03948nas 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 a

BACKGROUND: 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/144102616nas 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 a

Few 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/143603088nas 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 a

OBJECTIVES: 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/143003415nas a2200385 4500008004100000022001400041245011100055210006900166260001300235300001100248490000700259520232400266653003102590653000902621653002202630653002002652653002102672653003302693653001102726653002502737653001102762653002002773653000902793653003702802653001702839653001602856653002602872653001802898100001502916700001902931700001202950700001702962700001402979856003602993 1994 eng d a0895-435600aPhysical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.0 aPhysical disability in older adults a physiological approach Car c1994 Jul a747-600 v473 a

Measures of physical function have been developed primarily to assess health status, prognosis, and service needs. They are now, increasingly, being used as outcome measures in studies seeking to determine the causes of disability. However, the extent to which these standardized measures, as they currently are constituted, are meaningful for the evaluation of underlying pathophysiology is not defined. To assess evidence for an etiologic rationale for these measures, we evaluated self-report of difficulty in physical function in the Cardiovascular Health Study, a study of 5201 men and women 65 years and older in four U.S. communities. We determined (by factor analysis) that self-reported difficulty with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in one task is associated with having difficulty in the other tasks in the group. These groups include (1) activities primarily dependent on mobility and exercise tolerance; (2) complex activities heavily dependent on cognition and sensory input; (3) selected basic self-care activities; and (4) upper extremity activities. Groups 2 and 3 are similar, but not identical, to Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL), respectively. We then tested whether these groupings were associated with different underlying impairments. Multiple logistic regression analyses indicate that there are constellations of physiologic and disease characteristics significantly (p < 0.01) associated with difficulty in each of these four groups of activities, among 15 chronic diseases and conditions ascertained. Some diseases are uniquely associated with difficulty in one group of tasks; some overlap, and are associated with 2, 3 or 4 groups of tasks. The associations found with difficulty in performing tasks in groups 2 and 3 were frequently stronger than those with the larger groups of ADL or IADL tasks, suggesting increased specificity of associations found with these new groupings. These results suggest that re-grouping of tasks of daily life may provide a more refined physiologically-based outcome measure for use in evaluating causes of disability. The ability to define risk factors for disability may be enhanced by choosing outcome measures with a demonstrated physiologic rationale.

10aActivities of Daily Living10aAged10aAged, 80 and over10aChronic Disease10aDisabled Persons10aFactor Analysis, Statistical10aFemale10aGeriatric Assessment10aHumans10aLogistic Models10aMale10aOutcome Assessment (Health Care)10aRisk Factors10aSex Factors10aSocioeconomic Factors10aUnited States1 aFried, L P1 aEttinger, W, H1 aLind, B1 aNewman, A, B1 aGardin, J uhttps://chs-nhlbi.org/node/141702199nas 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 a

Cardiovascular 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/141402745nas a2200529 4500008004100000022001400041245011300055210006900168260001300237300001100250490000700261520128200268653001601550653000901566653002501575653002401600653001501624653002101639653002501660653002401685653003601709653001101745653001901756653001101775653003401786653002001820653000901840653001301849653002601862653002601888653002401914653001901938653001201957653001501969653001701984653001502001653001702016653002402033100002102057700001702078700001702095700001702112700001702129700001702146700001602163856003602179 1995 eng d a0167-527300aIschemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the Cardiovascular Health Study.0 aIschemic episodes in 24h ambulatory electrocardiograms of elderl c1995 Sep a165-750 v513 a

We examined correlates of ischemic episodes in 24-h ambulatory electrocardiograms (ECG) in a sample of 1511 men and women 65 years old and older. Ischemic episodes had a high prevalence period during early afternoon and also during morning hours after awakening, and the overall prevalence was 13% in men and 9% in women (P < 0.001 for gender difference). The prevalence was 9.6% in participants with no history of myocardial infarction and no major or minor resting ECG abnormalities. In multivariate analysis by logistic regression, being on digitalis medication was associated with over a three-fold risk of ischemic episodes, with an odds ratio (95% confidence limits) of 3.21 (1.80 to 5.74). Left ventricular hypertrophy by ECG and atrial fibrillation had almost a three-fold excess risk of ischemic episodes, with odds ratios 2.81 (1.37 to 5.74) and 2.63 (1.17 to 5.91), respectively. Isolated ST-T abnormalities had almost a two-fold excess of ischemic episodes, with an odds ratio of 1.89 (1.01 to 3.54). Being overweight was associated with a 33% reduced likelihood of ischemic episodes after adjustment for other factors, with an odds ratio of 0.67 (0.46 to 0.98). It is concluded that the prevalence of silent ischemic episodes is high in older men and women.

