb, J, D1 aRodriguez, B1 aYano, K1 aSalonen, J, T1 aNyyssönen, K1 aTuomainen, T-P1 aHedblad, B1 aEngstrom, G1 aBerglund, G1 aLoewel, H1 aKoenig, W1 aHense, H, W1 aMeade, T, W1 aCooper, J, A1 aDe Stavola, B1 aKnottenbelt, C1 aMiller, G, J1 aCooper, J, A1 aBauer, K, A1 aRosenberg, R, D1 aSato, S1 aKitamura, A1 aNaito, Y1 aIso, H1 aSalomaa, V1 aHarald, K1 aRasi, V1 aVahtera, E1 aJousilahti, P1 aPalosuo, T1 aDucimetiere, P1 aAmouyel, P1 aArveiler, D1 aEvans, A, E1 aFerrieres, J1 aJuhan-Vague, I1 aBingham, A1 aSchulte, H1 aAssmann, G1 aCantin, B1 aLamarche, B1 aDesprés, J-P1 aDagenais, G, R1 aTunstall-Pedoe, H1 aLowe, G, D O1 aWoodward, M1 aBen-Shlomo, Y1 aDavey Smith, G1 aPalmieri, V1 aYeh, J, L1 aMeade, T, W1 aRudnicka, A1 aBrennan, P1 aKnottenbelt, C1 aCooper, J, A1 aRidker, P1 aRodeghiero, F1 aTosetto, A1 aShepherd, J1 aLowe, G, D O1 aFord, I1 aRobertson, M1 aBrunner, E1 aShipley, M1 aFeskens, E, J M1 aDi Angelantonio, E1 aKaptoge, S1 aLewington, S1 aLowe, G, D O1 aSarwar, N1 aThompson, S, G1 aWalker, M1 aWatson, S1 aWhite, I, R1 aWood, A, M1 aDanesh, J uhttps://chs-nhlbi.org/node/107903160nas a2200541 4500008004100000022001400041245007500055210006900130260001300199300001200212490000700224520168000231653001601911653000901927653002201936653001001958653002801968653001901996653002002015653001902035653001102054653002502065653001902090653001102109653002602120653000902146653001602155653003202171653002602203653002002229653003002249653001602279653002202295653001802317100002002335700002202355700002102377700002002398700002102418700001802439700002002457700002202477700002102499700002202520700002102542700001902563856003602582 2009 eng d a1758-535X00aTotal and cause-specific mortality in the cardiovascular health study.0 aTotal and causespecific mortality in the cardiovascular health s c2009 Dec a1251-610 v643 aBACKGROUND: Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.
METHODS: A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.
RESULTS: Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E epsilon4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.
CONCLUSIONS: In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.
10aAge Factors10aAged10aAged, 80 and over10aAging10aCardiovascular Diseases10aCause of Death10aChronic Disease10aCohort Studies10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aKaplan-Meier Estimate10aMale10aProbability10aProportional Hazards Models10aRetrospective Studies10aRisk Assessment10aSeverity of Illness Index10aSex Factors10aSurvival Analysis10aUnited States1 aNewman, Anne, B1 aSachs, Michael, C1 aArnold, Alice, M1 aFried, Linda, P1 aKronmal, Richard1 aCushman, Mary1 aPsaty, Bruce, M1 aHarris, Tamara, B1 aRobbins, John, A1 aBurke, Gregory, L1 aKuller, Lewis, H1 aLumley, Thomas uhttps://chs-nhlbi.org/node/112403143nas a2200457 4500008004100000022001400041245011900055210006900174260001300243300001200256490000700268520183100275653001602106653000902122653002202131653001002153653001502163653002802178653001902206653001902225653003502244653001102279653002502290653001102315653002502326653000902351653003002360653003202390653002002422653003002442653001602472653002202488653001802510100002102528700002202549700001802571700002002589700002002609700002002629856003602649 2009 eng d a1758-535X00aTrajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study.0 aTrajectories of dehydroepiandrosterone sulfate predict mortality c2009 Dec a1268-740 v643 aBACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual's ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging.
METHODS: Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged >or=65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points.
RESULTS: Overall, there was a slight decline in DHEAS levels over time (-0.013 microg/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p < .001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32-2.33) and extreme variability (HR 1.89, CI 1.47-2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88-1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p < .001).
CONCLUSIONS: Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.
10aAge Factors10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiovascular Diseases10aCause of Death10aCohort Studies10aDehydroepiandrosterone Sulfate10aFemale10aGeriatric Assessment10aHumans10aLongitudinal Studies10aMale10aPredictive Value of Tests10aProportional Hazards Models10aRisk Assessment10aSeverity of Illness Index10aSex Factors10aSurvival Analysis10aUnited States1 aCappola, Anne, R1 aO'Meara, Ellen, S1 aGuo, Wensheng1 aBartz, Traci, M1 aFried, Linda, P1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/112302966nas a2200445 4500008004100000022001400041245011400055210006900169260001600238300001200254490000800266520170200274653001601976653000901992653002202001653001502023653002402038653001102062653002502073653001802098653001102116653002502127653000902152653001502161653003002176653001602206653001402222653002002236653003202256653003002288653001602318100002202334700001602356700002502372700002302397700002202420700002002442700002202462856003602484 2009 eng d a1879-191300aUsefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure.0 aUsefulness of myeloperoxidase levels in healthy elderly subjects c2009 May 01 a1269-740 v1033 aIncreased systemic myeloperoxidase (MPO) has been associated with both the presence and severity of heart failure (HF). This study tested the hypothesis that increased systemic MPO in apparently healthy elderly subjects may predict increased risk of developing HF. Systemic MPO was measured in all available samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS). After excluding subjects without available blood samples or with a history of prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were included. A total of 569 subjects developed incident HF during 7.2 +/- 2.3 years of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher risk of developing incident HF after adjusting for MI, age, gender, systolic blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus, and any subclinical cardiovascular disease (hazard ratio 1.34, 95% confidence interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after censoring subjects with incident MI before incident HF, even when adjusted for C-reactive protein and cystatin C (hazard ratio 1.46, 95% confidence interval 1.08 to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation between increased MPO and HF risk was stronger in subjects without traditional cardiovascular risk factors ( AIM: To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores. METHODS: Comparability study on a subset of 405 participants, aged >or=70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants. RESULTS: The TICS explained 67% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered. CONCLUSIONS: 3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults. BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD. METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus. RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76). CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans. BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate. METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006. RESULTS: A total of 390 participants had an incident stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories. CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk. BACKGROUND: Kidney disease is a risk factor for mortality and cardiovascular disease in older adults, but the separate and combined effects of albuminuria and cystatin C, a novel marker of glomerular filtration, are not known. METHODS: We examined associations of these markers with mortality and cardiovascular outcomes during a median follow-up of 8.3 years in 3291 older adults in the Cardiovascular Health Study. Kidney disease was assessed using urinary albumin/creatinine ratio (ACR), cystatin C and Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR). We defined subgroups based on presence of microalbuminuria (MA, ACR > 30 mg/g) and categories of normal kidney function (cystatin C < 1.0 mg/L and eGFR > 60 mL/min/1.73 m(2)); preclinical kidney disease (cystatin C level > 1.0 mg/l but eGFR > 60 mL/min/1.73 m(2)); and chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). Cox proportional hazards models were used to examine associations between these six subgroups and all-cause or cardiovascular mortality, myocardial infarction and heart failure. RESULTS: One thousand one hundred fifty (34.9%) had normal kidney function (12.2% with MA), 1518 (46.1%) had preclinical kidney disease (17.9% with MA) and 622 (18.9%) had CKD (47% with MA). After adjustment, the presence of either preclinical kidney disease or MA was associated with an over 50% increase in mortality risk; the presence of both was associated with a 2.4-fold mortality risk. Those with CKD and MA were at highest risk, with a nearly 4-fold mortality risk. CONCLUSION: Elevated cystatin C and albuminuria are common, identify different subsets of the older population, and are independent, graded risk factors for cardiovascular disease and mortality. BACKGROUND: Alcohol consumption appears to be protective for cardiovascular disease; however, its relationship with kidney disease is unclear. METHODS: This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged ≥65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, <1 drink, 1-6 drinks, 7-13 drinks and ≥14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFR(cys) was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFR(cys)) loss >3 mL/min/1.73 m(2)/year. RESULTS: Eight percent of the cohort reported former alcohol use and 52% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95% confidence interval: none = reference; former = 1.18, 0.89-1.56; <1 drink = 1.20, 0.99-1.47; 1-6 = 1.18, 0.95-1.45; 7-13 = 1.10, 0.80-1.53; >14 = 0.89, 0.61-1.13). Results were similar with kidney function decline as a continuous outcome. CONCLUSIONS: Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease. CONTEXT: Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults. OBJECTIVE: To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later. MAIN OUTCOME MEASURE: Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater. RESULTS: Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95% CI, 2.8-6.4) for weight, 4.0 (95% CI, 2.6-6.0) for fat mass, 4.2 (95% CI, 2.8-6.2) for waist circumference, 2.4 (95% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (+/-2 kg), those who gained the most weight from 50 years of age to baseline (> or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95% CI, 1.9-4.3) and 2.0 (95% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less. CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes. BACKGROUND: In cross-sectional analyses, C-reactive protein (CRP) levels are inversely related to levels of kidney function. The relationship between kidney function and subsequent changes in CRP is unknown. METHODS: We studied 4,364 individuals from the Cardiovascular Health Study, a longitudinal cohort of community-dwelling older adults. Baseline eGFRcys was estimated using cystatin C. CRP was measured at baseline and after 3 and 7 years of follow-up; slopes of change in CRP were calculated. RESULTS: The mean (SD) age of the cohort was 72 (5.2) years; mean (SD) eGFRcys was 78.9 (18.4) ml/min/1.73 m(2). The median (interquartile range IQR) baseline CRP was 2.39 (1.22, 4.33) mg/l; the median (IQR) yearly change in CRP was -0.0051 (-0.020 to 0.27) mg/l/year. After adjustment for demographic characteristics and the initial level of CRP, each standard deviation lower baseline eGFR was associated with a small and non-significant yearly increase in CRP (0.032 mg/l/year; 95% CI: -0.005 to 0.070, p = 0.094). CONCLUSIONS: We did not find a relationship between eGFR and subsequent changes in CRP. The association between kidney function and CRP in cross-sectional analyses may reflect unmeasured confounding by atherosclerosis; alternatively, the burden of comorbidity and interval mortality in this population may have masked a stronger longitudinal association between kidney function and change in CRP. Further study in younger populations may clarify whether impaired kidney function leads to change in inflammation over time. OBJECTIVE: Fibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above. METHODS: Fibrosis markers and depressive symptoms were assessed in 870 participants (age=80.9+/-5.9 yrs, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D > or = 8). Covariates included demographic and clinical variables. RESULTS: Depression was associated with higher levels of PIP (median=411.0, inter-quartile range (IQR)=324.4-472.7 ng/mL vs. 387.6, IQR=342.0-512.5 ng/mL, p=0.006) and CITP (4.99, IQR=3.53-6.85 vs. 4.53, IQR=3.26-6.22 microg/L, p=0.024), but not PIIIINP (4.07, IQR=2.75-5.54 microg/L vs. 3.58, IQR=2.71-5.01 microg/L, p=0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p=0.014; WBC, p=0.075; fibrinogen, p=0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers. CONCLUSIONS: Depression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role. BACKGROUND: Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. METHODS AND RESULTS: Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3. CONCLUSIONS: We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF. BACKGROUND: Sudden cardiac death (SCD) can be the first manifestation of cardiovascular disease. Development of screening methods for higher/lower risk is critical. METHODS: The Cardiovascular Health Study is a population-based study of risk factors for coronary heart disease and stroke those 65 years or older. Forty-nine (of 1649) with usable Holters and in normal sinus rhythm had SCD during follow-up and were matched with 2 controls, alive at the time of death of the case and not experiencing SCD on follow-up. Univariate and multivariate conditional logistic regression determined the association of Holter-based information and SCD. RESULTS: In univariate models, the upper half of ventricular premature contraction (VPC) counts, abnormal heart rate turbulence, decreased normalized low-frequency power, increased T-wave alternans (TWA), and decreased the short-term fractal scaling exponent (DFA(1)) were associated with SCD, but time domain heart rate variability was not. In multivariate models, the upper half of VPC counts (odds ratio [OR], 6.6) and having TWA of 37 muV or greater on channel 2 (OR, 4.8) were independently associated with SCD. Also, the upper half of VPC counts (OR, 6.9) and having a DFA(1) of less than 1.05 (OR, 5.0) were independently associated with SCD. When additive effects were explored, having both higher VPCs and higher TWA was associated with an OR of 8.2 for SCD compared with 2.6 for having either. Also, having both higher VPCs and lower DFA(1) was associated with an OR of 9.6 for SCD compared with 3.1 for having either. CONCLUSIONS: Results support a potential role for 24-hour Holter recordings to identify older adults at increased or lower risk of SCD. CONTEXT: Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk for hospitalization or death. OBJECTIVES: To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n = 2918). MAIN OUTCOME MEASURES: New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors. RESULTS: Cardiac troponin T was detectable (≥3.00 pg/mL) in 2794 participants (66.2%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95% confidence interval [CI], 5.8-7.2; adjusted hazard ratio [aHR], 2.48; 95% CI, 2.04-3.00) for HF and an incidence rate of 4.8 (95% CI, 4.3-5.4; aHR, 2.91; 95% CI, 2.37-3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95% CI, 1.4-1.8 and 1.1; 95% CI, 0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50% (n = 393, 22%) was associated with a greater risk for HF (aHR, 1.61; 95% CI, 1.32-1.97) and cardiovascular death (aHR, 1.65; 95% CI, 1.35-2.03) and a decrease of more than 50% (n = 247, 14%) was associated with a lower risk for HF (aHR, 0.73; 95% CI, 0.54-0.97) and cardiovascular death (aHR, 0.71; 95% CI, 0.52-0.97) compared with participants with 50% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death. CONCLUSION: In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death. BACKGROUND: Atherosclerotic renovascular disease is associated with an increased risk of cardiovascular disease (CVD) events. This study examines associations between Doppler-derived parameters from the renal artery and renal parenchyma and all-cause mortality and fatal and nonfatal CVD events in a cohort of elderly Americans. STUDY DESIGN: Cohort study. SETTING: A subset of participants from the Cardiovascular Health Study (CHS). Through an ancillary study, 870 (70% recruitment) Forsyth County, NC, CHS participants consented to undergo renal duplex sonography to define the prevalence of renovascular disease in the elderly, resulting in 726 (36% men; mean age, 77 years) technically adequate complete studies included in this investigation. PREDICTOR: Renal duplex sonography-derived Doppler signals from the main renal arteries and renal parenchyma. Spectral analysis from Doppler-shifted frequencies and angle of insonation were used to estimate renal artery peak systolic and end diastolic velocity (both in meters per second). Color Doppler was used to identify the corticomedullary junction. Using a 3-mm Doppler sample, the parenchymal peak systolic and end diastolic frequency shift (both in kilohertz) were obtained. Resistive index was calculated as (1 - [end diastolic frequency shift/peak systolic frequency shift]) using Doppler samples from the hilar arteries of the left or right kidney with the higher main renal artery peak systolic velocity. OUTCOMES & MEASUREMENTS: Proportional hazard regression analysis was used to determine associations between renal duplex sonography-derived Doppler signals and CVD events and all-cause mortality adjusted for accepted cardiovascular risk factors. Index CVD outcomes were defined as coronary events (angina, myocardial infarction, and coronary artery bypass grafting/percutaneous coronary intervention), cerebrovascular events (stroke or transient ischemic attack), and any CVD event (angina, congestive heart failure, myocardial infarction, stroke, transient ischemic attack, and coronary artery bypass grafting [CABG]/percutaneous transluminal coronary intervention [PTCI]). RESULTS: During follow-up, 221 deaths (31%), 229 CVD events (32%), 122 coronary events (17%), and 92 cerebrovascular events (13%) were observed. Renal duplex sonography-derived Doppler signals from the renal parenchyma were associated independently with all-cause mortality and CVD outcomes. In particular, increased parenchymal end diastolic frequency shift was associated significantly with any CVD event (HR, 0.73; 95% CI, 0.62-0.87; P < 0.001). Marginally significant associations were observed between increases in parenchymal end diastolic frequency shift and decreased risk of death (HR, 0.86; 95% CI, 0.73-1.00; P = 0.06) and decreased risk of cerebrovascular events (HR, 0.78; 95% CI, 0.61-1.01; P = 0.06). Parenchymal end diastolic frequency shift was not significantly predictive of coronary events (HR, 0.84; 95% CI, 0.67-1.06; P = 0.1). LIMITATIONS: CHS participants showed a "healthy cohort" effect that may underestimate the rate of CVD events in the general population. CONCLUSION: Renal duplex sonographic Doppler signals from the renal parenchyma showed significant associations with subsequent CVD events after controlling for other significant risk factors. In particular, a standard deviation increase in parenchymal end diastolic frequency shift was associated with 27% risk reduction in any CVD event. RATIONALE: Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood. OBJECTIVES: We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older. METHODS: Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects). MEASUREMENTS AND MAIN RESULTS: In summer, increases in RDI or percentage of sleep time at less than 90% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5% (95% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5°F) in temperature. CONCLUSIONS: Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk. OBJECTIVE: To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression. METHODS: Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA(1)) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates. RESULTS: Depression was associated with ANS dysfunction (DFA(1), p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23-2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05-2.83) when adjusting for independent HRV and inflammation predictors (DFA(1), heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001). CONCLUSION: Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures. Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. BACKGROUND: To estimate the associations of weight dynamics with physical functioning and mortality in older adults. METHODS: Longitudinal cohort study using prospectively collected data on weight, physical function, and health status in four U.S. Communities in the Cardiovascular Health Study. Included were 3,278 participants (2,013 women and 541 African Americans), aged 65 or older at enrollment, who had at least five weight measurements. Weight was measured at annual clinic visits between 1992 and 1999, and summary measures of mean weight, coefficient of variation, average annual weight change, and episodes of loss and gain (cycling) were calculated. Participants were followed from 1999 to 2006 for activities of daily living (ADL) difficulty, incident mobility limitations, and mortality. RESULTS: Higher mean weight, weight variability, and weight cycling increased the risk of new onset of ADL difficulties and mobility limitations. After adjustment for risk factors, the hazard ratio (95% confidence interval) for weight cycling for incident ADL impairment was 1.28 (1.12, 1.47), similar to that for several comorbidities in our model, including cancer and diabetes. Lower weight, weight loss, higher variability, and weight cycling were all risk factors for mortality, after adjustment for demographic risk factors, height, self-report health status, and comorbidities. CONCLUSIONS: Variations in weight are important indicators of future physical limitations and mortality in the elderly and may reflect difficulties in maintaining homeostasis throughout older ages. Monitoring the weight of an older person for fluctuations or episodes of both loss and gain is an important aspect of geriatric care. Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5-25). Overweight subjects (BMI: 25-30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects. OBJECTIVE: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). METHODS: Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. RESULTS: The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95% CI = 0.12-0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52-0.997) and pure AD (HR = 0.57; 95% CI = 0.36-0.90) among white subjects after adjustment for demographics, number of APOE epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. CONCLUSIONS: In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration. OBJECTIVES: To describe cross-sectional and longitudinal associations with dehydroepiandrosterone sulfate (DHEAS) and change in DHEAS with age. DESIGN: Longitudinal cohort study. SETTING: Pittsburgh, Pennsylvania. PARTICIPANTS: Cardiovascular Health Study All Stars study participants assessed in 2005/06 (N=989, mean age 85.2, 63.5% women, 16.5% African American). MEASUREMENTS: Health characteristics were assessed in 2005/06 according to DHEAS level, mean DHEAS and DHEAS change across age categories were tested, and linear and logistic regression was used to identify factors present in 1996/97 associated with continuous and categorical DHEAS change. RESULTS: Mean +/- standard deviation DHEAS was 0.555 +/- 0.414 microg/mL in 1996/97 and 0.482 +/- 0.449 microg/mL in 2005/06 for women and 0.845 +/- 0.520 microg/mL in 1996/97 and 0.658 +/- 0.516 microg/mL in 2005/06 for men. In 2005/06, DHEAS was lower in women and subjects with cardiovascular disease (CVD) and chronic pulmonary disease and higher for African Americans and subjects with hypertension and high cholesterol. Mean DHEAS change was greater in men (-0.200 microg/mL) than in women (-0.078 microg/mL) (P<.001). Each 1-year increase in age attenuated the effect of male sex by 0.01 microg/mL (P=.009), abolishing the sex difference in DHEAS change by age 79. Presence of CVD before the study period was associated with greater absolute DHEAS change (beta=-0.04 microg/mL, P=.04) and with the fourth quartile of DHEAS change versus the first to third quartiles (odds ratio=1.46, 95% confidence interval=1.03-2.05). CONCLUSION: DHEAS change continues into very old age, is not homogenous, is affected by sex, and is associated with prevalent CVD. Future studies should investigate factors that might accelerate DHEAS decline. BACKGROUND: Cross-sectional studies show that adiponectin is higher in older than in younger adults but long-term change in adiponectin, its determinants, and its relationship to functional decline or survival in the elderly population have not been evaluated. METHODS: We investigated predictors of longitudinal change in adiponectin, and the association of this adipokine or its antecedent change with physical deterioration and all-cause mortality in 988 participants in a population-based study who completed examinations in 1996-1997 and 2005-2006, had serial adiponectin measurements and underwent follow-up through June 2009. RESULTS: Adiponectin level rose significantly during follow-up, but the increase was smaller in blacks, was associated with declining weight or fasting glucose and, in men, lower albumin, and was affected by medications. Adiponectin was independently associated with greater physical decline, but the relationship for adiponectin change was driven by concomitant weight decrease. Both adiponectin and its change independently predicted mortality, even after adjustment for weight change. The association for adiponectin and mortality was observed in whites but not in blacks and only for levels in the upper range (hazard ratio = 1.85, 95% confidence interval = 1.36-2.52 per SD ≥ 20 mg/L), whereas that for adiponectin change was linear throughout in both racial groups (hazard ratio = 1.30, 95% confidence interval = 1.10-1.52 per SD). CONCLUSIONS: Adiponectin levels increase over time in long-lived adults and are associated with greater physical disability and mortality. Such increases may occur in response to age-related homeostatic dysregulation. Additional investigation is required to define the underlying mechanisms and whether this represents a marker or causal factor for mortality in this age group. BACKGROUND: Older women experience disability more commonly than their male peers. This disparity may be due, in part, to sex-based differences in the prevalence or the disabling effects of common medical conditions. The objectives of this analysis were to (a) quantify the extent to which excess disability in women is explained by higher prevalence of selected medical conditions and (b) evaluate whether the same conditions have differing effects on disability in men and women. METHODS: We analyzed cross-sectional data from 5,888 community-dwelling older men and women. Disability was defined as difficulty with greater than or equal to one activity of daily living. Thirteen medical conditions were assessed by self-report, testing, or record review. RESULTS: Controlling for age, race, education, and marital status, women were more likely to experience disability (odds ratio = 1.70, 95% confidence interval = 1.36-2.11). Higher prevalence of arthritis and obesity in women explained 30.2% and 12.9%, respectively, of the sex-based difference in disability rates, whereas male prevalent diseases like vascular conditions and emphysema narrowed the disability gap. Women with arthritis, hearing problems, coronary artery disease, congestive heart failure, stroke, and claudication were more likely to exhibit disability compared with men with the same conditions (p < .001). CONCLUSIONS: Efforts to lessen sex-based inequality in disability should focus on reducing the prevalence of arthritis and obesity. Future generations may see greater functional disparity if rates of vascular disease and emphysema rise among women. Several conditions were more often associated with disability in women, suggesting additional sex-based differences in the disablement process. BACKGROUND: Animal experiments suggest that circulating palmitoleic acid (cis-16:1n-7) from adipocyte de novo fatty acid synthesis may directly regulate insulin resistance and metabolic dysregulation. OBJECTIVE: We investigated the independent determinants of circulating palmitoleate in free-living humans and whether palmitoleate is related to lower metabolic risk and the incidence of diabetes. DESIGN: In a prospective cohort of 3630 US men and women in the Cardiovascular Health Study, plasma phospholipid fatty acids, anthropometric variables, blood lipids, inflammatory markers, and glucose and insulin concentrations were measured between 1992 and 2006 by using standardized methods. Independent determinants of plasma phospholipid palmitoleate and relations of palmitoleate with metabolic risk factors were investigated by using multivariable-adjusted linear regression. Relations with incident diabetes (296 incident cases) were investigated by using Cox proportional hazards. RESULTS: The mean (± SD) palmitoleate value was 0.49 ± 0.20% (range: 0.11-2.55%) of total fatty acids. Greater body mass index, carbohydrate intake, protein intake, and alcohol use were each independent lifestyle correlates of higher palmitoleate concentrations. In multivariable analyses that adjusted for these factors and other potential confounders, higher palmitoleate concentrations were independently associated with lower LDL cholesterol (P < 0.001), higher HDL cholesterol (P < 0.001), lower total:HDL-cholesterol ratio (P = 0.04), and lower fibrinogen (P < 0.001). However, palmitoleate was also associated with higher triglycerides (P < 0.001) and (in men only) with greater insulin resistance (P < 0.001). Palmitoleate was not significantly associated with incident diabetes. CONCLUSIONS: Adiposity (energy imbalance), carbohydrate consumption, and alcohol use-even within typical ranges-are associated with higher circulating palmitoleate concentrations. Circulating palmitoleate is robustly associated with multiple metabolic risk factors but in mixed directions, perhaps related to divergent lifestyle determinants or endogenous sources (liver, adipose tissue) of fatty acid synthesis. BACKGROUND: Many elderly adults fall every year, sometimes resulting in serious injury and hospitalization. Although impaired cognition is a risk factor for injurious falls, little is known about cognitive decline above the threshold of impairment and risk of serious falls in community-dwelling seniors. METHODS: In total, 702 of 5,356 older adults participating in the Cardiovascular Health Study experienced an injurious fall between 1990 and 2005, as indicated by hospitalization records. General cognition was measured annually with the Modified Mini-Mental State Examination and processing speed with the Digit Symbol Substitution Test. The Cox regression model was used to calculate hazard ratio and 95% confidence interval with and without time-dependent covariates and adjusted for known risk factors. RESULTS: Participants with slightly decreased Digit Symbol Substitution Test scores were at increased risk for a serious fall (hazard ratio = 1.58, 95% confidence interval = 1.15-2.17). The risk continued to increase with each quartile decrease in Digit Symbol Substitution Test score. Participants without prevalent cardiovascular disease at baseline and decreased Modified Mini-Mental State Examination scores (80-89) had a 45% increased risk for a serious fall and those at high risk for dementia (<80) were at twice the risk as participants scoring above 90 (hazard ratio = 2.16, 95% confidence interval = 1.60-2.91). CONCLUSIONS: Both decreased general cognition and decreased processing speed appear to be potential risk factors for serious falls in the elderly. When assessing the risk of serious falls in elderly patients, clinicians should consider usual factors like gait instability and sensory impairment as well as less obvious ones such as cardiovascular disease and cognitive function in nondemented adults. BACKGROUND: Hypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events. METHODS: We studied 4,311 participants aged 65-98 (61.2% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years. RESULTS: CVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >or=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl and 2.1 when BP >or=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP. CONCLUSION: Increased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia. Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation. Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization. Serum calcium levels are tightly regulated. We performed genome-wide association studies (GWAS) in population-based studies participating in the CHARGE Consortium to uncover common genetic variations associated with total serum calcium levels. GWAS of serum calcium concentrations was performed in 20 611 individuals of European ancestry for ∼2.5 million genotyped and imputed single-nucleotide polymorphisms (SNPs). The SNP with the lowest P-value was rs17251221 (P = 2.4 * 10(-22), minor allele frequency 14%) in the calcium-sensing receptor gene (CASR). This lead SNP was associated with higher serum calcium levels [0.06 mg/dl (0.015 mmol/l) per copy of the minor G allele] and accounted for 0.54% of the variance in serum calcium concentrations. The identification of variation in CASR that influences serum calcium concentration confirms the results of earlier candidate gene studies. The G allele of rs17251221 was also associated with higher serum magnesium levels (P = 1.2 * 10(-3)), lower serum phosphate levels (P = 2.8 * 10(-7)) and lower bone mineral density at the lumbar spine (P = 0.038), but not the femoral neck. No additional genomic loci contained SNPs associated at genome-wide significance (P < 5 * 10(-8)). These associations resemble clinical characteristics of patients with familial hypocalciuric hypercalcemia, an autosomal-dominant disease arising from rare inactivating mutations in the CASR gene. We conclude that common genetic variation in the CASR gene is associated with similar but milder features in the general population. INTRODUCTION: The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. METHODS: DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. RESULTS: After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. CONCLUSIONS: In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women. BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline. BACKGROUND AND OBJECTIVE: CRP has several potentially antibacterial effects, and variation in the CRP gene is known to influence CRP levels. Whether this variation influences risk of infection, and hence whether CRP has anti-infective activity in humans, is uncertain. METHODS: We evaluated a series of haplotype-tagging single nucleotide polymorphisms among 5374 individuals in the Cardiovascular Health Study, a cohort of older adults from four communities, who were followed for community-acquired pneumonia for 12-13 years. Secondarily, we evaluated whether these polymorphisms varied among men in the Health Professionals Follow-up Study who self-reported pneumonia on biennial questionnaires. RESULTS: There were 581 (507 white and 74 black) Cardiovascular Health Study participants with incident hospitalizations for pneumonia. No single nucleotide polymorphism or haplotypes were associated with risk among white Cardiovascular Health Study participants. Among black participants, the haplotype tagged by A790T was associated with lower risk of incident pneumonia (hazard ratio 0.5; 95% confidence interval: 0.3-0.9) and with higher CRP levels. In Health Professionals Follow-up Study, a separate haplotype was associated with less frequent self-reported pneumonia but not with circulating CRP levels. CONCLUSIONS: Some genetic variants in CRP may be associated with risk of pneumonia, but haplotypes associated with risk are variably associated with baseline CRP levels. If CRP is a relevant component of innate immunity in humans, the inducibility or tissue-specificity of expression may be at least as important as chronic circulating levels. BACKGROUND: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease. METHODS AND RESULTS: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment. CONCLUSIONS: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease. BACKGROUND: Type 2 diabetes has been described as a coronary heart disease (CHD) "risk equivalent." We tested whether cardiovascular and all-cause mortality rates were similar between participants with prevalent CHD vs diabetes in an older adult population in whom both glucose disorders and preexisting atherosclerosis are common. METHODS: The Cardiovascular Health Study is a longitudinal study of men and women (n=5784) aged > or =65 years at baseline who were followed from baseline (1989/1992-1993) through 2005 for mortality. Diabetes was defined by fasting plasma glucose > or =7.0 mmol/L or use of diabetes control medications. Prevalent CHD was determined by confirmed history of myocardial infarction, angina, or coronary revascularization. RESULTS: Following multivariable adjustment for other cardiovascular disease risk factors and subclinical atherosclerosis, CHD mortality risk was similar between participants with CHD alone vs diabetes alone (hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.83-1.30). The proportion of mortality attributable to prevalent diabetes (population-attributable risk percent=8.4%) and prevalent CHD (6.7%) was similar in women, but the proportion of mortality attributable to CHD (16.5%) as compared with diabetes (6.4%) was markedly higher in men. Patterns were similar for cardiovascular disease mortality. By contrast, the adjusted relative hazard of total mortality was lower among participants with CHD alone (HR 0.85, 95% CI, 0.75-0.96) as compared with those who had diabetes alone. CONCLUSIONS: Among older adults, diabetes alone confers a risk for cardiovascular mortality similar to that from established clinical CHD. The public health burden of both diabetes and CHD is substantial, particularly among women. BACKGROUND: Uncertainties persist about the magnitude of associations of diabetes mellitus and fasting glucose concentration with risk of coronary heart disease and major stroke subtypes. We aimed to quantify these associations for a wide range of circumstances. METHODS: We undertook a meta-analysis of individual records of diabetes, fasting blood glucose concentration, and other risk factors in people without initial vascular disease from studies in the Emerging Risk Factors Collaboration. We combined within-study regressions that were adjusted for age, sex, smoking, systolic blood pressure, and body-mass index to calculate hazard ratios (HRs) for vascular disease. FINDINGS: Analyses included data for 698 782 people (52 765 non-fatal or fatal vascular outcomes; 8.49 million person-years at risk) from 102 prospective studies. Adjusted HRs with diabetes were: 2.00 (95% CI 1.83-2.19) for coronary heart disease; 2.27 (1.95-2.65) for ischaemic stroke; 1.56 (1.19-2.05) for haemorrhagic stroke; 1.84 (1.59-2.13) for unclassified stroke; and 1.73 (1.51-1.98) for the aggregate of other vascular deaths. HRs did not change appreciably after further adjustment for lipid, inflammatory, or renal markers. HRs for coronary heart disease were higher in women than in men, at 40-59 years than at 70 years and older, and with fatal than with non-fatal disease. At an adult population-wide prevalence of 10%, diabetes was estimated to account for 11% (10-12%) of vascular deaths. Fasting blood glucose concentration was non-linearly related to vascular risk, with no significant associations between 3.90 mmol/L and 5.59 mmol/L. Compared with fasting blood glucose concentrations of 3.90-5.59 mmol/L, HRs for coronary heart disease were: 1.07 (0.97-1.18) for lower than 3.90 mmol/L; 1.11 (1.04-1.18) for 5.60-6.09 mmol/L; and 1.17 (1.08-1.26) for 6.10-6.99 mmol/L. In people without a history of diabetes, information about fasting blood glucose concentration or impaired fasting glucose status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors. INTERPRETATION: Diabetes confers about a two-fold excess risk for a wide range of vascular diseases, independently from other conventional risk factors. In people without diabetes, fasting blood glucose concentration is modestly and non-linearly associated with risk of vascular disease. FUNDING: British Heart Foundation, UK Medical Research Council, and Pfizer. OBJECTIVE: Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated. RESEARCH DESIGN AND METHODS: Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored. RESULTS: The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10(-18)). Substantial heterogeneity was present (I(2) = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10(-4)), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10(-13)), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10(-5)). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference. CONCLUSIONS: A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate. OBJECTIVES: This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people would provide additional prognostic information to that from traditional risk factors. BACKGROUND: Accurate cardiovascular risk stratification is challenging in elderly people. METHODS: NT-proBNP was measured at baseline and 2 to 3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal CHS (Cardiovascular Health Study). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders. RESULTS: NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR]: 3.05; 95% confidence interval [CI]: 2.46 to 3.78) and cardiovascular death (HR: 3.02; 95% CI: 2.36 to 3.86) compared with the lowest quintile (<47.5 pg/ml). The inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among participants with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR: 2.13; 95% CI: 1.68 to 2.71) and cardiovascular death (HR: 1.91; 95% CI: 1.43 to 2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR: 2.06; 95% CI: 1.56 to 2.72) and cardiovascular death (HR: 1.88; 95% CI: 1.37 to 2.57), whereas those who developed a >25% decrease to CONCLUSIONS: NT-proBNP levels independently predict heart failure and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk. BACKGROUND: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. OBJECTIVES: We assessed the association between egg intake and incident diabetes in older adults. DESIGN: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989-2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. RESULTS: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1-3 eggs/mo, 1-4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. CONCLUSION: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D. BACKGROUND: Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. METHODS AND RESULTS: We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. CONCLUSIONS: European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. Marine n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for bone health, but few studies have investigated the association with fish consumption. Our aim was to study associations of fish and EPA + DHA consumption with bone mineral density (BMD) and hip fracture risk and determine whether high linoleic acid (LA) intake, the major dietary n-6 PUFA, modifies the associations. The study population consisted of 5045 participants aged 65 years and older from the Cardiovascular Health Study. Data on BMD were available for 1305 participants. Food-frequency questionnaire was used to assess dietary intake, and hip fracture incidence was assessed prospectively by review of hospitalization records. After multivariable adjustment, femoral neck BMD was 0.01 g/cm(2) lower in the highest versus lowest tuna/other-fish intake category (p = .05 for trend). EPA + DHA intake (higher versus lower median of 0.32 g/day) was associated with lower femoral neck BMD (0.66 versus 0.71 g/cm(2), p < .001) among those with LA intake greater than the median 12.1 g/day (p = .03 for interaction). No significant associations were found with total-hip BMD. During mean follow-up of 11.1 years, 505 hip fractures occurred. Fish or EPA + DHA consumption was not significantly associated with fracture incidence [hazard ratio (HR) for extreme categories: HR = 1.23, 95% confidence interval (CI) 0.83-1.84 for tuna/other fish; HR = 1.16, 95% CI 0.91-1.49 for fried fish; and HR = 0.98, 95% CI 0.71-1.36 for EPA + DHA]. High LA intake did not modify these associations. In this large prospective cohort of older adults, fish consumption was associated with very small differences in BMD and had no association with hip fracture risk. BACKGROUND: The overall consumption of trans fatty acids (TFAs) increases the risk of coronary artery disease. However, multiple TFA isomers exist, each with potentially different health effects. Different food sources of these specific TFA isomers are not well established. OBJECTIVE: Our objective was to determine the major independent food sources of specific TFA isomers. DESIGN: We investigated relations of major potential food sources of TFAs, as assessed by serial food-frequency questionnaires, with 10 plasma phospholipid TFA isomers [5 trans (t-) 18:1, 3 t-18:2, and 2 t-16:1] in 3330 older adults in the Cardiovascular Health Study, a community-based multicenter cohort. Stepwise regression was used to identify independent major food sources of individual plasma phospholipid TFA isomers, which were adjusted for demographic, lifestyle, and dietary factors. RESULTS: All 5 t-18:1 isomers were similarly associated with foods commonly made with partially hydrogenated vegetable oils (PHVOs), including biscuits (0.51 higher SD of total 18:1 fatty acid concentrations per serving/d, P < 0.01), chips and/or popcorn (0.33 higher SD per serving/d, P = 0.02), margarine (0.32 higher SD per serving/d, P < 0.001), fried foods (0.32 higher SD per serving/d, P = 0.04), and bakery foods (0.23 higher SD per serving/d, P = 0.02). Each of the t-18:2 isomers were associated only with bakery foods (0.50 higher SD of total 18:2 fatty acid concentrations per serving/d, P < 0.001). Ruminant foods were major correlates of t-16:1n-7, including red meats (0.72 higher SD per serving/d, P < 0.001), butter (0.43 higher SD per serving/d, P < 0.001), and higher-fat dairy (0.37 higher SD per serving/d, P < 0.001). In contrast, t-16:1n-9 were derived mainly from margarine (0.31 higher SD per serving/d, P < 0.001). CONCLUSIONS: t-18:1 Isomers are similarly derived from multiple PHVO-containing foods. In contrast, t-18:2 and t-16:1n-9 isomers are derived from more-specific types of PHVO-containing foods. Ruminant foods are major sources of t-16:1n-7. Different TFA isomers and dietary sources should be considered when investigating health effects and interventions to lower TFAs. There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n = 6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p = 1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p = 2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease. Genetic variation in both innate and adaptive immune systems is associated with Crohn's disease (CD) susceptibility, but much of the heritability to CD remains unknown. We performed a genome-wide association study (GWAS) in 896 CD cases and 3204 healthy controls all of Caucasian origin as defined by multidimensional scaling. We found supportive evidence for 21 out of 40 CD loci identified in a recent CD GWAS meta-analysis, including two loci which had only nominally achieved replication (rs4807569, 19p13; rs991804, CCL2/CCL7). In addition, we identified associations with genes involved in tight junctions/epithelial integrity (ASHL, ARPC1A), innate immunity (EXOC2), dendritic cell biology [CADM1 (IGSF4)], macrophage development (MMD2), TGF-beta signaling (MAP3K7IP1) and FUT2 (a physiological trait that regulates gastrointestinal mucosal expression of blood group A and B antigens) (rs602662, P=3.4x10(-5)). Twenty percent of Caucasians are 'non-secretors' who do not express ABO antigens in saliva as a result of the FUT2 W134X allele. We demonstrated replication in an independent cohort of 1174 CD cases and 357 controls between the four primary FUT2 single nucleotide polymorphisms (SNPs) and CD (rs602662, combined P-value 4.90x10(-8)) and also association with FUT2 W143X (P=2.6x10(-5)). Further evidence of the relevance of this locus to CD pathogenesis was demonstrated by the association of the original four SNPs and CD in the recently published CD GWAS meta-analysis (rs602662, P=0.001). These findings strongly implicate this locus in CD susceptibility and highlight the role of the mucus layer in the development of CD. BACKGROUND: Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American. METHODS: We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations. RESULTS: African ancestry was inversely related to forced expiratory volume in 1 second (FEV(1)) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV(1)) in 4 to 5% of participants. CONCLUSIONS: Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National Institutes of Health and others.) BACKGROUND: Acute severe ulcerative colitis (UC) remains a significant clinical challenge and the ability to predict, at an early stage, those individuals at risk of colectomy for medically refractory UC (MR-UC) would be a major clinical advance. The aim of this study was to use a genome-wide association study (GWAS) in a well-characterized cohort of UC patients to identify genetic variation that contributes to MR-UC. METHODS: A GWAS comparing 324 MR-UC patients with 537 non-MR-UC patients was analyzed using logistic regression and Cox proportional hazards methods. In addition, the MR-UC patients were compared with 2601 healthy controls. RESULTS: MR-UC was associated with more extensive disease (P = 2.7 × 10(-6)) and a positive family history of UC (P = 0.004). A risk score based on the combination of 46 single nucleotide polymorphisms (SNPs) associated with MR-UC explained 48% of the variance for colectomy risk in our cohort. Risk scores divided into quarters showed the risk of colectomy to be 0%, 17%, 74%, and 100% in the four groups. Comparison of the MR-UC subjects with healthy controls confirmed the contribution of the major histocompatibility complex to severe UC (peak association: rs17207986, P = 1.4 × 10(-16)) and provided genome-wide suggestive association at the TNFSF15 (TL1A) locus (peak association: rs11554257, P = 1.4 × 10(-6)). CONCLUSIONS: A SNP-based risk scoring system, identified here by GWAS analyses, may provide a useful adjunct to clinical parameters for predicting the natural history of UC. Furthermore, discovery of genetic processes underlying disease severity may help to identify pathways for novel therapeutic intervention in severe UC. Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38,991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and approximately 2.5 million markers. Results with P < 5 × 10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain approximately 0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10(-5) increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care. BACKGROUND AND PURPOSE: Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed cross-sectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had >or=1 MRI infarct). RESULTS: The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P=4.64x10(-7)). Highly suggestive associations (P<1.0x10(-5)) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r(2)>0.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. CONCLUSIONS: This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed. Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using approximately 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels. BACKGROUND: Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA. METHODOLOGY/PRINCIPAL FINDINGS: We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01). CONCLUSIONS/SIGNIFICANCE: A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study. The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation. Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation. BACKGROUND: Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2,366,858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. METHODS AND RESULTS: Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance. CONCLUSIONS: This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF. OBJECTIVES: To determine the relative importance of geriatric impairments (in muscle strength, physical capacity, cognition, vision, hearing, and psychological status) and chronic diseases in predicting subsequent functional disability in longitudinal analyses. DESIGN: Longitudinal data from the Cardiovascular Health Study were analyzed. Multivariable Cox hazards regression modeling was used to analyze associations between time-dependent predictors and onset of disability in activities of daily living (ADLs) and mobility. SETTING: Four communities across the United States (Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Allegheny County, PA). PARTICIPANTS: Five thousand eight hundred eighty-eight elderly persons. MEASUREMENTS: Data were collected annually through in-person examinations. RESULTS: ADL disability developed in 15% of participants and mobility disability in 30%. A single multivariable model was developed that included demographics, marital status, body mass index, and number of impairments and diseases. The hazard ratios (HRs) of having one, two, and three or more geriatric impairments (vs none) for the outcome of ADL disability were 2.12 (95% confidence interval (CI)=1.63-2.75), 4.25 (95% CI=3.30-5.48), and 7.87 (95% CI=6.10-10.17), respectively, and for having one, two, and three or more chronic diseases were 1.75 (95% CI=1.41-2.19), 2.45 (95% CI=1.95-3.07), and 3.26 (95% CI=2.53-4.19), respectively. Similarly, the HRs of having one, two, and three or more impairments for the outcome of mobility disability were 1.48 (95% CI=1.27-1.73), 2.08 (95% CI=1.77-2.45), and 3.70 (95% CI=3.09-4.42), respectively, and for having one, two, and three or more diseases were 2.06 (95% CI=1.76-2.40), 2.80 (95% CI=2.36-3.31), and 4.20 (95% CI=3.44-5.14), respectively. CONCLUSION: Number of geriatric impairments was more strongly associated than number of chronic diseases with subsequent ADL disability and nearly as strongly associated with the subsequent mobility disability. BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults. METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest). CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults. BACKGROUND: Older adults are often advised to walk more, but randomized trials have not conclusively established the benefits of walking in this age group. Typical analyses based on observational data may have biased results. Here, we propose a "limited-bias," more interpretable estimate of the health benefits to sedentary healthy older adults of walking more, using longitudinal data from the Cardiovascular Health Study. METHODS: The number of city blocks walked per week, collected annually, was classified as sedentary (<7 blocks per week), somewhat active, or active (>or=28). Analysis was restricted to persons sedentary and healthy in the first 2 years. In Year 3, some became more active (the treatment groups). Self-rated health at Year 5 (follow-up) was regressed on walking at Year 3, with additional covariates from Year 2, when all were sedentary. RESULTS: At follow-up, 83.5% of those active at baseline had excellent, very good, or good self-rated health, as compared with 63.9% of the sedentary, an apparent benefit of 19.6 percentage points. After covariate adjustment, the limited-bias estimate of the benefit was 11.2 percentage points (95% confidence interval 3.7-18.6). Ten different outcome measures showed a benefit, ranging from 5 to 11 percentage points. Estimates from other study designs were smaller, less interpretable, and potentially more biased. CONCLUSIONS: In longitudinal studies where walking and health are ascertained at every wave, limited-bias estimates can provide better estimates of the benefits of walking. A surprisingly small increase in walking was associated with meaningful health benefits. AIMS: The aim of the study was to find the epidemiology of hip fractures in heart failure. The increasing survival rate for patients with heart failure places them at risk for other diseases of ageing, including osteoporosis. METHODS AND RESULTS: We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95% CI 1.2-2.93) and 1.59 (95% CI 0.93-2.72), respectively. Respective HRs for women were 1.75 (95% CI 1.27-2.4) and 1.41 (95% CI 0.98-2.03). Mortality hazard was approximately 2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone. CONCLUSION: Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure. BACKGROUND: Impaired kidney function is associated with increased risk for cardiovascular events. We evaluated whether kidney function is associated with atrial fibrillation (AF) risk in elderly persons. METHODS AND RESULTS: Subjects were participants in the Cardiovascular Health Study (CHS), a population-based cohort of ambulatory elderly. Measures of kidney function were cystatin C and creatinine-based estimated glomerular filtration rate (eGFR). Among the 4663 participants, 342 (7%) had AF at baseline and 579 (13%) developed incident AF during follow-up (mean 7.4 years). In unadjusted analyses, cystatin C quartiles were strongly associated with prevalent AF with a nearly 3-fold odds in the highest quartile compared with the lowest (HR=1.19, 95% CI [0.80-1.76] in quartile 2; HR=2.00, 95% CI [1.38-2.88] in quartile 3; and HR=2.87, 95% CI [2.03-4.07] in quartile 4). This increased risk for prevalent AF remained significant after multivariate adjustment. The risk for incident AF increased across cystatin C quartiles in the unadjusted analysis (HR=1.37, 95% CI [1.07-1.75] in quartile 2; HR=1.43, 95% CI [1.11-1.84] in quartile 3; and HR=1.88, 95% CI [1.47-2.41] in quartile 4); however, after multivariate adjustment, these findings were no longer significant. An estimated GFR <60 mL.min.1.73m(2) was associated with prevalent and incident AF in unadjusted, but not multivariate analyses. CONCLUSIONS: Impaired kidney function, as measured by cystatin C, is an independent marker of prevalent AF; however, neither cystatin C nor eGFR are predictors of incident AF. BACKGROUND: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus. METHODS AND RESULTS: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF. We replicated SNPs associated with AF after adjustment for the most significantly associated SNP in 5066 case and 30 661 referent subjects from the German Competence Network for Atrial Fibrillation, Atherosclerosis Risk In Communities Study, Cleveland Clinic Lone AF Study, Cardiovascular Health Study, and Rotterdam Study. All subjects were of European ancestry. A multimarker risk score composed of SNPs that tagged distinct AF susceptibility signals was constructed and tested for association with AF, and all results were subjected to meta-analysis. The previously reported SNP, rs2200733, was most significantly associated with AF (minor allele odds ratio 1.80, 95% confidence interval 1.50 to 2.15, P=1.2 x 10(-20)) in the discovery sample. Adjustment for rs2200733 genotype revealed 2 additional susceptibility signals marked by rs17570669 and rs3853445. A graded risk of AF was observed with an increasing number of AF risk alleles at SNPs that tagged these 3 susceptibility signals. CONCLUSIONS: We identified 2 novel AF susceptibility signals on chromosome 4q25. Consideration of multiple susceptibility signals at chromosome 4q25 identifies individuals with an increased risk of AF and may localize regulatory elements at the locus with biological relevance in the pathogenesis of AF. BACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline. METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin. RESULTS: During the study, 1059 subjects (26%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen. CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR. The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen concentrations, carotid intima-media thickness, and myocardial infarction or ischemic stroke in 3900 European-American Cardiovascular Health Study participants. To identify combinations of genetic main effects and interactions associated with outcomes, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were significantly associated with fibrinogen level (p < 0.005), but not with other outcomes. Fibrinogen levels were higher in individuals having FGB1437 (rs1800790) and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p= 0.03) interactions between IL-6 level and FGA and FGG promoter SNPs associated with fibrinogen levels were detected. We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD. OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. RESEARCH DESIGN AND METHODS: Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant. RESULTS: Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. CONCLUSIONS: Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations. OBJECTIVE: Since publication in 1995 of the National Institute of Neurological Disorders and Stroke (NINDS) trial of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke, the benefit and frequency of use of IV tPA in the elderly have remained uncertain. METHODS: We obtained data from the NINDS trial to summarize outcomes for randomized subjects older than 80 years. We used data from the Cardiovascular Health Study, a cohort study of 5888 elderly participants from 4 US communities followed longitudinally for stroke since 1989 to estimate the use of and hospital outcome after IV tPA in older adults following publication of the trial in 1995. RESULTS: In the NINDS trial, 44 subjects older than 80 years were randomized, and their 3-month functional outcomes were not significantly improved with IV tPA. Of 25 randomized to IV tPA, 4 experienced symptomatic intracranial hemorrhages within 36 hours of treatment. Compared with younger patients, older patients were 2.87 times more likely to experience a symptomatic intracranial hemorrhage within 36 hours of IV tPA (95% confidence interval, 1.04-7.93). Of 227 Cardiovascular Health Study participants hospitalized for ischemic stroke between 1995 and 2002, seven, whose mean age was 84 years, were treated with IV tPA (3.1%; 95% confidence interval 1.2-6.2). Two had symptomatic intracranial hemorrhages, 3 failed to improve, and 2 of the 7 had good outcomes. CONCLUSIONS: These data highlight the need to clarify the risk-benefit profile of IV tPA in ischemic stroke victims who are older than 80 years. BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an inflammatory enzyme expressed in atherosclerotic plaques, is a therapeutic target being assessed in trials of vascular disease prevention. We investigated associations of circulating Lp-PLA(2) mass and activity with risk of coronary heart disease, stroke, and mortality under different circumstances. METHODS: With use of individual records from 79 036 participants in 32 prospective studies (yielding 17 722 incident fatal or non-fatal outcomes during 474 976 person-years at risk), we did a meta-analysis of within-study regressions to calculate risk ratios (RRs) per 1 SD higher value of Lp-PLA(2) or other risk factor. The primary outcome was coronary heart disease. FINDINGS: Lp-PLA(2) activity and mass were associated with each other (r=0.51, 95% CI 0.47-0.56) and proatherogenic lipids. We noted roughly log-linear associations of Lp-PLA(2) activity and mass with risk of coronary heart disease and vascular death. RRs, adjusted for conventional risk factors, were: 1.10 (95% CI 1.05-1.16) with Lp-PLA(2) activity and 1.11 (1.07-1.16) with Lp-PLA(2) mass for coronary heart disease; 1.08 (0.97-1.20) and 1.14 (1.02-1.27) for ischaemic stroke; 1.16 (1.09-1.24) and 1.13 (1.05-1.22) for vascular mortality; and 1.10 (1.04-1.17) and 1.10 (1.03-1.18) for non-vascular mortality, respectively. RRs with Lp-PLA(2) did not differ significantly in people with and without initial stable vascular disease, apart from for vascular death with Lp-PLA(2) mass. Adjusted RRs for coronary heart disease were 1.10 (1.02-1.18) with non-HDL cholesterol and 1.10 (1.00-1.21) with systolic blood pressure. INTERPRETATION: Lp-PLA(2) activity and mass each show continuous associations with risk of coronary heart disease, similar in magnitude to that with non-HDL cholesterol or systolic blood pressure in this population. Associations of Lp-PLA(2) mass and activity are not exclusive to vascular outcomes, and the vascular associations depend at least partly on lipids. FUNDING: UK Medical Research Council, GlaxoSmithKline, and British Heart Foundation. OBJECTIVE: To examine associations between lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) antigen level (mass) and enzymatic activity (activity) and cardiovascular disease (CVD) in older adults. METHODS: We examined associations of Lp-PLA(2) mass and activity with incident myocardial infarction (MI; n=508), stroke (n=565) and CVD death (n=665) using Cox regressions adjusted for age, sex, ethnicity and CVD risk factors in 3949 older adults, aged > or =65 years at baseline, from the Cardiovascular Health Study (CHS). RESULTS: Lp-PLA(2) was associated with incident CVD events in these older adults. Hazard ratios (95% confidence intervals) for highest versus lowest tertiles of Lp-PLA(2) mass were 1.49 (1.19-1.85) for MI, 1.21 (0.98-1.49) for stroke and 1.11 (0.92-1.33) for CVD death. The highest tertile of Lp-PLA(2) activity was associated with MI (1.36; 1.09-1.70) and CVD death (1.23; 1.02-1.50). Combined Lp-PLA(2) tertile 3 and CRP>3mg/l, compared to Lp-PLA(2) tertile 1 and CRP<1mg/l, was associated with MI (2.29; 1.49-3.52) for Lp-PLA(2) mass and MI (1.66; 1.10-2.51) and CVD death (1.57; 1.08-2.26) for activity. For MI, both mass and activity added excess risk to elevated CRP alone ( approximately 20% excess risk) and activity added excess risk for CVD death ( approximately 12%). CONCLUSION: Lp-PLA(2) mass and activity were associated with incident CVD events in older adults in CHS. Lp-PLA(2) and CRP were independent and additive in prediction of events. While associations were modest, these results support further exploration of Lp-PLA(2) to identify older individuals at risk for CVD. OBJECTIVES: To describe retention according to age and visit type (clinic, home, telephone) and to determine characteristics associated with visit types for a longitudinal epidemiological study in older adults. DESIGN: Longitudinal cohort study. SETTING: Four U.S. clinical sites. PARTICIPANTS: Five thousand eight hundred eighty-eight Cardiovascular Health Study (CHS) participants aged 65 to 100 at 1989/90 or 1992/93 enrollment (58.6% female; 15.7% black). CHS participants were contacted every 6 months, with annual assessments through 1999 and in 2005/06 for the All Stars Study visit of the CHS cohort (aged 77-102; 66.5% female; 16.6% black). MEASUREMENTS: All annual contacts through 1999 (n=43,772) and for the 2005/06 visit (n=1,942). RESULTS: CHS had 43,772 total participant contacts from 1989 to 1999: 34,582 clinic visits (79.0%), 2,238 refusals (5.1%), 4,401 telephone visits (10.1%), 1,811 home visits (4.1%), and 740 other types (1.7%). In 2005/06, the All Stars participants of the CHS cohort had 36.6% clinic, 22.3% home, and 41.1% telephone visits. Compared with participants aged 65 to 69, odds ratios of not attending a CHS clinic visit were 1.82 (95% confidence interval (CI)=1.54-2.13), 2.94 (95% CI=2.45-3.57), 4.55 (95% CI=3.70-5.56), and 9.09 (95% CI=7.69-11.11) for those aged 70 to 74, 75 to 79, 80 to 84, and 85 and older, respectively, in sex-adjusted regression. In multivariable regression, participants with a 2005/06 clinic visit were younger, more likely to be male and in good health, and had had better cognitive and physical function 7 years earlier than participants with other visit types. Participants with home, telephone, and missing visits were similar on characteristics measured 7 years earlier. CONCLUSION: Offering home, telephone, and proxy visits are essential to optimizing follow-up of aging cohorts. Home visits increased in-person retention from 36.5% to 58.8% and diversified the cohort with respect to age, health, and physical functioning. Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV(1)) and its ratio to forced vital capacity (FEV(1)/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV(1)/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV(1) (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease. Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. BACKGROUND: Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum urate with gout and selected cardiovascular risk factors and coronary heart disease (CHD). METHODS AND RESULTS: Meta-analyses of genome-wide association studies (GWAS) were performed in 5 population-based cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology consortium for serum urate and gout in 28 283 white participants. The effect of the most significant single-nucleotide polymorphism at all genome-wide significant loci on serum urate was added to create a genetic urate score. Findings were replicated in the Women's Genome Health Study (n=22 054). Single-nucleotide polymorphisms at 8 genetic loci achieved genome-wide significance with serum urate levels (P=4×10(-8) to 2×10(-242) in SLC22A11, GCKR, R3HDM2-INHBC region, RREB1, PDZK1, SLC2A9, ABCG2, and SLC17A1). Only 2 loci (SLC2A9, ABCG2) showed genome-wide significant association with gout. The genetic urate score was strongly associated with serum urate and gout (odds ratio, 12.4 per 100 μmol/L; P=3×10(-39)) but not with blood pressure, glucose, estimated glomerular filtration rate, chronic kidney disease, or CHD. The lack of association between the genetic score and the latter phenotypes also was observed in the Women's Genome Health Study. CONCLUSIONS: The genetic urate score analysis suggested a causal relationship between serum urate and gout but did not provide evidence for one between serum urate and cardiovascular risk factors and CHD. This manuscript considers a data-mining approach for the prediction of mild obstructive sleep disordered breathing, defined as an elevated respiratory disturbance index (RDI), in 5,530 participants in a community-based study, the Sleep Heart Health Study. The prediction algorithm was built using modern ensemble learning algorithms, boosting in specific, which allowed for assessing potential high-dimensional interactions between predictor variables or classifiers. To evaluate the performance of the algorithm, the data were split into training and validation sets for varying thresholds for predicting the probability of a high RDI (≥7 events per hour in the given results). Based on a moderate classification threshold from the boosting algorithm, the estimated post-test odds of a high RDI were 2.20 times higher than the pre-test odds given a positive test, while the corresponding post-test odds were decreased by 52% given a negative test (sensitivity and specificity of 0.66 and 0.70, respectively). In rank order, the following variables had the largest impact on prediction performance: neck circumference, body mass index, age, snoring frequency, waist circumference, and snoring loudness. BACKGROUND: Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels. METHODS AND RESULTS: The setting of the study included 5 community-based studies for discovery comprising 23 608 European-ancestry participants: Atherosclerosis Risk In Communities Study, Cardiovascular Health Study, British 1958 Birth Cohort, Framingham Heart Study, and Rotterdam Study. All subjects had genome-wide single-nucleotide polymorphism (SNP) scans and at least 1 phenotype measured: FVII activity/antigen, FVIII activity, and vWF antigen. Each study used its genotype data to impute to HapMap SNPs and independently conducted association analyses of hemostasis measures using an additive genetic model. Study findings were combined by meta-analysis. Replication was conducted in 7604 participants not in the discovery cohort. For FVII, 305 SNPs exceeded the genome-wide significance threshold of 5.0x10(-8) and comprised 5 loci on 5 chromosomes: 2p23 (smallest P value 6.2x10(-24)), 4q25 (3.6x10(-12)), 11q12 (2.0x10(-10)), 13q34 (9.0x10(-259)), and 20q11.2 (5.7x10(-37)). Loci were within or near genes, including 4 new candidate genes and F7 (13q34). For vWF, 400 SNPs exceeded the threshold and marked 8 loci on 6 chromosomes: 6q24 (1.2x10(-22)), 8p21 (1.3x10(-16)), 9q34 (<5.0x10(-324)), 12p13 (1.7x10(-32)), 12q23 (7.3x10(-10)), 12q24.3 (3.8x10(-11)), 14q32 (2.3x10(-10)), and 19p13.2 (1.3x10(-9)). All loci were within genes, including 6 new candidate genes, as well as ABO (9q34) and VWF (12p13). For FVIII, 5 loci were identified and overlapped vWF findings. Nine of the 10 new findings were replicated. CONCLUSIONS: New genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders. Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from 2 different cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, n = 399; CHS-CS, n = 77) and AD (ADNI, n = 188; CHS, n = 36). In both AD and MCI groups, higher body mass index was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia. RATIONALE: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials. OBJECTIVE: To examine the relationship of parity with diabetes and markers of glucose homeostasis in older women. RESEARCH DESIGN AND METHODS: We used data from the female participants in the Cardiovascular Health Study, a longitudinal cohort of adults aged >or=65 years. These data included an assessment of parity (baseline) and fasting serum levels of glucose, insulin, and medication use (baseline and follow-up). We estimated both the cross-sectional relationship of parity with baseline diabetes and the relationship of parity with incident diabetes. RESULTS: In unadjusted analyses, women with grand multiparity (>or=5 live births) had a higher prevalence of diabetes at baseline compared with those with fewer births and with nulliparous women (25 vs. 12 vs. 15%; P < 0.001). In regression models controlling for age and race, grand multiparity was associated with increased prevalence of diabetes (prevalence ratio 1.57 [95% CI 1.20-2.06]); with addition of demographic and clinical factors to the model, the association was attenuated (1.33 [1.00-1.77]). In final models that included body anthropometrics, the association was no longer significant (1.21 [0.86-1.49]). In those without diabetes at baseline, parity was not associated with incident diabetes or with fasting glucose; however, there was a modest association of parity with fasting insulin and homeostasis assessment model of insulin resistance. CONCLUSIONS: Grand multiparity is associated with diabetes in elderly women in cross-sectional analyses. This relationship seems to be confounded and/or mediated by variation in body weight and sociodemographic factors by parity status. In older nondiabetic women, higher parity does not pose an ongoing risk of developing diabetes. Little is known about how many years of life and disability-free years seniors can gain through exercise. Using data from the Cardiovascular Health Study, the authors estimated the extra years of life and self-reported healthy life (over 11 years) and years without impairment in activities of daily living (over 6 years) associated with quintiles of physical activity (PA) in older adults from different age groups. They estimated PA from the Minnesota Leisure Time Activities Questionnaire. Multivariable linear regression adjusted for health-related covariates. The relative gains in survival and years of healthy life (YHL) generally were proportionate to the amount of PA, greater among those 75+, and higher in men. Compared with being sedentary, the most active men 75+ had 1.49 more YHL (95% CI: 0.79, 2.19), and the most active women 75+ had 1.06 more YHL (95% CI: 0.44, 1.68). Seniors over age 74 experience the largest relative gains in survival and healthy life from physical activity. OBJECTIVES: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation. METHODS: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline. RESULTS: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold. CONCLUSION: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment. BACKGROUND: Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. Mitochondrial genetic variation may contribute to altered susceptibility to the frailty syndrome in older adults. METHODOLOGY/PRINCIPAL FINDINGS: To assess potential mitochondrial genetic contributions to the likelihood of frailty, mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study (1989-1990, 1992-1993). At baseline, frailty was identified as the presence of three or more of five indicators (weakness, slowness, shrinking, low physical activity, and exhaustion). mtDNA variation was assessed in a pilot study, including 315 individuals selected as extremes of the frailty phenotype, using an oligonucleotide sequencing microarray based on the Revised Cambridge Reference Sequence. Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons: mt146, mt204, and mt228. In addition to pilot participants, 4,459 additional men and women with frailty classifications, and an overlapping subset of 4,453 individuals with grip strength measurements, were included in the study population genotyped at mt204 and mt228. In the study population, the mt204 C allele was associated with greater likelihood of frailty (adjusted odds ratio = 2.04, 95% CI = 1.07-3.60, p = 0.020) and lower grip strength (adjusted coefficient = -2.04, 95% CI = -3.33- -0.74, p = 0.002). CONCLUSIONS: This study supports a role for mitochondrial genetic variation in the frailty syndrome and later life muscle strength, demonstrating the importance of the mitochondrial genome in complex geriatric phenotypes. BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson's disease (PD), they typically have limited information for clinical diagnosis. METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD. RESULTS: We identified 60 cases with prevalent PD (1.0%; 95% confidence interval, CI = 0.8-1.3%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95% CI = 0.26-0.95) and for those who smoked ≥50 pack-years (OR = 0.53; 95% CI = 0.29-0.96). Estimates for smoking were similar when ≥2 data sources were required. Estimates for self-report alone were attenuated towards null. CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible. PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults. DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated. RESULTS: The prevalence of a major depressive state was higher in women, and increased with advancing age. The probability of becoming depressed increased with advancing age among the healthy but not the sick. Women showed a greater probability than men of becoming depressed, regardless of health status. Major depressive symptoms persisted over one-year intervals in about 60% of the healthy and 75% of the sick, with little difference between men and women. IMPLICATIONS: Clinically significant depressive symptoms occur commonly in older adults, especially women, increase with advancing age, are associated with poor self-rated health, and are largely intransigent. In order to limit the deleterious consequences of depression among older adults, increased attention to prevention, screening, and treatment is warranted. A self-rated health item could be used in clinical settings to refine the prognosis of late-life depression. BACKGROUND AND PURPOSE: In the discussion on the cost-effectiveness of screening, precise estimates of severe asymptomatic carotid stenosis are vital. Accordingly, we assessed the prevalence of moderate and severe asymptomatic carotid stenosis by age and sex using pooled cohort data. METHODS: We performed an individual participant data meta-analysis (23 706 participants) of 4 population-based studies (Malmö Diet and Cancer Study, Tromsø, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study). Outcomes of interest were asymptomatic moderate (> or =50%) and severe carotid stenosis (> or =70%). RESULTS: Prevalence of moderate asymptomatic carotid stenosis ranged from 0.2% (95% CI, 0.0% to 0.4%) in men aged <50 years to 7.5% (5.2% to 10.5%) in men aged > or =80 years. For women, this prevalence increased from 0% (0% to 0.2%) to 5.0% (3.1% to 7.5%). Prevalence of severe asymptomatic carotid stenosis ranged from 0.1% (0.0% to 0.3%) in men aged <50 years to 3.1% (1.7% to 5.3%) in men aged > or =80. For women, this prevalence increased from 0% (0.0% to 0.2%) to 0.9% (0.3% to 2.4%). CONCLUSIONS: The prevalence of severe asymptomatic carotid stenosis in the general population ranges from 0% to 3.1%, which is useful information in the discussion on the cost-effectiveness of screening. BACKGROUND: Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women. METHODS AND RESULTS: A total of 1927 men and 2495 women > or =40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men < or =70 years of age (adjusted hazard ratio 1.10 [95% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of any age. Among men 40 to 70 years old, those with AHI > or =30 were 68% more likely to develop coronary heart disease than those with AHI <5. Obstructive sleep apnea predicted incident heart failure in men but not in women (adjusted hazard ratio 1.13 [95% confidence interval 1.02 to 1.26] per 10-unit increase in AHI). Men with AHI > or =30 were 58% more likely to develop heart failure than those with AHI <5. CONCLUSIONS: Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal. Numerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1.6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR=1.60, 95% confidence interval [CI], 1.06-2.36; Population attributable fraction=6.7%, 95%CI, 1.0-10.3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR=2.02, 95%CI, 1.31-3.12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR=2.40, 95%CI, 1.40-4.12) than those with secondary VTE (RR=1.08, 95%CI, 0.63-1.85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE. Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16-25 years) and high (>25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with >25 years of SHS exposure and >25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0-15 years) SHS exposure and < or =25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD. The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95% CI = 0.90, 1.84) in ARIC and 1.80 (95% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study. BACKGROUND: Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the allele frequency and its clinical penetrance in community-dwelling African Americans. METHODS: Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls. RESULTS: One hundred nineteen (3.23%) of 3,712 ARIC and 17 (2.12%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38% vs 15%, relative risk 2.62, P = .04) and mortality (76% vs 53%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender- and ethnically matched controls. In ARIC (all subjects <65 years old), there were no differences between carriers and noncarriers in mortality, frequency of congestive heart failure, or findings consistent with cardiac amyloidosis. CONCLUSIONS: Heterozygosity for the amyloidogenic TTR V122I mutation is relatively common in community-dwelling African Americans. Before the age of 65 years, the allele has no discernible impact on cardiac function or mortality. After the age of 70 years, carriers show a higher frequency of congestive failure and greater mortality with more echocardiographic evidence suggestive of cardiac amyloidosis, findings consistent with age-dependent clinical penetrance of this autosomal dominant gene. STUDY OBJECTIVES: To compare health-related quality of life (HR-QOL) across subgroups defined by sleep disturbances and ethnicity. METHODS: Men (47%) and women (53%) Sleep Heart Health Study participants age 40 and older (N = 5237) underwent overnight polysomnography and completed self-report questionnaires on symptoms of sleep disturbances. The physical and mental composite scales (PCS and MCS) of the Medical Outcomes Study 36-item short form survey assessed HR-QOL and were compared to sleep data. RESULTS: Participants self-identified as Caucasian/White (n = 4482, 86%), African American/Black (n = 490, 9%), or Hispanic/Mexican American (n = 265, 5%). The prevalence of obstructive sleep apnea (OSA) was 17%, frequent snoring was 34%, difficulty initiating or maintaining sleep (DIMS; insomnia symptoms) was 30%, and excessive daytime sleepiness (EDS) was 25%. African American participants with frequent snoring, insomnia symptoms, or EDS had significantly poorer physical health compared to Caucasians (p < 0.001). Hispanics with frequent snoring, insomnia symptoms, or EDS had significantly poorer mental health than Caucasian participants (p <0.001). Neither PCS nor MCS scores differed significantly across ethnic subgroups for participants with moderate to severe OSA (respiratory disturbance index > 15, 4% desaturation). CONCLUSIONS: Across ethnic/racial subgroups, sleep disturbances are associated with worse physical and better mental HR-QOL than the U.S. norm, but this relationship may be moderated by comorbid health conditions. This study replicates and extends prior research indicating differences among minority and non-minority participants and highlights the need for future studies of sleep disturbances with larger samples of minorities that control for comorbid health conditions. RATIONALE: The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain. OBJECTIVE: To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort. METHODS: Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHI(REM)) and non-REM (AHI(NREM)) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36. MEASUREMENTS AND MAIN RESULTS: AHI(REM) was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHI(NREM) x AHI(REM) was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHI(NREM) was associated with the ESS score (beta = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (beta = -0.12; 95% CI, -0.42 to -0.01) and mental (beta = -0.20; 95% CI, -0.20 to -0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHI(REM). CONCLUSIONS: In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption. CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater. BACKGROUND: Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture. METHODS: Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline. RESULTS: During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women. CONCLUSIONS: Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown. BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. OBJECTIVE: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes. DESIGN: Prospective cohort study from 1992 to 2006. SETTING: Four U.S. communities. PATIENTS: 3736 adults in the Cardiovascular Health Study. MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women. RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. LIMITATION: Results could be affected by measurement error or residual confounding. CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. STUDY OBJECTIVES: Sleep continuity is commonly assessed with polysomnographic measures such as sleep efficiency, sleep stage percentages, and the arousal index. The aim of this study was to examine whether the transition rate between different sleep stages could be used as an index of sleep continuity to predict self-reported sleep quality independent of other commonly used metrics. DESIGN AND SETTING: Analysis of the Sleep Heart Health Study polysomnographic data. PARTICIPANTS: A community cohort. MEASUREMENTS AND RESULTS: Sleep recordings on 5,684 participants were deemed to be of sufficient quality to allow visual scoring of NREM and REM sleep. For each participant, we tabulated the frequency of transitions between wake, NREM sleep, and REM sleep. An overall transition rate was determined as the number of all transitions per hour sleep. Stage-specific transition rates between wake, NREM sleep, and REM sleep were also determined. A 5-point Likert scale was used to assess the subjective experience of restless and light sleep the morning after the sleep study. Multivariable regression models showed that a high overall sleep stage transition rate was associated with restless and light sleep independent of several covariates including total sleep time, percentages of sleep stages, wake time after sleep onset, and the arousal index. Compared to the lowest quartile of the overall transition rate (<7.76 events/h), the odds ratios for restless sleep were 1.27, 1.42, and 1.38, for the second (7.77-10.10 events/h), third (10.11-13.34 events/h), and fourth (≥13.35 events/h) quartiles, respectively. Analysis of stage-specific transition rates showed that transitions between wake and NREM sleep were also independently associated with restless and light sleep. CONCLUSIONS: Assessing overall and stage-specific transition rates provides a complementary approach for assessing sleep continuity. Incorporating such measures, along with conventional metrics, could yield useful insights into the significance of sleep continuity for clinical outcomes. BACKGROUND: We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups. METHODS: We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts in the age range 45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study) (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874 [16.2%] were African Americans). The risk algorithm included age, sex, body mass index, systolic blood pressure, electrocardiographic PR interval, hypertension treatment, and heart failure. RESULTS: We found 1359 incident AF events in 100 074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years; and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4 cases/1000 person-years). The strongest risk factors in all samples were age and heart failure. The relative risks for incident AF associated with risk factors were comparable across cohorts and race groups. After recalibration for baseline incidence and risk factor distribution, the Framingham algorithm, reported in C statistic, performed reasonably well in all samples: AGES, 0.67 (95% confidence interval [CI], 0.64-0.71); CHS whites, 0.68 (95% CI, 0.66-0.70); and CHS African Americans, 0.66 (95% CI, 0.61-0.71). Risk factors combined in the algorithm explained between 47.0% (AGES) and 63.6% (FHS) of the population-attributable risk. CONCLUSIONS: Risk of incident AF in community-dwelling whites and African Americans can be assessed reliably by routinely available and potentially modifiable clinical variables. Seven risk factors accounted for up to 64% of risk. BACKGROUND: The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model. METHODS AND RESULTS: Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5%) participants developed heart failure over 5 years versus 364 (6.8%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2% versus 2.8%, 9.0% versus 7.0%, 15.9% versus 13.7%, and 24.6% versus 30.8% for the <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5% to 10% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results. CONCLUSIONS: The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts. BACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model. METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring. RESULTS: The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR. CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings. OBJECTIVES: The objective of this study was to investigate the associations of mitral annular calcification, aortic annular calcification, and aortic valve sclerosis with covert magnetic resonance imaging (MRI)-defined brain infarcts. BACKGROUND: Clinically silent brain infarcts defined by MRI are associated with increased risk for cognitive decline, dementia, and future overt stroke. Left-sided cardiac valvular and annular calcifications are suspected as risk factors for clinical ischemic stroke. METHODS: A total of 2,680 CHS (Cardiovascular Health Study) participants without clinical histories of stroke or transient ischemic attack underwent brain MRI in 1992 and 1993, 1 to 2 years before echocardiographic exams (1994 to 1995). RESULTS: The mean age of the participants was 74.5 ± 4.8 years, and 39.3% were men. The presence of any annular or valvular calcification (mitral annular calcification, aortic annular calcification, or aortic valve sclerosis), mitral annular calcification alone, or aortic annular calcification alone was significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular or valve calcification remained associated with covert brain infarcts (risk ratio: 1.24; 95% confidence interval: 1.05 to 1.47). The degree of annular or valvular calcification severity showed a direct relation with the presence of covert MRI findings. CONCLUSIONS: Left-sided cardiac annular and valvular calcifications are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening in the progression of annular and valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk for cognitive impairment and future stroke. BACKGROUND: Thrombosis and inflammation are critical in stroke etiology, but associations of coagulation and inflammation gene variants with stroke, and particularly factor VII levels, are inconclusive. OBJECTIVES: To test the associations between 736 single-nucleotide polymorphisms (SNPs) between tagging haplotype patterns of 130 coagulation and inflammation genes, and stroke events, in the 5888 participants aged ≥ 65 years of the observational Cardiovascular Health Study cohort. PATIENTS/METHODS: With 16 years of follow-up, age-adjusted and sex-adjusted Cox models were used to estimate associations of SNPs and FVIIc levels with future stroke. RESULTS: Eight hundred and fifteen strokes occurred in 5255 genotyped participants without baseline stroke (748 ischemic strokes; 586 among whites). Among whites, six SNPs were associated with stroke, with a nominal P-value of < 0.01: rs6046 and rs3093261 (F7); rs4918851 and rs3781387 (HABP2); and rs3138055 (NFKB1A) and rs4648004 (NFKB1). Two of these SNPs were associated with FVIIc levels (units of percentage activity): rs6046 (β = -18.5, P = 2.38 × 10(-83)) and rs3093261 (β = 2.99, P = 3.93 × 10(-6)). After adjustment for age, sex, race, and cardiovascular risk factors, the association of FVIIc quintiles (Q) with stroke were as follows (hazard ratio; 95% confidence interval): Q1, reference; Q2, 1.4, 1.1-1.9); Q3, 1.1, 0.8-1.5); Q4, 1.5, 1.1-2.0); and Q5, 1.6, 1.2-2.2). Associations between SNPs and stroke were independent of FVIIc levels. CONCLUSIONS: Variations in FVII-related genes and FVIIc levels were associated with risk of incident ischemic stroke in this elderly cohort, suggesting a potential causal role for FVII in stroke etiology. Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression. BACKGROUND: Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts. METHODS AND RESULTS: The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7 × 10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7 × 10(-6)), MTHFD1L (rs6922269, P=5.1 × 10(-10)), APOE (rs429358; P=2.7×10(-18)), ZNF627 (rs4804611; P=5.0 × 10(-8)), CXCL12 (rs501120; P=1.4 × 10(-6)) and LPL (rs268; P=2.7 × 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities. CONCLUSIONS: Prospective analyses of white participants replicated several reported cross-sectional CHD-SNP associations. The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process. The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23,634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47,539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk. We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29,136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34,433) and the Women's Genome Health Study (n=23,019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=4.7×10(-10)), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P=9.5×10(-10)), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P=3.3×10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=3.8×10(-6)), as well as diastolic blood pressure (P=5.0×10(-8)) and hypertension (P=3.7×10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P=3.0×10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions. BACKGROUND: Prospective data suggest that sleep-disordered breathing enhances risk for incident and recurrent cardiovascular disease (CVD). However, a reverse causal pathway whereby incident CVD causes or worsens sleep-disordered breathing has not been studied. METHODS AND RESULTS: A total of 2721 Sleep Heart Health Study participants (mean age 62, standard deviation=10 years; 57% women; 23% minority) without CVD at baseline underwent 2 polysomnograms 5 years apart. Incident CVD events, including myocardial infarction, congestive heart failure, and stroke, were ascertained and adjudicated. The relation of incident CVD to change in apnea-hypopnea index between the 2 polysomnograms was tested with general linear models, with adjustment for age, sex, race, study center, history of diabetes mellitus, change in body mass index, change in neck circumference, percent sleep time spent in supine sleep, and time between the 2 polysomnograms. Incident CVD occurred in 95 participants between the first and second polysomnograms. Compared with participants without incident CVD, those with incident CVD experienced larger increases in apnea-hypopnea index between polysomnograms. The difference in adjusted mean apnea-hypopnea index change between subjects with and without incident CVD was 2.75 events per hour (95% confidence interval, 0.26 to 5.24; P=0.032). This association persisted after subjects with central sleep apnea were excluded. Compared with participants without incident CVD, participants with incident CVD had greater increases in both mean obstructive and central apnea indices, by 1.75 events per hour (95% confidence interval, 0.10 to 1.75; P=0.04) and by 1.07 events per hour (95% confidence interval, 0.40 to 1.74; P=0.001), respectively. CONCLUSIONS: In a diverse, community-based sample of middle-aged and older adults, incident CVD was associated with worsening sleep-disordered breathing over 5 years. OBJECTIVES: This study was conducted to evaluate mineral metabolism markers as potential risk factors for calcific aortic valve disease. BACKGROUND: Mineral metabolism disturbances are common among older people and may contribute to cardiac valvular calcification. Associations of serum mineral metabolism markers with cardiac valvular calcification have not been evaluated in a well-characterized general population of older adults. METHODS: We measured serum levels of phosphate, calcium, parathyroid hormone, and 25-hydroxyvitamin D in 1,938 Cardiovascular Health Study participants who were free of clinical cardiovascular disease and who underwent echocardiographic measurements of aortic valve sclerosis (AVS), mitral annular calcification (MAC), and aortic annular calcification (AAC). We used logistic regression models to estimate associations of mineral metabolism markers with AVS, MAC, and AAC after adjustment for relevant confounding variables, including kidney function. RESULTS: The respective prevalences of AVS, MAC, and AAC were 54%, 39%, and 44%. Each 0.5 mg/dl higher serum phosphate concentration was associated with greater adjusted odds of AVS (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.04 to 1.31, p = 0.01), MAC (OR: 1.12, 95% CI: 1.00 to 1.26, p = 0.05), and AAC (OR: 1.12, 95% CI: 0.99 to 1.25, p = 0.05). In contrast, serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations were not associated with aortic or mitral calcification. CONCLUSIONS: Higher serum phosphate levels within the normal range were associated with valvular and annular calcification in a community-based cohort of older adults. Phosphate may be a novel risk factor for calcific aortic valve disease and warrants further study. OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants. BACKGROUND AND PURPOSE: Carotid intima-media thickness and electrocardiographic left ventricular hypertrophy are 2 subclinical cardiovascular disease measures associated with increased risk of total and ischemic strokes. Increased intima-media thickness and electrocardiographic left ventricular hypertrophy also may reflect end-organ hypertensive effects. Information is scant on the associations of these subclinical measures with intracerebral hemorrhage (ICH). We hypothesized that greater carotid intima-media thickness and the presence of electrocardiographic left ventricular hypertrophy would be independently associated with increased ICH incidence. METHODS: Among 18,155 participants initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS), we assessed carotid intima-media thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy. Over a median of 18 years of follow-up, 162 incident ICH events occurred. RESULTS: After adjustment for other ICH risk factors, carotid intima-media thickness was associated positively with incidence of ICH in both ARIC and CHS. The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both studies). In CHS, having a carotid plaque was associated with a 2-fold (95% CI, 1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95% CI, 0.76-2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy carried a hazard ratio of ICH of 1.7 (95% CI, 0.77-3.7) in CHS and 2.8 (95% CI, 1.2-6.4) in ARIC. CONCLUSIONS: Our data suggest that people with carotid atherosclerosis and possibly left ventricular hypertrophy are at increased risk not only of ischemic stroke, but also of ICH. OBJECTIVE: The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis. METHODS: This study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association study to identify risk factors in other regions of the genome. A total of 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies. RESULTS: Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (P=0.002), but not variants in CYP2C8 (P=0.073) or UGTs (P=0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (P<0.001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P=1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (odds ratio: 0.48; 95% confidence interval: 0.36-0.63). CONCLUSION: We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin. BACKGROUND: Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown. OBJECTIVE: To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants. DESIGN: The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older. PARTICIPANTS: 1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2) were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003. MAIN MEASURES: The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol. KEY RESULTS: During 9.7 years of follow-up, 5% of the cohort progressed to ESRD, and 61% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD. CONCLUSIONS: Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD. BACKGROUND AND OBJECTIVES: There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke. RESULTS: Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95% CI, 1.55, 2.83). CONCLUSIONS: Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution. Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60, 95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment. BACKGROUND: Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of KIF6 (719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or KIF6 variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older. METHODS: Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI). RESULTS: Among white participants the FRS was improved by addition of KIF6 719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24). CONCLUSIONS: While none of these risk markers individually or in combination improved risk prediction among women, a combination of KIF6 719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies. Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR <60 ml/min per 1.73 m(2)): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications. BACKGROUND: Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality. METHODS: A cohort of 5888 individuals (mean 72.8 ± 5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables. RESULTS: At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all p < 0.001). Individuals with both depressive symptoms and physical inactivity had greater cardiovascular mortality than those with either individually (p < 0.001, log rank test). Physical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease. CONCLUSIONS: Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status. BACKGROUND: The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS: We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS: After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS: In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.). BACKGROUND: The optimal blood pressure level to minimize the risk of ischemic stroke (IS) in older adults is undetermined. Cerebral white matter lesions (WML), prevalent in older adults, may be a marker for vulnerability to IS. We aimed at determining the relationship between diastolic blood pressure (DBP) levels and IS in the presence of WML. METHODS: The Cardiovascular Health Study population (N = 3,345, age ≥ 65 years, N = 3,345) was followed between 1989 and 2002 for IS incidence. Survival analysis included quintiles of DBP analyzed within WML levels controlling for age and cardiovascular disease. RESULTS: DBP had no effect on IS incidence in low WML levels but had a marginally significant J-curve relationship with IS in high WML levels: the adjusted hazard ratio for IS in the lowest (<63 mmHg) and highest (≥ 80) DBP quintiles compared with the third (nadir, 69-73 mmHg) was 1.64 (95% confidence interval: 0.93-2.9) and 1.83 (95% confidence interval: 1.06-3.15), respectively. CONCLUSIONS: In older adults with low-grade WML, low DBP may not pose a risk for IS. However, in high-grade WML, IS risk may increase in DBP less than 69 mmHg but is highest more than 80 mmHg. People with high-grade WML may be at risk of IS in high and low DBP. Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 ± 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with ~2-3% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with ~2-2.5% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another. OBJECTIVE: To identify specific ECG and clinical predictors that separate atherosclerotic sudden cardiac death (SCD) from incident coronary heart disease (CHD) (non-fatal events and non-sudden death) in the combined cohorts of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. METHODS: This analysis included 18,497 participants (58% females, 24% black individuals, mean age 58 years) who were initially free of clinical CHD. A competing risk analysis was conducted to examine the prognostic significance of baseline clinical characteristics and an extensive electronic database of ECG measurements for prediction of 229 cases of SCD as a first event versus 2297 incident CHD cases (2122 non-fatal events and 175 non-sudden death) that occurred during a median follow-up time of 13 years in the Cardiovascular Health Study and 14 years in the Atherosclerosis Risk in Communities study. RESULTS: After adjusting for common CHD risk factors, a number of clinical characteristics and ECG measurements were independently predictive of SCD and CHD. However, the risk of SCD versus incident CHD was significantly different for race/ethnicity, hypertension, body mass index (BMI), heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2. Black race/ethnicity (compared to non-black) was predictive of high SCD risk but less risk of incident CHD (p value for differences in the risk (HR) for SCD versus CHD <0.0001). Hypertension, increased heart rate, prolongation of QTc and abnormally inverted T wave were stronger predictors of high SCD risk compared to CHD (p value=0.0460, 0.0398, 0.0158 and 0.0265, respectively). BMI was not predictive of incident CHD but was predictive of high SCD risk in a quadratic fashion (p value=0.0220). On the other hand, elevated ST height as measured at the J point and that measured at 60 ms after the J point in V2 were not predictive of SCD but were predictive of high incident CHD risk (p value=0.0251 and 0.0155, respectively). CONCLUSIONS: SCD and CHD have many risk factors in common. Hypertension, race/ethnicity, BMI, heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2 have the potential to separate between the risks of SCD and CHD. These results need to be validated in another cohort. While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations. BACKGROUND AND PURPOSE: Few studies have assessed post-glucose load measures of insulin resistance and ischemic stroke risk, and data are sparse for older adults. We investigated whether fasting and post-glucose load measures of insulin resistance were related to incident ischemic stroke in nondiabetic, older adults. METHODS: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without prevalent diabetes or stroke at baseline, followed for 17 years for incident ischemic stroke. The Gutt insulin sensitivity index was calculated from baseline body weight and from fasting and 2-hour postload insulin and glucose; a lower Gutt index indicates higher insulin resistance. RESULTS: Analyses included 3442 participants (42% men) with a mean age of 73 years. Incidence of ischemic stroke was 9.8 strokes per 1000 person-years. The relative risk (RR) for lowest quartile versus highest quartile of Gutt index was 1.64 (95% CI, 1.24-2.16), adjusted for demographics and prevalent cardiovascular and kidney disease. Similarly, the adjusted RR for highest quartile versus lowest quartile of 2-hour glucose was 1.84 (95% CI, 1.39-2.42). In contrast, the adjusted RR for highest quartile versus lowest quartile of fasting insulin was 1.10 (95% CI, 0.84-1.46). CONCLUSIONS: In nondiabetic, older adults, insulin resistance measured by Gutt index or 2-hour glucose, but not by fasting insulin, was associated with risk of incident ischemic stroke. BACKGROUND: De novo lipogenesis (DNL) is an endogenous pathway whereby carbohydrates and proteins are converted to fatty acids. DNL could affect coronary heart disease (CHD) or sudden cardiac arrest (SCA) via generation of specific fatty acids. Whether these fatty acids are prospectively associated with SCA or other CHD events is unknown. OBJECTIVE: The objective was to investigate the relations of 4 fatty acids in the DNL pathway-palmitic acid (16:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and cis-vaccenic acid (18:1n-7)-with incident CHD, including fatal CHD, nonfatal myocardial infarction (NFMI), and SCA. DESIGN: A community-based prospective study was conducted in 2890 men and women aged ≥65 y, who were free of known CHD at baseline and who were followed from 1992 to 2006. Cardiovascular disease risk factors and plasma phospholipid fatty acids were measured at baseline by using standardized methods. Incident CHD was ascertained prospectively and was centrally adjudicated by using medical records. Risk was assessed by using multivariable-adjusted Cox proportional hazards. RESULTS: During 29,835 person-years of follow-up, 631 CHD and 71 SCA events occurred. Both 18:1n-7 and 16:1n-9 were associated with a higher risk of SCA [multivariable-adjusted hazard ratio (95% CI) for the interquintile range: 7.63 (2.58, 22.6) for 18:1n-7 and 2.30 (1.16, 4.55) for 16:1n-9] but not of total CHD, fatal CHD, or NFMI. In secondary analyses censored to mid-follow-up (7 y) to minimize the effects of changes in concentrations over time, 16:1n-9 was also associated with a significantly higher risk of total CHD (2.11; 1.76, 2.54), including a higher risk of CHD death, NFMI, and SCA; 16:0 and 16:1n-7 were not associated with clinical CHD outcomes. CONCLUSION: Higher plasma phospholipid 18:1n-7 and 16:1n-9 concentrations were prospectively associated with an elevated risk of SCA but not of other CHD events, except in secondary analyses. CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE: To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES: Survival rates and life expectancy. RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults. The Minnesota Code (MC) and Novacode (Nova) are the most widely used electrocardiographic (ECG) classification systems. The comparative strengths of their classifications for Q- and ST-T-wave abnormalities in predicting coronary heart disease (CHD) events and total mortality have not been evaluated separately by gender. We studied standard 12-lead electrocardiograms at rest from 4,988 participants in the Cardiovascular Health Study. Average age at baseline was 73 years, 60% of participants were women 85% were white, and 22% had a history of cardiovascular disease or presence of ECG myocardial infarction by MC or Nova. Starting in 1989 with an average 17-year follow-up, 65% of participants died and 33% had incident CHD in a cohort free of cardiovascular disease at baseline. Of these, electrocardiograms with major Q-wave or major ST-T abnormalities by MC or Nova predicted increased risk for CHD events and total mortality with no significant differences in predictability between men and women. The study also found that women had fewer major Q-wave changes but more major ST-T abnormalities than men. However, there were no gender differences in predicting CHD events and total mortality. In conclusion, ECG classification systems for myocardial infarction/ischemia abnormalities by MC or Nova are valuable and useful for men and women in clinical trials and epidemiologic studies. Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study. Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50,000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2,000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16,324 EA and 3898 AA participants from the Candidate Gene Association Resource (CARe) consortium. Our aim was the discovery of new genomic loci and more detailed characterization of existing loci associated with FVII levels. In EAs, we identified three new loci associated with FVII, of which APOA5 on chromosome 11q23 and HNF4A on chromosome 20q12-13 were replicated in a sample of 4289 participants from the Whitehall II study. We confirmed four previously reported FVII-associated loci (GCKR, MS4A6A, F7 and PROCR) in CARe EA samples. In AAs, the F7 and PROCR regions were significantly associated with FVII. Several of the FVII-associated regions are known to be associated with lipids and other cardiovascular-related traits. At the F7 locus, there was evidence of at least five independently associated SNPs in EAs and three independent signals in AAs. Though the variance in FVII explained by the existing loci is substantial (20% in EA and 10% in AA), larger sample sizes and investigation of lower frequency variants may be required to identify additional FVII-associated loci in EAs and AAs and further clarify the relationship between FVII and other CVD risk factors. Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7)) and FNDC1 (p-value = 3.0×10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish. For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (~20,000), African American (~9,000), American Indian (~6,000), Mexican American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific Islander/Native Hawaiian (~175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits. Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries. BACKGROUND: Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. METHODS AND RESULTS: A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between ≈2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log–transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4×10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4×10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9×10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log–transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. CONCLUSIONS: Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported. Cerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3'-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n = 888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P = 0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3'-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently predicted six of the non-synonymous single nucleotide polymorphisms (H170R, P496L, V1183M, L1518M, D1823N and V1952M) to be functional, with four being exclusively or mainly detected in subjects with severe white matter lesions. In four individuals with rare non-synonymous single nucleotide polymorphisms, we noted anterior temporal lobe hyperintensity, hyperintensity in the external capsule, lacunar infarcts or subcortical lacunar lesions. None of the observed abnormalities were specific to cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. This is the first comprehensive study investigating (i) the frequency of NOTCH3 variations in community-dwelling elderly and (ii) their effect on cerebral small vessel disease related magnetic resonance imaging phenotypes. We show that the NOTCH3 gene is highly variable with both common and rare single nucleotide polymorphisms spreading across the gene, and that common variants at the NOTCH3 gene increase the risk of age-related white matter lesions in hypertensives. Additional investigations are required to explore the biological mechanisms underlying the observed association. Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance. Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4 × 10(-9)), PNPLA3 (rs738409, P = 5.8 × 10(-9)), RELA (rs1049728, P = 2.7 × 10(-16)), and SH2B3 (rs3184504, P = 2.9 × 10(-17)). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function. OBJECTIVE: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. METHODS: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. RESULTS: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 × 10(-9) ; p(replication) = 1.3 × 10(-7) ; p(combined) = 4.0 × 10(-15) ). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10(-9) ), rs11869977 (p = 5.7 × 10(-9) ), rs936393 (p = 6.8 × 10(-9) ), rs3744017 (p = 7.3 × 10(-9) ), and rs1055129 (p = 4.1 × 10(-8) ). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). INTERPRETATION: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P< 5.0 × 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P= 1.0 × 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P= 3.8 × 10(-32)) and SLC22A12 (P= 2.1 × 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P= 2.7 × 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants. Insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) are involved in cell replication, proliferation, differentiation, protein synthesis, carbohydrate homeostasis and bone metabolism. Circulating IGF-I and IGFBP-3 concentrations predict anthropometric traits and risk of cancer and cardiovascular disease. In a genome-wide association study of 10 280 middle-aged and older men and women from four community-based cohort studies, we confirmed a known association of single nucleotide polymorphisms in the IGFBP3 gene region on chromosome 7p12.3 with IGFBP-3 concentrations using a significance threshold of P < 5 × 10(-8) (P = 3.3 × 10(-101)). Furthermore, the same IGFBP3 gene locus (e.g. rs11977526) that was associated with IGFBP-3 concentrations was also associated with the opposite direction of effect, with IGF-I concentration after adjustment for IGFBP-3 concentration (P = 1.9 × 10(-26)). A novel and independent locus on chromosome 7p12.3 (rs700752) had genome-wide significant associations with higher IGFBP-3 (P = 4.4 × 10(-21)) and higher IGF-I (P = 4.9 × 10(-9)) concentrations; when the two measurements were adjusted for one another, the IGF-I association was attenuated but the IGFBP-3 association was not. Two additional loci demonstrated genome-wide significant associations with IGFBP-3 concentration (rs1065656, chromosome 16p13.3, P = 1.2 × 10(-11), IGFALS, a confirmatory finding; and rs4234798, chromosome 4p16.1, P = 4.5 × 10(-10), SORCS2, a novel finding). Together, the four genome-wide significant loci explained 6.5% of the population variation in IGFBP-3 concentration. Furthermore, we observed a borderline statistically significant association between IGF-I concentration and FOXO3 (rs2153960, chromosome 6q21, P = 5.1 × 10(-7)), a locus associated with longevity. These genetic loci deserve further investigation to elucidate the biological basis for the observed associations and clarify their possible role in IGF-mediated regulation of cell growth and metabolism. Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts. Pulse pressure and triglycerides were lower, high density lipids were higher, and a perceptual speed task and gait speed were better in LLFS. Age-specific comparisons showed differences that would be consistent with a higher peak, later onset of decline or slower rate of change across age in LLFS participants. These findings suggest several priority phenotypes for inclusion in future genetic analysis to identify loci contributing to exceptional survival. OBJECTIVES: To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it. DESIGN: Longitudinal cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57% female, 15% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included. MEASUREMENTS: Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors. RESULTS: Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N = 2,733). Participants with high BP (n = 293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n = 350). Rates were similar for those with history of hypertension who were uncontrolled (n = 110) or controlled (n = 87) at baseline and for those who were newly diagnosed (n = 96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results. CONCLUSION: High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted. CONTEXT: The physiological importance of endogenous testosterone (T) in older women is poorly understood. OBJECTIVE: The aim of the study was to determine the association of higher total and free T levels with bone mineral density (BMD), lean body mass, and fat mass in elderly women. DESIGN: Total and free T were measured using sensitive assays in 232 community-dwelling women aged 67-94 yr who were enrolled in the Cardiovascular Health Study and had dual-energy x-ray absorptiometry scans. Cross-sectional analyses were performed to examine associations between total and free T and BMD and body composition. RESULTS: In adjusted models, total T was directly associated with BMD at the lumbar spine (P = 0.04) and hip (P = 0.001), but not body composition outcomes, in all women, and after excluding estrogen users and adjusting for estradiol (P = 0.04 and 0.01, respectively). Free T was positively related to hip BMD, lean body mass, and body fat (all P < 0.05), with more than 10% differences in each outcome between women at the highest and lowest ends of the free T range, with attenuation after excluding estrogen users and adjusting for estradiol. CONCLUSIONS: In the setting of the low estradiol levels found in older women, circulating T levels were associated with bone density. Women with higher free T levels had greater lean body mass, consistent with the anabolic effect of T, and, in contrast to men, greater fat mass. Mechanistic studies are required to determine whether a causal relationship exists between T, bone, and body composition in this population and the degree to which any T effects are estrogen-independent. BACKGROUND AND PURPOSE: Little is known about the acute precipitants of ischemic stroke, although evidence suggests infections contribute to risk. We hypothesized that acute hospitalization for infection is associated with the short-term risk of stroke. METHODS: The case-crossover design was used to compare hospitalization for infection during case periods (90, 30, or 14 days before an incident ischemic stroke) and control periods (equivalent time periods exactly 1 or 2 years before stroke) in the Cardiovascular Health Study, a population-based cohort of 5888 elderly participants from 4 US sites. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. Confirmatory analyses assessed hazard ratios of stroke from Cox regression models, with hospitalization for infection as a time-varying exposure. RESULTS: During a median follow-up of 12.2 years, 669 incident ischemic strokes were observed in participants without a baseline history of stroke. Hospitalization for infection was more likely during case than control time periods; for 90 days before stroke, OR=3.4 (95% CI, 1.8 to 6.5). The point estimates of risks were higher when we examined shorter intervals: for 30 days, OR=7.3 (95% CI, 1.9 to 40.9), and for 14 days, OR=8.0 (95% CI, 1.7 to 77.3). In survival analyses, risk of stroke was associated with hospitalization for infection in the preceding 90 days, adjusted hazard ratio=2.4 (95% CI, 1.6 to 3.4). CONCLUSIONS: Hospitalization for infection is associated with a short-term increased risk of stroke, with higher risks observed for shorter intervals preceding stroke. BACKGROUND: Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals. METHODS AND RESULTS: -Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58% women, 17% blacks, 68% hypertension, 3600 had brain magnetic resonance imaging in 1992-1993, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11%) subjects had concurrent impairments and 3086 (66%) were intact on all 3 measures. Between 1992 and 1999, 651 (21%) became impaired in all 3 domains. Hypertensive individuals were more likely to be impaired at baseline (odds ratio 1.23, 95% confidence interval 1.04 to 1.42, P=0.01) and become impaired during the follow-up (hazard ratio=1.3, 95% confidence interval 1.02 to 1.66, P=0.037). A greater degree of white matter hyperintensities was associated with impairments in the 3 domains (P=0.007) and mediated the association with hypertension (P=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21% hazard ratio change). Impairments in the 3 domains increased subsequent disability with hypertension (P<0.0001). Hypertension mortality also was increased in those impaired (compared with unimpaired hypertensive individuals: HR=1.10, 95% confidence interval 1.04 to 1.17, P=0.004). CONCLUSIONS: Hypertension increases the risk of concurrent impairments in mobility, cognition, and mood, which increases disability and mortality. This association is mediated in part by microvascular brain injury. Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). STUDY OBJECTIVE: The Epworth Sleepiness Scale (ESS) has been used to detect patients with potential sleep disordered breathing (SDB). Recently, a 4-Variable screening tool was proposed to identify patients with SDB, in addition to the STOP and STOP-Bang questionnaires. This study evaluated the abilities of the 4-Variable screening tool, STOP, STOP-Bang, and ESS questionnaires in identifying subjects at risk for SDB. METHODS: A total of 4,770 participants who completed polysomnograms in the baseline evaluation of the Sleep Heart Health Study (SHHS) were included. Subjects with RDIs ≥ 15 and ≥ 30 were considered to have moderate-to-severe or severe SDB, respectively. Variables were constructed to approximate those in the questionnaires. The risk of SDB was calculated by the 4-Variable screening tool according to Takegami et al. The STOP and STOP-Bang questionnaires were evaluated including variables for snoring, tiredness/sleepiness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender. Sleepiness was evaluated using the ESS questionnaire and scores were dichotomized into < 11 and ≥ 11. RESULTS: The STOP-Bang questionnaire had higher sensitivity to predict moderate-to-severe (87.0%) and severe (70.4%) SDB, while the 4-Variable screening tool had higher specificity to predict moderate-to-severe and severe SDB (93.2% for both). CONCLUSIONS: In community populations such as the SHHS, high specificities may be more useful in excluding low-risk patients, while avoiding false positives. However, sleep clinicians may prefer to use screening tools with high sensitivities, like the STOP-Bang, in order to avoid missing cases that may lead to adverse health consequences and increased healthcare costs. BACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied. METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)). RESULTS: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline. CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression. BACKGROUND: The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. METHODS AND RESULTS: We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95% CI, 1.16-1.69; P=0.0005). CONCLUSIONS: In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans. OBJECTIVES: The goal of this paper was to determine whether assessment of left ventricular ejection fraction (LVEF) enhances prediction of new-onset heart failure (HF) and cardiovascular mortality over and above N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in older adults. BACKGROUND: Elevated NT-proBNP levels are common in older adults and are associated with increased risk of HF. METHODS: NT-proBNP and LVEF were measured in 4,137 older adults free of HF. Repeat measures of NT-proBNP were performed 2 to 3 years later and echocardiography was repeated 5 years later (n = 2,375), with a median follow-up of 10.7 years. The addition of an abnormal (<55%) LVEF (n = 317 [7.7%]) to initially elevated or rising NT-proBNP levels was evaluated to determine risk of HF or cardiovascular mortality. Changes in NT-proBNP levels were also assessed for estimating the risk of conversion from a normal to abnormal LVEF. RESULTS: For participants with a low baseline NT-proBNP level (<190 pg/ml; n = 2,918), addition of an abnormal LVEF did not improve the estimation of risk of HF and identified a moderate increase in adjusted risk for cardiovascular mortality (hazard ratio: 1.69 [95% confidence interval: 1.22 to 2.31]). Among those whose NT-proBNP subsequently increased ≥25% to ≥190 pg/ml, an abnormal LVEF was likewise associated with an increased risk of cardiovascular mortality but not HF. Participants with an initially high NT-proBNP level (≥190 pg/ml) were at greater risk overall for both outcomes, and those with an abnormal LVEF were at the highest risk. However, an abnormal LVEF did not improve model classification or risk stratification for either endpoint when added to demographic factors and change in NT-proBNP. An initially elevated NT-proBNP or rising level was associated with an increased risk of developing an abnormal LVEF. CONCLUSIONS: Assessment of LVEF in HF-free older adults based on NT-proBNP levels should be considered on an individual basis, as such assessments do not routinely improve prognostication. BACKGROUND: Leukocyte telomere length (LTL) is related to diseases of aging, but studies of mortality have been inconsistent. METHODS: We evaluated LTL in relation to total mortality and specific cause of death in 1,136 participants of the Cardiovascular Health Study who provided blood samples in 1992-1993 and survived through 1997-1998. LTL was measured by Southern blots of the terminal restriction fragments. Cause of death was classified by a committee of physicians reviewing death certificates, medical records, and informant interviews. RESULTS: A total of 468 (41.2%) deaths occurred over 6.1 years of follow-up in participants with mean age of 73.9 years (SD 4.7), 65.4% female, and 14.8% African American. Although increased age and male gender were associated with shorter LTLs, African Americans had significantly longer LTLs independent of age and sex (p < .001). Adjusted for age, sex, and race, persons with the shortest quartile of LTL were 60% more likely to die during follow-up than those within the longest quartile (hazard ratio: 1.61, 95% confidence interval: 1.22-2.12, p = .001). The association remained after adjustment for cardiovascular disease risk factors. Evaluations of cause of death found LTL to be related to deaths due to an infectious disease etiology (hazard ratio: 2.80, 95% confidence interval: 1.32-5.94, p = .007), whereas a borderline association was found for cardiac deaths (hazard ratio: 1.82, 95% confidence interval: 0.95-3.49, p = .07) in adjusted models. Risk estimates for deaths due to cancer, dementia, and ischemic stroke were not significant. CONCLUSION: These data weakly corroborate prior findings of associations between LTL and mortality in the elderly. AIMS/HYPOTHESIS: Type 2 diabetes is an established risk factor for cardiovascular disease (CVD). This increased risk may be due in part to the increased levels of inflammatory factors associated with diabetes. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a risk marker for CVD and has pro-inflammatory effects in atherosclerotic plaques. We therefore sought to determine whether Lp-PLA(2) levels partially explain the greater prevalence of subclinical CVD and greater incidence of CVD outcomes associated with type 2 diabetes in the Cardiovascular Health Study. METHODS: We conducted a cross-sectional and prospective study of 4,062 men and women without previous CVD from the Cardiovascular Health Study (1989 to 2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Subclinical disease was determined at baseline and incident CVD was ascertained annually. We used logistic regression for cross-sectional analyses and Cox proportional hazards models for incident analyses. RESULTS: At baseline, Lp-PLA(2) mass did not differ significantly by type 2 diabetes status; however, Lp-PLA(2) activity was significantly higher among type 2 diabetic individuals. Baseline subclinical disease was significantly associated with baseline diabetes and this association was similar in models unadjusted or adjusted for Lp-PLA(2) (OR 1.68 [95% CI 1.31-2.15] vs OR 1.67 [95% CI 1.30-2.13]). Baseline type 2 diabetes was also significantly associated with incident CVD events, including fatal CHD, fatal myocardial infarction (MI) and non-fatal MI in multivariable analyses. There were no differences in these estimates after further adjustment for Lp-PLA(2) activity. CONCLUSIONS/INTERPRETATION: In this older cohort, differences in Lp-PLA(2) activity did not explain any of the excess risk for subclinical disease or CVD outcomes related to diabetes. Several studies have reported that taller individuals are at greater risk of venous thromboembolism (VTE). We hypothesised that longer leg length would be positively associated with incident VTE, and would explain the height association. LITE ascertained VTE in a prospective population-based sample of 21,860 individuals aged 45 and older. Leg length was measured as standing height minus torso length. Cox regression models were adjusted for age, race, sex, waist circumference, diabetes, and factor VIII. To evaluate whether leg length was associated with VTE risk independent of height, we standardised leg length and height per 1 standard deviation (SD), and then included them simultaneously in Cox regression models. A total of 641 incident VTE cases accrued over a median follow-up of 16 years. Participants in the highest quintile of leg length were at 59% (95% CI: 22%-108%) greater risk of VTE, relative to the lowest quintile. For height, risk was 45% (12%-88%) greater for those in the highest quintile, compared to the lowest. When leg length and height were modelled simultaneously leg length remained associated with VTE risk (HR per 1 SD: 1.21 (1.04-1.40) while height was unrelated (HR per 1 SD: 1.00 (0.86-1.16). To conclude, participants with longer legs were at greater risk of incident VTE, and leg length explained the relation of height to VTE. It remains to be established whether this finding is due to greater venous surface area, a larger number of venous valves, or greater hydrostatic pressure among individuals with longer legs. BACKGROUND AND OBJECTIVES: Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years. RESULTS: Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant. CONCLUSIONS: Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI. BACKGROUND: Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined. METHODS: We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176). RESULTS: Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p = .55), as compared with smaller changes for both. CONCLUSION: Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously. Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors. OBJECTIVES: To determine whether disease burden is associated with frailty independent of diagnosed chronic disease and whether physiological measurements provide greater understanding of the etiology of frailty. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: Two thousand four hundred thirty-seven participants in the Cardiovascular Health Study, 1992/93 examination (mean age 74.8 ± 4.8, 43.4% male, 95.8% white). MEASUREMENTS: Disease burden and frailty were tabulated using 10-point scales (0 = healthy, 10 = unhealthy). Disease burden was the sum of measurements characterizing the vasculature, brain, kidneys, lungs, and glucose metabolism. Frailty was assessed using the frailty index reported by Fried. Multivariate linear models were used to determine the association between disease burden (predictor) and frailty (outcome). RESULTS: Unadjusted, 1-point-higher disease burden was associated with a 0.28-point-higher frailty score (P < .001). White matter grade, forced vital capacity, and cystatin-C were particularly strongly and significantly associated with frailty. Disease burden attenuated the association between frailty and age by 29%, and disease burden and age had similar associations with frailty. Disease burden attenuated the association between frailty and fibrinogen, Factor VIII, and C-reactive protein by 32%, 56%, and 83%, respectively. Frailty was associated with diagnosed depression, stroke, cognitive impairment, arthritis, and pulmonary disease but not coronary heart disease, diabetes mellitus, or kidney disease in the presence of a summary of disease burden. In the adjusted model, disease burden remained significantly associated with frailty (β = 0.11, P < .001). CONCLUSION: Disease burden was independently and significantly associated with frailty. These results emphasize that typically unrecognized physiological changes may contribute significantly to frailty. The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (≥ 30 kg/m²) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints for obesity, although BMI-defined overweight (25-29.9 kg/m² was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints. INTRODUCTION: Genetic discoveries are validated through the meta-analysis of genome-wide association scans in large international consortia. Because environmental variables may interact with genetic factors, investigation of differing genetic effects for distinct levels of an environmental exposure in these large consortia may yield additional susceptibility loci undetected by main effects analysis. We describe a method of joint meta-analysis (JMA) of SNP and SNP by Environment (SNP × E) regression coefficients for use in gene-environment interaction studies. METHODS: In testing SNP × E interactions, one approach uses a two degree of freedom test to identify genetic variants that influence the trait of interest. This approach detects both main and interaction effects between the trait and the SNP. We propose a method to jointly meta-analyze the SNP and SNP × E coefficients using multivariate generalized least squares. This approach provides confidence intervals of the two estimates, a joint significance test for SNP and SNP × E terms, and a test of homogeneity across samples. RESULTS: We present a simulation study comparing this method to four other methods of meta-analysis and demonstrate that the JMA performs better than the others when both main and interaction effects are present. Additionally, we implemented our methods in a meta-analysis of the association between SNPs from the type 2 diabetes-associated gene PPARG and log-transformed fasting insulin levels and interaction by body mass index in a combined sample of 19,466 individuals from five cohorts. CONTEXT: Disturbances in mineral metabolism are associated with lower bone mineral density and fracture; however, previous human studies have assessed individual mineral metabolism markers in isolation. OBJECTIVE: We assessed serum concentrations of 25-hydroxyvitamin D (25-OHD), PTH, and bone-specific alkaline phosphatase (BAP) concentrations individually, and in combination, in association with the long-term risk of hip fracture among a general population of older adults. DESIGN AND SETTING: We studied 2294 participants from the Cardiovascular Health Study (mean age 74 yr) who were ambulatory and free of hip fracture and known cardiovascular disease at baseline. We used proportional hazards models to evaluate associations of baseline serum 25-OHD, PTH, and BAP concentrations with the time to first hospitalized hip fracture. RESULTS: During a median of 13 yr of follow-up, 242 participants (10.6%) developed an incident hip fracture. Serum 25-OHD concentrations less than 15 ng/ml were associated with a 61% greater adjusted risk of fracture (95% confidence interval 12-132% greater). In contrast, neither serum PTH nor BAP concentrations were significantly associated with fracture risk. The association of 25-OHD deficiency with hip fracture was not significantly altered by either PTH or BAP concentrations. CONCLUSIONS: Serum concentrations of 25-OHD, but not PTH or BAP, are associated with long-term hip fracture risk among ambulatory older adults. These data suggest that 25-OHD is the most relevant mineral metabolism marker of fracture risk among older people. BACKGROUND AND PURPOSE: Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. METHODS: We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. RESULTS: Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. CONCLUSIONS: Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors. BACKGROUND: Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality as well as with sudden death in women. OBJECTIVE: The purpose of this study was to examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population. METHODS: The risk of SCD associated with baseline NT-proBNP was examined in 5,447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP. RESULTS: Over a median follow-up of 12.5 years (maximum 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95% confidence interval [2.9, 6.1]; P <.001) in the highest quintile compared with in the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the fifth versus the first quintile of 2.5 (95% confidence interval [1.6, 3.8]; P <.001). CONCLUSION: NT-proBNP provides information regarding the risk of SCD in a community-based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions. OBJECTIVES: To estimate the likelihood of, and factors associated with, recovery from exhaustion in older adults. DESIGN: Secondary analysis of a cohort study. SETTING: Six annual examinations in four U.S. communities. PARTICIPANTS: Four thousand five hundred eighty-four men and women aged 69 and older. MEASUREMENTS: Exhaustion was considered present when a participant responded "a moderate amount" or "most of the time" to either of two questions: "How often have you had a hard time getting going?" and "How often does everything seem an effort?" RESULTS: Of the 964 participants who originally reported exhaustion, 634 (65.8%) were exhaustion free at least once during follow-up. When data from all time points were considered, 48% of those who reported exhaustion were exhaustion free the following year. After adjustment for age, sex, race, education, and marital status, 1-year recovery was less likely in individuals with worse self-rated health and in those who were taking six or more medications or were obese, depressed, or had musculoskeletal pain or history of stroke. In proportional hazards models, the following risk factors were associated with more persistent exhaustion over 5 years: poor self-rated health, six or more medications, obesity, and depression. Recovery was not less likely in participants with a history of cancer or heart disease. CONCLUSION: Exhaustion is common in old age but is dynamic, even in those with a history of cancer and congestive heart failure. Recovery is especially likely in seniors who have a positive perception of their overall health, take few medications, and are not obese or depressed. These findings support the notion that resiliency is associated with physical and psychological well-being. BACKGROUND: Although long-chain omega-3 fatty acid (n-3 FA) consumption estimated via food-frequency questionnaires has been associated with a higher incidence of diabetes, limited prospective data on diabetes risk are available that use objective biomarkers of n-3 FAs. OBJECTIVE: We sought to examine the relation between plasma phospholipid n-3 FAs and incident diabetes. DESIGN: We prospectively analyzed data in 3088 older men and women (mean age: 75 y) from the Cardiovascular Health Study (1992-2007). Plasma phospholipid n-3 FAs were measured by using gas chromatography, and incident diabetes was ascertained by using information on hypoglycemic agents and serum glucose. We used Cox proportional hazards models to estimate multivariable-adjusted relative risks. RESULTS: During a median follow-up of 10.6 y, 204 new cases of diabetes occurred. In a multivariable model that controlled for age, sex, race, clinic site, body mass index, alcohol intake, smoking, physical activity, LDL cholesterol, and linoleic acid, relative risks (95% CIs) for diabetes were 1.0 (reference), 0.96 (0.65, 1.43), 1.03 (0.69, 1.54), and 0.64 (0.41, 1.01) across consecutive quartiles of phospholipid eicosapentaenoic acid and docosahexaenoic acid (P for trend = 0.05). Corresponding relative risks (95% CIs) for phospholipid α-linolenic acid (ALA) were 1.0 (reference), 0.93 (0.65, 1.34), 0.99 (0.68, 1.44), and 0.57 (0.36, 0.90) (P for trend = 0.03). CONCLUSIONS: With the use of objective biomarkers, long-chain n-3 FAs and ALA were not associated with a higher incidence of diabetes. Individuals with the highest concentrations of both types of FAs had lower risk of diabetes. Depression and natriuretic peptides predict heart failure (HF) progression, but the unique contributions of depression and biomarkers associated with HF outcomes are not known. The present study determined the additive predictive value of depression and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) for new-onset HF in HF-free subjects and mortality in patients with HF. The participants in the Cardiovascular Health Study were assessed for depressive symptoms using the Center for Epidemiologic Studies Depression Scale and NT-proBNP using an electrochemiluminescence immunoassay. The validated cutoff values for depression (Center for Epidemiologic Studies Depression Scale ≥8) and NT-proBNP (≥190 pg/ml) were used. The risks of incident HF and mortality (cardiovascular disease-related and all-cause) were examined during a median follow-up of 11 years, adjusting for demographics, clinical factors, and health behaviors. In patients with HF (n = 208), depression was associated with an elevated risk of cardiovascular disease mortality (hazard ratios [HR] 2.07, 95% confidence interval [CI] 1.31 to 3.27) and all-cause mortality (HR 1.49, 95% CI 1.05 to 2.11), independent of the NT-proBNP level and covariates. The combined presence of depression and elevated NT-proBNP was associated with substantially elevated covariate-adjusted risks of cardiovascular disease mortality (HR 5.42, 95% CI 2.38 to 12.36) and all-cause mortality (HR 3.72, 95% CI 2.20 to 6.37). In the 4,114 HF-free subjects, new-onset HF was independently predicted by an elevated NT-proBNP level (HR 2.27, 95% CI 1.97 to 2.62) but not depression (HR 1.08, 95% CI 0.92 to 1.26) in covariate-adjusted analysis. In conclusion, depression and NT-proBNP displayed additive predictive value for mortality in patients with HF. These associations can be explained by complementary pathophysiologic mechanisms. The presence of both elevated depression and NT-proBNP levels might improve the identification of patients with HF with a high risk of mortality. BACKGROUND: Despite widespread use, there are no data on initiation of thyroid hormone use in older people. We report the prevalence of thyroid hormone use and predictors of thyroid hormone initiation in a population of older men and women. METHODS: Thyroid hormone medication data were collected annually from 1989 to 2006 in community-dwelling individuals aged 65 years and older enrolled in the Cardiovascular Health Study (N = 5,888). Associations of age, sex, race, body mass index, education, and coronary heart disease with initiation were evaluated using discrete-time survival analysis. RESULTS: In 1989-1990, 8.9% (95% confidence interval 8.1%-9.7%) of participants were taking a thyroid hormone preparation, increasing to 20.0% (95% confidence interval 8.2%-21.8%) over 16 years. The average initiation rate was 1% per year. The initiation rate was nonlinear with age, and those aged 85 years and older initiated thyroid hormone more than twice as frequently as those aged 65-69 years (hazard ratio = 2.34; 95% confidence interval 1.43-3.85). White women were more likely to initiate thyroid hormone than any other race and sex group. Higher body mass index was independently associated with higher risk for initiation (p = .002) as was greater education (p = .02) and prevalent coronary heart disease (p = .03). CONCLUSIONS: Thyroid hormone use is common in older people. The indications and benefits of thyroid hormone use in older individuals with the highest rate of thyroid hormone initiation-the oldest old, overweight and obese individuals, and those with coronary heart disease-should be investigated. BACKGROUND AND PURPOSE: To determine whether progression of MRI-defined vascular disease predicts subsequent vascular events in the elderly. METHODS: The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows us to address this question because its participants had 2 MRI scans≈5 years apart and have been followed for ≈9 years since the follow-up scan for incident vascular events. RESULTS: Both MRI-defined incident infarcts and worsened white matter grade were significantly associated with heart failure, stroke, and death, but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened white matter grade were present for heart failure (hazard ratio, 1.79; 95% confidence interval, 1.18-2.73), stroke (hazard ratio, 2.58; 95% confidence interval, 1.53-4.36), death (hazard ratio, 1.69; 95% confidence interval, 1.28-2.24), and cardiovascular death (hazard ratio, 1.97; 95% confidence interval, 1.24-3.14). CONCLUSIONS: Progression of MRI-defined vascular disease identifies elderly people at increased risk for subsequent heart failure, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown. BACKGROUND: The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals. METHODS AND RESULTS: In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3-17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups. CONCLUSIONS: In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133. INTRODUCTION: We examined whether heart rate turbulence (HRT) and C-reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk. METHODS AND RESULTS: One thousand two hundred and seventy-two individuals, age ≥ 65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low-risk group [HR 7.9, 95% confidence interval (CI) 2.8-22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95% CI 1.5-4.0, P = 0.016] and [HR 2.7, 95% CI 1.2-5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low-risk individuals [HR 2.5, 95% CI 1.3-5.1, P = 0.009]. Among low risk, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. CONCLUSIONS: Abnormal HRT independently adds to risk stratification of low, intermediate and high-risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk. BACKGROUND: As the heart failure population continues to age, disability is becoming an increasingly important issue. Our objective was to identify risk factors for the onset of disability in activities of daily living among older persons with heart failure. METHODS: The study population included participants with newly diagnosed heart failure from the Cardiovascular Health Study, a longitudinal study of community-living, older persons. Data were collected through annual examinations. Cox regression modeling was used to examine associations between time-dependent predictors and onset of disability. RESULTS: Of 461 participants newly diagnosed with heart failure (mean age 78.7 [SD 5.89]), 23% subsequently developed disability. The first year after heart failure diagnosis was the period of greatest risk for onset of disability (chi-square P value <.001). Factors that were independently associated with disability included: impaired gait speed (HR 2.29, 95% CI 1.34-3.90); impaired cognition (HR 1.87, 95% CI 1.14-3.05); and depressive symptoms (HR 1.72, 95% CI 1.04-2.83). CONCLUSIONS: Onset of disability is a common occurrence among older persons newly diagnosed with heart failure. Risk factors for onset of disability in this population are potentially modifiable, and should be routinely assessed in an effort to reduce disability in this growing population. BACKGROUND/AIMS: Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults. METHODS: The association of baseline urate (µmol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 µmol/l), middle (300-500 µmol/l), and high (>500 µmol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD. RESULTS: Women had significantly lower urate concentrations than did men [316.8 µmol/l (SD 88.0) vs. 367.4 µmol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 µmol/l (OR 1.69, 95% CI 1.03-2.78) but not for urate >500 µmol/l (OR 1.55, 95% CI 0.72-3.32) in men. A negative linear term was significant for urate <500 µmol/l, and across the entire range a convex quadratic term was significant. CONCLUSIONS: Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk. Low circulating concentrations of 25-hydroxyvitamin D (25(OH)D) are associated with adverse health outcomes in diverse populations. However, 25(OH)D concentrations vary seasonally with varying exposure to sunlight, so single measurements may poorly reflect long-term 25(OH)D exposure. The authors investigated cyclical trends in average serum 25(OH)D concentrations among 2,298 individuals enrolled in the Cardiovascular Health Study of community-based older adults (1992-1993). A sinusoidal model closely approximated observed 25(OH)D concentrations and fit the data significantly better than did a mean model (P < 0.0001). The mean annual 25(OH)D concentration was 25.1 ng/mL (95% confidence interval: 24.7, 25.5), and the mean peak-trough difference was 9.6 ng/mL (95% confidence interval: 8.5, 10.7). Male sex, higher latitude of study site, and greater physical activity levels were associated with larger peak-trough difference in 25(OH)D concentration (each P < 0.05). Serum concentrations of intact parathyroid hormone and bone-specific alkaline phosphatase also varied in a sinusoidal fashion (P < 0.0001), inversely to 25(OH)D. In conclusion, serum 25(OH)D varies in a sinusoidal manner, with large seasonal differences relative to mean concentration and laboratory evidence of biologic sequelae. Single 25(OH)D measurements might not capture overall vitamin D status, and the extent of misclassification could vary by demographic and behavioral factors. Accounting for collection time may reduce bias in research studies and improve decision-making in clinical care. BACKGROUND: Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease. METHODS: We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4.56 kg/m(2) higher BMI, 12.6 cm higher waist circumference, and 0.083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios. RESULTS: Individual records were available for 221,934 people in 17 countries (14,297 incident cardiovascular disease outcomes; 1.87 million person-years at risk). Serial adiposity assessments were made in up to 63,821 people (mean interval 5.7 years [SD 3.9]). In people with BMI of 20 kg/m(2) or higher, HRs for cardiovascular disease were 1.23 (95% CI 1.17-1.29) with BMI, 1.27 (1.20-1.33) with waist circumference, and 1.25 (1.19-1.31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1.07 (1.03-1.11) with BMI, 1.10 (1.05-1.14) with waist circumference, and 1.12 (1.08-1.15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of -0.0001, -0.0001, and 0.0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement -0.19%, -0.05%, and -0.05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0.95, 95% CI 0.93-0.97) than for waist circumference (0.86, 0.83-0.89) or waist-to-hip ratio (0.63, 0.57-0.70). INTERPRETATION: BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids. FUNDING: British Heart Foundation and UK Medical Research Council. BACKGROUND AND OBJECTIVES: Mounting evidence suggests that 1,25-dihydroxyvitamin D prevents the progression of chronic kidney disease (CKD). It is not clear whether "nutritional" forms of vitamin D affect GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We tested whether serum 25-hydroxyvitamin D concentration (25(OH)D), a measure of total vitamin D intake from cutaneous synthesis and dietary consumption, is associated with loss of estimated GFR among 1705 older adults with predominantly normal baseline kidney function participating in the Cardiovascular Health Study. Baseline 25(OH)D was measured by HPLC-tandem mass spectrometry. GFR was estimated at baseline and 4 years later using the CKD-EPI formula, with rapid GFR loss defined as 12 ml/min per 1.73 m(2) or more over 4 years. RESULTS: Rapid GFR loss was observed for 207 participants (12%). Each 10 ng/ml lower 25(OH)D was associated with a 25% greater risk of rapid GFR loss (95% confidence interval [CI] 5%, 49%, P = 0.01), adjusting for potential confounding characteristics. Compared with 25(OH)D ≥30 ng/ml, 25(OH)D concentrations 15 to 29 ng/ml and <15 ng/ml were associated with 29% (95% CI -13%, 91%) and 68% (95% CI 1%, 177%) greater adjusted risks of rapid GFR loss, respectively. Magnitudes of association were largest among participants with diabetes. RESULTS: were similar evaluating a composite outcome of rapid GFR loss, end stage renal disease, and death. Conclusions Insufficient 25(OH)D may be a modifiable risk factor for early GFR loss. We recommend clinical trials to determine whether vitamin D supplementation prevents the development and progression of CKD. OBJECTIVES: To examine the association between 25-hydroxyvitamin D (25(OH)D) and physical function in adults of advanced age. DESIGN: Cross-sectional and longitudinal analysis of physical function over 3 years of follow-up in the Cardiovascular Health Study All Stars. SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Community-dwelling adults aged 77 to 100 (N = 988). MEASUREMENTS: Serum 25-hydroxyvitamin D 25(OH)D), Short Physical Performance Battery (SPPB), and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADLs) disability were assessed at baseline and every 6 months over 3 years of follow-up. RESULTS: Almost one-third (30.8%) of participants were deficient in 25(OH)D (<20 ng/mL). SPPB scores were lower in those with deficient 25(OH)D (mean (standard error) 6.53 (0.24)) than in those with sufficient 25(OH)D (≥30 ng/mL) (7.15 (0.25)) after adjusting for sociodemographic characteristics, season, health behaviors, and chronic conditions (P = .006). Grip strength adjusted for body size was also lower in those with deficient 25(OH)D than in those with sufficient 25(OH)D (24.7 (0.6) kg vs 26.0 (0.6) kg, P = .02). Participants with deficient 25(OH)D were more likely to have prevalent mobility (OR = 1.44, 95% confidence interval (CI)) = 0.96-2.14) and ADL disability (OR = 1.51, 95% CI = 1.01-2.25) at baseline than those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at greater risk of incident mobility disability over 3 years of follow-up (hazard ratio = 1.56, 95% CI = 1.06-2.30). CONCLUSION: Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability in community-dwelling older adults. Moreover, vitamin D deficiency predicted incident mobility disability. BACKGROUND: Individual measures and previous composite measures of subclinical vascular disease defined high risk for cardiovascular events, but did not detect low and modest risk. A different approach might better describe the spectrum from low to high risk. Methods and Results. In the Cardiovascular Health Study, 3,252 participants without history of clinical cardiovascular disease (M ± SD 74.3 years ± 5.1, 63% women, 17% African Americans) had noninvasive vascular assessments in 1992-1993. We assigned a score of 0, 1, or 2 (no, mild, or severe abnormalities) to ankle-arm index, electrocardiogram, and common carotid intima-media thickness, based on clinical cutoffs. A summary index (range 0-6, absent to severe disease) summed individual scores. Abdominal aortic ultrasound and brain magnetic resonance imaging were collected in a subsample. Mortality and incident cardiovascular events were identified through June 2008. Event and death rates increased across index grades. Comparing grades 1 to 5+ with absent disease, and adjusting for demographics, hazard ratios for cardiovascular events within 8 years ranged from 1.1 (95% confidence interval 0.8-1.6) to 4.7 (3.4-6.9) and, for mortality, from 1.5 (1.0-2.3) to 5.0 (3.3-7.7) (p for trend across grades <.001 for both outcomes). Adjustment for cardiovascular risk factors did not substantially change the associations. The index improved mortality risk classification over demographics and risk factors in participants who did not die during the follow-up. Including in the index the aortic ultrasound and the brain magnetic resonance imaging further improved risk classification. CONCLUSIONS: Older adults with minimal subclinical vascular disease had low cardiovascular events risk and mortality. This approach might more fully account for vascular burden. BACKGROUND AND AIMS: Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women's Health and Aging Study (WHAS). METHODS: Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality. RESULTS: Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive. CONCLUSIONS: We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included. BACKGROUND: The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive drugs. OBJECTIVE: To examine the association between SBP and HF risk in the elderly. DESIGN: Competing-risks proportional hazards modelling of incident HF risk, using 10-year follow-up data from two NIH-sponsored cohort studies: the Cardiovascular Health Study (inception: 1989-90 and 1992-3) and the Health ABC Study (inception: 1997-8). SETTING: Community-based cohorts. PARTICIPANTS: 4408 participants (age, 72.8 (4.9) years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive drugs at baseline. MAIN OUTCOME MEASURES: Incident HF, defined as first adjudicated hospitalisation for HF. RESULTS: Over 10 years, 493 (11.2%) participants developed HF. Prehypertension (120-139 mm Hg), stage 1 (140-159 mm Hg), and stage 2 (≥160 mm Hg) hypertension were associated with escalating HF risk; HRs versus optimal SBP (<120 mm Hg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI 1.23 to 2.16; p=0.001), 2.21 (95% CI 1.65 to 2.96; p<0.001) and 2.60 (95% CI 1.85 to 3.64; p<0.001), respectively. Overall 255/493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than in men; no race-SBP interaction was seen. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mm Hg in men and 112 mm Hg in women. CONCLUSIONS: There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mm Hg; over half of incident HF events occur in individuals with SBP <140 mm Hg. OBJECTIVE: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI). DESIGN: : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data. SETTING: Community. PARTICIPANTS: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping. MEASUREMENTS: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status. RESULTS: : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis. CONCLUSIONS: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process. OBJECTIVES: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study). BACKGROUND: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health. METHODS: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality. RESULTS: There were 384 participants (17%) with serum 25-OHD concentrations <15 ng/ml and 570 (25%) with serum PTH concentrations ≥ 65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9% greater (95% confidence interval [CI]: 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI: 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29% greater (95% CI: 5% to 55% greater) risk for mortality. Serum PTH concentrations ≥ 65 pg/ml were associated with a 30% greater risk for heart failure (95% CI: 6% to 61% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events. CONCLUSIONS: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways. Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5% were men and 15.3% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14% increased risk of HF (95% CI: 3%-26%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95% CI: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95% CI: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women. CONTEXT: Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. OBJECTIVE: To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. DESIGN, SETTING, AND PARTICIPANTS: Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). MAIN OUTCOME MEASURES: Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. RESULTS: Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. CONCLUSIONS: Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age. BACKGROUND: Previous studies suggest that the ε4 and ε2 alleles of apolipoprotein E (APOE) may be associated with decreased and increased risks of CKD, respectively, but there are limited data in older adults. We evaluated the associations of apolipoprotein E alleles with kidney function among older adults in the cardiovascular health study (CHS). METHODS: Caucasian participants had APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for longitudinal analysis). APOE variation was evaluated as an additive model with number of ε2, ε3 and ε4 alleles. GFR was estimated using the CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m2. The secondary outcome was rapid progression defined by annual loss of eGFR > 3 ml/min/1.73 m2. RESULTS: Mean eGFRcreat was 72 ml/min/1.73 m2 (25% CKD). Compared with the ε3 allele, the APOE ε4 allele was associated with reduced risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval (CI) 0.79 (0.67 - 0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68 - 0.96) per allele. Results were consistent using eGFRcys. There was no association of the ε2 allele with CKD or between the apolipoprotein E gene with rapid progression. CONCLUSIONS: The apolipoprotein ε4 allele was associated with lower odds of CKD in elderly Caucasian individuals. Future research should confirm these findings in other races and explore mechanisms to explain these results. Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research. BACKGROUND: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. METHODS AND RESULTS: Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (≈60% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46×10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65×10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6×10(-5)), CYBA (rs3794624, P=6.3×10(-5)), and rs1122608 (LDLR, P=0.0026). CONCLUSIONS: Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI. BACKGROUND: For the elderly, the association between waist circumference (WC) and mortality considering body mass index (BMI) remains unclear, and thereby also the evidence base for using these anthropometric measures in clinical practice. This meta-analysis examined the association between WC categories and (cause-specific) mortality within BMI categories. Furthermore, the association of continuous WC with lowest and increased mortality risks was examined. METHODS: Age- and smoking-adjusted relative risks (RRs) of mortality associated with WC-BMI categories and continuous WC (including WC and WC(2)) were calculated by the investigators and pooled by means of random-effects models. RESULTS: During a 5-year-follow-up of 32 678 men and 25 931 women, we ascertained 3318 and 1480 deaths, respectively. A large WC (men: ≥102 cm, women: ≥88 cm) was associated with increased all-cause mortality RRs for those in the 'healthy' weight {1.7 [95% confidence interval (CI): 1.2-2.2], 1.7 (95% CI: 1.3-2.3)}, overweight [1.1(95% CI: 1.0-1.3), 1.4 (95%: 1.1-1.7)] and obese [1.1 (95% CI: 1.0-1.3), 1.6 (95% CI: 1.3-1.9)] BMI category compared with the 'healthy' weight (20-24.9 kg/m(2)) and a small WC (<94 cm, men; <80 cm, women) category. Underweight was associated with highest all-cause mortality RRs in men [2.2 (95% CI: 1.8-2.8)] and women [2.3 (95% CI: 1.8-3.1]. We found a J-shaped association for continuous WC with all-cause, cardiovascular (CVD) and cancer, and a U-shaped association with respiratory disease mortality (P < 0.05). An all-cause (CVD) mortality RR of 2.0 was associated with a WC of 132 cm (123 cm) in men and 116 cm (105 cm) in women. CONCLUSIONS: Our results showed increased mortality risks for elderly people with an increased WC-even across BMI categories- and for those who were classified as 'underweight' using BMI. The results provide a solid basis for re-evaluation of WC cut-points in ageing populations. BACKGROUND: The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD). METHODS AND RESULTS: Among 3710 community-living individuals ≥ 65 years of age without diabetes mellitus at baseline, fetuin-A was measured in serum collected in 1992 to 1993. Participants were followed up for 10.6 years (median) for incident diabetes mellitus. Cox regression models evaluated the association of fetuin-A with incident diabetes mellitus. Interaction terms evaluated heterogeneity by age, sex, race, and CVD. Mean age was 75 years; 60 were female; 15 were black; and 16 had CVD. Mean fetuin-A concentrations were 0.47 ± 0.10 g/L. During follow-up, 305 incident diabetes cases occurred. Each 0.10-g/L (SD)-greater fetuin-A was associated with 19 higher risk of diabetes mellitus (hazard ratio, 1.19; 95 confidence interval, 1.06-1.33) after adjustment for demographics, lifestyle factors, albumin, kidney function, and CVD. Further adjustment for potential mediators (body mass index, waist circumference, hypertension, lipids, and C-reactive protein) moderately attenuated the association (hazard ratio, 1.13; 95 confidence interval, 1.00-1.28). Results were similar by sex, race, and CVD status but were stronger in persons <75 years old (P for interaction=0.01). CONCLUSIONS: Higher fetuin-A is associated with incident diabetes mellitus in older persons regardless of sex, race, or prevalent CVD status. The association may be attenuated in those ≥ 75 years of age. Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10(-6). Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis. BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges. BACKGROUND: Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure. METHODS AND RESULTS: Among 3326 US men and women ≥65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results. CONCLUSIONS: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF. CONTEXT: Type 2 diabetes in normal-weight adults (body mass index [BMI] <25) is a representation of the metabolically obese normal-weight phenotype with unknown mortality consequences. OBJECTIVE: To test the association of weight status with mortality in adults with new-onset diabetes in order to minimize the influence of diabetes duration and voluntary weight loss on mortality. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011. A total of 2625 participants with incident diabetes contributed 27,125 person-years of follow-up. Included were men and women (age >40 years) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI. Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater. MAIN OUTCOME MEASURES: Total, cardiovascular, and noncardiovascular mortality. RESULTS: The proportion of adults who were normal weight at the time of incident diabetes ranged from 9% to 21% (overall 12%). During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes (18 were not classified). The rates of total, cardiovascular, and noncardiovascular mortality were higher in normal-weight participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively) than in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and noncardiovascular mortality were 2.08 (95% CI, 1.52-2.85), 1.52 (95% CI, 0.89-2.58), and 2.32 (95% CI, 1.55-3.48), respectively. CONCLUSION: Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese. BACKGROUND: Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. METHODS AND RESULTS: Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. CONCLUSIONS: Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation. BACKGROUND: Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. FINDINGS: We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. INTERPRETATION: Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. FUNDING: US National Kidney Foundation. BACKGROUND: Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk). METHODS AND RESULTS: In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65-0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=1.19 [95% confidence interval, 1.12-1.27]). Further adjustment for diabetes mellitus or insulin resistance, protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome, attenuated the association in the lower range. There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio=1.31 [1.15-1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality. CONCLUSIONS: Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as it relates to older adults. BACKGROUND: Repeated myocardial microinjuries lead to collagen deposition and fibrosis, thereby increasing the risk of clinical heart failure. Little is known about the longitudinal association between increases in myocardial injury and the biology of collagen synthesis and deposition. METHODS AND RESULTS: Repeated measures of highly sensitive cardiac troponin T (cTnT) were obtained in participants of the Cardiovascular Health Study (N=353; mean age, 74±6 years; 52% women) at baseline and at 3 years follow-up. Biomarkers of collagen metabolism were obtained at follow-up and included carboxyterminal propeptide of procollagen type I, carboxyterminal telopeptide of type I collagen, and aminoterminal propeptide of procollagen III. Multivariable linear regression analyses were used to examine the association between baseline cTnT and changes in cTnT with collagen metabolism markers at follow-up adjusting for demographics, heart failure status, and cardiovascular risk factors. Results indicated that cTnT increases over 3-years were significantly associated with higher levels of carboxyterminal telopeptide of type I collagen (β=0.22, P<0.001) and aminoterminal propeptide of procollagen III (β=0.12, P=0.035) at follow-up when adjusting for demographic, clinical, and biochemical covariates including baseline cTnT. These associations were stronger in patients with heart failure than in control subjects. Conclusions- Increases in myocardial microinjury measured by changes in cTnT adversely affect markers of collagen metabolism. These findings are important to the biology of myocardial fibrosis and tissue repair. Serial evaluation of cTnT combined with collagen metabolism markers may further elucidate the pathophysiology of heart failure. Changes in cardiovascular physiology in Parkinson's disease (PD) are common and may occur prior to diagnostic parkinsonian motor signs. We investigated associations of electrocardiographic (ECG) abnormalities, orthostasis, heart rate variability, and carotid stenosis with the risk of PD diagnosis in the Cardiovascular Health Study, a community-based cohort of older adults. ECG abnormality, orthostasis (symptomatic or asymptomatic), heart rate variability (24-hour Holter monitoring), and any carotid stenosis (≥1%) by ultrasound were modeled as primary predictors of incident PD diagnosis using multivariable logistic regression. Incident PD cases were identified by at least 1 of the following: self-report, antiparkinsonian medication use, and ICD-9. If unadjusted models were significant, they were adjusted or stratified by age, sex, and smoking status, and those in which predictors were still significant (P ≤ .05) were also adjusted for race, diabetes, total cholesterol, low-density lipoprotein, blood pressure, body mass index, physical activity, education level, stroke, and C-reactive protein. Of 5888 participants, 154 incident PD cases were identified over 14 years of follow-up. After adjusting models with all covariates, those with any ECG abnormality (odds ratio [OR], 1.45; 95% CI, 1.02-2.07; P = .04) or any carotid stenosis (OR, 2.40; 95% CI, 1.40-4.09; P = .001) at baseline had a higher risk of incident PD diagnosis. Orthostasis and heart rate variability were not significant predictors. This exploratory study suggests that carotid stenosis and ECG abnormalities occur prior to motor signs in PD, thus serving as potential premotor features or risk factors for PD diagnosis. Replication is needed in a population with more thorough ascertainment of PD onset. BACKGROUND AND OBJECTIVES: Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic β cell, effects on glucose tolerance, and risk of diabetes are not clear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, β cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose ≥126 mg/dl, nonfasting glucose ≥200 mg/dl, or use of glucose-lowering medications. RESULTS: Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2% higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%; P<0.001) and a 1.1% lower insulin sensitivity index (95% CI, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented β cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437 participants (9.3%) developed diabetes. eGFR was not associated with the risk of incident diabetes. CONCLUSIONS: Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased. BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF). OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF. DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression. RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535). CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133. AIMS/HYPOTHESIS: Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes. METHODS: We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype. RESULTS: The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 × 10(-4)), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings. CONCLUSIONS/INTERPRETATION: Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes. CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations. Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations. BACKGROUND: The association between changes in IGF-I and IGF binding protein (IGFBP) levels and mortality in older adults is unknown. STUDY DESIGN: Participants were 997 persons 77 to 100 yr old enrolled in the Cardiovascular Health Study All Stars Study. Plasma levels of IGF-I, IGFBP-1, and IGFBP-3 were assessed at two study examinations (1996-1997 and 2005-2006). Mortality was assessed between 2006 and 2010. RESULTS: Cumulative mortality (CM) was similar among individuals who had at least 10% decreases over time in IGF-I levels (CM = 29.6%), individuals who had at least 10% increases over time in IGF-I levels (CM = 24.7%), and individuals who had IGF-I levels remaining within ±10% over time (CM = 23.5%). Adjusted for age, sex, race, diabetes, body mass index, creatinine, albumin, and C-reactive protein, decreasing IGF-I level had no significant association with overall cancer mortality or noncancer mortality. Levels of IGFBP-1 increased markedly over time by 38% (median). Individuals with the largest increases in IGFBP-1 level over time had significantly increased risk of mortality. The adjusted hazard ratio per sd of IGFBP-1 change was 1.40 for overall cancer mortality (95% confidence interval = 1.10, 1.77; P = 0.01) and 1.14 for noncancer mortality (95% confidence interval = 1.02, 1.27; P = 0.02). Changes in IGFBP-3 levels were not significantly associated with mortality. CONCLUSION: Among older adults, decreasing IGF-I level over time does not predict subsequent all-cause mortality, whereas increasing IGFBP-1 predicts increased risk of mortality. BACKGROUND: Risk scores for prediction of coronary heart disease (CHD) in older adults are needed. OBJECTIVE: To develop a sex-specific CHD risk prediction model for older adults that accounts for competing risks for death. DESIGN: 2 observational cohort studies, using data from 4946 participants in the Cardiovascular Health Study (CHS) and 4303 participants in the Rotterdam Study (RS). SETTING: Community settings in the United States (CHS) and Rotterdam, the Netherlands (RS). PARTICIPANTS: Persons aged 65 years or older who were free of cardiovascular disease. MEASUREMENTS: A composite of nonfatal myocardial infarction and coronary death. RESULTS: During a median follow-up of 16.5 and 14.9 years, 1166 CHS and 698 RS participants had CHD events, respectively. Deaths from noncoronary causes largely exceeded the number of CHD events, complicating accurate CHD risk predictions. The prediction model had moderate ability to discriminate between events and nonevents (c-statistic, 0.63 in both U.S. and European men and 0.67 and 0.68 in U.S. and European women). The model was well-calibrated; predicted risks were in good agreement with observed risks. Compared with the Framingham point scores, the prediction model classified elderly U.S. persons into higher risk categories but elderly European persons into lower risk categories. Differences in classification accuracy were not consistent and depended on cohort and sex. Adding newer cardiovascular risk markers to the model did not substantially improve performance. LIMITATION: The model may be less applicable in nonwhite populations, and the comparison Framingham model was not designed for adults older than 79 years. CONCLUSION: A CHD risk prediction model that accounts for deaths from noncoronary causes among older adults provided well-calibrated risk estimates but was not substantially more accurate than Framingham point scores. Moreover, adding newer risk markers did not improve accuracy. These findings emphasize the difficulties of predicting CHD risk in elderly persons and the need to improve these predictions. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; The Netherlands Organisation for Scientific Research; and the Netherlands Organisation for Health Research and Development. AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly, and shares several risk factors with diastolic dysfunction, including hypertension and advanced age. The purpose of this study is to examine diastolic dysfunction as a risk for incident AF. METHODS AND RESULTS: We examined the association of echocardiographic parameters of diastolic function with the incidence of AF in 4480 participants enrolled in the Cardiovascular Health Study, an ongoing cohort of community-dwelling older adults from four US communities. Participants underwent baseline echocardiography in 1989-1990 and were followed for incident AF on routine follow-up and hospitalizations. After 50 941 person-years of follow-up (median follow-up time 12.1 years), 1219 participants developed AF. In multivariable-adjusted age-stratified Cox models, diastolic echocardiographic parameters were significantly associated with the risk of incident AF. The most significant parameters were the Doppler peak E-wave velocity and left atrial diameter, which demonstrated a positive nonlinear association [HR 1.5 (CI 1.3-1.9) and HR 1.7 (CI 1.4-2.1) for highest vs. lowest quintile, respectively], and Doppler A-wave velocity time integral, which displayed a U-shaped relationship with the risk of AF [HR 0.7 (CI 0.6-0.9) for middle vs. lowest quintile]. Each diastolic parameter displayed a significant association with adjusted NT-proBNP levels, although the nature of the association did not entirely parallel the risk of AF. Further cluster analysis revealed unique patterns of diastolic function that may identify patients at risk for AF. CONCLUSION: In a community-based population of older adults, echocardiographic measures of diastolic function are significantly associated with an increased risk of AF. OBJECTIVES: This study sought to examine the potential utility of echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for heart failure (HF) risk stratification in concert with a validated clinical HF risk score in older adults. BACKGROUND: Without clinical guidance, echocardiography and natriuretic peptides have suboptimal test characteristics for population-wide HF risk stratification. However, the value of these tests has not been examined in concert with a clinical HF risk score. METHODS: We evaluated the improvement in 5-year HF risk prediction offered by adding an echocardiographic score and/or NT-proBNP levels to the clinical Health Aging and Body Composition (ABC) HF risk score (base model) in 3,752 participants of the CHS (Cardiovascular Health Study) (age 72.6 ± 5.4 years; 40.8% men; 86.5% white). The echocardiographic score was derived as the weighted sum of independent echocardiographic predictors of HF. We assessed changes in Bayesian information criterion (BIC), C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). We examined also the weighted NRI across baseline HF risk categories under multiple scenarios of event versus nonevent weighting. RESULTS: Reduced left ventricular ejection fraction, abnormal E/A ratio, enlarged left atrium, and increased left ventricular mass were independent echocardiographic predictors of HF. Adding the echocardiographic score and NT-proBNP levels to the clinical model improved BIC (echocardiography: -43, NT-proBNP: -64.1, combined: -68.9; all p < 0.001) and C index (baseline: 0.746; echocardiography: +0.031, NT-proBNP: +0.027, combined: +0.043; all p < 0.01), and yielded robust IDI (echocardiography: 43.3%, NT-proBNP: 42.2%, combined: 61.7%; all p < 0.001), and NRI (based on Health ABC HF risk groups; echocardiography: 11.3%; NT-proBNP: 10.6%, combined: 16.3%; all p < 0.01). Participants at intermediate risk by the clinical model (5% to 20% 5-yr HF risk; 35.7% of the cohort) derived the most reclassification benefit. Echocardiography yielded modest reclassification when used sequentially after NT-proBNP. CONCLUSIONS: In older adults, echocardiography and NT-proBNP offer significant HF risk reclassification over a clinical prediction model, especially for intermediate-risk individuals. OBJECTIVE: The trajectory of cognitive decline in patients with late-onset Alzheimer's disease varies widely. Genetic variations in CLU, PICALM, and CR1 are associated with Alzheimer's disease, but it is unknown whether they exert their effects by altering cognitive trajectory in elderly individuals at risk for the disease. METHOD: The authors developed a Bayesian model to fit cognitive trajectories in a cohort of elderly subjects and test for genetic effects. They first validated the model's ability to detect the previously established effects of APOE ε4 alleles on age at cognitive decline and of psychosis on the rate of cognitive decline in 802 subjects from the Cardiovascular Health Cognition Study who did not have dementia at study entry and developed incident dementia during follow-up. The authors then evaluated the effects of CLU, PICALM, and CR1 on age and rate of decline in 1,831 subjects who did not have dementia at study entry and then did or did not develop incident dementia by study's end. RESULTS: The model generated robust fits to the observed cognitive trajectory data, and validation analysis supported the model's utility. CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. Associations remained after accounting for the effects of APOE and demographic factors. CONCLUSIONS: Evaluation of cognitive trajectories provides a powerful approach to dissecting genetic effects on the processes leading to cognitive deterioration and Alzheimer's disease. AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels. As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits. OBJECTIVES: This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting. BACKGROUND: FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown. METHODS: Plasma FGF-23 was measured in 3,107 community-living persons ≥ 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status. RESULTS: Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (p interactions all <0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95% CI: 1.32 to 2.83) for incident HF, and 1.49 (95% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95% CI: 1.05 to 1.59), 1.37 (95% CI: 0.99 to 1.89), and 1.07 (95% CI: 0.79 to 1.45). CONCLUSIONS: FGF-23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD. The QT interval (QT) is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE) studies: the Atherosclerosis Risk in Communities study and Women's Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P≤1.20×10(-4)): ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P≤1.37×10(-5)): one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD) patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT across multiple populations, that novel signals exist in African Americans, and that the SNPs identified as strong candidates for functional evaluation implicate gene regulatory dysfunction in QT prolongation. There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ∼170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ∼0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000. BACKGROUND: Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ∼50,000 SNPs across ∼2100 candidate genes to identify genetic variants for ABI. METHODS AND RESULTS: We studied subjects of European ancestry from 8 studies (n=21,547, 55% women, mean age 44-73 years) and African American ancestry from 5 studies (n=7267, 60% women, mean age 41-73 years) involved in the candidate gene association resource (CARe) consortium. In each ethnic group, additive genetic models were used (with each additional copy of the minor allele corresponding to the given beta) to test each SNP for association with continuous ABI (excluding ABI>1.40) and PAD (defined as ABI<0.90) using linear or logistic regression with adjustment for known PAD risk factors and population stratification. We then conducted a fixed-effects inverse-variance weighted meta-analyses considering a p<2×10(-6) to denote statistical significance. RESULTS: In the European ancestry discovery meta-analyses, rs2171209 in SYTL3 (β=-0.007, p=6.02×10(-7)) and rs290481 in TCF7L2 (β=-0.008, p=7.01×10(-7)) were significantly associated with ABI. None of the SNP associations for PAD were significant, though a SNP in CYP2B6 (p=4.99×10(-5)) was among the strongest associations. These 3 genes are linked to key PAD risk factors (lipoprotein(a), type 2 diabetes, and smoking behavior, respectively). We sought replication in 6 population-based and 3 clinical samples (n=15,440) for rs290481 and rs2171209. However, in the replication stage (rs2171209, p=0.75; rs290481, p=0.19) and in the combined discovery and replication analysis the SNP-ABI associations were no longer significant (rs2171209, p=1.14×10(-3); rs290481, p=8.88×10(-5)). In African Americans, none of the SNP associations for ABI or PAD achieved an experiment-wide level of significance. CONCLUSIONS: Genetic determinants of ABI and PAD remain elusive. Follow-up of these preliminary findings may uncover important biology given the known gene-risk factor associations. New and more powerful approaches to PAD gene discovery are warranted. CONTEXT: Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE: To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies. MAIN OUTCOME MEASURE: Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up. RESULTS: Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism. CONCLUSION: Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor. Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. RATIONALE: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. OBJECTIVES: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. METHODS: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV(1) and its ratio to FVC (FEV(1)/FVC) both less than their respective lower limits of normal as determined by published reference equations. MEASUREMENTS AND MAIN RESULTS: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV(1)/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis. CONCLUSIONS: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction. The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans. Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. OBJECTIVES: To determine the relationship between heart rate response during low-grade physical exertion (6-min walk) with mortality and adverse cardiovascular outcomes in the elderly. METHODS: Participants in the Cardiovascular Health Study who completed a 6-min walk test were included. We used delta heart rate (difference between postwalk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with (1) all-cause mortality and (2) incident coronary heart disease event, using multivariable Cox regression models. RESULTS: We included 2,224 participants (mean age 77 ± 4 years; 60% women; 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.40] and incident coronary heart disease (HR 1.37, 95% CI 1.05-1.78) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (p for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked. CONCLUSION: Impaired chronotropic response during a 6-min walk test was associated with an increased risk of mortality and incident coronary heart disease among the elderly. This association was attenuated after adjusting for distance walked. OBJECTIVE: Arterial and ventricular stiffening are characteristics of diabetes and aging which confer significant morbidity and mortality; advanced glycation endproducts (AGE) are implicated in this stiffening pathophysiology. We examined the association between HbA(1c), an AGE, with arterial and ventricular stiffness measures in older individuals without diabetes. RESEARCH DESIGN & METHODS: Baseline HbA(1c) was measured in 830 participants free of diabetes defined by fasting glucose or medication use in the Cardiovascular Health Study, a population-based cohort study of adults aged ≥ 65 years. We performed cross-sectional analyses using baseline exam data including echocardiography, ankle and brachial blood pressure measurement, and carotid ultrasonography. We examined the adjusted associations between HbA(1c) and multiple arterial and ventricular stiffness measures by linear regression models and compared these results to the association of fasting glucose (FG) with like measures. RESULTS: HbA(1c) was correlated with fasting and 2-hour postload glucose levels (r = 0.21; p<0.001 for both) and positively associated with greater body-mass index and black race. In adjusted models, HbA(1c) was not associated with any measure of arterial or ventricular stiffness, including pulse pressure (PP), carotid intima-media thickness, ankle-brachial index, end-arterial elastance, or left ventricular mass (LVM). FG levels were positively associated with systolic, diastolic and PP and LVM. CONCLUSIONS: In this sample of older adults without diabetes, HbA(1c) was not associated with arterial or ventricular stiffness measures, whereas FG levels were. The role of AGE in arterial and ventricular stiffness in older adults may be better assessed using alternate AGE markers. BACKGROUND: Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN. CONCLUSIONS: We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry. BACKGROUND: Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke. METHODS AND RESULTS: Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5% (95% confidence interval, 51.3-53.7) for men and 39.9% (95% confidence interval, 38.7-41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22% to 41%, compared with individuals who had or developed hypertension by 55 years of age, 42% to 69%, suggesting a dose-response effect for the length of time at high BP levels. CONCLUSIONS: Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD. AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice. METHODS AND RESULTS: We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height. CONCLUSION: Independent from sex, increased height is significantly associated with the risk of AF. OBJECTIVES AND METHODS: The purpose of this study was to examine the incidence of mild cognitive impairment (MCI) and patterns of progression from incident MCI to dementia in 285 cognitively normal subjects (mean age, 78.9 years) in the Cardiovascular Health Study-Cognition Study from 1998-1999 to 2010-2011. RESULTS: Two hundred (70%) of the participants progressed to MCI; the age-adjusted incidence of MCI was 111.09 (95% confidence interval, 88.13-142.95) per 1,000 person-years. A total of 107 (53.5%) of the incident MCI subjects progressed to dementia. The mean time from MCI to dementia was 2.8 ± 1.8 years. Forty (20%) of the incident MCI cases had an "unstable" course: 19 (9.5%) converted to MCI and later returned to normal; 10 (5%) converted to MCI, to normal, and later back to MCI; 7 (3.5%) converted to MCI, to normal, to MCI, and later to dementia; and 4 (2%) converted to MCI, to normal, and later to dementia. There was an increased mortality rate among the cognitively normal group (110.10 per 1,000 person-years) compared to those with incident MCI who converted to dementia (41.32 per 1,000 person-years). CONCLUSIONS: The majority of the subjects aged >80 years developed an MCI syndrome, and half of them progressed to dementia. Once the MCI syndrome was present, the symptoms of dementia appeared within 2 to 3 years. Progression from normal to MCI or from normal to MCI to dementia is not always linear; subjects who developed MCI and later returned to normal can subsequently progress to dementia. Competing mortality and morbidity influence the study of incident MCI and dementia in population cohorts. Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults. OBJECTIVE: Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes. RESEARCH DESIGN AND METHODS: We performed a cohort study of 3,138 Cardiovascular Health Study participants (age ≥ 65 years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR). RESULTS: A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21% (95% CI 6-41) and 11% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22% (4-43) and 4% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models. CONCLUSIONS: Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship. OBJECTIVES: To examine the association between kidney function and all-cause mortality in octogenarians. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Community. PARTICIPANTS: Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants. MEASUREMENTS: Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models. RESULTS: Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ). CONCLUSION: Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) . Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. BACKGROUND: Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression). METHODS: LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima-media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black). RESULTS: Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (β [SE] = -132 [47] bp, p < .01), age (β [SE] = -107 [46], p = .02) or carotid thickness (β [SE] = -95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%. CONCLUSION: LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age. CONTEXT: Estimates of lifetime risk for total cardiovascular disease (CVD) may provide projections of the future population burden of CVD and may assist in clinician-patient risk communication. To date, no lifetime risk estimates of total CVD have been reported. OBJECTIVES: To calculate lifetime risk estimates of total CVD by index age (45, 55, 65, 75 years) and risk factor strata and to estimate years lived free of CVD across risk factor strata. DESIGN, SETTING, AND PARTICIPANTS: Pooled survival analysis of as many as 905,115 person-years of data from 1964 through 2008 from 5 National Heart, Lung, and Blood Institute-funded community-based cohorts: Framingham Heart Study, Framingham Offspring Study, Atherosclerosis Risk in Communities Study, Chicago Heart Association Detection Project in Industry Study, and Cardiovascular Health Study. All participants were free of CVD at baseline with risk factor data (blood pressure [BP], total cholesterol [TC], diabetes, and smoking status) and total CVD outcome data. MAIN OUTCOME MEASURES: Any total CVD event (including fatal and nonfatal coronary heart disease, all forms of stroke, congestive heart failure, and other CVD deaths). RESULTS: At an index age of 45 years, overall lifetime risk for total CVD was 60.3% (95% CI, 59.3%-61.2%) for men and 55.6% (95% CI, 54.5%-56.7%) for women. Men had higher lifetime risk estimates than women across all index ages. At index ages 55 and 65 years, men and women with at least 1 elevated risk factor (BP, 140-149/90-99 mm Hg; or TC, 200-239 mg/dL; but no diabetes or smoking), 1 major risk factor, or at least 2 major risk factors (BP, ≥160/100 mm Hg or receiving treatment; TC, ≥240 mg/dL or receiving treatment; diabetes mellitus; or current smoking) had lifetime risk estimates to age 95 years that exceeded 50%. Despite an optimal risk factor profile (BP, <120/80 mm Hg; TC, <180 mg/dL; and no smoking or diabetes), men and women at the index age of 55 years had lifetime risks (through 85 years of age) for total CVD of greater than 40% and 30%, respectively. Compared with participants with at least 2 major risk factors, those with an optimal risk factor profile lived up to 14 years longer free of total CVD. CONCLUSIONS: Lifetime risk estimates for total CVD were high (>30%) for all individuals, even those with optimal risk factors in middle age. However, maintenance of optimal risk factor levels in middle age was associated with substantially longer morbidity-free survival. BACKGROUND: The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults. METHODS: We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event. RESULTS: We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7% vs. 29.6% among men, 6.4% vs. 20.5% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6% vs. 37.5% among men, <1% vs. 18.3% among women) and fatal or nonfatal stroke (2.3% vs. 8.3% among men, 5.3% vs. 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts. CONCLUSIONS: Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.). CONTEXT: The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. OBJECTIVE: To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). MAIN OUTCOME MEASURES: Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. RESULTS: The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. CONCLUSION: In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction. INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) has been consistently associated with cardiovascular disease (CVD) risk factors and predictive of CVD outcomes; furthermore, it is consistently higher among type 2 diabetics than nondiabetics. However, the relationships of circulating Lp-PLA(2) mass and activity with incident type 2 diabetes mellitus have not been examined. Therefore, the purpose of this study was to determine the association of Lp-PLA(2) mass and activity with type 2 diabetes among older adults. METHODS: We conducted analyses of Lp-PLA(2) and prevalent and incident diabetes among 5474 men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Diabetes status was ascertained annually with medication inventories and repeated blood glucose measurements. Generalized linear and Cox proportional hazards models were used to adjust for confounding factors including body mass index and inflammation. RESULTS: At baseline, the top two quintiles of Lp-PLA(2) activity were significantly associated with prevalent type 2 diabetes with a multivariable relative risk = 1.35 [95% confidence interval (CI) = 1.11-1.63] for quintile 4, and relative risk = 1.33 (95% CI = 1.07-1.66) for quintile 5. Among participants free of diabetes at baseline, we found a significant positive association with both the homeostatic model assessment for insulin resistance and β-cell function per SD increase in Lp-PLA(2) activity (P values for both <0.01). In prospective analyses, the risk of incident type 2 diabetes was significantly higher among those in the highest quintile of Lp-PLA(2) activity [multivariable hazard ratio = 1.45 (95% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA(2) mass was not significantly associated with incident type 2 diabetes. DISCUSSION: Lp-PLA(2) activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis. CONTEXT: Data on thyroid function in the oldest old are sparse, and existing studies show conflicting evidence on the relationship between thyroid function and mortality in this age group. OBJECTIVE: We describe longitudinal changes in thyroid function in a cohort of elderly individuals and determine the relationship between thyroid function and mortality. DESIGN, SETTING, AND PARTICIPANTS: Eight hundred forty-three participants in the Cardiovascular Health Study All Stars Study who were not taking thyroid medications and had thyroid function testing in 2005-2006 (mean age 85 yr). MAIN OUTCOME MEASURE: Thyroid-stimulating hormone (TSH), free T(4) (FT4), total T(3), and thyroid peroxidase antibody status were measured in 1992-1993 and 2005-2006. Deaths were ascertained through February 2011. RESULTS: There was a statistically significant 13% increase in TSH, 1.7% increase in FT4, and 13% decrease in total T(3) over the 13-yr period. Two hundred eighty-seven deaths occurred over a median follow-up of 5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.66-1.43], TSH level (HR per milliunits per liter 0.94, 95% CI 0.88-1.01), or persistent thyroid peroxidase antibody positivity (HR 1.09, 95% CI 0.62-1.92), and death. However, FT4 was positively associated with death (HR per nanograms per deciliter 2.57, 95% CI 1.32-5.02). CONCLUSIONS: TSH increased over time in these older individuals. This elevation was not associated with increased or decreased mortality, although higher FT4 levels were associated with death. These findings raise concern for treatment of mild elevations of TSH in advanced age. Further studies are needed to determine the potential benefit of treating age-related changes in thyroid function. BACKGROUND: Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging. METHODS: We examined associations of long-term change in C-reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality in 1,051 participants in the Cardiovascular Health Study All Stars Study. Biomarkers were measured in 1996-1997 and 2005-2006. RESULTS: In 2005-2006, median age was 84.9 years, 63% were women and 17% non-white; 21% had at least a doubling in CRP over time and 23% had at least a doubling in IL-6. Adjusting for demographics, CVD risk factors, and 1996-1997 CRP level, each doubling in CRP change over 9 years was associated with higher risk of physical or cognitive impairment (odds ratio 1.29; 95% confidence interval 1.15, 1.45). Results were similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not CRP, was associated with incident CVD events; hazard ratio (95% confidence interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16, 1.65]). In models containing both change and 2005-2006 level, only level was associated with CVD events and mortality. CONCLUSIONS: Although increases in inflammation markers over 9 years were associated with higher concurrent risk of functional impairment and subsequent CVD events and mortality, final levels of each biomarker appeared to be more important in determining risk of subsequent events than change over time. Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process. BACKGROUND: Studies demonstrate existence of inflammation in prevalent Parkinson's disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study. METHODS: Blood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases. RESULTS: Risk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR]=1.5, 95% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95% CI: 0.2, 0.8). CONCLUSIONS: Although inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset. To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules. The susceptibility of older adults to the health effects of air pollution is well-recognized. Advanced age may act as a partial surrogate for conditions associated with aging. The authors investigated whether gerontologic frailty (a clinical health status metric) modified the association between ambient level of ozone or particulate matter with an aerodynamic diameter less than 10 µm and lung function in 3,382 older adults using 7 years of follow-up data (1990-1997) from the Cardiovascular Health Study and its Environmental Factors Ancillary Study. Monthly average pollution and annual frailty assessments were related to up to 3 repeated measurements of lung function using cumulative summaries of pollution and frailty histories that accounted for duration as well as concentration. Frailty history was found to modify long-term associations of pollutants with forced vital capacity. For example, the decrease in forced vital capacity associated with a 70-ppb/month greater cumulative sum of monthly average ozone exposure was 12.3 mL (95% confidence interval: 10.4, 14.2) for a woman who had spent the prior 7 years prefrail or frail as compared with 4.7 mL (95% confidence interval: 3.8, 5.6) for a similar woman who was robust during all 7 years (interaction P < 0.001). CONTEXT: Studies of long-term outcomes of subclinical hypothyroidism have assessed only baseline thyroid function, despite natural transitions to euthyroidism and overt hypothyroidism over time. OBJECTIVE: We provide estimates of persistence, resolution, and progression of subclinical hypothyroidism over 4 yr, stratified by baseline TSH, anti-thyroid peroxidase antibody (TPOAb) status, age, and sex. DESIGN, SETTING, AND PARTICIPANTS: Participants were 3996 U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study. Subclinical hypothyroidism was detected at baseline in 459 individuals not taking thyroid medication. MAIN OUTCOME MEASURE: Thyroid function was evaluated at 2 and 4 yr and initiation of thyroid medication annually. Results were stratified by baseline TSH, TPOAb status, age, and sex. RESULTS: Persistence of subclinical hypothyroidism was 56% at 2 and 4 yr. At 2 yr, resolution was more common with a TSH of 4.5-6.9 mU/liter (46 vs. 10% with TSH 7-9.9 mU/liter and 7% with TSH ≥10 mU/liter; P < 0.001) and with TPOAb negativity (48 vs. 15% for positive; P < 0.001). Higher TSH and TPOAb positivity were independently associated with lower likelihood of reversion to euthyroidism (P < 0.05). TSH of 10 mU/liter or higher was independently associated with progression to overt hypothyroidism (P < 0.05). Transitions between euthyroidism and subclinical hypothyroidism were common between 2 and 4 yr. Age and sex did not affect transitions. CONCLUSIONS: Subclinical hypothyroidism persists for 4 yr in just over half of older individuals, with high rates of reversion to euthyroidism in individuals with lower TSH concentrations and TPOAb negativity. Future studies should examine the impact of transitions in thyroid status on clinical outcomes. BACKGROUND: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. METHODOLOGY/PRINCIPAL FINDINGS: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05). CONCLUSIONS/SIGNIFICANCE: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension. BACKGROUND: Although nonesterified fatty acids (NEFA) have been positively associated with coronary heart disease risk factors, limited and inconsistent data are available on the relation between NEFA and sudden cardiac death. METHODS AND RESULTS: Using a prospective design, we studied 4657 older men and women (mean age, 75 years) from the Cardiovascular Health Study (1992-2006) to evaluate the association between plasma NEFA and the risk of sudden cardiac death in older adults. Plasma concentrations of NEFA were measured using established enzymatic methods, and sudden death was adjudicated using medical records, death certificates, proxy interview, and autopsy reports. We used Cox proportional hazard models to estimate multivariable-adjusted relative risks. During a median follow-up of 10.0 years, 221 new cases of sudden cardiac death occurred. In a multivariable model adjusting for age, sex, race, clinic site, alcohol intake, smoking, prevalent coronary heart disease and heart failure, and self-reported health status, relative risks (95% confidence interval) for sudden cardiac death were 1.0 (ref), 1.15 (0.81-1.64), 1.06 (0.72-1.55), and 0.91 (0.60-1.38) across consecutive quartiles of NEFA concentration. In secondary analyses restricted to the first 5 years of follow-up, we also did not observe a statistically significant association between plasma NEFA and sudden cardiac death. CONCLUSIONS: Our data do not provide evidence for an association between plasma NEFA measured late in life and the risk of sudden cardiac death in older adults. BACKGROUND: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk. OBJECTIVES: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort. DESIGN: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis. RESULTS: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05). CONCLUSIONS: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD. BACKGROUND: The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. METHODS AND RESULTS: We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)). CONCLUSIONS: This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. OBJECTIVES: To characterize longitudinal patterns of musculoskeletal pain in a community sample of older adults over a 6-year period and to identify factors associated with persistence of pain. DESIGN: Secondary analysis of the Cardiovascular Health Study. SETTING: Community-based cohort drawn from four U.S. counties. PARTICIPANTS: Five thousand ninety-three men and women aged 65 and older. MEASUREMENTS: Over a 6-year period, pain was assessed each year using a single question about the presence of pain in any bones or joints during the last year. If affirmative, participants were queried about pain in seven locations (hands, shoulders, neck, back, hips, knees, feet). Participants were categorized according to the percentage of time that pain was present and according to the intermittent or chronic pattern of pain. Factors associated with persistent pain during five remaining years of the study were identified. RESULTS: Over 6 years, 32% of participants reported pain for three or more consecutive years, and 32% reported pain intermittently. Of those who reported pain the first year, 54% were pain free at least once during the follow-up period. Most of the pain at specific body locations was intermittent. Factors associated with remission of pain over 5 years included older age, male sex, better self-rated health, not being obese, taking fewer medications, and having fewer depressive symptoms. Approximately half of those with pain reported fewer pain locations the following year. CONCLUSION: Musculoskeletal pain in older adults, despite high prevalence, is often intermittent. The findings refute the notion that pain is an inevitable, unremitting, or progressive consequence of aging. OBJECTIVES: The aim of this study was to evaluate the association between physical activity and changes in levels of highly sensitive troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the subsequent risk of the development of heart failure (HF) in community-dwelling older adults. BACKGROUND: Higher baseline levels of cTnT and NT-proBNP and increases over time correlate with the risk of HF in older adults. Factors modifying these levels have not been identified. METHODS: NT-proBNP and cTnT were measured at baseline and 2 to 3 years later in adults 65 years of age and older free of HF participating in the Cardiovascular Health Study. Self-reported physical activity and walking pace were combined into a composite score. An increase was prespecified for NT-proBNP as a >25% increment from baseline to ≥190 pg/ml and for cTnT as a >50% increment from baseline in participants with detectable levels (≥3 pg/ml). RESULTS: A total of 2,933 participants free of HF had NT-proBNP and cTnT measured at both time points. The probability of an increase in biomarker concentrations between baseline and follow-up visits was inversely related to the physical activity score. Compared with participants with the lowest score, those with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33 to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for comorbidities and baseline levels. A higher activity score associated with a lower long-term incidence of HF. Moreover, at each level of activity, an increase in either biomarker still identified those at higher risk. CONCLUSIONS: These findings suggest that moderate physical activity has protective effects on early heart failure phenotypes, preventing cardiac injury and neurohormonal activation. OBJECTIVE: To examine the relation of fatty acid-binding protein (FABP)4 and nonesterified fatty acids (NEFAs) to diabetes in older adults. RESEARCH DESIGN AND METHODS: We ascertained incident diabetes among 3,740 Cardiovascular Health Study participants (1992-2007) based on the use of hypoglycemic medications, fasting glucose ≥ 126 mg/dL, or nonfasting glucose ≥ 200 mg/dL. FABP4 and NEFA were measured on specimens collected between 1992 and 1993. RESULTS: Mean age of the 3,740 subjects studied was 74.8 years. For each SD increase in log FABP4, hazard ratios (HRs) for diabetes were 1.35 (95% CI 1.10-1.65) for women and 1.45 (1.13-1.85) for men controlling for age, race, education, physical activity, cystatin C, alcohol intake, smoking, self-reported health status, and estrogen use for women (P for sex-FABP4 interaction 0.10). BMI modified the FABP4-diabetes relation (P = 0.009 overall; 0.02 for women and 0.135 for men), in that statistically significant higher risk of diabetes was mainly seen in men with BMI <25 kg/m(2) (HR per SD: 1.78 [95% CI 1.13-2.81]). There was a modest and nonsignificant association of NEFA with diabetes (P(trend) = 0.21). However, when restricted to the first 5 years of follow-up, multivariable-adjusted HRs for diabetes were 1.0 (ref.), 1.68 (95% CI 1.12-2.53), and 1.63 (1.07-2.50) across consecutive tertiles of NEFA (P(trend) = 0.03). CONCLUSIONS: Plasma FABP4 was positively associated with incident diabetes in older adults, and such association was statistically significant in lean men only. A significant positive association between plasma NEFA and incident diabetes was observed during the first 5 years of follow-up. Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women ≥65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 ± 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults. BACKGROUND: the rate of performance decline may influence the risk of disability or death. METHODS: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998-99, and the rate of performance change between 1992-93 and 1998-99, to the risk of death or disability in 2005-06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992-93 and 1998-99. RESULTS: participants' age averaged 79.4 in 1998-99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95% CI: 1.16 -1.96) and a 1.27 RR of death (95% CI: 1.07 -1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35% (95% CI: 1.13 -1.61) and death by 31% (95% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF. CONCLUSION: performance trajectories independently predict death and disability. BACKGROUND: No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously. METHODS AND RESULTS: We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6% had CVD and 5.0% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2% and 15.7%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95% CI, 0.60, 1.00). CONCLUSIONS: CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events. BACKGROUND: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m(2) at enrollment. PREDICTOR: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)). OUTCOME: Infection-related hospitalizations during a median follow-up of 11.5 years. RESULTS: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2). When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m(2) was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2). LIMITATIONS: No measures of urinary protein, study limited to principal discharge diagnosis. CONCLUSIONS: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals. OBJECTIVE: To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by magnetic resonance imaging (MRI), are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study. METHODS: Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, we assessed white matter grade (range, 0-9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred. RESULTS: After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0 to 1, 2, 3, and 4 to 9 were 1.00, 1.68 (0.86-3.30), 3.52 (1.80-6.89), and 3.96 (1.90-8.27), respectively (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI-defined brain infarcts were 1.00, 1.97 (1.10-3.54), 2.00 (0.83-4.78), and 3.12 (1.31-7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049). INTERPRETATION: Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis. An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8. BACKGROUND: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration. OBJECTIVE: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D. DESIGN: Cohort study. SETTING: The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis. PARTICIPANTS: 1621 white older adults. MEASUREMENTS: Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death. RESULTS: Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24% higher risk in adjusted analyses (95% CI, 9% to 42%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively. LIMITATION: The observational study was restricted to white participants. CONCLUSION: Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk. PRIMARY FUNDING SOURCE: National Institutes of Health. BACKGROUND: Sleepiness is one of the most burdensome symptoms of sleep-disordered breathing (SDB). While caffeine is frequently used to avert sleepiness, the association between SDB and caffeine use has not been thoroughly explored. The current study examined whether SDB is associated with caffeine consumption and if factors such as sex, age, and daytime sleepiness explain or modify the association. METHODS: Data from the Sleep Heart Health Study, a community-based study on the consequences of SDB, were used to characterize the association between SDB and caffeine intake. SDB was assessed with full-montage polysomnography. Caffeine use was quantified as the number of cans of soda or the cups of coffee or tea consumed daily. The Epworth Sleepiness Scale was used to assess daytime sleepiness. Multivariable negative binomial regression models were used to characterize the independent association between SDB and caffeine use. RESULTS: Caffeinated soda, but not tea or coffee, intake was independently associated with SDB severity. Compared with participants without SDB, the relative ratios for caffeinated soda consumption in women with mild, moderate, and severe SDB were 1.20 (CI, 1.03-1.41), 1.46 (CI, 1.14-1.87), and 1.73 (CI, 1.23-2.42), respectively. For men, an association was only noted with severe SDB and caffeinated soda use. Age did not modify the SDB-caffeine association, and sleepiness could not explain the observed associations. CONCLUSIONS: SDB is independently associated with caffeinated soda use in the general community. Identifying excessive caffeine used in SDB has potential significance given the cardiovascular effects of caffeine and untreated SDB. BACKGROUND: Slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests. HYPOTHESIS: We hypothesise that slower information processing explains this association, while tests of language or memory will not. METHODS: Data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index). RESULTS: In linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association. CONCLUSIONS: We conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait. BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts. METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. RESULTS: Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03). CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L. BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L. Leukocyte telomere length (LTL) is linked to cardiovascular disease (CVD); however, it is unclear if LTL has an etiologic role in CVD. To gain insight into the LTL and CVD relationship, a cohort study of CVD mortality and single nucleotide polymorphisms (SNPs) in OBFC1 and TERC, genes related to LTL, was conducted among 3271 Caucasian participants ages ≥65 years enrolled 1989-1990 in the Cardiovascular Health Study. Leukocyte DNA was genotyped for SNPs in OBFC1 (rs4387287 and rs9419958) and TERC (rs3772190) that were previously associated with LTL through genome-wide association studies. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The OBFC1 SNPs were in linkage disequilibrium (r(2)=0.99), and both SNPs were similarly associated with CVD mortality in women. For women, there was a decreased risk of CVD death associated with the minor allele (rs4387287), HR=0.7; 95% CI: 0.5-0.9 (CC vs. AC) and HR=0.5; 95% CI: 0.20-1.4 (CC vs. AA) (P-trend <0.01). For men there was no association, HR=1.0; 95% CI: 0.7-1.3 (CC vs. AC) and HR=1.7; 95% CI: 0.8-3.6 (CC vs. AA) (P-trend=0.64). These findings support the hypothesis that telomere biology and associated genes may play a role in CVD-related death, particularly among women. OBJECTIVE: To delineate the associations of total adiponectin, high-molecular-weight (HMW) adiponectin, and the HMW-to-total adiponectin ratio with diabetes in older adults. RESEARCH DESIGN AND METHODS: Total and HMW adiponectin were measured in a population-based study of older adults. The relations of total adiponectin, HMW adiponectin, and their ratio with incident diabetes (n = 309) were assessed in 3,802 individuals. RESULTS: Total and HMW adiponectin were highly correlated (r = 0.94). Analysis using cubic splines revealed that the associations between total and HMW adiponectin and new-onset diabetes were not linear. Specifically, after adjustment for confounders, there were similar inverse relationships for total (hazard ratio per SD 0.49 [95% CI 0.39-0.63]) and HMW adiponectin (0.42 [0.32-0.56]) with diabetes up to values of 20 and 10 mg/L, respectively, above which the associations plateaued. These associations persisted after adjustment for potential mediators (blood pressure, lipids, C-reactive protein, and homeostasis model assessment of insulin resistance [HOMA-IR]). There was, however, evidence of interaction by HOMA-IR in the lower range of adiponectin, with stronger inverse associations among insulin-sensitive than insulin-resistant participants. HMW-to-total adiponectin ratio showed a linear adjusted association with outcome, but this was abolished by inclusion of mediating variables. CONCLUSIONS: In this older cohort, increasing concentrations of total and HMW adiponectin were associated with comparably lower risks of diabetes, but these associations leveled off with further increases above concentrations of 20 and 10 mg/L, respectively. The more pronounced risk decreases at the lower range among participants without insulin resistance support a role for adiponectin that is independent of baseline hyperinsulinemia, but this will require further investigation. BACKGROUND: Trans-fatty acid (TFA) consumption is associated with risk of coronary heart disease, and trans-18:2, but not trans-18:1, in red blood cell membranes has been associated with sudden cardiac arrest. Abnormal heart rate variability (HRV) reflects autonomic dysfunction and predicts cardiac death. Relationships between TFA consumption and HRV remain understudied. We determined whether total TFA consumption, as well as trans-18:1 and trans-18:2 TFA consumption, was independently associated with HRV in 2 independent cohorts in the United States and Portugal. METHODS AND RESULTS: In 2 independent cohorts of older US adults (Cardiovascular Health Study [CHS], age 72±5 years, 1989/1995) and young Portuguese adults (Porto, age 19±2 years, 2008/2010), we assessed habitual TFA intake by food frequency questionnaires in CHS (separately estimating trans-18:1 and trans-18:2) and multiple 24-hour recalls in Porto (estimating total TFA only, which in a subset correlated with circulating trans-18:2 but not trans-18:1, suggesting that we captured the former). HRV was assessed using 24-hour Holters in CHS (n=1076) and repeated short-term (5-minute) ECGs in Porto (n=160). We used multivariate-adjusted linear regression to relate TFA consumption to HRV cross-sectionally (CHS, Porto) and longitudinally (CHS). In CHS, higher trans-18:2 consumption was associated with lower 24-hour SD of all normal-to-normal intervals both cross-sectionally (-12%; 95% CI, -19% to -6%; P=0.001) and longitudinally (-15%; 95% CI, -25% to -4%; P= 0.009) and lower 24-hour SD of 5-minute average N-N intervals and mean of the 5-minute SD of N-N intervals calculated over 24 hours (P<0.05 each). Higher trans-18:1 consumption in CHS was associated with more favorable 24-hour HRV in particular time-domain indices (24-hour SD of all normal-to-normal intervals, SD of 5-minute average N-N intervals, mean of the 5-minute SD of N-N intervals calculated over 24 hours; P<0.05 each). In Porto, each higher SD TFA consumption was associated with 4% lower 5-minute 24-hour SD of all normal-to-normal intervals (95% CI, -8% to -1%; P=0.04) and 7% lower 5-minute square root of the mean of the squares of successive N-N differences (95% CI, -13% to -1%; P=0.04). CONCLUSIONS: Trans-18:2 consumption is associated with specific, less favorable indices of HRV in both older and young adults. Trans-18:1 consumption is associated with more favorable HRV indices in older adults. Our results support the need to investigate potential HRV-related mechanisms, whereby trans-18:2 may increase arrhythmic risk. Ultraconserved elements in the human genome likely harbor important biological functions as they are dosage sensitive and are able to direct tissue-specific expression. Because they are under purifying selection, variants in these elements may have a lower frequency in the population but a higher likelihood of association with complex traits. We tested a set of highly constrained SNPs (hcSNPs) distributed genome-wide among ultraconserved and nearly ultraconserved elements for association with seven traits related to reproductive (age at natural menopause, number of children, age at first child, and age at last child) and overall [longevity, body mass index (BMI), and height] fitness. Using up to 24,047 European-American samples from the National Heart, Lung, and Blood Institute Candidate Gene Association Resource (CARe), we observed an excess of associations with BMI and height. In an independent replication panel the most strongly associated SNPs showed an 8.4-fold enrichment of associations at the nominal level, including three variants in previously identified loci and one in a locus (DENND1A) previously shown to be associated with polycystic ovary syndrome. Finally, using 1430 family trios, we showed that the transmissions from heterozygous parents to offspring of the derived alleles of rare (frequency ≤ 0.5%) hcSNPs are not biased, particularly after adjusting for the rates of genotype missingness and error in the data. The lack of transmission bias ruled out an immediately and strongly deleterious effect due to the rare derived alleles, consistent with the observation that mice homozygous for the deletion of ultraconserved elements showed no overt phenotype. Our study also illustrated the importance of carefully modeling potential technical confounders when analyzing genotype data of rare variants. BACKGROUND AND PURPOSE: Mobility disability is a serious and frequent adverse health outcome associated with aging. Early identification of individuals at risk for mobility disability is important if interventions to prevent disability are to be instituted. The objectives of this prospective study were to (1) determine the magnitude of stance time variability (STV) that discriminates individuals who currently have mobility disability (prevalent mobility disability) and (2) determine the magnitude of STV that predicts a new onset of mobility disability at 1 year (incident mobility disability). METHODS: A total of 552 community-dwelling older adults were evaluated as part of the Cardiovascular Health Study, a longitudinal cohort study. Stance time, in milliseconds, was determined from 2 passes on a 4-m computerized walkway at self-selected walking speed, and STV was defined as the standard deviation from approximately 12 individual steps. Mobility disability was defined as self-reported difficulty walking a one-half mile. Receiver operating characteristic (ROC) curves were plotted to determine an optimal cutoff value for STV for prevalent and incident mobility disability, and the area under the receiver operating characteristic curve (AUC) was computed. RESULTS: The optimal cutoff score for STV (maximizing sensitivity and specificity) for prevalent mobility disability was 0.037 seconds (sensitivity = 65%, specificity = 65%, AUC = 0.70) and for incident 1-year mobility disability was 0.034 seconds (sensitivity = 61%, specificity = 60%, AUC = 0.65). The use of likelihood ratios demonstrated a gradient of risk across values of STV, with mobility risk increasing as values of STV increased. DISCUSSION AND CONCLUSION: Values of STV may be useful in identifying older adults with mobility disability and at risk for future disability. We recommend the more conservative estimate for identifying risk, STV = 0.034 seconds, which maximizes the sensitivity and minimizes false negatives. The relatively modest values on the validity indices could possibly be improved by increasing the reliability of the measurement of STV. Clinicians should interpret the cutoff values liberally and use STV in conjunction with other measures until further work is completed to validate STV as an indicator of mobility disability. Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals, and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software. WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age-related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores. Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function. CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal. BACKGROUND: Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis, body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study. METHODS: Cognitive performance was assessed with the modified Mini-Mental State Examination, the Digit Symbol Substitution Test, and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline. RESULTS: The final sample was comprised of 2,681 women (57.9%) and 1,949 men (42.1%) aged 73 ± 5.2 and 73.9 ± 5.6 years, respectively. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease. CONCLUSIONS: Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by preexisting conditions. UNLABELLED: The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78 years). We find a small independent association in women but not in men. INTRODUCTION: The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30 mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78 years. METHODS: From the Cardiovascular Health Study (41 % male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5 years. BMD was performed in a subset of 1,208 participants. RESULTS: There were 313 hip fractures during follow-up (7.7 % of men; 11.7 % of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95 % CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009 g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women. CONCLUSIONS: In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria. A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 × 10(-67), P = 3.98 × 10(-5), P = 6.97 × 10(-9), and P = 5.33 × 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 × 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 × 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 × 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout. BACKGROUND: High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels. METHODS AND RESULTS: We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374; P=9.06×10(-9)) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73×10(-8)) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004). CONCLUSIONS: We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results. BACKGROUND: Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). METHODS AND RESULTS: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. CONCLUSIONS: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF. BACKGROUND: Atrial fibrillation (AF) prediction models have unclear clinical utility given the absence of AF prevention therapies and the immutability of many risk factors. Premature atrial contractions (PACs) play a critical role in AF pathogenesis and may be modifiable. OBJECTIVE: To investigate whether PAC count improves model performance for AF risk. DESIGN: Prospective cohort study. SETTING: 4 U.S. communities. PATIENTS: A random subset of 1260 adults without prevalent AF enrolled in the Cardiovascular Health Study between 1989 and 1990. MEASUREMENTS: The PAC count was quantified by 24-hour electrocardiography. Participants were followed for the diagnosis of incident AF or death. The Framingham AF risk algorithm was used as the comparator prediction model. RESULTS: In adjusted analyses, doubling the hourly PAC count was associated with a significant increase in AF risk (hazard ratio, 1.17 [95% CI, 1.13 to 1.22]; P < 0.001) and overall mortality (hazard ratio, 1.06 [CI, 1.03 to 1.09]; P < 0.001). Compared with the Framingham model, PAC count alone resulted in similar AF risk discrimination at 5 and 10 years of follow-up and superior risk discrimination at 15 years. The addition of PAC count to the Framingham model resulted in significant 10-year AF risk discrimination improvement (c-statistic, 0.65 vs. 0.72; P < 0.001), net reclassification improvement (23.2% [CI, 12.8% to 33.6%]; P < 0.001), and integrated discrimination improvement (5.6% [CI, 4.2% to 7.0%]; P < 0.001). The specificity for predicting AF at 15 years exceeded 90% for PAC counts more than 32 beats/h. LIMITATION: This study does not establish a causal link between PACs and AF. CONCLUSION: The addition of PAC count to a validated AF risk algorithm provides superior AF risk discrimination and significantly improves risk reclassification. Further study is needed to determine whether PAC modification can prospectively reduce AF risk. PRIMARY FUNDING SOURCE: American Heart Association, Joseph Drown Foundation, and National Institutes of Health. OBJECTIVE: We sought to determine whether in the absence of clinical stroke, people with atrial fibrillation experience faster cognitive decline than people without atrial fibrillation. METHODS: We conducted a longitudinal analysis in the Cardiovascular Health Study, a community-based study of 5,888 men and women aged 65 years and older, enrolled in 1989/1990 or 1992/1993. Participants did not have atrial fibrillation or a history of stroke at baseline. Participants were censored when they experienced incident clinical stroke. Incident atrial fibrillation was identified by hospital discharge diagnosis codes and annual study ECGs. The main outcome was rate of decline in mean scores on the 100-point Modified Mini-Mental State Examination (3MSE), administered annually up to 9 times. RESULTS: Analyses included 5,150 participants, of whom 552 (10.7%) developed incident atrial fibrillation during a mean of 7 years of follow-up. Mean 3MSE scores declined faster after incident atrial fibrillation compared with no prior atrial fibrillation. For example, the predicted 5-year decline in mean 3MSE score from age 80 to age 85 was -6.4 points (95% confidence interval [CI]: -7.0, -5.9) for participants without a history of atrial fibrillation, but was -10.3 points (95% CI: -11.8, -8.9) for participants experiencing incident atrial fibrillation at age 80, a 5-year difference of -3.9 points (95% CI: -5.3, -2.5). CONCLUSIONS: In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation. BACKGROUND: It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts. METHODS: In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2% women; and 26.6% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, ≥65 years; 58.2% women; and 15.4% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors. RESULTS: In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively. CONCLUSIONS: Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted. Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip. RATIONALE: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. OBJECTIVES: To determine bidirectional relationships between cognition and pneumonia. METHODS: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. MEASUREMENTS AND MAIN RESULTS: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. CONCLUSIONS: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence. BACKGROUND: Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown. METHODS: We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline ≥ 3ml/min/year. RESULTS: Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14% increased hazard of rapid decline (95% confidence interval, 10% to 17%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline. CONCLUSIONS: Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults. BACKGROUND: Recent reports have linked variability in visit-to-visit systolic blood pressure (SBP) to risk of mortality and stroke, independent of the effect of mean SBP level. This study aimed to evaluate whether variability in SBP is associated with all-cause mortality, incident myocardial infarction (MI), and incident stroke, independent of mean SBP or trends in SBP levels over time. METHODS: The Cardiovascular Health Study is a longitudinal cohort study of vascular risk factors and disease in the elderly. Participants who attended their first 5 annual clinic visits and experienced no event before the 5th visit were eligible (n = 3,852). Primary analyses were restricted to participants not using antihypertensive medications throughout the first 5 clinic visits (n = 1,642). Intraindividual SBP variables were defined using each participant's 5-visit blood pressure measures. Cox proportional hazards models estimated adjusted hazard ratios (HRs) per SD increase in intraindividual SBP variability, adjusted for intraindividual SBP mean and change over time. RESULTS: Over a mean follow-up of 9.9 years, there were 844 deaths, 203 MIs, and 195 strokes. Intraindividual SBP variability was significantly associated with increased risk of mortality (HR = 1.13; 95% confidence interval (CI) = 1.05-1.21) and of incident MI (HR = 1.20; 95%CI = 1.06-1.36), independent of the effect from adjustment factors. Intraindividual SBP variability was not associated with risk of stroke (HR = 1.03; 95% CI = 0.89-1.21). CONCLUSIONS: Long-term visit-to-visit SBP variability was independently associated with a higher risk of subsequent mortality and MI but not stroke. More research is needed to determine the relationship of BP variability with cardiovascular risk and the clinical implications. OBJECTIVES: This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD). BACKGROUND: The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated. METHODS: Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee. RESULTS: Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT ≥12.10 vs. 5.01 to 12.09 vs. ≤ 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95% CI: 1.01 to 1.06). CONCLUSIONS: The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors. BACKGROUND: Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear. OBJECTIVE: To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults. METHODS AND RESULTS: Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992-1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996-1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95% CI (-0.17, -0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis. CONCLUSIONS: Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors. BACKGROUND: Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega-3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. METHODS AND RESULTS: In the community-based Cardiovascular Health Study, 3660 participants aged ≥ 65 underwent brain MRI in 1992-1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992-1993 and related to cross-sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend = 0.001) in the highest versus lowest long-chain omega-3 PUFA quartile. Higher long-chain omega-3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate-chain omega-3 PUFA alpha-linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha-linolenic acid intake. CONCLUSIONS: Among older adults, higher phospholipid long-chain omega-3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long-chain omega-3 PUFAs, on brain health in later life. The role of plant-derived alpha-linolenic acid in brain health requires further investigation. We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3'untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels. BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin. BACKGROUND: The health of older adults declines over time, but there are many ways of measuring health. It is unclear whether all health measures decline at the same rate or whether some aspects of health are less sensitive to aging than others. METHODS: We compared the decline in 13 measures of physical, mental, and functional health from the Cardiovascular Health Study: hospitalization, bed days, cognition, extremity strength, feelings about life as a whole, satisfaction with the purpose of life, self-rated health, depression, digit symbol substitution test, grip strength, activities of daily living, instrumental activities of daily living, and gait speed. Each measure was standardized against self-rated health. We compared the 5-year change to see which of the 13 measures declined the fastest and the slowest. RESULTS: The 5-year change in standardized health varied from a decline of 12 points (out of 100) for hospitalization to a decline of 17 points for gait speed. In most comparisons, standardized health from hospitalization and bed days declined the least, whereas health measured by activities of daily living, instrumental activities of daily living, and gait speed declined the most. These rankings were independent of age, sex, mortality patterns, and the method of standardization. CONCLUSIONS: All of the health variables declined, on average, with advancing age, but at significantly different rates. Standardized measures of mental health, cognition, quality of life, and hospital utilization did not decline as fast as gait speed, activities of daily living, and instrumental activities of daily living. Public health interventions to address problems with gait speed, activities of daily living, and instrumental activities of daily living may help older adults to remain healthier in all dimensions. BACKGROUND: High rates of disability associated with chronic airway obstruction may be caused by impaired pulmonary function, pulmonary symptoms, other chronic diseases, or systemic inflammation. METHODS: We analyzed data from the Cardiovascular Health Study, a longitudinal cohort of 5888 older adults. Categories of lung function (normal; restricted; borderline, mild-moderate, and severe obstruction) were delineated by baseline spirometry (without bronchodilator). Disability-free years were calculated as total years alive and without self-report of difficulty performing &γτ;1 Instrumental Activities of Daily Living over 6 years of follow-up. Using linear regression, we compared disability-free years by lung disease category, adjusting for demographic factors, body mass index, smoking, cognition, and other chronic co-morbidities. Among participants with airflow obstruction, we examined the association of respiratory factors (FEV1 and dyspnea) and non-respiratory factors (ischemic heart disease, congestive heart failure, diabetes, muscle weakness, osteoporosis, depression and cognitive impairment) on disability-free years. RESULTS: The average disability free years were 4.0 out of a possible 6 years. Severe obstruction was associated with 1 fewer disability-free year compared to normal spirometry in the adjusted model. For the 1,048 participants with airway obstruction, both respiratory factors (FEV1 and dyspnea) and non-respiratory factors (heart disease, coronary artery disease, diabetes, depression, osteoporosis, cognitive function, and weakness) were associated with decreased disability-free years. CONCLUSIONS: Severe obstruction is associated with greater disability compared to patients with normal spirometery. Both respiratory and non-respiratory factors contribute to disability in older adults with abnormal spirometry. BACKGROUND: Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored. METHODS: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE)' Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses. RESULTS: We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002), vs. current smokers (β = 0.001, p = 0.95, p(interaction) = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5 x 10(-5)), vs. former/never smokers (β = 0.006, p = 0.05, p(interaction) = 0.08). CONCLUSIONS: These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results. CLINICAL TRIAL REGISTRATION: NCT00000611. BACKGROUND: Preventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals. METHODS: This was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization. RESULTS: The crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15%). The 30-day and 1-year mortality were 16.5% and 31.5%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38% of pneumonia cases occurred in adults < 65 years of age. The 30-day and 1-year mortality were 12.5% and 25.7% in those < 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance. CONCLUSIONS: Pneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model. Suppose that we need to classify a population of subjects into several well-defined ordered risk categories for disease prevention or management with their "baseline" risk factors/markers. In this article, we present a systematic approach to identify subjects using their conventional risk factors/markers who would benefit from a new set of risk markers for more accurate classification. Specifically for each subgroup of individuals with the same conventional risk estimate, we present inference procedures for the reclassification and the corresponding correct re-categorization rates with the new markers. We then apply these new tools to analyze the data from the Cardiovascular Health Study sponsored by the US National Heart, Lung, and Blood Institute. We used Framingham risk factors plus the information of baseline anti-hypertensive drug usage to identify adult American women who may benefit from the measurement of a new blood biomarker, CRP, for better risk classification in order to intensify prevention of coronary heart disease for the subsequent 10 years. BACKGROUND- Familial dilated cardiomyopathy (DCM) is a genetically heterogeneous disease with >30 known genes. TTN truncating variants were recently implicated in a candidate gene study to cause 25% of familial and 18% of sporadic DCM cases. METHODS AND RESULTS- We used an unbiased genome-wide approach using both linkage analysis and variant filtering across the exome sequences of 48 individuals affected with DCM from 17 families to identify genetic cause. Linkage analysis ranked the TTN region as falling under the second highest genome-wide multipoint linkage peak, multipoint logarithm of odds, 1.59. We identified 6 TTN truncating variants carried by individuals affected with DCM in 7 of 17 DCM families (logarithm of odds, 2.99); 2 of these 7 families also had novel missense variants that segregated with disease. Two additional novel truncating TTN variants did not segregate with DCM. Nucleotide diversity at the TTN locus, including missense variants, was comparable with 5 other known DCM genes. The average number of missense variants in the exome sequences from the DCM cases or the ≈5400 cases from the Exome Sequencing Project was ≈23 per individual. The average number of TTN truncating variants in the Exome Sequencing Project was 0.014 per individual. We also identified a region (chr9q21.11-q22.31) with no known DCM genes with a maximum heterogeneity logarithm of odds score of 1.74. CONCLUSIONS- These data suggest that TTN truncating variants contribute to DCM cause. However, the lack of segregation of all identified TTN truncating variants illustrates the challenge of determining variant pathogenicity even with full exome sequencing. OBJECTIVES: to investigate whether psychosocial pathways mediate the association between neighbourhood socioeconomic disadvantage and stroke. METHODS: prospective cohort study with a follow-up of 11.5 years. SETTING: the Cardiovascular Health Study, a longitudinal population-based cohort study of older adults ≥65 years. MEASUREMENTS: the primary outcome was adjudicated incident ischaemic stroke. Neighbourhood socioeconomic status (NSES) was measured using a composite of six census-tract variables. Psychosocial factors were assessed with standard measures for depression, social support and social networks. RESULTS: of the 3,834 white participants with no prior stroke, 548 had an incident ischaemic stroke over the 11.5-year follow-up. Among whites, the incident stroke hazard ratio (HR) associated with living in the lowest relative to highest NSES quartile was 1.32 (95% CI = 1.01-1.73), in models adjusted for individual SES. Additional adjustment for psychosocial factors had a minimal effect on hazard of incident stroke (HR = 1.31, CI = 1.00-1.71). Associations between NSES and stroke incidence were not found among African-Americans (n = 785) in either partially or fully adjusted models. CONCLUSIONS: psychosocial factors played a minimal role in mediating the effect of NSES on stroke incidence among white older adults. AIM: To examine the association of plasma fatty acid-binding protein 4 (FABP4) with incident heart failure. METHODS AND RESULTS: In a prospective study of 4179 participants from the Cardiovascular Health Study, we measured plasma FABP4 on blood specimens collected between 1992 and 1993. Incident heart failure was adjudicated by an endpoint committee and we used a Cox proportional hazards model to calculate hazard ratios (HRs) of heart failure. The average age at baseline was 75 years. During a median follow-up of 10.7 years, 1182 cases of incident heart failure occurred. We observed a positive association between FABP4 and heart failure in the minimally adjusted models [HR 1.32, 95% confidence interval (CI) 1.25-1.38 per 1 SD higher FABP4] that was attenuated upon adjustment for potential confounders, mostly kidney function and body mass index (corresponding HR 1.09, 95% CI 1.01-1.17). In a subsample of heart failure cases with available data on LV systolic function, FABP4 was not associated with heart failure with or without preserved LV systolic function. Exclusion of people with unintentional weight loss and self-reported fair/poor health status did not alter the conclusion. CONCLUSION: An elevated plasma concentration of FABP4 was associated with a modestly higher risk of heart failure in older adults in the USA after adjustment for confounding factors. OBJECTIVE: Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008. RESULTS: Mean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88-0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93-1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85-0.97) and 0.87 (0.79-0.95), respectively]. CONCLUSIONS: The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes. CONTEXT: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis. OBJECTIVE: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults. DESIGN AND SETTING: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease. PARTICIPANTS: Participants included 2008 women and 1329 men ≥65 years from the 1996 to 1997 Cardiovascular Health Study visit. MAIN OUTCOME MEASURES: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants. RESULTS: Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95% CI = 0.01-0.06 g/cm(2)). During 9.6 ± 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95% CI = 0.78-1.15, and 1.09 with 95% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions). CONCLUSIONS: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk. OBJECTIVES: In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain. METHODS: C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH. RESULTS: Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35-9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97-1.48]). CONCLUSION: In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD. Genome-wide association studies (GWASs) primarily performed in European-ancestry (EA) populations have identified numerous loci associated with body mass index (BMI). However, it is still unclear whether these GWAS loci can be generalized to other ethnic groups, such as African Americans (AAs). Furthermore, the putative functional variant or variants in these loci mostly remain under investigation. The overall lower linkage disequilibrium in AA compared to EA populations provides the opportunity to narrow in or fine-map these BMI-related loci. Therefore, we used the Metabochip to densely genotype and evaluate 21 BMI GWAS loci identified in EA studies in 29,151 AAs from the Population Architecture using Genomics and Epidemiology (PAGE) study. Eight of the 21 loci (SEC16B, TMEM18, ETV5, GNPDA2, TFAP2B, BDNF, FTO, and MC4R) were found to be associated with BMI in AAs at 5.8 × 10(-5). Within seven out of these eight loci, we found that, on average, a substantially smaller number of variants was correlated (r(2) > 0.5) with the most significant SNP in AA than in EA populations (16 versus 55). Conditional analyses revealed GNPDA2 harboring a potential additional independent signal. Moreover, Metabochip-wide discovery analyses revealed two BMI-related loci, BRE (rs116612809, p = 3.6 × 10(-8)) and DHX34 (rs4802349, p = 1.2 × 10(-7)), which were significant when adjustment was made for the total number of SNPs tested across the chip. These results demonstrate that fine mapping in AAs is a powerful approach for both narrowing in on the underlying causal variants in known loci and discovering BMI-related loci. PURPOSE: Single nucleotide polymorphisms (SNPs) located near or within the COL5A1 gene, at 9q34.2-q34.3 chromosomal region have been reported in association with central corneal thickness (CCT). Using family linkage analysis, we identified a keratoconus susceptibility locus at 9q34. These findings led us to perform an association study between COL5A1 variation and keratoconus susceptibility. METHODS: A Caucasian case-control cohort of 222 keratoconus patients and 3324 controls was selected as the discovery panel. An independent case-control panel of 304 cases and 518 controls and a family panel of 186 subjects were replicated for genotyping and association. Forty-four SNPs (21 for discovery and 23 for fine-mapping) spanning 300 kilobases in and around COL5A1 were genotyped and tested for genetic association. Logistic regression models implemented in PLINK were used to test for association in case controls. Generalized estimating equation models accounting for familial correlations implemented in genome-wide interaction analyses with family data were used for association testing in families. RESULTS: Two CCT associated SNPs (rs1536482 and rs7044529 near and within COL5A1) were identified in the keratoconus discovery cohort (P values of 6.5 × 10(-3) and 7.4 × 10(-3)). SNP rs1536482 was replicated in the second case-control sample (P = 0.02), and SNP rs7044529 was replicated in a keratoconus family panel (P = 0.03). Meta P values of rs1536482 and rs7044529 in the keratoconus cohorts were 1.5 × 10(-4) (odds ratio [OR] = 1.30) and 2.9 × 10(-3) (OR = 1.39). After Bonferroni correction, the association of SNP rs1536482 remained significant (P = 6.5 × 10(-3)). CONCLUSIONS: SNPs in the COL5A1 region, which regulate normal variation in CCT, may play a role in the thinning associated with keratoconus. Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined. BACKGROUND: Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. METHODS: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. RESULTS: Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. CONCLUSIONS: Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium. OBJECTIVE: Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992-1993. RESULTS: Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P<0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2-2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (-0.3 mg/dL [95% CI, -1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P=0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant. CONCLUSIONS: Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal. Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 × 10(-12); rs35897051, P = 3.32 × 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 × 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of ∼80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study. Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 × 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8); RREB1: p = 5.7 × 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity. Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case-control studies. In the combined data from these two stages, additional genome-wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10(-13) for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10(-6) ) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations. BACKGROUND- Palmitic acid (16:0), stearic acid (18:0), palmitoleic acid (16:1n-7), and oleic acid (18:1n-9) are major saturated and monounsaturated fatty acids that affect cellular signaling and metabolic pathways. They are synthesized via de novo lipogenesis and are the main saturated and monounsaturated fatty acids in the diet. Levels of these fatty acids have been linked to diseases including type 2 diabetes mellitus and coronary heart disease. METHODS AND RESULTS- Genome-wide association studies were conducted in 5 population-based cohorts comprising 8961 participants of European ancestry to investigate the association of common genetic variation with plasma levels of these 4 fatty acids. We identified polymorphisms in 7 novel loci associated with circulating levels of ≥1 of these fatty acids. ALG14 (asparagine-linked glycosylation 14 homolog) polymorphisms were associated with higher 16:0 (P=2.7×10(-11)) and lower 18:0 (P=2.2×10(-18)). FADS1 and FADS2 (desaturases) polymorphisms were associated with higher 16:1n-7 (P=6.6×10(-13)) and 18:1n-9 (P=2.2×10(-32)) and lower 18:0 (P=1.3×10(-20)). LPGAT1 (lysophosphatidylglycerol acyltransferase) polymorphisms were associated with lower 18:0 (P=2.8×10(-9)). GCKR (glucokinase regulator; P=9.8×10(-10)) and HIF1AN (factor inhibiting hypoxia-inducible factor-1; P=5.7×10(-9)) polymorphisms were associated with higher 16:1n-7, whereas PKD2L1 (polycystic kidney disease 2-like 1; P=5.7×10(-15)) and a locus on chromosome 2 (not near known genes) were associated with lower 16:1n-7 (P=4.1×10(-8)). CONCLUSIONS- Our findings provide novel evidence that common variations in genes with diverse functions, including protein-glycosylation, polyunsaturated fatty acid metabolism, phospholipid modeling, and glucose- and oxygen-sensing pathways, are associated with circulating levels of 4 fatty acids in the de novo lipogenesis pathway. These results expand our knowledge of genetic factors relevant to de novo lipogenesis and fatty acid biology. BACKGROUND: Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study. METHODS AND RESULTS: Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genome-wide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10(-7)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43×10(-7)) for left ventricular mass, rs7213314 in WIPI1 (P=1.68×10(-7)) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57×10(-8)) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02×10(-7)) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN. CONCLUSIONS: In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes. BACKGROUND: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. RESULTS: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258). CONCLUSIONS: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking. BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes. METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy. RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3±0.23 (beta ± standard error), p = 6.6×10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (∼2%), the quality of the imputation was moderate (r(2) ∼0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension. CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases. Accelerated lung function decline is a key COPD phenotype; however, its genetic control remains largely unknown. We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility. BACKGROUND: Height is inversely associated with incident coronary disease and total stroke, but few studies have examined the association between height and intraparenchymal hemorrhage (IPH). We hypothesized that height would be inversely associated with incident IPH in the combined cohorts of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. METHODS: Data on Caucasian and African American participants were used to estimate the association of height at baseline with incident IPH verified by clinician review of medical records and imaging reports. Sex-specific Cox proportional hazards regression models were used to calculate hazard ratios. RESULTS: A total of 20,983 participants initially free of stroke (11,788 women and 9195 men) were followed for an average of 15.9 years (standard deviation [SD] 5.1 years). Incident IPH occurred in 115 women and 73 men. Sex, but not age, race, study, or blood pressure, modified the association (P = .03). After adjustment for risk factors (age, systolic blood pressure, triglycerides, low-density lipoprotein cholesterol, fibrinogen, and race), among women, height was significantly inversely associated with incident IPH (hazard ratio [HR] per SD [6.3 cm] was 0.81; 95% confidence interval [CI] 0.66-0.99; P = .04). The HR for tertile 3 vs 1 in women was 0.63 (95% CI 0.37-1.08). Among men, height was not linearly associated with incident IPH (HR per SD [6.7 cm] was 1.09; 95% CI 0.84-1.40; P = .52). CONCLUSIONS: This large prospective study provides evidence that shorter height may be a risk factor for incident IPH in women. While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ≥65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: (1) per each 1 g/dL decrease in hemoglobin and (2) development of anemia by the WHO criteria. Among participants without baseline anemia, hemoglobin decreased by 0.4 g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1 g/dL decrease) predicted subsequent mortality in men and women. Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life. Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = -0.009 mmol/L (95% CI: -0.013, -0.005), P < 0.0001] and insulin [-0.020 ln-pmol/L (95% CI: -0.024, -0.017), P < 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age. METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort. RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% CI, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 8.3), 8.9 (95% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest. CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults. BACKGROUND: Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown. OBJECTIVE: Investigate inflammatory markers' individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD). METHODS: In 3888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA₂) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA₂ values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA₂ was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events. RESULTS: CHD incidence (per 1000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR = 1.50, p < 0.01) or highest IL-6 tertile (HR = 1.40, p < 0.05), but not with highest Lp-PLA₂ tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index. CONCLUSION: The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation. BACKGROUND: Inflammation is linked to adverse cardiovascular events, but its association with sudden cardiac death (SCD) has been controversial. Older subjects, who are at particular risk for SCD, were underrepresented in previous studies addressing this issue. OBJECTIVE: The purpose of this study was to study the association between inflammation and SCD in a community-based population of older adults. METHODS: In the Cardiovascular Health Study, 5806 and 5382 participants had measurements of C-reactive protein (CRP) and interleukin-6 (IL6), respectively, and were followed for up to 17 years. SCD risk as a function of baseline IL-6 and CRP was assessed in the overall population and in a group of participants without known prevalent cardiac disease. RESULTS: In univariate analyses, both IL-6 (hazard ratio [HR] 1.79 for 1+ log IL-6, 95% confidence interval [CI] 1.50-2.13; 5th vs 1st quintile HR 3.36, 95% CI 2.24-5.05) and CRP (HR 1.31 for 1+ log CRP, 95% CI 1.18-1.45; 5th vs 1st quintile HR 2.00, 95% CI 1.40-2.87) were associated with SCD risk. In covariate-adjusted analyses, accounting for baseline risk factors, incident myocardial infarction, and heart failure, the association with SCD risk persisted for IL-6 (HR 1.26 for 1+ log IL-6, 95% CI 1.02-1.56; 5th vs 1st quintile HR 1.63, 95% CI 1.03-2.56) but was significantly attenuated for CRP (HR 1.13 for 1+ log CRP, 95% CI 1.00-1.28; 5th vs 1st quintile HR 1.34, 95% CI 0.88-2.05). Similar findings were observed in participants without prevalent cardiac disease. CONCLUSION: Greater burden of inflammation, assessed by IL-6 levels, is associated with SCD risk beyond traditional risk factors, incident myocardial infarction, and heart failure. Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m², respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data. BACKGROUND: Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance as compared with matched controls. Insulin resistance leads to structural abnormalities in the heart, such as increased left atrial size, left ventricular mass, and alterations in transmitral velocity that can precede the diagnosis of HF. It is not known whether insulin resistance precedes the development of HF or whether the relationship between insulin resistance and HF is present among adults with HF caused by nonischemic heart disease. METHODS AND RESULTS: We examined 4425 participants (60% women) from the Cardiovascular Health Study after excluding those with HF, myocardial infarction, or treated diabetes mellitus at baseline. We used Cox proportional hazards models to estimate the relative risk of incident HF associated with fasting insulin measured at study entry. There were 1216 cases of incident HF (1103 without antecedent myocardial infarction) during a median follow-up of 12 years (maximum, 19 years). Fasting insulin levels were positively associated with the risk of incident HF (hazard ratio, 1.10; 95% confidence interval, 1.05-1.15, per SD change) when adjusted for age, sex, race, field center, physical activity, smoking, alcohol intake, high-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure, and waist circumference. The association between fasting insulin levels and incident HF was similar for HF without antecedent myocardial infarction (hazard ratio, 1.10; 95% confidence interval, 1.05-1.15). Measures of left atrial size, left ventricular mass, and peak A velocity at baseline were associated both with fasting insulin levels and with HF; however, additional statistical adjustment for these parameters did not completely attenuate the insulin-HF estimate (hazard ratio, 1.08; 95% confidence interval, 1.03-1.14 per 1-SD increase in fasting insulin). CONCLUSIONS: Fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF in Cardiovascular Health Study participants, including those without an antecedent myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133. BACKGROUND: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels are influenced by both genes and the environment. Genome-wide association studies (GWAS) have identified ~100 common genetic variants associated with HDL-C, LDL-C, and/or TG levels, mostly in populations of European descent, but little is known about the modifiers of these associations. Here, we investigated whether GWAS-identified SNPs for lipid traits exhibited heterogeneity by sex in the Population Architecture using Genomics and Epidemiology (PAGE) study. RESULTS: A sex-stratified meta-analysis was performed for 49 GWAS-identified SNPs for fasting HDL-C, LDL-C, and ln(TG) levels among adults self-identified as European American (25,013). Heterogeneity by sex was established when phet < 0.001. There was evidence for heterogeneity by sex for two SNPs for ln(TG) in the APOA1/C3/A4/A5/BUD13 gene cluster: rs28927680 (p(het) = 7.4 x 10(-7)) and rs3135506 (p(het) = 4.3 x 10(-4)one SNP in PLTP for HDL levels (rs7679; p(het) = 9.9 x 10(-4)), and one in HMGCR for LDL levels (rs12654264; p(het) = 3.1 x 10(-5)). We replicated heterogeneity by sex in five of seventeen loci previously reported by genome-wide studies (binomial p = 0.0009). We also present results for other racial/ethnic groups in the supplementary materials, to provide a resource for future meta-analyses. CONCLUSIONS: We provide further evidence for sex-specific effects of SNPs in the APOA1/C3/A4/A5/BUD13 gene cluster, PLTP, and HMGCR on fasting triglyceride levels in European Americans from the PAGE study. Our findings emphasize the need for considering context-specific effects when interpreting genetic associations emerging from GWAS, and also highlight the difficulties in replicating interaction effects across studies and across racial/ethnic groups. OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype. METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3). RESULTS: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). INTERPRETATION: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity. RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty. CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function. BACKGROUND: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque. METHODS: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model. RESULTS: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10(-5)), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05). CONCLUSIONS: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries. OBJECTIVES: This study sought to estimate lifetime risk for heart failure (HF) by sex and race. BACKGROUND: Prior estimates of lifetime risk for developing HF range from 20% to 33% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made. METHODS: Using public-release and internal datasets from National Heart, Lung, and Blood Institute-sponsored cohorts, we estimated lifetime risks for developing HF to age 95 years, with death free of HF as the competing event, among participants in the CHA (Chicago Heart Association Detection Project in Industry), ARIC (Atherosclerosis Risk in Communities), and CHS (Cardiovascular Health Study) cohorts. RESULTS: There were 39,578 participants (33,652 [85%] white; 5,926 [15%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30% to 42% in white men, 20% to 29% in black men, 32% to 39% in white women, and 24% to 46% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher blood pressure and body mass index at all ages in both blacks and whites, and did not diminish substantially with advancing index age. CONCLUSIONS: These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks. OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids. DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800). RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed. CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits. BACKGROUND: Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown. METHODS AND RESULTS: We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2±5.2 years) in the Cardiovascular Health Study (CHS; 1992-2006) and 3577 middle-aged adults (mean age, 54.1±5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987-2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95% confidence interval, 1.02-1.76) and 1.57 (95% confidence interval, 1.11-2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95% confidence interval, 1.23-2.50) and 1.92 (95% confidence interval, 1.22-3.03) for 24:1, respectively (P for trend ≤0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard. CONCLUSIONS: Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans. OBJECTIVE: White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST). METHODS: Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58% women, 84% white) with WMH (0-9 points), DSST (0-90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5-18.1] years). RESULTS: WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio [HR; 95% confidence interval {CI}] for WMH >3 points = 1.48 [1.35-1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27-1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95% CI] = 0.66 [0.55-0.81] and 0.72 [0.62-0.83], respectively). CONCLUSIONS: WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH. OBJECTIVES: This study sought to determine whether the combined trajectories of cardiac biomarkers identify those older adults with initial low levels who have an increased risk for structural heart disease, incident heart failure (HF), and cardiovascular (CV) death. BACKGROUND: Initial low levels of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) identify older adults at lower risk for CV events. METHODS: We performed an observational study among older adults without prevalent HF in the CHS (Cardiovascular Health Study). NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years. In those with low baseline levels, a significant increase was defined as cardiac troponin T (cTnT) >50% and NT-proBNP >25% increase to >190 pg/ml. Left ventricular ejection fraction and left ventricular mass were measured by echocardiography at baseline and 5 years. Cox regression was used to estimate the association of change in biomarkers with HF and CV mortality. RESULTS: Among 2,008 participants with initially low biomarker concentrations, significant increases occurred in 14.8% for cTnT only, 13.2% for NT-proBNP only, and 6.1% for both. After 10 years, cumulative HF incidence was 50.4% versus 12.2% among those with both biomarkers versus neither biomarker increased. The adjusted relative risk comparing those with increases in both biomarkers versus neither biomarker was 3.56 for incident HF (95% confidence interval: 2.56 to 4.97) and 2.98 for CV mortality (95% confidence interval: 2.98 to 4.26). Among 1,340 participants with serial echocardiography, the frequency of new abnormal left ventricular ejection fraction was 11.8% versus 4% for those with increases in both biomarkers versus neither biomarker (p = 0.007). CONCLUSIONS: Among older adults without HF with initially low cTnT and NT-proBNP, the long-term trajectory of both biomarkers predicts systolic dysfunction, incident HF, and CV death. Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease. Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. BACKGROUND: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation. METHODS AND RESULTS: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. CONCLUSIONS: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism. OBJECTIVE: Residence in a socioeconomically disadvantaged community is associated with mortality, but the mechanisms are not well understood. We examined whether socioeconomic features of the residential neighborhood contribute to poststroke mortality and whether neighborhood influences are mediated by traditional behavioral and biologic risk factors. METHODS: We used data from the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ≥65 years. Residential neighborhood disadvantage was measured using neighborhood socioeconomic status (NSES), a composite of 6 census tract variables representing income, education, employment, and wealth. Multilevel Cox proportional hazard models were constructed to determine the association of NSES to mortality after an incident stroke, adjusted for sociodemographic characteristics, stroke type, and behavioral and biologic risk factors. RESULTS: Among the 3,834 participants with no prior stroke at baseline, 806 had a stroke over a mean 11.5 years of follow-up, with 168 (20%) deaths 30 days after stroke and 276 (34%) deaths at 1 year. In models adjusted for demographic characteristics, stroke type, and behavioral and biologic risk factors, mortality hazard 1 year after stroke was significantly higher among residents of neighborhoods with the lowest NSES than those in the highest NSES neighborhoods (hazard ratio 1.77, 95% confidence interval 1.17-2.68). CONCLUSION: Living in a socioeconomically disadvantaged neighborhood is associated with higher mortality hazard at 1 year following an incident stroke. Further work is needed to understand the structural and social characteristics of neighborhoods that may contribute to mortality in the year after a stroke and the pathways through which these characteristics operate. Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype-phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Architecture Using Genomics and Epidemiology (PAGE) study. Despite their biological plausibility, we were unable to detect significant SNP × smoking interactions. BACKGROUND: The contribution of obesity to hypoxemia has not been reported in a community-based study. Our hypothesis was that increasing obesity would be independently associated with lower SpO2 in an ambulatory elderly population. METHODS: The Cardiovascular Health Study ascertained resting SpO2 in 2,252 subjects over age 64. We used multiple linear regression to estimate the association of body mass index (BMI) with SpO2 and to adjust for potentially confounding factors. Covariates including age, sex, race, smoking, airway obstruction (based on spirometry), self reported diagnosis of emphysema, asthma, heart failure, and left ventricular function (by echocardiography) were evaluated. RESULTS: Among 2,252 subjects the mean and median SpO2 were 97.6% and 98.0% respectively; 5% of subjects had SpO2 values below 95%. BMI was negatively correlated with SpO2 (Spearman R = -0.27, P < .001). The mean difference in SpO2 between the lowest and highest BMI categories (< 25 kg/m(2) and ≥ 35 kg/m(2)) was 1.33% (95% CI 0.89-1.78%). In multivariable linear regression analysis, SpO2 was significantly inversely associated with BMI (1.4% per 10 units of BMI, 95% CI 1.2-1.6, for whites/others, and 0.87% per 10 units of BMI, 95% CI 0.47-1.27, for African Americans). CONCLUSIONS: We found a narrow distribution of SpO2 values in a community-based sample of ambulatory elderly. Obesity was a strong independent contributor to a low SpO2, with effects comparable to or greater than other factors clinically associated with lower SpO2. CONTEXT: Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies. OBJECTIVE: We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism. DESIGN, SETTING, AND PARTICIPANTS: The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations. MAIN OUTCOME MEASURE: We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5-6.9, 7.0-9.9, and 10.0-19.9 mU/liter). RESULTS: There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.93-1.36], HF (HR, 1.05; 95% CI, 0.97-1.27), or CV death (HR, 1.07; 95% CI, 0.87-1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death. CONCLUSIONS: Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism. BACKGROUND: Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes mellitus and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF). METHODS AND RESULTS: To test the hypothesis that plasma concentration of FFAs is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and >65 years old from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per SD of FFAs. During a median follow-up of 10.5 years, a total of 1286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12% (95% confidence interval, 6%-19%) higher risk of HF. Controlling for time-varying diabetes mellitus and coronary heart disease did not change the results (hazard ratio per SD, 1.16 [95% confidence interval, 1.09-1.23]). CONCLUSIONS: A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biological mechanisms by which FFAs may influence the risk of HF and determine whether FFAs could serve as a novel pharmacological target for HF prevention. BACKGROUND: Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention. OBJECTIVE: To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements. DESIGN: Prospective cohort study. SETTING: 4 U.S. communities. PARTICIPANTS: 2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline. MEASUREMENTS: Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed. RESULTS: During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile. LIMITATION: Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding. CONCLUSION: Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults. PRIMARY FUNDING SOURCE: National Institutes of Health. Numerous common genetic variants that influence plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride distributions have been identified via genome-wide association studies (GWAS). However, whether or not these associations are age-dependent has largely been overlooked. We conducted an association study and meta-analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or ≥50 years of age; females: pre- or postmenopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age-specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet < 0.05). The association between rs174547 (FADS1) and LDL-C in males displayed the most evidence for heterogeneity between age groups (Phet = 1.74E-03, I(2) = 89.8), with a significant association in older males (P = 1.39E-06) but not younger males (P = 0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP-trait associations despite large sample sizes. AIMS/HYPOTHESIS: We sought to derive and validate a cardiovascular disease (CVD) prediction algorithm for older adults with diabetes, and evaluate the incremental benefit of adding novel circulating biomarkers and measures of subclinical atherosclerosis. METHODS: As part of the Cardiovascular Health Study (CHS), a population-based cohort of adults aged ≥65 years, we examined the 10 year risk of myocardial infarction, stroke and cardiovascular death in 782 older adults with diabetes, in whom 265 events occurred. We validated predictive models in 843 adults with diabetes, who were followed for 7 years in a second cohort, the Multi-Ethnic Study of Atherosclerosis (MESA); here 71 events occurred. RESULTS: The best fitting standard model included age, smoking, systolic blood pressure, total and HDL-cholesterol, creatinine and the use of glucose-lowering agents; however, this model had a C statistic of 0.64 and poorly classified risk in men. Novel biomarkers did not improve discrimination or classification. The addition of ankle-brachial index, electrocardiographic left ventricular hypertrophy and internal carotid intima-media thickness modestly improved discrimination (C statistic 0.68; p = 0.002) and classification (net reclassification improvement [NRI] 0.12; p = 0.01), mainly in those remaining free of CVD. Results were qualitatively similar in the MESA, with a change in C statistic from 0.65 to 0.68 and an NRI of 0.09 upon inclusion of subclinical disease measures. CONCLUSIONS/INTERPRETATION: Standard clinical risk factors and novel biomarkers poorly discriminate and classify CVD risk in older adults with diabetes. The inclusion of subclinical atherosclerotic measures modestly improves these features, but to develop more robust risk prediction, a better understanding of the pathophysiology and determinants of CVD in this patient group is needed. BACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas. RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts. CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF. This study examined whether different associations between risk factors and atrial fibrillation (AF) according to race could explain the lower incidence of AF in blacks. Baseline risk factor information was obtained from interviews, clinical examinations, and echocardiography in 4,774 white and 911 black Cardiovascular Health Study participants aged 65 and older without a history of AF at baseline in 1989/90 or 1992/93. Incident AF was determined according to hospital discharge diagnosis or annual study electrocardiogram. Cox regression was used to assess associations between risk factors and race and incident AF. During a mean 11.2 years of follow-up, 1,403 whites and 182 blacks had incident AF. Associations between all examined risk factors were similar in both races, except left ventricular posterior wall thickness, which was more strongly associated with AF in blacks (per 0.2 cm, blacks: hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.44-2.06; whites: HR = 1.30, 95% CI = 1.18-1.43). Overall, the relative risk of AF was 25% lower in blacks than whites after adjustment for age and sex (HR = 0.75, 95% CI = 0.64-0.87) and 45% lower after adjustment for all considered risk factors (HR = 0.55, 95% CI = 0.35-0.88). Different associations of the considered risk factors and incident AF by race do not explain the lower incidence of AF in blacks. Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 ± 4.9 years, 69.7% were women, and 21% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 ± 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels ≥65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95% confidence interval 36.1 to 204), 5.2 pg/ml (95% confidence interval 3.0 to 7.4), and 17 g (95% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases. STUDY QUESTION: Do genetic associations identified in genome-wide association studies (GWAS) of age at menarche (AM) and age at natural menopause (ANM) replicate in women of diverse race/ancestry from the Population Architecture using Genomics and Epidemiology (PAGE) Study? SUMMARY ANSWER: We replicated GWAS reproductive trait single nucleotide polymorphisms (SNPs) in our European descent population and found that many SNPs were also associated with AM and ANM in populations of diverse ancestry. WHAT IS KNOWN ALREADY: Menarche and menopause mark the reproductive lifespan in women and are important risk factors for chronic diseases including obesity, cardiovascular disease and cancer. Both events are believed to be influenced by environmental and genetic factors, and vary in populations differing by genetic ancestry and geography. Most genetic variants associated with these traits have been identified in GWAS of European-descent populations. STUDY DESIGN, SIZE, DURATION: A total of 42 251 women of diverse ancestry from PAGE were included in cross-sectional analyses of AM and ANM. MATERIALS, SETTING, METHODS: SNPs previously associated with ANM (n = 5 SNPs) and AM (n = 3 SNPs) in GWAS were genotyped in American Indians, African Americans, Asians, European Americans, Hispanics and Native Hawaiians. To test SNP associations with ANM or AM, we used linear regression models stratified by race/ethnicity and PAGE sub-study. Results were then combined in race-specific fixed effect meta-analyses for each outcome. For replication and generalization analyses, significance was defined at P < 0.01 for ANM analyses and P < 0.017 for AM analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We replicated findings for AM SNPs in the LIN28B locus and an intergenic region on 9q31 in European Americans. The LIN28B SNPs (rs314277 and rs314280) were also significantly associated with AM in Asians, but not in other race/ethnicity groups. Linkage disequilibrium (LD) patterns at this locus varied widely among the ancestral groups. With the exception of an intergenic SNP at 13q34, all ANM SNPs replicated in European Americans. Three were significantly associated with ANM in other race/ethnicity populations: rs2153157 (6p24.2/SYCP2L), rs365132 (5q35/UIMC1) and rs16991615 (20p12.3/MCM8). While rs1172822 (19q13/BRSK1) was not significant in the populations of non-European descent, effect sizes showed similar trends. LIMITATIONS, REASONS FOR CAUTION: Lack of association for the GWAS SNPs in the non-European American groups may be due to differences in locus LD patterns between these groups and the European-descent populations included in the GWAS discovery studies; and in some cases, lower power may also contribute to non-significant findings. WIDER IMPLICATIONS OF THE FINDINGS: The discovery of genetic variants associated with the reproductive traits provides an important opportunity to elucidate the biological mechanisms involved with normal variation and disorders of menarche and menopause. In this study we replicated most, but not all reported SNPs in European descent populations and examined the epidemiologic architecture of these early reported variants, describing their generalizability and effect size across differing ancestral populations. Such data will be increasingly important for prioritizing GWAS SNPs for follow-up in fine-mapping and resequencing studies, as well as in translational research. BACKGROUND: 9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS). METHODS AND RESULTS: We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B. CONCLUSIONS: Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease. UNLABELLED: BACKGROUND/STUDY CONTEXT: The objective of this study was to examine sequential and simultaneous approaches to multiple imputation of missing data in a longitudinal data set where losses due to death were common. METHODS: Comparison of results from analyses and simulations of time to incident difficulty of activities of daily living (ADL) in the Cardiovascular Health Study when missing data were imputed simultaneously or sequentially. RESULTS: Results differed with imputation methods. The largest proportional differences in 12 risk factor parameter estimates were heart failure by 106%, social support by 33%, and arthritis by 27%. CONCLUSION: Decedents' final characteristics were influential on future imputations of those with missing values. OBJECTIVES: This study sought to identify risk factors for the occurrence of all-cause hospital admissions among older persons after heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors for admission when evaluated in the context of other relevant clinical data. BACKGROUND: Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk for hospital admission after heart failure diagnosis. With the aging of the population with heart failure, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common. METHODS: The study population included participants with a new diagnosis of heart failure in the Cardiovascular Health Study, a longitudinal study of community-living older persons. Data were collected through annual examinations and medical-record reviews. Geriatric conditions assessed were slow gait, muscle weakness (defined as weak grip), cognitive impairment, and depressive symptoms. Anderson-Gill regression modeling was used to determine the predictors of hospital admission after heart failure diagnosis. RESULTS: Of the 758 participants with a new diagnosis of heart failure, the mean rate of hospital admission was 7.9 per 10 person-years (95% CI: 7.4 to 8.4). Independent risk factors for hospital admission included diabetes mellitus (HR: 1.36; 95% CI: 1.13 to 1.64), New York Heart Association functional class III or IV (HR: 1.32; 95% CI: 1.11 to 1.57), chronic kidney disease (HR: 1.32; 95% CI: 1.14 to 1.53), slow gait (HR: 1.28; 95% CI: 1.06 to 1.55), depressed ejection fraction (HR: 1.25; 95% CI: 1.04 to 1.51), depression (HR: 1.23; 95% CI: 1.05 to 1.45), and muscle weakness (HR: 1.19; 95% CI: 1.00 to 1.42). CONCLUSIONS: Geriatric conditions are important, and potentially modifiable, risk factors for hospital admission in heart failure that should be routinely assessed at the time of heart failure diagnosis. Insulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). We tested whether risk factors would differ for DM that was preceded predominantly by IR, β-cell dysfunction, or both among 4,384 older adults (mean age, 72.7 (standard deviation, 5.6) years) in the Cardiovascular Health Study, which was conducted in North Carolina, California, Maryland, and Pennsylvania (1989-2007). When evaluating established risk factors, we found older age, greater adiposity, higher systolic blood pressure, a lower high-density lipoprotein cholesterol level, a higher triglyceride level, and a lower alcohol intake to be independently associated with greater IR but, conversely, with better β-cell function (P < 0.001). The prospective associations between some risk factors and incident DM varied significantly depending on whether DM was preceded predominantly by IR, β-cell dysfunction, or both. For example, obesity and lower high-density lipoprotein cholesterol levels were positively associated with DM preceded predominantly by IR (hazard ratio (HR) = 5.02, 95% confidence interval (CI): 2.81, 9.00; and HR = 1.97, 95% CI: 1.32, 2.93, respectively), with a significant association with and an insignificant trend toward a lower risk of DM preceded predominantly by β-cell dysfunction (HR = 0.33, 95% CI: 0.14, 0.80; and HR = 0.78, 95% CI: 0.43, 1.39, respectively). In conclusion, among older adults, DM risk factors were differentially associated with DM preceded predominantly by IR or β-cell dysfunction. Biologic and clinical implications of putative subtypes of DM require further investigation. Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits. BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. METHODS AND RESULTS: Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. CONCLUSION: A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe. STUDY OBJECTIVES: Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population. DESIGN SETTING: Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS). PATIENTS OR PARTICIPANTS: 1,233 elderly participants from the CHS and SHHS. MEASUREMENTS AND RESULTS: The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p < 0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p < 0.01). As expected, slow wave sleep was better preserved in females compared to males (22% total sleep time vs. 9% total sleep time, p < 0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] ≥ 5/h) was more prevalent in males compared to females (60% vs. 46%, p < 0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI ≥ 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI ≥ 5 and < 15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts. OBJECTIVE: CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes. METHODS AND RESULTS: We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults. CONCLUSIONS: CD14 independently predicts risk mortality in older adults. Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3 × 10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations. CONTEXT: Adiponectin is atheroprotective in the laboratory, but prospective studies have shown opposite associations with cardiovascular disease (CVD) in healthy middle-aged populations (protective) and older cohorts (adverse). Whether this relates to different proportions of high-molecular-weight (HMW) adiponectin is unknown. OBJECTIVE: The aim of the study was to test the hypothesis that total adiponectin is directly associated, but HMW adiponectin is inversely related, with CVD in older adults. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 3290 participants free of prevalent CVD in a longitudinal cohort study of U.S. adults aged 65 yr and older. MAIN OUTCOME MEASURES: We measured incident CVD (n = 1291), comprising coronary heart disease and ischemic stroke. RESULTS: Total and HMW adiponectin were tightly correlated (r = 0.94). Cubic splines adjusted for potential confounders revealed that the associations of total and HMW adiponectin with CVD were U-shaped, with inflection points of 20 and 10 mg/liter, respectively. After controlling for potential confounding, levels of total and HMW adiponectin below these cutpoints tended to be inversely associated with incident CVD, driven by their significant or near-significant relations with coronary heart disease [hazard ratio (HR), 0.85 per sd increase; 95% confidence interval (CI), 0.75-96; and HR, 0.87; 95% CI, 0.75-1.01, respectively]. These associations were abrogated by additional inclusion of putative metabolic intermediates. Above these cutpoints, however, both total and HMW adiponectin were significantly directly associated with CVD after adjustment for confounders and, particularly, mediators (HR, 1.20 per sd increase; 95% CI, 1.06-1.35; and HR, 1.12; 95% CI, 1.02-1.24, respectively). CONCLUSION: In community-living elders, total and HMW adiponectin showed similar U-shaped relationships with CVD. The inverse relation in the lower range, but not the direct association at the higher end, disappeared after inclusion of putative intermediates, suggesting that high levels may reflect adverse processes separate from adiponectin's beneficial glycometabolic properties. PURPOSE: Use of specific antihypertensive medications (AHTs) has been hypothesized to increase breast cancer risk, but results across published studies are inconsistent. METHODS: We re-evaluated the relationship between AHT use and breast cancer risk in a prospective cohort of 3,201 women ≥65 years of age at recruitment now with more than double the length of follow-up (12 vs. 5 years) and substantially more breast cancer diagnoses (188 compared with 75 cases). We estimated the association between AHT use overall as well as use of specific formulations (based on data collected annually) and breast cancer risk using multivariate-adjusted Cox regression. RESULTS: Compared with women who reported no use of AHTs, women who had used calcium channel blockers (CCB) within the past two years had a 1.6-fold increased risk of breast cancer (95 % confidence interval (CI): 1.0-2.5), and in particular, recent users of immediate-release CCBs had a 2.4-fold increased risk (95 % CI: 1.3-4.5). Neither ever nor recent use of any other type of AHT was associated with breast cancer risk. CONCLUSIONS: While the observed association between immediate-release CCBs and breast cancer risk is based on a small sample size and needs to be interpreted cautiously, this result is consistent with others in the literature. However, given declines in use of these preparations in favor of sustained-release CCBs, which was not related to risk, the potential clinical and public health impact of this association is limited. This study also adds to the evidence that other commonly used AHTs are not strongly related to breast cancer risk. BACKGROUND: The pulmonary function measures of forced expiratory volume in 1 second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome-wide association studies (GWASs) have identified numerous loci associated with FEV1 and FEV1/FVC, but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWASs may explain the significant associations between FEV1/FVC and 2 genes: ADAM19 and HTR4. METHODS AND RESULTS: We sequenced ADAM19 and its promoter region along with the ≈21-kb portion of HTR4 harboring GWAS single-nucleotide polymorphisms for pulmonary function and analyzed associations with FEV1/FVC among 3983 participants of European ancestry from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Meta-analysis of common variants in each region identified statistically significant associations (316 tests; P<1.58×10(-4)) with FEV1/FVC for 14 ADAM19 single-nucleotide polymorphisms and 24 HTR4 single-nucleotide polymorphisms. After conditioning on the sentinel GWASs hit in each gene (ADAM19 rs1422795, minor allele frequency=0.33 and HTR4 rs11168048, minor allele frequency=0.40], 1 single-nucleotide polymorphism remained statistically significant (ADAM19 rs13155908, minor allele frequency=0.12; P=1.56×10(-4)). Analysis of rare variants (minor allele frequency <1%) using sequence kernel association test did not identify associations with either region. CONCLUSIONS: Sequencing identified 1 common variant associated with FEV1/FVC independent of the sentinel ADAM19 GWAS hit and supports the original HTR4 GWAS findings. Rare variants do not seem to underlie GWAS associations with pulmonary function for common variants in ADAM19 and HTR4. BACKGROUND: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress--such as diabetes, chronic kidney disease and aging--where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined. METHODS: To test the hypothesis that circulating levels of N(ɛ)-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older. RESULTS: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase=1.11, 95% confidence interval [CI]=1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke. CONCLUSIONS: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML's value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population. OBJECTIVES: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts. BACKGROUND: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. METHODS: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race. RESULTS: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold. CONCLUSIONS: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay. One of the main perceived advantages of using a case-cohort design compared with a nested case-control design in an epidemiologic study is the ability to evaluate with the same subcohort outcomes other than the primary outcome of interest. In this paper, we show that valid inferences about secondary outcomes can also be achieved in nested case-control studies by using the inclusion probability weighting method in combination with an approximate jackknife standard error that can be computed using existing software. Simulation studies demonstrate that when the sample size is sufficient, this approach yields valid type 1 error and coverage rates for the analysis of secondary outcomes in nested case-control designs. Interestingly, the statistical power of the nested case-control design was comparable with that of the case-cohort design when the primary and secondary outcomes were positively correlated. The proposed method is illustrated with the data from a cohort in Cardiovascular Health Study to study the association of C-reactive protein levels and the incidence of congestive heart failure. OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health. OBJECTIVE: The metabolic syndrome (MetS) may contribute to the pathogenesis of venous thromboembolism (VTE), but this association requires additional investigation. APPROACH AND RESULTS: We performed a patient-level meta-analysis of case-control and cohort studies that evaluated the role of MetS and risk of unprovoked VTE. For case-control studies, odds ratios and 95% confidence intervals were calculated using logistic regression analysis to estimate the influence of individual variables on the risk of VTE; χ(2) tests for trend were used to investigate the effect of increasing number of components of MetS on the risk of VTE and to explore the influence of abdominal obesity on this relationship. For cohort studies, hazard ratios and 95% confidence interval were calculated using multivariable Cox regression analysis. Six case-control studies were included (908 cases with unprovoked VTE and 1794 controls): in multivariate analysis, MetS was independently associated with VTE (odds ratio, 1.91; 95% confidence interval, 1.57-2.33), and both MetS and abdominal obesity were better predictors of unprovoked VTE than obesity defined by the body mass index. Two prospective cohort studies were included (26,531 subjects and 289 unprovoked VTE events): age, obesity, and abdominal obesity, but not MetS were associated with VTE. CONCLUSIONS: Case-control but not prospective cohort studies support an association between MetS and VTE. Abdominal adiposity is a strong risk factor for VTE. BACKGROUND: Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality. STUDY DESIGN: Observational. SETTING & POPULATION: 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies. PREDICTORS: We estimated the association of rs13038305 with eGFRcys and serum creatinine-based eGFR (eGFRcr) and performed longitudinal analyses of the associations of eGFRcys with mortality and cardiovascular events following adjustment for rs13038305. OUTCOMES: We assessed reclassification by genotype-adjusted eGFRcys across CKD categories: <45, 45-59, 60-89, and ≥ 90 mL/min/1.73 m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFRcys category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis. RESULTS: In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%) was associated with a 6.4% lower cystatin C concentration, 5.5-mL/min/1.73 m(2) higher eGFRcys, and 36% [95% CI, 29%-41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14-1.20) and mortality (HR, 1.22; 95% CI, 1.19-1.24) per 10-mL/min/1.73 m(2) lower eGFRcys were similar with or without rs13038305 adjustment. 1,134 (7.7%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, -0.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD. LIMITATIONS: rs13038305 explains only a small proportion of cystatin C variation. CONCLUSIONS: Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest. BACKGROUND AND PURPOSE: Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke. METHODS: We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression. RESULTS: Among 29,595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black), 1261 developed stroke (12% hemorrhagic) during 280,549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure. CONCLUSIONS: Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations. BACKGROUND: Common variation at the 11p11.2 locus, encompassing MADD, ACP2, NR1H3, MYBPC3, and SPI1, has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. METHODS AND RESULTS: Sequencing (mean depth, 38×) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At NR1H3, 53 rare variants were jointly associated with FI (P=2.73×10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28×10(-3)). Conditioning on 2 previously associated variants at MADD (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11:47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at NR1H3, lies in intron 2 of NR1H3, and is a predicted binding site for forkhead box A1 (FOXA1), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11:47227430 A allele disrupted FOXA1 binding and reduced FOXA1-dependent transcriptional activity. CONCLUSIONS: Sequencing at 11p11.2-NR1H3 identified rare variation associated with FI. One variant, chr11:47227430, seems to be functional, with the rare A allele reducing transcription factor FOXA1 binding and FOXA1-dependent transcriptional activity. Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited. BACKGROUND: Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population. METHODS: We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes. RESULTS: During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14-1.70), coronary heart disease (HR 1.72, 95%CI 1.11-2.66), heart failure (HR 2.87, 95%CI 2.17-3.80), stroke (HR 1.56, 95%CI 0.99-2.46), AF (HR 5.75, 95%CI 4.43-7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9-67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51-2.66), AF (HR 4.25, 95%CI 3.28-5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8-32.1). CONCLUSION: Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation. BACKGROUND: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk. METHODS AND RESULTS: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026). CONCLUSION: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings. OBJECTIVES: To determine whether elderly people with different patterns of magnetic resonance imaging (MRI) findings have different long-term outcomes. DESIGN: Longitudinal cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older were recruited (N = 5,888); 3,660 of these underwent MRI, and 3,230 without a stroke before MRI were included in these analyses. MEASUREMENTS: Cluster analysis of brain MRI findings was previously used to define five clusters: normal, atrophy, simple infarct, leukoaraiosis, and complex infarct. Participants were subsequently classified as healthy if they rated their health as excellent, very good, or good and as able if they did not report any limitations in activities of daily living (ADLs). Mean years of life (YoL), years of healthy life (YHL), and years of able life (YAL) were calculated over 16 years after the MRI and compared between clusters using unadjusted and adjusted regression analyses. RESULTS: Mean age of participants was 75.0. With 16 years of follow-up, mean YoL was 11.3; YHL, 8.0; and YAL, 8.4. Outcomes differed significantly between clusters. With or without adjustments, outcomes were all significantly better in the normal than complex infarct cluster. The three remaining clusters had intermediate results, significantly different from the normal and complex infarct clusters but not usually from one another. Over 16 years of follow-up, participants in the complex infarct cluster (n = 368) spent the largest percentage of their 8.4 years alive being sick (38%) and not able (38%). CONCLUSION: Findings on MRI scans in elderly adults are associated not only with long-term survival, but also with long-term self-rated health and limitation in ADLs. The combination of infarcts and leukoaraiosis carried the worst prognosis, presumably reflecting small vessel disease. AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. CONCLUSION: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. Genome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNP×SNP interactions associated with HDL levels. We performed a GWIS in the Rotterdam Study (RS) cohort I (RS-I) using the GLIDE tool which leverages the massively parallel computing power of Graphics Processing Units (GPUs) to perform linear regression on all genome-wide pairs of SNPs. By performing a meta-analysis together with Rotterdam Study cohorts II and III (RS-II and RS-III), we were able to filter 181 interaction terms with a p-value<1 · 10-8 that replicated in the two independent cohorts. We were not able to replicate any of these interaction term in the AGES, ARIC, CHS, ERF, FHS and NFBC-66 cohorts (Ntotal = 30,011) when adjusting for multiple testing. Our GWIS resulted in the consistent finding of a possible interaction between rs774801 in ARMC8 (ENSG00000114098) and rs12442098 in SPATA8 (ENSG00000185594) being associated with HDL levels. However, p-values do not reach the preset Bonferroni correction of the p-values. Our study suggest that even for highly genetically determined traits such as HDL the sample sizes needed to detect SNP×SNP interactions are large and the 2-step filtering approaches do not yield a solution. Here we present our analysis plan and our reservations concerning GWIS. BACKGROUND: Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited. METHODS: We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor β1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years. RESULTS: Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 μg/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor β1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk. CONCLUSION: In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship. Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy‐methyl‐lysine (CML) are associated with risk of hip fracture.We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68–102 years; 39.8% male) for a median of 9.22 years (range, 0.01–12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD)measurement. There were 348 hip fractures during follow‐up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant‐years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95% confidence interval [CI], 1.16–1.40]; p<0.001). Sequential adjustment for age, gender, race/ethnicity,body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95% CI, 1.05–1.31; p=0.006).In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures. BACKGROUND: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort. METHODS AND RESULTS: Among 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both. CONCLUSIONS: High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults. Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (i.e., a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant. OBJECTIVE: We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. BACKGROUND: The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored. METHODS: Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS). RESULTS: Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29). CONCLUSION: The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population. BACKGROUND: There is limited information on genetic factors associated with sudden cardiac arrest (SCA). OBJECTIVE: To assess the association of common variation in genes in fatty acid pathways with SCA risk. METHODS: We selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases. RESULTS: Eight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lower SCA risk (95% confidence interval -16% to -1%) in the replication phase. CONCLUSIONS: While none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation. BACKGROUND: The association between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL-C (>80 mg/dL). METHODS AND RESULTS: Using pooled data from 6 community-based cohorts we examined CHD and total mortality risks across a broad range of HDL-C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex-stratified associations of HDL-C with the hazard for CHD events and total mortality, using HDL-C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person-years of follow-up. In men, the association between HDL-C and CHD events was inverse and linear across most HDL-C values; however at HDL-C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL-C and CHD events was inverse and linear across lower values of HDL-C, however at HDL-C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL-C, however mortality risks observed in participants with very high HDL-C were attenuated after adjustment for traditional risk factors. CONCLUSIONS: We did not observe further reductions in CHD risk with HDL-C values higher than 90 mg/dL in men and 75 mg/dL in women. IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event. OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression. BACKGROUND: Detection of "any cognitive impairment" is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives. METHODS: We developed and validated a brief Dementia Screening Indicator using data from four large, ongoing cohort studies (the Cardiovascular Health Study [CHS]; the Framingham Heart Study [FHS]; the Health and Retirement Study [HRS]; the Sacramento Area Latino Study on Aging [SALSA]) to help clinicians identify a subgroup of high-risk patients to target for cognitive screening. RESULTS: The final Dementia Screening Indicator included age (1 point/year; ages, 65-79 years), less than 12 years of education (9 points), stroke (6 points), diabetes mellitus (3 points), body mass index less than 18.5 kg/m(2) (8 points), requiring assistance with money or medications (10 points), and depressive symptoms (6 points). Accuracy was good across the cohorts (Harrell's C statistic: CHS, 0.68; FHS, 0.77; HRS, 0.76; SALSA, 0.78). CONCLUSIONS: The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening. BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS. DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events. METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events. RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women. CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest. OBJECTIVE: With aging, kidney function declines, as evidenced by reduced glomerular filtration rate. It is controversial whether or not high protein intake accelerates this decline. The aim of this study was to determine whether high protein intake was associated with declines in kidney function among older patients. METHODS: We examined whether dietary protein is associated with change in kidney function (mean follow-up 6.4 y [SD = 1.4, range = 2.5-7.9] in the Cardiovascular Health Study (N = 3623). We estimated protein intake using a food frequency questionnaire and estimated glomerular filtration rate from cystatin C. Associations between protein intake and kidney function were determined by linear and logistic regression models. RESULTS: Average protein intake was 19% of energy intake (SD = 5%). Twenty-seven percent (n = 963) of study participants had rapid decline in kidney function, as defined by (ΔeGFRcysC > 3 mL•min•1.73 m(2)). Protein intake (characterized as g/d and % energy/d), was not associated with change in estimated glomerular filtration rate (P > 0.05 for all comparisons). There were also no significant associations when protein intake was separated by source (animal and vegetable). CONCLUSION: These data suggest that higher protein intake does not have a major effect on kidney function decline among elderly men and women. BACKGROUND: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time. OBJECTIVE: To identify factors associated with transition between states of disability and independent function in obstructive lung disease. METHODS: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression. RESULTS: The prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and <7 blocks: RR 0.73 and 95% CI 0.61-0.86). Increased strength (RR 1.16 and 95% CI 1.05-1.29) was associated with resolving IADL impairment. CONCLUSIONS: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability. BACKGROUND: It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults. METHODS: Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes. RESULTS: Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04). CONCLUSION: Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes. This prospective study examined the effect of widowhood on physical activity by comparing widowed elders to health status-, age-, and sex-matched married controls. Participants included 396 married controls and 396 widows/widowers age 64-91 (M age = 72.7 years) who experienced the death of their spouse while participating in the Cardiovascular Health Study. Compared to married controls, widowed men, but not women, were more likely to increase their physical activity following the death of their spouse. However, this increased level of activity was not sustained and declines as time since spousal death passes. Moreover, during the year before spousal death, soon-to-be widowed men, but not women, increase their physical activity. Our results suggest that widowed men experience significant changes in physical activity and that the transition to widowhood contribute to these changes. PURPOSE: We sought to improve a previous algorithm to ascertain Parkinson's disease (PD) in the Cardiovascular Health Study by incorporating additional data from Medicare outpatient claims. We compared our results to the previous algorithm in terms of baseline prevalence and incidence of PD, as well as associations with baseline smoking characteristics. METHODS: Our original case ascertainment used self-reported diagnosis, antiparkinsonian medication, and hospitalization discharge International Classification of Diseases-Ninth version code. In this study, we incorporated additional data from fee-for-service Medicare claims, extended follow-up time, review of hospitalization records, and adjudicated cause of death. Two movement disorders specialists adjudicated final PD status. We used logistic regression models and controlled for age, sex, African American race, and education. RESULTS: We identified 75 additional cases but reclassified 80 previously identified cases as not having PD. We observed significant inverse association with smoking status (odds ratio = 0.42; 95% confidence interval (CI) = 0.22, 0.79), and inverse linear trends with pack-years (p = 0.005), and cigarettes per day (p = 0.019) with incident PD. All estimates were stronger than those from the previous algorithm. CONCLUSIONS: Our enhanced method did not alter prevalence and incidence estimates compared with our previous algorithm. However, our enhanced method provided stronger estimates of association, potentially due to reduced level of disease misclassification. BACKGROUND: Decreased glomerular filtration rate (GFR) leads to reduced production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 (25[OH]D3). Effects of low GFR on vitamin D catabolism are less well understood. We tested associations of estimated GFR (eGFR) with the circulating concentration of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), the most abundant product of 25(OH)D3 catabolism, across populations with a wide range of GFRs. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 9,596 participants in 5 cohort studies and clinical trials: the Diabetes Control and Complications Trial (N=1,193), Multi-Ethnic Study of Atherosclerosis (N=6,470), Cardiovascular Health Study (N=932), Seattle Kidney Study (N=289), and Hemodialysis Study (N=712). PREDICTOR: eGFR. OUTCOME: Circulating 24,25(OH)2D3 concentration. MEASUREMENTS: GFR was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation. Vitamin D metabolites were measured by mass spectrometry. RESULTS: Circulating 24,25(OH)2D3 concentration was correlated with circulating 25(OH)D3 concentration (Pearson r range, 0.64-0.88). This correlation was weaker with lower eGFRs. Moreover, the increment in 24,25(OH)2D3 concentration associated with higher 25(OH)D3 concentration (slope) was lower with lower eGFRs: 2.06 (95% CI, 2.01-2.10), 1.77 (95% CI, 1.74-1.81), 1.55 (95% CI, 1.48-1.62), 1.17 (95% CI, 1.05-1.29), 0.92 (95% CI, 0.74-1.10), 0.61 (95% CI, 0.22-1.00), and 0.37 (95% CI, 0.35-0.39) ng/mL of 24,25(OH)2D3 per 10 ng/mL of 25(OH)D3 for eGFRs≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2 and end-stage renal disease treated with hemodialysis, respectively. As a result, at a 25(OH)D3 concentration of 20 ng/mL, mean 24,25(OH)2D3 concentrations were 2.92 (95% CI, 2.87-2.96), 2.68 (95% CI, 2.64-2.72), 2.35 (95% CI, 2.26-2.45), 1.92 (95% CI, 1.74-2.10), 1.69 (95% CI, 1.43-1.95), 1.14 (95% CI, 0.62-1.66), and 1.04 (95% CI,1.02-1.07) ng/mL for each category, respectively. This interaction was independent of other relevant clinical characteristics. Race, diabetes, urine albumin excretion, and circulating parathyroid hormone and fibroblast growth factor 23 concentrations more modestly modified the association of 24,25(OH)2D3 with 25(OH)D3. LIMITATIONS: Lack of direct pharmacokinetic measurements of vitamin D catabolism. CONCLUSIONS: Lower eGFR is associated strongly with reduced vitamin D catabolism, as measured by circulating 24,25(OH)2D3 concentration. BACKGROUND: QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations. METHODS: Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16,398), African (n = 5,437), American Indian (n = 5,032), Hispanic (n = 1,143), and Asian (n = 932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran's Q test. RESULTS: Of 21 SNPs, 7 showed consistent direction of effect across all 5 populations, and an additional 9 had estimated effects that were consistent across 4 populations. Despite consistent direction of effect, 9 of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity. CONCLUSIONS: These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT. BACKGROUND: African Americans (AAs) have a higher prevalence of extreme ischemic white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) than do European Americans (EAs) based on the Cardiovascular Health Study (CHS) score. Ischemic white matter disease, limited to the deep white matter, may be biologically distinct from disease in other regions and may reflect a previously observed trend toward an increased risk of subcortical lacunar infarcts in AAs. We hypothesized that extreme deep WMH volume (DWMV) or periventricular volume (PV) may also have a higher prevalence in AAs. Thus, we studied extreme CHS scores and extreme DWMV and PV in a healthy population enriched for cardiovascular disease risk factors. METHODS: We imaged the brains of 593 subjects who were first-degree relatives of probands with early onset coronary disease prior to 60 years of age. WMHs were manually delineated on 3-tesla cranial MRI by a trained radiology reader; the location and volume of lesions were characterized using automated software. DWMV and PV were measured directly with automated software, and the CHS score was determined by a neuroradiologist. Volumes were characterized as being in the upper 25% versus lower 75% of total lesion volume. Volumes in the upper versus the remaining quartiles were examined for AA versus EA race using multiple logistic regression (generalized estimating equations adjusted for family relatedness) and adjusted for major vascular disease risk factors including age ≥55 years versus <55, sex, current smoking, obesity, hypertension, diabetes and low-density lipoprotein >160 mg/dl. RESULTS: Participants were 58% women and 37% AAs, with a mean age of 51.5 ± 11.0 years (range, 29-74 years). AAs had significantly higher odds of having extreme DWMVs (odds ratio, OR, 1.8; 95% confidence interval, CI, 1.2-2.9; p = 0.0076) independently of age, sex, hypertension and all other risk factors. AAs also had significantly higher odds of having extreme CHS scores ≥3 (OR, 1.3; 95% CI, 1.1-3.6; p = 0.025). Extreme PV was not significantly associated with AA race (OR, 1.3; 95% CI, 0.81-2.1; p = 0.26). CONCLUSIONS: AAs from families with early-onset cardiovascular disease are more likely to have extreme DWMVs (a subclinical form of cerebrovascular disease) and an extreme CHS score, but not extreme PV, independently of age and other cardiovascular disease risk factors. These findings suggest that this AA population is at an increased risk for DWMV and may be at an increased risk for future subcortical stroke. Longitudinal studies are required to see if DWMV is predictive of symptomatic subcortical strokes in this population. BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction. METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41% higher risk of incident AF in MESA (hazard ratio, 1.41; 95% confidence interval, 1.13-1.76; P=0.003) and a 30% higher risk of incident AF in CHS (hazard ratio, 1.30; 95% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23. CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF. BACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function. RESULTS: The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82). CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted. BACKGROUND: Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown. METHODS AND RESULTS: We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β's pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05). CONCLUSIONS: Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted. Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-β and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-β and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-β and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-β and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-β and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death. FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity. BACKGROUND: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. METHODS: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. RESULTS: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. CONCLUSIONS: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue. INTRODUCTION: D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations. MATERIALS AND METHODS: We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis. RESULTS: Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p<2.0×10(-6). The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p=0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p=0.006). No additional SNPs were significantly associated with D-dimer. CONCLUSIONS: Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics. The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. PURPOSE: Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci. METHODS: Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study. RESULTS: Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05×10(-8) and P=6.36×10(-6), respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value<0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing. CONCLUSIONS: While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations. Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged ≥ 65 years) enrolled in 1989-1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10% of the variation in height (P = 6.0 × 10(-8)). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets. OBJECTIVE: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA. APPROACH AND RESULTS: Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0×10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9×10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3×10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0×10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0×10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke. CONCLUSIONS: We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release. BACKGROUND: Dimethylarginines (DMA) interfere with nitric oxide formation by inhibiting nitric oxide synthase (asymmetrical DMA [ADMA]) and l-arginine uptake into the cell (ADMA and symmetrical DMA [SDMA]). In prospective clinical studies, ADMA has been characterized as a cardiovascular risk marker, whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterize the environmental and genetic contributions to interindividual variability of these biomarkers. METHODS AND RESULTS: This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (Framingham Heart Study [FHS; n=2992], Gutenberg Health Study [GHS; n=4354], and Multinational Monitoring of Trends and Determinants in Cardiovascular Disease Study [MONICA]/Cooperative Health Research in the Augsburg Area, Augsburg, Bavaria, Germany [KORA] F3 [n=581]) and identified replicated loci (DDAH1, MED23, Arg1, and AGXT2) associated with the interindividual variability in ADMA, l-arginine, and SDMA. Experimental in silico and in vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants, and various cardiometabolic risk factors. AGXT2 variants were not associated with poststroke survival in the Leeds study or were they associated with incident stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. CONCLUSIONS: These genome-wide association study support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and l-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. BACKGROUND: Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs. METHODS AND RESULTS: To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), γ-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1×10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2×10(-15), 5.0×10(-11), 7.6×10(-65), and 2.4×10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1×10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3×10(-72), 2.6×10(-151), and 6.3×10(-140), respectively). CONCLUSIONS: Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition. IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES: Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS: During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE: In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk. PURPOSE: Sudden cardiac death (SCD) is an important cause of mortality in the adult population. Height has been associated with cardiac hypertrophy and an increased risk of arrhythmias but also with decreased risk of coronary heart disease, suggesting a complex association with SCD. METHODS: We examined the association of adult height with the risk of physician-adjudicated SCD in two large population-based cohorts: the Cardiovascular Health Study and the Atherosclerosis Risk in Communities study. RESULTS: Over an average follow-up time of 11.7 years in Cardiovascular Health Study, there were 199 (3.6%) cases of SCD among 5556 participants. In Atherosclerosis Risk in Communities study, over 12.6 years, there were 227 (1.5%) cases of SCD among 15,633 participants. In both cohorts, there was a trend toward decreased SCD with taller height. In fixed effects meta-analysis, the pooled hazard ratio per 10 cm of height was 0.84; 95% confidence interval, 0.73-0.98; P = .03. The association of increased height with lower risk of SCD was slightly attenuated after inclusion of risk factors associated with height, such as hypertension and left ventricular hypertrophy. The association appeared stronger among men than women in both cohorts. CONCLUSIONS: In two population-based prospective cohorts of different ages, greater height was associated with lower risk of SCD. BACKGROUND: Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study. METHODS: The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model. RESULTS: Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring. CONCLUSION: The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans. BACKGROUND: Little is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation. OBJECTIVES: This study sought to describe the epidemiology of SSS. METHODS: This analysis included 20,572 participants (mean baseline age 59 years, 43% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of ≥ 50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review. RESULTS: During an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41% lower risk of SSS than whites (HR: 0.59; 95% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro-B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060. CONCLUSIONS: Blacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years. AIMS: It is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults. METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged ≥65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses. RESULTS: Over a median follow-up of 12.5years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95% CI, 1.70-3.40]) than black men (1.39 [0.83-2.34]); this finding did not reach statistical significance (P for interaction=0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs. (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P=0.07). CONCLUSIONS: Overall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study. BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5×10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06-1.14; P=2.2×10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7×10(-11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8×10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26-1.39; P=2.0×10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9×10(-9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6×10(-19)), GJA1 (P=2.66×10(-6)), and TBX5 (P=1.36×10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). CONCLUSIONS: We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation. Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function. C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women's Health Initiative (WHI) and KORA studies. We observed array-wide significance (p < 2.2 × 10(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10(-6); CRP, p = 4.2 × 10(-71); APOE, p = 1.6 × 10(-6)). The fourth significant locus, CD36 (p = 1.6 × 10(-6)), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p = 1.8 × 10(-5)) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p = 1.5 × 10(-10)). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p = 2.0 × 10(-6); CD36, p = 1.4 × 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent. BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. BACKGROUND: Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. METHODS: We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women ≥65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. RESULTS: For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). CONCLUSIONS: Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause. OBJECTIVE: To evaluate associations between Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity with risk of dementia and its subtypes. METHODS: Analysis were completed on 3320 participants of the Cardiovascular Health Study (CHS), a population-based longitudinal study of community-dwelling adults age ≥65 years followed for an average of 5.4 years. Baseline serum Lp-PLA2 mass was measured using a sandwich enzyme immunoassay and Lp-PLA2 activity utilized a tritiated-platelet activating factor activity assay. Cox proportional hazards regression assessed the relative risk of incident dementia with higher baseline Lp-PLA2 adjusting for demographics, cardiovascular disease (CVD) and risk factors, inflammation markers and apolipoprotein E (APOE) genotype. RESULTS: Each standard deviation higher Lp-PLA2 mass and activity were related to increased risk of dementia (fully adjusted HR: 1.11 per SD, 95% CI: 1.00-1.24 for mass; HR: 1.12 per SD, 95% CI: 1.00-1.26 for activity). Persons in the highest quartile of Lp-PLA2 mass were 50% more likely to develop dementia than those in the lowest quartile in adjusted models (HR: 1.49; 95% CI: 1.08-2.06). Among dementia subtypes, the risk of AD was increased two-fold in the highest compared to lowest quartile of Lp-PLA2 mass (adjusted HR: 1.98, 95% CI: 1.22-3.21). Results were attenuated in models of mixed dementia and VaD. Lp-PLA2 activity also doubled the risk of mixed dementia in the highest compared to lowest quartile (HR: 2.21, 95% CI: 1.12-4.373). INTERPRETATION: These data support Lp-PLA2 as a risk factor for dementia independent of CVD and its risk factors. Further study is required to clarify the role of Lp-PLA2-related mechanisms in dementia subtypes. BACKGROUND: Genetics can be used to predict drug effects and generate hypotheses around alternative indications. To support Losmapimod, a p38 mitogen-activated protein kinase inhibitor in development for acute coronary syndrome, we characterized gene variation in MAPK11/14 genes by exome sequencing and follow-up genotyping or imputation in participants well-phenotyped for cardiovascular and metabolic traits. METHODS AND RESULTS: Investigation of genetic variation in MAPK11 and MAPK14 genes using additive genetic models in linear or logistic regression with cardiovascular, metabolic, and biomarker phenotypes highlighted an association of RS2859144 in MAPK14 with myeloperoxidase in a dyslipidemic population (Genetic Epidemiology of Metabolic Syndrome Study), P=2.3×10(-6)). This variant (or proxy) was consistently associated with myeloperoxidase in the Framingham Heart Study and Cardiovascular Health Study studies (replication meta-P=0.003), leading to a meta-P value of 9.96×10(-7) in the 3 dyslipidemic groups. The variant or its proxy was then profiled in additional population-based cohorts (up to a total of 58 930 subjects) including Cohorte Lausannoise, Ely, Fenland, European Prospective Investigation of Cancer, London Life Sciences Prospective Population Study, and the Genetics of Obesity Associations study obesity case-control for up to 40 cardiovascular and metabolic traits. Overall analysis identified the same single nucleotide polymorphisms to be nominally associated consistently with glomerular filtration rate (P=0.002) and risk of obesity (body mass index ≥30 kg/m(2), P=0.004). CONCLUSIONS: As myeloperoxidase is a prognostic marker of coronary events, the MAPK14 variant may provide a mechanistic link between p38 map kinase and these events, providing information consistent with current indication of Losmapimod for acute coronary syndrome. If replicated, the association with glomerular filtration rate, along with previous biological findings, also provides support for kidney diseases as alternative indications. Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA. Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged ≥65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16% to 20% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95% CI, 1.07-1.72 and risk ratio, 1.43; 95% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95% CI, 1.17-2.08 and hazard ratio, 1.55; 95% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension. BACKGROUND: C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. METHODS AND RESULTS: We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P<3.1×10(-3) for replication, P<2.0×10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0×10(-6)) and rs646776 (P=3.1×10(-5)). CONCLUSIONS: We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes. BACKGROUND AND PURPOSE: Genome-wide association studies have revealed multiple common variants associated with known risk factors for ischemic stroke (IS). However, their aggregate effect on risk is uncertain. We aimed to generate a multilocus genetic risk score (GRS) for IS based on genome-wide association studies data from clinical-based samples and to establish its external validity in prospective population-based cohorts. METHODS: Three thousand five hundred forty-eight clinic-based IS cases and 6399 controls from the Wellcome Trust Case Control Consortium 2 were used for derivation of the GRS. Subjects from the METASTROKE consortium served as a replication sample. The validation sample consisted of 22 751 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. We selected variants that had reached genome-wide significance in previous association studies on established risk factors for IS. RESULTS: A combined GRS for atrial fibrillation, coronary artery disease, hypertension, and systolic blood pressure significantly associated with IS both in the case-control samples and in the prospective population-based studies. Subjects in the top quintile of the combined GRS had >2-fold increased risk of IS compared with subjects in the lowest quintile. Addition of the combined GRS to a simple model based on sex significantly improved the prediction of IS in the combined clinic-based samples but not in the population-based studies, and there was no significant improvement in net reclassification. CONCLUSIONS: A multilocus GRS based on common variants for established cardiovascular risk factors was significantly associated with IS both in clinic-based samples and in the general population. However, the improvement in clinical risk prediction was found to be small. Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL-18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL-18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P=1.9×10(-32)) and in the IL-1 gene family region of chromosome 2 for IL-1ra (rs6743376, P=2.3×10(-26)). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P=2.7×10(-19)). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4. OBJECTIVES: This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. BACKGROUND: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. METHODS: We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). RESULTS: We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. CONCLUSIONS: The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. BACKGROUND: Cardiac mortality and electrophysiological dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults. METHODS AND RESULTS: We evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard deviation of all normal-to-normal intervals (Ptrend=0.009, 0.02, 0.06, respectively) and ultralow-frequency power (Ptrend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with a higher short-term fractal scaling exponent (Ptrend=0.003) and lower Poincaré ratio (Ptrend=0.02), markers of less erratic sinus patterns. CONCLUSIONS: Greater total leisure-time activity, and walking alone, as well, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life. Physical activity influences inflammation, and both affect brain structure and Alzheimer's disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor α (TNFα) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3±4.8 years) and 39 patients with AD (81.9±5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNFα measures, and year-9 volumetric brain MRI scans. We examined how prior physical activity intensity and TNFα related to subsequent total and regional brain volumes. Physical activity intensity was measured using the modified Minnesota Leisure Time Physical Activities questionnaire at year 1 of the study, when all subjects included here were cognitively intact. Stability of measures was established for exercise intensity over 9 years and TNFα over 3 years in a subset of subjects who had these measurements at multiple time points. When considered together, more intense physical activity intensity and lower serum TNFα were both associated with greater total brain volume on follow-up MRI scans. TNFα, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNFα may independently influence brain structure in older adults. BACKGROUND: Although free fatty acids have been positively associated with risk factors for stroke, the role of plasma free fatty acids in the development of stroke has not been elucidated in older adults. AIMS: We sought to examine the association between plasma free fatty acids and incident stroke. METHODS: Prospective cohort of 4369 men and women≥65 years of age in the Cardiovascular Health Study. Plasma levels of free fatty acids were measured at the 1992-1993 examination and stroke events were adjudicated by a committee of experts including neurologists and neuroradiologists. Cox regression was used to estimate the relative risk of stroke associated with free fatty acids concentrations. RESULTS: The average age among participants was 75±5·2 years. During a median follow-up of 11·4 years, 732 incident strokes occurred. The crude incidence rates of stroke were 14·5, 14·9, and 17·6 per 1000 person-years across increasing tertiles of plasma free fatty acids. The adjusted hazard ratio (95% confidence interval) for incident stroke was 1·05 (0·97-1·14) per standard deviation increase in plasma free fatty acids. Restriction to ischemic stroke did not alter the results [hazard ratio (95% confidence interval): 1·04 (0·96-1·14) per standard deviation higher free fatty acids], and there was no effect modification by adiposity (P interaction=0·18) or by diabetes (P interaction=0·15). CONCLUSION: Our data did not show an association of plasma free fatty acids with incident stroke among community dwelling older adults. Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults. BACKGROUND: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF. METHODS AND RESULTS: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0. CONCLUSIONS: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk. BACKGROUND: While self-reported trans-fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t-16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2) and cardiovascular disease (CVD) or total mortality are not well established. METHODS AND RESULTS: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non-CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person-years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t-18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, P-trend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, P-trend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, P-trend=0.01). t/c-18:2 was positively related to total mortality (HR=1.19, P-trend=0.05), total CHD (HR=1.67, P-trend=0.002), and nonfatal CHD (HR=2.06, P-trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t-16:1n9 nor t-18:1 was significantly associated with total mortality or CVD, nor was c/t-18:2 if we excluded early cases. CONCLUSIONS: Among circulating TFAs, t/t-18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c-18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t-18:2 isomers. Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes, but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the Cardiovascular Health Study, an observational cohort of community-dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14, 95% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death because of cardiovascular disease, dementia, infection, and respiratory causes but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality differentially in men and women (HR 1.17, 95% CI 1.08 to 1.26 for men; HR 1.02, 95% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a cohort of community-dwelling older subjects, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and noncardiovascular mortality. BACKGROUND AND PURPOSE: Beyond the Framingham Stroke Risk Score, prediction of future stroke may improve with a genetic risk score (GRS) based on single-nucleotide polymorphisms associated with stroke and its risk factors. METHODS: The study includes 4 population-based cohorts with 2047 first incident strokes from 22,720 initially stroke-free European origin participants aged ≥55 years, who were followed for up to 20 years. GRSs were constructed with 324 single-nucleotide polymorphisms implicated in stroke and 9 risk factors. The association of the GRS to first incident stroke was tested using Cox regression; the GRS predictive properties were assessed with area under the curve statistics comparing the GRS with age and sex, Framingham Stroke Risk Score models, and reclassification statistics. These analyses were performed per cohort and in a meta-analysis of pooled data. Replication was sought in a case-control study of ischemic stroke. RESULTS: In the meta-analysis, adding the GRS to the Framingham Stroke Risk Score, age and sex model resulted in a significant improvement in discrimination (all stroke: Δjoint area under the curve=0.016, P=2.3×10(-6); ischemic stroke: Δjoint area under the curve=0.021, P=3.7×10(-7)), although the overall area under the curve remained low. In all the studies, there was a highly significantly improved net reclassification index (P<10(-4)). CONCLUSIONS: The single-nucleotide polymorphisms associated with stroke and its risk factors result only in a small improvement in prediction of future stroke compared with the classical epidemiological risk factors for stroke. BACKGROUND AND PURPOSE: Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%). METHODS: Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting. RESULTS: Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate (P=0.59) and severe stenosis (P=0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80-0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85-0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application. CONCLUSIONS: A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS. BACKGROUND: Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed. METHODS: This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009). RESULTS: At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease. CONCLUSIONS: Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined. BACKGROUND: Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope. METHODS AND RESULTS: We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61-1.14). CONCLUSIONS: The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE. CONTEXT: Microvascular disease is a leading cause of cognitive impairment. Approximately 50% of people with a hip fracture have cognitive impairment. OBJECTIVE: We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [≥ 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk. SETTING: The Cardiovascular Health Cognition Study. PATIENTS: Three thousand, one-hundred six participants (mean age, ∼ 79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098). MAIN OUTCOME MEASURE: Incident hip fracture. RESULTS: There were 488 participants (16%) with mild cognitive impairment (MCI) and 564 (18%) with dementia. There were 337 incident hip fractures, of which 19% occurred in participants with MCI and 26% in participants with dementia. Adjusted hazard ratios (HR) and 95% confidence interval for hip fracture in participants with MCI were 2.45 (1.67-3.61) and for dementia 2.35 (1.57-3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55-0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk. CONCLUSIONS: ACR attenuates part of the risk of hip fracture in people with dementia, suggesting that these disorders share a common pathogenesis. BACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk. PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders. METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease. RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis. CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier. Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine's association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged ≥65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults. Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75% Asians, 21% Whites, and 4% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races. OBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address. METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period. RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95% CI: 1.2-3.3), angina (OR: 1.6, 95% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95% CI: 1.0-2.1). CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations. OBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age. BACKGROUND AND AIMS: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. METHODS: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. RESULTS: For the ANU-ADRI using available data, the MAP study c-statistic was 0·637 (95% CI 0·596-0·678), for the KP study it was 0·740 (0·712-0·768) and for the CVHS it was 0·733 (0·691-0·776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). CONCLUSION: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up. OBJECTIVES: To develop and validate 10-year cumulative incidence functions of intracerebral hemorrhage (ICH) and ischemic stroke (IS). METHODS: We used data on 27,493 participants from 3 population-based cohort studies: the Atherosclerosis Risk in Communities Study, median age 54 years, 45% male, median follow-up 20.7 years; the Rotterdam Study, median age 68 years, 38% male, median follow-up 14.3 years; and the Cardiovascular Health Study, median age 71 years, 41% male, median follow-up 12.8 years. Among these participants, 325 ICH events, 2,559 IS events, and 9,909 nonstroke deaths occurred. We developed 10-year cumulative incidence functions for ICH and IS using stratified Cox regression and competing risks analysis. Basic models including only established nonlaboratory risk factors were extended with diastolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, body mass index, waist-to-hip ratio, and glomerular filtration rate. The cumulative incidence functions' performances were cross-validated in each cohort separately by Harrell C-statistic and calibration plots. RESULTS: High total cholesterol/high-density lipoprotein cholesterol ratio decreased the ICH rates but increased IS rates (p for difference across stroke types <0.001). For both the ICH and IS models, C statistics increased more by model extension in the Atherosclerosis Risk in Communities and Cardiovascular Health Study cohorts. Improvements in C statistics were reproduced by cross-validation. Models were well calibrated in all cohorts. Correlations between 10-year ICH and IS risks were moderate in each cohort. CONCLUSIONS: We developed and cross-validated cumulative incidence functions for separate prediction of 10-year ICH and IS risk. These functions can be useful to further specify an individual's stroke risk. BACKGROUND: Genome-wide association studies for body mass index (BMI) previously identified a locus near TMEM18. We conducted targeted sequencing of this region to investigate the role of common, low-frequency, and rare variants influencing BMI. METHODS AND RESULTS: We sequenced TMEM18 and regions downstream of TMEM18 on chromosome 2 in 3976 individuals of European ancestry from 3 community-based cohorts (Atherosclerosis Risk in Communities, Cardiovascular Health Study, and Framingham Heart Study), including 200 adults selected for high BMI. We examined the association between BMI and variants identified in the region from nucleotide position 586 432 to 677 539 (hg18). Rare variants (minor allele frequency, <1%) were analyzed using a burden test and the sequence kernel association test. Results from the 3 cohort studies were meta-analyzed. We estimate that mean BMI is 0.43 kg/m(2) higher for each copy of the G allele of single-nucleotide polymorphism rs7596758 (minor allele frequency, 29%; P=3.46×10(-4)) using a Bonferroni threshold of P<4.6×10(-4). Analyses conditional on previous genome-wide association study single-nucleotide polymorphisms associated with BMI in the region led to attenuation of this signal and uncovered another independent (r(2)<0.2), statistically significant association, rs186019316 (P=2.11×10(-4)). Both rs186019316 and rs7596758 or proxies are located in transcription factor binding regions. No significant association with rare variants was found in either the exons of TMEM18 or the 3' genome-wide association study region. CONCLUSIONS: Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function. BACKGROUND: Atherosclerosis, the precursor to coronary heart disease and stroke, is characterized by an accumulation of fatty cells in the arterial intimal-medial layers. Common carotid intima media thickness (cIMT) and plaque are subclinical atherosclerosis measures that predict cardiovascular disease events. Previously, genome-wide association studies demonstrated evidence for association with cIMT (SLC17A4) and plaque (PIK3CG). METHODS AND RESULTS: We sequenced 120 kb around SLC17A4 (6p22.2) and 251 kb around PIK3CG (7q22.3) among 3669 European ancestry participants from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Framingham Heart Study (FHS) in Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Primary analyses focused on 438 common variants (minor allele frequency ≥1%), which were independently meta-analyzed. A 3' untranslated region CCDC71L variant (rs2286149), upstream from PIK3CG, was the most significant finding in cIMT (P=0.00033) and plaque (P=0.0004) analyses. A SLC17A4 intronic variant was also associated with cIMT (P=0.008). Both were in low linkage disequilibrium with the genome-wide association study single nucleotide polymorphisms. Gene-based tests including T1 count and sequence kernel association test for rare variants (minor allele frequency <1%) did not yield statistically significant associations. However, we observed nominal associations for rare variants in CCDC71L and SLC17A3 with cIMT and of the entire 7q22 region with plaque (P=0.05). CONCLUSIONS: Common and rare variants in PIK3CG and SLC17A4 regions demonstrated modest association with subclinical atherosclerosis traits. Although not conclusive, these findings may help to understand the genetic architecture of regions previously implicated by genome-wide association studies and identify variants within these regions for further investigation in larger samples. BACKGROUND: The cardiac sodium channel SCN5A regulates atrioventricular and ventricular conduction. Genetic variants in this gene are associated with PR and QRS intervals. We sought to characterize further the contribution of rare and common coding variation in SCN5A to cardiac conduction. METHODS AND RESULTS: In Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study, we performed targeted exonic sequencing of SCN5A (n=3699, European ancestry individuals) and identified 4 common (minor allele frequency >1%) and 157 rare variants. Common and rare SCN5A coding variants were examined for association with PR and QRS intervals through meta-analysis of European ancestry participants from CHARGE, National Heart, Lung, and Blood Institute's Exome Sequencing Project (n=607), and the UK10K (n=1275) and by examining Exome Sequencing Project African ancestry participants (n=972). Rare coding SCN5A variants in aggregate were associated with PR interval in European and African ancestry participants (P=1.3×10(-3)). Three common variants were associated with PR and QRS interval duration among European ancestry participants and one among African ancestry participants. These included 2 well-known missense variants: rs1805124 (H558R) was associated with PR and QRS shortening in European ancestry participants (P=6.25×10(-4) and P=5.2×10(-3), respectively) and rs7626962 (S1102Y) was associated with PR shortening in those of African ancestry (P=2.82×10(-3)). Among European ancestry participants, 2 novel synonymous variants, rs1805126 and rs6599230, were associated with cardiac conduction. Our top signal, rs1805126 was associated with PR and QRS lengthening (P=3.35×10(-7) and P=2.69×10(-4), respectively) and rs6599230 was associated with PR shortening (P=2.67×10(-5)). CONCLUSIONS: By sequencing SCN5A, we identified novel common and rare coding variants associated with cardiac conduction. BACKGROUND: Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women. METHODS: In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 ± 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty. RESULTS: Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women. CONCLUSIONS: Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging. BACKGROUND: Individual measurements of inflammation have been utilized to assess adverse outcomes risk in older adults with varying degrees of success. This study was designed to identify biologically informed, aggregate measures of inflammation for optimal risk assessment and to inform further biological study of inflammatory pathways. METHODS: In total, 15 nuclear factor-kappa B-mediated pathway markers of inflammation were first measured in baseline serum samples of 1,155 older participants in the InCHIANTI population. Of these, C-reactive protein, interleukin-1-receptor antagonist, interleukin-6, interleukin-18, and soluble tumor necrosis factor-α receptor-1 were independent predictors of 5-year mortality. These five inflammatory markers were measured in baseline serum samples of 5,600 Cardiovascular Health Study participants. A weighted summary score, the first principal component summary score, and an inflammation index score were developed from these five log-transformed inflammatory markers, and their prediction of 10-year all-cause mortality was evaluated in Cardiovascular Health Study and then validated in InCHIANTI. RESULTS: The inflammation index score that included interleukin-6 and soluble tumor necrosis factor-α receptor-1 was the best predictor of 10-year all-cause mortality in Cardiovascular Health Study, after adjusting for age, sex, education, race, smoking, and body mass index (hazards ratio = 1.62; 95% CI: 1.54, 1.70) compared with all other single and combined measures. The inflammation index score was also the best predictor of mortality in the InCHIANTI validation study (hazards ratio 1.33; 95% CI: 1.17-1.52). Stratification by sex and CVD status further strengthened the association of inflammation index score with mortality. CONCLUSION: A simple additive index of serum interleukin-6 and soluble tumor necrosis factor-α receptor-1 best captures the effect of chronic inflammation on mortality in older adults among the 15 biomarkers measured. AIMS/HYPOTHESIS: Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits. METHODS: We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (≤5 h or ≥9 h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene × behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk. RESULTS: Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95% CI 1.08, 1.61; p = 0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05). CONCLUSIONS/INTERPRETATION: Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes. BACKGROUND: Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits. METHODS AND RESULTS: The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with ≥1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency ≥1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test. CONCLUSIONS: We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci. BACKGROUND: Subclinical hypothyroidism is common in the elderly, yet its relationship with weight and body composition is unclear. OBJECTIVE: We examined the relationship between subclinical hypothyroidism and weight change and body composition in older adults. METHODS: A total of 427 subclinically hypothyroid and 2864 euthyroid U.S. individuals ≥65 years old enrolled in the Cardiovascular Health Study and not taking thyroid preparations were included. Analyses of 6-year weight change were performed, compared by thyroid status. A cross-sectional analysis of thyroid status and body composition was performed in a subset of 1276 participants who had dual-energy x-ray absorptiometry scans. Models were risk factor-adjusted and stratified by sex. RESULTS: Overall, participants lost weight during follow-up (-0.38 kg/y in men, -0.37 kg/y in women). Subclinical hypothyroidism, when assessed at a single time point or persisting over 2 years, was not associated with a difference in weight change compared with euthyroidism. Subclinical hypothyroidism was also not associated with differences in lean mass, fat mass, or percent fat compared with euthyroidism. A TSH level 1 mU/L higher within the euthyroid or subclinical hypothyroid range was associated with a 0.51-kg higher baseline weight in women only (P < .001) but not with weight change in either sex. A 1 ng/dL higher free T4 level was associated with lower baseline weight and 0.32 kg/y greater weight loss in women only (P = .003). Baseline weight and weight change did not differ by T3 levels. CONCLUSIONS: Our data do not support a clinically significant impact of subclinical hypothyroidism on weight status in the elderly. BACKGROUND: Subclinical thyroid dysfunction is common in the elderly, yet its relationship with hip fracture and bone mineral density (BMD) is unclear. OBJECTIVE: We examined the association between endogenous subclinical hyper- and hypothyroidism and hip fracture and BMD in older adults. METHODS: A total of 4936 US individuals 65 years old or older enrolled in the Cardiovascular Health Study and not taking thyroid preparations were included. Analyses of incident hip fracture were performed by thyroid status, over a median follow-up of 12 years. A cross-sectional analysis of thyroid status and BMD was performed in a subset of 1317 participants who had dual-energy x-ray absorptiometry scans. Models were adjusted for risk factors and stratified by sex. RESULTS: No association was found between subclinical hypothyroidism and incident hip fracture compared with euthyroidism, when assessed at a single time point or persisting at two time points, in either women [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.69-1.20 for a single and HR 0.79, 95% CI 0.52-1.21 for two time points] or men (HR 1.27, 95% CI 0.82-1.95 for a single and HR 1.09, 95% CI 0.57-2.10 for two time points). Likewise, no association was found between subclinical hyperthyroidism and incident hip fracture in either sex (HR 1.11, 95% CI 0.55-2.25 in women and HR 1.78, 95% CI 0.56-5.66 in men). No association was found between subclinical thyroid dysfunction and BMD at the lumbar spine, total hip, or femoral neck sites. CONCLUSIONS: Our data suggest no association between subclinical hypothyroidism or subclinical hyperthyroidism and hip fracture risk or BMD in older men and women. Additional data are needed to improve the precision of estimates for subclinical hyperthyroidism and in men. OBJECTIVES: To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer. DESIGN: Cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals born between June 30, 1918, and June 30, 1921 (N = 2,082; aged 70-75 at baseline (1992-93)). MEASUREMENTS: A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older. RESULTS: A 1-point lower SVD score was associated with 1.22 greater odds (95% confidence interval = 1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking. CONCLUSION: A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival. Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78±5 and 21% reported limitation in ≥1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP ≤65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of ≤65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders. BACKGROUND: Genome-wide association studies (GWAS) have identified common genetic variants that predispose to atrial fibrillation (AF). It is unclear whether rare and low-frequency variants in genes implicated by such GWAS confer additional risk of AF. OBJECTIVE: To study the association of genetic variants with AF at GWAS top loci. METHODS: In the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study, we selected and sequenced 77 target gene regions from GWAS loci of complex diseases or traits, including 4 genes hypothesized to be related to AF (PRRX1, CAV1, CAV2, and ZFHX3). Sequencing was performed in participants with (n = 948) and without (n = 3330) AF from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Massachusetts General Hospital. RESULTS: One common variant (rs11265611; P = 1.70 × 10(-6)) intronic to IL6R (interleukin-6 receptor gene) was significantly associated with AF after Bonferroni correction (odds ratio 0.70; 95% confidence interval 0.58-0.85). The variant was not genotyped or imputed by prior GWAS, but it is in linkage disequilibrium (r(2) = .69) with the single-nucleotide polymorphism, with the strongest association with AF so far at this locus (rs4845625). In the rare variant joint analysis, damaging variants within the PRRX1 region showed significant association with AF after Bonferroni correction (P = .01). CONCLUSIONS: We identified 1 common single-nucleotide polymorphism and 1 gene region that were significantly associated with AF. Future sequencing efforts with larger sample sizes and more comprehensive genome coverage are anticipated to identify additional AF-related variants. BACKGROUND: Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients. METHODS AND RESULTS: Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup. CONCLUSIONS: Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF. CONTEXT: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. OBJECTIVE: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). DATA SOURCES AND STUDY SELECTION: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. DATA EXTRACTION: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. DATA SYNTHESIS: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. CONCLUSIONS: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes. Increased levels of plasma troponins and natriuretic peptides are markers of cardiac dysfunction associated with increased risk of cardiovascular disease. Little information exists on cardiac dysfunction and occurrence of venous thromboembolism (VTE). In two prospective epidemiological cohorts, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with VTE occurrence. The Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS) measured plasma TnT and NT-proBNP in 13,719 men or women with no history of venous thrombosis, coronary heart disease, or heart failure and followed them for approximately 10 years for VTE occurrence (n = 348 VTEs). In both ARIC and CHS, TnT was associated positively with incidence of total VTE and provoked VTE, but not with unprovoked VTE: age, race, and sex-adjusted hazard ratios for total VTE in the pooled analysis were 1.00, 0.85, 1.36, 1.51, and 1.98 (p-trend <0.0001) across five categories of TnT. In contrast, the association of NT-proBNP with VTE was positive in ARIC (hazard ratios approximately 2.5-fold for the highest versus lowest NT-proBNP quintiles), but non-existent in CHS. OBJECTIVE: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease. METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI: 1.23-4.13) and 1.53 (95% CI: 1.06-2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI: 1.02-4.83) and 1.69 (95% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L. CONCLUSION: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. BACKGROUND: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults. METHODS: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell's c-statistic were calculated. RESULTS: In 4,384 Cardiovascular Health Study participants (61% women, 14% black; mean baseline age, 72 ± 5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI = 0.062, P = .015, and NRI = 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT did not result in a significant NRI for either outcome, it was significant among those without incident disease. CONCLUSIONS: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events. Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. IMPORTANCE: The risk of cardiovascular disease (CVD) after infection is poorly understood. OBJECTIVE: To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. DESIGN, SETTINGS, AND PARTICIPANTS: We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, ≥65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status. EXPOSURES: Hospitalization for pneumonia. MAIN OUTCOMES AND MEASURES: Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease). RESULTS: Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant. CONCLUSIONS AND RELEVANCE: Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD. BACKGROUND AND PURPOSE: Emerging evidence suggests that atrial disease is associated with vascular brain injury in the absence of atrial fibrillation. METHODS: The Cardiovascular Health Study prospectively enrolled community-dwelling adults aged ≥65 years. Among participants who underwent MRI, we examined associations of ECG left atrial abnormality with brain infarcts and leukoaraiosis. P-wave terminal force in lead V1 was the primary measure of left atrial abnormality; P-wave area and duration were secondary predictors. We excluded participants with atrial fibrillation before or on their index ECG. Primary outcomes were incident infarcts and worsening leukoaraiosis from initial to follow-up scan ≈5 years later. Secondary outcomes were prevalent infarcts and degree of leukoaraiosis on initial MRI. Relative risk (RR) and linear regression models were adjusted for vascular risk factors. RESULTS: Among 3129 participants with ≥1 scan, each SD increase in P-wave terminal force in lead V1 was associated with a 0.05-point (95% confidence interval [CI], 0.0003-0.10) higher baseline white matter grade on a 10-point scale. P-wave terminal force in lead V1 was associated with prevalent infarcts of any type (RR per SD, 1.09; 95% CI, 1.04-1.16) and more so with prevalent nonlacunar infarcts (RR per SD, 1.22; 95% CI, 1.08-1.38). Among 1839 participants with 2 scans, P-wave terminal force in lead V1 was associated with worsening leukoaraiosis (RR per SD, 1.09; 95% CI, 1.01-1.18), but not with incident infarcts (RR per SD, 1.06; 95% CI, 0.93-1.20). Sensitivity analyses adjusting for incident atrial fibrillation found similar results. P-wave area and duration were not associated with outcomes. CONCLUSIONS: ECG left atrial abnormality is associated with vascular brain injury in the absence of documented atrial fibrillation. BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies. Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity. C-reactive protein (CRP) concentration is a heritable systemic marker of inflammation that is associated with cardiovascular disease risk. Genome-wide association studies have identified CRP-associated common variants associated in ∼25 genes. Our aims were to apply exome sequencing to (1) assess whether the candidate loci contain rare coding variants associated with CRP levels and (2) perform an exome-wide search for rare variants in novel genes associated with CRP levels. We exome-sequenced 6050 European-Americans (EAs) and 3109 African-Americans (AAs) from the NHLBI-ESP and the CHARGE consortia, and performed association tests of sequence data with measured CRP levels. In single-variant tests across candidate loci, a novel rare (minor allele frequency = 0.16%) CRP-coding variant (rs77832441-A; p.Thr59Met) was associated with 53% lower mean CRP levels (P = 2.9 × 10(-6)). We replicated the association of rs77832441 in an exome array analysis of 11 414 EAs (P = 3.0 × 10(-15)). Despite a strong effect on CRP levels, rs77832441 was not associated with inflammation-related phenotypes including coronary heart disease. We also found evidence for an AA-specific association of APOE-ε2 rs7214 with higher CRP levels. At the exome-wide significance level (P < 5.0 × 10(-8)), we confirmed associations for reported common variants of HNF1A, CRP, IL6R and TOMM40-APOE. In gene-based tests, a burden of rare/lower frequency variation in CRP in EAs (P ≤ 6.8 × 10(-4)) and in retinoic acid receptor-related orphan receptor α (RORA) in AAs (P = 1.7 × 10(-3)) were associated with CRP levels at the candidate gene level (P < 2.0 × 10(-3)). This inquiry did not elucidate novel genes, but instead demonstrated that variants distributed across the allele frequency spectrum within candidate genes contribute to CRP levels. Fetuin-A, a serum protein that regulates calcium mineralization, has been associated with bone mineral density (BMD) in several cross-sectional human studies, suggesting a possible beneficial effect on clinically important measures of bone health. Fetuin-A and incidence of subsequent fracture was assessed in 4714 men and women ≥65 years of age. Proportional hazards models were used to estimate risk of incident hip (hospital discharge ICD-9 codes) and composite fracture (hip, pelvis, humerus, or proximal forearm; hospital discharge ICD-9 codes and Medicare claims data). A total of 576 participants had an incident hip fracture (median follow-up 11.2 years) and 768 had an incident composite fracture (median follow-up 6.9 years). In unadjusted analyses, there was no association between fetuin-A (per SD increase) and risk of hip fracture (hazard ratio [HR], 0.96; 95% CI, 0.88 to 1.05) or composite fracture (HR, 0.99; 95% CI, 0.92 to 1.06). Results were not significantly changed after adjustment for potential confounding variables. Analyses modeling fetuin-A in quartiles or within a subset with available BMD measures also showed no statistically significant association with risk of hip or composite fracture. Though fetuin-A was positively associated with areal BMD in partially adjusted models (total hip: β, 0.013 g/cm(2) ; 95% CI, 0.005 to 0.021; femoral neck: β, 0.011 g/cm(2) ; 95% CI, 0.004 to 0.018; and lumbar spine: β, 0.007 g/cm(2) ; 95% CI, 0.001 to 0.028), these associations were no longer significant after further adjustment for BMI and in final multivariate models. In this large sample of community-dwelling older adults, a small positive association between fetuin-A and areal BMD appeared attributable to confounding variables and we found no evidence of an association between fetuin-A and risk of clinical fracture. Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3% men) from CHS and 11,509 participants (44.9% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population. BACKGROUND: Histidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample. METHODS AND RESULTS: By conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (β=0.26; P=1.2×10(-13)). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%; P=1.2×10(-4)). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18; P=1.9×10(-4)). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in HAL were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium. CONCLUSIONS: Three LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between HAL gene variation and CHD are warranted. AIM: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP). METHODS: We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-β (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study. RESULTS: Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-β (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP. CONCLUSIONS: Isolated hyperglycemia is associated with higher serum concentrations of TGF-β, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined. Diabetes mellitus exerts a strong effect on atherosclerotic cardiovascular disease risk into older age (beyond ages 70-74 years). This effect is particularly noticeable with regard to coronary artery disease and cerebral microvascular disease. Thus, diabetes mellitus in older adults deserves the same careful medical attention as it does in middle age. OBJECTIVES: The purpose of this study was to determine the prevalence of clinically relevant comorbidities and measures of physical and cognitive impairment in elderly persons with incident heart failure (HF). BACKGROUND: Comorbidities and functional and cognitive impairments are common in the elderly and often associated with greater mortality risk. METHODS: We examined the prevalence of 9 comorbidities and 4 measures of functional and cognitive impairments in 558 participants from the Cardiovascular Health Study who developed incident HF between 1990 and 2002. Participants were followed prospectively until mid-2008 to determine their mortality risk. RESULTS: Mean age of participants was 79.2 ± 6.3 years with 52% being men. Sixty percent of participants had ≥3 comorbidities, and only 2.5% had none. Twenty-two percent and 44% of participants had ≥1 activity of daily living (ADL) and ≥1 instrumental activity of daily living (IADL) impaired respectively. Seventeen percent of participants had cognitive impairment (modified mini-mental state exam score <80, scores range between 0 and 100). During follow up, 504 participants died, with 1-, 5-, and 10-year mortality rates of 19%, 56%, and 83%, respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality risk: diabetes mellitus (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.33 to 2.03), chronic kidney disease (HR: 1.32; 95% CI: 1.07 to 1.62 for moderate disease; HR: 3.00; 95% CI: 1.82 to 4.95 for severe), cerebrovascular disease (HR: 1.53; 95% CI: 1.22 to 1.92), depression (HR: 1.44; 95% CI: 1.09 to 1.90), functional impairment (HR: 1.30; 95% CI: 1.04 to 1.63 for 1 IADL impaired; HR: 1.49; 95% CI: 1.07 to 2.04 for ≥2 IADL impaired), and cognitive impairment (HR: 1.33; 95% CI: 1.02 to 1.73). Other comorbidities (hypertension, coronary heart disease, peripheral arterial disease, atrial fibrillation, and obstructive airway disease) and measures of functional impairments (ADLs and 15-ft walk time) were not associated with mortality. CONCLUSIONS: Elderly patients with incident HF have a high burden of comorbidities and functional and cognitive impairments. Some of these conditions are associated with greater mortality risk. BACKGROUND: Impaired pulmonary function (IPF) and left ventricular systolic dysfunction (LVSD) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of IPF and LVSD with heart failure, cardiovascular mortality and all-cause mortality, and their impact on risk classification using a continuous net reclassification index. METHODS AND RESULTS: We followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years. LVSD was defined as LV ejection fraction <55%. IPF was defined as: forced expiratory volume in 1 second:forced vital capacity <70%, and predicted forced expiratory volume in 1 second <80%. Outcomes included heart failure hospitalization, cardiovascular mortality, all-cause mortality, and composite outcome. LVSD was detected in 128 subjects (6%), IPF in 441 (19%) and both in 38 (2%). Compared to those without LVSD or IPF, there was a significantly increased cardiovascular risk for groups of LVSD only, IPF only, and LVSD plus IPF, adjusted hazard ratio (95% CI) 2.1 (1.5-3.0), 1.7 (1.4-2.1), and 3.2 (2.0-5.1) for HF; 1.8 (1.2-2.6), 1.4 (1.1-1.8), and 2.8 (1.7-4.7) for cardiovascular mortality; 1.3 (1.0-1.8), 1.7 (1.4-1.9), and 2.1 (1.5-3.0) for all-cause mortality, and 1.6 (1.3-2.1), 1.7 (1.5-1.9), and 2.4 (1.7-3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when IPF was added to the adjusted model with LVSD or LVSD to IPF. CONCLUSIONS: While risk of cardiovascular outcomes was the highest among elderly with both LVSD and IPF, risk was comparable between subjects with IPF alone and those with LVSD alone. This observation, combined with improved risk classification by adding IPF to LVSD or LVSD to IPF, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment. OBJECTIVES: To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period. DESIGN: Retrospective analysis of a cohort study. SETTING: Participants were recruited from North Carolina, California, Maryland, and Pennsylvania. PARTICIPANTS: Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N=897). MEASUREMENTS: Plasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06). RESULTS: At baseline, mean age was 76.3±3.6, and 18.5% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3% for IGF-I, 59.7% for IGFBP-1, -13.4% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: -3.7% for IGF-I, 25.6% for IGFBP-1, -6.4% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up. CONCLUSION: Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality. OBJECTIVE: To investigate the effects of trans fatty acids (TFAs) on type 2 diabetes mellitus (DM) by specific TFA subtype or method of assessment. RESEARCH DESIGN AND METHODS: In the Cardiovascular Health Study, plasma phospholipid trans (t)-16:1n9, t-18:1, and cis (c)/t-, t/c-, and t/t-18:2 were measured in blood drawn from 2,919 adults aged 74 ± 5 years and free of prevalent DM in 1992. Dietary TFA was estimated among 4,207 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 or 1996. Incident DM was defined through 2010 by medication use or blood glucose levels. Risks were assessed by Cox proportional hazards. RESULTS: In biomarker analyses, 287 DM cases occurred during 30,825 person-years. Both t-16:1n9 (extreme quartile hazard ratio 1.59 [95% CI 1.04-2.42], P-trend = 0.04) and t-18:1 (1.91 [1.20-3.03], P-trend = 0.01) levels were associated with higher incident DM after adjustment for de novo lipogenesis fatty acids. In dietary analyses, 407 DM cases occurred during 50,105 person-years. Incident DM was positively associated with consumption of total TFAs (1.38 [1.03-1.86], P-trend = 0.02), t-18:1 (1.32 [1.00-1.76], P-trend = 0.04), and t-18:2 (1.41 [1.05-1.89], P-trend = 0.02). After further adjustment for other dietary habits, however, the associations of estimated dietary TFA with DM were attenuated, and only nonsignificant positive trends remained. CONCLUSIONS: Among older adults, plasma phospholipid t-16:1n9 and t-18:1 levels were positively related to DM after adjustment for de novo lipogenesis fatty acids. Estimated dietary TFA was not significantly associated with DM. These findings highlight the need for further observational, interventional, and experimental studies of the effects TFA on DM. BACKGROUND: The relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts. OBJECTIVES: To evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke. PATIENTS/METHODS: We measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n = 5411), both with and without inhibitory anti-factor XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~ 50 000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2 years. RESULTS: The minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (β = - 34.2 ± 3.5 nm; P = 3.3 × 10(-22) ; minor allele frequency [MAF] = 0.23) and African-Americans (β = - 31.1 ± 7.9 nm; P = 9.0 × 10(-5) ; MAF = 0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (β = 16.3 nm; P = 4.3 × 10(-9) ; MAF = 0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95% confidence interval CI 1.01-1.17; P = 0.03) for pTG, 1.06 (95% CI 0.98-1.15; P = 0.17) for pTG/FXIa(-) , and 1.11 (95% CI 1.02-1.21; P = 0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n = 834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (β = - 0.02; standard error = 0.08; P = 0.81). CONCLUSIONS: These results support the importance of contact activation pathway-dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex vivo and in vivo. OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF. BACKGROUND AND OBJECTIVES: CKD is associated with mortality. Accurate prediction tools for mortality may guide clinical decision-making, particularly among elderly persons with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prediction equation was developed for 5-year risk of mortality among participants with CKD in the Cardiovascular Health Study. Sixteen candidate predictor variables were explored, which included demographics, physical examination measures, comorbidity, medication use, and kidney function measures (eGFR calculated from serum creatinine and the CKD Epidemiology Collaboration equation and the urine albumin-to-creatinine ratio). Models were developed using Cox regression and evaluated using c statistics. A final parsimonious model was externally validated in an independent cohort of community-living elders with CKD in the Health, Aging, and Body Composition Study. RESULTS: The development cohort included 828 participants who had a mean age of 80 (±5.6) years and an eGFR of 47 (±11) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-51) mg/g. The validation cohort included 789 participants who had a mean age of 74 (±2.8) years and an eGFR of 50 (±9) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-42) mg/g. The final model for 5-year mortality risk included age, sex, race, eGFR, urine albumin-to-creatinine ratio, smoking, diabetes mellitus, and history of heart failure and stroke (c statistic=0.72; 95% confidence interval, 0.68 to 0.74). When a point-based system was assigned for each of nine variables in the equation, the estimated risk of death within 5 years ranged from 3.8% among participants with the lowest scores to 83.6% among participants with nine points. The model performed fair in external validation (c statistic=0.69; 95% confidence interval, 0.64 to 0.74). CONCLUSIONS: A simple prediction tool using nine readily available clinical variables can assist in predicting 5-year mortality risk in elderly patients with CKD, which may be useful in counseling patients and guiding clinical decision making. SCOPE: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid. METHODS AND RESULTS: We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid. CONCLUSION: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes. BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD. Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical approach, mixed membership trajectory models, to capture the variety of such pathways in 652 participants in the Cardiovascular Health Study Cognition Study over 22 years of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with a peak probability of MCI between 95 and 100 years of age and only a 50% probability of dementia by age 100; an "intermediate" profile with a peak probability of MCI between 85 and 90 years of age and progression to dementia between 90 and 95 years; and an "unhealthy" profile with a peak probability of progressing to MCI between ages 75 and 80 years and to dementia between the ages of 80 and 85 years. Hypertension, education, race, and the ϵ4 allele of the apolipoprotein E gene all affected the closeness of an individual to 1 or more of the canonical trajectories. These results provide new insights into the natural history of Alzheimer disease and evidence for a potential difference in the pathophysiology of the development of dementia. Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk. BACKGROUND AND AIMS: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification). METHODS: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993. RESULTS: Among Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048). CONCLUSION: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk. BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 3,244 participants 65 years or older in the community-based Cardiovascular Health Study. PREDICTOR: Plasma FGF-23 concentrations. OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department. MEASUREMENTS: We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status. RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95% CI, 0.85-1.35). In stratified analysis by CKD status (36.5% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95% CI, 0.89-1.62). LIMITATIONS: Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses. CONCLUSIONS: In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar. OBJECTIVE: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. METHODS: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. RESULTS: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-β, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 μm per doubling of TGF-β, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. CONCLUSIONS: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults. Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance. Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII :C) and VWF antigen (VWF :Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII :C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII :C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, Ile581Thr, P = 5.10 × 10(-7) in EAs and P = 3.88 × 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg,P = 6.30 × 10(-9) in EAs and P = 2.98 × 10(-2) in AAs. Significant associations for FVIII :C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P = 8.02 × 10(-10) ), with VWF rs1800380 in AAs (P = 5.62 × 10(-11) ), and with MAT1A rs2236568 in AAs (P51.69 × 10(-6) ). We replicated previously reported associations of FVIII :C and VWF :Ag with the ABO blood group, VWF rs1063856(Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII :C and VWF :Ag in both EAs and AAs. OBJECTIVE: Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. RESULTS: We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m(2) higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h). CONCLUSIONS: Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet—specifically higher carbohydrate and lower fat composition—and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants. BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS: We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. RESULTS: Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS: Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia. General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. METHODS: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. RESULTS: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. CONCLUSIONS: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways. BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)). CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants. BACKGROUND: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. OBJECTIVES: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. DESIGN: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. RESULTS: We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. CONCLUSIONS: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. BACKGROUND: Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. METHODS: We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years). RESULTS: During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates. CONCLUSIONS: The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper. BACKGROUND: When examining older adults' health behaviors and psychological health, it is important to consider the social context. PURPOSE: The purpose of this study was to examine in older adult marriages whether each spouse's physical activity predicted changes in their own (actor effects) and their partner's (partner effects) depressive symptoms. Gender differences were also examined. METHOD: Each spouse within 1260 married couples (at baseline) in the Cardiovascular Health Study completed self-report measures at wave 1 (1989-1990), wave 3 (1992-1993), and wave 7 (1996-1997). Dyadic path analyses were performed. RESULTS: Husbands' physical activity significantly predicted own decreased depressive symptoms (actor effect). For both spouses, own physical activity did not significantly predict the spouse's depressive symptoms (partner effects). However, husbands' physical activity and depressive symptoms predicted wives' physical activity and depressive symptoms (partner effects), respectively. Depressive symptoms did not predict physical activity. CONCLUSION: Findings suggest that husbands' physical activity is particularly influential for older married couples' psychological health. Mobility and function are important predictors of survival. However, their combined impact on mortality in adults ≥65 years with heart failure (HF) is not well understood. This study examined the role of gait speed and instrumental activities of daily living (IADL) in all-cause mortality in a cohort of 1,119 community-dwelling Cardiovascular Health Study participants ≥65 years with incident HF. Data on HF and mortality were collected through annual examinations or contact during the 10-year follow-up period. Slower gait speed (<0.8 m/s vs ≥0.8 m/s) and IADL impairment (≥1 vs 0 areas of dependence) were determined from baseline and follow-up assessments. A total of 740 (66%) of the 1,119 participants died during the follow-up period. Multivariate Cox proportional hazards models showed that impairments in either gait speed (hazard ratio 1.37, 95% confidence interval 1.10 to 1.70; p = 0.004) or IADL (hazard ratio 1.56, 95% confidence interval 1.29-1.89; p <0.001), measured within 1 year before the diagnosis of incident HF, were independently associated with mortality, adjusting for sociodemographic and clinical characteristics. The combined presence of slower gait speed and IADL impairment was associated with a greater risk of mortality and suggested an additive relation between gait speed and IADL. In conclusion, gait speed and IADL are important risk factors for mortality in adults ≥65 years with HF, but the combined impairments of both gait speed and IADL can have an especially important impact on mortality. BACKGROUND: Pneumonia is associated with high risk of heart failure (HF) in the short term (30 days) postinfection. Whether this association persists beyond this period is unknown. METHODS: We studied 5,613 elderly (≥65 years) adults enrolled in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities. Participants had no clinical diagnosis of HF at enrollment, and they were followed up through December 2010. Hospitalizations for pneumonia were identified using validated International Classification of Disease Ninth Revision codes. A centralized committee adjudicated new-onset HF events. Using Cox regression, we estimated adjusted hazard ratios (HRs) of new-onset HF at different time intervals after hospitalization for pneumonia. RESULTS: A total of 652 participants hospitalized for pneumonia during follow-up were still alive and free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the time of their hospitalization, new-onset HF occurred in 22 cases between 31 and 90 days (HR 6.9, 95% CI 4.46-10.63, P < .001), 14 cases between 91 days and 6 months (HR 3.2, 95% CI 1.88-5.50, P < .001), 20 cases between 6 months and 1 year (HR 2.6, 95% CI 1.64-4.04, P < .001), 76 cases between 1 and 5 years (HR 1.7, 95% CI 1.30-2.12, P < .001), and 71 cases after 5 years (HR 2.0, 95% CI 1.56-2.58, P < .001). Results were robust to sensitivity analyses using stringent definitions of pneumonia and extreme assumptions for potential informative censoring. CONCLUSION: Hospitalization for pneumonia is associated with increased risk of new-onset HF in the intermediate and long term. Studies should characterize the mechanisms of this association in order to prevent HF in elderly pneumonia survivors. OBJECTIVES: To evaluate the association between performance on a single chair stand and moderate to severe exertional dyspnea. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study. PARTICIPANTS: Community-dwelling individuals aged 65 and older (N = 4,413; mean age 72.6; female, n = 2,518 (57.1%); nonwhite, n = 199 (4.5%); obese, n = 788 (17.9%); history of smoking, n = 2,410 (54.6%)). MEASUREMENTS: Performance on single chair stand (poor (unable to rise without arm use) vs normal (able to rise without arm use)), moderate to severe exertional dyspnea (American Thoracic Society grade ≥2), age, sex, ethnicity, obesity, smoking, frailty status (Fried-defined nonfrail, prefrail, frail), high cardiopulmonary risk (composite of cardiopulmonary diseases and diabetes mellitus), spirometric impairment, arthritis, depression, stroke, and kidney disease. RESULTS: Poor performance on the single chair stand was established in 369 (8.4%) and moderate to severe exertional dyspnea in 773 (17.5%). Prefrail status was established in 2,210 (50.1%), frail status in 360 (8.2%), arthritis in 2,241 (51.4%), high cardiopulmonary risk in 2,469 (55.9%), spirometric impairment in 1,076 (24.4%), kidney disease in 111 (2.5%), depression in 107 (2.4%), and stroke in 93 (2.1%). In multivariable regression models, poor performance on the single chair stand was associated with moderate to severe exertional dyspnea (unadjusted odds ratio (OR) = 3.48, 95% confidence interval (CI) = 2.78-4.36; adjusted OR = 1.85, 95% CI = 1.41-2.41). CONCLUSION: Poor performance on a single chair stand was associated with an adjusted 85% greater likelihood of moderate to severe exertional dyspnea than normal performance. These results suggest that reduced proximal muscle function of the lower extremities is associated with moderate to severe exertional dyspnea, even after adjusting for multiple confounders. OBJECTIVES: The purpose of this study was to examine the prognostic significance of left ventricular (LV) mass for cardiovascular disease (CVD) events in older adults with and without metabolic syndrome (MetS) and diabetes mellitus (DM). BACKGROUND: MetS and DM are associated with increased CVD risk, but it is unclear in these groups whether subclinical CVD as shown by increased LV mass improves risk prediction compared to standard risk factors in older individuals. METHODS: We studied 3,724 adults (mean 72.4 ± 5.4 years of age, 61.0% female, 4.4% African-American) from the Cardiovascular Health Study who had MetS but not DM or had DM alone or had neither condition. Cox regression was used to examine the association of LV mass, (alone and indexed by height and body surface area [BSA]) as determined by echocardiography, with CVD events, including coronary heart disease (CHD), stroke, heart failure (HF), and CVD death, as well as total mortality. We also assessed the added prediction, discriminative value, and net reclassification improvement (NRI) for clinical utility of LV mass compared to standard risk factors. RESULTS: Over a mean follow-up of 14.2 ± 6.3 years, 2,180 subjects experienced CVD events, including 986 CVD deaths. After adjustment for age, sex and standard risk factors, LV mass was positively associated with CVD events in those with MetS (hazard ratio [HR]: 1.4, p < 0.001) and without MetS (HR: 1.4, p < 0.001), but not DM (HR: 1.0, p = 0.62), with similar findings for LV mass indexed for height or BSA. Adding LV mass to standard risk factors moderately improved the prediction accuracy in the overall sample and MetS group from changes in C-statistics (p < 0.05). Categorical-free net reclassification improvement increased significantly by 17% to 19% in those with MetS. Findings were comparable for CHD, CVD mortality, and total mortality. CONCLUSIONS: LV mass is associated with increased CVD risk and provides modest added prediction and clinical utility compared to standard risk factors in older persons with and without MetS but not with DM. AIMS: To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. METHODS AND RESULTS: We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10(-6)); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). CONCLUSION: The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain. BACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). STUDY DESIGN: Collaborative meta-analysis. SETTING & POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants). SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events. PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions. OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. RESULTS: 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR. LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code. CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD. BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain. STUDY DESIGN: Meta-analysis of cohort studies. SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts. SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium. PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions. OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension. LIMITATIONS: AKI identified by diagnostic code. CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension. OBJECTIVES: To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function DESIGN: Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). SETTING: Community. PARTICIPANTS: Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). MEASUREMENTS: Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) RESULTS: Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. CONCLUSION: Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. BACKGROUND: The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. METHODS AND RESULTS: We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). CONCLUSIONS: We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms. BACKGROUND: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals. METHODS: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models. RESULTS: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, -0.006). CONCLUSIONS: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed. Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. BACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors. RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50). CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association. OBJECTIVES: This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH). BACKGROUND: The natural history of LVH, an important risk factor for HF, is heterogeneous. METHODS: NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression. RESULTS: Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers. CONCLUSIONS: The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention. The purpose of this study was to use a novel imaging biomarker to assess associations between physical activity (PA), body mass index (BMI), and brain structure in normal aging, mild cognitive impairment, and Alzheimer's dementia. We studied 963 participants (mean age: 74.1 ± 4.4 years) from the multisite Cardiovascular Health Study including healthy controls (n = 724), Alzheimer's dementia patients (n = 104), and people with mild cognitive impairment (n = 135). Volumetric brain images were processed using tensor-based morphometry to analyze regional brain volumes. We regressed the local brain tissue volume on reported PA and computed BMI, and performed conjunction analyses using both variables. Covariates included age, sex, and study site. PA was independently associated with greater whole brain and regional brain volumes and reduced ventricular dilation. People with higher BMI had lower whole brain and regional brain volumes. A PA-BMI conjunction analysis showed brain preservation with PA and volume loss with increased BMI in overlapping brain regions. In one of the largest voxel-based cross-sectional studies to date, PA and lower BMI may be beneficial to the brain across the spectrum of aging and neurodegeneration. INTRODUCTION: The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL)--repetitive DNA sequences that may mark biologic aging--is not well-established. Few prior studies (mainly cross-sectional) have been conducted in older adults, and few studies have evaluated PF. METHODS: We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (mean ± SD age, 73 ± 5 yr at baseline) in the Cardiovascular Health Study, with serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL, and changes in cumulatively averaged PA and PF against changes in TL. RESULTS: Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (P trend = 0.007 and 0.04, respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. CONCLUSIONS: Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults. OBJECTIVE: Interleukin (IL) -2 receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels. APPROACH AND RESULTS: We measured baseline levels of sIL-2Rα in 4408 European American (EA) and 766 African American (AA) adults from the Cardiovascular Health Study (CHS) and examined associations with baseline CVD risk factors, subclinical CVD, and incident CVD events. We also performed a genome-wide association study for sIL-2Rα in CHS (2964 EAs and 683 AAs) and further combined CHS EA results with those from two other EA cohorts in a meta-analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Rα was positively associated with current smoking, type 2 diabetes mellitus, hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen, internal carotid wall thickness, all-cause mortality, CVD mortality, and incident CVD, stroke, and heart failure. When adjusted for baseline CVD risk factors and subclinical CVD, associations with all-cause mortality, CVD mortality, and heart failure remained significant in both EAs and AAs. In the EA genome-wide association study analysis, we observed 52 single-nucleotide polymorphisms in the chromosome 10p15-14 region, which contains IL2RA, IL15RA, and RMB17, that reached genome-wide significance (P<5×10(-8)). The most significant single-nucleotide polymorphism was rs7911500 (P=1.31×10(-75)). The EA meta-analysis results were highly consistent with CHS-only results. No single-nucleotide polymorphisms reached statistical significance in the AAs. CONCLUSIONS: These results support a role for sIL-2Rα in atherosclerosis and provide evidence for multiple-associated single-nucleotide polymorphisms at chromosome 10p15-14. BACKGROUND: Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes. OBJECTIVE: By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes. DESIGN: A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes. RESULTS: Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47% lower risk of diabetes (95% CI: 23%, 63%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33% (95% CI: 6%, 53%; P-trend: 0.02) and 37% (95% CI: 11%, 55%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32% lower risk for fourth vs. first quartile; P-trend: 0.04). CONCLUSIONS: These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at clinicaltrials.gov as NCT00005133. BACKGROUND: Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks can be triggered by dietary factors that are themselves associated with serum urate levels. Tomato consumption is an anecdotal trigger of gout flares. This study aimed to measure the frequency of tomato consumption as a self-reported trigger of gout attacks in a large New Zealand sample set, and to test the hypothesis that tomato consumption is associated with serum urate levels. METHODS: Two thousand fifty one New Zealanders (of Māori, Pacific Island, European or other ancestry) with clinically-ascertained gout were asked about gout trigger foods. European individuals from the Atherosclerosis Risk In Communities (ARIC; n = 7517) Study, Cardiovascular Health Study (CHS; n = 2151) and Framingham Heart Study (FHS; n = 3052) were used to test, in multivariate-adjusted analyses, for association between serum urate and tomato intake. RESULTS: Seventy one percent of people with gout reported having ≥1 gout trigger food. Of these 20% specifically mentioned tomatoes, the 4(th) most commonly reported trigger food. There was association between tomato intake and serum urate levels in the ARIC, CHS and FHS combined cohort (β = 0.66 μmolL(-1) increase in serum urate per additional serve per week; P = 0.006) - evident in both sexes (men: β = 0.84 μmolL(-1), P = 0.035; women: β = 0.59 μmolL (-1), P = 0.041). CONCLUSIONS: While our descriptive and observational data are unable to support the claim that tomato consumption is a trigger of gout attacks, the positive association between tomato consumption and serum urate levels suggests that the self-reporting of tomatoes as a dietary trigger by people with gout has a biological basis. BACKGROUND: We sought to determine the impacts of serum and dietary potassium measures on glucose metabolism and diabetes risk in older adults. METHODS: Among participants of the Cardiovascular Health Study, a community-based cohort of older American adults, we examined a) cross-sectional associations between potassium and measures of insulin sensitivity and secretion estimated from oral glucose tolerance tests and b) longitudinal associations of serum and dietary potassium with diabetes risk. RESULTS: Among 4,754 participants aged ≥65 years at baseline, there were 445 cases of incident diabetes during a median follow-up of 12 years. In multivariate models, baseline serum and dietary potassium were both associated with lower insulin sensitivity and greater insulin secretion. Compared with those with a serum potassium ≥4.5 mEq/L, participants with a serum potassium <4.0mEq/L had an adjusted mean difference in Matsuda insulin sensitivity index of -0.18 (-0.39, 0.02). Compared with those in the highest quartile, participants in the lowest quartile of dietary potassium intake had a corresponding adjusted mean difference in Matsuda insulin sensitivity index of -0.61 (-0.94, -0.29). In multivariate models, neither serum nor dietary potassium intake was associated with long-term diabetes risk. CONCLUSIONS: Although we did not identify serum and dietary potassium as risk factors for incident diabetes in older adults, results from cross-sectional analyses suggest that both may be associated with increased insulin resistance. This relationship with insulin resistance needs to be confirmed, and its importance on diabetes risk, cardiovascular risk, and conditions specific to older adults should be determined as well. BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB. METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined. RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57). CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L). BACKGROUND: Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes. OBJECTIVES: We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs. DESIGN: In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively. RESULTS: At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes. CONCLUSIONS: In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes. Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95% CI 1.03, 1.95) in whites and 1.72 (95% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans. BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention. IMPORTANCE: Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk. OBJECTIVE: To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome. DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013. MAIN OUTCOMES AND MEASURES: Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis). RESULTS: We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 × 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 × 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke). CONCLUSIONS AND RELEVANCE: Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy. Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline. BACKGROUND: The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned. METHODS AND RESULTS: RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64). CONCLUSIONS: There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association. BACKGROUND: Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset. OBJECTIVE: The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF). METHODS: In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses. RESULTS: Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF. CONCLUSION: The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain. PURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults. METHODS: 1963 men and 2729 women ≥65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori. RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and ≥6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women. CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them. OBJECTIVE: We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS: Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history. RESULTS: Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes. CONCLUSIONS: Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults. OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels. DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations. CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed. IMPORTANCE: Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE: To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION: Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES: The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS: Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE: Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures. CONTEXT: The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned. OBJECTIVE: This study aimed to determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS: US community-dwelling adults years of older (n = 2843) enrolled onto the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range. MAIN OUTCOME MEASURES: Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death were measured. RESULTS: No departures from linearity were detected. Higher TSH was negatively associated (P = .03) and higher FT4 was positively associated (P = .007) with mortality. Higher FT4 was associated with atrial fibrillation (P < .001) and heart failure (P = .004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (P < .05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure, and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all P < .05). Total T3 was not associated with any outcome. CONCLUSIONS: Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people. Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function. Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m(2), and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals. OBJECTIVE: Resting heart rate (RHR) is an established predictor of myocardial infarction (MI) and mortality, but the relationship between variation in RHR over a period of several years and health outcomes is unclear. We evaluated the relationship between long-term variation in RHR and the risks of incident MI and mortality among older adults. METHODS: 1991 subjects without cardiovascular disease from the Cardiovascular Health Study were included. RHR was taken from resting ECGs at the first five annual study visits. RHR mean, trend and variation were estimated with linear regression. Subjects were followed for incident MI and death until December 2010. HRs for RHR mean, trend and variation are reported for differences of 10 bpm, 2 bpm/year and 2 bpm, respectively. RESULTS: 262 subjects had an incident MI event (13%) and 1326 died (67%) during 12 years of median follow-up. In primary analyses adjusted for cardiovascular risk factors, RHR mean (HR 1.12; 95% CI 1.05 to 1.20) and variation (HR 1.08; 95% CI 1.03 to 1.13) were associated with the risk of death while trend was not. None of the RHR variables were significantly associated with the risk of incident MI events; however, CIs were wide and the MI associations with RHR variables were not significantly different from the mortality associations. Adjusting for additional variables did not affect estimates, and there were no significant interactions with sex. CONCLUSIONS: Variation in RHR over a period of several years represents a potential predictor of long-term mortality among older persons free of cardiovascular disease. BACKGROUND: Studies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown. OBJECTIVES: The goal of this study was to determine whether PVC frequency ascertained using a 24-h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort. METHODS: We studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death. RESULTS: Those in the upper quartile versus the lowest quartile of PVC frequency had a multivariable-adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio [OR]: 3.10; 95% confidence interval [CI]: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15-year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%). CONCLUSIONS: In a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death. The purpose of this study was to identify, at the voxel level, brain regions associated with the time to develop mild cognitive impairment (MCI) or Alzheimer's disease (AD) from normal cognition. We analyzed incident MCI (n = 58) or AD (n = 151) in 292 cognitively normal participants in the Cardiovascular Health Study-Cognition Study (mean age = 79.2 ± 3.6 years). We used segmented, modulated grey matter maps from 3D (spoiled gradient echo) MRI scans obtained in 1998/99 (with clinical follow-up through 2012) that were smoothed with a 3-D 4 mm Gaussian filter. We fit approximately 1.92 million voxel-level Cox proportional hazard models to examine the grey matter volume effect on time to event, adjusting for age, sex, and diabetes. We used the significance threshold of p < 0.005 with contiguity threshold of at least 68 voxels (false detection probability <2.5×10 -8). Areas within the mesial temporal lobe (MTL), anterior temporal lobe, hippocampus, and posterior cingulate gyrus were associated with time to MCI or AD. The presence of white matter lesions (a marker of small vessel disease in the brain) was associated with the volumes of the MTL and precuneus; MRI-identified infarcts also predicted MTL volume. These findings are important because we identified critical brain regions that predict a person's increased likelihood of developing MCI or AD over a decade prior to the onset of clinical symptoms; these critical brain regions were themselves affected by the presence of vascular disease. BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. RESULTS: A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10(-8)). Four loci were suggestive (P<1×10(-5)) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10(-6)); 12q13.13 (rs4761974, P=8.71×10(-7)); 20p12.1 (rs6135309, P=3.69×10(-6)); and 4p15.31 (rs7664442, P=2.26×10(-6)). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden. CONCLUSIONS: Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors. BACKGROUND: As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed. METHODS AND RESULTS: The Cardiovascular Health Study is a population-based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima-media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6 ± 5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: -1.34 (95% confidence interval [CI], -2.18, -0.49) and -1.41 (95% CI, -2.03, -0.8) for abnormal left ventricular (LV) ejection fraction, -0.5 (95% CI, -0.78, -0.22) and -0.62 (95% CI, -0.87, -0.36) per SD increase in LV mass, -0.5 (95% CI, -0.7, -0.29) and -0.79 (95% CI, -0.99, -0.58) for IMT, -0.5 (95% CI, -0.64, -0.37) and -0.79 (95% CI, -0.94, -0.65) for N-terminal pro-brain natriuretic peptide, -1.08 (95% CI, -1.34, -0.83) and -0.73 (95% CI, -0.97, -0.5) for high-sensitivity troponin-T, and -0.26 (95% CI, -0.42, -0.09) and -0.23 (95% CI, -0.41, -0.05) for procollagen-III N-terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease. CONCLUSIONS: In this population-based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons. OBJECTIVE: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans. APPROACH AND RESULTS: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged ≥65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95% CI, 12.5-14.3) among other African Americans and 13.3 years (95% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites. CONCLUSIONS: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans. Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke and cardiovascular (CV) death. Whether modifiable lifestyle risk factors are associated with these CV outcomes in AF is unknown. Among Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS) participants with incident AF, we estimated the risk of composite endpoint of ischemic stroke or CV death associated with candidate modifiable risk factor (smoking, heavy alcohol consumption, or high body mass index [BMI]), and computed the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) of incorporating each factor into the CHA2DS2-VASc. Among 1222 ARIC (mean age: 63.4) and 756 CHS (mean age: 79.1) participants with incident AF, during mean follow-up of 6.9 years and 5.7 years, there were 332 and 335 composite events respectively. Compared with never smokers, current smokers had a higher incidence of the composite endpoint in ARIC [HR: 1.65 (1.21-2.26)] but not in CHS [HR: 1.05 (0.69-1.61)]. In ARIC, the addition of current smoking did not improve risk prediction over and above the CHA2DS2-VASc. No significant associations were observed with alcohol consumption or BMI with CVD outcomes in AF patients from either cohort. Smoking is associated with an increased risk of ischemic stroke or CV death in ARIC, which comprised mostly middle-aged to young-old (65-74 years), but not in CHS, which comprised mostly middle-old or oldest-old (≥75 years) adults with AF. However, addition of smoking to the CHA2DS2-VASc score did not improve risk prediction of these outcomes. INTRODUCTION: Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation. METHODS: We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study. RESULTS: Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size. CONCLUSION: Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production. BACKGROUND: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality. OBJECTIVE: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011. METHODS: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models. RESULTS: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality. CONCLUSIONS: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations. OBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality. DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality. SETTING: Cardiovascular Health Study. PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 ± 4.7, 40% male, 83% white). MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality. RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 ± 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% confidence interval (CI) = 17-62%) higher odds of frailty than of nonfrailty and 16% (95% CI = 3-30%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95% CI = 1.10-1.23) and frailty (HR = 1.82, 95% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other. CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes. BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function. METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking ¼ - ½ mile or climbing 10 steps within 3 years. RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥ 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve. CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality. BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke. BACKGROUND: Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. METHODS: We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. RESULTS: In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). CONCLUSIONS: QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders. OBJECTIVES: To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability. DESIGN: Prospective cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded. MEASUREMENTS: Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models. RESULTS: Over an average of 7.0 years of follow-up, 660 individuals (16.3%) developed incident AF, and 3,112 (77%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure. CONCLUSION: These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions. OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI). APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50). CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD. BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7. BACKGROUND: Although guidelines suggest that older adults engage in regular physical activity (PA) to reduce cardiovascular disease (CVD), surprisingly few studies have evaluated this relationship, especially in those >75 years. In addition, with advancing age the ability to perform some types of PA might decrease, making light-moderate exercise such as walking especially important to meet recommendations. METHODS AND RESULTS: Prospective cohort analysis among 4207 US men and women of a mean age of 73 years (standard deviation=6) who were free of CVD at baseline in the Cardiovascular Health Study were followed from 1989 to 1999. PA was assessed and cumulatively updated over time to minimize misclassification and assess the long-term effects of habitual activity. Walking (pace, blocks, combined walking score) was updated annually from baseline through 1999. Leisure-time activity and exercise intensity were updated at baseline, 1992, and 1996. Incident CVD (fatal or nonfatal myocardial infarction, coronary death, or stroke) was adjudicated using medical records. During 41,995 person-years of follow-up, 1182 CVD events occurred. After multivariable adjustment, greater PA was inversely associated with coronary heart disease, stroke (especially ischemic stroke), and total CVD, even in those ≥75 years. Walking pace, distance, and overall walking score, leisure-time activity, and exercise intensity were each associated with lower risk. For example, in comparison with a walking pace <2 mph, those that habitually walked at a pace >3 mph had a lower risk of coronary heart disease (0.50; confidence interval, 0.38-0.67), stroke (0.47; confidence interval, 033-0.66), and CVD (0.50; confidence interval, 0.40-0.62). CONCLUSIONS: These data provide empirical evidence supporting PA recommendations, in particular, walking, to reduce the incidence of CVD among older adults. BACKGROUND: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse. METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic. RESULTS: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models. CONCLUSION: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life. INTRODUCTION: Increasing life expectancy has resulted in a larger population of older individuals at risk of dementia. METHODS: The Cardiovascular Health Study-Cognition Study followed 532 participants from 1998-99 (mean age 79) to 2013 (mean age 93) for death and dementia. RESULTS: Risk of death was determined by extent of coronary artery calcium, high-sensitivity cardiac troponin, brain natriuretic peptide, and white matter grade. Significant predictors of dementia were age, apolipoprotein-E4, vocabulary raw score, hippocampal volume, ventricular size, cognitive performance, and number of blocks walked. By 2013, 160 of 532 were alive, including 19 cognitively normal. Those with normal cognition had higher grade education, better cognition test scores, greater hippocampal volume, faster gait speed, and number of blocks walked as compared with survivors who were demented. DISCUSSION: Few survived free of dementia and disability. Prevention and delay of cognitive decline for this older population is an imperative. OBJECTIVES: To determine whether older adult spouses' frailty states and depressive symptoms are interrelated over time. DESIGN: Longitudinal, dyadic path analysis using the Actor-Partner Interdependence Model. SETTING: Data were from baseline (1989-90), Wave 3 (1992-93), and Wave 7 (1996-97), all waves in which frailty and depressive symptoms were measured, of the Cardiovascular Health Study (CHS), a multisite, longitudinal, observational study of risk factors for cardiovascular disease in adults aged 65 and older. PARTICIPANTS: Spouses in 1,260 community-dwelling married couples. MEASUREMENTS: Frailty was measured using the CHS criteria, categorized as nonfrail, prefrail, or frail. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale. RESULTS: Within individuals (actor effects), greater frailty predicted greater subsequent depressive symptoms, and greater depressive symptoms predicted greater subsequent frailty. Between spouses (partner effects), an individual's greater frailty predicted the spouse's greater frailty, and an individual's greater depressive symptoms predicted the spouse's greater depressive symptoms. CONCLUSION: Frailty and depressive symptoms are interrelated in older adult spouses. For older couples, interventions to prevent or treat frailty and depression that focus on couples may be more effective than those that focus on individuals. BACKGROUND: Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. METHODS AND RESULTS: Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare & Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI. CONCLUSIONS: The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations. BACKGROUND: The successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia. OBJECTIVES: The authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores. METHODS: We evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years). RESULTS: Thirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25% of deaths were caused by CHD and 16% by dementia. Approximately 64% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia. CONCLUSIONS: In subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133). The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up. Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P < 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02-1.12, P = 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30-1.93 per standard deviation increase in BMI, P = 5.8 × 10). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE. Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I. Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults. Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates. Setting: General community. Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up. Interventions: Not applicable. Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx. Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes. Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men. Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases. OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings. APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15% and worsening white matter grade in 27%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses. CONCLUSIONS: Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ. Reports on the associations between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with guidelines from the American Cancer Society and American Heart Association for disease prevention in relation to cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n = 3,491), were free of CVD and cancer. Total and cause-specific mortality, as well as incidence of cancer and CVD, were lower with higher guideline concordance. Independent of body mass index, blood pressure, total cholesterol, and fasting plasma glucose, better health behaviors (diet, physical activity, and alcohol consumption) were associated with lower mortality (2-sided P < 0.0001). Among individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers, those with poor concordance with health behavior recommendations had higher mortality compared with those who had the highest concordance with these behavioral recommendations (adjusted mortality hazard ratio = 1.82, 95% confidence interval: 1.25, 2.67). Older adults who are concordant with recommendations for cancer and CVD prevention have reduced rates of chronic disease and mortality. Interventions to achieve and maintain healthy lifestyle behaviors may offer benefits both in the presence and absence of adverse traditional clinical risk factors. Importance: Ischemic strokes may accelerate long-term functional decline apart from their acute effects on neurologic function. Objective: To test whether the increase in long-term disability is steeper after than before the event for ischemic stroke but not myocardial infarction (MI). Design, Settings, and Participants: In the population-based, prospective cohort Cardiovascular Health Study (1989-2013), longitudinal follow-up was conducted for a mean (SD) of 13 (6.2) years. Follow-up data were used until September 1, 2013; data analysis was performed from August 1, 2013, to June 1, 2016. Models based on generalized estimating equations adjusted for baseline covariates and included a test for different slopes of disability before and after the event. Participants included 5888 Medicare-eligible individuals 65 years or older who were not institutionalized, expected to reside in the area for 3 or more years, and able to provide informed consent. Exclusions were needing a wheelchair, receiving hospice care, and undergoing radiotherapy or chemotherapy. Exposures: Ischemic stroke and MI. Main Outcomes and Measures: Annual assessments with a disability scale (measuring activities of daily living [ADLs] and instrumental ADLs). The number of ADLs and instrumental ADLs (range, 0-12) that the participant could not perform was analyzed continuously. Results: The mean (SD) age of the entire cohort (n = 5888) was 72.8 (5.6) years; 2495 (42.4%) were male. During follow-up, 382 (6.5%) participants had ischemic stroke and 395 (6.7%) had MI with 1 or more disability assessment after the event. There was a mean of 3.7 (2.4) visits before stroke and 3.7 (2.3) visits after stroke; there was a mean of 3.8 (2.5) visits before MI and 3.8 (2.4) visits after MI. The increase in disability near the time of the event was greater for stroke (0.88 points on the disability scale; 95% CI, 0.57 to 1.20; P < .001) than MI (0.20 points on the disability scale; 95% CI, 0.06 to 0.35; P = .006). The annual increase in disability before stroke (0.06 points per year; 95% CI, 0.002 to 0.12; P = .04) more than tripled after stroke (0.15 additional points per year; 95% CI, 0.004 to 0.30; P = .04). The annual increase in disability before MI (0.04 points per year; 95% CI, 0.004 to 0.08; P = .03) did not change significantly after MI (0.02 additional points per year; 95% CI, -0.07 to 0.11; P = .69). Conclusions and Relevance: In this large, population-based study, a trajectory of increasing disability became significantly steeper after stroke but not after MI. Thus, in addition to the acute brain injury and consequent impairment, ischemic stroke may also be associated with potentially treatable long-term adverse effects on the brain that lead to accelerated functional decline. BACKGROUND AND PURPOSE: Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke. METHODS: In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations). RESULTS: Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only. CONCLUSIONS: Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes. Context: Obesity is associated with poor bone mineralization and quality. Fibroblast growth factor 23 (FGF23) plays an important role in skeletal physiology. Objective: To test hypothesis that greater adiposity results in higher FGF23 levels among individuals with normal estimated glomerular filtration rate (eGFR). Design, Setting, Participants: Cross-sectional analyses among participants with eGFR ≥60 mL/min/1.73m2. We assessed the association between crude [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR); n = 5610] and refined (abdominal adipose tissue area by computed tomography; n = 1313) measures of adiposity and FGF23 using multivariable linear regression. Main Outcome Measure: Serum FGF23. Results: FGF23 was higher across BMI categories (BMI <25: 37.7; BMI 25 to 29.99: 38.7; BMI 30 to 39.99: 39.8; BMI ≥40: 40.9 pg/mL, unadjusted P trend < 0.0001). The association between BMI and FGF23 was independent of known confounders of FGF23 (adjusted β = +7.2% higher FGF23 per 10 kg/m2; P < 0.0001). Similar results were observed using WC and WHR. Abdominal adipose tissue area was also independently associated with higher FGF23 (P < 0.01). Notably, the positive associations between FGF23 and adiposity were observed despite the fact that eGFR did not decline and serum phosphate levels did not increase with adiposity. Conclusion: In a large cohort with normal kidney function, adiposity was associated with higher FGF23 levels independent of known confounders, including eGFR and phosphate. Further studies are needed to evaluate the causes of higher FGF23 in settings of greater adiposity and the potential impact on skeletal health. Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist. BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation. BACKGROUND: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. METHODS AND RESULTS: We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P<5.0×10-8 and 2.5×10-6, respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P=5.03×10-8, stage-2 P=8.64×10-3, joint P=2.63×10-8) and mean arterial pressure (stage-1 P=3.59×10-9, stage-2 P=2.35×10-2, joint P=2.64×10-8). Three previously reported BP loci (WBP1L, NT5C2, and ATP2B1) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P=8.55×10-6, stage-2 P=1.62×10-5, joint P=3.28×10-9) and mean arterial pressure (stage-1 P=9.19×10-7, stage-2 P=9.69×10-5, joint P=2.15×10-9) phenotypes. Fourteen genes (TMEM180, ACTR1A, SUFU, ARL3, SFXN2, WBP1L, CYP17A1, C10orf32, C10orf32-ASMT, AS3MT, CNNM2, and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes (P=1.27×10-4 and 3.30×10-4, respectively). CONCLUSIONS: We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians. BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis. RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results. CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid. Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP- and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes. Among 3804 patients, 7 clinical factors and 9 SNPs were significantly associated with HFpEF; the most notable of which was rs6996224, a SNP associated with transforming growth factor-beta receptor 3. Most SNPs were associated with HFpEF only in the absence of a clinical predictor. Significant SNPs represented genes involved in myocyte proliferation, transforming growth factor-beta/erbB signaling, and extracellular matrix formation. These findings suggest that genetic factors may be more important in some phenotypes than others. The identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes. Here, we analyzed the association between 137,086 rare (minor allele frequency (MAF) <1%) coding or splice site variants and 15 hematological traits in up to 308,572 participants. We found 56 such rare coding or splice site variants at P<5x10-8, including 31 that are associated with a blood-cell phenotype for the first time. All but one of these 31 new independent variants map to loci previously implicated in hematopoiesis by genome-wide association studies (GWAS). This includes a rare splice acceptor variant (rs146597587, MAF = 0.5%) in interleukin 33 (IL33) associated with reduced eosinophil count (P = 2.4x10-23), and lower risk of asthma (P = 2.6x10-7, odds ratio [95% confidence interval] = 0.56 [0.45-0.70]) and allergic rhinitis (P = 4.2x10-4, odds ratio = 0.55 [0.39-0.76]). The single new locus identified in our study is defined by a rare p.Arg172Gly missense variant (rs145535174, MAF = 0.05%) in plasminogen (PLG) associated with increased platelet count (P = 6.8x10-9), and decreased D-dimer concentration (P = 0.018) and platelet reactivity (P<0.03). Finally, our results indicate that searching for rare coding or splice site variants in very large sample sizes can help prioritize causal genes at many GWAS loci associated with complex human diseases and traits. The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (β=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (β=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (β=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk. Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension. INTRODUCTION: We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci. METHODS: We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions. RESULTS: We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ toxicity, and NDUFS3, SLC25A11, ATP5H, and APP were differentially expressed in the temporal cortex. DISCUSSION: Network analyses identified novel LOAD candidate genes. We demonstrated a functional role for four of these in a C. elegans model and found enrichment of differentially expressed genes in the temporal cortex. BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. BACKGROUND: Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability. METHODS: We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual. RESULTS: Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (≥10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (≥20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74). CONCLUSIONS: Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly. BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk. BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D. BACKGROUND/OBJECTIVES: Few studies have the requisite phenotypic information to define metabolic patterns that may inform our understanding of the pathophysiology and consequences of diabetes in older adults. We sought to characterize clusters of older adults on the basis of shared metabolic features. DESIGN: Population-based prospective cohort study. SETTING: Four U.S. Cardiovascular Health Study field centers. PARTICIPANTS: Individuals aged 65 and older taking no glucose-lowering agents (N = 2,231). MEASUREMENTS: K-means cluster analysis of 11 metabolic parameters (fasting and postload serum glucose and plasma insulin, fasting C-peptide, body mass index, C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), albuminuria, carboxymethyl lysine (an advanced glycation end-product), procollagen III N-terminal propeptide (a fibrotic marker)) and their associations with incident cardiovascular disease, diabetes, disability, and mortality over 8 to 14.5 years of follow-up and with measures of subclinical cardiovascular disease. RESULTS: A 6-cluster solution provided robust differentiation into distinct, identifiable clusters. Cluster A (n = 739) had the lowest glucose and insulin and highest eGFR and the lowest rates of all outcomes. Cluster B (n = 419) had high glucose and insulin and intermediate rates of most outcomes. Cluster C (n = 118) had the highest insulin. Cluster D (n = 129) had the highest glucose with much lower insulin. Cluster E (n = 314) had the lowest eGFR and highest albuminuria. Cluster F (n = 512) had the highest CRP. Rates of CVD, mortality, and subclinical atherosclerosis were highest in clusters C, D, and E and were similar to rates in participants with treated diabetes. Incidence of disability was highest in Cluster C. CONCLUSION: Clustering according to metabolic parameters identifies distinct phenotypes that are strongly associated with clinical and functional outcomes, even at advanced age. AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers. DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies. Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia. BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS: Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD. Importance: According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. Objective: To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. Exposures: Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). Main Outcomes and Measures: The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. Results: Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. Conclusions and Relevance: Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD. BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described. METHODS: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL. RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10-8) and in the race-combined analysis (P = 1.5 × 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls. CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus. Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels. BACKGROUND: Studies have shown strong positive associations between serum urate (SU) levels and chronic kidney disease (CKD) risk; however, whether the relation is causal remains uncertain. We evaluate whether genetic data are consistent with a causal impact of SU level on the risk of CKD and estimated glomerular filtration rate (eGFR). METHODS AND FINDINGS: We used Mendelian randomization (MR) methods to evaluate the presence of a causal effect. We used aggregated genome-wide association data (N = 110,347 for SU, N = 69,374 for gout, N = 133,413 for eGFR, N = 117,165 for CKD), electronic-medical-record-linked UK Biobank data (N = 335,212), and population-based cohorts (N = 13,425), all in individuals of European ancestry, for SU levels and CKD. Our MR analysis showed that SU has a causal effect on neither eGFR level nor CKD risk across all MR analyses (all P > 0.05). These null associations contrasted with our epidemiological association findings from the 4 population-based cohorts (change in eGFR level per 1-mg/dl [59.48 μmol/l] increase in SU: -1.99 ml/min/1.73 m2; 95% CI -2.86 to -1.11; P = 8.08 × 10(-6); odds ratio [OR] for CKD: 1.48; 95% CI 1.32 to 1.65; P = 1.52 × 10(-11)). In contrast, the same MR approaches showed that SU has a causal effect on the risk of gout (OR estimates ranging from 3.41 to 6.04 per 1-mg/dl increase in SU, all P < 10-3), which served as a positive control of our approach. Overall, our MR analysis had >99% power to detect a causal effect of SU level on the risk of CKD of the same magnitude as the observed epidemiological association between SU and CKD. Limitations of this study include the lifelong effect of a genetic perturbation not being the same as an acute perturbation, the inability to study non-European populations, and some sample overlap between the datasets used in the study. CONCLUSIONS: Evidence from our series of causal inference approaches using genetics does not support a causal effect of SU level on eGFR level or CKD risk. Reducing SU levels is unlikely to reduce the risk of CKD development. We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex. In a separate replication cohort of autopsied subjects (n = 173), more pTau pathology was again observed in subjects with longer VNTR regions (p = 0.031). Unlike MUC6, AP2A2 is highly expressed in human brain. AP2A2 expression was lower in a subset analysis of brain samples from persons with longer versus shorter VNTR regions (p = 0.014 normalizing with AP2B1 expression). Double-label immunofluorescence studies showed that AP2A2 protein often colocalized with neurofibrillary tangles in LOAD but was not colocalized with pTau proteinopathy in progressive supranuclear palsy, or with TDP-43 proteinopathy. In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD. Importance: Keratoconus is a condition in which the cornea progressively thins and protrudes in a conical shape, severely affecting refraction and vision. It is a major indication for corneal transplant. To discover new genetic loci associated with keratoconus and better understand the causative mechanism of this disease, we performed a genome-wide association study on patients with keratoconus. Objective: To identify genetic susceptibility regions for keratoconus in the human genome. Design, Setting, and Participants: This study was conducted with data from eye clinics in Australia, the United States, and Northern Ireland. The discovery cohort of individuals with keratoconus and control participants from Australia was genotyped using the Illumina HumanCoreExome single-nucleotide polymorphism array. After quality control and data cleaning, genotypes were imputed against the 1000 Genomes Project reference panel (phase III; version 5), and association analyses were completed using PLINK version 1.90. Single-nucleotide polymorphisms with P < 1.00 × 10-6 were assessed for replication in 3 additional cohorts. Control participants were drawn from the cohorts of the Blue Mountains Eye Study and a previous study of glaucoma. Replication cohorts were from a previous keratoconus genome-wide association study data set from the United States, a cohort of affected and control participants from Australia and Northern Ireland, and a case-control cohort from Victoria, Australia. Data were collected from January 2006 to March 2019. Main Outcomes and Measures: Associations between keratoconus and 6 252 612 genetic variants were estimated using logistic regression after adjusting for ancestry using the first 3 principal components. Results: The discovery cohort included 522 affected individuals and 655 control participants, while the replication cohorts included 818 affected individuals (222 from the United States, 331 from Australia and Northern Ireland, and 265 from Victoria, Australia) and 3858 control participants (2927 from the United States, 229 from Australia and Northern Ireland, and 702 from Victoria, Australia). Two novel loci reached genome-wide significance (defined as P < 5.00 × 10-8), with a P value of 7.46 × 10-9 at rs61876744 in patatin-like phospholipase domain-containing 2 gene (PNPLA2) on chromosome 11 and a P value of 6.35 × 10-12 at rs138380, 2.2 kb upstream of casein kinase I isoform epsilon gene (CSNK1E) on chromosome 22. One additional locus was identified with a P value less than 1.00 × 10-6 in mastermind-like transcriptional coactivator 2 (MAML2) on chromosome 11 (P = 3.91 × 10-7). The novel locus in PNPLA2 reached genome-wide significance in an analysis of all 4 cohorts (P = 2.45 × 10-8). Conclusions and Relevance: In this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11. Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers. Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018. Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years. Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis. Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes. Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies. BACKGROUND: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. METHODS: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV and FEV/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV/FVC <0·7 and FEV <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. FINDINGS: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. INTERPRETATION: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth. FUNDING: US National Institutes of Health, Wellcome Trust. OBJECTIVE: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. METHODS: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. RESULTS: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. INTERPRETATION: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses. BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results. INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency. BACKGROUND: Low walking ability is highly prevalent with advancing age and predicts major health outcomes. Metabolomics may help to better characterize differences in walking ability among older adults, providing insight into potentially altered molecular processes underlying age-related decline in functioning. We sought to identify metabolites and metabolic pathways associated with high versus low walking ability among 120 participants ages 79-95 from the CHS All Stars study. METHODS: Using a nested case-control design, 60 randomly selected participants with low walking ability were matched one-to-one on age, gender, race, and fasting time with 60 participants with high walking ability. High versus low walking ability was defined as being in the best versus worst tertiles for both gait speed (≥0.9 vs <0.7 m/s) and the Walking Ability Index (7-9 vs 0-1). Using liquid chromatography-mass spectrometry, 569 metabolites were identified in overnight-fasting plasma. RESULTS: Ninety-six metabolites were associated with walking ability, where 24% were triacylglycerols. Triacylglycerols that were higher among those with high walking ability consisted mostly of polyunsaturated fatty acids, whereas triacylglycerols that were lower among those with high walking ability consisted mostly of saturated or monounsaturated fatty acids. Body composition partly explained associations between some metabolites and walking ability. Proline and arginine metabolism was a top pathway associated with walking ability. CONCLUSION: These results may partly reflect pathways of modifiable risk factors, including excess dietary lipids and lack of physical activity, contributing to obesity and further alterations in metabolic pathways that lead to age-related decline in walking ability in this older adult cohort. Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. Objective: To assess performance of the PCE across clinical BMI categories. Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020. Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35). Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE. Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13 601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ≥20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics. Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction. Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all < 0.05 to < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris. Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry. Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood. Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65 251 participants aged 18 to 102 years of whom 53 701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018). Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1 less than 80% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1 greater than or equal to 80% predicted. Main Outcomes and Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities. Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4% women, 48.5% never-smokers), 4582 (8.5%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3% vs 31.4%; prevalence ratio [PR], 1.68 [95% CI, 1.55-1.82]), underweight (prevalence, 1.4% vs 1.0%; PR, 2.20 [95% CI, 1.72-2.82]), female sex (prevalence, 60.3% vs 59.0%; PR, 1.07 [95% CI, 1.01-1.13]), and current smoking (prevalence, 25.2% vs 17.5%; PR, 1.33 [95% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95% CI, 0.7-1.6]; adjusted HR, 1.95 [95% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95% CI, 2.1-3.4]; adjusted HR, 1.55 [95% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95% CI, 4.9-7.5]; adjusted HR, 1.90 [95% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95% CI, 3.7-5.8]; adjusted HR, 1.30 [95% CI, 1.18-1.42]). Conclusions and Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal. CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied. OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (≥40 years). DESIGN: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis. SETTING: Population-based cohort studies. PARTICIPANTS: 30 780 participants (56.1% female, 69.8% non-Hispanic white) without a diagnosis of diabetes by age 40. INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of diabetes medications. RESULTS: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI ≥ 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49% and 44% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations. CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator. The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death. Among 1299 older adults with 24-h Holter monitoring data at baseline, followed for approximately 15 years, 190 incident hip fractures occurred. Increased heart rate variability was independently associated with reduced risk of hip fracture among female participants. PURPOSE: Autonomic nervous system function modulates bone remodeling in rodent osteoporosis models. We tested whether cardiovascular autonomic function is associated with hip fracture risk in humans. METHODS: Participants were 1299 subjects from the Cardiovascular Health Study (mean age 72.8 years). Eight heart rate variability (HRV) measures (time and frequency domains, detrended fluctuation analysis variables, and heart rate turbulence) were derived from 24-h Holter monitor scans in sinus rhythm. Median follow-up for incident hip fracture was 14.7 years [IQR 9.1, 20.2]. Cox proportional hazards models were used to calculate hazard ratios (95% confidence intervals, CI). RESULTS: There were 144 hip fractures among 714 women (1.31 [1.06, 1.61] per 100-person years) and 46 among 585 men (0.62 [0.43, 0.90] per 100 person-years). From among HRV variables examined, a one standard deviation (SD) higher variation between normal heart beats over 24 h (the SD of NN intervals [SDNN]) was associated with a multivariable-adjusted lower hip fracture risk (HR [Formula: see text] 0.80; 95% CI 0.65-0.99; p = 0.04) in women. The adjusted association between very low frequency power, and hip fracture was borderline statistically significant in women (HR [Formula: see text] 0.82; 95% CI, 0.66-1.00; p = 0.06). When the 8 HRV variables were considered conjointly and adjusted for each other's association with hip fracture risk, a 1 SD higher SDNN value was significantly associated with reduced hip fracture risk in women (HR 0.74; 95% CI, 0.50-0.99; p = 0.05). No HRV variables were associated with hip fracture in men. CONCLUSIONS: In older women, increased heart rate variation is associated with hip fracture risk. OBJECTIVE: Cardiovascular risk factors (CVRFs) are associated with increased risk of cognitive decline, but little is known about how early adult CVRFs and those across the life course might influence late-life cognition. To test the hypothesis that CVRFs across the adult life course are associated with late-life cognitive changes, we pooled data from 4 prospective cohorts (n = 15,001, ages 18-95). METHODS: We imputed trajectories of body mass index (BMI), fasting glucose (FG), systolic blood pressure (SBP), and total cholesterol (TC) for older adults. We used linear mixed models to determine the association of early adult, midlife, and late-life CVRFs with late-life decline on global cognition (Modified Mini-Mental State Examination [3MS]) and processing speed (Digit Symbol Substitution Test [DSST]), adjusting for demographics, education, and cohort. RESULTS: Elevated BMI, FG, and SBP (but not TC) at each time period were associated with greater late-life decline. Early life CVRFs were associated with the greatest change, an approximate doubling of mean 10-year decline (an additional 3-4 points for 3MS or DSST). Late-life CVRFs were associated with declines in early late life (<80 years) but with gains in very late life (≥80 years). After adjusting for CVRF exposures at all time periods, the associations for early adult and late-life CVRFs persisted. CONCLUSIONS: We found that imputed CVRFs across the life course, especially in early adulthood, were associated with greater late-life cognitive decline. Our results suggest that CVRF treatment in early adulthood could benefit late-life cognition, but that treatment in very late life may not be as helpful for these outcomes. BACKGROUND: Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited. OBJECTIVE: To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline. METHODS: Using a pooled study of 4 prospective cohorts (ages 20-89), we imputed adult life course depressive symptoms trajectories based on Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and calculated time-weighted averages for early adulthood (ages 20-49), mid-life (ages 50-69), and late-life (ages 70-89) for 6,122 older participants. Adjusted pooled logistic and mixed-effects models estimated associations of imputed depressive symptoms with two cognitive outcomes: cognitive impairment defined by established criteria and a composite cognitive score. RESULTS: In separate models, elevated depressive symptoms in each life stage were associated with cognitive outcomes: early adulthood OR for cognitive impairment = 1.59 (95%CI: 1.35,1.87); mid-life OR = 1.94 (95%CI:1.16, 3.26); and late-life OR = 1.77 (95%CI:1.42, 2.21). When adjusted for depressive symptoms in the other life-stages, elevated depressive symptoms in early adulthood (OR = 1.73; 95%CI: 1.42,2.11) and late-life (OR = 1.43; 95%CI: 1.08,1.89) remained associated with cognitive impairment and were also associated with faster rates of cognitive decline (p < 0.05). CONCLUSION: Imputing depressive symptom trajectories from pooled cohorts may help expand data across the life course. Our findings suggest early adulthood depressive symptoms may be a risk factor for cognitive impairment independent of mid- or late-life depressive symptoms. BACKGROUND: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF. METHODS: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF. RESULTS: Among 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.31]; <0.01) and 15% (adjusted HR, 1.15 [95% CI, 1.05-1.25]; <0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. CONCLUSIONS: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time. Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits. Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs. Elevated common carotid artery intima-media thickness (carotid IMT) and diminished flow-mediated dilation (FMD) are early subclinical indicators of atherosclerosis. Serum total non-esterified fatty acid (NEFA) concentrations have been positively associated with subclinical atherosclerosis. The relations between individual NEFA, carotid IMT and FMD have as yet to be assessed. We investigated the associations between fasting serum individual NEFA, carotid IMT and FMD among Cardiovascular Health Study (CHS) participants with ( = 255 for carotid IMT, 301 for FMD) or without ( = 1314 for carotid IMT, 1462 for FMD) known atherosclerotic cardiovascular disease (ASCVD). Using archived samples (fasting) collected from 1996-1997 (baseline), 35 individual NEFAs were measured using gas chromatography. Carotid IMT and estimated plaque thickness (mean of maximum internal carotid IMT) were determined in 1998-1999. FMD was measured in 1997-1998. Linear regression adjusted by the Holm-Bonferroni method was used to assess relations between individual NEFA, carotid IMT and FMD. In multivariable adjusted linear regression models per SD increment, the non-esterified fatty acid conjugated linoleic acid (-18:2 CLA) was positively associated with carotid IMT [β (95% CI): 44.8 (19.2, 70.4), = 0.025] among participants with, but not without, ASCVD [2.16 (-6.74, 11.5), = 1.000]. Non-esterified -palmitoleic acid (16:1n-7) was positively associated with FMD [19.7 (8.34, 31.0), = 0.024] among participants without, but not with ASCVD. No significant associations between NEFAs and estimated plaque thickness were observed. In older adults, serum non-esterified CLA and palmitoleic acid were positively associated with carotid IMT and FMD, respectively, suggesting potential modifiable biomarkers for arteriopathy. BACKGROUND: Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF). OBJECTIVES: This study sought to evaluate whether CHIP is associated with incident HF. METHODS: CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses. RESULTS: Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction. CONCLUSIONS: CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF. BACKGROUND: Lower antioxidant serum concentrations have been linked to declines in lean mass and physical function in older adults. Yet population data on the effect of dietary antioxidants on loss of muscle strength and physical function are lacking. OBJECTIVE: We sought to determine the association of antioxidant intake [vitamin C, vitamin E, and total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin)] with annualized change in grip strength and gait speed in adults from the Framingham Offspring study. METHODS: This prospective cohort study included participants with a valid FFQ at the index examination and up to 2 prior examinations and at ≥2 measures of primary outcomes: grip strength (n = 2452) and/or gait speed (n = 2422) measured over 3 subsequent examinations. Annualized change in grip strength (kg/y) and change in gait speed (m/s/y) over the follow-up period were used. Linear regression was used to calculate β coefficients and P values, adjusting for covariates. RESULTS: Mean ± SD age of participants was 61 ± 9 y (range: 33-88 y). Median intakes (IQR, mg/d) of vitamin C, vitamin E, and total carotenoid across available examinations were 209.2 (133.1-394.2), 27.1 (7.4-199.0), and 15.3 (10.4-21.3), respectively. The mean follow-up time was ∼12 ± 2 y (range: 4.5-15.4 y). In the sex-combined sample, higher intakes of total carotenoids, lycopene, and lutein + zeaxanthin were associated with increased annualized change in grip strength [β (SE) per 10-mg higher intake/d, range: 0.0316 (0.0146) to 0.1223 (0.0603) kg/y)]. All antioxidants except for vitamin C were associated with faster gait speed [β (SE) per 10-mg higher intake/d, range: 0.00008 (0.00004) to 0.0187 (0.0081) m/s/y]. CONCLUSIONS: Higher antioxidant intake was associated with increase in grip strength and faster gait speed in this cohort of adults. This finding highlights the need for a randomized controlled trial of dietary antioxidants and their effect on muscle strength and physical function. BACKGROUND: Cut-points to define slow walking speed have largely been derived from expert opinion. METHODS: Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not. RESULTS: Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants. CONCLUSIONS: Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without. Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders. BACKGROUND: research on the association between hearing impairment and psychosocial outcomes is not only limited but also yielded mixed results. METHODS: we investigated associations between annual self-reports of hearing problems, depressive symptoms and social network strength among 5,888 adults from the Cardiovascular Health Study over a period of 9 years. Social network strength and depressive symptoms were defined using the Lubben Social Network Scale (LSNS), and the Center for Epidemiological Studies Depression Scale (CES-D). RESULTS: hearing problems were associated with weaker social networks and more depressive symptoms. These association differed for prevalent versus incident hearing problems. Participants with prevalent hearing problems scored an adjusted 0.47 points lower (95% CI: -2.20, -0.71) on the LSNS and 0.71 points higher (95% CI: 0.23, 1.19) on the CES-D than those without hearing problems. Participants with incident hearing problems had a greater decline of 0.12 points (95% CI: -0.12, -0.03) per year in social network score than individuals with no hearing problems after adjusting for confounders. Females appeared to be more vulnerable to changes in social network strength than males (P-value for interaction = 0.02), but not for changes in depressive score. Accounting for social network score did not appear to attenuate the association between hearing problems and depressive score. CONCLUSION: findings suggest that older adults with prevalent hearing problems may be more at risk for depression, but individuals with incident hearing problems may be at greater risk for a winnowing of their social network. Importance: Little is known about the association of trimethylamine N-oxide (TMAO), a novel plasma metabolite derived from L-carnitine and phosphatidylcholine, and related metabolites (ie, choline, betaine, carnitine, and butyrobetaine) with risk of death among older adults in the general population. Objective: To investigate the associations of serial measures of plasma TMAO and related metabolites with risk of total and cause-specific death (ie, deaths from cardiovascular diseases [CVDs] and non-CVDs) among older adults in the US. Design, Setting, and Participants: This prospective cohort study involved 5333 participants from the Cardiovascular Health Study-a community-based longitudinal cohort of adults aged 65 years or older-who were followed up from June 1, 1989, to December 31, 2015. Participants were from 4 communities in the US (Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania). Data were analyzed from March 17 to June 23, 2021. Exposures: Plasma TMAO, choline, betaine, carnitine, and butyrobetaine levels were measured using stored samples from baseline (June 1, 1989, to May 31, 1990, or November 1, 1992, to June 31, 1993) and follow-up examination (June 1, 1996, to May 31, 1997). Measurements were performed through stable-isotope dilution liquid chromatography with tandem mass spectrometry using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Main Outcomes and Measures: Deaths (total and cause specific) were adjudicated by a centralized Cardiovascular Health Study events committee based on information from medical records, laboratory and diagnostic reports, death certificates, and/or interviews with next of kin. The associations of each metabolite with mortality were assessed using Cox proportional hazards regression models. Results: Among 5333 participants in the analytic sample, the mean (SD) age was 73 (6) years; 2149 participants (40.3%) were male, 3184 (59.7%) were female, 848 (15.9%) were African American, 4450 (83.4%) were White, and 35 (0.01%) were of other races (12 were American Indian or Alaska Native, 4 were Asian or Pacific Islander, and 19 were of other races or ethnicities). During a median follow-up of 13.2 years (range, 0-26.9 years), 4791 deaths occurred. After adjustment for potential confounders, the hazard ratios for death from any cause (ie, total mortality) comparing extreme quintiles (fifth vs first) of plasma concentrations were 1.30 (95% CI, 1.17-1.44) for TMAO, 1.19 (95% CI, 1.08-1.32) for choline, 1.26 (95% CI, 1.15-1.40) for carnitine, and 1.26 (95% CI, 1.13-1.40) for butyrobetaine. Plasma betaine was not associated with risk of death. The extent of risk estimates was similar for CVD and non-CVD mortality. Conclusions and Relevance: In this cohort study, plasma concentrations of TMAO and related metabolites were positively associated with risk of death. These findings suggest that circulating TMAO is an important novel risk factor associated with death among older adults. Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome-wide association study to identify sCD163-associated variants. Methods and Results We measured plasma sCD163 in 5214 adults (aged ≥65 years, 58.7% women, 16.2% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow-up was 26 years. Genome-wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all-cause mortality (hazard ratio [HR], 1.08 [95% CI, 1.04-1.12] per SD increase), cardiovascular disease mortality (HR, 1.15 [95% CI, 1.09-1.21]), incident coronary heart disease (HR, 1.10 [95% CI, 1.04-1.16]), and incident heart failure (HR, 1.18 [95% CI, 1.12-1.25]). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome-wide association studies identified 38 variants on chromosome 2 near (top result rs62165726, =3.3×10),19 variants near chromosome 17 gene (rs55714927, =1.5×10), and 18 variants near chromosome 11 gene . These regions replicated in the European ancestry ADDITION-PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781 =7.1×10) in the region, and 3 variants (rs115391969 =4.3×10) near the chromosome 16 gene Conclusions Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure. We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the Trans-Omics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlation" as the fraction of phenotypic correlation explained by genetics. Finally, we quantify the enrichment of correlations between phenotypic domains, each of which is comprised of multiple phenotypes. Altogether, we demonstrate that the observed correlations between complex human phenotypes depend on the genetic background of the individuals, their gender, and their environment. BACKGROUND: Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established. METHODS: Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes. RESULTS: The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (=0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI ( interaction=0.04) and WC ( interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each). CONCLUSIONS: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes. To evaluate the association of nonesterified fatty acids (NEFA) with dysglycemia in older adults, NEFA levels were measured among participants in the Cardiovascular Health Study (United States; enrolled 1989-1993). Associations with insulin sensitivity and pancreatic β-cell function, and with incident type 2 diabetes mellitus (DM), were examined. The sample comprised 2,144 participants (aged 77.9 (standard deviation, 4.5) years). Participant data from the Cardiovascular Health Study visit in 1996-1997 was used with prospective follow-up through 2010. Fasting and postload NEFA showed significant associations with lower insulin sensitivity and pancreatic β-cell function, individually and on concurrent adjustment. Over median follow-up of 9.7 years, 236 cases of DM occurred. Postload NEFA were associated with risk of DM (per standard deviation, hazard ratio = 1.18, 95% confidence interval: 1.08, 1.29), but fasting NEFA were not (hazard ratio = 1.12, 95% confidence interval: 0.97, 1.29). The association for postload NEFA persisted after adjustment for putative intermediates, and after adjustment for fasting NEFA. Sex and body mass index modified these associations, which were stronger for fasting NEFA with DM in men but were accentuated for postload NEFA in women and among leaner individuals. Fasting and postload NEFA were related to lower insulin sensitivity and pancreatic β-cell function, but only postload NEFA were associated with increased DM. Additional study into NEFA metabolism could uncover novel potential targets for diabetes prevention in elders. OBJECTIVE: We evaluated whether measures of glucose dysregulation are associated with subclinical cardiac dysfunction, as assessed by speckle-tracking echocardiography, in an older population. METHODS: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without coronary heart disease, atrial fibrillation, or heart failure at baseline. We evaluated fasting insulin resistance (IR) with the homeostatic model of insulin resistance (HOMA-IR) and estimated the Matsuda insulin sensitivity index (ISI) and insulin secretion with an oral glucose tolerance test. Systolic and diastolic cardiac mechanics were measured with speckle-tracking analysis of echocardiograms. Multi-variable adjusted linear regression models were used to investigate associations of insulin measures and cardiac mechanics. RESULTS: Mean age for the 2433 included participants was 72.0 years, 33.6% were male, and 3.7% were black. After adjustment for age, sex, race, site, speckle-tracking analyst, echo image and quality score, higher HOMA-IR, lower Matsuda ISI, and higher insulin secretion were each associated with worse left ventricular (LV) longitudinal strain and LV early diastolic strain rate (p-value < 0.005); however, associations were significantly attenuated after adjustment for waist circumference, with the exception of Matsuda ISI and LV longitudinal strain (increase in strain per standard deviation increment in Matsuda ISI = 0.18; 95% confidence interval = 0.03-0.33). CONCLUSION: In this cross-sectional study of older adults, associations of glucose dysregulation with subclinical cardiac dysfunction were largely attenuated after adjusting for central adiposity. Importance: Higher intake of dietary fiber has been associated with lower inflammation, but whether there are differences in this association by source of dietary fiber (ie, cereal, vegetable, or fruit) has not been studied to date. Objectives: To evaluate the associations of total fiber intake and source (ie, cereal, vegetable, and fruit fiber intake) with inflammation and to evaluate whether inflammation mediates the inverse association between dietary fiber intake and cardiovascular disease (CVD). Design, Setting, and Participants: At the baseline visit (1989-1990) of 4125 adults aged 65 years or older in an ongoing US cohort study, dietary intake was assessed by a food frequency questionnaire among study participants without prevalent CVD (stroke and myocardial infarction) at enrollment. Inflammation was assessed from blood samples collected at baseline with immunoassays for markers of inflammation. Multivariable linear regression models tested the association of dietary fiber intake with inflammation. Also assessed was whether each inflammatory marker and its composite derived from principal component analysis mediated the association of baseline cereal fiber intake with development of CVD (stroke, myocardial infarction, and atherosclerotic cardiovascular death) through June 2015. Data from June 1, 1989, through June 30, 2015, were analyzed. Exposures: Total fiber intake and sources of fiber (cereal, vegetable, and fruit). Main Outcomes and Measures: Systemic markers of inflammation. Cardiovascular disease was the outcome in the mediation analysis. Results: Of 4125 individuals, 0.1% (n = 3) were Asian or Pacific Islander, 4.4% (n = 183) were Black, 0.3% (n = 12) were Native American, 95.0% (n = 3918) were White, and 0.2% (n = 9) were classified as other. Among these 4125 individuals (2473 women [60%]; mean [SD] age, 72.6 [5.5] years; 183 Black individuals [4.4%]; and 3942 individuals of other races and ethnicitites [95.6%] [ie, race and ethnicity other than Black, self-classified by participant]), an increase in total fiber intake of 5 g/d was associated with significantly lower concentrations of C-reactive protein (adjusted mean difference, -0.05 SD; 95% CI, -0.08 to -0.01 SD; P = .007) and interleukin 1 receptor antagonist (adjusted mean difference, -0.04 SD; 95% CI, -0.07 to -0.01 SD; P < .02) but with higher concentrations of soluble CD163 (adjusted mean difference, 0.05 SD; 95% CI, 0.02-0.09 SD; P = .005). Among fiber sources, only cereal fiber was consistently associated with lower inflammation. Similarly, cereal fiber intake was associated with lower CVD incidence (adjusted hazard ratio, 0.90; 95% CI, 0.81-1.00; 1941 incident cases). The proportion of the observed association of cereal fiber with CVD mediated by inflammatory markers ranged from 1.5% for interleukin 18 to 14.2% for C-reactive protein, and 16.1% for their primary principal component. Conclusions and Relevance: Results of this study suggest that cereal fiber intake was associated with lower levels of various inflammatory markers and lower risk of CVD and that inflammation mediated approximately one-sixth of the association between cereal fiber intake and CVD. Importance: Hearing and vision problems are individually associated with increased dementia risk, but the impact of having concurrent hearing and vision deficits, ie, dual sensory impairment (DSI), on risk of dementia, including its major subtypes Alzheimer disease (AD) and vascular dementia (VaD), is not well known. Objective: To evaluate whether DSI is associated with incident dementia in older adults. Design, Setting, and Participants: This prospective cohort study from the Cardiovascular Health Study (CHS) was conducted between 1992 and 1999, with as many as 8 years of follow-up. The multicenter, population-based sample was recruited from Medicare eligibility files in 4 US communities with academic medical centers. Of 5888 participants aged 65 years and older in CHS, 3602 underwent cranial magnetic resonance imaging and completed the modified Mini-Mental State Examination in 1992 to 1994 as part of the CHS Cognition Study. A total of 227 participants were excluded due to prevalent dementia, leaving a total of 3375 participants without dementia at study baseline. The study hypothesis was that DSI would be associated with increased risk of dementia compared with no sensory impairment. The association between the duration of DSI with risk of dementia was also evaluated. Data analysis was conducted from November 2019 to February 2020. Exposures: Hearing and vision impairments were collected via self-report at baseline and as many as 5 follow-up visits. Main Outcomes and Measures: All-cause dementia, AD, and VaD, classified by a multidisciplinary committee using standardized criteria. Results: A total of 2927 participants with information on hearing and vision at all available study visits were included in the analysis (mean [SD] age, 74.6 [4.8] years; 1704 [58.2%] women; 455 [15.5%] African American or Black; 2472 [85.5%] White). Compared with no sensory impairment, DSI was associated with increased risk of all-cause dementia (hazard ratio [HR], 2.60; 95% CI, 1.66-2.06; P < .001), AD (HR, 3.67; 95% CI, 2.04-6.60; P < .001) but not VaD (HR, 2.03; 95% CI, 1.00-4.09; P = .05). Conclusions and Relevance: In this cohort study, DSI was associated with increased risk of dementia, particularly AD. Evaluation of hearing and vision in older adults may help to identify those at high risk of developing dementia. BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke. METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models. RESULTS: We observed associations of intermediate monocytes, early-activated CD4 T cells, and both CD4 and CD8 T cells producing interleukin-4 after cytokine stimulation (T and T, respectively) with higher risk for incident stroke; effect sizes ranged from 35% to 62% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women. CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention. The biological mechanisms underlying decline in physical function with age remain unclear. We examined the plasma proteomic profile associated with longitudinal changes in physical function measured by gait speed and grip strength in community-dwelling adults. We applied an aptamer-based platform to assay 1154 plasma proteins on 2854 participants (60% women, aged 76 years) in the Cardiovascular Health Study (CHS) in 1992-1993 and 1130 participants (55% women, aged 54 years) in the Framingham Offspring Study (FOS) in 1991-1995. Gait speed and grip strength were measured annually for 7 years in CHS and at cycles 7 (1998-2001) and 8 (2005-2008) in FOS. The associations of individual protein levels (log-transformed and standardized) with longitudinal changes in gait speed and grip strength in two populations were examined separately by linear mixed-effects models. Meta-analyses were implemented using random-effects models and corrected for multiple testing. We found that plasma levels of 14 and 18 proteins were associated with changes in gait speed and grip strength, respectively (corrected p < 0.05). The proteins most strongly associated with gait speed decline were GDF-15 (Meta-analytic p = 1.58 × 10 ), pleiotrophin (1.23 × 10 ), and TIMP-1 (5.97 × 10 ). For grip strength decline, the strongest associations were for carbonic anhydrase III (1.09 × 10 ), CDON (2.38 × 10 ), and SMOC1 (7.47 × 10 ). Several statistically significant proteins are involved in the inflammatory responses or antagonism of activin by follistatin pathway. These novel proteomic biomarkers and pathways should be further explored as future mechanisms and targets for age-related functional decline. Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity < 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011-2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Of 33,546 participants (mean age 52 yr, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events ( = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95% confidence interval [CI], 0.80-0.82) and in NHANES (C-statistic, 0.83; 95% CI, 0.80-0.86). Among participants with predicted probabilities ⩾ 15%, 3.2 would need to undergo spirometry to detect one case of SAO. Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies. CONTEXT: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain. OBJECTIVE: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. DESIGN AND SETTING: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study. PARTICIPANTS: 5019 U.S. adults aged ≥65 years. EXPOSURE: Plasma TMAO. MAIN OUTCOME MEASURES: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400). RESULTS: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm*100 [-0.34,1.17] per TMAO doubling; men: 0.19[-1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P < 0.01). Higher TMAO was significantly associated with risk of hip fracture in adults with overweight or obesity (BMI ≥ 25) (HR [95% CI]:1.17[1.05,1.31]), but not normal or underweight. CONCLUSIONS: Among older US men and women, TMAO was not significantly associated with risk of hip fracture or BMD overall. Exploratory analyses suggested a significant association between higher TMAO and hip fracture when BMI was elevated, which merits further study. BACKGROUND: The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence. METHODS: We analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40-75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD. RESULTS: Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59-0.77) or high to non-high (HR, 0.57; 95% CI 0.41-0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29-0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26-2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84-2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69-3.42) also showed an increased risk of incident ASCVD. CONCLUSIONS: Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account. BACKGROUND AND OBJECTIVES: There are disparities in the prevalence of obesity by race, and the relationship between obesity and cognitive decline is unclear. The objective of this study was to determine whether obesity is independently associated with cognitive decline and whether the association between obesity and cognitive decline differs in Black and White adults. We hypothesized that obesity is associated with greater cognitive decline compared with normal weight and that the effect of obesity on cognitive decline is more pronounced in Black adults compared with their White counterparts. METHODS: We pooled data from 28,867 participants free of stroke and dementia (mean, SD: age 61 [10.7] years at the first cognitive assessment, 55% female, 24% Black, and 29% obese) from 6 cohorts. The primary outcome was the annual change in global cognition. We performed linear mixed-effects models with and without time-varying cumulative mean systolic blood pressure (SBP) and fasting plasma glucose (FPG). Global cognition was set to a t-score metric (mean 50, SD 10) at a participant's first cognitive assessment; a 1-point difference represents a 0.1 SD difference in global cognition across the 6 cohorts. The median follow-up was 6.5 years (25th percentile, 75th percentile: 5.03, 20.15). RESULTS: Obese participants had lower baseline global cognition than normal-weight participants (difference in intercepts, -0.36 [95% CI, -0.46 to -0.17]; < 0.001). This difference in baseline global cognition was attenuated but was borderline significant after accounting for SBP and FPG (adjusted differences in intercepts, -0.19 [95% CI, -0.39 to 0.002]; = 0.05). There was no difference in the rate of decline in global cognition between obese and normal-weight participants (difference in slope, 0.009 points/year [95% CI, -0.009 to 0.03]; = 0.32). After accounting for SBP and FPG, obese participants had a slower decline in global cognition (adjusted difference in slope, 0.03 points/year slower [95% CI, 0.01 to 0.05]; < 0.001). There was no evidence that race modified the association between body mass index and global cognitive decline ( = 0.34). DISCUSSION: These results suggest that obesity is associated with lower initial cognitive scores and may potentially attenuate declines in cognition after accounting for BP and FPG. IMPORTANCE: While the Australian National University-Alzheimer Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), and Lifestyle for Brain Health (LIBRA) dementia risk tools have been widely used, a large body of new evidence has emerged since their publication. Recently, Cognitive Health and Dementia Risk Index (CogDrisk) and CogDrisk for Alzheimer disease (CogDrisk-AD) risk tools have been developed for the assessment of dementia and AD risk, respectively, using contemporary evidence; comparison of the relative performance of these risk tools is limited. OBJECTIVE: To evaluate the performance of CogDrisk, ANU-ADRI, CAIDE, LIBRA, and modified LIBRA (LIBRA with age and sex estimates from ANU-ADRI) in estimating dementia and AD risks (with CogDrisk-AD and ANU-ADRI). DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study obtained data from the Rush Memory and Aging Project (MAP), the Cardiovascular Health Study Cognition Study (CHS-CS), and the Health and Retirement Study-Aging, Demographics and Memory Study (HRS-ADAMS). Participants who were free of dementia at baseline were included. The factors were component variables in the risk tools that included self-reported baseline demographics, medical risk factors, and lifestyle habits. The study was conducted between November 2021 and March 2023, and statistical analysis was performed from January to June 2023. MAIN OUTCOMES AND MEASURES: Risk scores were calculated based on available factors in each of these cohorts. Area under the receiver operating characteristic curve (AUC) was calculated to measure the performance of each risk score. Multiple imputation was used to assess whether missing data may have affected estimates for dementia risk. RESULTS: Among the 6107 participants in 3 validation cohorts included for this study, 2184 participants without dementia at baseline were available from MAP (mean [SD] age, 80.0 [7.6] years; 1606 [73.5%] female), 548 participants without dementia at baseline were available from HRS-ADAMS (mean [SD] age, 79.5 [6.3] years; 288 [52.5%] female), and 3375 participants without dementia at baseline were available from CHS-CS (mean [SD] age, 74.8 [4.9] years; 1994 [59.1%] female). In all 3 cohorts, a similar AUC for dementia was obtained using CogDrisk, ANU-ADRI, and modified LIBRA (MAP cohort: CogDrisk AUC, 0.65 [95% CI, 0.61-0.69]; ANU-ADRI AUC, 0.65 [95% CI, 0.61-0.69]; modified LIBRA AUC, 0.65 [95% CI, 0.61-0.69]; HRS-ADAMS cohort: CogDrisk AUC, 0.75 [95% CI, 0.71-0.79]; ANU-ADRI AUC, 0.74 [95% CI, 0.70-0.78]; modified LIBRA AUC, 0.75 [95% CI, 0.71-0.79]; CHS-CS cohort: CogDrisk AUC, 0.70 [95% CI, 0.67-0.72]; ANU-ADRI AUC, 0.69 [95% CI, 0.66-0.72]; modified LIBRA AUC, 0.70 [95% CI, 0.68-0.73]). The CAIDE and LIBRA also provided similar but lower AUCs than the 3 aforementioned tools (eg, MAP cohort: CAIDE AUC, 0.50 [95% CI, 0.46-0.54]; LIBRA AUC, 0.53 [95% CI, 0.48-0.57]). The performance of CogDrisk-AD and ANU-ADRI in estimating AD risks was also similar. CONCLUSIONS AND RELEVANCE: CogDrisk and CogDrisk-AD performed similarly to ANU-ADRI in estimating dementia and AD risks. These results suggest that CogDrisk and CogDrisk-AD, with a greater range of modifiable risk factors compared with other risk tools in this study, may be more informative for risk reduction. BACKGROUND: The 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) clinical practice guideline proposed an updated definition for heart failure (HF) stages. OBJECTIVES: This study aimed to compare prevalence and prognosis of HF stages according to classification/definition originally described in 2013 and 2022 ACC/AHA/HFSA definitions. METHODS: Study participants from 3 longitudinal cohorts (the MESA [Multi-Ethnic Study of Atherosclerosis], CHS [Cardiovascular Health Study], and the FHS [Framingham Heart Study]), were categorized into 4 HF stages according to the 2013 and 2022 criteria. Cox proportional hazards regression was used to assess predictors of progression to symptomatic HF and adverse clinical outcomes associated with each HF stage. RESULTS: Among 11,618 study participants, according to the 2022 staging, 1,943 (16.7%) were healthy, 4,348 (37.4%) were in stage A (at risk), 5,019 (43.2%) were in stage B (pre-HF), and 308 (2.7%) were in stage C/D (symptomatic HF). Compared to the classification/definition originally described in 2013, the 2022 ACC/AHA/HFSA approach resulted in a higher proportion of individuals with stage B HF (increase from 15.9% to 43.2%); this shift disproportionately involved women as well as Hispanic and Black individuals. Despite the 2022 criteria designating a greater proportion of individuals as stage B, the relative risk of progression to symptomatic HF remained similar (HR: 10.61; 95% CI: 9.00-12.51; P < 0.001). CONCLUSIONS: New standards for HF staging resulted in a substantial shift of community-based individuals from stage A to stage B. Those with stage B HF in the new system were at high risk for progression to symptomatic HF. We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals. BACKGROUND AND PURPOSE: Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atherosclerotic disease in patients with AF in the prospective population-based Cardiovascular Health Study. METHODS: We included participants aged ≥65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques). RESULTS: A total of 1398 participants were included (55.2% female, 61.7% aged 65-74 years). The maximum carotid stenosis was <50%, 50%-99%, and 100% in 94.5%, 5%, and 0.5% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6% and 8.9% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5-15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA₂DS₂-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95% confidence interval = 1.18-1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05). CONCLUSIONS: Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohort of individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population. IMPORTANCE: Sphingolipids, including ceramides and sphingomyelins, may influence the pathophysiology and risk of sudden cardiac death (SCD) through multiple biological activities. Whether the length of the fatty acid acylated to plasma sphingolipid species is associated with SCD risk is not known. OBJECTIVE: To determine whether the saturated fatty acid length of plasma ceramides and sphingomyelins influences the association with SCD risk. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, multivariable Cox proportional hazards regression models were used to examine the association of sphingolipid species with SCD risk. The study population included 4612 participants in the Cardiovascular Health Study followed up prospectively for a median of 10.2 (IQR, 5.5-11.6) years. Baseline data were collected from January 1992 to December 1995 during annual examinations. Data were analyzed from February 11, 2020, to September 9, 2023. EXPOSURES: Eight plasma sphingolipid species (4 ceramides and 4 sphingomyelins) with saturated fatty acids of 16, 20, 22, and 24 carbons. MAIN OUTCOME AND MEASURE: Association of plasma ceramides and sphingomyelins with saturated fatty acids of different lengths with SCD risk. RESULTS: Among the 4612 CHS participants included in the analysis (mean [SD] age, 77 [5] years; 2724 [59.1%] women; 6 [0.1%] American Indian; 4 [0.1%] Asian; 718 [15.6%] Black; 3869 [83.9%] White, and 15 [0.3%] Other), 215 SCD cases were identified. In adjusted Cox proportional hazards regression analyses, plasma ceramides and sphingomyelins with palmitic acid (Cer-16 and SM-16) were associated with higher SCD risk per higher SD of log sphingolipid levels (hazard ratio [HR] for Cer-16, 1.34 [95% CI, 1.12-1.59]; HR for SM-16, 1.37 [95% CI, 1.12-1.67]). Associations did not differ by baseline age, sex, race, or body mass index. No significant association of SCD with sphingolipids with very-long-chain saturated fatty acids was observed after correction for multiple testing (HR for ceramide with arachidic acid, 1.06 [95% CI, 0.90-1.24]; HR for ceramide with behenic acid, 0.92 [95% CI, 0.77-1.10]; HR for ceramide with lignoceric acid, 0.92 [95% CI, 0.77-1.09]; HR for sphingomyelin with arachidic acid, 0.83 [95% CI, 0.71-0.98]; HR for sphingomyelin with behenic acid, 0.84 [95% CI, 0.70-1.00]; HR for sphingomyelin with lignoceric acid, 0.86 [95% CI, 0.72-1.03]). CONCLUSIONS AND RELEVANCE: The findings of this large, population-based cohort study of SCD identified that higher plasma levels of Cer-16 and SM-16 were associated with higher risk of SCD. Future studies are needed to examine the underlying mechanism of these associations. Background The association of circulating trimethylamine--oxide (TMAO) with stroke has received limited attention. To address this gap, we examined the associations of serial measures of plasma TMAO with incident ischemic stroke. Methods and Results We used a prospective cohort design with data pooled from 2 cohorts. The settings were the CHS (Cardiovascular Health Study), a cohort of older adults, and the MESA (Multi-Ethnic Study of Atherosclerosis), both in the United States. We measured plasma concentrations of TMAO at baseline and again during the follow-up using high-performance liquid chromatography and mass spectrometry. We assessed the association of plasma TMAO with incident ischemic stroke using proportional hazards regression adjusted for risk factors. The combined cohorts included 11 785 participants without a history of stroke, on average 73 (CHS) and 62 (MESA) years old at baseline, including 60% (CHS) and 53% (MESA) women. We identified 1031 total incident ischemic strokes during a median 15-year follow-up in the combined cohorts. In multivariable analyses, TMAO was significantly associated with incident ischemic stroke risk (hazard ratios comparing a doubling of TMAO: 1.11 [1.03-1.18], =0.004). The association was linear over the range of TMAO concentrations and appeared restricted to those without diagnosed coronary heart disease. An association with hemorrhagic stroke was not found. Conclusions Plasma TMAO levels are associated with incident ischemic stroke in a diverse population. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005133. BACKGROUND: Frailty assessment promises to identify older adults at risk for adverse consequences following stressors and target interventions to improve health outcomes. The Physical Frailty Phenotype (PFP) is a widely-studied, well validated assessment but incorporates performance-based slow walk and grip strength criteria that challenge its use in some clinical settings. Variants replacing performance-based elements with self-reported proxies have been proposed. Our study evaluated whether commonly available disability self-reports could be substituted for the performance-based criteria in the PFP while still identifying as "frail" the same subpopulations of individuals. METHODS: Parallel analyses were conducted in 3393 female and 2495 male Cardiovascular Health Study, Round 2 participants assessed in 1989-90. Candidate self-reported proxies for the phenotype's "slowness" and "weakness" criteria were evaluated for comparable prevalence and agreement by mode of measurement. For best-performing candidates: Frailty status (3 + positive criteria out of 5) was compared for prevalence and agreement between the PFP and mostly self-reported versions. Personal characteristics were compared between those adjudicated as frail by (a) only a self-reported version; (b) only the PFP; (c) both, using bivariable analyses and multinomial logistic regression. RESULTS: Self-reported difficulty walking ½ mile was selected as a proxy for the phenotype's slowness criterion. Two self-reported weakness proxies were examined: difficulty transferring from a bed or chair or gripping with hands, and difficulty as just defined or in lifting a 10-pound bag. Prevalences matched to within 4% between self-reported and performance-based criteria in the whole sample, but in all cases the self-reported prevalence for women exceeded that for men by 11% or more. Cross-modal agreement was moderate, with by-criterion and frailty-wide Kappa statistics of 0.55-0.60 in all cases. Frail subgroups (a), (b), (c) were independently discriminated (p < 0.05) by race, BMI, and depression in women; by age in men; and by self-reported health for both. CONCLUSIONS: Commonly used self-reported disability items cannot be assumed to stand in for performance-based criteria in the PFP. We found subpopulations identified as frail by resultant phenotypes versus the original phenotype to systematically differ. Work to develop self-reported proxies that more closely replicate their objective phenotypic counterparts than standard disability self-reports is needed. X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.