02024nas 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 a
The 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/74703412nas 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/78103864nas 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/144102954nas 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/143603196nas 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/144803088nas 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/143002266nas 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/142501804nas 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/58702395nas 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/143402295nas 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/141403165nas a2200409 4500008004100000022001400041245018100055210006900236260001300305300001200318490000700330520198400337653000902321653002202330653001902352653002802371653002102399653001902420653001502439653001602454653001502470653001102485653002602496653002402522653002402546653001702570100001502587700001702602700001302619700001502632700001502647700001302662700001102675700001602686700001702702856003602719 1995 eng d a1079-564200aFibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly. Results from The Cardiovascular Health Study.0 aFibrinogen and factor VIII but not factor VII are associated wit c1995 Sep a1269-790 v153 aNo studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, fibrinogen was significantly associated with carotid artery stenosis, internal (but not common) carotid artery wall thickness, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly.
10aAged10aAged, 80 and over10aBlood Pressure10aCardiovascular Diseases10aCarotid Stenosis10aCohort Studies10aFactor VII10aFactor VIII10aFibrinogen10aHumans10aMultivariate Analysis10aProspective Studies10aRegression Analysis10aRisk Factors1 aTracy, R P1 aBovill, E, G1 aYanez, D1 aPsaty, B M1 aFried, L P1 aHeiss, G1 aLee, M1 aPolak, J, F1 aSavage, P, J uhttps://chs-nhlbi.org/node/141602401nas 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/141202060nas a2200349 4500008004100000022001400041245008100055210006900136260001300205300001100218490000700229520111600236653000901352653001801361653003001379653002801409653002401437653001501461653001601476653001501492653001101507653001201518653002001530653002401550653001801574100001501592700001801607700001701625700001701642700001501659856003601674 1995 eng d a0009-914700aLaboratory methods and quality assurance in the Cardiovascular Health Study.0 aLaboratory methods and quality assurance in the Cardiovascular H c1995 Feb a264-700 v413 aThe Cardiovascular Health Study is an observational cohort study of risk factors for cardiovascular disease in 5201 participants, ages > or = 65 years. We report the methods and quality-assurance results for blood procurement, processing, shipping, storage, and sample analysis used during the first examination period (May 1989-June 1990). The most frequent difficulty in phlebotomy and processing was the requirement of more than one venipuncture (in 2.6% of the participants). The CVs for control materials ranged from 0.93% for glucose to 10.7% for insulin; most were < 4%. In addition to standard quality-assurance methods, we applied two other methods: technical error calculation for replicates, and weighted linear regression to assess time trend in results of control materials. After outliers were excluded, technical error values ranged from 1.7 for uric acid to 18.8 for insulin. Factor VII and factor VIII had slight trends over the 12-month analysis period. Results of quality-assurance analyses used to resolve problems were successful, thereby improving the second laboratory examination.
10aAged10aBlood Glucose10aBlood Specimen Collection10aCardiovascular Diseases10aChemistry, Clinical10aFactor VII10aFactor VIII10aFibrinogen10aHumans10aInsulin10aQuality Control10aRegression Analysis10aTriglycerides1 aCushman, M1 aCornell, E, S1 aHoward, P, R1 aBovill, E, G1 aTracy, R P uhttps://chs-nhlbi.org/node/142102686nas 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/141502703nas 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/145503022nas 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/146002360nas 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/146402798nas 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/145901871nas 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/147402820nas 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/148702375nas 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/147002784nas 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/150602876nas 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/147103691nas 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/149002957nas 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/148403373nas 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/147302375nas 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/146903216nas 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/150402255nas 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/150203916nas 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/149703226nas 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/151003278nas 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/149403834nas 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/149802677nas 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/60002554nas 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/60202885nas 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/152402701nas 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/59503451nas a2200349 4500008004100000022001400041245011600055210006900171260001600240300000900256490000800265520247500273653000902748653001002757653001202767653002202779653002802801653002402829653001902853653002202872653001302894653001102907653002702918653002402945653001702969100001502986700001703001700001703018700001703035700001403052856003503066 1999 eng d a0098-748400aThe role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.0 arole of APOE epsilon4 in modulating effects of other risk factor c1999 Jul 07 a40-60 v2823 aCONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD.
OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline.
DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study.
SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively.
MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus.
RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele.
CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.
10aAged10aAging10aAlleles10aApolipoproteins E10aCardiovascular Diseases10aCognition Disorders10aCohort Studies10aDiabetes Mellitus10aGenotype10aHumans10aMental Status Schedule10aProspective Studies10aRisk Factors1 aHaan, M, N1 aShemanski, L1 aJagust, W, J1 aManolio, T A1 aKuller, L uhttps://chs-nhlbi.org/node/59702678nas 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/62403286nas 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/61003508nas a2200433 4500008004100000022001400041245012900055210006900184260001300253300001200266490000700278520228200285653001002567653003002577653002802607653001502635653002302650653003302673653001102706653001102717653001802728653001602746653001702762653001702779653002302796653002602819653003002845653001802875653001702893100002002910700001602930700001702946700001202963700001802975700001602993700001603009700001403025856003503039 2001 eng d a1047-279700aArea characteristics and individual-level socioeconomic position indicators in three population-based epidemiologic studies.0 aArea characteristics and individuallevel socioeconomic position c2001 Aug a395-4050 v113 aPURPOSE: There is growing interest in incorporating area indicators into epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual-level data from three epidemiologic studies, we investigated how different area indicators are interrelated, how measures for different sized areas compare, and the relation between area and individual-level social position indicators.
METHODS: The interrelations between 13 area indicators of wealth/income, education, occupation, and other socioenvironmental characteristics were investigated using correlation coefficients and factor analyses. The extent to which block-group measures provide information distinct from census tract measures was investigated using intraclass correlation coefficients. Loglinear models were used to investigate associations between area and individual-level indicators.
RESULTS: Correlations between area measures were generally in the 0.5--0.8 range. In factor analyses, six indicators of income/wealth, education, and occupation loaded on one factor in most geographic sites. Correlations between block-group and census tract measures were high (correlation coefficients 0.85--0.96). Most of the variability in block-group indicators was between census tracts (intraclass correlation coefficients 0.72--0.92). Although individual-level and area indicators were associated, there was evidence of important heterogeneity in area of residence within individual-level income or education categories. The strength of the association between individual and area measures was similar in the three studies and in whites and blacks, but blacks were much more likely to live in more disadvantaged areas than whites.
CONCLUSIONS: Area measures of wealth/income, education, and occupation are moderately to highly correlated. Differences between using census tract or block-group measures in contextual investigations are likely to be relatively small. Area and individual-level indicators are far from perfectly correlated and provide complementary information on living circumstances. Differences in the residential environments of blacks and whites may need to be taken into account in interpreting race differences in epidemiologic studies.
10aAdult10aBlack or African American10aCardiovascular Diseases10aDemography10aEducational Status10aFactor Analysis, Statistical10aHumans10aIncome10aLinear Models10aOccupations10aRisk Factors10aSocial Class10aSocial Environment10aSocioeconomic Factors10aStatistics, Nonparametric10aUnited States10aWhite People1 aDiez-Roux, A, V1 aKiefe, C, I1 aJacobs, D, R1 aHaan, M1 aJackson, S, A1 aNieto, F, J1 aPaton, C, C1 aSchulz, R uhttps://chs-nhlbi.org/node/65702679nas 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/62802779nas 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/63303882nas a2200481 4500008004100000022001400041245006900055210006800124260001300192300001200205490000700217520256500224653000902789653001002798653000802808653003002816653001902846653001002865653002802875653002802903653002402931653003002955653001902985653002103004653002403025653001803049653001803067653001803085653001103103653003103114653001803145653002203163100001703185700002003202700001903222700001703241700001403258700001303272700001803285700001503303710004703318856003503365 2001 eng d a1079-500600aAssociations of subclinical cardiovascular disease with frailty.0 aAssociations of subclinical cardiovascular disease with frailty c2001 Mar aM158-660 v563 aBACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology.
METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing.
RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05).
CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.
10aAged10aAnkle10aArm10aBlack or African American10aBlood Pressure10aBrain10aCardiovascular Diseases10aCarotid Artery Diseases10aCerebral Infarction10aCerebrovascular Disorders10aCohort Studies10aEchocardiography10aElectrocardiography10aFrail Elderly10aHealth Status10aHeart Failure10aHumans10aMagnetic Resonance Imaging10aUnited States10aVascular Diseases1 aNewman, A, B1 aGottdiener, J S1 aMcBurnie, M, A1 aHirsch, C, H1 aKop, W, J1 aTracy, R1 aWalston, J, D1 aFried, L P1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/64003361nas 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/63002661nas 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/64602959nas 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/63400710nas a2200241 4500008004100000022001400041245010000055210006900155260001300224300000900237490000700246653000900253653001000262653002800272653002100300653001100321653003100332100002000363700001300383700002000396700001700416856003500433 2001 eng d a0003-994200aPatterns on cranial magnetic resonance imaging in elderly people and vascular disease outcomes.0 aPatterns on cranial magnetic resonance imaging in elderly people c2001 Dec a20740 v5810aAged10aBrain10aCardiovascular Diseases10aCluster Analysis10aHumans10aMagnetic Resonance Imaging1 aLongstreth, W T1 aDiehr, P1 aBeauchamp, N, J1 aManolio, T A uhttps://chs-nhlbi.org/node/66902599nas 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/65202810nas 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/63502622nas 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/63602960nas 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/71103016nas 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/70702711nas 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/69002593nas a2200289 4500008004100000022001400041245006100055210005900116260001600175300001100191490000700202520180400209653000902013653001502022653002802037653002102065653001402086653002402100653001102124653001502135653003102150653002402181653002402205100002102229700001802250856003502268 2002 eng d a0277-671500aRegression-based variable clustering for data reduction.0 aRegressionbased variable clustering for data reduction c2002 Mar 30 a921-410 v213 aIn many studies it is of interest to cluster states, counties or other small regions in order to obtain improved estimates of disease rates or other summary measures, and a more parsimonious representation of the country as a whole. This may be the case if there are too many to summarize concisely, and/or many regions with a small number of cases. By merging the regions into larger geographic areas, we obtain more cases within each area (and hence lower standard errors for parameter estimates), as well as fewer areas to summarize in terms of disease rates. The resulting clusters should be such that regions within the same cluster are similar in terms of their disease rates. In this paper we present a clustering algorithm which uses data at the subject-specific level in order to cluster the original regions into a reduced set of larger areas. The proposed clustering algorithm expresses the clustering goals in terms of a regression framework. This formulation of the problem allows the regions to be clustered in terms of their association with the response, and confounding variables measured at the subject-specific level may be easily incorporated during the clustering process. Additionally, this framework allows estimation and testing of the association between the areas and the response. The statistical properties and performance of the algorithm were evaluated via simulation studies, and the results are promising. Additional simulations illustrate the importance of controlling for confounding variables during the clustering process, rather than after the clusters are determined. The algorithm is illustrated with data from the Cardiovascular Health Study. Although developed with a specific application in mind, the method is applicable to a wide range of problems.
10aAged10aAlgorithms10aCardiovascular Diseases10aCluster Analysis10aCognition10aComputer Simulation10aHumans10aInfarction10aMagnetic Resonance Imaging10aModels, Statistical10aRegression Analysis1 aMcClelland, R, L1 aKronmal, R, A uhttps://chs-nhlbi.org/node/68102775nas 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/70403196nas 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/75302922nas 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/73802636nas a2200481 4500008004100000022001400041245010300055210006900158260001600227300001100243490000800254520123900262653003901501653000901540653001201549653001901561653002801580653001901608653001601627653002101643653004001664653002201704653001901726653001101745653001401756653002701770653002601797653003401823653002001857653001101877653001801888100002301906700002301929700002201952700002001974700001901994700002402013700001902037700001702056700002402073700002202097856003502119 2003 eng d a1524-453900aBeta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly.0 aBeta2adrenergic receptor polymorphisms and risk of incident card c2003 Apr 22 a2021-40 v1073 aBACKGROUND: Genetic polymorphisms at codons 16 and 27 of the beta2-adrenergic receptor have been associated with altered response to sympathetic stimulation. We examined these polymorphisms in relation to cardiovascular event risk in the Cardiovascular Health Study.
METHODS AND RESULTS: A total of 808 black and 4441 white participants (mean age, 73 years) were genotyped for the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenergic receptor. There were 702 incident coronary events, 438 ischemic strokes, and 1136 combined cardiovascular events during 7 to 10 years of follow-up. Allele frequencies differed by race but not by age or hypertension status. Glu27 carriers had a lower risk of coronary events than Gln27 homozygotes (hazard ratio, 0.82; 95% CI, 0.70 to 0.95), and there was a suggestion of decreased risk among Gly16 carriers compared with Arg16 homozygotes (hazard ratio, 0.88; 95% CI, 0.72 to 1.07). There was no association of beta2-adrenergic receptor genotype with ischemic stroke or combined cardiovascular events.
CONCLUSIONS: The Glu27 allele of the beta2-adrenergic receptor was associated with a lower risk of incident coronary events in this elderly population.
10aAfrican Continental Ancestry Group10aAged10aAlleles10aBrain Ischemia10aCardiovascular Diseases10aCohort Studies10aComorbidity10aCoronary Disease10aEuropean Continental Ancestry Group10aFollow-Up Studies10aGene Frequency10aHumans10aIncidence10aLinkage Disequilibrium10aPolymorphism, Genetic10aReceptors, Adrenergic, beta-210aRisk Assessment10aStroke10aUnited States1 aHeckbert, Susan, R1 aHindorff, Lucia, A1 aEdwards, Karen, L1 aPsaty, Bruce, M1 aLumley, Thomas1 aSiscovick, David, S1 aTang, Zhonghua1 aDurda, Peter1 aKronmal, Richard, A1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/73303409nas 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/73103344nas 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/72302424nas 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/74502460nas 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/71702997nas 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/75502971nas 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/74403028nas a2200421 4500008004100000022001400041245013400055210006900189260001300258300001000271490000600281520176500287653001002052653002002062653002802082653002702110653002102137653001902158653003802177653001802215653002302233653001102256653001702267653002202284653002002306653002402326653003002350653002602380653003102406653001802437100002002455700002202475700001802497700001702515700001902532700002002551856003502571 2003 eng d a1520-951200aRecruitment of healthy adults into a study of overnight sleep monitoring in the home: experience of the Sleep Heart Health Study.0 aRecruitment of healthy adults into a study of overnight sleep mo c2003 Mar a13-240 v73 aThe Sleep Heart Health Study (SHHS) is a prospective cohort study using participants from several ongoing cardiovascular and respiratory disease research projects to investigate the relationship between sleep-disordered breathing and cardiovascular disease. This study design required unusual and different recruiting techniques to meet the study's enrollment goal of between 6000 and 6600 participants. Individuals were recruited to undergo an overnight home polysomnogram, completion of several questionnaires, and collection of a small amount of physical examination data. This article describes the methods used to recruit these participants and how these procedures influenced the final participation rate and the representativeness of SHHS to its parent cohorts. Of 30,773 people eligible for recruitment into SHHS, attempts were made to enroll 11,145 (36%). Of those contacted, 6441 ultimately agreed to participate (58%). Recruitment rates (38 to 91%) varied among sites. SHHS participants were slightly younger (63.0 vs. 65.0 years, p < 0.001), had more years of education (14.1 vs. 13.7, p < 0.001), more likely to snore (34% vs. 23%, p < 0.001), had higher Epworth sleepiness scores (7.7 vs. 6.5, p < 0.001), slightly higher higher systolic and diastolic blood pressures (127.6/73.9 vs. 127.2/72.1, p < 0.001 for diastolic only), and a slightly higher body mass index (BMI) (28.5 vs. 27.5, p < 0.001). We conclude that it is feasible to recruit existing participants from one large-scale epidemiologic study into another with a high degree of success. However, the characteristics of the new cohort may vary in several respects from their original cohorts and therefore interpretation of study results will have to consider these differences.
10aAdult10aBody Mass Index10aCardiovascular Diseases10aCatchment Area, Health10aCircadian Rhythm10aCohort Studies10aDisorders of Excessive Somnolence10aHealth Status10aHome Care Services10aHumans10aHypertension10aPatient Selection10aPolysomnography10aProspective Studies10aSeverity of Illness Index10aSleep Apnea Syndromes10aSurveys and Questionnaires10aUnited States1 aLind, Bonnie, K1 aGoodwin, James, L1 aHill, Joel, G1 aAli, Tauqeer1 aRedline, Susan1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/73602224nas 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/76003093nas 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/75603011nas 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/75703280nas 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/79803482nas 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/77703248nas a2200385 4500008004100000022001400041245012500055210006900180260001700249300001000266490000700276520210200283653000902385653002102394653002802415653001902443653001102462653003102473653002502504653000902529653002602538653001502564653002402579653002902603653002002632653001802652100002402670700002502694700002302719700002302742700002202765700001902787700002102806856003502827 2004 eng d a1538-574400aAssociations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study.0 aAssociations between renovascular disease and prevalent cardiova c2004 Jan-Feb a25-350 v383 aAtherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity >/= 1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. 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 RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p = 0.002), previous myocardial infarction (p < 0.001), >/= 25% diameter-reducing internal carotid artery stenosis (p = 0.010), increased carotid intimal medial thickness (p = 0.003), and major electrocardiographic abnormalities (p = 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.
10aAged10aArteriosclerosis10aCardiovascular Diseases10aCohort Studies10aHumans10aHypertension, Renovascular10aLongitudinal Studies10aMale10aMultivariate Analysis10aPrevalence10aProspective Studies10aRenal Artery Obstruction10aUltrasonography10aUnited States1 aEdwards, Matthew, S1 aHansen, Kimberley, J1 aCraven, Timothy, E1 aBleyer, Anthony, J1 aBurke, Gregory, L1 aLevy, Pavel, J1 aDean, Richard, H uhttps://chs-nhlbi.org/node/76500672nas a2200217 4500008004100000022001400041245010600055210006900161260001700230300000900247490000700256653000900263653002800272653002500300653001100325653001700336100002300353700002200376700002100398856003500419 2004 eng d a1076-746000aThe Cardiovascular Health Study: a national treasure of cardiovascular information about the elderly.0 aCardiovascular Health Study a national treasure of cardiovascula c2004 Mar-Apr a57-80 v1310aAged10aCardiovascular Diseases10aGeriatric Assessment10aHumans10aRisk Factors1 aWenger, Nanette, K1 aWeber, Michael, A1 aScheidt, Stephen uhttps://chs-nhlbi.org/node/76900699nas 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/77302653nas a2200241 4500008004100000022001400041245010400055210006900159260001300228300000900241490000700250520190000257653001502157653002802172653002502200653003702225653001502262653001102277653002702288653002402315110003702339856003502376 2004 eng d a1741-826700aCollaborative meta-analysis of prospective studies of plasma fibrinogen and cardiovascular disease.0 aCollaborative metaanalysis of prospective studies of plasma fibr c2004 Feb a9-170 v113 aBACKGROUND: Many long-term studies have reported on associations of plasma fibrinogen concentration with cardiovascular disease, but few have been large enough to provide reliable estimates in different circumstances. Moreover, most published prospective studies have related disease risk only to baseline values of plasma fibrinogen (which can lead to substantial underestimation of any risk relationships) and have corrected only for baseline values of possible confounding factors (which can lead to residual biases).
OBJECTIVES: By appropriate combination of data from individual participants from all relevant prospective studies in a systematic 'meta-analysis', with correction for regression dilution, the Fibrinogen Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age- and sex-specific associations of plasma fibrinogen with coronary heart disease (and, where data are sufficient, with other vascular diseases). It will also help to determine to what extent such associations are independent of possible confounding factors.
METHODS: A central database has been established containing data on plasma fibrinogen, sex and other potential confounding factors, age at baseline fibrinogen measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of fibrinogen and potential confounding factors is being sought to allow study-specific correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available prospective studies of plasma fibrinogen will yield information on more than 10000 incident cardiovascular deaths and events among the approximately 200000 total participants who have been monitored, on average, for about 10 years.
10aBiomarkers10aCardiovascular Diseases10aCooperative Behavior10aData Interpretation, Statistical10aFibrinogen10aHumans10aMeta-Analysis as Topic10aProspective Studies1 aFibrinogen Studies Collaboration uhttps://chs-nhlbi.org/node/78502237nas a2200337 4500008004100000022001400041245008600055210006900141260001700210300001100227490000700238520129400245653000901539653002101548653002801569653001401597653001801611653001301629653002101642653001101663653001501674653003001689653001701719653001201736100002501748700002001773700002201793700002501815700002401840856003501864 2004 eng d a1076-746000aLifestyles of older adults: can we influence cardiovascular risk in older adults?0 aLifestyles of older adults can we influence cardiovascular risk c2004 May-Jun a153-600 v133 aInfluences of lifestyle habits on cardiovascular disease risk among older adults are not well established. The authors present evidence from the Cardiovascular Health Study that dietary, physical activity, and smoking habits assessed late in life are associated with cardiovascular disease risk among adults aged 65 years or older. Persons consuming fatty fish twice per week had a 47% lower risk of coronary death compared with those who consumed fatty fish less than once per month, while cereal fiber intake (about two whole-grain bread slices per day) was associated with a 14% lower risk of myocardial infarction or stroke. Modest alcohol intake (1-6 drinks per week) predicted the fewest subclinical cerebrovascular abnormalities. Compared with little activity, moderate and high leisure-time activity predicted 28% and 44% lower mortality, respectively, while compared with nonexercisers, low, moderate, and high exercise intensity predicted 30%, 37%, and 53% more years of healthy life, respectively. Former and current smokers had 25% and 44% fewer years of healthy life than those who never smoked; lifetime smoking (pack-years) predicted higher mortality. Clinical practice and public health implications, gaps in knowledge, and future research directions are summarized.
10aAged10aAlcohol Drinking10aCardiovascular Diseases10aDiet Fads10aDietary Fiber10aExercise10aFeeding Behavior10aHumans10aLife Style10aPredictive Value of Tests10aRisk Factors10aSmoking1 aMozaffarian, Dariush1 aFried, Linda, P1 aBurke, Gregory, L1 aFitzpatrick, Annette1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/77900961nas a2200313 4500008004100000022001400041245010900055210006900164260001700233300001000250490000700260653000900267653002800276653002400304653002800328653002200356653004200378653001800420653001100438653002000449653001700469653002500486653001700511100002400528700002000552700001900572700002100591856003500612 2004 eng d a1076-746000aMedications and cardiovascular health in older adults: room for improvement in prevention and treatment.0 aMedications and cardiovascular health in older adults room for i c2004 May-Jun a161-70 v1310aAged10aAntihypertensive Agents10aAtrial Fibrillation10aCardiovascular Diseases10aDiabetes Mellitus10aHealth Knowledge, Attitudes, Practice10aHeart Failure10aHumans10aHyperlipidemias10aHypertension10aHypolipidemic Agents10aRisk Factors1 aRhoads, Caroline, S1 aPsaty, Bruce, M1 aOlson, Jean, L1 aFurberg, Curt, D uhttps://chs-nhlbi.org/node/78002977nas 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/80902657nas 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/78702879nas 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/76402390nas 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/81102748nas 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/75201906nas a2200313 4500008004100000022001400041245010300055210006900158260001700227300001100244490000700255520098400262653000901246653002801255653002801283653001801311653001101329653002501340653001501365653002001380653001701400100002301417700002101440700002301461700002101484700002001505710003201525856003501557 2004 eng d a1076-746000aSubclinical cardiovascular disease in older adults: insights from the Cardiovascular Health Study.0 aSubclinical cardiovascular disease in older adults insights from c2004 May-Jun a137-510 v133 aKnowledge about the epidemiology of subclinical cardiovascular disease (SCVD) in older adults may hold the key for improved opportunities for primary prevention of cardiovascular disease (CVD), a top clinical and public health priority. This review reports findings on the prevalence of SCVD and the ability of SCVD measures to predict incident and adverse outcomes from one of the largest (N=5888) and most comprehensive prospective observational studies on SCVD in older adults, the Cardiovascular Health Study. According to a composite index that combined SCVD measures from different vascular beds, the overall prevalence of SCVD was 37%, making it as common as clinically overt CVD in older adults. SCVD measures strongly predicted incident CVD, stroke, mortality, frailty, and physical and cognitive decline, even after adjustment for traditional CVD risk factors. Ongoing research will address the potential use of SCVD for clinical decision making in older adults.
10aAged10aCardiovascular Diseases10aCoronary Artery Disease10aHeart Failure10aHumans10aLongitudinal Studies10aPrevalence10aRisk Assessment10aRisk Factors1 aChaves, Paulo, H M1 aKuller, Lewis, H1 aO'Leary, Daniel, H1 aManolio, Teri, A1 aNewman, Anne, B1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/77802841nas 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/77203889nas a2200337 4500008004100000022001400041245011100055210006900166260001600235300001200251490000800263520291100271653000903182653002803191653002003219653001103239653002003250653002503270653001703295100002403312700002003336700001803356700002103374700001703395700002903412700002003441700001703461700002103478700001703499856003503516 2005 eng d a1538-359800aCardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors.0 aCardiovascular mortality risk in chronic kidney disease comparis c2005 Apr 13 a1737-450 v2933 aCONTEXT: Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.
OBJECTIVE: To compare traditional and novel risk factors as predictors of cardiovascular mortality.
DESIGN, SETTING, AND PATIENTS: A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.
MAIN OUTCOME MEASURES: Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.
RESULTS: Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference = .15).
CONCLUSIONS: Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.
10aAged10aCardiovascular Diseases10aChronic Disease10aHumans10aKidney Diseases10aLongitudinal Studies10aRisk Factors1 aShlipak, Michael, G1 aFried, Linda, F1 aCushman, Mary1 aManolio, Teri, A1 aPeterson, Do1 aStehman-Breen, Catherine1 aBleyer, Anthony1 aNewman, Anne1 aSiscovick, David1 aPsaty, Bruce uhttps://chs-nhlbi.org/node/83103855nas 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/82603216nas 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/84003025nas 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/83303094nas 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/86503543nas 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/81703279nas 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/83602852nas 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/85503069nas 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/84603299nas 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/87801665nas 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/94102437nas 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/86303674nas 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/87704065nas a2200433 4500008004100000022001400041245011900055210006900174260001600243300001100259490000800270520281000278653000903088653001503097653002803112653001503140653001503155653001403170653003103184653001103215653001103226653002503237653001403262653003203276653003303308653001703341100002403358700001603382700002003398700002003418700002003438700002903458700002403487700002203511700001703533700002203550700002403572856003503596 2006 eng d a1539-370400aCystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.0 aCystatin C and prognosis for cardiovascular and kidney outcomes c2006 Aug 15 a237-460 v1453 aBACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).
OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.
DESIGN: Cohort study.
SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.
PARTICIPANTS: 4663 elderly persons.
MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).
RESULTS: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.
LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.
CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.
10aAged10aBiomarkers10aCardiovascular Diseases10aCreatinine10aCystatin C10aCystatins10aGlomerular Filtration Rate10aHumans10aKidney10aLongitudinal Studies10aPrognosis10aProportional Hazards Models10aRenal Insufficiency, Chronic10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aNewman, Anne, B1 aStehman-Breen, Catherine1 aSeliger, Stephen, L1 aKestenbaum, Brian1 aPsaty, Bruce1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/91203633nas a2200517 4500008004100000022001400041245016400055210006900219260001300288300001100301490000700312520215100319653001002470653002202480653001602502653000902518653001202527653002002539653002802559653002102587653001902608653000802627653004002635653001902675653002202694653001102716653001102727653001702738653002202755653002202777653001002799653002502809653000902834653001602843653001802859653002402877653001802901100002502919700002402944700002302968700002502991700002203016700002103038700002103059856003503080 2006 eng d a0026-049500aLipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation.0 aLipoprotein subclass and particle size differences in AfroCaribb c2006 Jan a96-1020 v553 aDespite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.
10aAdult10aAfrican Americans10aAge Factors10aAged10aAlleles10aBody Mass Index10aCardiovascular Diseases10aCaribbean Region10aCohort Studies10aDNA10aEuropean Continental Ancestry Group10aGene Frequency10aGenetic Variation10aHumans10aLipase10aLipoproteins10aLipoproteins, HDL10aLipoproteins, LDL10aLiver10aLongitudinal Studies10aMale10aMiddle Aged10aParticle Size10aTrinidad and Tobago10aUnited States1 aMiljkovic-Gacic, Iva1 aBunker, Clareann, H1 aFerrell, Robert, E1 aKammerer, Candace, M1 aEvans, Rhobert, W1 aPatrick, Alan, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/87203809nas 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/91802947nas 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/92302785nas a2200361 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520173700263653000902000653002202009653002002031653001802051653002802069653002702097653002202124653002202146653001102168653002602179653001702205653001802222653001702240100002302257700002402280700002102304700001902325700002402344700002002368856003502388 2006 eng d a0149-599200aNew-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study.0 aNewonset diabetes and risk of allcause and cardiovascular mortal c2006 Sep a2012-70 v293 aOBJECTIVE: Cardiovascular risk associated with new-onset diabetes is not well characterized. We hypothesized that risk of all-cause and cardiovascular mortality would be similar among participants with and without new-onset diabetes in the first years of follow-up and rise over time for new-onset diabetes.
RESEARCH DESIGN AND METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of cardiovascular risk factors in adults aged > or =65 years. We used CHS participants to define a cohort (n = 282) with new-onset diabetes during 11 years of follow-up. New-onset diabetes was defined by initiation of antidiabetes medication or by fasting plasma glucose >125 mg/dl among CHS participants without diabetes at study entry. Three CHS participants without diabetes were matched for age, sex, and race to each participant with new-onset diabetes at the time of diabetes identification (n = 837). Survival analysis provided adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality.
RESULTS: During a median of 5.9 years of follow-up, there were 352 deaths, of which 41% were cardiovascular. In adjusted analyses, new-onset diabetes was associated with an HR of 1.9 (95% CI 1.4-2.5) for all-cause and 2.2 (1.4-3.4) for cardiovascular mortality compared with no diabetes. Mortality risks were elevated within 2 years of onset, especially cardiovascular risk (4.3 [95% CI 1.7-10.8]), and did not increase over time.
CONCLUSIONS: Our findings indicate that there may be a mortality differential soon after diabetes onset in older adults and suggest that long-term macrovascular damage from atherosclerosis may not be primarily responsible for increased risk.
10aAged10aAged, 80 and over10aAtherosclerosis10aBlood Glucose10aCardiovascular Diseases10aDiabetes Complications10aDiabetes Mellitus10aFollow-Up Studies10aHumans10aKaplan-Meier Estimate10aRisk Factors10aSurvival Rate10aTime Factors1 aSmith, Nicholas, L1 aBarzilay, Joshua, I1 aKronmal, Richard1 aLumley, Thomas1 aEnquobahrie, Daniel1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/91403255nas 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/89803298nas 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/88003566nas 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/88602331nas 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/90902454nas 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/93503099nas 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/94903594nas 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/96703135nas 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/94002953nas 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/96203097nas 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/99704735nas a2200925 4500008004100000022001400041245013000055210006900185260001300254300000900267490000700276520238700283653005102670653002802721653001102749653002202760110003402782700001802816700001502834700001302849700001502862700001502877700001402892700001502906700001602921700001602937700001402953700001502967700001602982700001202998700001503010700001603025700001403041700001503055700002003070700001603090700001503106700001403121700001603135700002003151700001403171700001303185700001403198700001403212700001203226700001703238700001503255700002203270700001403292700001403306700002103320700001403341700001903355700002003374700001503394700001403409700001803423700001503441700001503456700002703471700001403498700001803512700001703530700001503547700001403562700001003576700001403586700001703600700001603617700001603633700001503649700002303664700001503687700001603702700001603718700001403734700001403748700001203762856003503774 2007 eng d a1741-826700aCollaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases.0 aCollaborative metaanalysis of individual participant data from o c2007 Feb a3-110 v143 aBACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors.
OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes.
METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aCardiovascular Diseases10aHumans10aPhospholipases A21 aLp-PLA2 Studies Collaboration1 aBallantyne, C1 aCushman, M1 aPsaty, B1 aFurberg, C1 aKhaw, K, T1 aSandhu, M1 aOldgren, J1 aRossi, G, P1 aMaiolino, G1 aCesari, M1 aLenzini, L1 aJames, S, K1 aRimm, E1 aCollins, R1 aAnderson, J1 aKoenig, W1 aBrenner, H1 aRothenbacher, D1 aBerglund, G1 aPersson, M1 aBerger, P1 aBrilakis, E1 aMcConnell, J, P1 aKoenig, W1 aSacco, R1 aElkind, M1 aTalmud, P1 aRimm, E1 aCannon, C, P1 aPackard, C1 aBarrett-Connor, E1 aHofman, A1 aKardys, I1 aWitteman, J, C M1 aCriqui, M1 aCorsetti, J, P1 aRainwater, D, L1 aMoss, A, J1 aRobins, S1 aBloomfield, H1 aCollins, D1 aPackard, C1 aWassertheil-Smoller, S1 aRidker, P1 aBallantyne, C1 aCannon, C, P1 aCushman, M1 aDanesh, J1 aGu, D1 aHofman, A1 aNelson, J, J1 aThompson, S1 aZalewski, A1 aZariffa, N1 aDi Angelantonio, E1 aKaptoge, S1 aThompson, A1 aThompson, S1 aWalker, M1 aWatson, S1 aWood, A uhttps://chs-nhlbi.org/node/94302577nas 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/99208392nas a2202725 4500008004100000022001400041245020200055210006900257260000900326300001100335490000700346520180300353653001302156653001502169653002802184653002302212653001302235653001102248653001702259653002002276653001102296653002202307653002402329653001702353653001802370110004002388700001402428700001302442700001402455700001902469700001502488700001202503700001502515700001602530700001502546700001702561700002002578700001502598700001802613700002202631700001702653700001502670700001402685700001402699700001202713700001202725700001502737700001602752700002002768700001702788700001602805700001702821700001802838700002102856700001802877700001502895700001502910700001502925700001502940700002302955700002302978700002203001700001703023700001603040700001403056700001503070700001503085700001403100700001603114700001903130700001903149700001403168700001603182700001403198700001603212700001603228700001503244700001403259700001503273700001803288700002003306700001503326700001403341700001803355700001803373700001603391700002103407700001503428700001503443700001803458700002003476700001703496700001403513700001703527700001503544700001503559700001303574700001703587700001803604700001403622700001603636700001803652700001403670700001303684700001403697700001803711700001703729700001703746700001603763700001703779700001503796700002203811700001203833700001103845700001203856700001103868700001603879700001203895700001703907700001503924700001803939700001803957700001903975700001203994700002104006700001304027700001404040700001504054700001604069700001604085700001504101700001404116700001704130700001204147700001404159700001404173700001504187700001404202700001404216700001704230700001704247700001404264700001804278700001904296700001704315700001604332700002004348700001204368700001304380700001304393700001604406700001304422700001904435700001404454700001404468700002304482700001504505700001604520700001304536700001704549700001504566700001504581700001604596700001504612700001404627700001404641700001604655700001804671700001904689700002204708700001504730700001904745700001604764700001604780700001804796700001604814700001604830700001604846700001404862700001604876700001404892700002204906700001704928700001704945700001804962700001704980700001304997700001205010700001305022700001205035700001605047700001605063700001705079700001705096700001705113700001805130700001605148700001405164700001305178700001205191700001405203700001805217700001505235700001505250700001505265700001405280700001605294700001205310700001705322700001005339700001705349700002005366700001605386700001505402700002305417700001505440700001705455700001305472700001605485700001305501700001105514700001405525700001605539700001605555700001405571700001505585700001605600700001505616856003505631 2007 eng d a0393-299000aThe Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.0 aEmerging Risk Factors Collaboration analysis of individual data c2007 a839-690 v223 aMany long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
10aAlbumins10aBiomarkers10aCardiovascular Diseases10aDatabases, Factual10aFar East10aHumans10aInflammation10aLeukocyte Count10aLipids10aLipoproteins, HDL10aProspective Studies10aRisk Factors10aTriglycerides1 aEmerging Risk Factors Collaboration1 aDanesh, J1 aErqou, S1 aWalker, M1 aThompson, S, G1 aTipping, R1 aFord, C1 aPressel, S1 aWalldius, G1 aJungner, I1 aFolsom, A, R1 aChambless, L, E1 aKnuiman, M1 aWhincup, P, H1 aWannamethee, S, G1 aMorris, R, W1 aWilleit, J1 aKiechl, S1 aSanter, P1 aMayr, A1 aWald, N1 aEbrahim, S1 aLawlor, D A1 aYarnell, J, W G1 aGallacher, J1 aCasiglia, E1 aTikhonoff, V1 aNietert, P, J1 aSutherland, S, E1 aBachman, D, L1 aKeil, J, E1 aCushman, M1 aPsaty, B M1 aTracy, R P1 aTybjaerg-Hansen, A1 aNordestgaard, B, G1 aFrikke-Schmidt, R1 aGiampaoli, S1 aPalmieri, L1 aPanico, S1 aVanuzzo, D1 aPilotto, L1 aSimons, L1 aMcCallum, J1 aFriedlander, Y1 aFowkes, F, G R1 aLee, A, J1 aSmith, F, B1 aTaylor, J1 aGuralnik, J1 aPhillips, C1 aWallace, R1 aBlazer, D1 aKhaw, K, T1 aJansson, J, H1 aDonfrancesco, C1 aSalomaa, V1 aHarald, K1 aJousilahti, P1 aVartiainen, E1 aWoodward, M1 aD'Agostino, R, B1 aWolf, P, A1 aVasan, R S1 aPencina, M, J1 aBladbjerg, E, M1 aJorgensen, T1 aMoller, L1 aJespersen, J1 aDankner, R1 aChetrit, A1 aLubin, F1 aRosengren, A1 aWilhelmsen, L1 aLappas, G1 aEriksson, H1 aBjorkelund, C1 aCremer, P1 aNagel, D1 aTilvis, R1 aStrandberg, T1 aRodriguez, B1 aBouter, L, M1 aHeine, R, J1 aDekker, J, M1 aNijpels, G1 aStehouwer, C, D A1 aRimm, E1 aPai, J1 aSato, S1 aIso, H1 aKitamura, A1 aNoda, H1 aGoldbourt, U1 aSalomaa, V1 aSalonen, J, T1 aNyyssönen, K1 aTuomainen, T-P1 aDeeg, D1 aPoppelaars, J, L1 aMeade, T1 aCooper, J1 aHedblad, B1 aBerglund, G1 aEngstrom, G1 aDöring, A1 aKoenig, W1 aMeisinger, C1 aMraz, W1 aKuller, L1 aSelmer, R1 aTverdal, A1 aNystad, W1 aGillum, R1 aMussolino, M1 aHankinson, S1 aManson, J1 aDe Stavola, B1 aKnottenbelt, C1 aCooper, J, A1 aBauer, K, A1 aRosenberg, R, D1 aSato, S1 aNaito, Y1 aHolme, I1 aNakagawa, H1 aMiura, H1 aDucimetiere, P1 aJouven, X1 aCrespo, C1 aGarcia-Palmieri, M1 aAmouyel, P1 aArveiler, D1 aEvans, A1 aFerrieres, J1 aSchulte, H1 aAssmann, G1 aShepherd, J1 aPackard, C1 aSattar, N1 aCantin, B1 aLamarche, B1 aDesprés, J-P1 aDagenais, G, R1 aBarrett-Connor, E1 aWingard, D1 aBettencourt, R1 aGudnason, V1 aAspelund, T1 aSigurdsson, G1 aThorsson, B1 aTrevisan, M1 aWitteman, J1 aKardys, I1 aBreteler, M1 aHofman, A1 aTunstall-Pedoe, H1 aTavendale, R1 aLowe, G, D O1 aBen-Shlomo, Y1 aHoward, B, V1 aZhang, Y1 aBest, L1 aUmans, J1 aOnat, A1 aMeade, T, W1 aNjolstad, I1 aMathiesen, E1 aLochen, M, L1 aWilsgaard, T1 aGaziano, J, M1 aStampfer, M1 aRidker, P1 aUlmer, H1 aDiem, G1 aConcin, H1 aRodeghiero, F1 aTosetto, A1 aBrunner, E1 aShipley, M1 aBuring, J1 aCobbe, S, M1 aFord, I1 aRobertson, M1 aHe, Y1 aIbanez, A, M1 aFeskens, E, J M1 aKromhout, D1 aCollins, R1 aDi Angelantonio, E1 aKaptoge, S1 aLewington, S1 aOrfei, L1 aPennells, L1 aPerry, P1 aRay, K1 aSarwar, N1 aScherman, M1 aThompson, A1 aWatson, S1 aWensley, F1 aWhite, I, R1 aWood, A, M uhttps://chs-nhlbi.org/node/98403584nas 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/98203065nas 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/93602852nas 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/92203109nas 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/96502586nas 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/93003388nas 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/98502245nas 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/90702703nas 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/103902837nas 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/97602927nas 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/101902746nas 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/101502806nas 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/98603226nas 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/102201807nas 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/105002896nas 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/100803343nas 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/102403196nas 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/99903076nas 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/106203134nas 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/101603435nas 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/102103049nas 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/113003161nas 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/115302610nas 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/107203044nas 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/105703764nas 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/115401931nas a2200241 4500008004100000022001400041245012100055210006900176260001600245300001200261490000700273520115700280653000901437653002801446653002601474653001501500653002701515653002401542653002601566653002401592110003701616856003601653 2009 eng d a0277-671500aCorrecting for multivariate measurement error by regression calibration in meta-analyses of epidemiological studies.0 aCorrecting for multivariate measurement error by regression cali c2009 Mar 30 a1067-920 v283 aWithin-person variability in measured values of multiple risk factors can bias their associations with disease. The multivariate regression calibration (RC) approach can correct for such measurement error and has been applied to studies in which true values or independent repeat measurements of the risk factors are observed on a subsample. We extend the multivariate RC techniques to a meta-analysis framework where multiple studies provide independent repeat measurements and information on disease outcome. We consider the cases where some or all studies have repeat measurements, and compare study-specific, averaged and empirical Bayes estimates of RC parameters. Additionally, we allow for binary covariates (e.g. smoking status) and for uncertainty and time trends in the measurement error corrections. Our methods are illustrated using a subset of individual participant data from prospective long-term studies in the Fibrinogen Studies Collaboration to assess the relationship between usual levels of plasma fibrinogen and the risk of coronary heart disease, allowing for measurement error in plasma fibrinogen and several confounders.
10aBias10aCardiovascular Diseases10aEpidemiologic Studies10aFibrinogen10aMeta-Analysis as Topic10aModels, Statistical10aMultivariate Analysis10aRegression Analysis1 aFibrinogen Studies Collaboration uhttps://chs-nhlbi.org/node/107802544nas 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/110801824nas a2200241 4500008004100000022001400041245010400055210006900159260001300228300001100241490001400252520108000266653002801346653003801374653003401412653001101446653002801457653001701485100001301502700001601515700001501531856003601546 2009 eng d a1538-783600aGenome-wide association studies of cardiovascular risk factors: design, conduct and interpretation.0 aGenomewide association studies of cardiovascular risk factors de c2009 Jul a308-110 v7 Suppl 13 aRelying on known biology, candidate-gene studies have been only modestly successful in identifying genetic variants associated with cardiovascular risk factors. Genome-wide association (GWA) studies, in contrast, allow broad scans across millions of loci in search of unsuspected genetic associations with phenotypes. The large numbers of statistical tests in GWA studies and the large sample sizes required to detect modest-sized associations have served as a powerful incentive for the development of large collaborative efforts such as the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. This article uses published data on three phenotypes, fibrinogen, uric acid, and electrocardiographic QT interval duration, from the CHARGE Consortium to describe several methodologic issues in the design, conduct, and interpretation of GWA studies, including the use of imputation and the need for additional genotyping. Even with large studies, novel genetic loci explain only a small proportion of the variance of cardiovascular phenotypes.
10aCardiovascular Diseases10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aQuantitative Trait Loci10aRisk Factors1 aBis, J C1 aGlazer, N L1 aPsaty, B M uhttps://chs-nhlbi.org/node/111702540nas 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/106903110nas 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/113902825nas 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/108103520nas 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/107502919nas 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/109302675nas 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/114402624nas 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/110302827nas 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/110203160nas 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/112302525nas a2200385 4500008004100000022001400041245017000055210006900225260000900294300001000303490000700313520137000320653000901690653002201699653001001721653002801731653002401759653001101783653001101794653002401805653002501829653000901854653003001863653003701893653002401930653001701954653001401971653001801985100002102003700002002024700001902044700001502063700002502078856003602103 2009 eng d a1423-020800aUsing telephone and informant assessments to estimate missing Modified Mini-Mental State Exam scores and rates of cognitive decline. The cardiovascular health study.0 aUsing telephone and informant assessments to estimate missing Mo c2009 a55-650 v333 aAIM: 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.
10aAged10aAged, 80 and over10aAging10aCardiovascular Diseases10aCognition Disorders10aFemale10aHumans10aInterviews as Topic10aLongitudinal Studies10aMale10aPredictive Value of Tests10aPsychiatric Status Rating Scales10aRegression Analysis10aRisk Factors10aROC Curve10aUnited States1 aArnold, Alice, M1 aNewman, Anne, B1 aDermond, Norma1 aHaan, Mary1 aFitzpatrick, Annette uhttps://chs-nhlbi.org/node/109702881nas a2200385 4500008004100000022001400041245009900055210006900154260001300223300001100236490000700247520182100254653000902075653001602084653002802100653001502128653001502143653001102158653003102169653001802200653001102218653000902229653002602238653001702264100002002281700001602301700002102317700002002338700001302358700002002371700002402391700002402415700002002439856003602459 2010 eng d a1460-238500aAlbuminuria, impaired kidney function and cardiovascular outcomes or mortality in the elderly.0 aAlbuminuria impaired kidney function and cardiovascular outcomes c2010 May a1560-70 v253 aBACKGROUND: 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.
10aAged10aAlbuminuria10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aMale10aMyocardial Infarction10aRisk Factors1 aRifkin, Dena, E1 aKatz, Ronit1 aChonchol, Michel1 aFried, Linda, F1 aCao, Jie1 ade Boer, Ian, H1 aSiscovick, David, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/114902789nas a2200409 4500008004100000022001400041245011600055210006900171260000900240300001200249490000800261520159600269653000901865653001501874653002301889653002801912653001901940653002801959653001101987653002201998653003102020653001102051653002602062653002502088653000902113653003002122100002002152700001602172700002002188700002202208700002502230700002002255700002402275700002402299700002002323856003602343 2010 eng d a1660-211000aAssociation between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.0 aAssociation between baseline kidney function and change in CRP a c2010 ac114-210 v1153 aBACKGROUND: 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.
10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney Function Tests10aLongitudinal Studies10aMale10aResidence Characteristics1 aRifkin, Dena, E1 aKatz, Ronit1 aFried, Linda, F1 aKestenbaum, Bryan1 aJenny, Nancy, Swords1 aNewman, Anne, B1 aSiscovick, David, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/119003367nas a2200481 4500008004100000022001400041245009900055210006900154260001300223300001100236490000700247520202200254653000902276653002202285653001502307653002302322653002802345653002002373653001502393653002402408653002802432653001202460653001102472653001302483653001902496653001802515653001102533653002702544653000902571653002602580653002202606653001602628653003702644653001702681653002602698100001902724700001902743700001802762700002002780700002502800700002402825856003602849 2010 eng d a1090-213900aAssociation between depressive symptoms and fibrosis markers: the Cardiovascular Health Study.0 aAssociation between depressive symptoms and fibrosis markers the c2010 Feb a229-350 v243 aOBJECTIVE: 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.
10aAged10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCollagen Type I10aDepression10aElectrocardiography10aEndomyocardial Fibrosis10aFatigue10aFemale10aFibrosis10aHealth Surveys10aHeart Failure10aHumans10aInflammation Mediators10aMale10aMultivariate Analysis10aPeptide Fragments10aProcollagen10aPsychiatric Status Rating Scales10aRisk Factors10aSocioeconomic Factors1 aKop, Willem, J1 aKuhl, Emily, A1 aBarasch, Eddy1 aJenny, Nancy, S1 aGottlieb, Stephen, S1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/113203876nas a2200385 4500008004100000022001400041245015500055210006900210260001600279300001300295490000800308520273900316653000903055653001503064653002803079653001903107653001103126653001803137653001103155653001403166653000903180653003003189653000903219653003203228653001503260653001803275100003003293700002303323700002703346700002403373700001903397700001403416700002403430856003603454 2010 eng d a1538-359800aAssociation of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.0 aAssociation of serial measures of cardiac troponin T using a sen c2010 Dec 08 a2494-5020 v3043 aCONTEXT: 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.
10aAged10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aPredictive Value of Tests10aRisk10aSensitivity and Specificity10aTroponin T10aUnited States1 adeFilippi, Christopher, R1 ade Lemos, James, A1 aChristenson, Robert, H1 aGottdiener, John, S1 aKop, Willem, J1 aZhan, Min1 aSeliger, Stephen, L uhttps://chs-nhlbi.org/node/124504577nas a2200337 4500008004100000022001400041245012700055210006900182260001300251300001100264490000700275520357600282653000903858653002803867653001903895653001103914653001103925653002003936653000903956653001703965653001703982653003703999100002304036700002304059700002404082700002504106700002504131700002204156700002504178856003604203 2010 eng d a1523-683800aAssociations between renal duplex parameters and adverse cardiovascular events in the elderly: a prospective cohort study.0 aAssociations between renal duplex parameters and adverse cardiov c2010 Feb a281-900 v553 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aCohort Studies10aFemale10aHumans10aKidney Diseases10aMale10aRenal Artery10aRisk Factors10aUltrasonography, Doppler, Duplex1 aPearce, Jeffrey, D1 aCraven, Timothy, E1 aEdwards, Matthew, S1 aCorriere, Matthew, A1 aCrutchley, Teresa, A1 aFleming, Shawn, H1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/116303245nas a2200433 4500008004100000022001400041245014400055210006900199260001300268300001100281490000700292520199000299653000902289653003802298653001502336653002302351653002802374653001902402653001902421653001602440653002402456653002402480653001102504653002202515653001502537653001102552653001702563653001802580653002002598653000902618653001702627100001902644700002202663700002202685700002402707700002002731700002402751856003602775 2010 eng d a1534-779600aAutonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression.0 aAutonomic nervous system dysfunction and inflammation contribute c2010 Sep a626-350 v723 aOBJECTIVE: 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.
10aAged10aAutonomic Nervous System Diseases10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCause of Death10aCohort Studies10aComorbidity10aDepressive Disorder10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Rate10aHumans10aInflammation10aInterleukin-610aLeukocyte Count10aMale10aRisk Factors1 aKop, Willem, J1 aStein, Phyllis, K1 aTracy, Russell, P1 aBarzilay, Joshua, I1 aSchulz, Richard1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/121602853nas a2200373 4500008004100000022001400041245013400055210006900189260001300258300001000271490000700281520177600288653003102064653001602095653002202111653001602133653002802149653001102177653002202188653001802210653001102228653001402239653000902253653002402262653001702286653001802303653001802321100002102339700002002360700001802380700002002398700002502418856003602443 2010 eng d a1758-535X00aBody weight dynamics and their association with physical function and mortality in older adults: the Cardiovascular Health Study.0 aBody weight dynamics and their association with physical functio c2010 Jan a63-700 v653 aBACKGROUND: 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.
10aActivities of Daily Living10aAge Factors10aAged, 80 and over10aBody Weight10aCardiovascular Diseases10aFemale10aFollow-Up Studies10aHealth Status10aHumans10aLongevity10aMale10aProspective Studies10aRisk Factors10aSurvival Rate10aUnited States1 aArnold, Alice, M1 aNewman, Anne, B1 aCushman, Mary1 aDing, Jingzhong1 aKritchevsky, Stephen uhttps://chs-nhlbi.org/node/109403095nas a2200397 4500008004100000022001400041245017000055210006900225260001300294300001000307490000700317520189000324653002102214653000902235653002202244653001502266653002802281653002802309653003502337653001102372653001102383653002502394653000902419653002602428653002402454653002102478653001802499100002202517700002402539700002102563700002102584700001802605700001802623700002002641856003602661 2010 eng d a1532-541500aCardiovascular disease is associated with greater incident dehydroepiandrosterone sulfate decline in the oldest old: the cardiovascular health study all stars study.0 aCardiovascular disease is associated with greater incident dehyd c2010 Mar a421-60 v583 aOBJECTIVES: 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.
10aAge Distribution10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCross-Sectional Studies10aDehydroepiandrosterone Sulfate10aFemale10aHumans10aLongitudinal Studies10aMale10aMultivariate Analysis10aRegression Analysis10aSex Distribution10aUnited States1 aSanders, Jason, L1 aBoudreau, Robert, M1 aCappola, Anne, R1 aArnold, Alice, M1 aRobbins, John1 aCushman, Mary1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/116803375nas a2200505 4500008004100000022001400041245016800055210006900223260001300292300001200305490000700317520190800324653001602232653001602248653000902264653001002273653002502283653002802308653001902336653002802355653001902383653002802402653001102430653001802441653001102459653001802470653000902488653002102497653003202518653001702550653001602567653001702583653001802600100002002618700002102638700002402659700001902683700001802702700002002720700002802740700002302768700002202791700002002813856003602833 2010 eng d a1758-535X00aChange in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study.0 aChange in circulating adiponectin in advanced old age determinan c2010 Nov a1208-140 v653 aBACKGROUND: 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.
10aAdiponectin10aAge Factors10aAged10aAging10aAnalysis of Variance10aCardiovascular Diseases10aCause of Death10aChi-Square Distribution10aCohort Studies10aCross-Sectional Studies10aFemale10aHealth Status10aHumans10aLinear Models10aMale10aPhysical Fitness10aProportional Hazards Models10aRisk Factors10aSex Factors10aTime Factors10aUnited States1 aKizer, Jorge, R1 aArnold, Alice, M1 aStrotmeyer, Elsa, S1 aIves, Diane, G1 aCushman, Mary1 aDing, Jingzhong1 aKritchevsky, Stephen, B1 aChaves, Paulo, H M1 aHirsch, Calvin, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/121402933nas a2200397 4500008004100000022001400041245010700055210006900162260001300231300001200244490000700256520183200263653000902095653001402104653002802118653002002146653001902166653001602185653002802201653002102229653001402250653001102264653002202275653001102297653000902308653001202317653001502329653002102344100002402365700002702389700002002416700002002436700002002456700002302476856003602499 2010 eng d a1758-535X00aChronic medical conditions and the sex-based disparity in disability: the Cardiovascular Health Study.0 aChronic medical conditions and the sexbased disparity in disabil c2010 Dec a1325-310 v653 aBACKGROUND: 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.
10aAged10aArthritis10aCardiovascular Diseases10aChronic Disease10aCohort Studies10aComorbidity10aCross-Sectional Studies10aDisabled Persons10aEmphysema10aFemale10aHearing Disorders10aHumans10aMale10aObesity10aPrevalence10aSex Distribution1 aWhitson, Heather, E1 aLanderman, Lawrence, R1 aNewman, Anne, B1 aFried, Linda, P1 aPieper, Carl, F1 aCohen, Harvey, Jay uhttps://chs-nhlbi.org/node/122003132nas a2200469 4500008004100000022001400041245015000055210006900205260001300274300001000287490000700297520179300304653001602097653000902113653002202122653001902144653002802163653002102191653002102212653002202233653001102255653001902266653001102285653002502296653001102321653000902332653003202341653001602373653001202389653002602401653001802427100002002445700002102465700002202486700002202508700002202530700001802552700001902570700001702589700002002606856003602626 2010 eng d a1941-722500aCombined association of lipids and blood pressure in relation to incident cardiovascular disease in the elderly: the cardiovascular health study.0 aCombined association of lipids and blood pressure in relation to c2010 Feb a161-70 v233 aBACKGROUND: 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.
10aAge Factors10aAged10aAged, 80 and over10aBlood Pressure10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Mellitus10aFemale10aHealth Surveys10aHumans10aLikelihood Functions10aLipids10aMale10aProportional Hazards Models10aSex Factors10aSmoking10aSocioeconomic Factors10aUnited States1 aWong, Nathan, D1 aLopez, Victor, A1 aRoberts, Craig, S1 aSolomon, Henry, A1 aBurke, Gregory, L1 aKuller, Lewis1 aTracy, Russell1 aYanez, David1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/114505209nas a2201129 4500008004100000022001400041245009100055210006900146260001600215300001300231490000600244520200900250653001502259653001002274653000902284653002202293653002802315653001002343653002102353653003202374653003202406653003102438653003102469653001902500653004002519653001102559653001702570653003402587653001102621653000902632653002702641653002102668653001602689653003602705653002002741653001602761100001802777700001702795700001702812700002302829700002502852700002002877700002002897700001902917700001802936700002402954700002702978700001703005700001703022700001903039700002803058700002603086700001903112700002703131700002303158700001503181700002003196700002603216700002203242700001903264700002203283700002003305700002303325700002403348700001903372700002203391700002203413700002003435700001603455700002203471700001803493700002603511700002103537700002203558700002403580700002003604700001703624700002203641700002303663700002803686700001703714700001903731700001603750700002703766700002103793700002303814700002203837700002203859700002103881700001903902700002403921700002403945700002803969700001803997710002804015856003604043 2010 eng d a1553-740400aFour novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.0 aFour novel Loci 19q13 6q24 12q24 and 5q14 influence the microcir c2010 Oct 28 ae10011840 v63 aThere 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.
10aAdolescent10aAdult10aAged10aAged, 80 and over10aCardiovascular Diseases10aChild10aChild, Preschool10aChromosomes, Human, Pair 1210aChromosomes, Human, Pair 1910aChromosomes, Human, Pair 510aChromosomes, Human, Pair 610aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aGenetic Loci10aGenome-Wide Association Study10aHumans10aMale10aMeta-Analysis as Topic10aMicrocirculation10aMiddle Aged10aPolymorphism, Single Nucleotide10aRetinal Vessels10aYoung Adult1 aIkram, Kamran1 aSim, Xueling1 aXueling, Sim1 aJensen, Richard, A1 aCotch, Mary, Frances1 aHewitt, Alex, W1 aIkram, Arfan, M1 aWang, Jie, Jin1 aKlein, Ronald1 aKlein, Barbara, E K1 aBreteler, Monique, M B1 aCheung, Ning1 aLiew, Gerald1 aMitchell, Paul1 aUitterlinden, André, G1 aRivadeneira, Fernando1 aHofman, Albert1 ade Jong, Paulus, T V M1 aDuijn, Cornelia, M1 aKao, Linda1 aCheng, Ching-Yu1 aSmith, Albert, Vernon1 aGlazer, Nicole, L1 aLumley, Thomas1 aMcKnight, Barbara1 aPsaty, Bruce, M1 aJonasson, Fridbert1 aEiriksdottir, Gudny1 aAspelund, Thor1 aHarris, Tamara, B1 aLauner, Lenore, J1 aTaylor, Kent, D1 aLi, Xiaohui1 aIyengar, Sudha, K1 aXi, Quansheng1 aSivakumaran, Theru, A1 aMackey, David, A1 aMacgregor, Stuart1 aMartin, Nicholas, G1 aYoung, Terri, L1 aBis, Josh, C1 aWiggins, Kerri, L1 aHeckbert, Susan, R1 aHammond, Christopher, J1 aAndrew, Toby1 aFahy, Samantha1 aAttia, John1 aHolliday, Elizabeth, G1 aScott, Rodney, J1 aIslam, F, M Amirul1 aRotter, Jerome, I1 aMcAuley, Annie, K1 aBoerwinkle, Eric1 aTai, Shyong, E1 aGudnason, Vilmundur1 aSiscovick, David, S1 aVingerling, Johannes, R1 aWong, Tien, Y1 aGlobal BPgen Consortium uhttps://chs-nhlbi.org/node/124303247nas a2200409 4500008004100000022001400041245007500055210006900130260001300199300001200212490000700224520212300231653003102354653000902385653002202394653002702416653002802443653002102471653001102492653002202503653002502525653001802550653001102568653000902579653001402588653002602602653001702628653001702645653001802662100002402680700001702704700001702721700002302738700002002761700002002781856003602801 2010 eng d a1532-541500aGeriatric impairments and disability: the cardiovascular health study.0 aGeriatric impairments and disability the cardiovascular health s c2010 Sep a1686-920 v583 aOBJECTIVES: 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.
10aActivities of Daily Living10aAged10aAged, 80 and over10aCardiac Rehabilitation10aCardiovascular Diseases10aDisabled Persons10aFemale10aFollow-Up Studies10aGeriatric Assessment10aHealth Status10aHumans10aMale10aMorbidity10aRetrospective Studies10aRisk Factors10aTime Factors10aUnited States1 aChaudhry, Sarwat, I1 aMcAvay, Gail1 aNing, Yuming1 aAllore, Heather, G1 aNewman, Anne, B1 aGill, Thomas, M uhttps://chs-nhlbi.org/node/123202861nas a2200457 4500008004100000022001400041245009500055210006900150260001300219300001000232490000700242520164100249653000901890653002201899653002001921653002801941653001901969653002401988653001102012653002602023653001902049653001802068653001102086653001402097653000902111653002602120653001702146653002402163653001102187653001802198100001602216700001202232700001602244700001702260700002002277700001702297700002102314700001502335700001702350856003602367 2010 eng d a1590-372900aGlycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.0 aGlycosylated hemoglobin and the risk of death and cardiovascular c2010 Jan a15-210 v203 aBACKGROUND 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.
10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aDisease Progression10aFemale10aGlycated Hemoglobin A10aHealth Surveys10aHeart Failure10aHumans10aIncidence10aMale10aMyocardial Infarction10aRisk Factors10aStatistics as Topic10aStroke10aUnited States1 aChonchol, M1 aKatz, R1 aFried, L, F1 aSarnak, M, J1 aSiscovick, D, S1 aNewman, A, B1 aStrotmeyer, E, S1 aBertoni, A1 aShlipak, M G uhttps://chs-nhlbi.org/node/109102729nas a2200409 4500008004100000022001400041245014700055210006900202260001300271300000900284490000700293520152600300653000901826653002801835653002101863653001101884653001501895653003801910653002201948653001101970653001801981653000901999653002302008653002602031653003602057653000902093653001102102100001902113700002202132700002302154700002002177700002102197700001802218700002202236700002502258856003602283 2010 eng d a1469-180900aInteraction between fibrinogen and IL-6 genetic variants and associations with cardiovascular disease risk in the Cardiovascular Health Study.0 aInteraction between fibrinogen and IL6 genetic variants and asso c2010 Jan a1-100 v743 aThe 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.
10aAged10aCardiovascular Diseases10aCarotid Arteries10aFemale10aFibrinogen10aGenetic Predisposition to Disease10aGenetic Variation10aHumans10aInterleukin-610aMale10aModels, Biological10aMyocardial Infarction10aPolymorphism, Single Nucleotide10aRisk10aStroke1 aCarty, Cara, L1 aHeagerty, Patrick1 aHeckbert, Susan, R1 aJarvik, Gail, P1 aLange, Leslie, A1 aCushman, Mary1 aTracy, Russell, P1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/115802752nas a2200349 4500008004100000022001400041245015600055210006900211260001300280300001100293490000800304520167600312653005101988653000902039653002302048653002802071653001102099653001102110653002602121653002802147653002402175653000902199653001102208100002502219700001702244700001802261700002202279700002402301700002002325700002102345856003602366 2010 eng d a1879-148400aLipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and risk of cardiovascular disease in older adults: results from the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 LpPLA2 and risk of cardio c2010 Apr a528-320 v2093 aOBJECTIVE: 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.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aC-Reactive Protein10aCardiovascular Diseases10aFemale10aHumans10aMyocardial Infarction10aPopulation Surveillance10aProspective Studies10aRisk10aStroke1 aJenny, Nancy, Swords1 aSolomon, Cam1 aCushman, Mary1 aTracy, Russell, P1 aNelson, Jeanenne, J1 aPsaty, Bruce, M1 aFurberg, Curt, D uhttps://chs-nhlbi.org/node/113303482nas a2200481 4500008004100000022001400041245012000055210006900175260001300244300001200257490000700269520209400276653001602370653000902386653002202395653003102417653002502448653002802473653002802501653002602529653001102555653002502566653001602591653001102607653002002618653002502638653000902663653002602672653002102698653002202719653002202741653001402763653001802777100002402795700002102819700002402840700001902864700001802883700002102901700002202922700002002944856003602964 2010 eng d a1532-541500aLong-term retention of older adults in the Cardiovascular Health Study: implications for studies of the oldest old.0 aLongterm retention of older adults in the Cardiovascular Health c2010 Apr a696-7010 v583 aOBJECTIVES: 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.
10aAge Factors10aAged10aAged, 80 and over10aAmbulatory Care Facilities10aAnalysis of Variance10aCardiovascular Diseases10aChi-Square Distribution10aEpidemiologic Studies10aFemale10aGeriatric Assessment10aHouse Calls10aHumans10aLogistic Models10aLongitudinal Studies10aMale10aMultivariate Analysis10aPatient Dropouts10aPatient Selection10aResearch Subjects10aTelephone10aUnited States1 aStrotmeyer, Elsa, S1 aArnold, Alice, M1 aBoudreau, Robert, M1 aIves, Diane, G1 aCushman, Mary1 aRobbins, John, A1 aHarris, Tamara, B1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/118503867nas a2200745 4500008004100000022001400041245012900055210006900184260001300253300001100266490000600277520177500283653002802058653002102086653001102107653001702118653003402135653000902169653001102178653000902189653001702198653001402215100001602229700001902245700001902264700002102283700002202304700002002326700002302346700001902369700002402388700002202412700001902434700001902453700002002472700001902492700002102511700002002532700001202552700002002564700002102584700002302605700001202628700001902640700002002659700002102679700002002700700002202720700003002742700002102772700002302793700001902816700002602835700002002861700002802881700002102909700002002930700002002950700002402970700002402994700002803018700002103046700001803067856003603085 2010 eng d a1942-326800aMultiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.0 aMultiple genetic loci influence serum urate levels and their rel c2010 Dec a523-300 v33 aBACKGROUND: 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.
10aCardiovascular Diseases10aCoronary Disease10aFemale10aGenetic Loci10aGenome-Wide Association Study10aGout10aHumans10aMale10aRisk Factors10aUric Acid1 aYang, Qiong1 aKöttgen, Anna1 aDehghan, Abbas1 aSmith, Albert, V1 aGlazer, Nicole, L1 aChen, Ming-Huei1 aChasman, Daniel, I1 aAspelund, Thor1 aEiriksdottir, Gudny1 aHarris, Tamara, B1 aLauner, Lenore1 aNalls, Michael1 aHernandez, Dena1 aArking, Dan, E1 aBoerwinkle, Eric1 aGrove, Megan, L1 aLi, Man1 aKao, W, H Linda1 aChonchol, Michel1 aHaritunians, Talin1 aLi, Guo1 aLumley, Thomas1 aPsaty, Bruce, M1 aShlipak, Michael1 aHwang, Shih-Jen1 aLarson, Martin, G1 aO'Donnell, Christopher, J1 aUpadhyay, Ashish1 aDuijn, Cornelia, M1 aHofman, Albert1 aRivadeneira, Fernando1 aStricker, Bruno1 aUitterlinden, André, G1 aParé, Guillaume1 aParker, Alex, N1 aRidker, Paul, M1 aSiscovick, David, S1 aGudnason, Vilmundur1 aWitteman, Jacqueline, C1 aFox, Caroline, S1 aCoresh, Josef uhttps://chs-nhlbi.org/node/123502166nas a2200409 4500008004100000022001400041245011100055210006900166260001300235300001100248490000700259520100900266653003101275653001601306653000901322653002201331653002801353653001901381653001301400653001101413653002001424653001801444653001101462653002301473653001501496653000901511653003201520653001601552100002201568700001701590700002001607700002401627700002101651700002501672700002301697856003601720 2010 eng d a1063-865200aPhysical activity and years of healthy life in older adults: results from the cardiovascular health study.0 aPhysical activity and years of healthy life in older adults resu c2010 Jul a313-340 v183 aLittle 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.
10aActivities of Daily Living10aAge Factors10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aExercise10aFemale10aHealth Behavior10aHealth Status10aHumans10aLeisure Activities10aLife Style10aMale10aQuality-Adjusted Life Years10aSex Factors1 aHirsch, Calvin, H1 aDiehr, Paula1 aNewman, Anne, B1 aGerrior, Shirley, A1 aPratt, Charlotte1 aLebowitz, Michael, D1 aJackson, Sharon, A uhttps://chs-nhlbi.org/node/121902959nas a2200457 4500008004100000022001400041245010200055210006900157260001600226300001200242490000700254520169400261653000901955653002201964653001001986653001801996653002802014653002402042653001102066653001102077653002502088653003102113653000902144653002702153653001902180653002902199653001502228653003002243653003102273100001902304700001502323700001602338700001702354700001402371700001702385700001502402700001902417700001302436700001602449856003602465 2010 eng d a1526-632X00aPhysical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study.0 aPhysical activity predicts gray matter volume in late adulthood c2010 Oct 19 a1415-220 v753 aOBJECTIVES: 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.
10aAged10aAged, 80 and over10aBrain10aBrain Mapping10aCardiovascular Diseases10aCognition Disorders10aFemale10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMental Status Schedule10aMotor Activity10aNeuropsychological Tests10aOdds Ratio10aPredictive Value of Tests10aSurveys and Questionnaires1 aErickson, K, I1 aRaji, C, A1 aLopez, O, L1 aBecker, J, T1 aRosano, C1 aNewman, A, B1 aGach, H, M1 aThompson, P, M1 aHo, A, J1 aKuller, L H uhttps://chs-nhlbi.org/node/123902877nas a2200385 4500008004100000022001400041245013900055210006900194260001300263300001100276490000600287520178700293653003002080653002802110653001902138653001502157653001102172653001102183653001702194653000902211653003602220653002402256653001702280653001102297100001602308700001302324700002002337700001802357700001702375700001502392700001602407700001502423700001702438856003602455 2011 eng d a1538-783600aAssociation of coagulation-related and inflammation-related genes and factor VIIc levels with stroke: the Cardiovascular Health Study.0 aAssociation of coagulationrelated and inflammationrelated genes c2011 Feb a267-740 v93 aBACKGROUND: 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.
10aBlood Coagulation Factors10aCardiovascular Diseases10aCohort Studies10aFactor VII10aFemale10aHumans10aInflammation10aMale10aPolymorphism, Single Nucleotide10aProspective Studies10aRisk Factors10aStroke1 aZakai, N, A1 aLange, L1 aLongstreth, W T1 aO'Meara, E, S1 aKelley, J, L1 aFornage, M1 aNikerson, D1 aCushman, M1 aReiner, A, P uhttps://chs-nhlbi.org/node/125103311nas a2200601 4500008004100000022001400041245020900055210006900264260001600333300001100349490000800360520151200368653001001880653002201890653000901912653002801921653001901949653004001968653001102008653001502019653003802034653001502072653001102087653000902098653001602107653001402123653003602137653001702173100002502190700002102215700002402236700002002260700002302280700002002303700001902323700002302342700002002365700001202385700001602397700002302413700001802436700002102454700001902475700002202494700002102516700002202537700002102559700002102580700001702601700003002618700002502648856003602673 2011 eng d a1528-002000aAssociation of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).0 aAssociation of genomic loci from a cardiovascular gene SNP array c2011 Jan 06 a268-750 v1173 aSeveral 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.
