The Cardiovascular Health Study: design and rationale. - Fried, L P; Borhani, N O; Enright, P; Furberg, C D; Gardin, J M; Kronmal, R A; Kuller, L H; Manolio, T A; Mittelmark, M B; Newman, A (Ann Epidemiol, 1991)
The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.
Keywords: Aged; Cerebrovascular Disorders; Coronary Disease; Epidemiologic Methods; Female; Health Status; Humans; Longitudinal Studies; Male; Physical Examination; Research Design; Risk Factors; United States

Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group. - O'Leary, D H; Polak, J F; Wolfson, S K; Bond, M G; Bommer, W; Sheth, S; Psaty, B M; Sharrett, A R; Manolio, T A (Stroke, 1991)
Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.
Keywords: Age Factors; Aged; Arteriosclerosis; Carotid Arteries; Carotid Artery Diseases; Carotid Artery, Internal; Female; Humans; Image Interpretation, Computer-Assisted; Image Processing, Computer-Assisted; Male; Prospective Studies; Ultrasonography

Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. The Cardiovascular Health Study Collaborative Research Group. - Psaty, B M; Lee, M; Savage, P J; Rutan, G H; German, P S; Lyles, M (J Clin Epidemiol, 1992)
The Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary heart disease and stroke, recruited 5201 community-dwelling adults aged 65 years or older. To assess the prevalence of medication use at baseline, we used the method of medication inventory and transcribed information about drug names and doses from prescription bottles. Using a specially-written computer program, persons without a knowledge of drug nomenclature coded 10,511 (89%) of the 11,846 medicines entered. We compared the results of the medication inventory and answers to questions on specific medications for reliability and validity. The use of beta-blockers and beta-agonists assessed by the method of medication inventory, but not by the method of directed recall, was associated with a significant effect on mean heart rate. Among 5197 participants with medication data, 76.1% were taking at least one medicine, and the mean number of drugs per person was 2.28. Among those with a reported history of high blood pressure, participants with cardiovascular disease (CVD) were more likely to be treated, and they were more likely to be taking beta-blockers and calcium-channel blockers than those without CVD. Daily aspirin use was also more common among those with CVD (30.5% of women and 43.2% of men) than among those without CVD (14.0% of women and 14.0% of men). The prevalence of post-menopausal estrogen use differed significantly among the four clinical centers (range = 5.5%-22.5% of women). We conclude that this method of assessing medications was easy to use and provided estimates of exposure to drugs that may affect risk of cardiovascular disease.
Keywords: Aged; Aged, 80 and over; Cerebrovascular Disorders; Coronary Disease; Data Collection; Drug Utilization; Female; Humans; Male; Prospective Studies; Risk Factors; United States

Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. - O'Leary, D H; Polak, J F; Kronmal, R A; Kittner, S J; Bond, M G; Wolfson, S K; Bommer, W; Price, T R; Gardin, J M; Savage, P J (Stroke, 1992)
BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.
Keywords: Aged; Arteriosclerosis; Cardiomegaly; Carotid Artery Diseases; Cerebrovascular Disorders; Coronary Disease; Female; Humans; Male; Medical Records; Prevalence; Regression Analysis; Risk Factors; Ultrasonography

The distribution of coagulation factors VII and VIII and fibrinogen in adults over 65 years. Results from the Cardiovascular Health Study. - Tracy, R P; Bovill, E G; Fried, L P; Heiss, G; Lee, M H; Polak, J F; Psaty, B M; Savage, P J (Ann Epidemiol, 1992)
The Cardiovascular Health Study (CHS) was designed to examine cardiovascular disease and its risk factors in older adults. We report here the distributions of the coagulation factors fibrinogen, factor VII, and factor VIII in a population-based cohort of men and women 65 years or older. In other studies of middle-aged individuals, these factors were shown to be associated with cardiovascular risk. In the CHS cohort, all three factors were elevated, compared to levels reported in middle-aged individuals, and fibrinogen and factor VIII values were higher in each successive age group; factor VII values, in contrast, declined slightly with age in the CHS cohort. Compared to white subjects, blacks had higher values for fibrinogen and factor VIII and lower values for factor VII. While women had markedly higher values for factor VII and factor VIII than men at all ages in the CHS, mean fibrinogen values were not different between men and women.
Keywords: African Continental Ancestry Group; Age Factors; Aged; Cardiovascular Diseases; Cohort Studies; Factor VII; Factor VIII; Female; Fibrinogen; Humans; Male; Middle Aged; Risk Factors

Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study. - Gardin, J M; Wong, N D; Bommer, W; Klopfenstein, H S; Smith, V E; Tabatznik, B; Siscovick, D; Lobodzinski, S; Anton-Culver, H; Manolio, T A (J Am Soc Echocardiogr, 1992)
The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults.
Keywords: Allied Health Personnel; Cerebrovascular Disorders; Coronary Disease; Echocardiography; Echocardiography, Doppler; Humans; Prospective Studies; Quality Control; Risk Factors; United States

Eligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study. - Manolio, T A; Furberg, C D; Wahl, P W; Tracy, R P; Borhani, N O; Gardin, J M; Fried, L P; O'Leary, D H; Kuller, L H (Ann Intern Med, 1992)
OBJECTIVES: To assess the proportion of community-dwelling adults aged 65 years or older who are eligible for referral for lipoprotein analysis and intervention according to the National Cholesterol Education Program (NCEP) guidelines. DESIGN: Cross-sectional study based on examinations and questionnaires collected in 1989 and 1990. SETTING: Four communities in the U.S. in the Cardiovascular Health Study (CHS), a study of risk factors for heart disease and stroke in older adults. PARTICIPANTS: A sample of 4810 men and women ages 65 to 100 randomly selected and recruited from Health Care Financing Administration Medicare eligibility lists for the four communities; not institutionalized, not wheelchair-bound, not currently receiving therapy for cancer, not currently taking lipid-lowering medications, and not having eaten in the preceding 9 hours. MEASUREMENTS: Total cholesterol and lipoprotein analysis measured in all participants. RESULTS: Total cholesterol levels were less than 5.17 mmol/L (200 mg/dL) in 37% of participants, 5.17 to 6.19 mmol/L (200 to 239 mg/dL) in 39%, and 6.20 mmol/L (240 mg/dL) or greater in 24%. Compared with their counterparts, older participants, especially those over 80 years of age, were more likely to have levels below 5.17 mmol/L, as were men, nonwhites, and those with coronary heart disease or two or more coronary heart disease risk factors (P less than 0.008 for all values). Based on this screening measurement, 2174 participants were eligible for lipoprotein analysis, 80% were eligible for dietary or drug therapy using NCEP guidelines. Overall, 46% of CHS participants were eligible for lipoprotein analysis and 36% for intervention by NCEP guidelines, based on a single cholesterol measurement. CONCLUSION: A substantial proportion of older adults in this community sample were eligible for lipoprotein analysis and intervention. Prospective studies of elderly persons are needed to determine the risk for incident coronary heart disease according to NCEP classifications and the benefits of lipid-lowering treatments in persons in this age group so that intervention strategies may best be targeted to an appropriately high-risk group.
Keywords: Age Factors; Aged; Aged, 80 and over; Cerebrovascular Disorders; Cholesterol, LDL; Coronary Disease; Eligibility Determination; Female; Humans; Hypercholesterolemia; Longitudinal Studies; Male; Primary Prevention; Referral and Consultation; Risk Factors; United States

Isolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study. - Psaty, B M; Furberg, C D; Kuller, L H; Borhani, N O; Rautaharju, P M; O'Leary, D H; Bild, D E; Robbins, J; Fried, L P; Reid, C (JAMA, 1992)
OBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above. DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg. MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis. RESULTS: Among the 2189 men and women in this analysis, 195 (9%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001). CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.
Keywords: Aged; Aged, 80 and over; Cardiomegaly; Cardiovascular Diseases; Carotid Artery Diseases; Cerebrovascular Disorders; Coronary Disease; Cross-Sectional Studies; Echocardiography; Electrocardiography; Female; Humans; Hypertension; Male; Myocardial Infarction; Prospective Studies; Risk Factors; Systole

Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group. - Ettinger, W H; Wahl, P W; Kuller, L H; Bush, T L; Tracy, R P; Manolio, T A; Borhani, N O; Wong, N D; O'Leary, D H (Circulation, 1992)
BACKGROUND: Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old. METHODS AND RESULTS: Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease. CONCLUSIONS: Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use.
Keywords: Aged; Aging; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Female; Health Status; Humans; Lipids; Lipoproteins; Male; Multivariate Analysis; Triglycerides

Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group. - Furberg, C D; Manolio, T A; Psaty, B M; Bild, D E; Borhani, N O; Newman, A; Tabatznik, B; Rautaharju, P M (Am J Cardiol, 1992)
Electrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29% in the entire cohort, 19% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Chi-Square Distribution; Electrocardiography; Female; Heart Diseases; Humans; Logistic Models; Male; Prevalence; Risk Factors; Sex Factors; United States

Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. - Rutan, G H; Hermanson, B; Bild, D E; Kittner, S J; LaBaw, F; Tell, G S (Hypertension, 1992)
The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.
Keywords: Aged; Aging; Dementia; Demography; Female; Health Status; Humans; Hypotension, Orthostatic; Male; Multivariate Analysis; Nervous System Diseases; Prevalence; Risk Factors

Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study. - Bild, D E; Fitzpatrick, A; Fried, L P; Wong, N D; Haan, M N; Lyles, M; Bovill, E; Polak, J F; Schulz, R (J Am Geriatr Soc, 1993)
OBJECTIVE: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older. DESIGN: Observational population-based study. SETTING: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. PARTICIPANTS: 5,201 men and women aged 65 years and older. MEASUREMENTS: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined. MAIN RESULTS: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups. CONCLUSIONS: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.
Keywords: Activities of Daily Living; Age Distribution; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Humans; Male; Prevalence; Sex Distribution; Socioeconomic Factors

Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. - Newman, A B; Siscovick, D S; Manolio, T A; Polak, J; Fried, L P; Borhani, N O; Wolfson, S K (Circulation, 1993)
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.
Keywords: Aged; Ankle; Arm; Arteriosclerosis; Blood Pressure Determination; Cardiovascular Diseases; Female; Humans; Male; Multivariate Analysis; Peripheral Vascular Diseases; Population Surveillance; Predictive Value of Tests; Risk Factors

Assessment of cerebrovascular disease in the Cardiovascular Health Study. - Price, T R; Psaty, B; O'Leary, D; Burke, G; Gardin, J (Ann Epidemiol, 1993)
The Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.
Keywords: Aged; Aged, 80 and over; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Female; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Prevalence

Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group. - Manolio, T A; Furberg, C D; Shemanski, L; Psaty, B M; O'Leary, D H; Tracy, R P; Bush, T L (Circulation, 1993)
BACKGROUND: Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women. METHODS AND RESULTS: Present and past estrogen use was ascertained in 2955 women > or = 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12% of these women and past use by an additional 26.5%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P < .0001). Estrogen users also had lower levels of subclinical disease as measured by carotid intimal-medial thickness, carotid stenosis grade, ECG left ventricular mass, and Doppler mitral peak flow velocities (each P < .02). Relations were similar in younger and older women (65 to 74 versus > or = 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids. CONCLUSIONS: Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life.
Keywords: Aged; Aging; Cardiovascular Diseases; Carotid Arteries; Carotid Stenosis; Electrocardiography; Estrogen Replacement Therapy; Female; Heart; Heart Ventricles; Humans; Patient Compliance; Risk Factors; Smoking; Ultrasonography

Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study. - Manolio, T A; Ettinger, W H; Tracy, R P; Kuller, L H; Borhani, N O; Lynch, J C; Fried, L P (Circulation, 1993)
BACKGROUND: Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths. METHODS AND RESULTS: This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6% of men and 3.7% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes. CONCLUSIONS: Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies.
Keywords: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cholesterol; Female; Health Status; Humans; Longitudinal Studies; Male; Prevalence; Probability; Regression Analysis; Risk Factors

Prevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study. - Mittelmark, M B; Psaty, B M; Rautaharju, P M; Fried, L P; Borhani, N O; Tracy, R P; Gardin, J M; O'Leary, D H (Am J Epidemiol, 1993)
The Cardiovascular Health Study is a population-based longitudinal study of 5,201 adults aged 65 years and older. Prevalences of myocardial infarction, angina pectoris, congestive heart failure, peripheral artery disease, stroke, and transient ischemic attack were ascertained between June 1989 and May 1990 in participants recruited from Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pennsylvania. A medical history was taken to obtain self-reports of prevalent disease. For all participants, use of nitrates was ascertained to document angina, electrocardiograms were used to document prevalent myocardial infarction, and ankle-arm blood pressure studies were used to document peripheral artery disease. Self-reports of disease that were not confirmed by examination findings were further investigated by examination of medical records. Reported disease that was confirmed by examination findings or by medical records was classified as "definite." Disease that was documented by examination, but not reported by the participant, was classified as "unreported." The prevalence rates of definite myocardial infarction and angina were 11% and 15%, respectively, among men aged 65-69 years, 18% and 17% among men aged 80-84 years, 4% and 8% among women aged 65-69 years, and 3% and 13% among women aged 80-84 years. Twenty-three percent of men and 38% of women with electrocardiographic evidence of myocardial infarction did not report it. These results suggest that prevalent disease estimates based only on self-report may underestimate the prevalence of cardiovascular diseases in older Americans.
Keywords: Age Factors; Aged; Aged, 80 and over; Bias; California; Cardiovascular Diseases; Electrocardiography; Female; Health Surveys; Humans; Longitudinal Studies; Male; Maryland; Mass Screening; North Carolina; Pennsylvania; Population Surveillance; Prevalence; Reproducibility of Results

Properties of the random zero sphygmomanometer. - Kronmal, R A; Rutan, G H; Manolio, T A; Borhani, N O (Hypertension, 1993)
The random zero sphygmomanometer is widely used in studies involving blood pressure measurement because it is believed to eliminate digit preference and reduce measurement error. We performed blood pressure measurements sequentially using random zero and standard sphygmomanometers in random order in 1,356 participants in the Cardiovascular Health Study. Despite adherence to the manufacturer's instructions, we observed a substantially nonuniform distribution of zero levels generated by the random zero sphygmomanometer and a disturbing correlation between the zero level and blood pressures taken with the standard sphygmomanometer. With the random zero device, the pooled estimated slopes for the regression of standard systolic and diastolic pressures on the zero level were -0.71 and -0.17, respectively (both p < 0.0001). The only plausible explanation for this relation between the random zero device and the standard device is that by some unknown mechanism the subject's blood pressure is influencing the zero level. Systolic and diastolic blood pressures measured with the random zero device were, respectively, 1.65 and 1.84 mm Hg lower (both p < 0.0001) than standard blood pressures. Digit preference was detectable in the uncorrected blood pressure and zero level measured with the random zero device but was eliminated after calculation of the corrected blood pressure. For most epidemiological studies, the random zero sphygmomanometer offers no significant advantage over the standard sphygmomanometer. It may still be useful in those epidemiological studies and clinical trials where blinding is important.
Keywords: Aged; Blood Pressure; Blood Pressure Determination; Cohort Studies; Diastole; Humans; Regression Analysis; Systole

Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. - Tell, G S; Fried, L P; Hermanson, B; Manolio, T A; Newman, A B; Borhani, N O (Ann Epidemiol, 1993)
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)
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Epidemiologic Methods; Female; Humans; Male