10aAge Factors10aAged10aArrhythmias, Cardiac10aAtrial Fibrillation10aCalifornia10aCircadian Rhythm10aDigitalis Glycosides10aElectrocardiography10aElectrocardiography, Ambulatory10aFemale10aHealth Surveys10aHumans10aHypertrophy, Left Ventricular10aLogistic Models10aMale10aMaryland10aMultivariate Analysis10aMyocardial Infarction10aMyocardial Ischemia10aNorth Carolina10aObesity10aOdds Ratio10aPennsylvania10aPrevalence10aRisk Factors10aSex Characteristics1 aRautaharju, P, M1 aManolio, T A1 aFurberg, C D1 aSiscovick, D1 aNewman, A, B1 aBorhani, N O1 aGardin, J M uhttps://chs-nhlbi.org/node/145102798nas 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 a

The 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/146703061nas a2200433 4500008004100000022001400041245014300055210006900198260001300267300001200280490000700292520182800299653003202127653000902159653002202168653002802190653001002218653002902228653001402257653001902271653002802290653001402318653001102332653002502343653001102368653003102379653000902410653001702419100001802436700002002454700001502474700001702489700001502506700001702521700002102538700001502559700001702574856003602591 1997 eng d a0002-861400aThe association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.0 aassociation of antihypertensive agents with MRI white matter fin c1997 Dec a1423-330 v453 a

OBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults.

DESIGN: Cross-sectional study.

SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older.

PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension.

MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings).

RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors.

CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.

10aAdrenergic beta-Antagonists10aAged10aAged, 80 and over10aAntihypertensive Agents10aBrain10aCalcium Channel Blockers10aCognition10aCohort Studies10aCross-Sectional Studies10aDiuretics10aFemale10aGeriatric Assessment10aHumans10aMagnetic Resonance Imaging10aMale10aRisk Factors1 aHeckbert, S R1 aLongstreth, W T1 aPsaty, B M1 aMurros, K, E1 aSmith, N L1 aNewman, A, B1 aWilliamson, J, D1 aBernick, C1 aFurberg, C D uhttps://chs-nhlbi.org/node/149103373nas 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 a

OBJECTIVES: 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/147303916nas 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 a

OBJECTIVES: 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/149703834nas 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 a

CONTEXT: 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/149803367nas a2200361 4500008004100000022001400041245010800055210006900163260001600232300001100248490000800259520237700267653000902644653002902653653002102682653001902703653001102722653001102733653002502744653000902769653001502778653001702793653001802810100001902828700001702847700001702864700001702881700001702898700002002915700001902935700001502954856003602969 1998 eng d a0003-992600aTime trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.0 aTime trends in the use of cholesterollowering agents in older ad c1998 Sep 14 a1761-80 v1583 a

OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older.

SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit.

RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy.

CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.

10aAged10aAnticholesteremic Agents10aCholesterol, LDL10aCohort Studies10aFemale10aHumans10aHypercholesterolemia10aMale10aPrevalence10aRisk Factors10aUnited States1 aLemaitre, R, N1 aFurberg, C D1 aNewman, A, B1 aHulley, S, B1 aGordon, D, J1 aGottdiener, J S1 aMcDonald, R, H1 aPsaty, B M uhttps://chs-nhlbi.org/node/151302941nas 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 a

Peripheral 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/58601639nas a2200325 4500008004100000022001400041245006700055210006600122260001300188300000900201490000700210520076800217653000900985653002400994653003001018653001901048653001101067653000901078653002501087653003201112653001701144100001901161700001801180700001701198700001601215700001701231700001401248700001501262856003601277 1999 eng d a0884-873400aStroke risk in an elderly population with atrial fibrillation.0 aStroke risk in an elderly population with atrial fibrillation c1999 Jan a56-90 v143 a

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke varies widely depending on coexistent vascular disease. We assessed the stroke rate and predictive value of two published schemes for stroke risk stratification in a population-derived cohort of 259 elderly people with nonvalvular AF followed for a median of 5.3 years. The rate of ischemic stroke was 2.8% per year (95% confidence interval [CI] 1.9, 3.9). Thirty-one percent were predicted to be at low risk, and their stroke rate was 1.7% per year (95% CI 0.6, 3.8). Many people with AF in this population-derived cohort had relatively low rates of stroke. Further studies to reliably stratify stroke risk in patients with AF are needed.