10aAdult10aAfrican Americans10aAged10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aGenetic Predisposition to Disease10aHaplotypes10aHumans10aMale10aMiddle Aged10aPhenotype10aPolymorphism, Single Nucleotide10aRisk Factors1 aWassel, Christina, L1 aLange, Leslie, A1 aKeating, Brendan, J1 aTaylor, Kira, C1 aJohnson, Andrew, D1 aPalmer, Cameron1 aHo, Lindsey, A1 aSmith, Nicholas, L1 aLange, Ethan, M1 aLi, Yun1 aYang, Qiong1 aDelaney, Joseph, A1 aTang, Weihong1 aTofler, Geoffrey1 aRedline, Susan1 aTaylor, Herman, A1 aWilson, James, G1 aTracy, Russell, P1 aJacobs, David, R1 aFolsom, Aaron, R1 aGreen, David1 aO'Donnell, Christopher, J1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/156202891nas a2200325 4500008004100000022001400041245009900055210006900154260001600223300001100239490000800250520197500258653000902233653002802242653002402270653001102294653002202305653001102327653001402338653000902352653001602361653002002377653001702397653002602414100002102440700002402461700002002485700002402505856003602529 2011 eng d a1524-453900aAssociation of incident cardiovascular disease with progression of sleep-disordered breathing.0 aAssociation of incident cardiovascular disease with progression c2011 Mar 29 a1280-60 v1233 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMiddle Aged10aPolysomnography10aRisk Factors10aSleep Apnea Syndromes1 aChami, Hassan, A1 aResnick, Helaine, E1 aQuan, Stuart, F1 aGottlieb, Daniel, J uhttps://chs-nhlbi.org/node/127804125nas a2200745 4500008004100000022001400041245014300055210006900198260001600267300001300283490000700296520189000303653002802193653003002221653002702251653002502278653003802303653003402341653001302375653001102388653001602399653001502415653001502430653003602445653001702481100001802498700001602516700001702532700002302549700001902572700001902591700001902610700001902629700002002648700001602668700002002684700002202704700002002726700002402746700002402770700002102794700002402815700002102839700002202860700002102882700002302903700001902926700002202945700002102967700001702988700001903005700002203024700001903046700001403065700002203079700002203101700002403123700002503147700001803172700001803190700001803208710007203226710004503298856003603343 2011 eng d a1552-578300aCandidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe).0 aCandidate gene association study for diabetic retinopathy in per c2011 Sep 29 a7593-6020 v523 aPURPOSE: To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).
METHODS: Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades ≥ 14 and ≥ 30. The χ² analyses for each CARe cohort were combined by Cochran-Mantel-Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.
RESULTS: Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging α-l-iduronidase (IDUA) (P = 2.1 × 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.
CONCLUSIONS: Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts.
10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aDiabetic Nephropathies10aDiabetic Retinopathy10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHumans10aIduronidase10aOdds Ratio10aP-Selectin10aPolymorphism, Single Nucleotide10aRisk Factors1 aSobrin, Lucia1 aGreen, Todd1 aSim, Xueling1 aJensen, Richard, A1 aTai, Shyong, E1 aTay, Wan, Ting1 aWang, Jie, Jin1 aMitchell, Paul1 aSandholm, Niina1 aLiu, Yiyuan1 aHietala, Kustaa1 aIyengar, Sudha, K1 aBrooks, Matthew1 aBuraczynska, Monika1 aVan Zuydam, Natalie1 aSmith, Albert, V1 aGudnason, Vilmundur1 aDoney, Alex, S F1 aMorris, Andrew, D1 aLeese, Graham, P1 aPalmer, Colin, N A1 aSwaroop, Anand1 aTaylor, Herman, A1 aWilson, James, G1 aPenman, Alan1 aChen, Ching, J1 aGroop, Per-Henrik1 aSaw, Seang-Mei1 aAung, Tin1 aKlein, Barbara, E1 aRotter, Jerome, I1 aSiscovick, David, S1 aCotch, Mary, Frances1 aKlein, Ronald1 aDaly, Mark, J1 aWong, Tien, Y1 aFamily Investigation of Nephropathy and Diabetes-Eye Research Group1 aWellcome Trust Case Control Consortium 2 uhttps://chs-nhlbi.org/node/156703030nas a2200505 4500008004100000022001400041245004500055210004400100260001300144300001100157490000600168520171200174653001601886653002201902653002501924653001501949653002801964653002801992653002002020653001502040653002802055653001502083653002202098653001102120653003102131653001102162653001102173653002002184653002002204653000902224653002302233653001502256653002002271653001702291653001802308100001902326700002302345700001602368700002002384700002002404700002402424700002002448700002002468856003602488 2011 eng d a1555-905X00aChronic kidney disease in octogenarians.0 aChronic kidney disease in octogenarians c2011 Jun a1410-70 v63 aBACKGROUND 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.
10aAge Factors10aAged, 80 and over10aAnalysis of Variance10aBiomarkers10aCardiovascular Diseases10aChi-Square Distribution10aChronic Disease10aCreatinine10aCross-Sectional Studies10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLogistic Models10aMale10aModels, Biological10aPrevalence10aRisk Assessment10aRisk Factors10aUnited States1 aShastri, Shani1 aTighiouart, Hocine1 aKatz, Ronit1 aRifkin, Dena, E1 aFried, Linda, F1 aShlipak, Michael, G1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/128602955nas a2200481 4500008004100000022001400041245009200055210006900147260001300216300001100229490000700240520162800247653000901875653002201884653001501906653002801921653002001949653001501969653001501984653002401999653001102023653003102034653001802065653001102083653002002094653002802114653000902142653001602151653003002167653002602197653001702223100002302240700001602263700002002279700001602299700002002315700001702335700001902352700002102371700002102392700002402413856003602437 2011 eng d a1533-345000aCystatin C identifies chronic kidney disease patients at higher risk for complications.0 aCystatin C identifies chronic kidney disease patients at higher c2011 Jan a147-550 v223 aAlthough 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.
10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aChronic Disease10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aKidney Diseases10aKidney Failure, Chronic10aMale10aMiddle Aged10aPredictive Value of Tests10aRetrospective Studies10aRisk Factors1 aPeralta, Carmen, A1 aKatz, Ronit1 aSarnak, Mark, J1 aIx, Joachim1 aFried, Linda, F1 ade Boer, Ian1 aPalmas, Walter1 aSiscovick, David1 aLevey, Andrew, S1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/125603004nas a2200337 4500008004100000022001400041245013200055210006900187260001300256300001000269490000700279520201500286653000902301653002202310653002802332653001502360653002602375653001102401653001102412653000902423653001902432653003702451653001802488100001502506700001802521700002402539700002402563700001902587700002402606856003602630 2011 eng d a1468-201X00aDepressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study.0 aDepressive symptoms physical inactivity and risk of cardiovascul c2011 Mar a500-50 v973 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aDepression10aEpidemiologic Methods10aFemale10aHumans10aMale10aMotor Activity10aPsychiatric Status Rating Scales10aUnited States1 aWin, Sithu1 aParakh, Kapil1 aEze-Nliam, Chete, M1 aGottdiener, John, S1 aKop, Willem, J1 aZiegelstein, Roy, C uhttps://chs-nhlbi.org/node/127002703nas a2200373 4500008004100000022001400041245011000055210006900165260000900234300001100243490000700254520166000261653000901921653002201930653002801952653001101980653002401991653001902015653001102034653002202045653001102067653002502078653000902103653002402112653002402136653000802160100001702168700001902185700002202204700002002226700001902246700002802265856003602293 2011 eng d a1875-890800aGender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study.0 aGender differences in tea coffee and cognitive decline in the el c2011 a553-660 v273 aAlthough 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCoffee10aCognition Disorders10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aLongitudinal Studies10aMale10aProspective Studies10aSex Characteristics10aTea1 aArab, Lenore1 aBiggs, Mary, L1 aO'Meara, Ellen, S1 aLongstreth, W T1 aCrane, Paul, K1 aFitzpatrick, Annette, L uhttps://chs-nhlbi.org/node/131503101nas a2200493 4500008004100000022001400041245016400055210006900219260001600288300001200304490000700316520162000323653001001943653002201953653000901975653002801984653004002012653001502052653001102067653003802078653001102116653000902127653001602136653003602152100002002188700002102208700002102229700001702250700002402267700001802291700002302309700002302332700001802355700002102373700001902394700001902413700002202432700003002454700002102484700001702505700002402522700002502546856003602571 2011 eng d a1460-208300aA gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium.0 agenecentric association scan for Coagulation Factor VII levels i c2011 Sep 01 a3525-340 v203 aPolymorphisms 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.
10aAdult10aAfrican Americans10aAged10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFactor VII10aFemale10aGenetic Predisposition to Disease10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide1 aTaylor, Kira, C1 aLange, Leslie, A1 aZabaneh, Delilah1 aLange, Ethan1 aKeating, Brendan, J1 aTang, Weihong1 aSmith, Nicholas, L1 aDelaney, Joseph, A1 aKumari, Meena1 aHingorani, Aroon1 aNorth, Kari, E1 aKivimaki, Mika1 aTracy, Russell, P1 aO'Donnell, Christopher, J1 aFolsom, Aaron, R1 aGreen, David1 aHumphries, Steve, E1 aReiner, Alexander, P uhttps://chs-nhlbi.org/node/156813785nas a2204513 4500008004100000022001400041245009700055210006900152260001600221300001000237490000800247520127300255653001101528653000901539653001901548653002801567653002801595653001101623653003801634653003401672653001101706653001701717653002001734653003601754653001101790110008001801700002001881700002401901700002101925700002101946700002301967700002301990700002102013700002102034700002602055700002002081700001702101700002402118700002202142700001602164700003102180700002202211700002202233700001902255700001902274700002102293700001702314700001702331700001802348700001802366700001802384700001902402700001602421700001702437700002102454700002102475700001902496700002002515700001902535700001602554700001602570700002102586700002002607700002002627700002202647700001802669700001802687700001602705700001502721700002402736700002202760700001502782700002202797700002102819700002202840700002202862700001702884700001402901700002202915700001902937700002002956700001702976700002902993700002203022700002203044700001303066700001803079700003103097700002303128700002203151700001403173700001903187700002003206700001803226700002203244700002103266700002403287700002703311700002303338700001903361700002003380700002003400700002403420700002103444700002603465700001903491700002003510700002203530700002603552700002403578700002603602700001903628700002203647700002403669700002003693700001803713700002203731700001803753700002103771700002103792700002403813700001803837700002203855700002003877700002403897700001903921700002303940700001703963700002503980700001304005700002104018700001904039700002004058700001904078700002004097700002004117700002004137700002004157700002204177700003004199700001904229700001904248700002004267700002104287700002504308700002004333700002104353700002204374700002304396700002504419700002304444700001604467700002404483700002304507700001904530700001904549700002404568700002004592700002004612700001804632700001904650700001804669700001904687700002004706700001604726700002404742700002404766700002504790700002004815700002604835700002004861700001904881700002204900700002504922700002104947700002004968700002004988700002605008700001705034700002005051700001905071700001705090700002005107700002105127700002305148700002305171700002205194700001805216700002005234700001905254700002105273700001805294700002605312700002005338700002305358700002205381700001905403700002205422700002205444700002405466700001705490700002305507700001805530700001805548700002005566700002005586700002205606700002205628700002305650700002105673700002405694700002205718700002205740700001905762700001905781700002005800700001705820700002005837700001805857700001605875700001905891700002405910700001705934700001905951700002505970700002205995700001306017700002206030700003006052700002506082700002006107700002006127700002206147700002006169700002206189700002006211700002106231700001806252700002006270700002106290700001906311700002206330700002406352700001706376700001806393700001506411700002006426700001806446700002506464700001906489700002606508700001906534700002806553700001906581700003306600700001906633700001906652700001806671700002606689700002306715700001706738700002006755700002206775700002106797700002806818700001906846700002006865700001806885700002306903700001806926700002106944700001706965700001906982700001707001700002007018700001807038700002007056700002007076700002107096700002007117700001807137700002207155700002207177700001907199700001807218700002407236700002107260700003107281700002607312700002407338700002207362700002407384700002207408700001707430700002007447700002107467700001507488700002207503700001907525700002407544700002007568700001507588700001607603700002007619700002007639700002207659700001907681700002107700700001807721700002007739700002207759700001807781700001907799700002307818700001907841700002007860700002207880700002307902700002407925700001907949700002307968700001807991700002108009700002408030700001808054700001808072700002008090700001808110700001808128700002208146700001908168700002008187700002508207700002308232700002008255700002108275700002008296700002008316700002308336700002608359700002008385700002008405700002508425700002108450700002008471700002308491700002208514700002008536700002808556700002508584700002408609700002208633700001908655700001708674700002308691700003008714700002808744700002508772700002108797700002708818700002108845700002208866700002708888700002008915700002508935700002608960700001808986700002309004700002909027700001709056700002309073700001809096710002609114710002209140710002509162710002309187710002509210856003609235 2011 eng d a1476-468700aGenetic variants in novel pathways influence blood pressure and cardiovascular disease risk.0 aGenetic variants in novel pathways influence blood pressure and c2011 Sep 11 a103-90 v4783 aBlood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
10aAfrica10aAsia10aBlood Pressure10aCardiovascular Diseases10aCoronary Artery Disease10aEurope10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aHypertension10aKidney Diseases10aPolymorphism, Single Nucleotide10aStroke1 aInternational Consortium for Blood Pressure Genome-Wide Association Studies1 aEhret, Georg, B1 aMunroe, Patricia, B1 aRice, Kenneth, M1 aBochud, Murielle1 aJohnson, Andrew, D1 aChasman, Daniel, I1 aSmith, Albert, V1 aTobin, Martin, D1 aVerwoert, Germaine, C1 aHwang, Shih-Jen1 aPihur, Vasyl1 aVollenweider, Peter1 aO'Reilly, Paul, F1 aAmin, Najaf1 aBragg-Gresham, Jennifer, L1 aTeumer, Alexander1 aGlazer, Nicole, L1 aLauner, Lenore1 aZhao, Jing Hua1 aAulchenko, Yurii1 aHeath, Simon1 aSõber, Siim1 aParsa, Afshin1 aLuan, Jian'an1 aArora, Pankaj1 aDehghan, Abbas1 aZhang, Feng1 aLucas, Gavin1 aHicks, Andrew, A1 aJackson, Anne, U1 aPeden, John, F1 aTanaka, Toshiko1 aWild, Sarah, H1 aRudan, Igor1 aIgl, Wilmar1 aMilaneschi, Yuri1 aParker, Alex, N1 aFava, Cristiano1 aChambers, John, C1 aFox, Ervin, R1 aKumari, Meena1 aGo, Min Jin1 aHarst, Pim1 aKao, Wen Hong Linda1 aSjögren, Marketa1 aVinay, D G1 aAlexander, Myriam1 aTabara, Yasuharu1 aShaw-Hawkins, Sue1 aWhincup, Peter, H1 aLiu, Yongmei1 aShi, Gang1 aKuusisto, Johanna1 aTayo, Bamidele1 aSeielstad, Mark1 aSim, Xueling1 aNguyen, Khanh-Dung Hoang1 aLehtimäki, Terho1 aMatullo, Giuseppe1 aWu, Ying1 aGaunt, Tom, R1 aOnland-Moret, Charlotte, N1 aCooper, Matthew, N1 aPlatou, Carl, G P1 aOrg, Elin1 aHardy, Rebecca1 aDahgam, Santosh1 aPalmen, Jutta1 aVitart, Veronique1 aBraund, Peter, S1 aKuznetsova, Tatiana1 aUiterwaal, Cuno, S P M1 aAdeyemo, Adebowale1 aPalmas, Walter1 aCampbell, Harry1 aLudwig, Barbara1 aTomaszewski, Maciej1 aTzoulaki, Ioanna1 aPalmer, Nicholette, D1 aAspelund, Thor1 aGarcia, Melissa1 aChang, Yen-Pei, C1 aO'Connell, Jeffrey, R1 aSteinle, Nanette, I1 aGrobbee, Diederick, E1 aArking, Dan, E1 aKardia, Sharon, L1 aMorrison, Alanna, C1 aHernandez, Dena1 aNajjar, Samer1 aMcArdle, Wendy, L1 aHadley, David1 aBrown, Morris, J1 aConnell, John, M1 aHingorani, Aroon, D1 aDay, Ian, N M1 aLawlor, Debbie, A1 aBeilby, John, P1 aLawrence, Robert, W1 aClarke, Robert1 aHopewell, Jemma, C1 aOngen, Halit1 aDreisbach, Albert, W1 aLi, Yali1 aYoung, Hunter, J1 aBis, Joshua, C1 aKähönen, Mika1 aViikari, Jorma1 aAdair, Linda, S1 aLee, Nanette, R1 aChen, Ming-Huei1 aOlden, Matthias1 aPattaro, Cristian1 aBolton, Judith Hoffman, A1 aKöttgen, Anna1 aBergmann, Sven1 aMooser, Vincent1 aChaturvedi, Nish1 aFrayling, Timothy, M1 aIslam, Muhammad1 aJafar, Tazeen, H1 aErdmann, Jeanette1 aKulkarni, Smita, R1 aBornstein, Stefan, R1 aGrässler, Jürgen1 aGroop, Leif1 aVoight, Benjamin, F1 aKettunen, Johannes1 aHoward, Philip1 aTaylor, Andrew1 aGuarrera, Simonetta1 aRicceri, Fulvio1 aEmilsson, Valur1 aPlump, Andrew1 aBarroso, Inês1 aKhaw, Kay-Tee1 aWeder, Alan, B1 aHunt, Steven, C1 aSun, Yan, V1 aBergman, Richard, N1 aCollins, Francis, S1 aBonnycastle, Lori, L1 aScott, Laura, J1 aStringham, Heather, M1 aPeltonen, Leena1 aPerola, Markus1 aVartiainen, Erkki1 aBrand, Stefan-Martin1 aStaessen, Jan, A1 aWang, Thomas, J1 aBurton, Paul, R1 aArtigas, Maria, Soler1 aDong, Yanbin1 aSnieder, Harold1 aWang, Xiaoling1 aZhu, Haidong1 aLohman, Kurt, K1 aRudock, Megan, E1 aHeckbert, Susan, R1 aSmith, Nicholas, L1 aWiggins, Kerri, L1 aDoumatey, Ayo1 aShriner, Daniel1 aVeldre, Gudrun1 aViigimaa, Margus1 aKinra, Sanjay1 aPrabhakaran, Dorairaj1 aTripathy, Vikal1 aLangefeld, Carl, D1 aRosengren, Annika1 aThelle, Dag, S1 aCorsi, Anna Maria1 aSingleton, Andrew1 aForrester, Terrence1 aHilton, Gina1 aMcKenzie, Colin, A1 aSalako, Tunde1 aIwai, Naoharu1 aKita, Yoshikuni1 aOgihara, Toshio1 aOhkubo, Takayoshi1 aOkamura, Tomonori1 aUeshima, Hirotsugu1 aUmemura, Satoshi1 aEyheramendy, Susana1 aMeitinger, Thomas1 aWichmann, H-Erich1 aCho, Yoon Shin1 aKim, Hyung-Lae1 aLee, Jong-Young1 aScott, James1 aSehmi, Joban, S1 aZhang, Weihua1 aHedblad, Bo1 aNilsson, Peter1 aSmith, George Davey1 aWong, Andrew1 aNarisu, Narisu1 aStančáková, Alena1 aRaffel, Leslie, J1 aYao, Jie1 aKathiresan, Sekar1 aO'Donnell, Christopher, J1 aSchwartz, Stephen, M1 aIkram, Arfan, M1 aLongstreth, W T1 aMosley, Thomas, H1 aSeshadri, Sudha1 aShrine, Nick, R G1 aWain, Louise, V1 aMorken, Mario, A1 aSwift, Amy, J1 aLaitinen, Jaana1 aProkopenko, Inga1 aZitting, Paavo1 aCooper, Jackie, A1 aHumphries, Steve, E1 aDanesh, John1 aRasheed, Asif1 aGoel, Anuj1 aHamsten, Anders1 aWatkins, Hugh1 aBakker, Stephan, J L1 aGilst, Wiek, H1 aJanipalli, Charles, S1 aMani, Radha, K1 aYajnik, Chittaranjan, S1 aHofman, Albert1 aMattace-Raso, Francesco, U S1 aOostra, Ben, A1 aDemirkan, Ayse1 aIsaacs, Aaron1 aRivadeneira, Fernando1 aLakatta, Edward, G1 aOrrù, Marco1 aScuteri, Angelo1 aAla-Korpela, Mika1 aKangas, Antti, J1 aLyytikäinen, Leo-Pekka1 aSoininen, Pasi1 aTukiainen, Taru1 aWürtz, Peter1 aOng, Rick Twee-Hee1 aDörr, Marcus1 aKroemer, Heyo, K1 aVölker, Uwe1 aVölzke, Henry1 aGalan, Pilar1 aHercberg, Serge1 aLathrop, Mark1 aZelenika, Diana1 aDeloukas, Panos1 aMangino, Massimo1 aSpector, Tim, D1 aZhai, Guangju1 aMeschia, James, F1 aNalls, Michael, A1 aSharma, Pankaj1 aTerzic, Janos1 aKumar, Kranthi, M V1 aDenniff, Matthew1 aZukowska-Szczechowska, Ewa1 aWagenknecht, Lynne, E1 aFowkes, Gerald, F R1 aCharchar, Fadi, J1 aSchwarz, Peter, E H1 aHayward, Caroline1 aGuo, Xiuqing1 aRotimi, Charles1 aBots, Michiel, L1 aBrand, Eva1 aSamani, Nilesh, J1 aPolasek, Ozren1 aTalmud, Philippa, J1 aNyberg, Fredrik1 aKuh, Diana1 aLaan, Maris1 aHveem, Kristian1 aPalmer, Lyle, J1 aSchouw, Yvonne, T1 aCasas, Juan, P1 aMohlke, Karen, L1 aVineis, Paolo1 aRaitakari, Olli1 aGanesh, Santhi, K1 aWong, Tien, Y1 aTai, Shyong, E1 aCooper, Richard, S1 aLaakso, Markku1 aRao, Dabeeru, C1 aHarris, Tamara, B1 aMorris, Richard, W1 aDominiczak, Anna, F1 aKivimaki, Mika1 aMarmot, Michael, G1 aMiki, Tetsuro1 aSaleheen, Danish1 aChandak, Giriraj, R1 aCoresh, Josef1 aNavis, Gerjan1 aSalomaa, Veikko1 aHan, Bok-Ghee1 aZhu, Xiaofeng1 aKooner, Jaspal, S1 aMelander, Olle1 aRidker, Paul, M1 aBandinelli, Stefania1 aGyllensten, Ulf, B1 aWright, Alan, F1 aWilson, James, F1 aFerrucci, Luigi1 aFarrall, Martin1 aTuomilehto, Jaakko1 aPramstaller, Peter, P1 aElosua, Roberto1 aSoranzo, Nicole1 aSijbrands, Eric, J G1 aAltshuler, David1 aLoos, Ruth, J F1 aShuldiner, Alan, R1 aGieger, Christian1 aMeneton, Pierre1 aUitterlinden, André, G1 aWareham, Nicholas, J1 aGudnason, Vilmundur1 aRotter, Jerome, I1 aRettig, Rainer1 aUda, Manuela1 aStrachan, David, P1 aWitteman, Jacqueline, C M1 aHartikainen, Anna-Liisa1 aBeckmann, Jacques, S1 aBoerwinkle, Eric1 aVasan, Ramachandran, S1 aBoehnke, Michael1 aLarson, Martin, G1 aJarvelin, Marjo-Riitta1 aPsaty, Bruce, M1 aAbecasis, Goncalo, R1 aChakravarti, Aravinda1 aElliott, Paul1 aDuijn, Cornelia, M1 aNewton-Cheh, Christopher1 aLevy, Daniel1 aCaulfield, Mark, J1 aJohnson, Toby1 aCARDIoGRAM consortium1 aCKDGen Consortium1 aKidneyGen Consortium1 aEchoGen consortium1 aCHARGE-HF consortium uhttps://chs-nhlbi.org/node/132502348nas a2200469 4500008004100000022001400041245010400055210006900159260001300228300001000241490000600251520105900257653000901316653002201325653001001347653001901357653002801376653001901404653001101423653000901434653001101443653001401454653000901468653001601477653002801493653002001521100002001541700002001561700002701581700002201608700002101630700002001651700002301671700002101694700001901715700001901734700002601753700002301779700002301802700001701825856003601842 2011 eng d a1945-458900aHealth and function of participants in the Long Life Family Study: A comparison with other cohorts.0 aHealth and function of participants in the Long Life Family Stud c2011 Jan a63-760 v33 aIndividuals 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.
10aAged10aAged, 80 and over10aAging10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aFemale10aGait10aHumans10aLongevity10aMale10aMiddle Aged10aPsychomotor Performance10aResearch Design1 aNewman, Anne, B1 aGlynn, Nancy, W1 aTaylor, Christopher, A1 aSebastiani, Paola1 aPerls, Thomas, T1 aMayeux, Richard1 aChristensen, Kaare1 aZmuda, Joseph, M1 aBarral, Sandra1 aLee, Joseph, H1 aSimonsick, Eleanor, M1 aWalston, Jeremy, D1 aYashin, Anatoli, I1 aHadley, Evan uhttps://chs-nhlbi.org/node/126302802nas a2200469 4500008004100000022001400041245009700055210006900152260000900221300001000230490000700240520155000247653000901797653002801806653001501834653001501849653002401864653001101888653001501899653003101914653001101945653001101956653002001967653000901987653001601996653002202012653001702034653002202051100002302073700001602096700002102112700001602133700001602149700001702165700002502182700001602207700002202223700001602245700001702261700001802278856003602296 2011 eng d a1421-967000aKidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2).0 aKidney function decline in the elderly impact of lipoproteinasso c2011 a512-80 v343 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGeriatrics10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMiddle Aged10aPhospholipases A210aRisk Factors10aTreatment Outcome1 aPeralta, Carmen, A1 aKatz, Ronit1 aShlipak, Michael1 aDubin, Ruth1 aDeBoer, Ian1 aJenny, Nancy1 aFitzpatrick, Annette1 aKoro, Carol1 aKestenbaum, Bryan1 aIx, Joachim1 aSarnak, Mark1 aCushman, Mary uhttps://chs-nhlbi.org/node/134903026nas a2200469 4500008004100000022001400041245008000055210006900135260001300204300001000217490000700227520177200234653000902006653002202015653001002037653002002047653002802067653001902095653001602114653002102130653002202151653001102173653001102184653001702195653001502212653002502227653000902252653002402261653001202285653001102297653001302308100002802321700002402349700002102373700002402394700002002418700002002438700002202458700002202480700001802502856003602520 2011 eng d a1758-535X00aLeukocyte telomere length and mortality in the Cardiovascular Health Study.0 aLeukocyte telomere length and mortality in the Cardiovascular He c2011 Apr a421-90 v663 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aAging10aBody Mass Index10aCardiovascular Diseases10aCause of Death10aComorbidity10aCoronary Disease10aDiabetes Mellitus10aFemale10aHumans10aHypertension10aLeukocytes10aLongitudinal Studies10aMale10aProspective Studies10aSmoking10aStroke10aTelomere1 aFitzpatrick, Annette, L1 aKronmal, Richard, A1 aKimura, Masayuki1 aGardner, Jeffrey, P1 aPsaty, Bruce, M1 aJenny, Nancy, S1 aTracy, Russell, P1 aHardikar, Sheetal1 aAviv, Abraham uhttps://chs-nhlbi.org/node/126503031nas a2200361 4500008004100000022001400041245018100055210006900236260001300305300001100318490000700329520192100336653005102257653000902308653002802317653002802345653003002373653001102403653001102414653000902425653003202434653002402466653001702490100001702507700001602524700001302540700001502553700001602568700001602584700001502600700001802615856003602633 2011 eng d a1432-042800aLipoprotein-associated phospholipase A(2) and future risk of subclinical disease and cardiovascular events in individuals with type 2 diabetes: the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 and future risk of subcli c2011 Feb a329-330 v543 aAIMS/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.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aDiabetes Mellitus, Type 210aFemale10aHumans10aMale10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aNelson, T, L1 aKamineni, A1 aPsaty, B1 aCushman, M1 aJenny, N, S1 aHokanson, J1 aFurberg, C1 aMukamal, K, J uhttps://chs-nhlbi.org/node/125003433nas a2200481 4500008004100000022001400041245015800055210006900213260001300282300001100295490000700306520199800313653001602311653002202327653001502349653002302364653002802387653002802415653003802443653001102481653001102492653001702503653001802520653000902538653001402547653003002561653001702591653003202608653002202640653001802662100002002680700002102700700002002721700001802741700002402759700001902783700002002802700002802822700002302850700002202873700002002895856003602915 2011 eng d a1758-535X00aLongitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study.0 aLongitudinal changes in adiponectin and inflammatory markers and c2011 Oct a1100-70 v663 aBACKGROUND: 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.
10aAdiponectin10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aChi-Square Distribution10aEnzyme-Linked Immunosorbent Assay10aFemale10aHumans10aInflammation10aInterleukin-610aMale10aMortality10aPredictive Value of Tests10aRisk Factors10aSensitivity and Specificity10aSurvival Analysis10aUnited States1 aKizer, Jorge, R1 aArnold, Alice, M1 aJenny, Nancy, S1 aCushman, Mary1 aStrotmeyer, Elsa, S1 aIves, Diane, G1 aDing, Jingzhong1 aKritchevsky, Stephen, B1 aChaves, Paulo, H M1 aHirsch, Calvin, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/129602962nas a2200313 4500008004100000022001400041245014300055210006900198260001300267300001100280490000700291520201600298653002202314653002802336653002002364653002002384653002802404653001102432653001802443653001102461653000902472100002202481700002402503700002002527700002302547700002202570700002002592856003602612 2011 eng d a1532-541500aMeasurement of organ structure and function enhances understanding of the physiological basis of frailty: the Cardiovascular Health Study.0 aMeasurement of organ structure and function enhances understandi c2011 Sep a1581-80 v593 aOBJECTIVES: 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.
10aAged, 80 and over10aCardiovascular Diseases10aChronic Disease10aCost of Illness10aCross-Sectional Studies10aFemale10aFrail Elderly10aHumans10aMale1 aSanders, Jason, L1 aBoudreau, Robert, M1 aFried, Linda, P1 aWalston, Jeremy, D1 aHarris, Tamara, B1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/131806092nas a2201597 4500008004100000022001400041245012900055210006900184260001600253300001000269490000800279520159300287653001501880653002301895653002801918653003801946653003401984653001102018653001702029653001502046100001902061700001902080700001902099700001902118700002402137700001302161700002002174700002502194700002302219700002002242700001802262700002302280700002702303700002202330700002102352700002102373700001902394700002102413700001702434700001902451700002502470700001902495700002002514700002002534700002102554700002402575700001702599700002002616700002002636700002002656700002302676700002102699700002002720700001702740700001702757700001902774700001902793700002202812700002202834700002302856700002202879700002202901700002202923700002102945700002602966700002102992700002503013700001803038700001803056700002003074700001303094700002303107700002103130700001903151700001903170700001903189700001803208700001703226700002203243700001703265700004103282700002003323700002003343700001903363700002003382700002403402700001903426700002503445700001903470700001703489700001803506700001403524700002403538700001703562700002203579700001703601700002403618700001603642700002103658700002303679700002103702700002203723700001603745700002303761700002203784700002803806700002703834700001803861700001803879700002003897700002603917700002103943700002703964700002003991700002204011700002504033700002004058700002304078700001904101700002004120700002204140700002604162700002304188700002004211700002004231700002404251700002004275700001804295700002104313700002804334700003004362700002404392700001904416700002304435856003604458 2011 eng d a1524-453900aMeta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.0 aMetaanalysis of genomewide association studies in 80 000 subject c2011 Feb 22 a731-80 v1233 aBACKGROUND: C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels.
METHODS AND RESULTS: We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2) or the immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1) or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found a significant interaction of body mass index with LEPR (P<2.9×10(-6)). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained ≈5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease.
CONCLUSIONS: We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.
10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aRisk Factors10aVasculitis1 aDehghan, Abbas1 aDupuis, Josée1 aBarbalic, Maja1 aBis, Joshua, C1 aEiriksdottir, Gudny1 aLu, Chen1 aPellikka, Niina1 aWallaschofski, Henri1 aKettunen, Johannes1 aHenneman, Peter1 aBaumert, Jens1 aStrachan, David, P1 aFuchsberger, Christian1 aVitart, Veronique1 aWilson, James, F1 aParé, Guillaume1 aNaitza, Silvia1 aRudock, Megan, E1 aSurakka, Ida1 aGeus, Eco, J C1 aAlizadeh, Behrooz, Z1 aGuralnik, Jack1 aShuldiner, Alan1 aTanaka, Toshiko1 aZee, Robert, Y L1 aSchnabel, Renate, B1 aNambi, Vijay1 aKavousi, Maryam1 aRipatti, Samuli1 aNauck, Matthias1 aSmith, Nicholas, L1 aSmith, Albert, V1 aSundvall, Jouko1 aScheet, Paul1 aLiu, Yongmei1 aRuokonen, Aimo1 aRose, Lynda, M1 aLarson, Martin, G1 aHoogeveen, Ron, C1 aFreimer, Nelson, B1 aTeumer, Alexander1 aTracy, Russell, P1 aLauner, Lenore, J1 aBuring, Julie, E1 aYamamoto, Jennifer, F1 aFolsom, Aaron, R1 aSijbrands, Eric, J G1 aPankow, James1 aElliott, Paul1 aKeaney, John, F1 aSun, Wei1 aSarin, Antti-Pekka1 aFontes, João, D1 aBadola, Sunita1 aAstor, Brad, C1 aHofman, Albert1 aPouta, Anneli1 aWerdan, Karl1 aGreiser, Karin, H1 aKuss, Oliver1 aMeyer zu Schwabedissen, Henriette, E1 aThiery, Joachim1 aJamshidi, Yalda1 aNolte, Ilja, M1 aSoranzo, Nicole1 aSpector, Timothy, D1 aVölzke, Henry1 aParker, Alexander, N1 aAspelund, Thor1 aBates, David1 aYoung, Lauren1 aTsui, Kim1 aSiscovick, David, S1 aGuo, Xiuqing1 aRotter, Jerome, I1 aUda, Manuela1 aSchlessinger, David1 aRudan, Igor1 aHicks, Andrew, A1 aPenninx, Brenda, W1 aThorand, Barbara1 aGieger, Christian1 aCoresh, Joe1 aWillemsen, Gonneke1 aHarris, Tamara, B1 aUitterlinden, André, G1 aJarvelin, Marjo-Riitta1 aRice, Kenneth1 aRadke, Dörte1 aSalomaa, Veikko1 avan Dijk, Ko, Willems1 aBoerwinkle, Eric1 aVasan, Ramachandran, S1 aFerrucci, Luigi1 aGibson, Quince, D1 aBandinelli, Stefania1 aSnieder, Harold1 aBoomsma, Dorret, I1 aXiao, Xiangjun1 aCampbell, Harry1 aHayward, Caroline1 aPramstaller, Peter, P1 aDuijn, Cornelia, M1 aPeltonen, Leena1 aPsaty, Bruce, M1 aGudnason, Vilmundur1 aRidker, Paul, M1 aHomuth, Georg1 aKoenig, Wolfgang1 aBallantyne, Christie, M1 aWitteman, Jacqueline, C M1 aBenjamin, Emelia, J1 aPerola, Markus1 aChasman, Daniel, I uhttps://chs-nhlbi.org/node/126703083nas a2200469 4500008004100000022001400041245012500055210006900180260001300249300001100262490000600273520170600279653002101985653000902006653001502015653002802030653001902058653002502077653002702102653001102129653001102140653001402151653002602165653000902191653001602200653003102216653002202247653003002269653003202299653002602331653002002357653002102377653001702398653001802415100002302433700002202456700002702478700002402505700002402529700002402553856003602577 2011 eng d a1556-387100aN-terminal pro-B-type natriuretic peptide is associated with sudden cardiac death risk: the Cardiovascular Health Study.0 aNterminal proBtype natriuretic peptide is associated with sudden c2011 Feb a228-330 v83 aBACKGROUND: 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.