Serum fructosamine as a screening test for diabetes in the elderly: a pilot study. - Cefalu, W T; Ettinger, W H; Bell-Farrow, A D; Rushing, J T (J Am Geriatr Soc, 1993)
OBJECTIVE: To determine the value of serum glycated protein, measured as serum fructosamine, as a screening test for diabetes in the elderly. DESIGN: Cross-sectional pilot study. SETTING: Ambulatory research clinic in university setting. PATIENTS: One hundred fifty-seven consecutive community-dwelling participants in the Cardiovascular Health Study, average age 71.8 + 5 (mean +/- SD, range 65-88 years). MEASUREMENTS: Serum fructosamine levels (first and second generation assay) were obtained. All subjects who did not have a diagnosis of diabetes were given a 75-g glucose tolerance test (GTT). RESULTS: Twenty-six subjects (17%) (10 previously diagnosed, 16 undiagnosed and asymptomatic) had diabetes mellitus, and 38 subjects (24%) had impaired glucose tolerance by history or by the GTT (WHO criteria). Only the 16 asymptomatic diabetics were included in the analysis for the pilot study. There was a significant difference in the fasting fructosamine level between non-diabetics and asymptomatic diabetics for the first generation (2.06 +/- .21 vs 2.53 +/- .49 mMol/L, P < 0.0015) and second generation assay (221 +/- 27 vs 269 +/- 48 mMol/L, P < 0.0012). Receiver operator curves were constructed to evaluate the test characteristics of serum fructosamine. Using a point of > or = 2.3 mMol/L for the first-generation assay, the sensitivity to detect asymptomatic diabetes was 75%, specificity 83%, and positive predictive value 35%. To detect both diabetes and impaired glucose tolerance using a cutpoint of > or = 2.3 mMol/L, the sensitivity was 24%, specificity 95%, and positive predictive value 68%. Employing a cut point of 250 muMol/L for the second generation assay, the sensitivity to detect diabetes was 81%, specificity 87%, and positive predictive value 43%. However, to detect diabetes and glucose intolerance using the second generation assay, the sensitivity was 39% and specificity was 86%. CONCLUSION: This study demonstrated that a single measurement of either first or second generation fructosamine showed promise as a screening test for diabetes, but not impaired glucose tolerance, in older people.
Keywords: Aged; Diabetes Mellitus; Female; Fructosamine; Glucose Tolerance Test; Hexosamines; Humans; Insulin; Male; Pilot Projects; Predictive Value of Tests; Sensitivity and Specificity

Smoking and lung function in elderly men and women. The Cardiovascular Health Study. - Higgins, M W; Enright, P L; Kronmal, R A; Schenker, M B; Anton-Culver, H; Lyles, M (JAMA, 1993)
OBJECTIVE: To investigate relationships between cigarette smoking and pulmonary function in elderly men and women. DESIGN: Cross-sectional analysis of baseline data from a prospective, population-based study of risk factors, preclinical, and overt cardiovascular and pulmonary disease. SETTING: Defined communities in Forsyth County, North Carolina; Pittsburgh, Pa; Sacramento County, California; and Washington County, Maryland. POPULATION: A total of 5201 noninstitutionalized men and women 65 years of age and older. MAIN OUTCOME MEASURES: Pulmonary function; means of forced expiratory volume in 1 second (FEV1) and forced vital capacity and prevalence of low FEV1 levels. RESULTS: Prevalence of cigarette smoking was 10% to 20% and higher in women than men and in blacks than whites. Forced vital capacity and FEV1 levels were related positively to height and white race and negatively to age and waist girth. Age- and height-adjusted FEV1 means were 23% and 18% lower in male and female current smokers, respectively, than in never smokers but not reduced in never smokers currently living with a smoker. Smokers who quit before age 40 years had FEV1 levels similar to never smokers, but FEV1 levels were lower by 7% and 14% in smokers who quit at ages 40 to 60 years and older than 60 years, respectively. Lung function was related inversely to pack-years of cigarette use. Prevalence rates of impaired lung function were highest in current smokers and lowest in never smokers. Regression coefficients for the smoking variables were smaller in persons without cardiovascular or respiratory conditions than in the total cohort. CONCLUSIONS: Cigarette smoking is associated with reduced pulmonary function in elderly men and women. However, smokers who quit, even after age 60 years, have better pulmonary function than continuing smokers.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Anthropometry; Cardiovascular Diseases; Cross-Sectional Studies; European Continental Ancestry Group; Female; Forced Expiratory Volume; Humans; Lung Diseases; Male; Prevalence; Prospective Studies; Reference Values; Respiratory Function Tests; Risk Factors; Smoking; United States; Vital Capacity

Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack. - Polak, J F; O'Leary, D H; Kronmal, R A; Wolfson, S K; Bond, M G; Tracy, R P; Gardin, J M; Kittner, S J; Price, T R; Savage, P J (Radiology, 1993)
Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.
Keywords: Aged; Arteriosclerosis; Carotid Artery Diseases; Carotid Artery, Internal; Carotid Stenosis; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Ultrasonography

Spirometry reference values for women and men 65 to 85 years of age. Cardiovascular health study. - Enright, P L; Kronmal, R A; Higgins, M; Schenker, M; Haponik, E F (Am Rev Respir Dis, 1993)
Pulmonary function was assessed by spirometry in 5,201 ambulatory elderly participants of the Cardiovascular Health Study, sampled from four communities. A stringent quality assurance program exceeded American Thoracic Society (ATS) recommendations for spirometry. Less than 6% of the participants were unable to perform three acceptable spirometry maneuvers. A "healthy" subgroup of 777 women and men 65 to 85 yr of age was identified by excluding smokers and those with lung disease and other factors determined to independently, significantly, and negatively influence the FEV1. Results from black participants were examined separately. Reference equations and normal ranges for FEV1, FVC, and the FEV1/FVC ratio were determined from the healthy group. The results demonstrate differences in predicted values as great as 20% (0.5 to 1 L) for elderly patients when compared with the spirometry reference equations that are most commonly used in the United States.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Female; Forced Expiratory Volume; Humans; Male; Reference Values; Smoking; Spirometry; Vital Capacity

Temporal patterns of antihypertensive medication use among elderly patients. The Cardiovascular Health Study. - Psaty, B M; Savage, P J; Tell, G S; Polak, J F; Hirsch, C H; Gardin, J M; McDonald, R H (JAMA, 1993)
OBJECTIVES: To estimate the incidence of newly treated hypertension and to describe the patterns of antihypertensive medication use among those aged 65 years and older. DESIGN: Medicare eligibility lists from four US communities (Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pa) were used to obtain a representative sample of 5201 community-dwelling elderly for the Cardiovascular Health Study, a prospective cohort study of risk factors for coronary heart disease and stroke. Participants were examined at baseline and again 1 year later. The two examinations included standardized questionnaires, blood pressure measurements, and the assessment of medication use by medication inventory. In this cohort analysis, we excluded 231 subjects (4.4%) who did not return for follow-up, 69 (1.3%) who had missing data for medications, and another 495 (9.5%) who were taking "antihypertensive" medications for an indication other than high blood pressure. INTERVENTIONS: None. RESULTS: Among the 4406 participants, 1613 used antihypertensive medications at both visits. Between the two visits, 144 started and 115 stopped antihypertensive therapy. Among nonusers at baseline, the annual incidence of newly treated hypertension was 5.2% in women and 5.6% in men. Due to the number of participants who stopped therapy, the overall prevalence of antihypertensive treatment increased only slightly, from 40.7% to 41.1% in women and from 37.1% to 38.2% in men, during 1 year of follow-up. After adjustment for age, systolic blood pressure, number of antihypertensive drugs, diabetes, and cardiovascular disease, the newly treated hypertensives were about half as likely as the previously treated hypertensives to receive diuretics (odds ratio [OR], 0.59; P = .008) or beta-blockers (OR, 0.52; P = .01); and they were about twice as likely to receive calcium channel blockers (OR, 1.88; P < .004) or angiotensin converting enzyme inhibitors (OR, 2.40; P < .001). A similar pattern of within-person changes over time was apparent among the continuous users. CONCLUSIONS: Between June 1990 and June 1991, physicians were increasingly prescribing angiotensin converting enzyme inhibitors and calcium channel blockers in place of diuretics and beta-blockers for the treatment of hypertension in elderly patients, especially for those just starting therapy.
Keywords: Adrenergic beta-Antagonists; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cohort Studies; Diuretics; Drug Utilization; Female; Follow-Up Studies; Humans; Hypertension; Linear Models; Logistic Models; Male; Medicare; Practice Patterns, Physicians'; Recurrence; United States; Vasodilator Agents

Cardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study. - Manolio, T A; Furberg, C D; Rautaharju, P M; Siscovick, D; Newman, A B; Borhani, N O; Gardin, J M; Tabatznik, B (J Am Coll Cardiol, 1994)
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.
Keywords: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Diseases; Circadian Rhythm; Electrocardiography, Ambulatory; Female; Humans; Logistic Models; Longitudinal Studies; Male; Prevalence; Risk Factors; Sex Factors

Correlates of blood pressure in community-dwelling older adults. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group. - Tell, G S; Rutan, G H; Kronmal, R A; Bild, D E; Polak, J F; Wong, N D; Borhani, N O (Hypertension, 1994)
Although elevated blood pressure is an important predictor of cardiovascular disease and stroke in the elderly, little information exists on the distribution and risk factor correlates of blood pressure in this group. As part of the Cardiovascular Health Study, a population-based cohort study of 5201 men and women aged 65 to 101 years, we investigated correlates of systolic and diastolic blood pressure. Multiple regression analyses were conducted for all participants and a subgroup of 2482 without coronary heart disease and not on antihypertensive therapy (the "healthier" subgroup). In the total group, independent predictors of diastolic blood pressure included heart rate, aortic root dimension, creatinine, hematocrit, alcohol use, and black race (positive associations) and internal carotid artery wall thickness, mitral early/late peak flow velocity, white blood cell count, cigarette smoking, and age (negative associations). Positive predictors of systolic blood pressure included mitral late peak flow velocity, left ventricular mass, common carotid artery wall thickness, serum albumin, factor VII, diabetes, alcohol use, and age; negative predictors were coronary heart disease, uric acid, height, and smoking. In the healthier subgroup, positive predictors of diastolic blood pressure included heart rate, hematocrit, serum albumin, creatinine, and body weight, whereas mitral early/late peak flow velocity, serum potassium, smoking, and age inversely related to diastolic pressure. For the same group, common carotid artery wall thickness, left ventricular mass, serum albumin, factor VII, high-density lipoprotein cholesterol, and age were directly related to systolic blood pressure, whereas serum potassium was inversely related. Both systolic and diastolic pressures varied considerably by geographic site.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords: Aged; Aged, 80 and over; Aging; Blood Pressure; Cohort Studies; Coronary Disease; Female; Health Surveys; Humans; Hypertrophy, Left Ventricular; Male; Regression Analysis; United States

Correlates of QT prolongation in older adults (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group. - Rautaharju, P M; Manolio, T A; Psaty, B M; Borhani, N O; Furberg, C D (Am J Cardiol, 1994)
Keywords: Aged; Aged, 80 and over; Female; Humans; Logistic Models; Long QT Syndrome; Longitudinal Studies; Male; Sex Factors

Eating patterns of community-dwelling older adults: the Cardiovascular Health Study. - Kumanyika, S; Tell, G S; Shemanski, L; Polak, J; Savage, P J (Ann Epidemiol, 1994)
We analyzed eating patterns of 4643 adults (1988 men and 2655 women) aged 65 years and older at the time of their enrollment in the Cardiovascular Health Study. Diet was assessed with a qualitative, picture-sort food frequency questionnaire along with supplemental questions on other eating pattern variables. Consumption of high fat foods and low fiber foods was more frequent in older participants, men, minorities, and persons with body mass index > or = 30 kg/m2 and less common among persons who reported following self-prescribed or medically prescribed special diets. Few associations of consumption of specific food groups with disease status were identified. Participants with coronary heart disease, diabetes, hypertension, and cardiovascular disease were significantly more likely to report following a special diet and using low-calorie or low-sodium food products, however. Although the percentage of participants with prevalent disease who reported following special diets was relatively low from a clinical perspective, it was sufficiently high to suggest that controlling for dietary modifications may be important when attempting to identify associations of diet with prevalent disease in older populations.
Keywords: Aged; Aged, 80 and over; Body Mass Index; Cardiovascular Diseases; Cerebrovascular Disorders; Demography; Diet; Diet Surveys; Diet, Sodium-Restricted; Female; Humans; Male; Minority Groups; Prospective Studies; Risk Factors; Sex Factors

High density lipoprotein cholesterol subfractions in older people. - Ettinger, W H; Verdery, R B; Wahl, P W; Fried, L P (J Gerontol, 1994)
BACKGROUND: High density lipoprotein (HDL) may be an important risk factor for cardiovascular disease in older people. HDL is heterogeneous with several subfractions. This article describes the distribution and correlates of HDL2 cholesterol (C) and HDL3-C in older people. METHODS: HDL subfraction cholesterols were measured in 1,127 females and 825 males > or = 65 years old who participated in the Cardiovascular Health Study. Distributions of HDL subfraction cholesterols and bivariate and multivariate relationships were determined in cross-sectional analyses. RESULTS: Mean (+/- SD) concentrations of HDL subfractions were: HDL3-C (M .98 +/- .25, F 1.2 +/- .29 mmol/l), HDL2-C (M .09 +/- .08, F .13 +/- .09 mmol/l). HDL2-C, but not HDL3-C, was slightly higher with age. Using multivariate analysis, both HDL2-C and HDL3-C (in females) were inversely correlated with triglyceride, body weight, and fasting insulin; HDL3-C was inversely correlated with central fat distribution in women. Both HDL2-C and HDL3-C were lower in participants with prevalent cardiovascular disease. However, only HDL3-C was significantly inversely related to carotid stenosis, as measured by ultrasound. CONCLUSIONS: The slight increase in HDL-C with age appears to be due to an increase in the HDL2-C subfraction. HDL-C subfractions are independently related to triglyceride levels, body weight, and insulin concentrations in older people, all potentially modifiable risk factors. Both HDL2-C and HDL3-C are lower in older people with prevalent cardiovascular disease, although only HDL3-C was correlated with carotid atherosclerosis. These findings are consistent with the hypothesis that HDL subfractions are important risk factors for atherosclerotic cardiovascular disease in the elderly.
Keywords: Aged; Aged, 80 and over; Alcohol Drinking; Body Weight; Carotid Stenosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Drug Therapy; Female; Humans; Insulin; Lipoproteins, HDL; Lipoproteins, HDL2; Lipoproteins, HDL3; Male; Sex Factors; Socioeconomic Factors

Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. - Manolio, T A; Kronmal, R A; Burke, G L; Poirier, V; O'Leary, D H; Gardin, J M; Fried, L P; Steinberg, E P; Bryan, R N (Stroke, 1994)
BACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease. METHODS: Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors. RESULTS: Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound. CONCLUSIONS: Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.
Keywords: Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Atrophy; Brain; Cerebral Ventricles; Cerebrovascular Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Regression Analysis; Risk Factors; Sex Factors

A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study. - Bryan, R N; Manolio, T A; Schertz, L D; Jungreis, C; Poirier, V C; Elster, A D; Kronmal, R A (AJNR Am J Neuroradiol, 1994)
PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history. METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9. RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77% of the participants with histories of stroke but was also present in 23% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm. CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.
Keywords: Aged; Brain; Cerebral Infarction; Cerebral Ventricles; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Diagnosis, Differential; Feasibility Studies; Female; Humans; Image Interpretation, Computer-Assisted; Incidence; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mass Screening; Observer Variation; Pilot Projects; Prospective Studies; Risk Factors; United States