10aAged10aAtrial Fibrillation10aCerebrovascular Disorders10aCohort Studies10aHumans10aMale10aPoisson Distribution10aProportional Hazards Models10aRisk Factors1 aFeinberg, W, M1 aKronmal, R, A1 aNewman, A, B1 aKraut, M, A1 aBovill, E, G1 aCooper, L1 aHart, R, G uhttps://chs-nhlbi.org/node/152102834nas a2200385 4500008004100000022001400041245009400055210006900149260001600218300001100234490000800245520182100253653000902074653001902083653001202102653002402114653003002138653001702168653002402185653001102209653001102220653001402231653000902245653001502254653002202269653001302291100001502304700001502319700001702334700001302351700001502364700001702379700001702396856003502413 1999 eng d a0003-992600aTemporal trends in the use of anticoagulants among older adults with atrial fibrillation.0 aTemporal trends in the use of anticoagulants among older adults  c1999 Jul 26 a1574-80 v1593 a

BACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.

METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.

RESULTS: The use of warfarin increased 4-fold from 13% in 1990 to 50% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.

CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.

10aAged10aAnticoagulants10aAspirin10aAtrial Fibrillation10aCerebrovascular Disorders10aDrug Therapy10aElectrocardiography10aFemale10aHumans10aIncidence10aMale10aPrevalence10aTreatment Outcome10aWarfarin1 aSmith, N L1 aPsaty, B M1 aFurberg, C D1 aWhite, R1 aLima, J, A1 aNewman, A, B1 aManolio, T A uhttps://chs-nhlbi.org/node/59902787nas a2200337 4500008004100000022001400041245010800055210006900163260001300232300001100245490000800256520186600264653001602130653000902146653002202155653001102177653001102188653001102199653000902210653003002219653002002249653001702269653001502286653001902301100001802320700002102338700001702359700001902376700001902395856003502414 1999 eng d a0012-369200aUnderdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group.0 aUnderdiagnosis and undertreatment of asthma in the elderly Cardi c1999 Sep a603-130 v1163 a

OBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons.

PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study.

MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow.

RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40% were taking a sympathomimetic bronchodilator, 30% inhaled corticosteroids, 21% theophylline, and 18% oral corticosteroids; 39% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not.

CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.

10aAge Factors10aAged10aAged, 80 and over10aAsthma10aFemale10aHumans10aMale10aPeak Expiratory Flow Rate10aQuality of Life10aRisk Factors10aSpirometry10aVital Capacity1 aEnright, P, L1 aMcClelland, R, L1 aNewman, A, B1 aGottlieb, D, J1 aLebowitz, M, D uhttps://chs-nhlbi.org/node/60103847nas a2200421 4500008004100000022001400041245013700055210006900192260001600261300001200277490000800289520270400297653001003001653000903011653001903020653002803039653001103067653001103078653001703089653002003106653000903126653001603135653001203151653002003163653002603183653001203209100001603221700001603237700001503253700001403268700001603282700001503298700002103313700001703334700001903351700002003370856003503390 2000 eng d a0098-748400aAssociation of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.0 aAssociation of sleepdisordered breathing sleep apnea and hyperte c2000 Apr 12 a1829-360 v2833 a

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.

OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.

DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.

PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8% female).

MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.

RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (> or = 12% vs < 0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.

CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

10aAdult10aAged10aCohort Studies10aCross-Sectional Studies10aFemale10aHumans10aHypertension10aLogistic Models10aMale10aMiddle Aged10aObesity10aPolysomnography10aSleep Apnea Syndromes10aSnoring1 aNieto, F, J1 aYoung, T, B1 aLind, B, K1 aShahar, E1 aSamet, J, M1 aRedline, S1 aD'Agostino, R, B1 aNewman, A, B1 aLebowitz, M, D1 aPickering, T, G uhttps://chs-nhlbi.org/node/61303286nas 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 a

BACKGROUND: 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 a

INTRODUCTION: 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/61003882nas 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 a

BACKGROUND: 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 a

BACKGROUND: 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/63002533nas a2200493 4500008004100000022001400041245009000055210006900145260001600214300001200230490000800242520121300250653002101463653001601484653000901500653002201509653001701531653001501548653001201563653001901575653001601594653002501610653002801635653002101663653001501684653001101699653001101710653002001721653000901741653003001750653001501780653001701795653002101812653001601833653003101849653001701880100001701897700001801914700002201932700001501954700001901969700001601988856003502004 2001 eng d a1524-453900aCoronary artery calcification in older adults to age 99: prevalence and risk factors.0 aCoronary artery calcification in older adults to age 99 prevalen c2001 Nov 27 a2679-840 v1043 a

BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied.

METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60%) were women, and 143 (23%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile.

CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

10aAge Distribution10aAge Factors10aAged10aAged, 80 and over10aBlack People10aCalcinosis10aCalcium10aCohort Studies10aComorbidity10aCoronary Angiography10aCoronary Artery Disease10aCoronary Vessels10aDemography10aFemale10aHumans10aLogistic Models10aMale10aPredictive Value of Tests10aPrevalence10aRisk Factors10aSex Distribution10aSex Factors10aTomography, X-Ray Computed10aWhite People1 aNewman, A, B1 aNaydeck, B, L1 aSutton-Tyrrell, K1 aFeldman, A1 aEdmundowicz, D1 aKuller, L H uhttps://chs-nhlbi.org/node/66704256nas a2200469 4500008004100000022001400041245005500055210005300110260001300163300001200176490000700188520307600195653000903271653002203280653001903302653002103321653001203342653001103354653001803365653001103383653001403394653000903408653002003417653001403437653001503451653002103466653001803487653001603505100001503521700001703536700001503553700001703568700001403585700001803599700001403617700001303631700001403644700001303658700001903671710006103690856003503751 2001 eng d a1079-500600aFrailty in older adults: evidence for a phenotype.0 aFrailty in older adults evidence for a phenotype c2001 Mar aM146-560 v563 a

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.

METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.

RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).

CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

10aAged10aAged, 80 and over10aCohort Studies10aDisabled Persons10aFatigue10aFemale10aFrail Elderly10aHumans10aIncidence10aMale10aMuscle Weakness10aPhenotype10aPrevalence10aSex Distribution10aUnited States10aWeight Loss1 aFried, L P1 aTangen, C, M1 aWalston, J1 aNewman, A, B1 aHirsch, C1 aGottdiener, J1 aSeeman, T1 aTracy, R1 aKop, W, J1 aBurke, G1 aMcBurnie, M, A1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/63902473nas a2200373 4500008004100000022001400041245005700055210005500112260001300167300001200180490000700192520153600199653000901735653002201744653001001766653001601776653001601792653002801808653002601836653001101862653000901873653001101882653000901893653003001902653001701932653001701949653001201966100001601978700001601994700001302010700002402023700001702047856003502064 2001 eng d a0002-861400aGait variability in community-dwelling older adults.0 aGait variability in communitydwelling older adults c2001 Dec a1646-500 v493 a

OBJECTIVES: To describe gait variability at usual and fast walking speeds in community-dwelling older adults and to describe the effects of increasing gait speed on gait variability.

DESIGN: Cross-sectional, descriptive study.

SETTING: The Cardiovascular Health Study at the University of Pittsburgh.

PARTICIPANTS: Ninety-five community-living older adults, 54 women and 41 men, age 65 and older (mean age +/- standard deviation 79.4 +/- 3.37).

MEASUREMENTS: Gait measured at participant's usual and fast walking speed collected using an instrumented walkway. Step-length and step-width variability were determined using the coefficient of variation.

RESULTS: Step-length variability was greatest in those who walked the slowest (r = -0.66, P < .001); step-width variability was smallest in those who walked the slowest (r -0.37, P < .001). Individuals who could not increase their walking speed (<0.10 m/second) on command had an increase in step-length variability and a decrease in step-width variability, whereas those who could increase their speed (>0.10 m/second) had an increase in step-width variability when walking at a faster speed.

CONCLUSIONS: Step-length and step-width variability have opposite associations with gait speed in older adults. Improvement in step-length and step-width variability with attempted acceleration might be a key factor to examine in future studies of disability risk and therapeutic interventions.

10aAged10aAged, 80 and over10aAging10aBody Height10aBody Weight10aCross-Sectional Studies10aDisability Evaluation10aFemale10aGait10aHumans10aMale10aResidence Characteristics10aRisk Factors10aTime Factors10aWalking1 aBrach, J, S1 aBerthold, R1 aCraik, R1 aVanSwearingen, J, M1 aNewman, A, B uhttps://chs-nhlbi.org/node/67902295nas a2200325 4500008004100000022001400041245008100055210006900136260001300205300001000218490000800228520137300236653000901609653002201618653001901640653003301659653001101692653002901703653001101732653002501743653001501768653001901783100001801802700001501820700001801835700001701853700001701870710004701887856003501934 2001 eng d a1073-449X00aHormone replacement therapy is associated with higher FEV1 in elderly women.0 aHormone replacement therapy is associated with higher FEV1 in el c2001 Feb a423-80 v1633 a

Estrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.