10aAge Distribution10aAged10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aConfidence Intervals10aDeath, Sudden, Cardiac10aFemale10aHumans10aIncidence10aKaplan-Meier Estimate10aMale10aMiddle Aged10aNatriuretic Peptide, Brain10aPeptide Fragments10aPredictive Value of Tests10aProportional Hazards Models10aRetrospective Studies10aRisk Assessment10aSex Distribution10aTime Factors10aUnited States1 aPatton, Kristen, K1 aSotoodehnia, Nona1 aDeFilippi, Christopher1 aSiscovick, David, S1 aGottdiener, John, S1 aKronmal, Richard, A uhttps://chs-nhlbi.org/node/124202855nas a2200421 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520167800263653000901941653002201950653002001972653002801992653003702020653003302057653001102090653002202101653001102123653001902134653001402153653000902167653001502176653001402191653002602205653001702231653001602248653002102264653001402285653001702299653001802316100002102334700002102355700002102376856003602397 2011 eng d a1758-535X00aPredictors of thyroid hormone initiation in older adults: results from the cardiovascular health study.0 aPredictors of thyroid hormone initiation in older adults results c2011 Jul a809-140 v663 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aDose-Response Relationship, Drug10aDrug Administration Schedule10aFemale10aFollow-Up Studies10aHumans10aHypothyroidism10aIncidence10aMale10aPrevalence10aPrognosis10aRetrospective Studies10aRisk Factors10aSex Factors10aThyroid Hormones10aThyroxine10aTime Factors10aUnited States1 aSomwaru, Lily, L1 aArnold, Alice, M1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/129303482nas a2200481 4500008004100000022001400041245014000055210006900195260001300264300001000277490000600287520214200293653000902435653002202444653001002466653001502476653002802491653002502519653001902544653001302563653002002576653001102596653002202607653001802629653001102647653001402658653000902672653002202681653001302703653003002716653001602746653002402762653001802786653001802804100001802822700002402840700002202864700002302886700001402909700001902923700002202942856003602964 2011 eng d a1941-329700aThe relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: the Cardiovascular Health Study.0 arelationship between serum markers of collagen turnover and card c2011 Nov a733-90 v43 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCollagen10aCollagen Type I10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPeptide Fragments10aPeptides10aPredictive Value of Tests10aProcollagen10aProspective Studies10aStroke Volume10aSurvival Rate1 aBarasch, Eddy1 aGottdiener, John, S1 aAurigemma, Gerard1 aKitzman, Dalane, W1 aHan, Jing1 aKop, Willem, J1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/132102825nas a2200349 4500008004100000022001400041245013900055210006900194260001300263300001000276490000700286520178800293653000902081653002302090653002802113653001602141653003602157653001102193653001102204653001402215653000902229653002002238653001702258653002402275653002202299653001802321653001802339653003602357100002202393700002402415856003602439 2011 eng d a1540-816700aRelationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults.0 aRelationship of abnormal heart rate turbulence and elevated CRP c2011 Feb a122-70 v223 aINTRODUCTION: 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.
10aAged10aC-Reactive Protein10aCardiovascular Diseases10aComorbidity10aElectrocardiography, Ambulatory10aFemale10aHumans10aIncidence10aMale10aRisk Assessment10aRisk Factors10aStatistics as Topic10aSurvival Analysis10aSurvival Rate10aUnited States10aVentricular Premature Complexes1 aStein, Phyllis, K1 aBarzilay, Joshua, I uhttps://chs-nhlbi.org/node/125502896nas a2200361 4500008004100000022001400041245010300055210006900158260001300227300001200240490000700252520185800259653000902117653002802126653002402154653001702178653001102195653002102206653002902227653002102256653002002277653001702297100001902314700002002333700001702353700002402370700001802394700002202412700002002434700002202454700002202476856003602498 2011 eng d a1524-462800aRetinal microvascular signs and functional loss in older persons: the cardiovascular health study.0 aRetinal microvascular signs and functional loss in older persons c2011 Jun a1589-950 v423 aBACKGROUND AND PURPOSE: We hypothesized that retinal microvascular signs are associated with executive dysfunction, slow gait, and depressive mood, which are characteristic features of microvascular disease affecting frontal subcortical regions of the brain.
METHODS: In the Cardiovascular Health Study, 1744 participants (mean age, 78) free of stroke had retinal photographs and carotid ultrasound during the 1997 to 1998 visit. We examined the cross-sectional association of retinal signs with the digit-symbol substitution test (DSST) score, gait speed, the Center for Epidemiologic Studies-Depression score, and depressive mood, defined as Center for Epidemiologic Studies-Depression score >9 or antidepressant use.
RESULTS: After adjusting for potential confounders, retinal signs were associated with lower DSST score (generalized arteriolar narrowing and arteriovenous nicking), slower gait (retinopathy), and depressive mood (generalized arteriolar narrowing). A higher number of retinal signs was associated with lower DSST score (-0.76 and -2.79 points for 1 sign and ≥2 signs versus none; P<0.001) and slower gait (-0.009 and -0.083 m/s; P=0.047), but not with the square root of Center for Epidemiologic Studies-Depression score (0.079 and -0.208; P=0.072). In addition, coexistence of retinal signs (generalized arteriolar narrowing and arteriovenous nicking) and carotid atherosclerosis was associated with lower DSST score compared with either process alone (P for interaction <0.01). Notably, further adjustment for ventricular size, white matter disease, and infarcts on MRI did not attenuate the association.
CONCLUSIONS: Retinal signs are associated with executive dysfunction and slow gait, and possibly with depressive mood, suggesting a common process involving small vessels.
10aAged10aCardiovascular Diseases10aDepressive Disorder10aFrontal Lobe10aHumans10aMicrocirculation10aNeuropsychological Tests10aRetinal Diseases10aRetinal Vessels10aRisk Factors1 aKim, Dae, Hyun1 aNewman, Anne, B1 aHajjar, Ihab1 aStrotmeyer, Elsa, S1 aKlein, Ronald1 aNewton, Elizabeth1 aSarnak, Mark, J1 aBurke, Gregory, L1 aLipsitz, Lewis, A uhttps://chs-nhlbi.org/node/128304370nas a2200613 4500008004100000022001400041245016100055210006900216260001600285300001200301490000800313520260000321653001602921653001902937653002002956653002802976653001603004653002103020653002203041653001103063653001103074653000903085653001603094653002303110653003203133653002403165653002003189653001603209653001203225653001203237653002403249653002003273110004003293700001903333700002103352700003003373700002003403700001903423700001903442700001903461700002003480700002203500700002803522700001703550700002003567700001803587700001903605700001903624700001803643700002303661700001903684700001703703856003603720 2011 eng d a1474-547X00aSeparate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies.0 aSeparate and combined associations of bodymass index and abdomin c2011 Mar 26 a1085-950 v3773 aBACKGROUND: 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.
10aAge Factors10aBlood Pressure10aBody Mass Index10aCardiovascular Diseases10aCholesterol10aCholesterol, HDL10aDiabetes Mellitus10aFemale10aHumans10aMale10aMiddle Aged10aObesity, Abdominal10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aSex Factors10aSmoking10aSystole10aWaist Circumference10aWaist-Hip Ratio1 aEmerging Risk Factors Collaboration1 aWormser, David1 aKaptoge, Stephen1 aDi Angelantonio, Emanuele1 aWood, Angela, M1 aPennells, Lisa1 aThompson, Alex1 aSarwar, Nadeem1 aKizer, Jorge, R1 aLawlor, Debbie, A1 aNordestgaard, Børge, G1 aRidker, Paul1 aSalomaa, Veikko1 aStevens, June1 aWoodward, Mark1 aSattar, Naveed1 aCollins, Rory1 aThompson, Simon, G1 aWhitlock, Gary1 aDanesh, John uhttps://chs-nhlbi.org/node/156302877nas a2200361 4500008004100000022001400041245011400055210006900169260001300238300001100251490000700262520185800269653000902127653002202136653002802158653002002186653001102206653001102217653000902228653000902237653002202246100002002268700002102288700002202309700002102331700002202352700002002374700002002394700002402414700002102438700002002459856003602479 2011 eng d a1758-535X00aSubclinical vascular disease burden and risk for death and cardiovascular events in older community dwellers.0 aSubclinical vascular disease burden and risk for death and cardi c2011 Sep a986-930 v663 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCost of Illness10aFemale10aHumans10aMale10aRisk10aVascular Diseases1 aInzitari, Marco1 aArnold, Alice, M1 aPatel, Kushang, V1 aMercer, Laina, D1 aKarlamangla, Arun1 aDing, Jingzhong1 aPsaty, Bruce, M1 aWilliamson, Jeff, D1 aKuller, Lewis, H1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/130002894nas a2200385 4500008004100000022001400041245008200055210006900137260001600206300001200222490000700234520184400241653001602085653000902101653002202110653001502132653002802147653001902175653001102194653002202205653001102227653000902238653002402247653002402271653001402295100002202309700001602331700001702347700002002364700002002384700002402404700002002428700002402448856003602472 2011 eng d a1558-359700aVitamin D, parathyroid hormone, and cardiovascular events among older adults.0 aVitamin D parathyroid hormone and cardiovascular events among ol c2011 Sep 27 a1433-410 v583 aOBJECTIVES: 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.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aMale10aParathyroid Hormone10aProspective Studies10aVitamin D1 aKestenbaum, Bryan1 aKatz, Ronit1 ade Boer, Ian1 aHoofnagle, Andy1 aSarnak, Mark, J1 aShlipak, Michael, G1 aJenny, Nancy, S1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/132903030nas a2200517 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520161100263653000901874653002801883653001601911653002701927653002201954653001101976653002201987653001102009653001702020653001402037653001102051653000902062653001602071653001302087653002402100653003202124653001702156653002602173653001802199653001402217100001502231700001602246700002402262700002202286700002002308700002002328700002002348700002102368700002002389700002402409700002102433700002202454856003602476 2011 eng d a1524-456300aVitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.0 aVitamin D parathyroid hormone and sudden cardiac death results f c2011 Dec a1021-80 v583 aRecent 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.
10aAged10aCardiovascular Diseases10aComorbidity10aDeath, Sudden, Cardiac10aDiabetes Mellitus10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aKidney10aMale10aMiddle Aged10aMinerals10aParathyroid Hormone10aProportional Hazards Models10aRisk Factors10aSocioeconomic Factors10aUnited States10aVitamin D1 aDeo, Rajat1 aKatz, Ronit1 aShlipak, Michael, G1 aSotoodehnia, Nona1 aPsaty, Bruce, M1 aSarnak, Mark, J1 aFried, Linda, F1 aChonchol, Michel1 ade Boer, Ian, H1 aEnquobahrie, Daniel1 aSiscovick, David1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/135003509nas a2200493 4500008004100000022001400041245019600055210006900251260001300320300001100333490000700344520201000351653000902361653002002370653001602390653002802406653001102434653001102445653000902456653001402465653001402479653001502493653003102508653002002539653002402559100002702583700002502610700002702635700002002662700002502682700003002707700001902737700002502756700002202781700002002803700002202823700002102845700001902866700001502885700002202900700002802922710002902950856003602979 2012 eng d a1464-368500aThe association between waist circumference and risk of mortality considering body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving more than 58 000 elderly persons.0 aassociation between waist circumference and risk of mortality co c2012 Jun a805-170 v413 aBACKGROUND: 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.
10aAged10aBody Mass Index10aBody Weight10aCardiovascular Diseases10aFemale10aHumans10aMale10aMortality10aNeoplasms10aOverweight10aRespiratory Tract Diseases10aRisk Assessment10aWaist Circumference1 ade Hollander, Ellen, L1 aBemelmans, Wanda, Je1 aBoshuizen, Hendriek, C1 aFriedrich, Nele1 aWallaschofski, Henri1 aGuallar-Castillón, Pilar1 aWalter, Stefan1 aZillikens, Carola, M1 aRosengren, Annika1 aLissner, Lauren1 aBassett, Julie, K1 aGiles, Graham, G1 aOrsini, Nicola1 aHeim, Noor1 aVisser, Marjolein1 ade Groot, Lisette, Cpgm1 aWC elderly collaborators uhttps://chs-nhlbi.org/node/137603479nas a2200529 4500008004100000022001400041245012700055210006900182260001600251300001200267490000800279520193000287653003902217653002102256653000902277653002202286653002802308653002002336653002302356653002802379653003002407653004002437653001102477653001102488653001402499653001502513653001102528653000902539653001902548653001502567653003202582653003002614653001702644653002102661100001902682700001902701700002402720700002002744700002102764700002402785700002602809700002202835700001902857700001902876700001802895856003602913 2012 eng d a1524-453900aAssociation of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.0 aAssociation of fetuina with incident diabetes mellitus in commun c2012 May 15 a2316-220 v1253 aBACKGROUND: 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.
10aAfrican Continental Ancestry Group10aAge Distribution10aAged10aAged, 80 and over10aalpha-2-HS-Glycoprotein10aBody Mass Index10aC-Reactive Protein10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aLife Style10aLipids10aMale10aPilot Projects10aPrevalence10aProportional Hazards Models10aResidence Characteristics10aRisk Factors10aSex Distribution1 aIx, Joachim, H1 aBiggs, Mary, L1 aMukamal, Kenneth, J1 aKizer, Jorge, R1 aZieman, Susan, J1 aSiscovick, David, S1 aMozzaffarian, Dariush1 aJensen, Majken, K1 aNelson, Lauren1 aRuderman, Neil1 aDjoussé, Luc uhttps://chs-nhlbi.org/node/138003599nas a2200457 4500008004100000022001400041245008200055210006900137260001600206300001100222490000800233520234700241653001002588653000902598653002202607653002002629653001602649653002802665653001902693653003002712653001102742653001102753653002502764653000902789653001602798653001202814653001502826653001802841100002702859700002902886700001902915700001902934700002102953700002202974700002302996700001503019700002403034700002903058700001803087856003603105 2012 eng d a1538-359800aAssociation of weight status with mortality in adults with incident diabetes.0 aAssociation of weight status with mortality in adults with incid c2012 Aug 08 a581-900 v3083 aCONTEXT: 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.
10aAdult10aAged10aAged, 80 and over10aBody Mass Index10aBody Weight10aCardiovascular Diseases10aCause of Death10aDiabetes Mellitus, Type 210aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aObesity10aOverweight10aUnited States1 aCarnethon, Mercedes, R1 aDe Chavez, Peter, John D1 aBiggs, Mary, L1 aLewis, Cora, E1 aPankow, James, S1 aBertoni, Alain, G1 aGolden, Sherita, H1 aLiu, Kiang1 aMukamal, Kenneth, J1 aCampbell-Jenkins, Brenda1 aDyer, Alan, R uhttps://chs-nhlbi.org/node/140203420nas a2200517 4500008004100000022001400041245023700055210006900292260001600361300001000377490000600387520182700393653000902220653002202229653002802251653002102279653002102300653004002321653001102361653002502372653003402397653001302431653001102444653000902455653001602464653003602480653001702516653001102533653001802544100001902562700002102581700002002602700002302622700001802645700001902663700002302682700002302705700001402728700002002742700001602762700002002778700001902798700002502817700002402842856003602866 2012 eng d a1942-326800aAssociations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.0 aAssociations between incident ischemic stroke events and stroke c2012 Apr 01 a210-60 v53 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aEuropean Continental Ancestry Group10aFemale10aGenetics, Population10aGenome-Wide Association Study10aGenomics10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk Factors10aStroke10aTriglycerides1 aCarty, Cara, L1 aBůzková, Petra1 aFornage, Myriam1 aFranceschini, Nora1 aCole, Shelley1 aHeiss, Gerardo1 aHindorff, Lucia, A1 aHoward, Barbara, V1 aMann, Sue1 aMartin, Lisa, W1 aZhang, Ying1 aMatise, Tara, C1 aPrentice, Ross1 aReiner, Alexander, P1 aKooperberg, Charles uhttps://chs-nhlbi.org/node/137103754nas a2200493 4500008004100000022001400041245014600055210006900201260001600270300001200286490000800298520227800306653000902584653001602593653002802609653001902637653002702656653001102683653003102694653001102725653002802736653000902764653001602773653001702789100002102806700002502827700001902852700002002871700001902891700003202910700001802942700002302960700001902983700002303002700002203025700002603047700002403073700001803097700002103115700001803136700002203154710004803176856003603224 2012 eng d a1474-547X00aAssociations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.0 aAssociations of kidney disease measures with mortality and endst c2012 Nov 10 a1662-730 v3803 aBACKGROUND: 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.
10aAged10aAlbuminuria10aCardiovascular Diseases10aCause of Death10aDiabetic Nephropathies10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aRisk Factors1 aFox, Caroline, S1 aMatsushita, Kunihiro1 aWoodward, Mark1 aBilo, Henk, J G1 aChalmers, John1 aHeerspink, Hiddo, J Lambers1 aLee, Brian, J1 aPerkins, Robert, M1 aRossing, Peter1 aSairenchi, Toshimi1 aTonelli, Marcello1 aVassalotti, Joseph, A1 aYamagishi, Kazumasa1 aCoresh, Josef1 ade Jong, Paul, E1 aWen, Chi-Pang1 aNelson, Robert, G1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/608603348nas a2200397 4500008004100000022001400041245015900055210006900214260001600283300001200299490000800311520216300319653001602482653000902498653002202507653002002529653002802549653001102577653001902588653001102607653000902618653002102627100002002648700002002668700002102688700002402709700001902733700002102752700002402773700002202797700002702819700003002846700002002876700001802896856003602914 2012 eng d a1524-453900aAssociations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.0 aAssociations of total and highmolecularweight adiponectin with a c2012 Dec 18 a2951-610 v1263 aBACKGROUND: 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.
10aAdiponectin10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aFemale10aHealth Surveys10aHumans10aMale10aMolecular Weight1 aKizer, Jorge, R1 aBenkeser, David1 aArnold, Alice, M1 aMukamal, Kenneth, J1 aIx, Joachim, H1 aZieman, Susan, J1 aSiscovick, David, S1 aTracy, Russell, P1 aMantzoros, Christos, S1 adeFilippi, Christopher, R1 aNewman, Anne, B1 aDjoussé, Luc uhttps://chs-nhlbi.org/node/155303965nas a2200493 4500008004100000022001400041245019200055210006900247260001600316300001200332490000800344520243000352653002802782653003502810653002402845653002202869653001102891653002602902653001402928653002002942653001102962100002402973700002102997700002003018700002603038700001903064700002603083700001703109700002303126700002603149700002803175700001903203700002003222700002303242700001503265700002103280700002803301700001203329700002503341700002103366700002303387710002503410856003603435 2012 eng d a1474-547X00aCarotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.0 aCarotid intimamedia thickness progression to predict cardiovascu c2012 Jun 02 a2053-620 v3793 aBACKGROUND: Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association.
METHODS: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis.
FINDINGS: Of 21 eligible studies, 16 with 36,984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94-1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95-1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10-1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0·06 and r=-0·02).
INTERPRETATION: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.
FUNDING: Deutsche Forschungsgemeinschaft.
10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aDisease Progression10aFollow-Up Studies10aHumans10aMyocardial Infarction10aPrognosis10aRisk Assessment10aStroke1 aLorenz, Matthias, W1 aPolak, Joseph, F1 aKavousi, Maryam1 aMathiesen, Ellisiv, B1 aVölzke, Henry1 aTuomainen, Tomi-Pekka1 aSander, Dirk1 aPlichart, Matthieu1 aCatapano, Alberico, L1 aRobertson, Christine, M1 aKiechl, Stefan1 aRundek, Tatjana1 aDesvarieux, Moïse1 aLind, Lars1 aSchmid, Caroline1 aDasMahapatra, Pronabesh1 aGao, Lu1 aZiegelbauer, Kathrin1 aBots, Michiel, L1 aThompson, Simon, G1 aPROG-IMT Study Group uhttps://chs-nhlbi.org/node/138203251nas a2200517 4500008004100000022001400041245013800055210007000193260001300263300001100276490000700287520177900294653000902073653002102082653002502103653001502128653002002143653002802163653000902191653002702200653001102227653002202238653001802260653001102278653001402289653000902303653003602312653001502348653002402363653001702387653001202404653003102416653001802447100002402465700002102489700001902510700001902529700002202548700002202570700002002592700001802612700001802630700002402648700002502672856003602697 2012 eng d a1938-320700aCirculating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.0 aCirculating and dietary αlinolenic acid and incidence of congest c2012 Aug a269-740 v963 aBACKGROUND: 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.
10aAged10aAlcohol Drinking10aalpha-Linolenic Acid10aBiomarkers10aBody Mass Index10aCardiovascular Diseases10aDiet10aFatty Acid Desaturases10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPolymorphism, Single Nucleotide10aPrevalence10aProspective Studies10aRisk Factors10aSmoking10aSurveys and Questionnaires10aUnited States1 aLemaitre, Rozenn, N1 aSitlani, Colleen1 aSong, Xiaoling1 aKing, Irena, B1 aMcKnight, Barbara1 aSpiegelman, Donna1 aSacks, Frank, M1 aDjoussé, Luc1 aRimm, Eric, B1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/139604730nas a2200541 4500008004100000022001400041245013100055210006900186260001600255300001200271490000800283520307700291653003903368653000903407653001503416653003703431653002803468653001903496653003203515653004003547653001103587653003103598653001103629653002803640653000903668653001603677653002403693653002003717653001603737100002503753700002703778700001903805700002603824700002103850700001703871700002703888700001903915700002003934700002203954700002203976700001803998700001804016700002304034700002604057700002104083710004804104856003604152 2012 eng d a1538-359800aComparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.0 aComparison of risk prediction using the CKDEPI equation and the c2012 May 09 a1941-510 v3073 aCONTEXT: 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.
10aAfrican Continental Ancestry Group10aAged10aAlgorithms10aAsian Continental Ancestry Group10aCardiovascular Diseases10aCohort Studies10aDecision Support Techniques10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aModels, Theoretical10aRisk Assessment10aSex Factors1 aMatsushita, Kunihiro1 aMahmoodi, Bakhtawar, K1 aWoodward, Mark1 aEmberson, Jonathan, R1 aJafar, Tazeen, H1 aJee, Sun, Ha1 aPolkinghorne, Kevan, R1 aShankar, Anoop1 aSmith, David, H1 aTonelli, Marcello1 aWarnock, David, G1 aWen, Chi-Pang1 aCoresh, Josef1 aGansevoort, Ron, T1 aHemmelgarn, Brenda, R1 aLevey, Andrew, S1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/138502996nas a2200433 4500008004100000022001400041245013100055210006900186260001300255300001100268490000700279520163600286653003901922653000901961653002201970653002801992653004002020653001102060653002202071653001102093653004902104653004902153653003302202653002502235653000902260653001402269653003002283653001702313100002202330700002102352700002102373700002502394700002202419700002102441700002102462700002302483700002002506856003602526 2012 eng d a1945-719700aDecline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study.0 aDecline in circulating insulinlike growth factors and mortality c2012 Jun a1970-60 v973 aBACKGROUND: 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.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aLongitudinal Studies10aMale10aMortality10aPredictive Value of Tests10aRisk Factors1 aKaplan, Robert, C1 aBůzková, Petra1 aCappola, Anne, R1 aStrickler, Howard, D1 aMcGinn, Aileen, P1 aMercer, Laina, D1 aArnold, Alice, M1 aPollak, Michael, N1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/137403528nas a2200721 4500008004100000022001400041245014600055210006900201260000900270300001100279490000600290520139200296653002201688653002801710653004001738653002101778653002101799653002301820653001901843653001901862653003401881653001301915653001101928653002301939653003601962653002801998100001902026700001302045700001902058700001602077700002902093700002202122700002302144700002202167700002302189700002102212700002102233700002202254700002102276700001802297700002202315700002502337700002302362700002202385700001702407700002002424700002402444700001202468700002302480700002002503700002602523700002202549700002802571700002402599700001802623700002102641700002102662700002702683700001902710700002202729700001902751856003602770 2012 eng d a1932-620300aEvaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study.0 aEvaluation of the metabochip genotyping array in African America c2012 ae356510 v73 aThe Metabochip is a custom genotyping array designed for replication and fine mapping of metabolic, cardiovascular, and anthropometric trait loci and includes low frequency variation content identified from the 1000 Genomes Project. It has 196,725 SNPs concentrated in 257 genomic regions. We evaluated the Metabochip in 5,863 African Americans; 89% of all SNPs passed rigorous quality control with a call rate of 99.9%. Two examples illustrate the value of fine mapping with the Metabochip in African-ancestry populations. At CELSR2/PSRC1/SORT1, we found the strongest associated SNP for LDL-C to be rs12740374 (p = 3.5 × 10(-11)), a SNP indistinguishable from multiple SNPs in European ancestry samples due to high correlation. Its distinct signal supports functional studies elsewhere suggesting a causal role in LDL-C. At CETP we found rs17231520, with risk allele frequency 0.07 in African Americans, to be associated with HDL-C (p = 7.2 × 10(-36)). This variant is very rare in Europeans and not tagged in common GWAS arrays, but was identified as associated with HDL-C in African Americans in a single-gene study. Our results, one narrowing the risk interval and the other revealing an associated variant not found in Europeans, demonstrate the advantages of high-density genotyping of common and rare variation for fine mapping of trait loci in African American samples.
10aAfrican Americans10aCardiovascular Diseases10aCholesterol Ester Transfer Proteins10aCholesterol, HDL10aCholesterol, LDL10aChromosomes, Human10aCohort Studies10aGene Frequency10aGenome-Wide Association Study10aGenotype10aHumans10aMetabolic Diseases10aPolymorphism, Single Nucleotide10aQuantitative Trait Loci1 aBuyske, Steven1 aWu, Ying1 aCarty, Cara, L1 aCheng, Iona1 aAssimes, Themistocles, L1 aDumitrescu, Logan1 aHindorff, Lucia, A1 aMitchell, Sabrina1 aAmbite, Jose, Luis1 aBoerwinkle, Eric1 aBůzková, Petra1 aCarlson, Chris, S1 aCochran, Barbara1 aDuggan, David1 aEaton, Charles, B1 aFesinmeyer, Megan, D1 aFranceschini, Nora1 aHaessler, Jeffrey1 aJenny, Nancy1 aKang, Hyun, Min1 aKooperberg, Charles1 aLin, Yi1 aLe Marchand, Loïc1 aMatise, Tara, C1 aRobinson, Jennifer, G1 aRodriguez, Carlos1 aSchumacher, Fredrick, R1 aVoight, Benjamin, F1 aYoung, Alicia1 aManolio, Teri, A1 aMohlke, Karen, L1 aHaiman, Christopher, A1 aPeters, Ulrike1 aCrawford, Dana, C1 aNorth, Kari, E uhttps://chs-nhlbi.org/node/663402648nas a2200373 4500008004100000022001400041245018200055210006900237260001600306300001000322490000800332520153700340653000901877653002201886653001901908653002801927653001901955653001101974653002201985653001102007653001702018653001602035653002502051653000902076653001602085653001702101100001902118700002102137700001802158700002002176700001502196700002702211856003602238 2012 eng d a1524-453900aImpact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project.0 aImpact of blood pressure and blood pressure change during middle c2012 Jan 03 a37-440 v1253 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aFemale10aFollow-Up Studies10aHumans10aHypertension10aLife Tables10aLongitudinal Studies10aMale10aMiddle Aged10aRisk Factors1 aAllen, Norrina1 aBerry, Jarett, D1 aNing, Hongyan1 aVan Horn, Linda1 aDyer, Alan1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/608503315nas a2200529 4500008004100000022001400041245007000055210006700125260001300192300001200205490000700217520186700224653000902091653002202100653001802122653001902140653002302159653002802182653002102210653002102231653001902252653001502271653001202286653001102298653003102309653001102340653002302351653001502374653000902389653001402398653003002412653003202442653002402474653001702498653001802515653002402533100002002557700001602577700002402593700002002617700001902637700002202656700002402678700002302702700002402725856003602749 2012 eng d a1935-554800aInsulin resistance, cystatin C, and mortality among older adults.0 aInsulin resistance cystatin C and mortality among older adults c2012 Jun a1355-600 v353 aOBJECTIVE: 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.
10aAged10aAged, 80 and over10aBlood Glucose10aBlood Pressure10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aCohort Studies10aCystatin C10aFasting10aFemale10aGlomerular Filtration Rate10aHumans10aInsulin Resistance10aLife Style10aMale10aMortality10aPredictive Value of Tests10aProportional Hazards Models10aRenal Insufficiency10aRisk Factors10aTriglycerides10aWaist Circumference1 ade Boer, Ian, H1 aKatz, Ronit1 aChonchol, Michel, B1 aFried, Linda, F1 aIx, Joachim, H1 aKestenbaum, Bryan1 aMukamal, Kenneth, J1 aPeralta, Carmen, A1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/137203458nas a2200481 4500008004100000022001400041245009100055210006900146260001300215300001100228490000700239520210500246653002202351653002502373653002802398653002802426653001502454653001502469653002202484653001102506653003102517653001102548653001702559653002002576653000902596653001502605653003202620653002602652653001702678653001802695100001902713700001602732700002002748700002002768700002302788700002302811700002102834700002102855700002402876700002002900700002002920856003602940 2012 eng d a1532-541500aKidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.0 aKidney function and mortality in octogenarians Cardiovascular He c2012 Jul a1201-70 v603 aOBJECTIVES: 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) .
10aAged, 80 and over10aAnalysis of Variance10aCardiovascular Diseases10aChi-Square Distribution10aCreatinine10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney Diseases10aMale10aPrevalence10aProportional Hazards Models10aRetrospective Studies10aRisk Factors10aUnited States1 aShastri, Shani1 aKatz, Ronit1 aRifkin, Dena, E1 aFried, Linda, F1 aOdden, Michelle, C1 aPeralta, Carmen, A1 aChonchol, Michel1 aSiscovick, David1 aShlipak, Michael, G1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/139502993nas a2200421 4500008004100000022001400041245012600055210006900181260001300250300001100263490000700274520177100281653002202052653000902074653002202083653002802105653003502133653002002168653001502188653004002203653001102243653001102254653001502265653000902280653000902289653001602298653002502314100002202339700002802361700002402389700002102413700001802434700002102452700002002473700002202493700002002515856003602535 2012 eng d a1758-535X00aLeukocyte telomere length is associated with noninvasively measured age-related disease: The Cardiovascular Health Study.0 aLeukocyte telomere length is associated with noninvasively measu c2012 Apr a409-160 v673 aBACKGROUND: 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.
10aAfrican Americans10aAged10aAged, 80 and over10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aChronic Disease10aCystatin C10aEuropean Continental Ancestry Group10aFemale10aHumans10aLeukocytes10aLung10aMale10aMiddle Aged10aTelomere Homeostasis1 aSanders, Jason, L1 aFitzpatrick, Annette, L1 aBoudreau, Robert, M1 aArnold, Alice, M1 aAviv, Abraham1 aKimura, Masayuki1 aFried, Linda, F1 aHarris, Tamara, B1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/132803609nas a2200397 4500008004100000022001400041245007200055210006900127260001600196300001300212490000800225520257600233653001002809653000902819653001902828653002802847653001902875653002202894653001102916653001602927653001102943653002602954653000902980653001602989653001403005653000903019653001703028653001203045100002103057700001803078700001803096700001603114700001803130700002703148856003603175 2012 eng d a1538-359800aLifetime risk and years lived free of total cardiovascular disease.0 aLifetime risk and years lived free of total cardiovascular disea c2012 Nov 07 a1795-8010 v3083 aCONTEXT: 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.
10aAdult10aAged10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aForecasting10aHumans10aKaplan-Meier Estimate10aMale10aMiddle Aged10aMorbidity10aRisk10aRisk Factors10aSmoking1 aWilkins, John, T1 aNing, Hongyan1 aBerry, Jarett1 aZhao, Lihui1 aDyer, Alan, R1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/586103127nas a2200421 4500008004100000022001400041245004600055210004500101260001600146300001000162490000800172520205200180653001002232653002202242653000902264653002802273653001802301653004002319653001102359653001102370653000902381653001602390653000902406653002002415653001702435653001802452100002102470700001502491700001402506700002302520700001802543700001702561700002202578700002002600700002202620700002702642856003602669 2012 eng d a1533-440600aLifetime risks of cardiovascular disease.0 aLifetime risks of cardiovascular disease c2012 Jan 26 a321-90 v3663 aBACKGROUND: 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.).
10aAdult10aAfrican Americans10aAged10aCardiovascular Diseases10aCohort Effect10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aMiddle Aged10aRisk10aRisk Assessment10aRisk Factors10aUnited States1 aBerry, Jarett, D1 aDyer, Alan1 aCai, Xuan1 aGarside, Daniel, B1 aNing, Hongyan1 aThomas, Avis1 aGreenland, Philip1 aVan Horn, Linda1 aTracy, Russell, P1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/154104973nas a2200937 4500008004100000022001400041245006500055210006300120260001600183300001300199490000800212520237500220653000902595653001502604653002802619653002102647653001902668653001102687653001102698653001702709653000902726653001602735653002002751110004002771700003002811700001302841700001902854700002102873700002002894700002402914700002502938700001902963700001902982700002103001700002803022700002003050700002203070700002003092700002003112700002303132700001403155700002403169700001903193700002103212700002503233700001803258700002503276700002403301700002203325700001903347700001603366700002303382700003503405700002203440700002503462700002003487700002103507700002203528700001903550700002003569700003003589700001903619700001803638700001903656700002003675700002203695700002503717700001803742700002003760700002203780700002303802700002803825700002003853700002303873700002403896700001903920700001903939700002403958700001703982856003603999 2012 eng d a1538-359800aLipid-related markers and cardiovascular disease prediction.0 aLipidrelated markers and cardiovascular disease prediction c2012 Jun 20 a2499-5060 v3073 aCONTEXT: 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.