Physical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group. - Fried, L P; Ettinger, W H; Lind, B; Newman, A B; Gardin, J (J Clin Epidemiol, 1994)
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.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Chronic Disease; Disabled Persons; Factor Analysis, Statistical; Female; Geriatric Assessment; Humans; Logistic Models; Male; Outcome Assessment (Health Care); Risk Factors; Sex Factors; Socioeconomic Factors; United States

Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study. - Schulz, R; Mittelmark, M; Kronmal, R; Polak, J F; Hirsch, C H; German, P; Bookwala, J (J Aging Health, 1994)
Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.
Keywords: Aged; Cardiovascular Diseases; Data Collection; Female; Forecasting; Geriatric Assessment; Health Status; Humans; Male; Multivariate Analysis; Regression Analysis; Self-Assessment; Sex Factors; United States

Prevalence and correlates of respiratory symptoms and disease in the elderly. Cardiovascular Health Study. - Enright, P L; Kronmal, R A; Higgins, M W; Schenker, M B; Haponik, E F (Chest, 1994)
Spirometry was performed by 5,201 elderly participants of the Cardiovascular Health Study during their baseline examination and a subset of the ATS/DLD-78 respiratory questionnaire was administered by trained interviewers. In never smokers (46 percent of the cohort), the overall prevalence of chronic cough was 9 percent, chronic phlegm was 13 percent, attacks of wheezing with dyspnea were 8 percent, and grade 3 dyspnea on exertion was 10 percent. The prevalence of lung disease in current smokers (12 percent of the cohort) was 8/7 percent (men/women) with chronic bronchitis and 14/5 percent with emphysema. Overall, 6 percent reported asthma (a physician-confirmed history) and 12 percent reported hay fever. Using a logistic regression model, attacks of wheezing with dyspnea were strongly associated with a lower FEV1, coronary heart disease, heart failure, and a large waist size (in participants without a diagnosis of asthma, chronic bronchitis, or emphysema). Undiagnosed airways obstruction was twice as likely in women and those with lower income, and was associated with current and former smoking, pack-years of smoking, and chronic cough. Dyspnea on exertion (DOE) was three times or more likely if a participant reported heart failure, coronary heart disease, or emphysema; and much more likely if their FEV1 or FVC was substantially reduced. Dyspnea on exertion was also positively associated with older age, chronic bronchitis or asthma, a larger waist or hip size, pack-years of smoking, and less education. We conclude that DOE and attacks of wheezing with dyspnea are commonly associated with cardiovascular disease and a low FEV1 in those over 65 years and that airways obstruction frequently remains undiagnosed in the elderly.
Keywords: Aged; Aged, 80 and over; California; Cohort Studies; Female; Humans; Lung Diseases; Male; Maryland; Multivariate Analysis; North Carolina; Pennsylvania; Prevalence; Prognosis; Respiratory Tract Diseases; Spirometry; Surveys and Questionnaires

Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). - Furberg, C D; Psaty, B M; Manolio, T A; Gardin, J M; Smith, V E; Rautaharju, P M (Am J Cardiol, 1994)
Atrial fibrillation (AF) is a common arrhythmia in elderly persons and a common cause of embolic stroke. Most studies of the prevalence and correlates of AF have used selected, hospital-based populations. The Cardiovascular Health Study is a population-based, longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years. AF was diagnosed in 4.8% of women and in 6.2% of men at the baseline examination, and prevalence was strongly associated with advanced age in women. Prevalence of AF was 9.1% in men and women with clinical cardiovascular disease, 4.6% in patients with evidence of subclinical but no clinical cardiovascular disease, and only 1.6% in subjects with neither clinical nor subclinical cardiovascular disease. A history of congestive heart failure, valvular heart disease and stroke, echocardiographic evidence of enlarged left atrial dimension, abnormal mitral or aortic valve function, treated systemic hypertension, and advanced age were independently associated with the prevalence of AF. The low prevalence of AF in the absence of clinical and subclinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called "lone atrial fibrillation" in the elderly.
Keywords: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Blood Glucose; Cardiovascular Diseases; Chi-Square Distribution; Coronary Disease; Electrocardiography; Female; Humans; Male; Prevalence; Regression Analysis; Sampling Studies

Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. - Kuller, L; Borhani, N; Furberg, C; Gardin, J; Manolio, T; O'Leary, D; Psaty, B; Robbins, J (Am J Epidemiol, 1994)
The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36% in women and 38.7% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.
Keywords: Aged; Aged, 80 and over; Arteriosclerosis; Cardiovascular Diseases; Female; Humans; Logistic Models; Longitudinal Studies; Male; Prevalence; Risk Factors; United States

Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group. - Tell, G S; Polak, J F; Ward, B J; Kittner, S J; Savage, P J; Robbins, J (Circulation, 1994)
BACKGROUND: Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease. METHODS AND RESULTS: We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001). CONCLUSIONS: These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.
Keywords: Aged; Aged, 80 and over; Carotid Arteries; Carotid Stenosis; Cohort Studies; Female; Humans; Male; Smoking; Ultrasonography

Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group. - Enright, P L; Kronmal, R A; Manolio, T A; Schenker, M B; Hyatt, R E (Am J Respir Crit Care Med, 1994)
Maximal inspiratory pressure (MIP) was assessed in 4,443 ambulatory participants of the Cardiovascular Health Study, 65 yr of age and older, sampled from four communities. Maximal expiratory pressure (MEP) was also measured in 790 participants from a single clinic. Positive predictors of MIP included male sex, FVC, handgrip strength, and higher levels of lean body mass (or low bioelectric resistance). Negative predictors were age, current smoking, self-reported fair to poor general health, and waist size. Both participant and technician learning effects were noted, but there was no independent effect of race, hypertension, cardiovascular disease, or diabetes. A healthy subgroup was identified by excluding current smokers, those with fair to poor general health, or an FEV1 less than 65% of predicted. Mean values determined from the healthy group were 57/116 cm H2O (MIP/MEP) for women, and 83/174 for men. Lower limits of the normal range (fifth percentiles) were 45 to 60% of the mean predicted values. The reference equations derived from this group of healthy 65 to 85-yr-olds may be used by pulmonary function laboratories and respiratory therapists who evaluate the respiratory muscle strength of elderly patients.
Keywords: Aged; Aged, 80 and over; Aging; Body Constitution; Cardiovascular Diseases; Female; Humans; Male; Prospective Studies; Reference Values; Respiratory Function Tests; Respiratory Muscles; Risk Factors; Sex Characteristics; Smoking

Self-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group. - Ettinger, W H; Fried, L P; Harris, T; Shemanski, L; Schulz, R; Robbins, J (J Am Geriatr Soc, 1994)
OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people > or = 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Arthritis; Cardiovascular Diseases; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Disabled Persons; Female; Health Status; Health Surveys; Heart Diseases; Humans; Lung Diseases; Male; Observer Variation; Reproducibility of Results; Risk Factors; Sex Factors; United States

Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group. - Manolio, T A; Burke, G L; Psaty, B M; Newman, A B; Haan, M; Powe, N; Tracy, R P; O'Leary, D H (J Clin Epidemiol, 1995)
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.
Keywords: African Continental Ancestry Group; Aged; Cardiovascular Diseases; Carotid Arteries; European Continental Ancestry Group; Female; Geriatric Assessment; Humans; Male; Multivariate Analysis; Prevalence; Regression Analysis; Risk Factors; Sex Factors

Evidence for inflammation as a cause of hypocholesterolemia in older people. - Ettinger, W H; Harris, T; Verdery, R B; Tracy, R; Kouba, E (J Am Geriatr Soc, 1995)
Keywords: Age Factors; Aged; Analysis of Variance; C-Reactive Protein; Case-Control Studies; Cholesterol; Female; Fibrinogen; Humans; Hypolipoproteinemias; Inflammation; Interleukin-1; Interleukin-6; Male

Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly. Results from The Cardiovascular Health Study. - Tracy, R P; Bovill, E G; Yanez, D; Psaty, B M; Fried, L P; Heiss, G; Lee, M; Polak, J F; Savage, P J (Arterioscler Thromb Vasc Biol, 1995)
No studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, fibrinogen was significantly associated with carotid artery stenosis, internal (but not common) carotid artery wall thickness, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Cardiovascular Diseases; Carotid Stenosis; Cohort Studies; Factor VII; Factor VIII; Fibrinogen; Humans; Multivariate Analysis; Prospective Studies; Regression Analysis; Risk Factors

Hematological and biochemical laboratory values in older Cardiovascular Health Study participants. - Robbins, J; Wahl, P; Savage, P; Enright, P; Powe, N; Lyles, M (J Am Geriatr Soc, 1995)
OBJECTIVE: To define reference hematologic and biochemical lab values in older individuals. DESIGN: Randomly selected, age- and gender-stratified participants. SETTING: Visits by participants to four research clinics. PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home. MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count. RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories. CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice.
Keywords: Age Factors; Aged; Analysis of Variance; California; Cardiovascular Diseases; Cohort Studies; Female; Health Status; Humans; Male; Maryland; Middle Aged; North Carolina; Pennsylvania; Reference Values; Risk Factors; Sex Characteristics

High density lipoprotein cholesterol is associated with serum cortisol in older people. - Varma, V K; Rushing, J T; Ettinger, W H (J Am Geriatr Soc, 1995)
OBJECTIVE: To determine the associations between serum cortisol and HDL cholesterol, other lipoprotein lipids and cardiovascular risk factors, carotid atherosclerosis, and clinical heart disease in older people. DESIGN: A cross-sectional, observational, ancillary study of the Cardiovascular Health Study (CHS). POPULATION: A total of 245 community-dwelling people, 65 to 89 years old, were recruited consecutively for a 2-month period from the CHS cohort in Forsyth County, North Carolina. METHODS: Cortisol was measured by radioimmunoassay in serum collected between 7:00 and 10:00 AM after an overnight fast. Cortisol levels were correlated with lipoprotein lipids, insulin, glucose, body mass index, waist-hip ratio, prevalent coronary heart disease, hypertension, diabetes, and carotid atherosclerosis by B-mode ultrasound. RESULTS: Serum cortisol was correlated negatively (r = -.24) with body mass index and waist-hip ratio (r = -.16) but was not related significantly to fasting insulin or glucose. Cortisol was not associated significantly with triglyceride and low density lipoprotein cholesterol but showed a positive correlation (r = .21) with high density lipoprotein cholesterol. The relationship between cortisol and high density lipoprotein cholesterol persisted after adjustment for gender, body mass index, waist-hip ratio, cigarette and alcohol use, triglyceride level, and diabetes. There was a trend toward a negative correlation between cortisol and measures of carotid atherosclerosis, but no significant relationship was indicated between cortisol and prevalent coronary heart disease, hypertension, or diabetes. CONCLUSION: Endogenous glucocorticoid levels correlated with HDL cholesterol levels and may play a role in the physiologic regulation of high density lipoprotein levels in older people.
Keywords: Aged; Body Constitution; Body Mass Index; Cardiovascular Diseases; Carotid Stenosis; Cholesterol, HDL; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hydrocortisone; Hypertension; Male; Prevalence; Risk Factors

Ischemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the Cardiovascular Health Study. - Rautaharju, P M; Manolio, T A; Furberg, C D; Siscovick, D; Newman, A B; Borhani, N O; Gardin, J M (Int J Cardiol, 1995)
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.
Keywords: Age Factors; Aged; Arrhythmias, Cardiac; Atrial Fibrillation; California; Circadian Rhythm; Digitalis Glycosides; Electrocardiography; Electrocardiography, Ambulatory; Female; Health Surveys; Humans; Hypertrophy, Left Ventricular; Logistic Models; Male; Maryland; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; North Carolina; Obesity; Odds Ratio; Pennsylvania; Prevalence; Risk Factors; Sex Characteristics

Laboratory methods and quality assurance in the Cardiovascular Health Study. - Cushman, M; Cornell, E S; Howard, P R; Bovill, E G; Tracy, R P (Clin Chem, 1995)
The Cardiovascular Health Study is an observational cohort study of risk factors for cardiovascular disease in 5201 participants, ages > or = 65 years. We report the methods and quality-assurance results for blood procurement, processing, shipping, storage, and sample analysis used during the first examination period (May 1989-June 1990). The most frequent difficulty in phlebotomy and processing was the requirement of more than one venipuncture (in 2.6% of the participants). The CVs for control materials ranged from 0.93% for glucose to 10.7% for insulin; most were < 4%. In addition to standard quality-assurance methods, we applied two other methods: technical error calculation for replicates, and weighted linear regression to assess time trend in results of control materials. After outliers were excluded, technical error values ranged from 1.7 for uric acid to 18.8 for insulin. Factor VII and factor VIII had slight trends over the 12-month analysis period. Results of quality-assurance analyses used to resolve problems were successful, thereby improving the second laboratory examination.
Keywords: Aged; Blood Glucose; Blood Specimen Collection; Cardiovascular Diseases; Chemistry, Clinical; Factor VII; Factor VIII; Fibrinogen; Humans; Insulin; Quality Control; Regression Analysis; Triglycerides

Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. - Psaty, B M; Kuller, L H; Bild, D; Burke, G L; Kittner, S J; Mittelmark, M; Price, T R; Rautaharju, P M; Robbins, J (Ann Epidemiol, 1995)
The objective of this article is to describe the methods of assessing cardiovascular conditions among older adults recruited to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke. Medicare eligibility lists from four US communities were used to obtain a representative sample of 5201 community-dwelling elderly, who answered standardized questionnaires and underwent an extensive clinic examination at baseline. For each cardiovascular condition, self-reports were confirmed by components of the baseline examination or, if necessary, by a validation protocol that included either the review of medical records or surveys of treating physicians. Potential underreporting of a condition was detected either by the review of medical records at baseline for other self-reported conditions or, during prospective follow-up, by the investigation of potential incident events. For myocardial infarction, 75.5% of the self-reports in men and 60.6% in women were confirmed. Self-reported congestive heart failure was confirmed in 73.3% of men and 76.6% of women; stroke, in 59.6% of men and 53.8% of women; and transient ischemic attack, in 41.5% of men and 37.0% of women. Underreporting was also common. During prospective follow-up of an average of about 3 years per person, approximately 50% of men and 38% of women were hospitalized or investigated for at least one potential incident event; for each cardiovascular condition, about 1 to 4% of those investigated during prospective follow-up were found to have had the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords: Aged; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Electrocardiography; Epidemiologic Methods; False Negative Reactions; Female; Humans; Male; Population Surveillance; Prevalence; Prospective Studies; Reproducibility of Results; Risk Factors; Self Disclosure; United States

Reduced vital capacity in elderly persons with hypertension, coronary heart disease, or left ventricular hypertrophy. The Cardiovascular Health Study. - Enright, P L; Kronmal, R A; Smith, V E; Gardin, J M; Schenker, M B; Manolio, T A (Chest, 1995)
The Cardiovascular Health Study provided the opportunity to determine the association of subclinical and clinical cardiovascular disease with pulmonary function in a population sample of elderly adults. Included were 2,955 women and 2,246 men over age 64 years who were recruited for this observational study from four communities and completed extensive examinations that included spirometry, echocardiograms, and blood pressure. Current smokers, past smokers with >20 pack-years of smoking, and persons with a history of asthma, chronic bronchitis, or emphysema were excluded from this analysis, leaving 2,784 (55%) of the cohort. Systolic hypertension or coronary artery disease was associated with 40- to 100-mL decrements in FEV1, and 50- to 150-mL decrements in FVC, while a history of congestive heart failure was associated with 200 to 300 mL lower FEV1 and FVC values (p < 0.0001), after correcting for age, height, and waist size. Higher left ventricular (LV) mass was also significantly associated with a decrease in FEV1 and FVC in multivariate models. This relationship was strongest with the end-diastolic LV posterior wall thickness component of LV mass. In summary, FEV1 and FVC are reduced in elderly persons with hypertension, ischemic heart disease, higher disease, higher LV mass, and congestive heart failure, though the magnitude of these associations is relatively small unless heart failure supervenes. Substantial decrements in percent predicted FEV1 and FVC should not be attributed to the presence of uncomplicated ischemic heart disease or hypertension alone.
Keywords: Age Factors; Aged; Aged, 80 and over; Coronary Disease; Female; Forced Expiratory Volume; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Ventricular Function, Left; Vital Capacity

Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study. - Gardin, J M; Siscovick, D; Anton-Culver, H; Lynch, J C; Smith, V E; Klopfenstein, H S; Bommer, W J; Fried, L; O'Leary, D; Manolio, T A (Circulation, 1995)
BACKGROUND: Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older. METHODS AND RESULTS: M-mode LV mass adjusted for body weight increased modestly with age (P < .0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both P < .001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group, P < .001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all P < .001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (P < .0001). Multivariate analyses revealed male sex and presence of clinical CHD (both P < .001) to be independent predictors of LV akinesis or dyskinesis. CONCLUSIONS: Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly.
Keywords: Age Factors; Aged; Aged, 80 and over; Aging; Cohort Studies; Coronary Disease; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Male; Sex Factors; Systole

Subclinical disease as an independent risk factor for cardiovascular disease. - Kuller, L H; Shemanski, L; Psaty, B M; Borhani, N O; Gardin, J; Haan, M N; O'Leary, D H; Savage, P J; Tell, G S; Tracy, R (Circulation, 1995)
BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study. METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes. CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Female; Humans; Incidence; Longitudinal Studies; Male; Myocardial Infarction; Odds Ratio; Reference Values; Risk Factors

Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study. - Ives, D G; Fitzpatrick, A L; Bild, D E; Psaty, B M; Kuller, L H; Crowley, P M; Cruise, R G; Theroux, S (Ann Epidemiol, 1995)
While previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.
Keywords: Aged; Cerebrovascular Disorders; Coronary Disease; Epidemiologic Methods; Female; Hospitalization; Humans; Incidence; Longitudinal Studies; Male; Population Surveillance; Quality Control; United States

Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice? - Psaty, B M; Koepsell, T D; Yanez, N D; Smith, N L; Manolio, T A; Heckbert, S R; Borhani, N O; Gardin, J M; Gottdiener, J S; Rutan, G H (JAMA, 1995)
OBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults. DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3. RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%) and period 3 (+2.8%). CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.
Keywords: Aged; Antihypertensive Agents; Clinical Trials as Topic; Data Interpretation, Statistical; Drug Utilization Review; Female; Humans; Hypertension; Male; Practice Patterns, Physicians'; United States

Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators. - Cushman, M; Yanez, D; Psaty, B M; Fried, L P; Heiss, G; Lee, M; Polak, J F; Savage, P J; Tracy, R P (Am J Epidemiol, 1996)
The cross-sectional correlates of three hemostatic factors--fibrinogen, factor VII, and factor VIII--were examined in the Cardiovascular Health Study, a population-based cohort study of 5,201 subjects over age 65 years. Subjects were recruited in 1989-1990 in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. In multivariate linear regression models, cardiac risk factors significantly associated with fibrinogen were current smoking, race, lipids, and white blood count. In women, alcohol use, obesity, physical activity, and insulin level were also significant, while in men hypertension was correlated. The significant correlates of factor VII were lipids and white blood count in men and estrogen use, alcohol use, race, lipids, insulin level, white blood count, and obesity in women. The independent correlates of factor VIII were insulin, glucose, and race in both sexes; low density lipoprotein cholesterol, white blood count, and diuretic use in men; and alcohol use in women. In multivariate models, factors known to be modifiable risk factors for cardiovascular disease accounted for more of the population variance of these hemostatic factors in women than in men, especially for factor VII. The hemostatic factors may mediate some effects of risk factors on disease, and this should be considered in longitudinal studies.
Keywords: Age Distribution; Aged; Aged, 80 and over; Analysis of Variance; Cardiovascular Diseases; Cohort Studies; Factor VII; Factor VIII; Female; Fibrinogen; Humans; Linear Models; Logistic Models; Male; Prevalence; Risk Factors; Sex Distribution; United States

Asthma and its association with cardiovascular disease in the elderly. The Cardiovascular Health Study Research Group. - Enright, P L; Ward, B J; Tracy, R P; Lasser, E C (J Asthma, 1996)
Cardiovascular disease (CVD) is more prevalent in elderly than in middle-aged patients. Symptoms such as intermittent wheezing with dyspnea may then be due to either CVD or asthma. The objective of this study was to determine the prevalence and correlates of asthma in the elderly and their associations with CVD and CVD risk factors. A community sample of 5201 elderly persons from the Cardiovascular Health Study was asked if they had a physician diagnosis of asthma, and multiple cardiovascular risk and disease variables were measured. Six percent of the participants (309) recalled a history of asthma, and half of these were never smokers. Thirty percent of those with asthma were currently taking a bronchodilator, 14% inhaled steroids, and 10% oral prednisone. Men and women with asthma who were cigarette smokers were more likely to report a concurrent diagnosis of congestive heart failure than smokers without asthma (p = .04). However, when we determined the independent CVD correlates of asthma in this cohort, controlling for smoking status, age, gender, and diagnoses of chronic bronchitis and emphysema, only higher levels of high-density lipoprotein cholesterol (HDL-C) and higher plasma fibrinogen levels were significantly associated with asthma. It was concluded that asthma is as prevalent in the elderly as in middle-aged persons and is associated with higher HDL-C and higher fibrinogen levels, but not with prevalent cardiovascular disease.
Keywords: Aged; Aged, 80 and over; Asthma; Cardiovascular Diseases; Cohort Studies; Female; Humans; Lung; Male; Multivariate Analysis; Prevalence; Risk Factors; Sex Distribution; Smoking

Carotid artery measures are strongly associated with left ventricular mass in older adults (a report from the Cardiovascular Health Study). - Kronmal, R A; Smith, V E; O'Leary, D H; Polak, J F; Gardin, J M; Manolio, T A (Am J Cardiol, 1996)
Associations of carotid artery diameter and intimal-medial thickness by ultrasound with echocardiographic left ventricular (LV) structure were examined in 3,409 participants in the Cardiovascular Health Study, a population-based study of risk factors for coronary heart disease and stroke in men and women aged > or = 65 years. At baseline, sector-guided M-mode echocardiography and B-mode ultrasound were used to evaluate the left ventricle and carotid arteries, respectively. Common carotid artery diameter and intimal-medial thickness were significantly related to LV mass in correlational analysis (r=0.40 and 0.20, respectively, p<0.01), and each was independently associated with LV mass after adjustment for age, gender, weight, systolic and diastolic blood pressure, antihypertensive medication use, prior coronary heart disease, electrocardiographic abnormalities, high-density lipoprotein, and factor VII. We speculate that changes in the arterial wall affect impedance to LV ejection leading to increases in LV mass. Further follow-up of this cohort is in progress and will help to determine whether such carotid artery measures could, by exacerbating LV hypertrophy, constitute another important risk factor for adverse cardiovascular outcomes.
Keywords: Aged; Carotid Arteries; Cohort Studies; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Regression Analysis; Risk Factors; Ultrasonography

Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study. - Longstreth, W T; Manolio, T A; Arnold, A; Burke, G L; Bryan, N; Jungreis, C A; Enright, P L; O'Leary, D; Fried, L (Stroke, 1996)
BACKGROUND AND PURPOSE: Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. METHODS: Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. RESULTS: Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P < .01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV1), and income less than $50,000 per year. If excluded, FEV1 was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination. Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function. CONCLUSIONS: White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function.
Keywords: Age Factors; Aged; Aging; Blood Pressure; Brain; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Multivariate Analysis; Risk Factors; Sex Factors

Compensatory increase in common carotid artery diameter. Relation to blood pressure and artery intima-media thickness in older adults. Cardiovascular Health Study. - Polak, J F; Kronmal, R A; Tell, G S; O'Leary, D H; Savage, P J; Gardin, J M; Rutan, G H; Borhani, N O (Stroke, 1996)
BACKGROUND AND PURPOSE: Common carotid artery (CCA) diameter is thought to increase as a consequence of hypertension and may increase as the thickness of the arterial wall increases. The purpose of this study was to determine CCA dimensions and correlate them with clinical features. METHODS: We performed a cross-sectional, community-based study of adults 65 years of age and older, measuring inner and outer diameter of the CCA in vivo with carotid sonography. Findings were correlated against risk factors for atherosclerosis, CCA intima-media thickness (IMT), and echocardiographically determined left ventricular (LV) mass. RESULTS: Independent variables showing strong positive associations with outer and inner CCA diameter included age, male sex, height, weight, and systolic blood pressure. As an independent variable, LV mass (r = .40 and r = .37, respectively; P < .00001) had a strong positive relation to inner and outer CCA diameters. The relationship between diameter and IMT was different. In a model that controlled for age, sex, and estimated LV mass, an increase of 1 mm in CCA IMT corresponded to a 1.9 mm increase in the outer diameter of the artery (P < .00001) but was not significantly related to the inner diameter (slope = +0.07 mm; P = .26). CONCLUSIONS: Increase in the outer diameter of the CCA is associated with subject size, sex, age, echocardiographically estimated LV mass, and CCA IMT. Increases in internal diameter of the CCA have similar relationships but are not related to IMT. This supports the hypothesis that the human CCA dilates as the thickness of the artery wall increases.
Keywords: Aged; Blood Pressure; Carotid Artery, Common; Cross-Sectional Studies; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Male; Tunica Intima; Tunica Media

Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. - Cushman, M; Psaty, B M; Macy, E; Bovill, E G; Cornell, E S; Kuller, L H; Tracy, R P (Arterioscler Thromb Vasc Biol, 1996)
Studies suggest that thrombosis is important in the progression of atherosclerotic lesions. The biochemical markers prothrombin fragment 1-2 and fibrinopeptide A reflect in vivo thrombin generation and activity, respectively. As such, they are markers that might be associated with cardiovascular risk. From the Cardiovascular Health Study, a cohort study of 5201 persons over 65 years of age, 399 persons free of clinical cardiovascular disease (CVD) at the baseline examination were selected for study of specialized markers of hemostasis. We report the cross-sectional relationships of the thrombin markers to CVD risk factors and measures of subclinical CVD. The range of fragment 1-2 2 was 0.12 to 0.85 nmol/L. The range of fibrinopeptide A was 0.9 to 44.1 micrograms/L. High levels of fragment 1-2 and fibrinopeptide A were associated with age, with levels higher in women than men. Fragment 1-2 was associated with smoking; high levels of triglyceride, creatinine, and C-reactive protein; and low levels of glucose. Fibrinopeptide A was associated with high C-reactive protein and apolipoprotein(a) and lower ankle-brachial index. There were no significant associations of the thrombin markers with race, fibrinogen, alcohol consumption, diabetes, or most measures of subclinical CVD. Study findings support a hypothesis that there are physiological interrelationships between cardiac risk factors, hemostasis, inflammation, and progression of atherosclerosis.
Keywords: Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Hemostasis; Humans; Male; Risk Factors; Thrombin

Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study. - Jonas, H A; Kronmal, R A; Psaty, B M; Manolio, T A; Meilahn, E N; Tell, G S; Tracy, R P; Robbins, J A; Anton-Culver, H (Ann Epidemiol, 1996)
The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.
Keywords: Aged; Arteriosclerosis; Carotid Arteries; Carotid Stenosis; Cohort Studies; Confidence Intervals; Cross-Sectional Studies; Databases, Factual; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens; Female; Health Status Indicators; Humans; Odds Ratio; Progestins; Reproductive History; Ultrasonography; United States; Women's Health

Hypertension and outcomes research. From clinical trials to clinical epidemiology. - Psaty, B M; Siscovick, D S; Weiss, N S; Koepsell, T D; Rosendaal, F R; Lin, D; Heckbert, S R; Wagner, E H; Furberg, C D (Am J Hypertens, 1996)
Outcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.
Keywords: Clinical Trials as Topic; Epidemiologic Methods; Evidence-Based Medicine; Humans; Hypertension; Outcome Assessment (Health Care)

Lipoprotein levels in elderly patients with asthma. Cardiovascular Health Study Research Group. - Enright, P L; Lasser, E C; Ward, B J; Tracy, R P (J Allergy Clin Immunol, 1996)
Keywords: Aged; Aging; Arteriosclerosis; Asthma; Female; Humans; Lipoproteins; Male; Prospective Studies; Risk Factors; Sex Factors

Picture-sort method for administering a food frequency questionnaire to older adults. - Kumanyika, S; Tell, G S; Fried, L; Martel, J K; Chinchilli, V M (J Am Diet Assoc, 1996)
OBJECTIVE: To assess the validity of a picture-sort approach to administering the National Cancer Institute food frequency questionnaire to older adults. DESIGN: A picture-sort interview was conducted in each respondent's home. After the picture sort, a 24-hour recall interview was administered on the same occasion. Five additional in-home recall interviews were subsequently conducted at approximately 1-month intervals. SUBJECTS/SETTING: Forty-seven female and 49 male volunteers aged 66 to 100 years were recruited from among Cardiovascular Health Study participants from Maryland and North Carolina. MAIN OUTCOME MEASURES: Estimates from the picture sort and the recall for intakes of macronutrients, cholesterol, fiber, and selected vitamins and minerals exclusive of supplements. STATISTICAL ANALYSES: Comparison of means estimated by the two methods and correlation analyses were used. Correlations were adjusted under varied assumptions about the nature of the information contained in the six 24-hour recalls relative to respondents' usual intakes. RESULTS: After correction for attenuation, Pearson correlation coefficients for macronutrients ranged from .41 for protein to .74 for saturated fat and cholesterol. For vitamins and minerals, correlations ranged from .26 for beta carotene to .62 for calcium. APPLICATIONS: Picture-sort estimates of mean nutrient intakes were comparable with estimates based on 24-hour recalls, and correlations with reference data were similar to those reported in the literature for conventionally administered food frequency questionnaires. This dietary assessment method may, therefore, offer a way to simplify or structure responses to improve ease of administration and increase respondents' liking for the interview without loss of data quality.
Keywords: Aged; Aged, 80 and over; Audiovisual Aids; Data Interpretation, Statistical; Diet Records; Eating; Female; Humans; Interviews as Topic; Male; Mental Recall; Surveys and Questionnaires

Prevalence and correlates of snoring and observed apneas in 5,201 older adults. - Enright, P L; Newman, A B; Wahl, P W; Manolio, T A; Haponik, E F; Boyle, P J (Sleep, 1996)
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.
Keywords: Activities of Daily Living; Age Factors; Aged; Cardiovascular Diseases; Comorbidity; Female; Humans; Incidence; Lung Diseases; Male; Narcolepsy; Prevalence; Random Allocation; Sex Factors; Sleep Apnea Syndromes; Snoring

Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study. - Alcorn, H G; Wolfson, S K; Sutton-Tyrrell, K; Kuller, L H; O'Leary, D (Arterioscler Thromb Vasc Biol, 1996)
B-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5% (451/4741) overall, with a prevalence among men of 14.2% (278/1956) and prevalence among women of 6.2% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.
Keywords: Aged; Anthropometry; Aortic Aneurysm, Abdominal; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Comorbidity; Female; Humans; Male; Middle Aged; Pilot Projects; Prevalence; Reproducibility of Results; Risk Factors; Smoking; Ultrasonography; United States

Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study. - Manolio, T A; Kronmal, R A; Burke, G L; O'Leary, D H; Price, T R (Stroke, 1996)
BACKGROUND AND PURPOSE: Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease. METHODS: Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study. RESULTS: During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft. frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P < .001). Aspirin users had a 52% higher risk of stroke (relative risk, 1.52; 95% confidence interval, 1.1 to 2.0; P < .007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84% higher risk (relative risk, 1.84; 95% confidence interval, 1.2 to 2.8). CONCLUSIONS: Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.
Keywords: Age Factors; Aged; Cardiovascular Physiological Phenomena; Cerebrovascular Disorders; Cohort Studies; Female; Health Status; Humans; Incidence; Longitudinal Studies; Male; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Time Factors

Social support as a mediator in the relation between functional status and quality of life in older adults. - Newsom, J T; Schulz, R (Psychol Aging, 1996)
The relations among physical functioning, social support, depressive symptoms, and life satisfaction were examined in a national sample of 4,734 adults age 65 and older. Regression analyses were used to examine the relative importance of objective and subjective support measures in understanding the relation between physical impairment and quality of life. Impairment was associated with fewer friendship contacts, fewer family contacts, less perceived belonging support, and less perceived tangible aid, but only measures of perceived support predicted depressive symptomatology. A structural equation modeling approach was then used to explore the mediational role of perceived social support in the relation between impairment and quality of life variables. Results are consistent with the hypothesis that lower reported social support is an important reason for decreases in life satisfaction and increases in depressive symptoms found among older adult populations. Implications for understanding the role of social support in attenuating the effects of physical disability in older adults are discussed.
Keywords: Activities of Daily Living; Adaptation, Psychological; Aged; Aged, 80 and over; Aging; Depression; Disabled Persons; Geriatric Assessment; Health Status; Humans; Personal Satisfaction; Quality of Life; Sick Role; Social Support

Spirometry reference values for healthy elderly blacks. The Cardiovascular Health Study Research Group. - Enright, P L; Arnold, A; Manolio, T A; Kuller, L H (Chest, 1996)
Pulmonary function was assessed by spirometry in 497 black and 2,980 white ambulatory elderly male and female participants of the Cardiovascular Health Study. The quality assurance program prompted technicians to exceed American Thoracic Society recommendations for spirometry. A "healthy" subgroup of 235 black and 1,227 white participants age 65 years and older was identified by excluding current and former smoker, and those with self-reported asthma or emphysema, congestive heart failure, and poor-quality results of spirometry tests, since those factors were associated with a lower FEV1. Reference equations and normal ranges for elderly blacks for measurements of FEV1, FVC, and the FEV1/FVC ratio were then determined from the healthy group. These elderly blacks had an FVC about 6% lower than elderly whites, even after correcting for standing height, sitting height (trunk length), and age. The popular use of spirometry reference values from studies of middle-aged white subjects by applying a 12% race correction factor for black patients appears to overestimate predicted values.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; European Continental Ancestry Group; Female; Forced Expiratory Volume; Humans; Male; Reference Values; Spirometry; United States; Vital Capacity

Spousal similarity in subjective well-being: the Cardiovascular Health Study. - Bookwala, J; Schulz, R (Psychol Aging, 1996)
This study examines the extent to which one spouse's subjective well-being predicts that of the partner (N = 1,040 spousal pairs, 65 years or older). Prior research is extended in two ways: (a) The similarity of both affective domains (depressive symptoms, feelings about life as a whole, and satisfaction with the meaning and purpose of life) and nonaffective domains (perceived health) are examined, and (b) known predictors of well-being in older adults (sociodemographic variables, self and spouse health status variables, and exposure to common environmental events) are statistically controlled. Results indicate that one spouse's assessments of well-being and depression predict the other's well-being even after controlling for known predictors of these outcomes. Given the similarity of findings for affective and nonaffective domains, multiple mechanisms, including contagion, mate selection, and common environmental influences, are speculated as likely to contribute to this phenomenon.
Keywords: Activities of Daily Living; Adaptation, Psychological; Aged; Cardiovascular Diseases; Depression; Female; Geriatric Assessment; Humans; Male; Personal Satisfaction; Sick Role; Social Environment; Spouses

Thickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group. - O'Leary, D H; Polak, J F; Kronmal, R A; Savage, P J; Borhani, N O; Kittner, S J; Tracy, R; Gardin, J M; Price, T R; Furberg, C D (Stroke, 1996)
BACKGROUND AND PURPOSE: We investigated the relationships between prevalent coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD), and major established risk factors for atherosclerosis and intima-media thickness (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA) separately and in combination in older adults. We wished to determine whether a noninvasive measurement can serve as an indicator of clinically manifest atherosclerotic disease and to determine which of the two variables, CCA IMT or ICA IMT, is a better correlate. METHODS: IMT of the CCA and ICA was measured with duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular Health Study, a study of the risk factors and the natural history of cardiovascular disease in adults aged 65 years or more. Histories of CHD, peripheral arterial disease, and cerebrovascular disease were obtained during baseline examination. Risk factors included cholesterol levels, cigarette smoking, elevated blood pressure, diabetes, age, and sex. Relationships between risk factors and IMT were studied by multiple regression analysis and canonical variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs and ICAs were made by logistic regression, adjusting for age and sex. RESULTS: IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD than those without, even after controlling for sex (P < .001). IMT measurements in the ICA were greater than those in the CCA. Risk factors for ASD accounted for 17% and 18% of the variability in IMT in the CCA and ICA, respectively. These same risk factors accounted for 25% of the variability of a composite measurement consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to 1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to 1.13] and 1.17 [1.09 to 1.25]). CONCLUSIONS: Whereas CCA IMT is associated with major risk factors for atherosclerosis and existing CHD and ASD in older adults, this association is not as strong as that for ICA IMT. The combination of these measures relates more strongly to existing CHD and ASD and cerebrovascular disease risk factors than either taken alone.
Keywords: Adult; Aged; Arteriosclerosis; Blood Pressure; Carotid Artery, Common; Carotid Artery, Internal; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Coronary Disease; Diabetes Mellitus; Diabetic Angiopathies; Electrocardiography; Female; Humans; Male; Medical History Taking; Physical Examination; Prospective Studies; Regression Analysis; Risk Factors; Sex Characteristics; Smoking; Tunica Intima; Tunica Media; Ultrasonography

Utility of new electrocardiographic models for left ventricular mass in older adults. The Cardiovascular Health Study Collaborative Research Group. - Rautaharju, P M; Manolio, T A; Siscovick, D; Zhou, S H; Gardin, J M; Kronmal, R; Furberg, C D; Borhani, N O; Newman, A (Hypertension, 1996)
Several multivariate statistical models have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements. The validity of these algorithms has not been adequately evaluated. The objective of this investigation was to compare the associations between echocardiographic and electrocardiographic left ventricular mass values with clinical and subclinical indexes of coronary heart disease. The evaluation was performed with participants of the Cardiovascular Health Study, a population-based sample of 5201 men and women aged 65 years and older. Echocardiographic M-mode measurements of left ventricular mass were performed from videotape recordings with the use of a strictly standardized protocol. Electrocardiographic algorithms of the Novacode program and new algorithms derived from the Cardiovascular Health Study population were used for left ventricular mass prediction. Echocardiographic and electrocardiographic determinations of left ventricular mass were technically successful in 3410 (65.6%) and 5013 (96.4%) participants, respectively. The Novacode model overestimated echocardiographic left ventricular mass. Compared with the Novacode model, the new Cardiovascular Health Study electrocardiographic model, which includes adjustment for body weight, eliminated left ventricular mass prediction bias and improved the correlation between echocardiographic and electrocardiographic left ventricular mass from .33 to .54 in women and from .46 to .51 in men. Echocardiographic and electrocardiographic models both demonstrated similar and about equally strong associations with overt and subclinical disease and with risk factors for left ventricular hypertrophy. These observations demonstrate the potential utility of electrocardiographic models for left ventricular mass estimation.
Keywords: Age Factors; Aged; Echocardiography; Electrocardiography; Female; Humans; Hypertrophy, Left Ventricular; Linear Models; Male; Models, Cardiovascular; Obesity; Odds Ratio; Prognosis; Risk Factors; Sex Factors; Videotape Recording

White blood cell counts in persons aged 65 years or more from the Cardiovascular Health Study. Correlations with baseline clinical and demographic characteristics. - Bovill, E G; Bild, D E; Heiss, G; Kuller, L H; Lee, M H; Rock, R; Wahl, P W (Am J Epidemiol, 1996)
A higher white blood cell (WBC) count has been shown to be a risk factor for myocardial infarction and stroke in middle-aged populations. This study evaluated the relation between baseline WBC count and other risk factors, as well as subclinical and prevalent disease, in the Cardiovascular Health Study, an epidemiologic study of coronary heart disease and stroke in 5,201 persons aged 65 years or older. Baseline data were collected over a 12-month period in 1989-1990. WBC counts were statistically significantly higher in people with prevalent and subclinical atherosclerotic cardiovascular disease than in those who were free of disease. WBC counts correlated (p < 0.01) positively with coagulation factors, measures of glucose metabolism, creatinine, smoking, and triglycerides. In contrast, WBC counts correlated negatively with high density lipoprotein cholesterol, forced expiratory volume, forced vital capacity, and height. The correlations between WBC counts and risk factors were similar in both the entire cohort and the subgroup of persons who had never smoked. The authors conclude that WBC counts in the elderly are associated with prevalent and subclinical atherosclerotic cardiovascular disease, as well as its risk factors.
Keywords: Age Distribution; Aged; Aged, 80 and over; Cerebrovascular Disorders; Female; Humans; Leukocyte Count; Leukocytosis; Longitudinal Studies; Male; Myocardial Infarction; Prevalence; Reference Values; Risk Factors; United States

The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults. - Heckbert, S R; Longstreth, W T; Psaty, B M; Murros, K E; Smith, N L; Newman, A B; Williamson, J D; Bernick, C; Furberg, C D (J Am Geriatr Soc, 1997)
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.
Keywords: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Antihypertensive Agents; Brain; Calcium Channel Blockers; Cognition; Cohort Studies; Cross-Sectional Studies; Diuretics; Female; Geriatric Assessment; Humans; Magnetic Resonance Imaging; Male; Risk Factors

The association of antihypertensive medication with serum creatinine changes in older adults. - Smith, N L; Psaty, B M; Heckbert, S R; Lemaitre, R N; Kates, D M; Rutan, G H; Bleyer, A (Am J Hypertens, 1997)
Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.
Keywords: Aged; Antihypertensive Agents; Cohort Studies; Creatinine; Female; Humans; Male

Carrying the burden of cardiovascular risk in old age: associations of weight and weight change with prevalent cardiovascular disease, risk factors, and health status in the Cardiovascular Health Study. - Harris, T B; Savage, P J; Tell, G S; Haan, M; Kumanyika, S; Lynch, J C (Am J Clin Nutr, 1997)
Measured weight in old age, reported weight at age 50 y, and weight change from age 50 y to old age were studied in association with prevalent cardiovascular disease (CVD), CVD risk factors, and health status in a population of 4954 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). Heavier weight (i.e., generally weight in the fourth quartile for the cohort) at age 50 y was more closely associated with prevalent CVD than was current weight, with these associations stronger in women than in men. Heavier current weight and heavier weight at age 50 y were associated with cardiovascular risk factors, including higher blood pressure, lower high-density-lipoprotein cholesterol, and higher fasting insulin. Heavier weight at both time points was related to mobility problems in both men and women and to lower current physical activity levels; among women, strong associations were also seen with lower education and current income. Remaining within 10% of reported weight at age 50 y was associated with better health status as measured by reported health, mobility difficulty, number of medications, and prevalent CVD in men. Paradoxically, most cardiovascular risk factors were lowest for weight losers despite an association of weight loss with poorer health. In this cohort of persons aged > or = 65 y, heavier weight was associated with CVD and CVD risk factors, suggesting that prevention of overweight may prove beneficial in improving cardiovascular risk in older persons. Weight stability from age 50 y to old age was associated with better health status than was weight gain or loss.
Keywords: Aged; Blood Pressure; Body Constitution; Body Weight; Cardiovascular Diseases; Cholesterol, LDL; Female; Health Status; Humans; Insulin; Longitudinal Studies; Male; Middle Aged; Odds Ratio; Prevalence; Risk Factors; Sex Characteristics

Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. - Stewart, B F; Siscovick, D; Lind, B K; Gardin, J M; Gottdiener, J S; Smith, V E; Kitzman, D W; Otto, C M (J Am Coll Cardiol, 1997)
OBJECTIVES: The aim of this study was to determine the prevalence of aortic sclerosis and stenosis in the elderly and to identify clinical factors associated with degenerative aortic valve disease. BACKGROUND: Several lines of evidence suggest that degenerative aortic valve disease is not an inevitable consequence of aging and may be associated with specific clinical factors. METHODS: In 5,201 subjects > or = 65 years of age enrolled in the Cardiovascular Health Study, the relation between aortic sclerosis or stenosis identified on echocardiography and clinical risk factors for atherosclerosis was evaluated by using stepwise logistic regression analysis. RESULTS: Aortic valve sclerosis was present in 26% and aortic valve stenosis in 2% of the entire study cohort; in subjects > or = 75 years of age, sclerosis was present in 37% and stenosis in 2.6%. Independent clinical factors associated with degenerative aortic valve disease included age (twofold increased risk for each 10-year increase in age), male gender (twofold excess risk), present smoking (35% increase in risk) and a history of hypertension (20% increase in risk). Other significant factors included height and high lipoprotein(a) and low density lipoprotein cholesterol levels. CONCLUSIONS: Clinical factors associated with aortic sclerosis and stenosis can be identified and are similar to risk factors for atherosclerosis.
Keywords: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Female; Heart Valve Diseases; Humans; Male; Prospective Studies; Risk Factors; Sclerosis

Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study. - Yue, N C; Longstreth, W T; Elster, A D; Jungreis, C A; O'Leary, D H; Poirier, V C (Radiology, 1997)
PURPOSE: To determine the prevalence of clinically serious findings unrelated to stroke on cranial magnetic resonance (MR) images in a population of community-dwelling elderly people. MATERIALS AND METHODS: Neuroradiologists reviewed MR images of 3,672 people aged 65 years and older who were enrolled in a longitudinal, population-based study of cardiovascular and cerebrovascular disease. The neuroradiologists alerted MR imaging field centers about potentially serious abnormalities. Clinical information was obtained from clinical examinations performed before MR imaging, hospital discharge summaries, and the field centers at which MR imaging was performed. RESULTS: On 3,672 image sets, 64 (1.74%) clinically serious abnormalities were found. Among the presumptive diagnoses were 19 meningiomas (0.52%), six pituitary adenomas (0.16%), five cavernous malformations (0.14%), eight vascular stenoses (0.22%), four aneurysms (0.11%), two intraventricular masses (0.05%), two subdural fluid collections (0.05%), and two other tumors (0.05%). Only nine participants with these abnormalities required surgery. All but one of the meningiomas were in women, and the prevalence of the tumor decreased with increasing age. CONCLUSION: Physicians should be alert to the possible presence of clinically serious conditions in otherwise asymptomatic elderly individuals.
Keywords: Aged; Aged, 80 and over; Brain; Brain Diseases; Cardiovascular Diseases; Cohort Studies; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male