10aAged10aAged, 80 and over10aCohort Studies10aEstrogen Replacement Therapy10aFemale10aForced Expiratory Volume10aHumans10aLongitudinal Studies10aSpirometry10aVital Capacity1 aCarlson, C, L1 aCushman, M1 aEnright, P, L1 aCauley, J, A1 aNewman, A, B1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63102542nas 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 a

Associations 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/65402111nas a2200385 4500008004100000022001400041245009200055210006900147260001300216300001200229490000700241520101100248653000901259653002001268653003201288653003001320653001901350653001601369653002201385653001101407653001101418653003001429653000801459653000901467653001501476653003201491653003101523100001701554700001801571700002201589700001601611700001601627710004701643856003501690 2001 eng d a0895-435600aThe role of comorbidity in the assessment of intermittent claudication in older adults.0 arole of comorbidity in the assessment of intermittent claudicati c2001 Mar a294-3000 v543 a

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

10aAged10aAngina Pectoris10aArterial Occlusive Diseases10aCerebrovascular Disorders10aCohort Studies10aComorbidity10aDiabetes Mellitus10aFemale10aHumans10aIntermittent Claudication10aLeg10aMale10aPrevalence10aSensitivity and Specificity10aSurveys and Questionnaires1 aNewman, A, B1 aNaydeck, B, L1 aSutton-Tyrrell, K1 aPolak, J, F1 aKuller, L H1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/63802622nas 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 a

Disordered 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/63602974nas a2200397 4500008004100000022001400041245006500055210006400120260001300184300001200197490000700209520192800216653000902144653002502153653001602178653002802194653001102222653001802233653001102251653002502262653000902287653001402296653003202310653001702342653001802359653001602377653001602393100001702409700001302426700001402439700001502453700001802468700001502486710004002501856003502541 2001 eng d a0002-861400aWeight change in old age and its association with mortality.0 aWeight change in old age and its association with mortality c2001 Oct a1309-180 v493 a

OBJECTIVES: Previous studies of weight change and mortality in older adults have relied on self-reported weight loss, have not evaluated weight gain, or have had limited information on health status. Our objective was to determine whether 5% weight gain or loss in 3 years was predictive of mortality in a large sample of older adults.

DESIGN: Longitudinal observational cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: Four thousand seven hundred fourteen community-dwelling older adults, age 65 and older.

MEASUREMENTS: Weight gain or loss of 5% in a 3-year period was examined in relationship to baseline health status and interim health events. Risk for subsequent mortality was estimated in those with weight loss or weight gain compared with the group whose weight was stable.

RESULTS: Weight changes occurred in 34.6% of women and 27.3% of men, with weight loss being more frequent than gain. Weight loss was associated with older age, black race, higher weight, lower waist circumference, current smoking, stroke, any hospitalization, death of a spouse, activities of daily living disability, lower grip strength, and slower gait speed. Weight loss but not weight gain of 5% or more was associated with an increased risk of mortality that persisted after multivariate adjustment (Hazard ratio (HR) = 1.67, 95% CI = 1.29-2.15) and was similar in those with no serious illness in the period of weight change. Those with weight loss and low baseline weight had the highest crude mortality rate, although the HR for weight loss was similar for all tertiles of baseline weight and for those with or without a special diet, compared with those whose weight was stable.

CONCLUSIONS: This study confirms that even modest decline in body weight is an important and independent marker of risk of mortality in older adults.

10aAged10aAnalysis of Variance10aBody Weight10aChi-Square Distribution10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aMortality10aProportional Hazards Models10aRisk Factors10aUnited States10aWeight Gain10aWeight Loss1 aNewman, A, B1 aYanez, D1 aHarris, T1 aDuxbury, A1 aEnright, P, L1 aFried, L P1 aCardiovascular Study Research Group uhttps://chs-nhlbi.org/node/68302657nas 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 a

OBJECTIVE: 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/81502390nas 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 a

BACKGROUND: 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/81102437nas 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 a

OBJECTIVE: 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/89202634nas a2200301 4500008004100000022001400041245008300055210006900138260001600207300001100223490000700234520175200241653002401993653002402017653002802041653002302069653001102092653002502103653003102128653002902159100001702188700002002205700001702225700001702242700001902259700001902278856003502297 2006 eng d a1526-632X00aEducation and the cognitive decline associated with MRI-defined brain infarct.0 aEducation and the cognitive decline associated with MRIdefined b c2006 Aug 08 a435-400 v673 a

OBJECTIVE: To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct.

METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI.

RESULTS: In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct.

CONCLUSIONS: Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.

10aCerebral Infarction10aCognition Disorders10aCross-Sectional Studies10aEducational Status10aHumans10aLongitudinal Studies10aMagnetic Resonance Imaging10aNeuropsychological Tests1 aElkins, J, S1 aLongstreth, W T1 aManolio, T A1 aNewman, A, B1 aBhadelia, R, A1 aJohnston, S, C uhttps://chs-nhlbi.org/node/91105258nas 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 a

CONTEXT: 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/103903169nas a2200517 4500008004100000022001400041245012300055210006900178260001300247300000800260490000700268520180100275653002202076653000902098653002502107653002302132653003202155653001102187653001702198653001302215653001102228653000902239653001502248653003302263653003602296100001802332700001602350700001902366700001102385700001602396700001602412700001002428700002202438700001802460700001502478700001702493700001402510700001102524700001402535700001202549700001002561700001302571700001702584700001402601856003602615 2010 eng d a1468-624400aAdmixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.0 aAdmixture mapping of anklearm index identification of a candidat c2010 Jan a1-70 v473 a

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD.

METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus.

RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76).

CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

10aAfrican Americans10aAged10aAnkle Brachial Index10aChromosome Mapping10aChromosomes, Human, Pair 1110aFemale10aGenetic Loci10aGenotype10aHumans10aMale10aOdds Ratio10aPeripheral Vascular Diseases10aPolymorphism, Single Nucleotide1 aScherer, M, L1 aNalls, M, A1 aPawlikowska, L1 aZiv, E1 aMitchell, G1 aHuntsman, S1 aHu, D1 aSutton-Tyrrell, K1 aLakatta, E, G1 aHsueh, W-C1 aNewman, A, B1 aTandon, A1 aKim, L1 aKwok, P-Y1 aSung, A1 aLi, R1 aPsaty, B1 aReiner, A, P1 aHarris, T uhttps://chs-nhlbi.org/node/110902893nas a2200421 4500008004100000022001400041245016400055210006900219260001300288300001100301490000700312520168500319653002202004653001502026653001402041653001902055653003502074653001102109653000902120653002502129653001802154653001902172653001102191653002502202653000902227653002902236653001602265653001802281100001802299700001802317700001702335700001902352700001702371700001502388700001502403700001702418856003602435 2010 eng d a1758-535X00aConcurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.0 aConcurrent change in dehydroepiandrosterone sulfate and function c2010 Sep a976-810 v653 a

INTRODUCTION: The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging.

METHODS: DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline.

RESULTS: After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline.

CONCLUSIONS: In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

10aAged, 80 and over10aBiomarkers10aCognition10aCohort Studies10aDehydroepiandrosterone Sulfate10aFemale10aGait10aGeriatric Assessment10aHand Strength10aHealth Surveys10aHumans10aLongitudinal Studies10aMale10aNeuropsychological Tests10aSex Factors10aUnited States1 aSanders, J, L1 aCappola, A, R1 aArnold, A, M1 aBoudreau, R, M1 aChaves, P, H1 aRobbins, J1 aCushman, M1 aNewman, A, B uhttps://chs-nhlbi.org/node/120002861nas 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 a

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults.

METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest).

CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

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/109102959nas 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 a

OBJECTIVES: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation.

METHODS: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline.

RESULTS: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold.

CONCLUSION: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.

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/123902600nas a2200433 4500008004100000022001400041245010200055210006900157260000900226300001000235490000700245520145000252653000901702653002201711653002601733653001901759653001101778653001801789653001101807653001401818653000901832653001501841653002201856653001501878653002401893653001701917653001201934653003101946653001801977100001401995700001202009700001602021700001802037700002102055700001702076700002002093700001702113856003602130 2010 eng d a1423-020800aPost hoc Parkinson's disease: identifying an uncommon disease in the Cardiovascular Health Study.0 aPost hoc Parkinsons disease identifying an uncommon disease in t c2010 a241-90 v353 a

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson's disease (PD), they typically have limited information for clinical diagnosis.

METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.

RESULTS: We identified 60 cases with prevalent PD (1.0%; 95% confidence interval, CI = 0.8-1.3%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95% CI = 0.26-0.95) and for those who smoked ≥50 pack-years (OR = 0.53; 95% CI = 0.29-0.96). Estimates for smoking were similar when ≥2 data sources were required. Estimates for self-report alone were attenuated towards null.

CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

10aAged10aAged, 80 and over10aCardiovascular System10aCohort Studies10aFemale10aHealth Status10aHumans10aIncidence10aMale10aOdds Ratio10aParkinson Disease10aPrevalence10aProspective Studies10aRisk Factors10aSmoking10aSurveys and Questionnaires10aUnited States1 aTon, T, G1 aJain, S1 aBoudreau, R1 aThacker, E, L1 aStrotmeyer, E, S1 aNewman, A, B1 aLongstreth, W T1 aCheckoway, H uhttps://chs-nhlbi.org/node/123302768nas a2200421 4500008004100000022001400041245010100055210006900156260000900225300001000234490000700244520167200251653000901923653001501932653001901947653001101966653001101977653000901988653001301997653001902010653002202029653001702051653002402068653001702092653002102109653001602130653001402146100001202160700001402172700001902186700001202205700001802217700001702235700002002252700002102272700001702293856003602310 2011 eng d a1423-020800aThe risk of Parkinson disease associated with urate in a community-based cohort of older adults.0 arisk of Parkinson disease associated with urate in a communityba c2011 a223-90 v363 a

BACKGROUND/AIMS: Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults.

METHODS: The association of baseline urate (µmol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 µmol/l), middle (300-500 µmol/l), and high (>500 µmol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD.

RESULTS: Women had significantly lower urate concentrations than did men [316.8 µmol/l (SD 88.0) vs. 367.4 µmol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 µmol/l (OR 1.69, 95% CI 1.03-2.78) but not for urate >500 µmol/l (OR 1.55, 95% CI 0.72-3.32) in men. A negative linear term was significant for urate <500 µmol/l, and across the entire range a convex quadratic term was significant.

CONCLUSIONS: Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk.

10aAged10aCalifornia10aCohort Studies10aFemale10aHumans10aMale10aMaryland10aNorth Carolina10aParkinson Disease10aPennsylvania10aProspective Studies10aRisk Factors10aSex Distribution10aSex Factors10aUric Acid1 aJain, S1 aTon, T, G1 aBoudreau, R, M1 aYang, M1 aThacker, E, L1 aStudenski, S1 aLongstreth, W T1 aStrotmeyer, E, S1 aNewman, A, B uhttps://chs-nhlbi.org/node/129703088nas a2200697 4500008004100000022001400041245006500055210006300120260001300183300001200196490000700208520134600215653002201561653001001583653001901593653001601612653001301628653002401641653001101665653001401676653003001690653002601720653002701746653001801773100001301791700001901804700001701823700001401840700001701854700001801871700001401889700001701903700001401920700001701934700001401951700001601965700001601981700001501997700001502012700001402027700001602041700001702057700001602074700001602090700002202106700002102128700001802149700001302167700001602180700002002196700001602216700001402232700001102246700001902257700001702276700001602293700001502309700001502324700001502339856003602354 2013 eng d a1574-464700aAssociation of heat shock proteins with all-cause mortality.0 aAssociation of heat shock proteins with allcause mortality c2013 Aug a1367-760 v353 a

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

10aAged, 80 and over10aAging10aCause of Death10aForecasting10aGenotype10aHeat-Shock Proteins10aHumans10aLongevity10aPromoter Regions, Genetic10aRetrospective Studies10aTranscription, Genetic10aUnited States1 aBroer, L1 aDemerath, E, W1 aGarcia, M, E1 aHomuth, G1 aKaplan, R, C1 aLunetta, K, L1 aTanaka, T1 aTranah, G, J1 aWalter, S1 aArnold, A, M1 aAtzmon, G1 aHarris, T B1 aHoffmann, W1 aKarasik, D1 aKiel, D, P1 aKocher, T1 aLauner, L J1 aLohman, K, K1 aRotter, J I1 aTiemeier, H1 aUitterlinden, A G1 aWallaschofski, H1 aBandinelli, S1 aDörr, M1 aFerrucci, L1 aFranceschini, N1 aGudnason, V1 aHofman, A1 aLiu, Y1 aMurabito, J, M1 aNewman, A, B1 aOostra, B A1 aPsaty, B M1 aSmith, A V1 aDuijn, C M uhttps://chs-nhlbi.org/node/606104753nas a2201057 4500008004100000022001400041245017100055210006900226260001300295300001000308490000700318520203200325653001002357653002202367653000902389653002502398653001602423653002402439653001102463653002202474653003402496653001302530653001502543653001102558653000902569653002702578653001602605653003602621653000902657653001802666100001102684700001602695700001602711700001602727700001602743700001702759700001702776700001802793700001002811700002102821700001602842700001402858700002102872700001402893700001602907700001802923700001902941700001302960700001502973700001202988700001903000700001803019700001603037700001603053700001403069700001803083700001303101700001603114700001503130700001903145700001103164700001703175700001803192700001303210700001703223700001703240700001703257700001403274700001603288700001703304700001503321700001803336700001703354700001903371700001603390700002003406700001803426700001703444700002003461700001703481700001803498700001903516700002103535700001703556700001603573700001303589700002003602700001903622700001803641856003603659 2013 eng d a1556-387100aCommon genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.0 aCommon genetic variation near the connexin43 gene is associated  c2013 Mar a401-80 v103 a