10aAged10aBiomarkers10aCardiovascular Diseases10aCholesterol, HDL10aCohort Studies10aFemale10aHumans10aLipoproteins10aMale10aMiddle Aged10aRisk Assessment1 aEmerging Risk Factors Collaboration1 aDi Angelantonio, Emanuele1 aGao, Pei1 aPennells, Lisa1 aKaptoge, Stephen1 aCaslake, Muriel1 aThompson, Alexander1 aButterworth, Adam, S1 aSarwar, Nadeem1 aWormser, David1 aSaleheen, Danish1 aBallantyne, Christie, M1 aPsaty, Bruce, M1 aSundström, Johan1 aRidker, Paul, M1 aNagel, Dorothea1 aGillum, Richard, F1 aFord, Ian1 aDucimetiere, Pierre1 aKiechl, Stefan1 aKoenig, Wolfgang1 aDullaart, Robin, P F1 aAssmann, Gerd1 aD'Agostino, Ralph, B1 aDagenais, Gilles, R1 aCooper, Jackie, A1 aKromhout, Daan1 aOnat, Altan1 aTipping, Robert, W1 aGómez-de-la-Cámara, Agustín1 aRosengren, Annika1 aSutherland, Susan, E1 aGallacher, John1 aFowkes, Gerry, R1 aCasiglia, Edoardo1 aHofman, Albert1 aSalomaa, Veikko1 aBarrett-Connor, Elizabeth1 aClarke, Robert1 aBrunner, Eric1 aJukema, Wouter1 aSimons, Leon, A1 aSandhu, Manjinder1 aWareham, Nicholas, J1 aKhaw, Kay-Tee1 aKauhanen, Jussi1 aSalonen, Jukka, T1 aHoward, William, J1 aNordestgaard, Børge, G1 aWood, Angela, M1 aThompson, Simon, G1 aBoekholdt, Matthijs1 aSattar, Naveed1 aPackard, Chris1 aGudnason, Vilmundur1 aDanesh, John uhttps://chs-nhlbi.org/node/139903296nas a2200409 4500008004100000022001400041245013600055210006900191260001300260300001300273490000700286520212000293653005102413653000902464653002202473653002802495653003002523653001102553653001102564653001402575653002302589653000902612653001602621653003002637653001502667653002402682653000902706653001702715100001702732700001602749700001602765700001502781700001902796700001702815700001802832856003602850 2012 eng d a1945-719700aLipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study.0 aLipoproteinassociated phospholipase A2 LpPLA2 and future risk of c2012 May a1695-7010 v973 aINTRODUCTION: 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.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAged10aAged, 80 and over10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aFemale10aHumans10aIncidence10aInsulin Resistance10aMale10aMiddle Aged10aPredictive Value of Tests10aPrevalence10aProspective Studies10aRisk10aRisk Factors1 aNelson, T, L1 aBiggs, M, L1 aKizer, J, R1 aCushman, M1 aHokanson, J, E1 aFurberg, C D1 aMukamal, K, J uhttps://chs-nhlbi.org/node/136903074nas a2200481 4500008004100000022001400041245011600055210006900171260001300240300001000253490000700263520173100270653000902001653002202010653001002032653002302042653002802065653001402093653001902107653002802126653001102154653001102165653001702176653002702193653001802220653002502238653000902263653001702272653001202289100002002301700002102321700002102342700002402363700001802387700002302405700002002428700002002448700002802468700002002496700002002516700002002536856003602556 2012 eng d a1758-535X00aLong-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.0 aLongterm assessment of inflammation and healthy aging in late li c2012 Sep a970-60 v673 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aAging10aC-Reactive Protein10aCardiovascular Diseases10aCognition10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aInflammation10aInflammation Mediators10aInterleukin-610aLongitudinal Studies10aMale10aRisk Factors10aVermont1 aJenny, Nancy, S1 aFrench, Benjamin1 aArnold, Alice, M1 aStrotmeyer, Elsa, S1 aCushman, Mary1 aChaves, Paulo, H M1 aDing, Jingzhong1 aFried, Linda, P1 aKritchevsky, Stephen, B1 aRifkin, Dena, E1 aSarnak, Mark, J1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/136602441nas a2200385 4500008004100000022001400041245015700055210006900212260001600281300001100297490000800308520129400316653000901610653001801619653002801637653001101665653002901676653001801705653002501723653001101748653000901759653002401768653003101792653001601823653001201839653001701851653001801868653001901886100002201905700002101927700002301948700002001971700002801991856003602019 2012 eng d a1476-625600aModification of the association between ambient air pollution and lung function by frailty status among older adults in the Cardiovascular Health Study.0 aModification of the association between ambient air pollution an c2012 Aug 01 a214-230 v1763 aThe 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).
10aAged10aAir Pollution10aCardiovascular Diseases10aFemale10aForced Expiratory Volume10aFrail Elderly10aGeriatric Assessment10aHumans10aMale10aProspective Studies10aRespiratory Function Tests10aSex Factors10aSmoking10aTime Factors10aUnited States10aVital Capacity1 aEckel, Sandrah, P1 aLouis, Thomas, A1 aChaves, Paulo, H M1 aFried, Linda, P1 aMargolis, And, Helene G uhttps://chs-nhlbi.org/node/140003060nas a2200421 4500008004100000022001400041245010300055210006900158260001300227300001100240490000700251520187200258653002102130653000902151653002202160653001902182653002802201653001902229653002402248653001102272653001102283653001902294653002202313653002002335653002502355653000902380653001502389653001702404653003002421653003002451653002102481653001602502100002102518700002102539700002102560700002102581856003602602 2012 eng d a1945-719700aThe natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study.0 anatural history of subclinical hypothyroidism in the elderly the c2012 Jun a1962-90 v973 aCONTEXT: 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.
10aAge Distribution10aAged10aAged, 80 and over10aAutoantibodies10aCardiovascular Diseases10aCohort Studies10aDisease Progression10aFemale10aHumans10aHypothyroidism10aIodide Peroxidase10aLogistic Models10aLongitudinal Studies10aMale10aPrevalence10aRisk Factors10aSeroepidemiologic Studies10aSeverity of Illness Index10aSex Distribution10aThyrotropin1 aSomwaru, Lily, L1 aRariy, Chevon, M1 aArnold, Alice, M1 aCappola, Anne, R uhttps://chs-nhlbi.org/node/137302907nas a2200325 4500008004100000022001400041245010000055210006900155260000900224300001100233490000600244520199600250653000902246653002802255653002802283653001102311653001102322653000902333653001602342653001302358653002002371653002602391100002602417700002402443700002202467700001602489700002002505700002002525856003602545 2012 eng d a1932-620300aNocturia, sleep-disordered breathing, and cardiovascular morbidity in a community-based cohort.0 aNocturia sleepdisordered breathing and cardiovascular morbidity c2012 ae309690 v73 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aFemale10aHumans10aMale10aMiddle Aged10aNocturia10aPolysomnography10aSleep Apnea Syndromes1 aParthasarathy, Sairam1 aFitzgerald, MaryPat1 aGoodwin, James, L1 aUnruh, Mark1 aGuerra, Stefano1 aQuan, Stuart, F uhttps://chs-nhlbi.org/node/155803386nas a2200505 4500008004100000022001400041245011100055210006900166260001300235300001200248490000700260520193600267653000902203653002202212653001502234653002802249653001902277653002802296653002402324653001102348653002202359653001102381653001402392653002502406653000902431653001602440653002402456653003302480653003202513653002402545653001702569653001102586653002202597653001802619100002102637700002402658700001902682700001902701700002702720700002302747700002502770700002402795700002502819856003602844 2012 eng d a1938-320700aNovel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study.0 aNovel circulating fatty acid patterns and risk of cardiovascular c2012 Dec a1252-610 v963 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aCoronary Artery Disease10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aIncidence10aLongitudinal Studies10aMale10aMiddle Aged10aMyocardial Ischemia10aPrincipal Component Analysis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke10aTrans Fatty Acids10aUnited States1 aImamura, Fumiaki1 aLemaitre, Rozenn, N1 aKing, Irena, B1 aSong, Xiaoling1 aLichtenstein, Alice, H1 aMatthan, Nirupa, R1 aHerrington, David, M1 aSiscovick, David, S1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/141002961nas a2200397 4500008004100000022001400041245013600055210006900191260001300260300001300273490000700286520180700293653000902100653002202109653002802131653001102159653001102170653000902181653002502190653002402215653003002239100002402269700002102293700001702314700001602331700002502347700002402372700001902396700001302415700002102428700002202449700002102471700001802492700001702510856003602527 2012 eng d a1532-541500aPersistence and remission of musculoskeletal pain in community-dwelling older adults: results from the cardiovascular health study.0 aPersistence and remission of musculoskeletal pain in communitydw c2012 Aug a1393-4000 v603 aOBJECTIVES: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aHumans10aMale10aMusculoskeletal Pain10aRemission Induction10aResidence Characteristics1 aThielke, Stephen, M1 aWhitson, Heather1 aDiehr, Paula1 aO'Hare, Ann1 aKearney, Patricia, M1 aChaudhry, Sarwat, I1 aZakai, Neil, A1 aKim, Dae1 aSekaran, Nishant1 aSale, Joanna, E M1 aArnold, Alice, M1 aChaves, Paulo1 aNewman, Anne uhttps://chs-nhlbi.org/node/140103266nas a2200421 4500008004100000022001400041245022000055210006900275260001600344300000900360490000800369520191700377653003902294653001602333653000902349653002202358653002002380653002802400653001902428653003402447653001802481653004002499653001102539653002202550653001102572653002502583653000902608653001602617653003002633653001702663100002302680700001802703700001702721700001902738700002402757700002702781856003602808 2012 eng d a1524-453900aRacial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.0 aRacial differences in risks for first cardiovascular events and c2012 Jul 03 a50-90 v1263 aBACKGROUND: 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.
10aAfrican Continental Ancestry Group10aAge Factors10aAged10aAged, 80 and over10aAtherosclerosis10aCardiovascular Diseases10aCohort Studies10aContinental Population Groups10aEthnic Groups10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aResidence Characteristics10aRisk Factors1 aFeinstein, Matthew1 aNing, Hongyan1 aKang, Joseph1 aBertoni, Alain1 aCarnethon, Mercedes1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/139002549nas a2200433 4500008004100000022001400041245013900055210006900194260001300263300001100276490000800287520129900295653000901594653002201603653002801625653001901653653004001672653001101712653001101723653001501734653000901749653002601758653003601784653000901820653000801829653001601837653001501853653001301868100003101881700002801912700002401940700002001964700002001984700001702004700001902021700002102040700001802061856003602079 2012 eng d a1872-621600aTelomere-associated polymorphisms correlate with cardiovascular disease mortality in Caucasian women: the Cardiovascular Health Study.0 aTelomereassociated polymorphisms correlate with cardiovascular d c2012 May a275-810 v1333 aLeukocyte 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHumans10aLeukocytes10aMale10aPolymorphism, Genetic10aPolymorphism, Single Nucleotide10aRisk10aRNA10aSex Factors10aTelomerase10aTelomere1 aBurnett-Hartman, Andrea, N1 aFitzpatrick, Annette, L1 aKronmal, Richard, A1 aPsaty, Bruce, M1 aJenny, Nancy, S1 aBis, Josh, C1 aTracy, Russ, P1 aKimura, Masayuki1 aAviv, Abraham uhttps://chs-nhlbi.org/node/137502535nas a2200409 4500008004100000022001400041245007200055210006900127260000900196300001100205490000700216520142400223653001401647653000901661653002201670653002001692653002801712653002401740653002301764653001101787653001101798653000901809653001701818653002401835653002001859100002501879700001901904700002001923700002101943700002501964700001701989700002702006700001702033700002102050700001802071856003602089 2013 eng d a1423-020800aAdiposity and cognitive decline in the cardiovascular health study.0 aAdiposity and cognitive decline in the cardiovascular health stu c2013 a274-810 v403 aBACKGROUND: 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.
10aAdiposity10aAged10aAged, 80 and over10aBody Mass Index10aCardiovascular Diseases10aCognition Disorders10aElectric Impedance10aFemale10aHumans10aMale10aRisk Factors10aWaist Circumference10aWaist-Hip Ratio1 aLuchsinger, José, A1 aBiggs, Mary, L1 aKizer, Jorge, R1 aBarzilay, Joshua1 aFitzpatrick, Annette1 aNewman, Anne1 aLongstreth, William, T1 aLopez, Oscar1 aSiscovick, David1 aKuller, Lewis uhttps://chs-nhlbi.org/node/584903502nas a2200481 4500008004100000022001400041245014100055210006900196260001600265300001000281490000800291520213900299653000902438653002402447653002802471653002702499653001502526653001802541653001102559653001102570653001402581653000902595653001602604653003202620653002002652653001702672653001602689653001802705100001702723700002202740700002102762700001902783700001802802700002302820700002002843700002402863700001902887700001702906700002102923700002102944700001902965856003602984 2013 eng d a2168-611400aAtrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study.0 aAtrial fibrillation and the risk of sudden cardiac death the ath c2013 Jan 14 a29-350 v1733 aBACKGROUND: 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.
10aAged10aAtrial Fibrillation10aCardiovascular Diseases10aDeath, Sudden, Cardiac10aDemography10aEthnic Groups10aFemale10aHumans10aIncidence10aMale10aMiddle Aged10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aSex Factors10aUnited States1 aChen, Lin, Y1 aSotoodehnia, Nona1 aBůzková, Petra1 aLopez, Faye, L1 aYee, Laura, M1 aHeckbert, Susan, R1 aPrineas, Ronald1 aSoliman, Elsayed, Z1 aAdabag, Selcuk1 aKonety, Suma1 aFolsom, Aaron, R1 aSiscovick, David1 aAlonso, Alvaro uhttps://chs-nhlbi.org/node/585002901nas a2200469 4500008004100000022001400041245016500055210006900220260001300289300001200302490000700314520155100321653001401872653000901886653001801895653002801913653002801941653001301969653001101982653001101993653002802004653001702032653001202049653002302061653002502084653000902109653001602118653001202134653001702146653003102163100001902194700001902213700001602232700001902248700002002267700001802287700002002305700002402325700002202349700002402371856003602395 2013 eng d a1532-860000aCirculating 25-hydroxyvitamin D is associated with insulin resistance cross-sectionally but not longitudinally in older adults: The Cardiovascular Health Study.0 aCirculating 25hydroxyvitamin D is associated with insulin resist c2013 Dec a1788-940 v623 aBACKGROUND: 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.
10aAdiposity10aAged10aAnthropometry10aCardiovascular Diseases10aCross-Sectional Studies10aExercise10aFemale10aHumans10aHydroxycholecalciferols10aInflammation10aInsulin10aInsulin Resistance10aLongitudinal Studies10aMale10aMiddle Aged10aObesity10aRisk Factors10aSurveys and Questionnaires1 aDanziger, John1 aBiggs, Mary, L1 aNiemi, Matt1 aIx, Joachim, H1 aKizer, Jorge, R1 aDjoussé, Luc1 ade Boer, Ian, H1 aSiscovick, David, S1 aKestenbaum, Bryan1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/606203625nas a2200673 4500008004100000022001400041245014300055210006900198260001300267300001300280490000700293520182500300653002802125653003502153653002202188653001102210653002602221653001702247653001102264100002202275700001902297700002202316700001902338700001802357700001702375700001602392700002002408700001602428700001602444700001802460700001502478700001402493700001602507700001302523700001502536700001602551700001602567700001802583700001602601700001502617700001702632700002002649700001502669700001502684700001702699700001602716700001602732700001702748700001802765700001502783700001402798700001802812700001402830700002202844700001802866700001602884700001502900856003602915 2013 eng d a1432-042800aCommon carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.0 aCommon carotid intimamedia thickness does not add to Framingham c2013 Jul a1494-5020 v563 aAIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes.
METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added.
RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women.
CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.
10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aDiabetes Mellitus10aHumans10aMyocardial Infarction10aRisk Factors10aStroke1 aRuijter, H, M den1 aPeters, S, A E1 aGroenewegen, K, A1 aAnderson, T, J1 aBritton, A, R1 aDekker, J, M1 aEngstrom, G1 aEijkemans, M, J1 aEvans, G, W1 ade Graaf, J1 aGrobbee, D, E1 aHedblad, B1 aHofman, A1 aHolewijn, S1 aIkeda, A1 aKavousi, M1 aKitagawa, K1 aKitamura, A1 aKoffijberg, H1 aIkram, M, A1 aLonn, E, M1 aLorenz, M, W1 aMathiesen, E, B1 aNijpels, G1 aOkazaki, S1 aO'Leary, D H1 aPolak, J, F1 aPrice, J, F1 aRobertson, C1 aRembold, C, M1 aRosvall, M1 aRundek, T1 aSalonen, J, T1 aSitzer, M1 aStehouwer, C, D A1 aWitteman, J C1 aMoons, K, G1 aBots, M, L uhttps://chs-nhlbi.org/node/675102824nas a2200397 4500008004100000022001400041245011600055210006900171260001300240300001100253490000700264520170200271653000901973653002201982653002802004653003002032653001102062653001202073653001102085653001402096653002502110653000902135653001702144100002202161700002002183700002402203700001802227700002002245700002202265700002102287700001802308700002402326700002102350700001902371856003602390 2013 eng d a1935-554800aFetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the cardiovascular health study.0 aFetuinA type 2 diabetes and risk of cardiovascular disease in ol c2013 May a1222-80 v363 aOBJECTIVE: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aFemale10aFetuins10aHumans10aIncidence10aLongitudinal Studies10aMale10aRisk Factors1 aJensen, Majken, K1 aBartz, Traci, M1 aMukamal, Kenneth, J1 aDjoussé, Luc1 aKizer, Jorge, R1 aTracy, Russell, P1 aZieman, Susan, J1 aRimm, Eric, B1 aSiscovick, David, S1 aShlipak, Michael1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/155203070nas a2200445 4500008004100000022001400041245015700055210006900212260001300281300001100294490000800305520172400313653005102037653002202088653000902110653001502119653002302134653002802157653002102185653002102206653004002227653001102267653001102278653001402289653001702303653001802320653000902338653001602347653003202363653002402395653001702419100002202436700002202458700001702480700002202497700002702519700002202546700002002568856003602588 2013 eng d a1879-148400aImpact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: cardiovascular Health Study.0 aImpact of inflammatory biomarkers on relation of high density li c2013 Dec a246-510 v2313 aBACKGROUND: 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.
10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAfrican Americans10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCoronary Disease10aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aInflammation10aInterleukin-610aMale10aMiddle Aged10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aTehrani, David, M1 aGardin, Julius, M1 aYanez, David1 aHirsch, Calvin, H1 aLloyd-Jones, Donald, M1 aStein, Phyllis, K1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/616703229nas a2200541 4500008004100000022001400041245011500055210006900170260001600239300001100255490000700266520172200273653001501995653001002010653002202020653001602042653000902058653001802067653002002085653002802105653001902133653004002152653001102192653001902203653001802222653001102240653002602251653000902277653001602286653003002302653001402332653002002346653003002366653001602396653002202412653001702434653001802451653001602469100002102485700002102506700001802527700001802545700002302563700001402586700002402600700002702624856003602651 2013 eng d a1558-359700aLifetime risk for heart failure among white and black Americans: cardiovascular lifetime risk pooling project.0 aLifetime risk for heart failure among white and black Americans c2013 Apr 09 a1510-70 v613 aOBJECTIVES: 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.
10aAdolescent10aAdult10aAfrican Americans10aAge Factors10aAged10aAnthropometry10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aFemale10aHealth Surveys10aHeart Failure10aHumans10aKaplan-Meier Estimate10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aRisk Assessment10aSeverity of Illness Index10aSex Factors10aSurvival Analysis10aTime Factors10aUnited States10aYoung Adult1 aHuffman, Mark, D1 aBerry, Jarett, D1 aNing, Hongyan1 aDyer, Alan, R1 aGarside, Daniel, B1 aCai, Xuan1 aDaviglus, Martha, L1 aLloyd-Jones, Donald, M uhttps://chs-nhlbi.org/node/584703362nas a2200457 4500008004100000022001400041245015400055210006900209260001300278300001100291490000700302520203900309653000902348653002202357653001502379653001002394653002802404653002602432653001102458653001102469653001502480653003102495653000902526653001702535653002902552653001802581653001602599653001102615653001402626100002102640700002002661700002102681700002202702700002802724700002602752700002302778700002002801700002702821700002002848856003602868 2013 eng d a1534-779600aLong-term survival in adults 65 years and older with white matter hyperintensity: association with performance on the digit symbol substitution test.0 aLongterm survival in adults 65 years and older with white matter c2013 Sep a624-310 v753 aOBJECTIVE: 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.
10aAged10aApolipoprotein E410aBiomarkers10aBrain10aCardiovascular Diseases10aEpidemiologic Methods10aFemale10aHumans10aLife Style10aMagnetic Resonance Imaging10aMale10aNeuroimaging10aNeuropsychological Tests10aReaction Time10aSex Factors10aStroke10aSurvivors1 aRosano, Caterina1 aChang, Yue-Fang1 aKuller, Lewis, H1 aGuralnik, Jack, M1 aStudenski, Stephanie, A1 aAizenstein, Howard, J1 aGianaros, Peter, J1 aLopez, Oscar, L1 aLongstreth, William, T1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/610708187nas a2202209 4500008004100000022001400041245023300055210006900288260001600357300001200373490000800385520188600393653001502279653001002294653003902304653000902343653002202352653002802374653002802402653004002430653001102470653001502481653001702496653003802513653003402551653002302585653001102608653000902619653001602628653002602644653003602670653001702706653001102723653002702734653001602761100002502777700001502802700002002817700001902837700001902856700002302875700002202898700002002920700002102940700001702961700002402978700002003002700002303022700001803045700001903063700001703082700002303099700001803122700002003140700001603160700002003176700001903196700002803215700002103243700001703264700002503281700002203306700001903328700001703347700002003364700001603384700002003400700001803420700001903438700001903457700002003476700001603496700002003512700001503532700002203547700002103569700002103590700002503611700002303636700002103659700001903680700002003699700001703719700001703736700001703753700002103770700002203791700001903813700002703832700002003859700002403879700002503903700002103928700002003949700002603969700002803995700002104023700001904044700002204063700002304085700002304108700001304131700002504144700002304169700002204192700001904214700002004233700002204253700002004275700002004295700002204315700001804337700002104355700001804376700001904394700001904413700001504432700002704447700001704474700001904491700002204510700002304532700001804555700002404573700002004597700001904617700002404636700001604660700002004676700002204696700002004718700002404738700001804762700002104780700002104801700001904822700002804841700002204869700002004891700002204911700001704933700002104950700002304971700002404994700002305018700002205041700002105063700002205084700001705106700002705123700002205150700002405172700002205196700002405218700002905242700002005271700002305291700001805314700001805332700002005350700003005370700001905400700002205419700002205441700002105463700002105484700001905505700001805524700002005542700002005562700001805582700002205600700002505622700002305647700002005670700002005690700001805710700002305728700002005751700003005771710001905801710002205820710005405842710001905896710002605915856003605941 2013 eng d a1524-453900aMultiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.0 aMultiethnic metaanalysis of genomewide association studies in 10 c2013 Sep 17 a1310-240 v1283 aBACKGROUND: 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.
10aAdolescent10aAdult10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aCardiovascular Diseases10aCoronary Artery Disease10aEuropean Continental Ancestry Group10aFemale10aFibrinogen10aGenetic Loci10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHispanic Americans10aHumans10aMale10aMiddle Aged10aMyocardial Infarction10aPolymorphism, Single Nucleotide10aRisk Factors10aStroke10aVenous Thromboembolism10aYoung Adult1 aSabater-Lleal, Maria1 aHuang, Jie1 aChasman, Daniel1 aNaitza, Silvia1 aDehghan, Abbas1 aJohnson, Andrew, D1 aTeumer, Alexander1 aReiner, Alex, P1 aFolkersen, Lasse1 aBasu, Saonli1 aRudnicka, Alicja, R1 aTrompet, Stella1 aMälarstig, Anders1 aBaumert, Jens1 aBis, Joshua, C1 aGuo, Xiuqing1 aHottenga, Jouke, J1 aShin, So-Youn1 aLopez, Lorna, M1 aLahti, Jari1 aTanaka, Toshiko1 aYanek, Lisa, R1 aOudot-Mellakh, Tiphaine1 aWilson, James, F1 aNavarro, Pau1 aHuffman, Jennifer, E1 aZemunik, Tatijana1 aRedline, Susan1 aMehra, Reena1 aPulanic, Drazen1 aRudan, Igor1 aWright, Alan, F1 aKolcic, Ivana1 aPolasek, Ozren1 aWild, Sarah, H1 aCampbell, Harry1 aCurb, David1 aWallace, Robert1 aLiu, Simin1 aEaton, Charles, B1 aBecker, Diane, M1 aBecker, Lewis, C1 aBandinelli, Stefania1 aRäikkönen, Katri1 aWiden, Elisabeth1 aPalotie, Aarno1 aFornage, Myriam1 aGreen, David1 aGross, Myron1 aDavies, Gail1 aHarris, Sarah, E1 aLiewald, David, C1 aStarr, John, M1 aWilliams, Frances, M K1 aGrant, Peter, J1 aSpector, Timothy, D1 aStrawbridge, Rona, J1 aSilveira, Angela1 aSennblad, Bengt1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aFranco, Oscar, H1 aHofman, Albert1 avan Dongen, Jenny1 aWillemsen, Gonneke1 aBoomsma, Dorret, I1 aYao, Jie1 aJenny, Nancy, Swords1 aHaritunians, Talin1 aMcKnight, Barbara1 aLumley, Thomas1 aTaylor, Kent, D1 aRotter, Jerome, I1 aPsaty, Bruce, M1 aPeters, Annette1 aGieger, Christian1 aIllig, Thomas1 aGrotevendt, Anne1 aHomuth, Georg1 aVölzke, Henry1 aKocher, Thomas1 aGoel, Anuj1 aFranzosi, Maria Grazia1 aSeedorf, Udo1 aClarke, Robert1 aSteri, Maristella1 aTarasov, Kirill, V1 aSanna, Serena1 aSchlessinger, David1 aStott, David, J1 aSattar, Naveed1 aBuckley, Brendan, M1 aRumley, Ann1 aLowe, Gordon, D1 aMcArdle, Wendy, L1 aChen, Ming-Huei1 aTofler, Geoffrey, H1 aSong, Jaejoon1 aBoerwinkle, Eric1 aFolsom, Aaron, R1 aRose, Lynda, M1 aFranco-Cereceda, Anders1 aTeichert, Martina1 aIkram, Arfan, M1 aMosley, Thomas, H1 aBevan, Steve1 aDichgans, Martin1 aRothwell, Peter, M1 aSudlow, Cathie, L M1 aHopewell, Jemma, C1 aChambers, John, C1 aSaleheen, Danish1 aKooner, Jaspal, S1 aDanesh, John1 aNelson, Christopher, P1 aErdmann, Jeanette1 aReilly, Muredach, P1 aKathiresan, Sekar1 aSchunkert, Heribert1 aMorange, Pierre-Emmanuel1 aFerrucci, Luigi1 aEriksson, Johan, G1 aJacobs, David1 aDeary, Ian, J1 aSoranzo, Nicole1 aWitteman, Jacqueline, C M1 aGeus, Eco, J C1 aTracy, Russell, P1 aHayward, Caroline1 aKoenig, Wolfgang1 aCucca, Francesco1 aJukema, Wouter1 aEriksson, Per1 aSeshadri, Sudha1 aMarkus, Hugh, S1 aWatkins, Hugh1 aSamani, Nilesh, J1 aWallaschofski, Henri1 aSmith, Nicholas, L1 aTregouet, David1 aRidker, Paul, M1 aTang, Weihong1 aStrachan, David, P1 aHamsten, Anders1 aO'Donnell, Christopher, J1 aVTE Consortium1 aSTROKE Consortium1 aWellcome Trust Case Control Consortium 2 (WTCCC2)1 aC4D Consortium1 aCARDIoGRAM consortium uhttps://chs-nhlbi.org/node/615503114nas a2200433 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520194700251653000902198653002202207653002002229653001502249653001902264653002802283653003502311653002102346653002202367653001102389653001102400653000902411653002602420653002402446653001702470653001102487100001802498700001602516700001602532700001302548700001402561700002002575700001702595700001502612700001702627856003602644 2013 eng d a1432-042800aPrediction and classification of cardiovascular disease risk in older adults with diabetes.0 aPrediction and classification of cardiovascular disease risk in c2013 Feb a275-830 v563 aAIMS/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.
10aAged10aAged, 80 and over10aAtherosclerosis10aBiomarkers10aBlood Pressure10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aCholesterol, HDL10aDiabetes Mellitus10aFemale10aHumans10aMale10aMyocardial Infarction10aRegression Analysis10aRisk Factors10aStroke1 aMukamal, K, J1 aKizer, J, R1 aDjoussé, L1 aIx, J, H1 aZieman, S1 aSiscovick, D, S1 aSibley, C, T1 aTracy, R P1 aArnold, A, M uhttps://chs-nhlbi.org/node/585903235nas a2200445 4500008004100000022001400041245014100055210006900196260001600265300001100281490000800292520194000300653001002240653000902250653001502259653002802274653002102302653002402323653001102347653002202358653002102380653001102401653001402412653000902426653002202435653001602457653002402473653002402497653001802521653001402539100003302553700002202586700002202608700002402630700002002654700002402674700003002698700002502728856003602753 2013 eng d a1879-191300aRelation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study).0 aRelation of vitamin D and parathyroid hormone to cardiac biomark c2013 Feb 01 a418-240 v1113 aVitamin 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.
10aAdult10aAged10aBiomarkers10aCardiovascular Diseases10aEchocardiography10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Ventricles10aHumans10aIncidence10aMale10aMass Spectrometry10aMiddle Aged10aParathyroid Hormone10aProspective Studies10aUnited States10aVitamin D1 avan Ballegooijen, Adriana, J1 aVisser, Marjolein1 aKestenbaum, Bryan1 aSiscovick, David, S1 ade Boer, Ian, H1 aGottdiener, John, S1 adeFilippi, Christopher, R1 aBrouwer, Ingeborg, A uhttps://chs-nhlbi.org/node/155901869nas a2200349 4500008004100000022001400041245012800055210006900183260000900252300001000261490000700271520082100278653003101099653000901130653001401139653002701153653002801180653003701208653001101245653001101256653002501267653000901292653003701301653002401338653001901362100001701381700001701398700002401415700002101439700002301460856003601483 2013 eng d a1096-465700aResults differ by applying distinctive multiple imputation approaches on the longitudinal cardiovascular health study data.0 aResults differ by applying distinctive multiple imputation appro c2013 a27-430 v393 aUNLABELLED: 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.
10aActivities of Daily Living10aAged10aArthritis10aCardiac Rehabilitation10aCardiovascular Diseases10aData Interpretation, Statistical10aFemale10aHumans10aLongitudinal Studies10aMale10aOutcome Assessment (Health Care)10aRegression Analysis10aSocial Support1 aNing, Yuming1 aMcAvay, Gail1 aChaudhry, Sarwat, I1 aArnold, Alice, M1 aAllore, Heather, G uhttps://chs-nhlbi.org/node/585303693nas a2200421 4500008004100000022001400041245007800055210006900133260001600202300001200218490000600230520248800236653000902724653002802733653001902761653002802780653001102808653002502819653001902844653001102863653004902874653004902923653003302972653000903005653002103014653001003035653002903045653001703074653001803091100001603109700001403125700001803139700001803157700002103175700001703196700002203213856003603235 2013 eng d a1550-939700aSleep and insulin-like growth factors in the Cardiovascular Health Study.0 aSleep and insulinlike growth factors in the Cardiovascular Healt c2013 Dec 15 a1245-510 v93 aSTUDY 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.
10aAged10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aFemale10aGeriatric Assessment10aHealth Surveys10aHumans10aInsulin-Like Growth Factor Binding Protein 110aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aMale10aSex Distribution10aSleep10aSleep Apnea, Obstructive10aSomatomedins10aUnited States1 aShah, Neomi1 aRice, Tom1 aTracy, Daniel1 aRohan, Thomas1 aBůzková, Petra1 aNewman, Anne1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/618903680nas a2200625 4500008004100000022001400041245012100055210006900176260001300245300001100258490000700269520186000276653002202136653001602158653000902174653001502183653002802198653003102226653004002257653001102297653003802308653003402346653001502380653002402395653001102419653001402430653002702444653001802471653003302489653002002522653000902542653002202551653002602573653001402599653003602613653003302649653001402682653003202696653002402728653002002752653001702772653001702789653001802806100002002824700002002844700002002864700002302884700001802907700001202925700002002937700002102957700001802978700002202996856003603018 2013 eng d a1524-463600aSoluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults.0 aSoluble CD14 genomewide association analysis and relationship to c2013 Jan a158-640 v333 aOBJECTIVE: 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.
10aAfrican Americans10aAge Factors10aAged10aBiomarkers10aCardiovascular Diseases10aChromosomes, Human, Pair 510aEuropean Continental Ancestry Group10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHaplotypes10aHexosyltransferases10aHumans10aIncidence10aInflammation Mediators10aLinear Models10aLipopolysaccharide Receptors10aLogistic Models10aMale10aMembrane Proteins10aMultivariate Analysis10aPhenotype10aPolymorphism, Single Nucleotide10aPrincipal Component Analysis10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aReiner, Alex, P1 aLange, Ethan, M1 aJenny, Nancy, S1 aChaves, Paulo, H M1 aEllis, Jaclyn1 aLi, Jin1 aWalston, Jeremy1 aLange, Leslie, A1 aCushman, Mary1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/156403526nas a2200457 4500008004100000022001400041245012000055210006900175260001300244300001100257490000700268520223800275653001602513653001002529653000902539653002202548653001902570653002802589653002502617653001902642653002102661653001102682653001102693653000902704653002102713653003002734653001702764653001102781100002002792700002002812700002102832700001802853700002102871700002402892700002202916700002702938700002402965700002402989700001903013856003603032 2013 eng d a1945-719700aTotal and high-molecular-weight adiponectin and risk of coronary heart disease and ischemic stroke in older adults.0 aTotal and highmolecularweight adiponectin and risk of coronary h c2013 Jan a255-630 v983 aCONTEXT: 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.
10aAdiponectin10aAdult10aAged10aAged, 80 and over10aBrain Ischemia10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCoronary Disease10aFemale10aHumans10aMale10aMolecular Weight10aResidence Characteristics10aRisk Factors10aStroke1 aKizer, Jorge, R1 aBenkeser, David1 aArnold, Alice, M1 aDjoussé, Luc1 aZieman, Susan, J1 aMukamal, Kenneth, J1 aTracy, Russell, P1 aMantzoros, Christos, S1 aSiscovick, David, S1 aGottdiener, John, S1 aIx, Joachim, H uhttps://chs-nhlbi.org/node/613903251nas a2200493 4500008004100000022001400041245013700055210006900192260001300261300001100274490000800285520184100293653000902134653001302143653002802156653001902184653002802203653001902231653002102250653001502271653001102286653003102297653003702328653001102365653001602376653001402392653001102406653000902417653002102426653003202447653001102479653002202490100002002512700002002532700002102552700001902573700002402592700001802616700002202634700002402656700002002680700002102700856003602721 2014 eng d a1879-148400aAdvanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults.0 aAdvanced glycationglycoxidation endproduct carboxymethyllysine a c2014 Jul a116-210 v2353 aBACKGROUND: 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.
10aAged10aAlbumins10aAntihypertensive Agents10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aCreatinine10aFemale10aGlomerular Filtration Rate10aGlycation End Products, Advanced10aHumans10aImmunoassay10aIncidence10aLysine10aMale10aOxidative Stress10aProportional Hazards Models10aStroke10aTreatment Outcome1 aKizer, Jorge, R1 aBenkeser, David1 aArnold, Alice, M1 aIx, Joachim, H1 aMukamal, Kenneth, J1 aDjoussé, Luc1 aTracy, Russell, P1 aSiscovick, David, S1 aPsaty, Bruce, M1 aZieman, Susan, J uhttps://chs-nhlbi.org/node/657603889nas a2200493 4500008004100000022001400041245013300055210006900188260001300257300001000270490000700280520249200287653000902779653000902788653001502797653002802812653001502840653001502855653001102870653002202881653003102903653001102934653000902945653001602954653003602970653003303006653002003039653001703059653003003076653002403106653001803130100002603148700001803174700001603192700001603208700001703224700001903241700001603260700001803276700002103294700002003315700002403335856003603359 2014 eng d a1523-683800aAssociation of a cystatin C gene variant with cystatin C levels, CKD, and risk of incident cardiovascular disease and mortality.0 aAssociation of a cystatin C gene variant with cystatin C levels c2014 Jan a16-220 v633 aBACKGROUND: 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.