Correlates of performance-based measures of muscle function in the elderly: the Cardiovascular Health Study. - Hirsch, C H; Fried, L P; Harris, T; Fitzpatrick, A; Enright, P; Schulz, R (J Gerontol A Biol Sci Med Sci, 1997)
BACKGROUND: It is unknown how much age-related changes in muscle performance represent normal aging versus the effects of chronic disease and life style. We examined the correlates of four performance measures-gait speed, timed chair stands (TCS), grip strength, and maximal inspiratory pressure (MIP)-using baseline data from the Cardiovascular Health Study (CHS), a population-based study of risk factors for heart disease and stroke in persons > or = age 65. METHODS: We analyzed data from the 5,201 CHS participants. Variables were arranged into nine categories: Personal Characteristics, Anthropometry, Physical Condition, Reported Functional Status, Subjective Health, Psychological Factors, Symptoms, Cognitive Status, Habits and Lifestyle, and Prevalent Disease. Independent correlates were identified using stepwise linear regression. RESULTS: The regression models explained 17.7-25.4% of the observed variability. Although age significantly correlated with each measure, it explained little of the variability (< or = 5.7%). Anthropometric features plus physical condition explained 14.0-17.4% of the variability for grip strength and MIP, but 2.8-12.9% of the variability for gait speed and the log of TCS. Subjective health and psychological factors explained 1.8-9.4% of the variability in gait speed and the log of TCS, but < or = 1.2% of the variability in grip strength and MIP. Variables for prevalent disease explained < or = 1.3% of the variability in each measure. CONCLUSIONS: After age 64, age explained little of the variability in muscle performance in a large sample of mostly functionally intact, community-dwelling older persons. Complex measures such as gait speed were more associated with subjective factors than were direct measures of strength. Prevalent disease contributed surprisingly little to muscle performance.
Keywords: Aging; Anthropometry; Cardiovascular Physiological Phenomena; Female; Gait; Hand Strength; Health Status; Humans; Male; Middle Aged; Motor Activity; Muscles; Pressure; Regression Analysis; Respiration

Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The Cardiovascular Health Study. - Lee, M; Gardin, J M; Lynch, J C; Smith, V E; Tracy, R P; Savage, P J; Szklo, M; Ward, B J (Am Heart J, 1997)
This report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak flow velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated flow-velocity curve but not for the integral of the early peak flow velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease.
Keywords: Aged; Blood Flow Velocity; Blood Pressure; Diabetes Mellitus; Echocardiography; Female; Glucose Tolerance Test; Humans; Male; Mitral Valve; Residence Characteristics; Ventricular Function, Left

Dietary assessment using a picture-sort approach. - Kumanyika, S K; Tell, G S; Shemanski, L; Martel, J; Chinchilli, V M (Am J Clin Nutr, 1997)
Food-frequency questionnaires are usually administered as a list of foods to be checked off by the respondent or interviewer. Techniques in which participants sort into categories cards on which names or pictures of foods are printed can also be used to assess food intake. Food-frequency scores were obtained from a five-category picture sort administered to 4643 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). This one-step (qualitative) assessment yielded significant associations in expected directions between frequency scores and sex, age, race or ethnicity, body mass index, and use of a special diet. In the two-step (semiquantitative) version of this instrument, an interviewer documented specific frequencies and portion-size information for the foods in each sorting category. A substudy of the two-step version with 96 CHS participants indicated relative validity similar to that of conventionally administered food-frequency questionnaires. The one-step version may be broadly applicable to situations in which general food-pattern data can be informative and cost and time limitations are great. When it is feasible, the two-step picture sort may offer certain methodologic advantages because respondents have a chance to change their responses and the format may simplify the cognitive-response task. Sorting or picture-sort procedures deserve systematic attention in research on dietary assessment methods.
Keywords: Aged; Audiovisual Aids; Diet; Female; Food; Humans; Male; Nutrition Assessment; Surveys and Questionnaires

Does the association of risk factors and atherosclerosis change with age? An analysis of the combined ARIC and CHS cohorts. The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) investigators. - Howard, G; Manolio, T A; Burke, G L; Wolfson, S K; O'Leary, D H (Stroke, 1997)
INTRODUCTION: A decrease in the estimated relative risk of cerebrovascular and cardiovascular diseases associated with known disease risk factors has been observed among elderly cohorts, perhaps suggesting that continued risk factor management in the elderly may not be as efficacious as with younger age groups. In this paper, the differential magnitude of the association of risk factors with atherosclerosis across the age spectrum from 45 years to older than 75 years is presented. METHODS: Subclinical atherosclerosis as measured by carotid ultrasonography and risk factor prevalence were assessed using similar methods among participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study and among participants 65 years and older in the Cardiovascular Health Study (CHS). Pooling these two cohorts provided data on the relationship of risk factors and atherosclerosis on nearly 19,000 participants over a broad age range. Regression analyses were used to assess the consistency of the magnitude of the association of risk factors with atherosclerosis across the age spectrum separately for black and white participants in cross-sectional analyses. RESULTS: As expected, each of the risk factors was globally (across all ages) associated with increased atherosclerosis. However, the magnitude of the association did not differ across the age spectrum for hypertension, low density lipoprotein cholesterol (LDL-c), fibrinogen, or body mass index (BMI). For whites, there was a significantly greater impact of smoking and HDL-C among older age strata but a smaller impact of diabetes. For black women, the impact of HDL-C decreased among the older age strata. CONCLUSIONS: These data suggest that most risk factors continue to be associated with increased atherosclerosis at older ages, possibly suggesting a continued value in investigation of strategies to reduce atherosclerosis by controlling risk factors at older ages.
Keywords: African Americans; African Continental Ancestry Group; Aged; Aging; Arteriosclerosis; Body Mass Index; Cardiovascular Physiological Phenomena; Cardiovascular System; Carotid Arteries; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; European Continental Ancestry Group; Female; Fibrinogen; Health Status; Humans; Hypertension; Male; Middle Aged; Regression Analysis; Risk Factors; Sex Factors; Smoking; Tunica Intima; Tunica Media; Ultrasonography

Exercise intensity and subclinical cardiovascular disease in the elderly. The Cardiovascular Health Study. - Siscovick, D S; Fried, L; Mittelmark, M; Rutan, G; Bild, D; O'Leary, D H (Am J Epidemiol, 1997)
The authors assessed the cross-sectional association between intensity of exercise in later life and coronary heart disease risk factors and subclinical disease among 2,274 men and women, 65 years of age and older, who were participants in the Cardiovascular Health Study (CHS) during 1989-1990. Subjects were free of prior clinical cardiovascular disease or impairment of physical function. Exercise intensity was characterized as low, moderate, or high, based on highest intensity exercise reported over the 2 weeks prior to the CHS baseline examination. After adjustment for age, education, and postmenopausal hormone therapy (among women), there was an inverse dose-response relationship of exercise intensity with selected risk factors. By low, moderate, and high exercise intensity, respectively: fasting insulin-men, 15.6 microU/ml, 14.1 microU/ml, and 12.6 microU/ml, p for trend <0.001; women, 14.8 microU/ml, 13.8 microU/ml, and 12.0 microU/ml, p for trend = 0.01; serum fibrinogen-men, 316.2 mg/dl, 315.4 mg/dl, and 300.0 mg/dl, p for trend = 0.01; women, 327.3 mg/dl, 317.0 mg/dl, and 310.7 mg/dl, p for trend = 0.01; lower extremity arterial disease by percent with ankle-arm index <0.9-men, 18.3, 5.5, and 3.7, p for trend = 0.01; women, 10.0, 5.7, and 2.8, p for trend = 0.02; evidence of myocardial injury by cardiac infarction/injury score (CIIS)-men, 8.0, 6.0, 3.9, p for trend <0.001; women, 4.6, 3.9, and 3.6, p for trend = 0.03. Adjustment for smoking, alcohol consumption, and total kilocalories expended in exercise altered the findings only slightly. The authors conclude that intensity of exercise in later life is associated with favorable coronary disease risk factor levels and a reduced prevalence of several markers of subclinical disease.
Keywords: Aged; Cardiovascular Diseases; Cross-Sectional Studies; Energy Metabolism; Exercise; Female; Fibrinogen; Humans; Insulin; Life Style; Longitudinal Studies; Male; Prevalence; Risk Factors

Health effects of caregiving: the caregiver health effects study: an ancillary study of the Cardiovascular Health Study. - Schulz, R; Newsom, J; Mittelmark, M; Burton, L; Hirsch, C; Jackson, S (Ann Behav Med, 1997)
We propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used and the definition of what constitutes caregiving. Samples are often recruited through self-referral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.
Keywords: Activities of Daily Living; Aged; Arousal; Cardiovascular Diseases; Caregivers; Cerebrovascular Disorders; Coronary Disease; Cost of Illness; Female; Geriatric Assessment; Health Behavior; Health Status; Humans; Male; Psychophysiologic Disorders; Risk Factors; Spouses; Stress, Psychological

Health status of individuals with mild stroke. - Duncan, P W; Samsa, G P; Weinberger, M; Goldstein, L B; Bonito, A; Witter, D M; Enarson, C; Matchar, D (Stroke, 1997)
BACKGROUND AND PURPOSE: Diminished quality of life and limitations in higher levels of physical functioning are often underestimated in stroke and are not fully captured by measures such as the Barthel Index and the Rankin Outcome Scale. This study used additional measures to assess the health status of 304 persons with mild stroke and to compare these individuals with 184 persons with transient ischemic attack and 654 persons without history of stroke/transient ischemic attack but at elevated risk for stroke (asymptomatic group). METHODS: Subjects were recruited from the Academic Medical Center Consortium (inpatients), the Cardiovascular Health Study (population-based sample of community-dwelling persons 65 years and older), and United HealthCare (inpatients and outpatients typically younger than 65 years). Subjects were interviewed by telephone or in person to assess activities of daily living (Barthel Index), depression (Center for Epidemiological Studies Depression Scale), health status (MOS-36), and utility for current health state. RESULTS: Most respondents were independent on all Barthel items. The stroke group was more impaired on the MOS-36 than the asymptomatic group but similar to the group with transient ischemic attack. Health-related quality of life was lowest for persons with stroke. While symptom status and Barthel Index score were the strongest predictors of health status, the Barthel Index showed a consistent ceiling effect when compared with the physical function subscale of the MOS-36. CONCLUSIONS: The consequences of even mild stroke affect all dimensions of health except pain. Standardized assessment of persons with stroke must evaluate across the entire continuum of health-related functions.
Keywords: Age Distribution; Aged; Cerebrovascular Disorders; European Continental Ancestry Group; Female; Health Status; Humans; Ischemic Attack, Transient; Male; Middle Aged; Social Support

Incidence of and risk factors for atrial fibrillation in older adults. - Psaty, B M; Manolio, T A; Kuller, L H; Kronmal, R A; Cushman, M; Fried, L P; White, R; Furberg, C D; Rautaharju, P M (Circulation, 1997)
BACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF. CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.
Keywords: Adult; Aged; Atrial Fibrillation; Blood Glucose; Blood Pressure; Cerebrovascular Disorders; Cohort Studies; Coronary Disease; Electrocardiography; Female; Follow-Up Studies; Hospital Records; Humans; Incidence; Male; Prospective Studies; Risk Factors; United States

Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study. - Bryan, R N; Wells, S W; Miller, T J; Elster, A D; Jungreis, C A; Poirier, V C; Lind, B K; Manolio, T A (Radiology, 1997)
PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images. MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images. RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1% (86 of 389) in the 65-69-year age group to 42.9% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5%]) than in women (631 of 2,131 [29.6%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7% (218 of 1,856) and 10.1% (187 of 1,856) of lesions, respectively. CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.
Keywords: Aged; Brain; Cardiovascular Diseases; Cerebral Infarction; Cohort Studies; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Prevalence

Knowledge of risk among patients at increased risk for stroke. - Samsa, G P; Cohen, S J; Goldstein, L B; Bonito, A J; Duncan, P W; Enarson, C; DeFriese, G H; Horner, R D; Matchar, D B (Stroke, 1997)
BACKGROUND AND PURPOSE: Patients who recognize their increased risk for stroke are more likely to engage in (and comply with) stroke prevention practices than those who do not. We describe perceived risk of stroke among a nationally diverse sample of patients at increased risk for stroke and determine whether patients' knowledge of their stroke risk varied according to patients' demographic and clinical characteristics. METHODS: Respondents were recruited from the Academic Medical Center Consortium (n = 621, five academic medical centers, inpatients of varying age); the Cardiovascular Health Study (n = 321, population-based sample of persons aged 65+ years); and United HealthCare (n = 319, five health plans, inpatients and outpatients typically younger than 65 years). The primary outcome was awareness of being at risk for stroke. RESULTS: Only 41% of respondents were aware of their increased risk for stroke (including less than one half of patients with previous minor stroke). Approximately 74% of patients who recalled being told of their increased stroke risk by a physician acknowledged this risk in comparison with 28% of patients who did not recall being informed by a physician. Younger patients, depressed patients, those in poor current health, and those with a history of TIA were most likely to be aware of their stroke risk. CONCLUSIONS: Over one half of patients at increased risk of stroke are unaware of their risk. Healthcare providers play a crucial role in communicating information about risk, and successful communication encourages adoption of stroke prevention practices. Educational messages should be targeted toward patients least likely to be aware of their risk.
Keywords: Adult; Aged; Aged, 80 and over; Awareness; Cerebrovascular Disorders; Female; Humans; Knowledge; Male; Middle Aged; Multivariate Analysis; Risk Factors

Left ventricular mass in the elderly. The Cardiovascular Health Study. - Gardin, J M; Arnold, A; Gottdiener, J S; Wong, N D; Fried, L P; Klopfenstein, H S; O'Leary, D H; Tracy, R; Kronmal, R (Hypertension, 1997)
Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Body Weight; Cardiovascular Diseases; Cohort Studies; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Male; Prospective Studies; Risk Factors; Ventricular Function, Left

Lifetime smoking exposure affects the association of C-reactive protein with cardiovascular disease risk factors and subclinical disease in healthy elderly subjects. - Tracy, R P; Psaty, B M; Macy, E; Bovill, E G; Cushman, M; Cornell, E S; Kuller, L H (Arterioscler Thromb Vasc Biol, 1997)
Blood levels of C-reactive protein (CRP), a marker of inflammation, are related to cardiovascular disease risk. To determine cross-sectional correlates in the elderly, we measured CRP in 400 men and women older than 65 years and free of clinical cardiovascular disease at baseline as part of the Cardiovascular Health Study. Only 2% of the values were greater than 10 mg/L, the cut-point usually used to identify inflammation. CRP levels appeared tightly regulated, since there were strong bivariate correlations between CRP and the following: inflammation-sensitive proteins such as fibrinogen (r = .52); measures of fibrinolysis such as plasmin-antiplasmin complex (r = .23); pack-years of smoking (r = .30); and body mass index (r = .24; all P values < or = .001). The association with pack-years was independent of the length of time since cessation of smoking. CRP levels were also associated with coagulation factors VIIc, IXc, and Xc; HDL cholesterol (negative) and triglyceride; diabetes status; diuretic use; ECG abnormalities; and level of exercise. Because of effect modification, two multiple linear regression prediction models were developed for CRP, one each for never smokers and ever smokers. An a priori physiologic model was used to guide these analyses, which disallowed the use of other inflammation-sensitive variables such as fibrinogen. In never smokers, the independent predictors were body mass index (+), diabetes status (+), plasmin-antiplasmin complex (+), and the presence of ECG abnormalities (+); this model predicted 15% of the CRP population variance. In ever smokers, the predictors were body mass index (+), plasmin-antiplasmin complex (+), pack-years of smoking (+), HDL cholesterol (-), and ankle-arm blood pressure index (-); this model predicted 42% of the population variance. We conclude that levels of CRP in the healthy elderly are tightly regulated and reflect lifetime exposure to smoking as well as level of obesity, ongoing level of fibrinolysis, diabetes status, and level of subclinical atherothrombotic disease. Moreover, exposure to smoking affects the relation of CRP to these other factors.
Keywords: Aged; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Male; Multivariate Analysis; Risk Factors; Smoking