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.

OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans.

METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)).

RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.

CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

10aAdult10aAfrican Americans10aAged10aArrhythmias, Cardiac10aConnexin 4310aElectrocardiography10aFemale10aGenetic Variation10aGenome-Wide Association Study10aGenotype10aHeart Rate10aHumans10aMale10aMeta-Analysis as Topic10aMiddle Aged10aPolymorphism, Single Nucleotide10aRest10aUnited States1 aDeo, R1 aNalls, M, A1 aAvery, C, L1 aSmith, J, G1 aEvans, D, S1 aKeller, M, F1 aButler, A, M1 aBuxbaum, S, G1 aLi, G1 aQuibrera, Miguel1 aSmith, E, N1 aTanaka, T1 aAkylbekova, E, L1 aAlonso, A1 aArking, D E1 aBenjamin, E J1 aBerenson, G, S1 aBis, J C1 aChen, L, Y1 aChen, W1 aCummings, S, R1 aEllinor, P, T1 aEvans, M, K1 aFerrucci, L1 aFox, E, R1 aHeckbert, S R1 aHeiss, G1 aHsueh, W, C1 aKerr, K, F1 aLimacher, M, C1 aLiu, Y1 aLubitz, S, A1 aMagnani, J, W1 aMehra, R1 aMarcus, G, M1 aMurray, S, S1 aNewman, A, B1 aNjajou, O1 aNorth, K, E1 aPaltoo, D, N1 aPsaty, B M1 aRedline, S, S1 aReiner, A, P1 aRobinson, J, G1 aRotter, J I1 aSamdarshi, T, E1 aSchnabel, R B1 aSchork, N, J1 aSingleton, A, B1 aSiscovick, D1 aSoliman, E, Z1 aSotoodehnia, N1 aSrinivasan, S, R1 aTaylor, H, A1 aTrevisan, M1 aZhang, Z1 aZonderman, A, B1 aNewton-Cheh, C1 aWhitsel, E, A uhttps://chs-nhlbi.org/node/606303989nas 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 a

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.

DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.

METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.

RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95% CI 0.599 to 0.737) in men and 0.578 (95% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95% CI 0.612 to 0.749) and large increase in women to 0.690 (95% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3% (95% CI 0.0 to 7.6%, p = 0.050) and 9.6% (95% CI 6.1 to 16.4%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19% resulted in higher NRI of 15.9% (95% CI 6.1 to 20.6%, p < 0.001) in men and 23.3% (95% CI 13.8 to 62.5%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0% (95% CI 2.3 to 4.2%, p = 0.567) in men and 1.1% (95% CI 1.9 to 4.0%, p = 0.483) in women.

CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

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/680302836nas a2200277 4500008004100000022001400041245007000055210006900125260001600194520207400210100001102284700001602295700001602311700002002327700001802347700001702365700001802382700001502400700002002415700001602435700001802451700001502469700002002484700001802504856003602522 2016 eng d a1464-549100aBrain natriuretic peptide and insulin resistance in older adults.0 aBrain natriuretic peptide and insulin resistance in older adults c2016 Apr 213 a

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established.

METHODS: N-Terminal (NT)-proBNP was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance.

RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP).

CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. This article is protected by copyright. All rights reserved.

1 aKim, F1 aBiggs, M, L1 aKizer, J, R1 aBrutsaert, E, F1 ade Fillipi, C1 aNewman, A, B1 aKronmal, R, A1 aTracy, R P1 aGottdiener, J S1 aDjoussé, L1 ade Boer, I, H1 aPsaty, B M1 aSiscovick, D, S1 aMukamal, K, J uhttps://chs-nhlbi.org/node/7124