10aAged10aBias10aBiomarkers10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGenetic Variation10aGlomerular Filtration Rate10aHumans10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aRenal Insufficiency, Chronic10aRisk Assessment10aRisk Factors10aSeverity of Illness Index10aStatistics as Topic10aSurvival Rate1 aO'Seaghdha, Conall, M1 aTin, Adrienne1 aYang, Qiong1 aKatz, Ronit1 aLiu, Yongmei1 aHarris, Tamara1 aAstor, Brad1 aCoresh, Josef1 aFox, Caroline, S1 aKao, Linda, W H1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/658703905nas a2200745 4500008004100000022001400041245017300055210006900228260001300297300001200310490000700322520172200329653001002051653000902061653002802070653001902098653002802117653002702145653003502172653001902207653001102226653001102237653001702248653000902265653002702274653001602301653002002317653001702337100002102354700002802375700002202403700002202425700002602447700002202473700001902495700002502514700002602539700001602565700001902581700002202600700001402622700002002636700002002656700002202676700002002698700001702718700002402735700002602759700001802785700002002803700002302823700002102846700002502867700002502892700002802917700001902945700002002964700002202984700002103006700002503027700002103052700002303073700002703096856003603123 2014 eng d a1524-456300aCommon carotid intima-media thickness measurements do not improve cardiovascular risk prediction in individuals with elevated blood pressure: the USE-IMT collaboration.0 aCommon carotid intimamedia thickness measurements do not improve c2014 Jun a1173-810 v633 aCarotid 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.
10aAdult10aAged10aAntihypertensive Agents10aBlood Pressure10aCardiovascular Diseases10aCarotid Artery, Common10aCarotid Intima-Media Thickness10aCohort Studies10aFemale10aHumans10aHypertension10aMale10aMeta-Analysis as Topic10aMiddle Aged10aRisk Assessment10aRisk Factors1 aBots, Michiel, L1 aGroenewegen, Karlijn, A1 aAnderson, Todd, J1 aBritton, Annie, R1 aDekker, Jacqueline, M1 aEngström, Gunnar1 aEvans, Greg, W1 ade Graaf, Jacqueline1 aGrobbee, Diederick, E1 aHedblad, Bo1 aHofman, Albert1 aHolewijn, Suzanne1 aIkeda, Ai1 aKavousi, Maryam1 aKitagawa, Kazuo1 aKitamura, Akihiko1 aIkram, Arfan, M1 aLonn, Eva, M1 aLorenz, Matthias, W1 aMathiesen, Ellisiv, B1 aNijpels, Giel1 aOkazaki, Shuhei1 aO'Leary, Daniel, H1 aPolak, Joseph, F1 aPrice, Jacqueline, F1 aRobertson, Christine1 aRembold, Christopher, M1 aRosvall, Maria1 aRundek, Tatjana1 aSalonen, Jukka, T1 aSitzer, Matthias1 aStehouwer, Coen, D A1 aFranco, Oscar, H1 aPeters, Sanne, A E1 aRuijter, Hester, M den uhttps://chs-nhlbi.org/node/654903989nas a2200829 4500008004100000022001400041245011400055210006900169260001300238300001100251490000700262520179800269653001002067653000902077653002202086653002502108653002802133653001102161653004002172653001102212653001102223653000902234653001602243653002402259653003002283653001402313653003102327653002002358653001702378653001602395653001702411653001802428653001602446100001902462700001702481700001502498700001702513700001702530700001702547700001602564700001702580700001702597700002502614700001502639700001402654700001602668700002102684700001902705700001502724700001702739700001702756700001602773700002202789700002002811700002302831700002102854700001302875700001502888700001402903700001702917700001702934700001502951700001902966700001402985700001802999700001703017700001703034700001603051700001703067710003903084856003603123 2014 eng d a2047-488100aDevelopment and validation of an ankle brachial index risk model for the prediction of cardiovascular events.0 aDevelopment and validation of an ankle brachial index risk model c2014 Mar a310-200 v213 aBACKGROUND: 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.
10aAdult10aAged10aAged, 80 and over10aAnkle Brachial Index10aCardiovascular Diseases10aEurope10aEuropean Continental Ancestry Group10aFemale10aHumans10aMale10aMiddle Aged10aModels, Statistical10aPredictive Value of Tests10aPrognosis10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSex Factors10aTime Factors10aUnited States10aYoung Adult1 aFowkes, F, G R1 aMurray, G, D1 aButcher, I1 aFolsom, A, R1 aHirsch, A, T1 aCouper, D, J1 adeBacker, G1 aKornitzer, M1 aNewman, A, B1 aSutton-Tyrrell, K, C1 aCushman, M1 aLee, A, J1 aPrice, J, F1 aD'Agostino, R, B1 aMurabito, J, M1 aNorman, Pe1 aMasaki, K, H1 aBouter, L, M1 aHeine, R, J1 aStehouwer, C, D A1 aMcDermott, M, M1 aStoffers, H, E J H1 aKnottnerus, J, A1 aOgren, M1 aHedblad, B1 aKoenig, W1 aMeisinger, C1 aCauley, J, A1 aFranco, Oh1 aHunink, M, G M1 aHofman, A1 aWitteman, J C1 aCriqui, M, H1 aLanger, R, D1 aHiatt, W, R1 aHamman, R, F1 aAnkle Brachial Index Collaboration uhttps://chs-nhlbi.org/node/680303547nas a2200529 4500008004100000022001400041245011400055210006900169260000900238300001100247490000700258520201800265653003102283653000902314653002702323653002802350653002602378653001802404653001102422653001102433653002302444653002502467653000902492653001902501653002002520653003702540653004302577653002502620653002002645653003002665653001502695653001802710100002002728700002002748700001702768700002102785700001802806700001802824700002002842700001702862700002202879700001902901700002302920700001702943700002102960856003602981 2014 eng d a1423-035600aDisability and recovery of independent function in obstructive lung disease: the cardiovascular health study.0 aDisability and recovery of independent function in obstructive l c2014 a329-380 v883 aBACKGROUND: 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.
10aActivities of Daily Living10aAged10aCardiac Rehabilitation10aCardiovascular Diseases10aDisability Evaluation10aExercise Test10aFemale10aHumans10aIndependent Living10aLongitudinal Studies10aMale10aMotor Activity10aMuscle Strength10aOutcome Assessment (Health Care)10aPulmonary Disease, Chronic Obstructive10aRecovery of Function10aRisk Assessment10aSeverity of Illness Index10aSpirometry10aUnited States1 aFan, Vincent, S1 aLocke, Emily, R1 aDiehr, Paula1 aWilsdon, Anthony1 aEnright, Paul1 aYende, Sachin1 aAvdalovic, Mark1 aBarr, Graham1 aKapur, Vishesh, K1 aThomas, Rachel1 aKrishnan, Jerry, A1 aLovasi, Gina1 aThielke, Stephen uhttps://chs-nhlbi.org/node/656002957nas a2200373 4500008004100000022001400041245013400055210006900189260001300258300000900271490000800280520182700288653000902115653002502124653002802149653002802177653003002205653001102235653001402246653003202260653001702292100002502309700001902334700001602353700002402369700002502393700002002418700002402438700001902462700002202481700002402503700002002527856003602547 2014 eng d a1879-148400aFibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.0 aFibroblast growth factor 23 the anklebrachial index and incident c2014 Mar a91-60 v2333 aBACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.
METHODS: Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.
RESULTS: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).
CONCLUSIONS: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.
10aAged10aAnkle Brachial Index10aCardiovascular Diseases10aCross-Sectional Studies10aFibroblast Growth Factors10aHumans10aIncidence10aPeripheral Arterial Disease10aRisk Factors1 aGarimella, Pranav, S1 aIx, Joachim, H1 aKatz, Ronit1 aChonchol, Michel, B1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aSiscovick, David, S1 aShastri, Shani1 aHiramoto, Jade, S1 aShlipak, Michael, G1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/623903351nas a2200577 4500008004100000022001400041245011800055210006900173260001300242300001000255490000600265520177300271653001602044653000902060653002202069653001002091653001502101653002302116653002802139653001102167653001302178653001802191653001102209653001402220653000902234653002602243653002202269653001602291653001402307653002402321653002002345653001702365653001102382653001702393653003602410653001802446100001802464700002202482700001802504700001902522700001802541700002802559700002402587700001902611700002002630700001802650700002302668700002202691700002402713856003602737 2014 eng d a1941-308400aFibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study.0 aFibrosisrelated biomarkers and incident cardiovascular disease i c2014 Aug a583-90 v73 aBACKGROUND: 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.
10aAge Factors10aAged10aAged, 80 and over10aAging10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aFemale10aFibrosis10aHeart Failure10aHumans10aIncidence10aMale10aMyocardial Infarction10aPeptide Fragments10aProcollagen10aPrognosis10aProspective Studies10aRisk Assessment10aRisk Factors10aStroke10aTime Factors10aTransforming Growth Factor beta10aUnited States1 aAgarwal, Isha1 aGlazer, Nicole, L1 aBarasch, Eddy1 aBiggs, Mary, L1 aDjoussé, Luc1 aFitzpatrick, Annette, L1 aGottdiener, John, S1 aIx, Joachim, H1 aKizer, Jorge, R1 aRimm, Eric, B1 aSicovick, David, S1 aTracy, Russell, P1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/654103165nas a2200505 4500008004100000022001400041245011400055210006900169260001300238300001000251490000800261520171800269653001001987653000901997653002802006653001802034653001302052653001102065653004302076653001502119653003202134653001302166653001102179653000902190653001602199653004402215653003602259653001602295100001802311700001802329700002102347700002302368700001902391700003002410700001702440700002502457700002302482700002202505700002302527700001802550700001602568700002102584700001802605856003602623 2014 eng d a1879-247200aA genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups.0 agenetic association study of Ddimer levels with 50K SNPs from a c2014 Aug a462-70 v1343 aINTRODUCTION: 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.
10aAdult10aAged10aCardiovascular Diseases10aEthnic Groups10aFactor V10aFemale10aFibrin Fibrinogen Degradation Products10aFibrinogen10aGenetic Association Studies10aGenotype10aHumans10aMale10aMiddle Aged10aOligonucleotide Array Sequence Analysis10aPolymorphism, Single Nucleotide10aYoung Adult1 aWeng, Lu-Chen1 aTang, Weihong1 aRich, Stephen, S1 aSmith, Nicholas, L1 aRedline, Susan1 aO'Donnell, Christopher, J1 aBasu, Saonli1 aReiner, Alexander, P1 aDelaney, Joseph, A1 aTracy, Russell, P1 aPalmer, Cameron, D1 aYoung, Taylor1 aYang, Qiong1 aFolsom, Aaron, R1 aCushman, Mary uhttps://chs-nhlbi.org/node/661103142nas a2200445 4500008004100000022001400041245009800055210006900153260001300222300001100235490000700246520191900253653000902172653001002181653002802191653001102219653003802230653001302268653002002281653001102301653001402312653000902326653001402335653002602349653001702375653001802392653001802410100002202428700002102450700002102471700002102492700002402513700002302537700002002560700002302580700001902603700001802622700002002640856003602660 2014 eng d a1758-535X00aHeritability of and mortality prediction with a longevity phenotype: the healthy aging index.0 aHeritability of and mortality prediction with a longevity phenot c2014 Apr a479-850 v693 aBACKGROUND: 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.
10aAged10aAging10aCardiovascular Diseases10aFemale10aGenetic Predisposition to Disease10aGenotype10aHealth Behavior10aHumans10aLongevity10aMale10aPhenotype10aRetrospective Studies10aRisk Factors10aSurvival Rate10aUnited States1 aSanders, Jason, L1 aMinster, Ryan, L1 aBarmada, Michael1 aMatteini, Amy, M1 aBoudreau, Robert, M1 aChristensen, Kaare1 aMayeux, Richard1 aBorecki, Ingrid, B1 aZhang, Qunyuan1 aPerls, Thomas1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/628002589nas a2200361 4500008004100000022001400041245009100055210006900146260001600215300001000231490000800241520158100249653000901830653002801839653001401867653002401881653001501905653001101920653003101931653001801962653001101980653001101991653002002002653000902022653002902031100002002060700002402080700002002104700001602124700002802140700002302168856003602191 2014 eng d a1476-625600aKidney function and cognitive health in older adults: the Cardiovascular Health Study.0 aKidney function and cognitive health in older adults the Cardiov c2014 Jul 01 a68-750 v1803 aRecent 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.
10aAged10aCardiovascular Diseases10aCognition10aCognition Disorders10aCystatin C10aFemale10aGlomerular Filtration Rate10aHealth Status10aHumans10aKidney10aKidney Diseases10aMale10aNeuropsychological Tests1 aDarsie, Brendan1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFitzpatrick, Annette, L1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/636404043nas a2200769 4500008004100000022001400041245014200055210006900197260001300266300001100279490000800290520183700298653001002135653002202145653000902167653001502176653002302191653002802214653001802242653001102260653001702271653003802288653002502326653003402351653001102385653002702396653001602423653003602439653001702475100001802492700002002510700001202530700001902542700001802561700002302579700002402602700001702626700001802643700002302661700001702684700001802701700002302719700002402742700002102766700001702787700002002804700001902824700001502843700002702858700002302885700002102908700002102929700002802950700002202978700002803000700002003028700002203048700002103070700001903091700002103110700002203131700001903153700002003172700002403192700002103216856003603237 2014 eng d a1432-120300aLarge multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.0 aLarge multiethnic Candidate Gene Study for Creactive protein lev c2014 Aug a985-950 v1333 aC-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.
10aAdult10aAfrican Americans10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCD36 Antigens10aFemale10aGenetic Loci10aGenetic Predisposition to Disease10aGenetics, Population10aGenome-Wide Association Study10aHumans10aMeta-Analysis as Topic10aMiddle Aged10aPolymorphism, Single Nucleotide10aRisk Factors1 aEllis, Jaclyn1 aLange, Ethan, M1 aLi, Jin1 aDupuis, Josée1 aBaumert, Jens1 aWalston, Jeremy, D1 aKeating, Brendan, J1 aDurda, Peter1 aFox, Ervin, R1 aPalmer, Cameron, D1 aMeng, Yan, A1 aYoung, Taylor1 aFarlow, Deborah, N1 aSchnabel, Renate, B1 aMarzi, Carola, S1 aLarkin, Emma1 aMartin, Lisa, W1 aBis, Joshua, C1 aAuer, Paul1 aRamachandran, Vasan, S1 aGabriel, Stacey, B1 aWillis, Monte, S1 aPankow, James, S1 aPapanicolaou, George, J1 aRotter, Jerome, I1 aBallantyne, Christie, M1 aGross, Myron, D1 aLettre, Guillaume1 aWilson, James, G1 aPeters, Ulrike1 aKoenig, Wolfgang1 aTracy, Russell, P1 aRedline, Susan1 aReiner, Alex, P1 aBenjamin, Emelia, J1 aLange, Leslie, A uhttps://chs-nhlbi.org/node/655803736nas a2200577 4500008004100000022001400041245014100055210006900196260001300265490000600278520210100284653001002385653000902395653002802404653001802432653001002450653001102460653001302471653001102484653001802495653002002513653000902533653002502542653001602567653004002583653004002623653001202663653001502675653003602690653001402726653001702740653002702757100002402784700001102808700001802819700001902837700002502856700002102881700002002902700002102922700001902943700001702962700002002979700002202999700001903021700002003040700002303060700001803083700002103101856003603122 2014 eng d a2047-998000aA low-frequency variant in MAPK14 provides mechanistic evidence of a link with myeloperoxidase: a prognostic cardiovascular risk marker.0 alowfrequency variant in MAPK14 provides mechanistic evidence of c2014 Aug0 v33 aBACKGROUND: 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.
10aAdult10aAged10aCardiovascular Diseases10aDyslipidemias10aExome10aFemale10aGenotype10aHumans10aLinear Models10aLogistic Models10aMale10aMetabolic Syndrome X10aMiddle Aged10aMitogen-Activated Protein Kinase 1110aMitogen-Activated Protein Kinase 1410aObesity10aPeroxidase10aPolymorphism, Single Nucleotide10aPrognosis10aRisk Factors10aSequence Analysis, DNA1 aWaterworth, Dawn, M1 aLi, Li1 aScott, Robert1 aWarren, Liling1 aGillson, Christopher1 aAponte, Jennifer1 aSarov-Blat, Lea1 aSprecher, Dennis1 aDupuis, Josée1 aReiner, Alex1 aPsaty, Bruce, M1 aTracy, Russell, P1 aLin, Honghuang1 aMcPherson, Ruth1 aChissoe, Stephanie1 aWareham, Nick1 aEhm, Margaret, G uhttps://chs-nhlbi.org/node/661002976nas a2200397 4500008004100000022001400041245009900055210006900154260001600223300001200239490000800251520183600259653000902095653002802104653002802132653003602160653001102196653002202207653001802229653001502247653001102262653002302273653002502296653000902321653001902330653002402349653001202373100002602385700002202411700001802433700002002451700002402471700002202495700002502517856003602542 2014 eng d a1524-453900aPhysical activity and heart rate variability in older adults: the Cardiovascular Health Study.0 aPhysical activity and heart rate variability in older adults the c2014 May 27 a2100-100 v1293 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aCross-Sectional Studies10aElectrocardiography, Ambulatory10aFemale10aFollow-Up Studies10aHealth Status10aHeart Rate10aHumans10aLeisure Activities10aLongitudinal Studies10aMale10aMotor Activity10aProspective Studies10aWalking1 aSoares-Miranda, Luisa1 aSattelmair, Jacob1 aChaves, Paulo1 aDuncan, Glen, E1 aSiscovick, David, S1 aStein, Phyllis, K1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/636103126nas a2200457 4500008004100000022001400041245011500055210007000170260001600240300001200256490000800268520184400276653000902120653002502129653002802154653001902182653002102201653000902222653001102231653001102242653000902253653001402262653001802276653003202294653002402326653001702350653001102367653001802378100002202396700002502418700002402443700002102467700002002488700001802508700001902526700002202545700002202567700001902589700002402608856003602632 2014 eng d a1475-266200aPlasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study.0 aPlasma phospholipid and dietary αlinolenic acid mortality CHD an c2014 Oct 14 a1206-130 v1123 aPrevious 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.
10aAged10aalpha-Linolenic Acid10aCardiovascular Diseases10aCohort Studies10aCoronary Disease10aDiet10aFemale10aHumans10aMale10aMortality10aPhospholipids10aProportional Hazards Models10aProspective Studies10aRisk Factors10aStroke10aUnited States1 aFretts, Amanda, M1 aMozaffarian, Dariush1 aSiscovick, David, S1 aSitlani, Colleen1 aPsaty, Bruce, M1 aRimm, Eric, B1 aSong, Xiaoling1 aMcKnight, Barbara1 aSpiegelman, Donna1 aKing, Irena, B1 aLemaitre, Rozenn, N uhttps://chs-nhlbi.org/node/656203156nas a2200433 4500008004100000022001400041245012900055210006900184260001300253490000600266520193300272653000902205653002202214653001502236653002802251653001902279653001702298653001102315653002202326653001102348653001402359653000902373653001402382653001802396653001402414653003202428653002402460653002202484100001702506700002102523700002402544700001802568700001602586700001902602700001902621700002102640700002502661856003602686 2014 eng d a2047-998000aPlasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study.0 aPlasma phospholipid transfatty acids levels cardiovascular disea c2014 Aug0 v33 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aDietary Fats10aFemale10aFollow-Up Studies10aHumans10aIncidence10aMale10aMortality10aPhospholipids10aPrognosis10aProportional Hazards Models10aProspective Studies10aTrans Fatty Acids1 aWang, Qianyi1 aImamura, Fumiaki1 aLemaitre, Rozenn, N1 aRimm, Eric, B1 aWang, Molin1 aKing, Irena, B1 aSong, Xiaoling1 aSiscovick, David1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/660903179nas a2200529 4500008004100000022001400041245012900055210006900184260001600253300001000269490000800279520167700287653002101964653001601985653000902001653002202010653001502032653002802047653001902075653003202094653003102126653001102157653002202168653001802190653001102208653000902219653001402228653002402242653002002266653001702286653001802303653001702321653001802338100002402356700002102380700001902401700002102420700002002441700001902461700002502480700002202505700002002527700002402547700002402571700001802595856003602613 2014 eng d a1879-191300aPlasma-free fatty acids, fatty acid-binding protein 4, and mortality in older adults (from the Cardiovascular Health Study).0 aPlasmafree fatty acids fatty acidbinding protein 4 and mortality c2014 Sep 15 a843-80 v1143 aPlasma-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.
10aAge Distribution10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aCardiovascular Diseases10aCause of Death10aFatty Acid-Binding Proteins10aFatty Acids, Nonesterified10aFemale10aFollow-Up Studies10aHealth Status10aHumans10aMale10aPrognosis10aProspective Studies10aRisk Assessment10aRisk Factors10aSurvival Rate10aTime Factors10aUnited States1 aMiedema, Michael, D1 aMaziarz, Marlena1 aBiggs, Mary, L1 aZieman, Susan, J1 aKizer, Jorge, R1 aIx, Joachim, H1 aMozaffarian, Dariush1 aTracy, Russell, P1 aPsaty, Bruce, M1 aSiscovick, David, S1 aMukamal, Kenneth, J1 aDjoussé, Luc uhttps://chs-nhlbi.org/node/658403213nas a2200541 4500008004100000022001400041245011300055210006900168260001300237300001100250490000700261520163100268653001001899653003901909653000901948653002201957653001601979653003701995653002802032653001902060653001502079653004002094653001102134653003102145653001102176653002802187653000902215653001602224653001502240653003302255653001702288100001902305700002502324700001802349700002102367700002002388700001602408700002302424700002302447700001702470700001902487700001902506700002302525700002102548700001802569710004802587856003602635 2014 eng d a1523-175500aRelative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.0 aRelative risks of chronic kidney disease for mortality and endst c2014 Oct a819-270 v863 aSome 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.
10aAdult10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aAlbuminuria10aAsian Continental Ancestry Group10aCardiovascular Diseases10aCohort Studies10aCreatinine10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aKidney Failure, Chronic10aMale10aMiddle Aged10aOdds Ratio10aRenal Insufficiency, Chronic10aRisk Factors1 aWen, Chi, Pang1 aMatsushita, Kunihiro1 aCoresh, Josef1 aIseki, Kunitoshi1 aIslam, Muhammad1 aKatz, Ronit1 aMcClellan, William1 aPeralta, Carmen, A1 aWang, Haiyan1 ade Zeeuw, Dick1 aAstor, Brad, C1 aGansevoort, Ron, T1 aLevey, Andrew, S1 aLevin, Adeera1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/629502615nas a2200385 4500008004100000022001400041245012400055210006900179260000900248300001100257490000900268520150100277653000901778653002801787653002301815653001101838653001101849653001401860653002301874653002001897653002501917653000901942653002401951653003001975653001802005100002002023700002402043700002502067700001902092700001502111700002102126700002202147700002402169856003602193 2014 eng d a1687-981300aResidential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.0 aResidential relocation by older adults in response to incident c c2014 a9519710 v20143 aOBJECTIVE: 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.
10aAged10aCardiovascular Diseases10aCross-Over Studies10aFemale10aHumans10aIncidence10aLife Change Events10aLogistic Models10aLongitudinal Studies10aMale10aProspective Studies10aResidence Characteristics10aUnited States1 aLovasi, Gina, S1 aRichardson, John, M1 aRodriguez, Carlos, J1 aKop, Willem, J1 aAhmed, Ali1 aBrown, Arleen, F1 aGreenlee, Heather1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/633503245nas a2200517 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520180600267653000902073653002202082653001902104653002302123653002802146653002102174653002102195653002702216653002202243653001102265653001102276653001702287653001102304653002002315653001102335653000902346653003102355653001202386653002202398653001702420100002302437700002402460700002402484700001602508700002502524700002102549700001902570700002002589700002402609700001802633700002002651700002002671856003602691 2014 eng d a1879-148400aRisk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.0 aRisk factors for cardiovascular disease across the spectrum of o c2014 Nov a336-420 v2373 aOBJECTIVE: 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.
10aAged10aAged, 80 and over10aBlood Pressure10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Complications10aDiabetes Mellitus10aFemale10aHumans10aInflammation10aKidney10aKidney Diseases10aLipids10aMale10aNatriuretic Peptide, Brain10aObesity10aPeptide Fragments10aRisk Factors1 aOdden, Michelle, C1 aShlipak, Michael, G1 aWhitson, Heather, E1 aKatz, Ronit1 aKearney, Patricia, M1 adeFilippi, Chris1 aShastri, Shani1 aSarnak, Mark, J1 aSiscovick, David, S1 aCushman, Mary1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/658803162nas a2200529 4500008004100000022001400041245010700055210006900162260001300231300001000244490000700254520171700261653003101978653000902009653002202018653001002040653001502050653002702065653002802092653002102120653001102141653002202152653001802174653001802192653001102210653001402221653001102235653000902246653001502255653001402270653002602284653001802310100002402328700002102352700001802373700002402391700002002415700001802435700001902453700002102472700002202493700002402515700001902539700002002558700001802578856003602596 2014 eng d a1758-535X00aSerum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.0 aSerum carboxymethyllysine disability and frailty in older person c2014 Jun a710-60 v693 aBACKGROUND: 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.
10aActivities of Daily Living10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiac Rehabilitation10aCardiovascular Diseases10aDisabled Persons10aFemale10aFollow-Up Studies10aFrail Elderly10aHealth Status10aHumans10aIncidence10aLysine10aMale10aPrevalence10aPrognosis10aRetrospective Studies10aUnited States1 aWhitson, Heather, E1 aArnold, Alice, M1 aYee, Laura, M1 aMukamal, Kenneth, J1 aKizer, Jorge, R1 aDjoussé, Luc1 aIx, Joachim, H1 aSiscovick, David1 aTracy, Russell, P1 aThielke, Stephen, M1 aHirsch, Calvin1 aNewman, Anne, B1 aZieman, Susan uhttps://chs-nhlbi.org/node/624302829nas a2200421 4500008004100000022001400041245017500055210006900230260001300299300001100312490000700323520157500330653003101905653003901936653000901975653002201984653001902006653002802025653001302053653004002066653001102106653002202117653000902139653001502148653001102163653001402174653002502188653000902213653001702222653001802239653001202257100002302269700001602292700002002308700002002328700002302348856003602371 2014 eng d a1524-456300aSystolic and diastolic blood pressure, incident cardiovascular events, and death in elderly persons: the role of functional limitation in the Cardiovascular Health Study.0 aSystolic and diastolic blood pressure incident cardiovascular ev c2014 Sep a472-800 v643 aWhether 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.
10aActivities of Daily Living10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aBlood Pressure10aCardiovascular Diseases10aDiastole10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aGait10aHeart Rate10aHumans10aIncidence10aLongitudinal Studies10aMale10aRisk Factors10aSurvival Rate10aSystole1 aPeralta, Carmen, A1 aKatz, Ronit1 aNewman, Anne, B1 aPsaty, Bruce, M1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/639802567nas a2200397 4500008004100000022001400041245012500055210006900180260001300249300001100262490000700273520142300280653000901703653002201712653002801734653001901762653002401781653001101805653001401816653002501830653000901855653001401864653003001878653001701908653001701925100002101942700001901963700002101982700002302003700002002026700002002046700002202066700002102088700002402109856003602133 2014 eng d a1945-719700aTestosterone, dihydrotestosterone, and incident cardiovascular disease and mortality in the cardiovascular health study.0 aTestosterone dihydrotestosterone and incident cardiovascular dis c2014 Jun a2061-80 v993 aCONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this.
OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality.
DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection.
MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality.
RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both).
CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aCause of Death10aDihydrotestosterone10aHumans10aIncidence10aLongitudinal Studies10aMale10aMortality10aResidence Characteristics10aRisk Factors10aTestosterone1 aShores, Molly, M1 aBiggs, Mary, L1 aArnold, Alice, M1 aSmith, Nicholas, L1 aLongstreth, W T1 aKizer, Jorge, R1 aHirsch, Calvin, H1 aCappola, Anne, R1 aMatsumoto, Alvin, M uhttps://chs-nhlbi.org/node/627803118nas a2200373 4500008004100000022001400041245016800055210006900223260001300292300001600305490000700321520198600328653000902314653002802323653003502351653002102386653001602407653001102423653001102434653001402445653002502459653000902484653003102493653001702524653003202541653001102573653001802584100002202602700002002624700002102644700002302665700002002688856003602708 2014 eng d a1097-679500aWhat do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.0 aWhat do carotid intimamedia thickness and plaque add to the pred c2014 Sep a998-1005.e20 v273 aBACKGROUND: 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.
10aAged10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aCarotid Stenosis10aComorbidity10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aReproducibility of Results10aRisk Factors10aSensitivity and Specificity10aStroke10aSurvival Rate1 aGardin, Julius, M1 aBartz, Traci, M1 aPolak, Joseph, F1 aO'Leary, Daniel, H1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/656403607nas a2200433 4500008004100000022001400041245010100055210006900156260001600225300001100241490000800252520240100260653000902661653002002670653002802690653001902718653001602737653001102753653002002764653001102784653000902795653001602804653001402820653001702834100003202851700002302883700002302906700002002929700002302949700002502972700001702997700001703014700002103031700002403052700001903076700002403095700001803119856003603137 2015 eng d a1538-359800aAssociation between hospitalization for pneumonia and subsequent risk of cardiovascular disease.0 aAssociation between hospitalization for pneumonia and subsequent c2015 Jan 20 a264-740 v3133 aIMPORTANCE: 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.
10aAged10aAtherosclerosis10aCardiovascular Diseases10aCohort Studies10aComorbidity10aFemale10aHospitalization10aHumans10aMale10aMiddle Aged10aPneumonia10aRisk Factors1 aCorrales-Medina, Vicente, F1 aAlvarez, Karina, N1 aWeissfeld, Lisa, A1 aAngus, Derek, C1 aChirinos, Julio, A1 aChang, Chung-Chou, H1 aNewman, Anne1 aLoehr, Laura1 aFolsom, Aaron, R1 aElkind, Mitchell, S1 aLyles, Mary, F1 aKronmal, Richard, A1 aYende, Sachin uhttps://chs-nhlbi.org/node/666903390nas a2200517 4500008004100000022001400041245012400055210006900179260001300248300001000261490000700271520190100278653000902179653002402188653001002212653002102222653002802243653002702271653002402298653001102322653001602333653001902349653001102368653001802379653003102397653000902428653001602437653003002453653002402483653002402507653001702531653002202548100001802570700002002588700002002608700001902628700002102647700002302668700002202691700002602713700002302739700002402762700002602786700002402812856003602836 2015 eng d a1524-462800aAssociation between left atrial abnormality on ECG and vascular brain injury on MRI in the Cardiovascular Health Study.0 aAssociation between left atrial abnormality on ECG and vascular c2015 Mar a711-60 v463 aBACKGROUND 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.
10aAged10aAtrial Fibrillation10aBrain10aBrain Infarction10aCardiovascular Diseases10aCerebrovascular Trauma10aElectrocardiography10aFemale10aHeart Atria10aHeart Diseases10aHumans10aLinear Models10aMagnetic Resonance Imaging10aMale10aMiddle Aged10aPredictive Value of Tests10aProspective Studies10aRegression Analysis10aRisk Factors10aTreatment Outcome1 aKamel, Hooman1 aBartz, Traci, M1 aLongstreth, W T1 aOkin, Peter, M1 aThacker, Evan, L1 aPatton, Kristen, K1 aStein, Phyllis, K1 aGottesman, Rebecca, F1 aHeckbert, Susan, R1 aKronmal, Richard, A1 aElkind, Mitchell, S V1 aSoliman, Elsayed, Z uhttps://chs-nhlbi.org/node/666804486nas a2200901 4500008004100000022001400041245009600055210006900151260001600220300001100236490000700247520184700254653001002101653002202111653002302133653002802156653001902184653004002203653001002243653001102253653001902264653003802283653003402321653003802355653001102393653000902404653001102413653003602424653002902460653001702489100002202506700001802528700001902546700001902565700001402584700002102598700002102619700002002640700002402660700001902684700002802703700002002731700002202751700001202773700002402785700002402809700002102833700002002854700002102874700001902895700002102914700001602935700002002951700001502971700001902986700002003005700001803025700002103043700001803064700002203082700002403104700002303128700002303151700001903174700002603193700002203219700001903241700001903260700002103279700002103300700002403321700002403345700002003369700002003389710006503409710007403474856003603548 2015 eng d a1460-208300aAssociation of exome sequences with plasma C-reactive protein levels in >9000 participants.0 aAssociation of exome sequences with plasma Creactive protein lev c2015 Jan 15 a559-710 v243 aC-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.
10aAdult10aAfrican Americans10aC-Reactive Protein10aCardiovascular Diseases10aCohort Studies10aEuropean Continental Ancestry Group10aExome10aFemale10aGene Frequency10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHepatocyte Nuclear Factor 1-alpha10aHumans10aMale10aPlasma10aPolymorphism, Single Nucleotide10aReceptors, Interleukin-610aRisk Factors1 aSchick, Ursula, M1 aAuer, Paul, L1 aBis, Joshua, C1 aLin, Honghuang1 aWei, Peng1 aPankratz, Nathan1 aLange, Leslie, A1 aBrody, Jennifer1 aStitziel, Nathan, O1 aKim, Daniel, S1 aCarlson, Christopher, S1 aFornage, Myriam1 aHaessler, Jeffery1 aHsu, Li1 aJackson, Rebecca, D1 aKooperberg, Charles1 aLeal, Suzanne, M1 aPsaty, Bruce, M1 aBoerwinkle, Eric1 aTracy, Russell1 aArdissino, Diego1 aShah, Svati1 aWiller, Cristen1 aLoos, Ruth1 aMelander, Olle1 aMcPherson, Ruth1 aHovingh, Kees1 aReilly, Muredach1 aWatkins, Hugh1 aGirelli, Domenico1 aFontanillas, Pierre1 aChasman, Daniel, I1 aGabriel, Stacey, B1 aGibbs, Richard1 aNickerson, Deborah, A1 aKathiresan, Sekar1 aPeters, Ulrike1 aDupuis, Josée1 aWilson, James, G1 aRich, Stephen, S1 aMorrison, Alanna, C1 aBenjamin, Emelia, J1 aGross, Myron, D1 aReiner, Alex, P1 aCohorts for Heart and Aging Research in Genomic Epidemiology1 aNational Heart, Lung, and Blood Institute GO Exome Sequencing Project uhttps://chs-nhlbi.org/node/659703214nas a2200397 4500008004100000022001400041245014200055210006900197260001300266490000600279520204500285653000902330653002202339653002802361653001102389653001902400653001802419653002002437653001102457653002602468653001802494653000902512653001402521653002402535653003102559653002002590653001702610653001802627653001802645653003402663100001902697700002302716700002202739700001902761856003602780 2015 eng d a2047-998000aCardiovascular and Mortality Outcomes in the Elderly With Impaired Cardiac and Pulmonary Function: The Cardiovascular Health Study (CHS).0 aCardiovascular and Mortality Outcomes in the Elderly With Impair c2015 Dec0 v43 aBACKGROUND: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aHeart Diseases10aHeart Failure10aHospitalization10aHumans10aKaplan-Meier Estimate10aLung Diseases10aMale10aMortality10aProspective Studies10aRespiratory Function Tests10aRisk Assessment10aRisk Factors10aStroke Volume10aUnited States10aVentricular Dysfunction, Left1 aWaheed, Salman1 aChaves, Paulo, H M1 aGardin, Julius, M1 aCao, Jie, Jane uhttps://chs-nhlbi.org/node/693505255nas a2200949 4500008004100000022001400041245015700055210006900212260000900281300001300290490000700303520251800310653002202828653000902850653002802859653002802887653004002915653001102955653003402966653001103000653001703011653001403028653000903042653001603051653003603067653002203103100001903125700002103144700001603165700002203181700002603203700001603229700002103245700002303266700001603289700002003305700002203325700002203347700002103369700002303390700002303413700002003436700002203456700002303478700002103501700002203522700002003544700002103564700002203585700001803607700002003625700002503645700002203670700002303692700001703715700002103732700002303753700002403776700002003800700002103820700002203841700002503863700002803888700002203916700001403938700001903952700001903971700002003990700002604010700002404036700002704060700001904087700002404106700002204130700001604152700001904168700002304187700002104210700002004231700001804251856003604269 2015 eng d a1932-620300aDrug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.0 aDrugGene Interactions of Antihypertensive Medications and Risk o c2015 ae01404960 v103 aBACKGROUND: 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.
10aAfrican Americans10aAged10aAntihypertensive Agents10aCardiovascular Diseases10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aHypertension10aIncidence10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aTreatment Outcome1 aBis, Joshua, C1 aSitlani, Colleen1 aIrvin, Ryan1 aAvery, Christy, L1 aSmith, Albert, Vernon1 aSun, Fangui1 aEvans, Daniel, S1 aMusani, Solomon, K1 aLi, Xiaohui1 aTrompet, Stella1 aKrijthe, Bouwe, P1 aHarris, Tamara, B1 aQuibrera, Miguel1 aBrody, Jennifer, A1 aDemissie, Serkalem1 aDavis, Barry, R1 aWiggins, Kerri, L1 aTranah, Gregory, J1 aLange, Leslie, A1 aSotoodehnia, Nona1 aStott, David, J1 aFranco, Oscar, H1 aLauner, Lenore, J1 aStürmer, Til1 aTaylor, Kent, D1 aCupples, Adrienne, L1 aEckfeldt, John, H1 aSmith, Nicholas, L1 aLiu, Yongmei1 aWilson, James, G1 aHeckbert, Susan, R1 aBuckley, Brendan, M1 aIkram, Arfan, M1 aBoerwinkle, Eric1 aChen, Yii-Der Ida1 ade Craen, Anton, J M1 aUitterlinden, André, G1 aRotter, Jerome, I1 aFord, Ian1 aHofman, Albert1 aSattar, Naveed1 aSlagboom, Eline1 aWestendorp, Rudi, G J1 aGudnason, Vilmundur1 aVasan, Ramachandran, S1 aLumley, Thomas1 aCummings, Steven, R1 aTaylor, Herman, A1 aPost, Wendy1 aJukema, Wouter1 aStricker, Bruno, H1 aWhitsel, Eric, A1 aPsaty, Bruce, M1 aArnett, Donna uhttps://chs-nhlbi.org/node/687502584nas a2200445 4500008004100000022001400041245012100055210006900176260001600245300001100261490000800272520130700280653002101587653000901608653002201617653002201639653002201661653002801683653001601711653001301727653002201740653002401762653001101786653002201797653001101819653003101830653000901861653003001870653001701900653001501917653003201932653001701964653002101981100002002002700001802022700002102040700002002061700002102081856003602102 2015 eng d a1476-625600aEmpirically Derived Trajectories to Dementia Over 15 Years of Follow-up Identified by Using Mixed Membership Models.0 aEmpirically Derived Trajectories to Dementia Over 15 Years of Fo c2015 Aug 15 a366-740 v1823 aAlzheimer 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.
10aAge Distribution10aAged10aAged, 80 and over10aAlzheimer Disease10aApolipoprotein E410aCardiovascular Diseases10aComorbidity10aDementia10aDiabetes Mellitus10aDisease Progression10aFemale10aFollow-Up Studies10aHumans10aMagnetic Resonance Imaging10aMale10aMild Cognitive Impairment10aNeuroimaging10aPrevalence10aProportional Hazards Models10aRisk Factors10aSex Distribution1 aLecci, Fabrizio1 aJunker, Brian1 aKuller, Lewis, H1 aLopez, Oscar, L1 aBecker, James, T uhttps://chs-nhlbi.org/node/682202719nas a2200469 4500008004100000022001400041245010800055210006900163260001600232300001100248490000700259520132600266653000901592653001001601653002801611653001901639653002401658653002801682653003401710653003301744653002201777653001801799653003401817653001101851653002501862653002701887653002001914653002101934653002001955653001801975100002401993700002102017700001902038700002202057700002502079700002202104700002102126700002502147700002102172700002002193856003602213 2015 eng d a1097-025800aGeneralized estimating equations for genome-wide association studies using longitudinal phenotype data.0 aGeneralized estimating equations for genomewide association stud c2015 Jan 15 a118-300 v343 aMany longitudinal cohort studies have both genome-wide measures of genetic variation and repeated measures of phenotypes and environmental exposures. Genome-wide association study analyses have typically used only cross-sectional data to evaluate quantitative phenotypes and binary traits. Incorporation of repeated measures may increase power to detect associations, but also requires specialized analysis methods. Here, we discuss one such method-generalized estimating equations (GEE)-in the contexts of analysis of main effects of rare genetic variants and analysis of gene-environment interactions. We illustrate the potential for increased power using GEE analyses instead of cross-sectional analyses. We also address challenges that arise, such as the need for small-sample corrections when the minor allele frequency of a genetic variant and/or the prevalence of an environmental exposure is low. To illustrate methods for detection of gene-drug interactions on a genome-wide scale, using repeated measures data, we conduct single-study analyses and meta-analyses across studies in three large cohort studies participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium-the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Rotterdam Study.
10aAged10aAging10aCardiovascular Diseases10aCohort Studies10aComputer Simulation10aCross-Sectional Studies10aEpidemiologic Research Design10aGene-Environment Interaction10aGenetic Variation10aGenome, Human10aGenome-Wide Association Study10aHumans10aLongitudinal Studies10aMeta-Analysis as Topic10aModels, Genetic10aPharmacogenetics10aRisk Assessment10aUnited States1 aSitlani, Colleen, M1 aRice, Kenneth, M1 aLumley, Thomas1 aMcKnight, Barbara1 aCupples, Adrienne, L1 aAvery, Christy, L1 aNoordam, Raymond1 aStricker, Bruno, H C1 aWhitsel, Eric, A1 aPsaty, Bruce, M uhttps://chs-nhlbi.org/node/660203413nas a2200445 4500008004100000022001400041245010800055210006900163260001300232300001200245490000600257520216400263653000902427653002202436653002802458653001602486653002202502653001102524653002102535653001102556653003402567653002002601653000902621653002502630653001402655653003202669653002402701653002002725653001702745653001702762653001802779100001702797700001702814700002202831700002402853700001702877700001702894700002002911856003602931 2015 eng d a1876-759100aLV Mass as a Predictor of CVD Events in Older Adults With and Without Metabolic Syndrome and Diabetes.0 aLV Mass as a Predictor of CVD Events in Older Adults With and Wi c2015 Sep a1007-150 v83 aOBJECTIVES: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aComorbidity10aDiabetes Mellitus10aFemale10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLogistic Models10aMale10aMetabolic Syndrome X10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aHoang, Khiet1 aZhao, Yanglu1 aGardin, Julius, M1 aCarnethon, Mercedes1 aMukamal, Ken1 aYanez, David1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/682603704nas a2200589 4500008004100000022001400041245013900055210007000194260001300264300001200277490000700289520197000296653001002266653002202276653002102298653000902319653002802328653001902356653002802375653001102403653003802414653003402452653001102486653001402497653004102511653002602552653000902578653001602587653003602603653003202639653002402671653002002695653002102715653002202736100001702758700002102775700002002796700001902816700002602835700002502861700001202886700002002898700002202918700002002940700002002960700001702980700001802997700002003015700002203035700002103057856003603078 2015 eng d a1524-463600aPlasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.0 aPlasma Levels of Soluble Interleukin2 Receptor α Associations Wi c2015 Oct a2246-530 v353 aOBJECTIVE: 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.
10aAdult10aAfrican Americans10aAge Distribution10aAged10aCardiovascular Diseases10aCohort Studies10aCoronary Artery Disease10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aIncidence10aInterleukin-2 Receptor alpha Subunit10aKaplan-Meier Estimate10aMale10aMiddle Aged10aPolymorphism, Single Nucleotide10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aSex Distribution10aSurvival Analysis1 aDurda, Peter1 aSabourin, Jeremy1 aLange, Ethan, M1 aNalls, Mike, A1 aMychaleckyj, Josyf, C1 aJenny, Nancy, Swords1 aLi, Jin1 aWalston, Jeremy1 aHarris, Tamara, B1 aPsaty, Bruce, M1 aValdar, William1 aLiu, Yongmei1 aCushman, Mary1 aReiner, Alex, P1 aTracy, Russell, P1 aLange, Leslie, A uhttps://chs-nhlbi.org/node/680901068nas a2200361 4500008004100000022001400041245012200055210006900177260001300246300001100259490000700270653000900277653001000286653002800296653002800324653001100352653002500363653001100388653003100399653000900430653001700439653002500456653001900481100002000500700002100520700002600541700002000567700002000587700002000607700002200627700002100649856003600670 2015 eng d a1532-541500aSocial Network Size and Cranial Magnetic Resonance Imaging Findings in Older Adults: The Cardiovascular Health Study.0 aSocial Network Size and Cranial Magnetic Resonance Imaging Findi c2015 Nov a2430-20 v6310aAged10aBrain10aCardiovascular Diseases10aCross-Sectional Studies10aFemale10aGeriatric Assessment10aHumans10aMagnetic Resonance Imaging10aMale10aNeuroimaging10aSocial Participation10aSocial Support1 aFlatt, Jason, D1 aRosso, Andrea, L1 aAizenstein, Howard, J1 aSchulz, Richard1 aLongstreth, W T1 aNewman, Anne, B1 aFowler, Nicole, R1 aRosano, Caterina uhttps://chs-nhlbi.org/node/692802888nas a2200481 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520154100243653000901784653002201793653001601815653001501831653002801846653002501874653001501899653002401914653001101938653003101949653001801980653001101998653001402009653002802023653000902051653003202060653001502092100002502107700001902132700001602151700001902167700002402186700002202210700002502232700002402257700002202281700002402303700002302327700002002350856003602370 2015 eng d a1523-175500aUrinary uromodulin, kidney function, and cardiovascular disease in elderly adults.0 aUrinary uromodulin kidney function and cardiovascular disease in c2015 Nov a1126-340 v883 aUrinary 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.
10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCreatinine10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aProportional Hazards Models10aUromodulin1 aGarimella, Pranav, S1 aBiggs, Mary, L1 aKatz, Ronit1 aIx, Joachim, H1 aBennett, Michael, R1 aDevarajan, Prasad1 aKestenbaum, Bryan, R1 aSiscovick, David, S1 aJensen, Majken, K1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/677003025nas a2200469 4500008004100000022001400041245008200055210006900137260001300206300001300219490000700232520171300239653000901952653002801961653002501989653002402014653001102038653001802049653001102067653002802078653000902106653002202115653001602137653002402153653003302177100001902210700001902229700002102248700001802269700002102287700001902308700001602327700002302343700001802366700002002384700002602404700002502430700002002455700002402475700002002499856003602519 2015 eng d a1533-345000aUrine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.0 aUrine Collagen Fragments and CKD ProgressionThe Cardiovascular H c2015 Oct a2494-5030 v263 aTubulointerstitial 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.
10aAged10aCardiovascular Diseases10aCase-Control Studies10aDisease Progression10aFemale10aHeart Failure10aHumans10aKidney Failure, Chronic10aMale10aPeptide Fragments10aProcollagen10aProspective Studies10aRenal Insufficiency, Chronic1 aIx, Joachim, H1 aBiggs, Mary, L1 aMukamal, Kenneth1 aDjoussé, Luc1 aSiscovick, David1 aTracy, Russell1 aKatz, Ronit1 aDelaney, Joseph, A1 aChaves, Paulo1 aRifkin, Dena, E1 aHughes-Austin, Jan, M1 aGarimella, Pranav, S1 aSarnak, Mark, J1 aShlipak, Michael, G1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/666003330nas a2200421 4500008004100000022001400041245012500055210006900180260001300249490000600262520208400268653003102352653000902383653001502392653002802407653003502435653002102470653001102491653001102502653002302513653000902536653003102545653002202576653001602598653002402614653001802638653001502656100002602671700001802697700002202715700002402737700002302761700002002784700002102804700002402825700002302849856003602872 2015 eng d a2047-998000aYears of able life in older persons--the role of cardiovascular imaging and biomarkers: the Cardiovascular Health Study.0 aYears of able life in older personsthe role of cardiovascular im c2015 Apr0 v43 aBACKGROUND: 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.
10aActivities of Daily Living10aAged10aBiomarkers10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aEchocardiography10aFemale10aHumans10aIndependent Living10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aProcollagen10aProspective Studies10aStroke Volume10aTroponin I1 aAlshawabkeh, Laith, I1 aYee, Laura, M1 aGardin, Julius, M1 aGottdiener, John, S1 aOdden, Michelle, C1 aBartz, Traci, M1 aArnold, Alice, M1 aMukamal, Kenneth, J1 aWallace, Robert, B uhttps://chs-nhlbi.org/node/670703481nas a2200565 4500008004100000022001400041245008200055210006900137260001300206300001200219490000700231520189800238653002202136653001602158653000902174653001602183653002002199653002002219653002802239653001902267653004002286653001102326653001902337653003802356653003002394653001702424653001502441653001102456653001402467653002602481653002002507653002202527653000902549653002602558653001402584653003202598653002402630653002002654653001702674653001702691653001802708100002402726700002202750700002302772700001902795700002102814700002202835700002202857856003602879 2016 eng d a1524-463600aAPOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.0 aAPOL1 Genotype Kidney and Cardiovascular Disease and Death in Ol c2016 Feb a398-4030 v363 aOBJECTIVE: 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.
10aAfrican Americans10aAge Factors10aAged10aAlbuminuria10aApolipoproteins10aAtherosclerosis10aCardiovascular Diseases10aCause of Death10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenetic Predisposition to Disease10aHealth Status Disparities10aHeterozygote10aHomozygote10aHumans10aIncidence10aKaplan-Meier Estimate10aKidney Diseases10aLipoproteins, HDL10aMale10aMyocardial Infarction10aPhenotype10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aMukamal, Kenneth, J1 aTremaglio, Joseph1 aFriedman, David, J1 aIx, Joachim, H1 aKuller, Lewis, H1 aTracy, Russell, P1 aPollak, Martin, R uhttps://chs-nhlbi.org/node/693102806nas a2200385 4500008004100000022001400041245021100055210006900266260000900335300001300344490000700357520165000364653000902014653002102023653002402044653002802068653001102096653001102107653000902118653001602127653001202143653001202155653001102167100002002178700001902198700002002217700002202237700002402259700002202283700002002305700001902325700002302344700001702367856003602384 2016 eng d a1932-620300aAssociation of Smoking, Alcohol, and Obesity with Cardiovascular Death and Ischemic Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS).0 aAssociation of Smoking Alcohol and Obesity with Cardiovascular D c2016 ae01470650 v113 aAtrial 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.
10aAged10aAlcohol Drinking10aAtrial Fibrillation10aCardiovascular Diseases10aFemale10aHumans10aMale10aMiddle Aged10aObesity10aSmoking10aStroke1 aKwon, Younghoon1 aNorby, Faye, L1 aJensen, Paul, N1 aAgarwal, Sunil, K1 aSoliman, Elsayed, Z1 aLip, Gregory, Y H1 aLongstreth, W T1 aAlonso, Alvaro1 aHeckbert, Susan, R1 aChen, Lin, Y uhttps://chs-nhlbi.org/node/695003388nas a2200457 4500008004100000022001400041245012000055210006900175260001300244300001000257490000700267520205200274653000902326653001802335653001502353653002802368653002802396653003802424653001102462653003002473653001802503653003102521653001102552653002302563653002502586653000902611653001402620653001702634653003102651100001802682700001902700700002402719700002002743700002002763700002502783700002102808700002502829700002002854700002002874856003602894 2016 eng d a1532-541500aFibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.0 aFibroblast Growth Factor23 and Frailty in Elderly CommunityDwell c2016 Feb a270-60 v643 aOBJECTIVES: 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.
10aAged10aAnthropometry10aBiomarkers10aCardiovascular Diseases10aCross-Sectional Studies10aEnzyme-Linked Immunosorbent Assay10aFemale10aFibroblast Growth Factors10aFrail Elderly10aGlomerular Filtration Rate10aHumans10aIndependent Living10aLongitudinal Studies10aMale10aPhenotype10aRisk Factors10aSurveys and Questionnaires1 aBeben, Tomasz1 aIx, Joachim, H1 aShlipak, Michael, G1 aSarnak, Mark, J1 aFried, Linda, F1 aHoofnagle, Andrew, N1 aChonchol, Michel1 aKestenbaum, Bryan, R1 ade Boer, Ian, H1 aRifkin, Dena, E uhttps://chs-nhlbi.org/node/699005631nas a2200937 4500008004100000022001400041245013000055210006900185260001200254300001000266490000600276520305400282653000903336653001503345653002803360653001103388653001103399653000903410653001603419653003103435653002203466653002403488653002003512100001903532700002103551700001603572700002203588700001903610700002003629700001903649700001303668700002103681700002003702700002203722700001703744700001603761700001803777700002003795700001703815700001903832700002103851700001503872700001903887700002003906700001703926700002003943700002003963700002003983700002404003700002204027700001804049700001504067700002204082700002004104700002004124700002204144700003004166700001804196700002004214700002104234700001704255700001904272700001904291700002204310700002004332700002504352700002104377700002304398700001904421700002504440700002704465700001704492700001804509700002004527700002004547700002404567700001904591700001704610700003004627856003604657 2016 eng d a2213-859500aNatriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis.0 aNatriuretic peptides and integrated risk assessment for cardiova c2016 10 a840-90 v43 aBACKGROUND: 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.
10aAged10aBiomarkers10aCardiovascular Diseases10aFemale10aHumans10aMale10aMiddle Aged10aNatriuretic Peptide, Brain10aPeptide Fragments10aProspective Studies10aRisk Assessment1 aWilleit, Peter1 aKaptoge, Stephen1 aWelsh, Paul1 aButterworth, Adam1 aChowdhury, Raj1 aSpackman, Sarah1 aPennells, Lisa1 aGao, Pei1 aBurgess, Stephen1 aFreitag, Daniel1 aSweeting, Michael1 aWood, Angela1 aCook, Nancy1 aJudd, Suzanne1 aTrompet, Stella1 aNambi, Vijay1 aOlsen, Michael1 aEverett, Brendan1 aKee, Frank1 aArnlöv, Johan1 aSalomaa, Veikko1 aLevy, Daniel1 aKauhanen, Jussi1 aLaukkanen, Jari1 aKavousi, Maryam1 aNinomiya, Toshiharu1 aCasas, Juan-Pablo1 aDaniels, Lori1 aLind, Lars1 aKistorp, Caroline1 aRosenberg, Jens1 aMueller, Thomas1 aRubattu, Speranza1 aPanagiotakos, Demosthenes1 aFranco, Oscar1 ade Lemos, James1 aLuchner, Andreas1 aKizer, Jorge1 aKiechl, Stefan1 aSalonen, Jukka1 aWannamethee, Goya1 ade Boer, Rudolf1 aNordestgaard, Børge1 aAndersson, Jonas1 aJørgensen, Torben1 aMelander, Olle1 aBallantyne, Christie1 aDeFilippi, Christopher1 aRidker, Paul1 aCushman, Mary1 aRosamond, Wayne1 aThompson, Simon1 aGudnason, Vilmundur1 aSattar, Naveed1 aDanesh, John1 aDi Angelantonio, Emanuele uhttps://chs-nhlbi.org/node/856703152nas a2200529 4500008004100000022001400041245014400055210006900199260001300268300001000281490000700291520165800298653000901956653001001965653001801975653002801993653001202021653001102033653002202044653001202066653002702078653001902105653001102124653001402135653000902149653003202158653002402190653002002214653001702234653001802251653001802269100002402287700002002311700002102331700002402352700001902376700002102395700002402416700001802440700001902458700002302477700002202500700002402522700002002546700002002566856003602586 2016 eng d a1758-535X00aRelations of Postload and Fasting Glucose With Incident Cardiovascular Disease and Mortality Late in Life: The Cardiovascular Health Study.0 aRelations of Postload and Fasting Glucose With Incident Cardiova c2016 Mar a370-70 v713 aBACKGROUND: 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.
10aAged10aAging10aBlood Glucose10aCardiovascular Diseases10aFasting10aFemale10aFollow-Up Studies10aGlucose10aGlucose Tolerance Test10aHealth Surveys10aHumans10aIncidence10aMale10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aSurvival Rate10aUnited States1 aBrutsaert, Erika, F1 aShitole, Sanyog1 aBiggs, Mary, Lou1 aMukamal, Kenneth, J1 adeBoer, Ian, H1 aThacker, Evan, L1 aBarzilay, Joshua, I1 aDjoussé, Luc1 aIx, Joachim, H1 aSmith, Nicholas, L1 aKaplan, Robert, C1 aSiscovick, David, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/685002265nas a2200409 4500008004100000022001400041245012100055210006900176260001300245300001100258490000700269520108600276653003901362653000901401653002201410653002201432653001001454653002801464653001401492653001301506653004001519653001101559653002201570653001101592653003101603653000901634653002901643653001701672653001701689653001201706100002101718700002001739700002101759700001901780700002001799856003601819 2016 eng d a1552-527900aRisk of dementia and death in the long-term follow-up of the Pittsburgh Cardiovascular Health Study-Cognition Study.0 aRisk of dementia and death in the longterm followup of the Pitts c2016 Feb a170-830 v123 aINTRODUCTION: 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.
10aAfrican Continental Ancestry Group10aAged10aAged, 80 and over10aApolipoprotein E410aBrain10aCardiovascular Diseases10aCognition10aDementia10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aHumans10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aPennsylvania10aRisk Factors10aWalking1 aKuller, Lewis, H1 aLopez, Oscar, L1 aBecker, James, T1 aChang, Yuefang1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/687702493nas a2200349 4500008004100000022001400041245012600055210006900181260001300250300001100263490000700274520152300281653000901804653002201813653002801835653001501863653001101878653001801889653001101907653002501918653000901943653001701952653001201969653001801981100001601999700002002015700001602035700002002051700001702071700001902088856003602107 2016 eng d a1532-541500aSpousal Associations Between Frailty and Depressive Symptoms: Longitudinal Findings from the Cardiovascular Health Study.0 aSpousal Associations Between Frailty and Depressive Symptoms Lon c2016 Apr a824-300 v643 aOBJECTIVES: 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.
10aAged10aAged, 80 and over10aCardiovascular Diseases10aDepression10aFemale10aFrail Elderly10aHumans10aLongitudinal Studies10aMale10aRisk Factors10aSpouses10aUnited States1 aMonin, Joan1 aDoyle, Margaret1 aLevy, Becca1 aSchulz, Richard1 aFried, Terri1 aKershaw, Trace uhttps://chs-nhlbi.org/node/712703259nas a2200481 4500008004100000022001400041245010400055210006900159260001600228300001100244490000800255520187600263653001802139653002802157653001102185653002202196653001902218653002002237653002402257653001102281653002702292653004502319653001102364653000902375653002602384653001302410653001702423653002102440653002202461653001802483100002002501700002302521700002102544700002202565700002802587700002302615700002202638700001602660700002402676700002102700700002002721856003602741 2016 ENG d a1524-453900aStudy of Cardiovascular Health Outcomes in the Era of Claims Data: The Cardiovascular Health Study.0 aStudy of Cardiovascular Health Outcomes in the Era of Claims Dat c2016 Jan 12 a156-640 v1333 aBACKGROUND: 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.
10aBlood Glucose10aCardiovascular Diseases10aFemale10aFollow-Up Studies10aHealth Surveys10aHospitalization10aHospitals, Veterans10aHumans10aInsurance Claim Review10aInternational Classification of Diseases10aLipids10aMale10aManaged Care Programs10aMedicare10aRisk Factors10aSampling Studies10aTreatment Outcome10aUnited States1 aPsaty, Bruce, M1 aDelaney, Joseph, A1 aArnold, Alice, M1 aCurtis, Lesley, H1 aFitzpatrick, Annette, L1 aHeckbert, Susan, R1 aMcKnight, Barbara1 aIves, Diane1 aGottdiener, John, S1 aKuller, Lewis, H1 aLongstreth, W T uhttps://chs-nhlbi.org/node/693203488nas a2200481 4500008004100000022001400041245014400055210006900199260001600268300001400284490000800298520209000306653000902396653002202405653001502427653001802442653002802460653001902488653002202507653001102529653001102540653001402551653004902565653003302614653002502647653000902672653001602681653002402697653000902721100002502730700001702755700001402772700001902786700001802805700001802823700002002841700002002861700002102881700002102902700002502923700002202948856003602970 2017 eng d a1945-719700aThe Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.0 aAssociation Between IGFI and IGFBP3 and Incident Diabetes in an c2017 Dec 01 a4541-45470 v1023 aContext: 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.
10aAged10aAged, 80 and over10aBiomarkers10aBlood Glucose10aCardiovascular Diseases10aCohort Studies10aDiabetes Mellitus10aFemale10aHumans10aIncidence10aInsulin-Like Growth Factor Binding Protein 310aInsulin-Like Growth Factor I10aLongitudinal Studies10aMale10aNew England10aProspective Studies10aRisk1 aAneke-Nash, Chino, S1 aXue, XiaoNan1 aQi, Qibin1 aBiggs, Mary, L1 aCappola, Anne1 aKuller, Lewis1 aPollak, Michael1 aPsaty, Bruce, M1 aSiscovick, David1 aMukamal, Kenneth1 aStrickler, Howard, D1 aKaplan, Robert, C uhttps://chs-nhlbi.org/node/754710307nas a2202725 4500008004100000022001400041245012100055210006900176260001600245300001200261490000600273520278700279653001003066653000903076653002203085653002803107653001103135653003803146653003403184653002303218653001103241653000903252653003703261653001603298653001403314653003603328653002003364653001303384653002503397110005203422700002303474700002103497700001703518700001503535700002103550700001703571700002503588700002503613700002003638700001903658700001803677700001803695700001903713700002103732700002803753700002503781700002103806700002303827700002003850700001903870700001703889700002003906700002103926700001803947700001603965700002503981700002604006700002104032700001904053700002304072700002504095700002104120700001804141700002504159700003304184700002604217700003104243700001404274700001904288700002204307700002104329700001704350700002004367700002004387700002004407700001904427700002104446700002104467700002204488700002604510700001804536700002204554700002304576700002104599700002304620700001704643700002104660700002804681700002304709700001804732700002104750700002104771700001904792700002204811700001604833700002404849700002104873700002104894700001504915700002404930700002204954700002204976700001904998700001905017700002705036700002305063700002105086700001905107700002205126700001605148700002005164700002205184700002505206700001805231700002505249700002805274700001305302700002205315700001905337700001805356700002405374700002505398700002005423700002305443700001605466700001905482700002005501700002205521700001605543700002105559700002005580700001605600700002405616700002205640700002005662700001605682700002405698700002405722700002405746700002105770700002305791700002605814700002005840700002005860700001405880700001805894700001705912700002305929700002305952700001705975700001205992700002306004700002106027700002206048700002506070700002306095700001906118700002106137700002206158700001406180700002106194700002106215700001806236700002306254700001806277700001506295700001706310700001606327700001806343700002306361700002206384700001906406700002006425700002706445700001806472700001406490700002706504700001706531700001706548700001806565700001706583700001906600700001806619700002206637700002206659700001906681700001506700700001706715700001806732700001706750700001806767700001806785700002206803700002206825700002606847700001906873700002606892700002006918700001606938700001806954700002406972700001806996700002007014700001907034700001907053700002007072700002107092700001707113700002107130700002007151700001707171700001707188700002007205700002407225700001707249700002007266700002507286700003107311700002007342700001907362700002007381700001907401700001507420700002007435700001807455700002407473700002307497700002507520856003607545 2017 eng d a2374-244500aAssociation Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.0 aAssociation Between Telomere Length and Risk of Cancer and NonNe c2017 May 01 a636-6510 v33 aImportance: 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.
10aAdult10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGerm-Line Mutation10aHumans10aMale10aMendelian Randomization Analysis10aMiddle Aged10aNeoplasms10aPolymorphism, Single Nucleotide10aRisk Assessment10aTelomere10aTelomere Homeostasis1 aTelomeres Mendelian Randomization Collaboration1 aHaycock, Philip, C1 aBurgess, Stephen1 aNounu, Aayah1 aZheng, Jie1 aOkoli, George, N1 aBowden, Jack1 aWade, Kaitlin, Hazel1 aTimpson, Nicholas, J1 aEvans, David, M1 aWilleit, Peter1 aAviv, Abraham1 aGaunt, Tom, R1 aHemani, Gibran1 aMangino, Massimo1 aEllis, Hayley, Patricia1 aKurian, Kathreena, M1 aPooley, Karen, A1 aEeles, Rosalind, A1 aLee, Jeffrey, E1 aFang, Shenying1 aChen, Wei, V1 aLaw, Matthew, H1 aBowdler, Lisa, M1 aIles, Mark, M1 aYang, Qiong1 aWorrall, Bradford, B1 aMarkus, Hugh, Stephen1 aHung, Rayjean, J1 aAmos, Chris, I1 aSpurdle, Amanda, B1 aThompson, Deborah, J1 aO'Mara, Tracy, A1 aWolpin, Brian1 aAmundadottir, Laufey1 aStolzenberg-Solomon, Rachael1 aTrichopoulou, Antonia1 aOnland-Moret, Charlotte, N1 aLund, Eil1 aDuell, Eric, J1 aCanzian, Federico1 aSeveri, Gianluca1 aOvervad, Kim1 aGunter, Marc, J1 aTumino, Rosario1 aSvenson, Ulrika1 avan Rij, Andre1 aBaas, Annette, F1 aBown, Matthew, J1 aSamani, Nilesh, J1 avan t'Hof, Femke, N G1 aTromp, Gerard1 aJones, Gregory, T1 aKuivaniemi, Helena1 aElmore, James, R1 aJohansson, Mattias1 aMckay, James1 aScelo, Ghislaine1 aCarreras-Torres, Robert1 aGaborieau, Valerie1 aBrennan, Paul1 aBracci, Paige, M1 aNeale, Rachel, E1 aOlson, Sara, H1 aGallinger, Steven1 aLi, Donghui1 aPetersen, Gloria, M1 aRisch, Harvey, A1 aKlein, Alison, P1 aHan, Jiali1 aAbnet, Christian, C1 aFreedman, Neal, D1 aTaylor, Philip, R1 aMaris, John, M1 aAben, Katja, K1 aKiemeney, Lambertus, A1 aVermeulen, Sita, H1 aWiencke, John, K1 aWalsh, Kyle, M1 aWrensch, Margaret1 aRice, Terri1 aTurnbull, Clare1 aLitchfield, Kevin1 aPaternoster, Lavinia1 aStandl, Marie1 aAbecasis, Goncalo, R1 aSanGiovanni, John, Paul1 aLi, Yong1 aMijatovic, Vladan1 aSapkota, Yadav1 aLow, Siew-Kee1 aZondervan, Krina, T1 aMontgomery, Grant, W1 aNyholt, Dale, R1 avan Heel, David, A1 aHunt, Karen1 aArking, Dan, E1 aAshar, Foram, N1 aSotoodehnia, Nona1 aWoo, Daniel1 aRosand, Jonathan1 aComeau, Mary, E1 aBrown, Mark1 aSilverman, Edwin, K1 aHokanson, John, E1 aCho, Michael, H1 aHui, Jennie1 aFerreira, Manuel, A1 aThompson, Philip, J1 aMorrison, Alanna, C1 aFelix, Janine, F1 aSmith, Nicholas, L1 aChristiano, Angela, M1 aPetukhova, Lynn1 aBetz, Regina, C1 aFan, Xing1 aZhang, Xuejun1 aZhu, Caihong1 aLangefeld, Carl, D1 aThompson, Susan, D1 aWang, Feijie1 aLin, Xu1 aSchwartz, David, A1 aFingerlin, Tasha1 aRotter, Jerome, I1 aCotch, Mary, Frances1 aJensen, Richard, A1 aMunz, Matthias1 aDommisch, Henrik1 aSchaefer, Arne, S1 aHan, Fang1 aOllila, Hanna, M1 aHillary, Ryan, P1 aAlbagha, Omar1 aRalston, Stuart, H1 aZeng, Chenjie1 aZheng, Wei1 aShu, Xiao-Ou1 aReis, Andre1 aUebe, Steffen1 aHüffmeier, Ulrike1 aKawamura, Yoshiya1 aOtowa, Takeshi1 aSasaki, Tsukasa1 aHibberd, Martin, Lloyd1 aDavila, Sonia1 aXie, Gang1 aSiminovitch, Katherine1 aBei, Jin-Xin1 aZeng, Yi-Xin1 aFörsti, Asta1 aChen, Bowang1 aLandi, Stefano1 aFranke, Andre1 aFischer, Annegret1 aEllinghaus, David1 aFlores, Carlos1 aNoth, Imre1 aMa, Shwu-Fan1 aFoo, Jia, Nee1 aLiu, Jianjun1 aKim, Jong-Won1 aCox, David, G1 aDelattre, Olivier1 aMirabeau, Olivier1 aSkibola, Christine, F1 aTang, Clara, S1 aGarcia-Barcelo, Merce1 aChang, Kai-Ping1 aSu, Wen-Hui1 aChang, Yu-Sun1 aMartin, Nicholas, G1 aGordon, Scott1 aWade, Tracey, D1 aLee, Chaeyoung1 aKubo, Michiaki1 aCha, Pei-Chieng1 aNakamura, Yusuke1 aLevy, Daniel1 aKimura, Masayuki1 aHwang, Shih-Jen1 aHunt, Steven1 aSpector, Tim1 aSoranzo, Nicole1 aManichaikul, Ani, W1 aBarr, Graham1 aKahali, Bratati1 aSpeliotes, Elizabeth1 aYerges-Armstrong, Laura, M1 aCheng, Ching-Yu1 aJonas, Jost, B1 aWong, Tien, Yin1 aFogh, Isabella1 aLin, Kuang1 aPowell, John, F1 aRice, Kenneth1 aRelton, Caroline, L1 aMartin, Richard, M1 aSmith, George, Davey uhttps://chs-nhlbi.org/node/759403593nas a2200337 4500008004100000022001400041245014900055210006900204260001600273300001200289490000800301520258200309653002802891653002502919653001802944653001102962653001402973653001802987653001703005100001403022700001803036700002503054700001903079700001703098700002203115700001803137700001903155700002503174700002003199856003603219 2017 eng d a2168-617300aAssociation of Diabetic Macular Edema and Proliferative Diabetic Retinopathy With Cardiovascular Disease: A Systematic Review and Meta-analysis.0 aAssociation of Diabetic Macular Edema and Proliferative Diabetic c2017 Jun 01 a586-5930 v1353 aImportance: Previous studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients.
Objective: To examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes.
Data Sources: English-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy.
Study Selection: Among 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point.
Data Extraction and Synthesis: Two independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017.
Main Outcome and Measures: Incident CVD, including coronary heart disease, stroke, or death from cardiovascular causes.
Results: Among 7604 patients with type 2 diabetes, the prevalence of DME was 4.6% and PDR, 7.4%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95% CI, 1.49-3.67) compared with those without DME or PDR.
Conclusions and Relevance: Patients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.
10aCardiovascular Diseases10aDiabetic Retinopathy10aGlobal Health10aHumans10aIncidence10aMacular Edema10aRisk Factors1 aXie, Jing1 aIkram, Kamran1 aCotch, Mary, Frances1 aKlein, Barbara1 aVarma, Rohit1 aShaw, Jonathan, E1 aKlein, Ronald1 aMitchell, Paul1 aLamoureux, Ecosse, L1 aWong, Tien, Yin uhttps://chs-nhlbi.org/node/759703000nas a2200517 4500008004100000022001400041245014300055210006900198260001600267300001400283490000800297520149600305653000901801653002201810653002801832653003101860653002001891653002801911653001901939653000901958653001301967653001101980653002401991653002202015653001102037653001402048653002502062653000902087653001402096653003302110653002402143653001802167100002202185700002202207700002002229700002202249700001902271700002302290700002102313700002202334700002802356700002202384700002002406700002002426856003602446 2017 eng d a1476-625600aConcordance With Prevention Guidelines and Subsequent Cancer, Cardiovascular Disease, and Mortality: A Longitudinal Study of Older Adults.0 aConcordance With Prevention Guidelines and Subsequent Cancer Car c2017 Nov 15 a1168-11790 v1863 aReports 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.
10aAged10aAged, 80 and over10aAmerican Cancer Society10aAmerican Heart Association10aBody Mass Index10aCardiovascular Diseases10aCause of Death10aDiet10aExercise10aFemale10aGuideline Adherence10aHealthy Lifestyle10aHumans10aIncidence10aLongitudinal Studies10aMale10aNeoplasms10aPractice Guidelines as Topic10aProspective Studies10aUnited States1 aGreenlee, Heather1 aStrizich, Garrett1 aLovasi, Gina, S1 aKaplan, Robert, C1 aBiggs, Mary, L1 aLi, Christopher, I1 aRichardson, John1 aBurke, Gregory, L1 aFitzpatrick, Annette, L1 aFretts, Amanda, M1 aPsaty, Bruce, M1 aFried, Linda, P uhttps://chs-nhlbi.org/node/756303575nas a2200517 4500008004100000022001400041245012200055210006900177260001300246300001400259490000700273520210400280653001002384653000902394653002202403653001502425653001902440653002802459653002502487653001902512653002502531653001102556653002202567653001102589653001402600653003402614653002602648653002802674653000902702653001602711653002402727653002202751653001702773653001102790653001802801100002102819700002802840700001602868700002002884700002402904700002102928700002402949700002302973700002502996856003603021 2017 eng d a1524-462800aOmega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.0 aOmega3 Fatty Acids and Incident Ischemic Stroke and Its Atheroth c2017 Oct a2678-26850 v483 aBACKGROUND 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.
10aAdult10aAged10aAged, 80 and over10aBiomarkers10aBrain Ischemia10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aFatty Acids, Omega-310aFemale10aFollow-Up Studies10aHumans10aIncidence10aIntracranial Arteriosclerosis10aIntracranial Embolism10aIntracranial Thrombosis10aMale10aMiddle Aged10aProspective Studies10aRandom Allocation10aRisk Factors10aStroke10aUnited States1 aSaber, Hamidreza1 aYakoob, Mohammad, Yawar1 aShi, Peilin1 aLongstreth, W T1 aLemaitre, Rozenn, N1 aSiscovick, David1 aRexrode, Kathryn, M1 aWillett, Walter, C1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/749003338nas a2200457 4500008004100000022001400041245008600055210006900141260001200210300001200222490000700234520207200241653000902313653002202322653001802344653002302362653002802385653002202413653001102435653003102446653001102477653001402488653001202502653002502514653000902539653002402548653001702572653001802589100002402607700002402631700002002655700001902675700002002694700001802714700002802732700002202760700002102782700002002803700002102823856003602844 2018 eng d a1532-541500aMetabolic Clusters and Outcomes in Older Adults: The Cardiovascular Health Study.0 aMetabolic Clusters and Outcomes in Older Adults The Cardiovascul c2018 02 a289-2960 v663 aBACKGROUND/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.
10aAged10aAged, 80 and over10aBlood Glucose10aC-Reactive Protein10aCardiovascular Diseases10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aInsulin10aLongitudinal Studies10aMale10aProspective Studies10aRisk Factors10aUnited States1 aMukamal, Kenneth, J1 aSiscovick, David, S1 ade Boer, Ian, H1 aIx, Joachim, H1 aKizer, Jorge, R1 aDjoussé, Luc1 aFitzpatrick, Annette, L1 aTracy, Russell, P1 aBoyko, Edward, J1 aKahn, Steven, E1 aArnold, Alice, M uhttps://chs-nhlbi.org/node/853905160nas a2201237 4500008004100000022001400041245019700055210006900252260000900321300001300330490000700343520163700350653000901987653002801996653003502024653001102059653001102070653003202081653000902113653001602122653001402138653001702152100002402169700001202193700002502205700002902230700002702259700002302286700001702309700002102326700001902347700002102366700001702387700001802404700002802422700001502450700002002465700002502485700001902510700002102529700002302550700001702573700002002590700002302610700002002633700002702653700001802680700002302698700002302721700001902744700002202763700002002785700002102805700001702826700001902843700002102862700002302883700002402906700001602930700002202946700002602968700002102994700001903015700001803034700002003052700002003072700002103092700001803113700001603131700001903147700001903166700001503185700002203200700002303222700002403245700003003269700002103299700002103320700002303341700002003364700001903384700001803403700002103421700002003442700002603462700001903488700002103507700001803528700002003546700001903566700002603585700002503611700002403636700001903660700002003679700002003699700001403719700002503733700002003758700001903778700002103797700002003818700002303838710002503861856003603886 2018 eng d a1932-620300aPredictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.0 aPredictive value for cardiovascular events of common carotid int c2018 ae01911720 v133 aAIMS: 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.
10aAged10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aFemale10aHumans10aIntersectoral Collaboration10aMale10aMiddle Aged10aPrognosis10aRisk Factors1 aLorenz, Matthias, W1 aGao, Lu1 aZiegelbauer, Kathrin1 aNorata, Giuseppe, Danilo1 aEmpana, Jean, Philippe1 aSchmidtmann, Irene1 aLin, Hung-Ju1 aMcLachlan, Stela1 aBokemark, Lena1 aRonkainen, Kimmo1 aAmato, Mauro1 aSchminke, Ulf1 aSrinivasan, Sathanur, R1 aLind, Lars1 aOkazaki, Shuhei1 aStehouwer, Coen, D A1 aWilleit, Peter1 aPolak, Joseph, F1 aSteinmetz, Helmuth1 aSander, Dirk1 aPoppert, Holger1 aDesvarieux, Moïse1 aIkram, Arfan, M1 aJohnsen, Stein, Harald1 aStaub, Daniel1 aSirtori, Cesare, R1 aIglseder, Bernhard1 aBeloqui, Oscar1 aEngström, Gunnar1 aFriera, Alfonso1 aRozza, Francesco1 aXie, Wuxiang1 aParraga, Grace1 aGrigore, Liliana1 aPlichart, Matthieu1 aBlankenberg, Stefan1 aSu, Ta-Chen1 aSchmidt, Caroline1 aTuomainen, Tomi-Pekka1 aVeglia, Fabrizio1 aVölzke, Henry1 aNijpels, Giel1 aWilleit, Johann1 aSacco, Ralph, L1 aFranco, Oscar, H1 aUthoff, Heiko1 aHedblad, Bo1 aSuarez, Carmen1 aIzzo, Raffaele1 aZhao, Dong1 aWannarong, Thapat1 aCatapano, Alberico1 aDucimetiere, Pierre1 aEspinola-Klein, Christine1 aChien, Kuo-Liong1 aPrice, Jackie, F1 aBergström, Göran1 aKauhanen, Jussi1 aTremoli, Elena1 aDörr, Marcus1 aBerenson, Gerald1 aKitagawa, Kazuo1 aDekker, Jacqueline, M1 aKiechl, Stefan1 aSitzer, Matthias1 aBickel, Horst1 aRundek, Tatjana1 aHofman, Albert1 aMathiesen, Ellisiv, B1 aCastelnuovo, Samuela1 aLandecho, Manuel, F1 aRosvall, Maria1 aGabriel, Rafael1 ade Luca, Nicola1 aLiu, Jing1 aBaldassarre, Damiano1 aKavousi, Maryam1 ade Groot, Eric1 aBots, Michiel, L1 aYanez, David, N1 aThompson, Simon, G1 aPROG-IMT Study Group uhttps://chs-nhlbi.org/node/784605208nas a2200541 4500008004100000022001400041245012300055210006900178260001500247300001300262490000600275520365800281653001003939653000903949653002003958653002803978653001904006653002404025653001104049653001104060653002504071653000904096653001604105653003204121653002404153653002004177653001704197100001704214700002104231700002004252700002704272700002204299700002304321700001704344700002404361700002304385700002304408700001804431700002304449700002704472700002104499700001904520700002704539700002104566700002304587700002004610856003604630 2020 eng d a2574-380500aPerformance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.0 aPerformance of the Pooled Cohort Equations to Estimate Atheroscl c2020 10 01 ae20232420 v33 aImportance: 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.
10aAdult10aAged10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aCorrelation of Data10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors1 aKhera, Rohan1 aPandey, Ambarish1 aAyers, Colby, R1 aCarnethon, Mercedes, R1 aGreenland, Philip1 aNdumele, Chiadi, E1 aNambi, Vijay1 aSeliger, Stephen, L1 aChaves, Paulo, H M1 aSafford, Monika, M1 aCushman, Mary1 aXanthakis, Vanessa1 aVasan, Ramachandran, S1 aMentz, Robert, J1 aCorrea, Adolfo1 aLloyd-Jones, Donald, M1 aBerry, Jarett, D1 ade Lemos, James, A1 aNeeland, Ian, J uhttps://chs-nhlbi.org/node/862605260nas a2200553 4500008004100000022001400041245009600055210006900151260001500220300001400235490000800249520374200257653001003999653000904009653002204018653002804040653001104068653002904079653001104108653000904119653001804128653000904146653001604155653001504171653002604186653001504212653001804227653001904245100001804264700001904282700002404301700002004325700002504345700001804370700002404388700002404412700002004436700002104456700001704477700002504494700002104519700002404540700002204564700002304586700001704609700001804626700002604644856003604670 2021 eng d a1538-359800aAssociation Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.0 aAssociation Between Preserved Ratio Impaired Spirometry and Clin c2021 12 14 a2287-22980 v3263 aImportance: 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.
10aAdult10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aForced Expiratory Volume10aHumans10aLung10aLung Diseases10aMale10aMiddle Aged10aPrevalence10aRetrospective Studies10aSpirometry10aUnited States10aVital Capacity1 aWan, Emily, S1 aBalte, Pallavi1 aSchwartz, Joseph, E1 aBhatt, Surya, P1 aCassano, Patricia, A1 aCouper, David1 aDaviglus, Martha, L1 aDransfield, Mark, T1 aGharib, Sina, A1 aJacobs, David, R1 aKalhan, Ravi1 aLondon, Stephanie, J1 aNavas-Acien, Ana1 aO'Connor, George, T1 aSanders, Jason, L1 aSmith, Benjamin, M1 aWhite, Wendy1 aYende, Sachin1 aOelsner, Elizabeth, C uhttps://chs-nhlbi.org/node/911402911nas a2200421 4500008004100000022001400041245010100055210006900156260001500225300001600240490000700256520176000263653001502023653001002038653000902048653002202057653001002079653001902089653002802108653001402136653002602150653001902176653001102195653003102206653001102237653001702248653000902265653001602274653001702290653001602307100002002323700002202343700001602365700002002381700002302401700002902424856003602453 2021 eng d a1526-632X00aCardiovascular Risk Factors Across the Life Course and Cognitive Decline: A Pooled Cohort Study.0 aCardiovascular Risk Factors Across the Life Course and Cognitive c2021 04 27 ae2212-e22190 v963 aOBJECTIVE: 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.
10aAdolescent10aAdult10aAged10aAged, 80 and over10aAging10aBlood Pressure10aCardiovascular Diseases10aCognition10aCognitive Dysfunction10aCohort Studies10aFemale10aHeart Disease Risk Factors10aHumans10aHypertension10aMale10aMiddle Aged10aRisk Factors10aYoung Adult1 aYaffe, Kristine1 aVittinghoff, Eric1 aHoang, Tina1 aMatthews, Karen1 aGolden, Sherita, H1 aHazzouri, Adina, Zeki Al uhttps://chs-nhlbi.org/node/879204438nas a2200457 4500008004100000022001400041245009000055210006900145260001500214300001300229490000600242520319000248653000903438653001203447653002803459653001403487653001203501653001903513653001103532653001103543653000903554653001703563653002403580100002203604700002203626700001703648700002003665700002403685700001503709700002903724700002403753700001503777700002003792700002403812700002203836700002203858700001503880700002403895700002503919856003603944 2022 eng d a2574-380500aAssociation of Trimethylamine N-Oxide and Metabolites With Mortality in Older Adults.0 aAssociation of Trimethylamine NOxide and Metabolites With Mortal c2022 05 02 ae22132420 v53 aImportance: 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.
10aAged10aBetaine10aCardiovascular Diseases10aCarnitine10aCholine10aCohort Studies10aFemale10aHumans10aMale10aMethylamines10aProspective Studies1 aFretts, Amanda, M1 aHazen, Stanley, L1 aJensen, Paul1 aBudoff, Matthew1 aSitlani, Colleen, M1 aWang, Meng1 aOtto, Marcia, C de Olive1 aDiDonato, Joseph, A1 aLee, Yujin1 aPsaty, Bruce, M1 aSiscovick, David, S1 aSotoodehnia, Nona1 aTang, W, H Wilson1 aLai, Heidi1 aLemaitre, Rozenn, N1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/909103024nas a2200373 4500008004100000022001400041245012200055210006900177260001300246300001200259490000700271520193900278653000902217653001402226653002802240653002402268653001402292653001802306653001102324653000902335653003302344653001702377100002202394700002102416700001902437700002402456700002302480700002102503700002202524700002402546700002402570700002002594856003602614 2022 eng d a2047-998000aCirculating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study.0 aCirculating Androgen Concentrations and Risk of Incident Heart F c2022 Nov ae0269530 v113 aBackground Circulating androgen concentrations in men decline with age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone and incident heart failure (HF) but remains unstudied for free testosterone or the more potent androgen dihydrotestosterone (DHT). We hypothesized that total/free testosterone are inversely related, sex hormone-binding globulin is positively related, and total/free DHT bear a U-shaped relationship with incident HF. Methods and Results In a sample of men from the CHS (Cardiovascular Health Study) without atherosclerotic cardiovascular disease or HF, serum testosterone and DHT concentrations were measured by liquid chromatography-tandem mass spectrometry, and sex hormone-binding globulin by immunoassay. Free testosterone or DHT was calculated from total testosterone or total DHT, sex hormone-binding globulin, and albumin. We used Cox regression to estimate relative risks of HF after adjustment for potential confounders. In 1061 men (aged 76±5 years) followed for a median of 9.6 years, there were 368 HF events. After adjustment, lower calculated free testosterone was significantly associated with higher risk of HF (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]). Risk estimates for total testosterone (HR, 1.12 [95% CI, 0.99-1.26]), total DHT (HR, 1.10 [95% CI, 0.97-1.24]), calculated free dihydrotestosterone (HR, 1.09 [95% CI, 0.97-1.23]), and sex hormone-binding globulin (HR, 1.07 [95% CI, 0.95-1.21]) were directionally similar but not statistically significant. Conclusions Calculated free testosterone was inversely associated with incident HF, suggesting a contribution of testosterone deficiency to HF incidence among older men. Additional research is necessary to determine whether testosterone replacement therapy might be an effective strategy to lower HF risk in older men.
10aAged10aAndrogens10aCardiovascular Diseases10aDihydrotestosterone10aEstradiol10aHeart Failure10aHumans10aMale10aSex Hormone-Binding Globulin10aTestosterone1 aNjoroge, Joyce, N1 aTressel, William1 aBiggs, Mary, L1 aMatsumoto, Alvin, M1 aSmith, Nicholas, L1 aRosenberg, Emily1 aHirsch, Calvin, H1 aGottdiener, John, S1 aMukamal, Kenneth, J1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/925603432nas a2200457 4500008004100000022001400041245018200055210006900237260001300306300001200319490000700331520203700338653000902375653001702384653004602401653003202447653001502479653002802494653001102522653003402533653001802567653001102585653002502596653000902621100001702630700002302647700002002670700001902690700002502709700001802734700002202752700001802774700001802792700001902810700002602829700002002855700002002875700002202895700002102917856003602938 2022 eng d a2047-998000aCirculating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study.0 aCirculating Soluble CD163 Associations With Cardiovascular Outco c2022 Nov ae0243740 v113 aBackground 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.
10aAged10aAntigens, CD10aAntigens, Differentiation, Myelomonocytic10aAsialoglycoprotein Receptor10aBiomarkers10aCardiovascular Diseases10aFemale10aGenome-Wide Association Study10aHeart Failure10aHumans10aLongitudinal Studies10aMale1 aDurda, Peter1 aRaffield, Laura, M1 aLange, Ethan, M1 aOlson, Nels, C1 aJenny, Nancy, Swords1 aCushman, Mary1 aDeichgraeber, Pia1 aGrarup, Niels1 aJonsson, Anna1 aHansen, Torben1 aMychaleckyj, Josyf, C1 aPsaty, Bruce, M1 aReiner, Alex, P1 aTracy, Russell, P1 aLange, Leslie, A uhttps://chs-nhlbi.org/node/924503344nas a2200421 4500008004100000022001400041245015100055210006900206260001200275300001400287490000700301520211000308653001202418653002002430653002802450653001402478653001102492653000902503653001702512653001702529100001502546700001702561700001502578700002002593700002902613700002402642700001902666700002202685700002002707700002402727700002202751700002202773700002002795700002402815700002202839700002502861856003602886 2022 eng d a1524-463600aDietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.0 aDietary Meat Trimethylamine NOxideRelated Metabolites and Incide c2022 09 ae273-e2880 v423 aBACKGROUND: Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways.
METHODS: Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways.
RESULTS: After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01-1.30), 1.22 (1.07-1.39), and 1.18 (1.03-1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0-114.5), 7.8% (1.0-32.7), and 9.2% (2.2-44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98-1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association.
CONCLUSIONS: In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.
10aAnimals10aAtherosclerosis10aCardiovascular Diseases10aCarnitine10aHumans10aMeat10aMethylamines10aRisk Factors1 aWang, Meng1 aWang, Zeneng1 aLee, Yujin1 aLai, Heidi, T M1 aOtto, Marcia, C de Olive1 aLemaitre, Rozenn, N1 aFretts, Amanda1 aSotoodehnia, Nona1 aBudoff, Matthew1 aDiDonato, Joseph, A1 aMcKnight, Barbara1 aTang, W, H Wilson1 aPsaty, Bruce, M1 aSiscovick, David, S1 aHazen, Stanley, L1 aMozaffarian, Dariush uhttps://chs-nhlbi.org/node/918204351nas a2200373 4500008004100000022001400041245010200055210006900157260001600226300001200242490000600254520332100260653001003581653000903591653002803600653001903628653001803647653001103665653001103676653001703687653001603704653001703720100002103737700001903758700001803777700002203795700002003817700001703837700002003854700002203874700002103896700002403917856003603941 2022 eng d a2574-380500aIntake and Sources of Dietary Fiber, Inflammation, and Cardiovascular Disease in Older US Adults.0 aIntake and Sources of Dietary Fiber Inflammation and Cardiovascu c2022 Mar 01 ae2250120 v53 aImportance: 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.
10aAdult10aAged10aCardiovascular Diseases10aCohort Studies10aDietary Fiber10aFemale10aHumans10aInflammation10aMiddle Aged10aRisk Factors1 aShivakoti, Rupak1 aBiggs, Mary, L1 aDjoussé, Luc1 aDurda, Peter, Jon1 aKizer, Jorge, R1 aPsaty, Bruce1 aReiner, Alex, P1 aTracy, Russell, P1 aSiscovick, David1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/902503954nas a2200805 4500008004100000022001400041245007700055210006900132260001300201300001100214490000700225520175800232653001501990653002802005653002002033653002402053653001602077653001102093653000902104653001402113100001902127700001802146700002002164700002802184700001602212700002302228700002102251700001502272700002402287700002802311700002002339700001702359700002602376700002002402700001602422700001402438700001602452700002002468700001902488700002002507700001802527700002602545700002202571700002302593700002102616700002302637700002002660700001902680700002002699700002202719700002402741700001702765700002202782700002002804700002602824700001802850700002002868700001402888700002202902700002702924700001602951700002502967700002002992700002103012700002303033700001803056700002103074700001703095856003603112 2022 eng d a1474-972600aIntegrative analysis of clinical and epigenetic biomarkers of mortality.0 aIntegrative analysis of clinical and epigenetic biomarkers of mo c2022 Jun ae136080 v213 aDNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, P = 4.1 × 10 ) and negatively associated with longevity (Beta = -1.9, P = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.
10aBiomarkers10aCardiovascular Diseases10aDNA Methylation10aEpigenesis, Genetic10aEpigenomics10aHumans10aMale10aNeoplasms1 aHuan, Tianxiao1 aNguyen, Steve1 aColicino, Elena1 aOchoa-Rosales, Carolina1 aHill, David1 aBrody, Jennifer, A1 aSoerensen, Mette1 aZhang, Yan1 aBaldassari, Antoine1 aElhadad, Mohamed, Ahmed1 aToshiko, Tanaka1 aZheng, Yinan1 aDomingo-Relloso, Arce1 aLee, Dong, Heon1 aMa, Jiantao1 aYao, Chen1 aLiu, Chunyu1 aHwang, Shih-Jen1 aJoehanes, Roby1 aFornage, Myriam1 aBressler, Jan1 avan Meurs, Joyce, B J1 aDebrabant, Birgit1 aMengel-From, Jonas1 aHjelmborg, Jacob1 aChristensen, Kaare1 aVokonas, Pantel1 aSchwartz, Joel1 aGahrib, Sina, A1 aSotoodehnia, Nona1 aSitlani, Colleen, M1 aKunze, Sonja1 aGieger, Christian1 aPeters, Annette1 aWaldenberger, Melanie1 aDeary, Ian, J1 aFerrucci, Luigi1 aQu, Yishu1 aGreenland, Philip1 aLloyd-Jones, Donald, M1 aHou, Lifang1 aBandinelli, Stefania1 aVoortman, Trudy1 aHermann, Brenner1 aBaccarelli, Andrea1 aWhitsel, Eric1 aPankow, James, S1 aLevy, Daniel uhttps://chs-nhlbi.org/node/909402982nas a2200397 4500008004100000022001400041245011500055210006900170260001300239300001100252490000700263520181400270653001202084653002202096653002802118653003002146653001602176653001102192653002002203653002402223100002402247700002002271700002102291700002202312700002002334700002302354700002402377700002202401700002002423700001902443700002402462700002002486700002202506700002002528856003602548 2022 eng d a2352-396400aPlasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study.0 aPlasma epoxyeicosatrienoic acids and diabetesrelated cardiovascu c2022 Sep a1041890 v833 aBACKGROUND: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that may impact atherosclerosis, and animal experimental studies suggest EETs protect cardiac function. Plasma EETs are mostly esterified to phospholipids and part of an active pool. To address the limited information about EETs and CVD in humans, we conducted a prospective study of total plasma EETs (free + esterified) and diabetes-related CVD in the Cardiovascular Health Study (CHS).
METHODS: We measured 4 EET species and their metabolites, dihydroxyepoxyeicosatrienoic acids (DHETs), in plasma samples from 892 CHS participants with type 2 diabetes. We determined the association of EETs and DHETs with incident myocardial infarction (MI) and ischemic stroke using Cox regression.
FINDINGS: During follow-up (median 7.5 years), we identified 150 MI and 134 ischemic strokes. In primary, multivariable analyses, elevated levels of each EET species were associated with non-significant lower risk of incident MI (for example, hazard ratio for 1 SD higher 14,15-EET: 0.86, 95% CI: 0.72-1.02; p=0.08). The EETs-MI associations became significant in analyses further adjusted for DHETs (hazard ratio for 1 SD higher 14,15-EET adjusted for 14,15-DHET: 0.76, 95% CI: 0.63-0.91; p=0.004). Elevated EET levels were associated with higher risk of ischemic stroke in primary but not secondary analyses. Three DHET species were associated with higher risk of ischemic stroke in all analyses.
INTERPRETATION: Findings from this prospective study complement the extensive studies in animal models showing EETs protect cardiac function and provide new information in humans. Replication is needed to confirm the associations.
FUNDING: US National Institutes of Health.
10aAnimals10aArachidonic Acids10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aEicosanoids10aHumans10aIschemic Stroke10aProspective Studies1 aLemaitre, Rozenn, N1 aJensen, Paul, N1 aZeigler, Maxwell1 aFretts, Amanda, M1 aUmans, Jason, G1 aHoward, Barbara, V1 aSitlani, Colleen, M1 aMcKnight, Barbara1 aGharib, Sina, A1 aKing, Irena, B1 aSiscovick, David, S1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aTotah, Rheem, A uhttps://chs-nhlbi.org/node/917103102nas a2200361 4500008004100000022001400041245012400055210006900179260001500248300001200263490000700275520200300282653002002285653002802305653001902333653003702352653001102389653001602400653001702416100003402433700002102467700002502488700002402513700001802537700001902555700002402574700002202598700002502620700002002645700001902665700002002684856003602704 2022 eng d a2047-998000aPlasma Levels of Advanced Glycation Endproducts and Risk of Cardiovascular Events: Findings From 2 Prospective Cohorts.0 aPlasma Levels of Advanced Glycation Endproducts and Risk of Card c2022 08 02 ae0240120 v113 aBackground Advanced glycation endproducts (AGEs) have been linked to cardiovascular disease (CVD) in cohorts with and without diabetes. Data are lacking on prospective associations of various α-dicarbonyl-derived AGEs and incident CVD in the general population. We tested the hypothesis that major plasma AGEs are associated with new-onset CVD in 2 population-based cohorts of differing age and comorbidities. Methods and Results Analyses involved a random subcohort (n=466) from the Cardiovascular Health Study and a case-cohort sample (n=1631) from the Multi-Ethnic Study of Atherosclerosis. Five AGEs and 2 oxidative products were measured by liquid chromatography tandem mass spectrometry. Associations with CVD (myocardial infarction and stroke) were evaluated with Cox regression. Participants in the Cardiovascular Health Study were older than the Multi-Ethnic Study of Atherosclerosis, and had more comorbidities, along with higher levels of all AGEs. During median follow-up of 11 years, 439 participants in the Multi-Ethnic Study of Atherosclerosis and 200 in the Cardiovascular Health Study developed CVD. After multivariable adjustment, carboxymethyl-lysine, 3-deoxyglucosone hydroimidazolones and a summary variable of all measured AGEs (principal component 1) were significantly associated with incident CVD in the Cardiovascular Health Study (HRs [95% CI]: 1.20 [1.01, 1.42], 1.45 [1.23, 1.72], and 1.29 [1.06, 1.56], respectively), but not the Multi-Ethnic Study of Atherosclerosis. Oxidative products were not associated with CVD in either cohort. Conclusions We found α-dicarbonyl-derived AGEs to be associated with CVD in an older cohort, but not in a healthier middle-aged/older cohort. Our results suggest that AGEs may exert detrimental cardiovascular effects only under conditions of marked dicarbonyl and oxidative stress. Further investigation of α-dicarbonyl derivatives could lead to potential new strategies for CVD prevention in high-risk older populations.
10aAtherosclerosis10aCardiovascular Diseases10aCohort Studies10aGlycation End Products, Advanced10aHumans10aMiddle Aged10aRisk Factors1 aLamprea-Montealegre, Julio, A1 aArnold, Alice, M1 aMcClelland, Robyn, L1 aMukamal, Kenneth, J1 aDjoussé, Luc1 aBiggs, Mary, L1 aSiscovick, David, S1 aTracy, Russell, P1 aBeisswenger, Paul, J1 aPsaty, Bruce, M1 aIx, Joachim, H1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/917002957nas a2200313 4500008004100000022001400041245014500055210006900200260001600269300000800285490000700293520204400300653002002344653002802364653001902392653001102411653003102422653001102453653001402464653000902478653001602487653002402503653001702527100001402544700001502558700001502573700001902588856003602607 2023 eng d a1479-587600aAssociation between 5-year change in cardiovascular risk and the incidence of atherosclerotic cardiovascular diseases: a multi-cohort study.0 aAssociation between 5year change in cardiovascular risk and the c2023 Sep 02 a5890 v213 aBACKGROUND: 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.
10aAtherosclerosis10aCardiovascular Diseases10aCohort Studies10aFemale10aHeart Disease Risk Factors10aHumans10aIncidence10aMale10aMiddle Aged10aProspective Studies10aRisk Factors1 aYi, Jiayi1 aWang, Lili1 aGuo, Xinli1 aRen, Xiangpeng uhttps://chs-nhlbi.org/node/948602812nas a2200325 4500008004100000022001400041245014100055210006900196260001600265300001200281490000700293520182800300653000902128653001002137653002802147653001802175653001102193653001402204653001802218100002202236700002502258700001902283700002002302700002202322700002302344700003102367700002802398700002402426856003602450 2023 eng d a2047-998000aElevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.0 aElevated Plasma Levels of Ketone Bodies Are Associated With AllC c2023 Sep 05 ae0299600 v123 aBackground Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; =0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; =0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; =0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.
10aAged10aAging10aCardiovascular Diseases10aHeart Failure10aHumans10aIncidence10aKetone Bodies1 aNiezen, Sebastian1 aConnelly, Margery, A1 aHirsch, Calvin1 aKizer, Jorge, R1 aBenitez, Maria, E1 aMinchenberg, Scott1 aPerez-Matos, Maria, Camila1 aJiang, Zhenghui, Gordon1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/948505138nas a2201357 4500008004100000022001400041245012700055210006900182260001600251300000900267490000700276520124600283653002501529653002701554653001501581653002801596653002401624653003401648653001101682653001701693100002201710700002201732700002601754700001901780700001301799700001801812700002201830700001901852700002001871700002901891700002701920700002401947700001801971700001601989700002202005700001302027700002102040700002002061700001902081700002602100700002402126700001902150700002702169700002002196700002602216700002202242700001902264700002302283700002102306700001902327700001902346700002102365700002702386700002402413700002702437700001502464700002302479700001702502700001902519700002302538700002402561700001702585700003202602700002102634700002502655700002402680700001702704700002302721700002602744700002502770700001802795700002102813700001402834700002402848700002402872700001802896700002902914700001902943700002502962700001802987700002103005700002103026700002203047700001903069700002203088700001703110700002103127700001803148700002203166700001903188700002903207700002803236700002503264700002003289700002203309700002903331700002203360700002303382700001503405700002303420700001803443700002103461700001903482700002203501700001803523700002403541700001803565700002103583700002403604700002203628700002003650700002203670700002803692700002403720856003603744 2023 eng d a2041-172300aGenetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.0 aGenetic architecture of spatial electrical biomarkers for cardia c2023 Mar 14 a14110 v143 aThe 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
10aArrhythmias, Cardiac10aAtrioventricular Block10aBiomarkers10aCardiovascular Diseases10aElectrocardiography10aGenome-Wide Association Study10aHumans10aRisk Factors1 aYoung, William, J1 aHaessler, Jeffrey1 aBenjamins, Jan-Walter1 aRepetto, Linda1 aYao, Jie1 aIsaacs, Aaron1 aHarper, Andrew, R1 aRamirez, Julia1 aGarnier, Sophie1 aVan Duijvenboden, Stefan1 aBaldassari, Antoine, R1 aConcas, Maria, Pina1 aDuong, ThuyVy1 aFoco, Luisa1 aIsaksen, Jonas, L1 aMei, Hao1 aNoordam, Raymond1 aNursyifa, Casia1 aRichmond, Anne1 aSantolalla, Meddly, L1 aSitlani, Colleen, M1 aSoroush, Negin1 aThériault, Sébastien1 aTrompet, Stella1 aAeschbacher, Stefanie1 aAhmadizar, Fariba1 aAlonso, Alvaro1 aBrody, Jennifer, A1 aCampbell, Archie1 aCorrea, Adolfo1 aDarbar, Dawood1 aDe Luca, Antonio1 aDeleuze, Jean-Francois1 aEllervik, Christina1 aFuchsberger, Christian1 aGoel, Anuj1 aGrace, Christopher1 aGuo, Xiuqing1 aHansen, Torben1 aHeckbert, Susan, R1 aJackson, Rebecca, D1 aKors, Jan, A1 aLima-Costa, Maria, Fernanda1 aLinneberg, Allan1 aMacfarlane, Peter, W1 aMorrison, Alanna, C1 aNavarro, Pau1 aPorteous, David, J1 aPramstaller, Peter, P1 aReiner, Alexander, P1 aRisch, Lorenz1 aSchotten, Ulrich1 aShen, Xia1 aSinagra, Gianfranco1 aSoliman, Elsayed, Z1 aStoll, Monika1 aTarazona-Santos, Eduardo1 aTinker, Andrew1 aTrajanoska, Katerina1 aVillard, Eric1 aWarren, Helen, R1 aWhitsel, Eric, A1 aWiggins, Kerri, L1 aArking, Dan, E1 aAvery, Christy, L1 aConen, David1 aGirotto, Giorgia1 aGrarup, Niels1 aHayward, Caroline1 aJukema, Wouter1 aMook-Kanamori, Dennis, O1 aOlesen, Morten, Salling1 aPadmanabhan, Sandosh1 aPsaty, Bruce, M1 aPattaro, Cristian1 aRibeiro, Antonio, Luiz P1 aRotter, Jerome, I1 aStricker, Bruno, H1 aHarst, Pim1 aDuijn, Cornelia, M1 aVerweij, Niek1 aWilson, James, G1 aOrini, Michele1 aCharron, Philippe1 aWatkins, Hugh1 aKooperberg, Charles1 aLin, Henry, J1 aWilson, James, F1 aKanters, Jørgen, K1 aSotoodehnia, Nona1 aMifsud, Borbala1 aLambiase, Pier, D1 aTereshchenko, Larisa, G1 aMunroe, Patricia, B uhttps://chs-nhlbi.org/node/932204184nas a2200829 4500008004100000022001400041245017700055210006900232260001600301300001200317490000800329520172300337653001202060653001502072653002802087653002602115653002502141653001702166100002202183700002102205700002002226700001602246700001902262700002002281700002202301700001802323700001902341700002302360700002102383700002002404700002002424700002202444700002002466700002002486700001902506700002302525700002402548700002102572700002502593700001802618700002402636700002002660700002102680700002602701700002202727700001902749700001902768700001702787700002702804700002502831700001602856700002102872700002402893700001802917700002402935700002402959700001902983700002003002700002203022700002503044700002103069700002003090700002503110700001803135700002003153700002303173700002103196700002503217700001903242710005703261856003603318 2024 eng d a1524-453900aRole of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.0 aRole of Polyunsaturated Fat in Modifying Cardiovascular Risk Ass c2024 Jan 23 a305-3160 v1493 aBACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.
RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; =0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.
CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
10aAnimals10aBiomarkers10aCardiovascular Diseases10aDocosahexaenoic Acids10aFatty Acids, Omega-310aRisk Factors1 aLaguzzi, Federica1 aÅkesson, Agneta1 aMarklund, Matti1 aQian, Frank1 aGigante, Bruna1 aBartz, Traci, M1 aBassett, Julie, K1 aBirukov, Anna1 aCampos, Hannia1 aHirakawa, Yoichiro1 aImamura, Fumiaki1 aJäger, Susanne1 aLankinen, Maria1 aMurphy, Rachel, A1 aSenn, Mackenzie1 aTanaka, Toshiko1 aTintle, Nathan1 aVirtanen, Jyrki, K1 aYamagishi, Kazumasa1 aAllison, Matthew1 aBrouwer, Ingeborg, A1 ade Faire, Ulf1 aEiriksdottir, Gudny1 aFerrucci, Luigi1 aForouhi, Nita, G1 aGeleijnse, Johanna, M1 aHodge, Allison, M1 aKimura, Hitomi1 aLaakso, Markku1 aRiserus, Ulf1 avan Westing, Anniek, C1 aBandinelli, Stefania1 aBaylin, Ana1 aGiles, Graham, G1 aGudnason, Vilmundur1 aIso, Hiroyasu1 aLemaitre, Rozenn, N1 aNinomiya, Toshiharu1 aPost, Wendy, S1 aPsaty, Bruce, M1 aSalonen, Jukka, T1 aSchulze, Matthias, B1 aTsai, Michael, Y1 aUusitupa, Matti1 aWareham, Nicholas, J1 aOh, Seung-Won1 aWood, Alexis, C1 aHarris, William, S1 aSiscovick, David1 aMozaffarian, Dariush1 aLeander, Karin1 aFatty Acids and Outcomes Research Consortium (FORCE) uhttps://chs-nhlbi.org/node/9587