Preventive health behaviors among spousal caregivers. - Burton, L C; Newsom, J T; Schulz, R; Hirsch, C H; German, P S (Prev Med, 1997)
BACKGROUND: The physical and emotional burden of caring for a functionally impaired spouse may adversely affect the preventive health behavior of the caregiver. This study explores the relationship between caregiving and lifestyle health behaviors and use of preventive services. METHODS: The Caregiver Health Effects Study identified spousal caregivers among a sample of more than 3,000 married, community-dwelling older persons, from four counties in the United States, who were enrollees in the Cardiovascular Health Study. High-level caregivers were defined as having a spouse with an ADL impairment (n = 212) and moderate-level caregivers, a spouse with one or more IADL impairments (n = 222). For each caregiver, a control, matched for age and gender, was selected (n = 385). Structured interviews were conducted in the home, following enrollment. RESULTS: Being a high-level caregiver significantly increased the odds of not getting enough rest, not having enough time to exercise, not having time to rest to recuperate from illness, and forgetting to take prescription medications, compared with noncaregivers. These findings did not hold for moderate-level caregivers. The odds were not significantly different for either level of caregiver compared with noncaregivers for missing meals, missing doctor appointments, missing flu shots, and not refilling medications. Larger proportions of caregivers with a strong sense of control had good preventive health behaviors, compared with caregivers with a weak sense of control.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Analysis of Variance; Caregivers; Case-Control Studies; Chi-Square Distribution; Confidence Intervals; Exercise; Female; Health Behavior; Health Status; Health Surveys; Humans; Internal-External Control; Life Style; Logistic Models; Male; Odds Ratio; Preventive Health Services; Self Care; Social Support; Spouses; United States

Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the Cardiovascular Health Study and the Rural Health Promotion Project. - Tracy, R P; Lemaitre, R N; Psaty, B M; Ives, D G; Evans, R W; Cushman, M; Meilahn, E N; Kuller, L H (Arterioscler Thromb Vasc Biol, 1997)
Markers of inflammation, such as C-reactive protein (CRP), are related to risk of cardiovascular disease (CVD) events in those with angina, but little is known about individuals without prevalent clinical CVD. We performed a prospective, nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy elderly men and women). Case subjects (n = 146 men and women with incident CVD events including angina, myocardial infarction, and death) and control subjects (n = 146) were matched on the basis of sex and the presence or absence of significant subclinical CVD at baseline (average follow-up, 2.4 years). In women but not men, the mean CRP level was higher for case subjects than for control subjects (P < or = .05). In general, CRP was higher in those with subclinical disease. Most of the association of CRP with female case subjects versus control subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P < .05, adjusted for age and time of follow-up. Case-control differences were greatest when the time between baseline and the CVD event was shortest. The strongest associations were with myocardial infarction, and there was an overall odds ratio for incident myocardial infarction for men and women with subclinical disease (upper quartile versus lower three quartiles) of 2.67 (confidence interval [CI] = 1.04 to 6.81), with the relationship being stronger in women (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a similar study in the Rural Health Promotion Project, in which mean values of CRP were higher for female case subjects than for female control subjects, but no differences were apparent for men. Comparing the upper quintile with the lower four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In conclusion, CRP was associated with incident events in the elderly, especially in those with subclinical disease at baseline.
Keywords: Aged; Aging; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Male; Prospective Studies; Sex Factors

Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. - Price, T R; Manolio, T A; Kronmal, R A; Kittner, S J; Yue, N C; Robbins, J; Anton-Culver, H; O'Leary, D H (Stroke, 1997)
BACKGROUND AND PURPOSE: Infarctlike lesions are frequently detected in symptomatic and asymptomatic older persons undergoing cerebral MRI, but their significance in older adults has not been examined. We determined the prevalence of MRI infarcts in a population-based sample of men and women aged > or = 65 years and related these findings to demographic, cognitive, and neurological status. METHODS: MRI scanning was performed in 3660 Cardiovascular Health Study (CHS) participants after brief neurological examinations and tests of cognitive function. MRIs were read centrally for the presence of an infarct > or = 3 mm in diameter or smaller infarctlike lesions. RESULTS: MRI infarcts were detected in 1131 of 3647 participants with readable infarct information (31%) and in 961 of the subgroup of 3397 participants (28%) without known prior stroke ("silent" MRI infarcts). Smaller infarctlike lesions were found in 196 of 2516 participants who had no MRI infarcts > or = 3 mm. MRI infarcts were more common in participants who were older, had prior stroke, impaired cognition, visual field deficits, slowed repetitive finger tapping (all P < .0001), weakness on toe and heel walking, and history of memory loss, coma, or migraine headaches. Multivariate analysis in those without prior stroke showed strong associations of silent MRI infarcts with older age, history of migraines, lower digit symbol scores, and more abnormalities on neurological examination. CONCLUSIONS: MRI evidence of brain infarction is common in older men and women without a clinical history of stroke. Their strong associations with impaired cognition and neurological deficits suggest that they are neither silent nor innocuous.
Keywords: Aged; Aged, 80 and over; Cerebral Infarction; Cognition; Female; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination

Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study. - Newman, A B; Enright, P L; Manolio, T A; Haponik, E F; Wahl, P W (J Am Geriatr Soc, 1997)
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.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cross-Sectional Studies; Depression; Female; Geriatric Assessment; Health Surveys; Humans; Male; Prevalence; Psychotropic Drugs; Random Allocation; Risk Factors; Sex Factors; Sleep Wake Disorders; Social Support; Surveys and Questionnaires; United States

The Sleep Heart Health Study: design, rationale, and methods. - Quan, S F; Howard, B V; Iber, C; Kiley, J P; Nieto, F J; O'Connor, G T; Rapoport, D M; Redline, S; Robbins, J; Samet, J M; Wahl, P W (Sleep, 1997)
The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.
Keywords: Adult; Aged; Aged, 80 and over; Arteriosclerosis; Cohort Studies; Coronary Disease; Female; Humans; Hypertension; Longitudinal Studies; Male; Middle Aged; Polysomnography; Positive-Pressure Respiration; Prospective Studies; Research Design; Sleep Apnea Syndromes

Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study. - Yue, N C; Arnold, A M; Longstreth, W T; Elster, A D; Jungreis, C A; O'Leary, D H; Poirier, V C; Bryan, R N (Radiology, 1997)
PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex. MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex. RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race. CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.
Keywords: Aged; Aged, 80 and over; Aging; Brain; Cardiovascular Diseases; Cerebral Ventricles; Cohort Studies; Continental Population Groups; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Reproducibility of Results; Sex Factors

Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. - Fitzpatrick, A L; Daling, J R; Furberg, C D; Kronmal, R A; Weissfeld, J L (Cancer, 1997)
BACKGROUND: The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age > or = 65 years. METHODS: Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers. RESULTS: In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08). CONCLUSIONS: Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers.
Keywords: Age Factors; Aged; Breast Neoplasms; Calcium Channel Blockers; Cohort Studies; Estrogens; Female; Humans; Postmenopause; Proportional Hazards Models; Risk Factors

Aspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group. - Kronmal, R A; Hart, R G; Manolio, T A; Talbert, R L; Beauchamp, N J; Newman, A (Stroke, 1998)
BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.
Keywords: Aged; Aspirin; Brain Ischemia; Cardiovascular Diseases; Cerebral Hemorrhage; Cerebrovascular Disorders; Cohort Studies; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Incidence; Male; Regression Analysis; Risk Factors; Sex Factors; Time Factors

Asymptomatic internal carotid artery stenosis defined by ultrasound and the risk of subsequent stroke in the elderly. The Cardiovascular Health Study. - Longstreth, W T; Shemanski, L; Lefkowitz, D; O'Leary, D H; Polak, J F; Wolfson, S K (Stroke, 1998)
BACKGROUND AND PURPOSE: We sought in this study to relate carotid ultrasound findings in asymptomatic older adults to the 5-year risk of various cerebrovascular outcomes used in the Asymptomatic Carotid Atherosclerosis Study (ACAS). METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years and older. Analyses of internal carotid artery stenosis defined by multiple different cutoffs of peak systolic velocity, rather than one particular cutoff, were performed in the 5441 participants who underwent carotid ultrasound and lacked a history of transient ischemic attack or stroke. The 5-year risks of 7 cerebrovascular disease outcomes used in ACAS were estimated for each cutoff. RESULTS: Associations with the 5-year risk of outcomes were substantially elevated only at cutoffs with high peak systolic velocities. In this population, the number of people with such high velocities was small. For example, with a cutoff of approximately 2.5 m/s, suggesting a stenosis of >70%, the 5-year risk of an ipsilateral fatal or nonfatal stroke was 5%, and only 0.5% of the group had velocities at least this high. CONCLUSIONS: In a group of older adults likely to participate in a screening program, as evidenced by willingness to participate in CHS, high peak systolic velocities consistent with high-grade carotid stenosis were uncommon and risk of subsequent cerebrovascular disease outcomes was relatively low. These findings do not suggest that similar populations of older adults would benefit from a program using ultrasound to screen for asymptomatic carotid stenosis.
Keywords: Aged; Blood Flow Velocity; Carotid Artery, Internal; Carotid Stenosis; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Male; Prevalence; Risk Factors; Systole; Ultrasonography, Doppler

Body mass index and mortality in nonsmoking older adults: the Cardiovascular Health Study. - Diehr, P; Bild, D E; Harris, T B; Duxbury, A; Siscovick, D; Rossi, M (Am J Public Health, 1998)
OBJECTIVES: This study assesses the relationship of body mass index to 5-year mortality in a cohort of 4317 nonsmoking men and women aged 65 to 100 years. METHODS: Logistic regression analyses were conducted to predict mortality as a function of baseline body mass index, adjusting for demographic, clinical, and laboratory covariates. RESULTS: There was an inverse relationship between body mass index and mortality; death rates were higher for those who weighed the least. Inclusion of covariates had trivial effects on these results. People who had lost 10% or more of their body weight since age 50 had a relatively high death rate. When that group was excluded, there was no remaining relationship between body mass index and mortality. CONCLUSIONS: The association between higher body mass index and mortality often found in middle-aged populations was not observed in this large cohort of older adults. Over-weight does not seem to be a risk factor for 5-year mortality in this age group. Rather, the risks associated with significant weight loss should be the primary concern.
Keywords: Age Distribution; Aged; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cohort Studies; Female; Humans; Logistic Models; Male; Mortality; Predictive Value of Tests; Risk Factors; Sex Distribution; Smoking; Survival Analysis; United States; Weight Loss

Brain abnormalities in the elderly: frequency and predictors in the United States (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group. - Longstreth, W T (J Neural Transm Suppl, 1998)
PURPOSE: Characterize brain abnormalities in elderly people using cranial magnetic resonance imaging (MRI). METHODS: Comprehensive lists of people 65 years and older living in the United States of America were used to obtain a representative sample of 5,888 community-dwelling participants who underwent extensive standardized evaluations. A subset of 3,660 underwent MRI. Without clinical information, neuroradiologists evaluated each scan. RESULTS: Enlarged ventricles and sulci and prominent white matter changes were relatively common, even in a subset of the healthiest participants. Infarcts 3 mm or greater were present in 31% of all participants and 28% of those without a history of stroke. Most infarcts were clinically silent, small, and in the basal ganglia. Among those without a history of stroke, white matter changes were common but mostly of a mild degree. These changes were independently related to greater age, silent stroke, higher systolic blood pressure, lower forced expiratory volume in one second and income less than $50,000 per year. Changes were also associated with dysfunction, especially of cognition and the lower extremities. CONCLUSION: MRI abnormalities are common in elderly people. Cautious interpretation is appropriate because participants are healthier than the general population and the study's design is cross-sectional.
Keywords: Aged; Brain; Brain Diseases; Cerebral Infarction; Cerebrovascular Disorders; Humans; Magnetic Resonance Imaging; United States

A brain image database for structure/function analysis. - Letovsky, S I; Whitehead, S H; Paik, C H; Miller, G A; Gerber, J; Herskovits, E H; Fulton, T K; Bryan, R N (AJNR Am J Neuroradiol, 1998)
BACKGROUND AND PURPOSE: Lesion-deficit-based structure-function analysis has traditionally been empirical and nonquantitative. Our purpose was to establish a new brain image database (BRAID) that allows the statistical correlation of brain functional measures with anatomic lesions revealed by clinical brain images. METHODS: Data on 303 participants in the MR Feasibility Study of the Cardiovascular Health Study were tested for lesion/deficit correlations. Functional data were derived from a limited neurologic examination performed at the time of the MR examination. Image data included 3D lesion descriptions derived from the MR examinations by hand segmentation. MR images were normalized in-plane using local, linear Talairach normalization. A database was implemented to support spatial data structures and associated geometric and statistical operations. The database stored the segmented lesions, patient functional scores, and several anatomic atlases. Lesion-deficit association was sought by contingency testing (chi2-test) for every possible combination of each neurologic variable and each labeled atlas structure. Significant associations that confirmed accepted lesion-deficit relationships were sought. RESULTS: Two-hundred thirty-five infarctlike lesions in 117 subjects were viewed collectively after mapping into Talairach cartesian coordinates. Anatomic structures most strongly correlated with neurologic deficits tended to be situated in anatomically appropriate areas. For example, infarctlike lesions associated with visual field defects were correlated with structures in contralateral occipital structures, including the optic radiations and occipital gyri. CONCLUSION: Known lesion-deficit correlations can be established by a database using a standard coordinate system for representing spatial data and incorporating functional and structural data together with appropriate query mechanisms. Improvements and further applications of this methodology may provide a powerful technique for uncovering new structure-function relationships.
Keywords: Brain; Brain Mapping; Cerebral Infarction; Databases as Topic; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Neurologic Examination

Caregiving from the recipient's perspective: negative reactions to being helped. - Newsom, J T; Schulz, R (Health Psychol, 1998)
This study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.
Keywords: Activities of Daily Living; Aged; Caregivers; Chronic Disease; Depression; Disabled Persons; Factor Analysis, Statistical; Female; Helping Behavior; Humans; Internal-External Control; Longitudinal Studies; Male; Regression Analysis; Self Concept; Spouses; United States

Correlates and prevalence of benzodiazepine use in community-dwelling elderly. - Gleason, P P; Schulz, R; Smith, N L; Newsom, J T; Kroboth, P D; Kroboth, F J; Psaty, B M (J Gen Intern Med, 1998)
OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older. DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study. PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria. MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7). CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.
Keywords: Aged; Aged, 80 and over; Benzodiazepines; Cross-Sectional Studies; Drug Utilization; Female; Humans; Male; Practice Patterns, Physicians'; Socioeconomic Factors

Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort. - Sakkinen, P A; Cushman, M; Psaty, B M; Kuller, L H; Bajaj, S P; Sabharwal, A K; Boineau, R; Macy, E; Tracy, R P (Thromb Haemost, 1998)
The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Antithrombin III; Biomarkers; Cross-Sectional Studies; Disease Susceptibility; Female; Humans; Lipoproteins; Male; Prevalence; Protein C; Protein S; Reference Values; Risk Factors; Thrombosis

Correlates of daytime sleepiness in 4578 elderly persons: the Cardiovascular Health Study. - Whitney, C W; Enright, P L; Newman, A B; Bonekat, W; Foley, D; Quan, S F (Sleep, 1998)
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.
Keywords: Activities of Daily Living; Age Distribution; Aged; Aged, 80 and over; Brain; Cardiovascular Diseases; Circadian Rhythm; Cognition Disorders; Cohort Studies; Continental Population Groups; Cross-Sectional Studies; Disorders of Excessive Somnolence; Electrocardiography; Female; Health Status; Health Surveys; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prevalence; Sex Distribution

Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification. - Wahl, P W; Savage, P J; Psaty, B M; Orchard, T J; Robbins, J A; Tracy, R P (Lancet, 1998)
BACKGROUND: We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people. METHODS: We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93. FINDINGS: In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001). INTERPRETATION: Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose-tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications.
Keywords: African Americans; Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Male; Prevalence; Societies, Medical; World Health Organization

Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study. - Kuller, L; Fisher, L; McClelland, R; Fried, L; Cushman, M; Jackson, S; Manolio, T (Arterioscler Thromb Vasc Biol, 1998)
A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.
Keywords: African Americans; Aged; Cardiovascular Physiological Phenomena; Cohort Studies; European Continental Ancestry Group; Female; Health Status; Humans; Male; Multivariate Analysis; Prevalence; Regression Analysis; Risk Factors; Vascular Diseases

Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study. - Cushman, M; Rosendaal, F R; Psaty, B M; Cook, E F; Valliere, J; Kuller, L H; Tracy, R P (Thromb Haemost, 1998)
Coagulation factor V Leiden is a risk marker for venous thrombosis. For arterial thrombosis no large study to date has included population-based elderly patients. The Cardiovascular Health Study is a longitudinal study of 5,201 men and women over age 65. With 3.4-year follow-up, we studied 373 incident cases of myocardial infarction (MI), angina, stroke. or transient ischemic attack (TIA), and 482 controls. The odds ratios for each event with heterozygous factor V Leiden were: MI, 0.46 (95% CI 0.17 to 1.25); angina, 1.0 (95% CI 0.45 to 2.23); stroke, 0.77 (95% CI 0.35 to 1.70): TIA, 1.33 (95% CI 0.5 to 3.55); any outcome, 0.83 (95% CI 0.48 to 1.44). Adjustment for cardiovascular risk factors did not change relationships. In older adults factor V Leiden is not a risk factor for future arterial thrombosis.
Keywords: Adult; Age Factors; Aged; Arteries; Factor V; Female; Humans; Male; Middle Aged; Mutation; Risk Factors; Thrombosis

High body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study. - Visser, M; Langlois, J; Guralnik, J M; Cauley, J A; Kronmal, R A; Robbins, J; Williamson, J D; Harris, T B (Am J Clin Nutr, 1998)
Using data from the Cardiovascular Health Study, we studied the relation between body composition (fat mass and fat-free mass, assessed by bioelectrical impedance) and self-reported, mobility-related disability (difficulty walking or stair climbing) in 2714 women and 2095 men aged 65-100 y. In a cross-sectional analysis at baseline (1989-1990), disability was reported by 26.5% of the women and 16.9% of the men. A positive association was observed between fat mass and disability. The odds ratio for disability in the highest quintile of fat mass was 3.04 (95% CI: 2.18, 4.25) for women and 2.77 (95% CI: 1.82, 4.23) for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. In a longitudinal analysis among persons not reporting disability at baseline, 20.3% of the women and 14.8% of the men reported disability 3 y later. Fat mass at baseline was predictive of disability 3 y later, with odds ratios of 2.83 (95% CI: 1.80, 4.46) for women and 1.72 (95% CI: 1.03, 2.85) for men in the highest quintile of fat. The increased risk was not explained by age, physical activity, chronic disease, or other potential confounders. Low fat-free mass was not predictive of disability. The results showed that high body fatness is an independent predictor of mobility-related disability in older men and women. These findings suggest that high body fatness in old age should be avoided to decrease the risk of disability.
Keywords: Adipose Tissue; Aged; Aged, 80 and over; Body Composition; Cross-Sectional Studies; Disability Evaluation; Female; Geriatric Assessment; Health Surveys; Humans; Male; Obesity; Predictive Value of Tests; Walking

Hypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study. - Polak, J F; Shemanski, L; O'Leary, D H; Lefkowitz, D; Price, T R; Savage, P J; Brant, W E; Reid, C (Radiology, 1998)
PURPOSE: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US). MATERIALS AND METHODS: A cohort of 4, 886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk factors: age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressure, elevated low-density lipoprotein cholesterol level. RESULTS: Incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1,42,4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (p = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36,5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28, 7.41) were associated with ipsilateral, nonfatal stroke. CONCLUSION: In asymptomatic adults aged 65 years or older, that risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%.
Keywords: Aged; Aged, 80 and over; Carotid Artery, Internal; Carotid Stenosis; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Intracranial Arteriosclerosis; Male; Proportional Hazards Models; Risk; Ultrasonography, Doppler, Duplex; Ultrasonography, Doppler, Transcranial

Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. - Longstreth, W T; Bernick, C; Manolio, T A; Bryan, N; Jungreis, C A; Price, T R (Arch Neurol, 1998)
OBJECTIVE: To identify risk factors for and functional consequences of lacunar infarct in elderly people. METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings. RESULTS: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts. CONCLUSIONS: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.
Keywords: Aged; Cerebral Infarction; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Multivariate Analysis; Risk Factors

Left ventricular diastolic filling in the elderly: the cardiovascular health study. - Gardin, J M; Arnold, A M; Bild, D E; Smith, V E; Lima, J A; Klopfenstein, H S; Kitzman, D W (Am J Cardiol, 1998)
Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Blood Flow Velocity; Cardiovascular Diseases; Cohort Studies; Diastole; Echocardiography, Doppler; Electrocardiography; Female; Health Status; Heart Ventricles; Humans; Male; Ventricular Function, Left

Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group. - Redline, S; Sanders, M H; Lind, B K; Quan, S F; Iber, C; Gottlieb, D J; Bonekat, W H; Rapoport, D M; Smith, P L; Kiley, J P (Sleep, 1998)
This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.
Keywords: Electroencephalography; Electromyography; Feasibility Studies; Humans; Licensure; Polysomnography; Research Design; Sleep Apnea Syndromes; Teaching

Predicting future years of healthy life for older adults. - Diehr, P; Patrick, D L; Bild, D E; Burke, G L; Williamson, J D (J Clin Epidemiol, 1998)
Cost-effectiveness studies often need to compare the cost of a program to the lifetime benefits of the program, but estimates of lifetime benefits are not routinely available, especially for older adults. We used data from two large longitudinal studies of older adults (ages 65-100) to estimate transition probabilities from one health state to another, and used those probabilities to estimate the mean additional years of healthy life that an older adult of specified age, sex, and health status would experience. We found, for example, that 65-year-old women in excellent health can expect 16.8 years of healthy life in the future, compared to only 8.5 years for women in poor health. We also provide estimates of discounted years of healthy life and future life expectancy. These estimates may be used to extend the effective length of the study period in cost-effectiveness studies, to examine the impact of chronic diseases or risk factors on years of healthy life, or to investigate the relationship of years of life to years of healthy life. Several applications are described.
Keywords: Aged; Aged, 80 and over; Cost-Benefit Analysis; Female; Forecasting; Health Promotion; Health Status; Humans; Life Expectancy; Life Tables; Male; Probability; Quality-Adjusted Life Years; Sex Factors

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study. - Kuller, L H; Shemanski, L; Manolio, T; Haan, M; Fried, L; Bryan, N; Burke, G L; Tracy, R; Bhadelia, R (Stroke, 1998)
BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.
Keywords: African Continental Ancestry Group; Aged; Apolipoproteins E; Brain; Cardiovascular Diseases; Cerebral Infarction; Cognition; Cognition Disorders; European Continental Ancestry Group; Female; Genotype; Health Status; Humans; Magnetic Resonance Imaging; Male; Mental Status Schedule; Polymerase Chain Reaction; Risk Factors; Sex Factors; United States

Relationship between balance and abnormalities in cerebral magnetic resonance imaging in older adults. - Tell, G S; Lefkowitz, D S; Diehr, P; Elster, A D (Arch Neurol, 1998)
BACKGROUND: Falling is a major cause of disability and morbidity among older adults. Because poor balance is a major reason for frequent falls, assessment of balance and its risk factors are important. In this study, we postulated that cerebral changes identified on magnetic resonance (MR) imaging are related to balance, and that older adults with balance problems would have significantly greater prevalence of such brain abnormalities than older adults without balance problems. DESIGN AND MEASUREMENTS: Several measures of balance were examined in more than 700 community-dwelling older men and women, blacks and whites. Balance measures included dynamic posturography, functional reach, Romberg and 1-foot stand tests, tandem stand, and 1-foot stand. Cerebral MR imaging assessments included ventricular size, sulcal widening, white matter disease, and ischemic infarctions. Cardiovascular disease and hypertension were determined and controlled for in the analyses. RESULTS: A summary of the balance measures was significantly related to each of the 4 MR imaging measures, with those with poorer balance having more disease. The strongest associations with balance were seen for white matter disease and ventricular size. All but the ischemic infarction variable remained significantly associated with balance after adjustments for sex, race, age, cardiovascular disease, and hypertension. CONCLUSION: Cerebral changes identified by MR imaging are associated with poorer balance among older adults.
Keywords: Accidental Falls; Aged; Aging; Cerebral Cortex; Female; Humans; Magnetic Resonance Imaging; Male; Postural Balance; Risk Factors

Reliability of scoring respiratory disturbance indices and sleep staging. - Whitney, C W; Gottlieb, D J; Redline, S; Norman, R G; Dodge, R R; Shahar, E; Surovec, S; Nieto, F J (Sleep, 1998)
STUDY OBJECTIVES: Unattended, home-based polysomnography (PSG) is increasingly used in both research and clinical settings as an alternative to traditional laboratory-based studies, although the reliability of the scoring of these studies has not been described. The purpose of this study is to describe the reliability of the PSG scoring in the Sleep Heart Health Study (SHHS), a multicenter study of the relation between sleep-disordered breathing measured by unattended, in-home PSG using a portable sleep monitor, and cardiovascular outcomes. DESIGN: The reliability of SHHS scorers was evaluated based on 20 randomly selected studies per scorer, assessing both interscorer and intrascorer reliability. RESULTS: Both inter- and intrascorer comparisons on epoch-by-epoch sleep staging showed excellent reliability (kappa statistics >0.80), with stage 1 having the greatest discrepancies in scoring and stage 3/4 being the most reliably discriminated. The arousal index (number of arousals per hour of sleep) was moderately reliable, with an intraclass correlation (ICC) of 0.54. The scorers were highly reliable on various respiratory disturbance indices (RDIs), which incorporate an associated oxygen desaturation in the definition of respiratory events (2% to 5%) with or without the additional use of associated EEG arousal in the definition of respiratory events (ICC>0.90). When RDI was defined without considering oxygen desaturation or arousals to define respiratory events, the RDI was moderately reliable (ICC=0.74). The additional use of associated EEG arousals, but not oxygen desaturation, in defining respiratory events did little to increase the reliability of the RDI measure (ICC=0.77). CONCLUSIONS: The SHHS achieved a high degree of intrascorer and interscorer reliability for the scoring of sleep stage and RDI in unattended in-home PSG studies.
Keywords: Humans; Polysomnography; Reproducibility of Results; Research Design; Sleep Apnea Syndromes; Sleep Stages

Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study. - Fried, L P; Kronmal, R A; Newman, A B; Bild, D E; Mittelmark, M B; Polak, J F; Robbins, J A; Gardin, J M (JAMA, 1998)
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.
Keywords: African Americans; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Female; Follow-Up Studies; Health Surveys; Humans; Male; Mortality; Proportional Hazards Models; Prospective Studies; Risk Factors; United States

The role of neuroticism and mastery in spouse caregivers' assessment of and response to a contextual stressor. - Bookwala, J; Schulz, R (J Gerontol B Psychol Sci Soc Sci, 1998)
Data from more than 300 spousal caregivers and their care recipients were analyzed to demonstrate the effects of caregivers' personality attributes--neuroticism and mastery--on their assessment of a contextual stressor (the care recipient's behavioral and functional impairment) and on their experience of distress associated with that stressor. Caregivers who were high in neuroticism and/or low in mastery reported higher levels of behavioral and functional impairment in their disabled spouse and experienced more strain and depressive symptoms associated with caregiving relative to caregivers with lower neuroticism or higher mastery scores. We further showed that the widely reported association between caregiver-assessed impairment of the care recipient and caregiver outcomes can in part be explained by caregivers' personality attributes, such as neuroticism and mastery. Our findings that caregivers' personality variables are related to their assessment of a given objective stressor and their response to a given level of stress have implications for interventions targeting caregivers and for the use of caregivers as proxy informants.
Keywords: Aged; Caregivers; Depression; Female; Humans; Male; Neurotic Disorders; Personality; Personality Assessment; Stress, Psychological

Sex differences in brain aging: a quantitative magnetic resonance imaging study. - Coffey, C E; Lucke, J F; Saxton, J A; Ratcliff, G; Unitas, L J; Billig, B; Bryan, R N (Arch Neurol, 1998)
BACKGROUND: Little is known about the effect of sex on age-related changes in brain structure. METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained. RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex. CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.
Keywords: Age Distribution; Aged; Aged, 80 and over; Aging; Atrophy; Brain; Cerebrospinal Fluid; Diagnosis, Computer-Assisted; Female; Health Status; Humans; Magnetic Resonance Imaging; Male; Regression Analysis; Sex Characteristics; Sex Distribution

Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995. - Smith, N L; Psaty, B M; Pitt, B; Garg, R; Gottdiener, J S; Heckbert, S R (Arch Intern Med, 1998)
BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown. METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed. RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26% of prevalent CHF cases were treated in 1989-1990 compared with 36% of prevalent cases in 1994-1995. This 10% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40% were using ACE inhibitors. This 2% decrease was not statistically significant (P=.68). CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.
Keywords: Aged; Angiotensin-Converting Enzyme Inhibitors; Drug Utilization; Female; Heart Failure; Humans; Logistic Models; Male; Stroke Volume; Treatment Outcome; United States

Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study. - Lemaitre, R N; Furberg, C D; Newman, A B; Hulley, S B; Gordon, D J; Gottdiener, J S; McDonald, R H; Psaty, B M (Arch Intern Med, 1998)
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.
Keywords: Aged; Anticholesteremic Agents; Cholesterol, LDL; Cohort Studies; Female; Humans; Hypercholesterolemia; Male; Prevalence; Risk Factors; United States

Utilities for major stroke: results from a survey of preferences among persons at increased risk for stroke. - Samsa, G P; Matchar, D B; Goldstein, L; Bonito, A; Duncan, P W; Lipscomb, J; Enarson, C; Witter, D; Venus, P; Paul, J E; Weinberger, M (Am Heart J, 1998)
BACKGROUND: Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward hypothetical major stroke. METHODS AND RESULTS: Respondents were obtained from the Academic Medical Center Consortium (n = 621), the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45% of respondents considered major stroke to be a worse outcome than death, 15% were willing to trade off little or no survival to avoid a major stroke. CONCLUSIONS: Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable.
Keywords: Adult; Age Distribution; Aged; Aged, 80 and over; Attitude to Health; Female; Health Status; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Quality of Life; Sex Distribution; Surveys and Questionnaires; United States

Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology. - Sakkinen, P A; Macy, E M; Callas, P W; Cornell, E S; Hayes, T E; Kuller, L H; Tracy, R P (Am J Epidemiol, 1999)
An increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have established biovariability characteristics. When biovariability data have been reported, they usually represent a short time period, and, in any case, there is little consensus on how the information should be used. The authors performed a long-term (6-month) repeated measures study on 26 healthy individuals, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVI), and between individual (CVG) variability of 12 procoagulant, fibrinolysis, and inflammation assays, including total cholesterol for comparison. The results suggest acceptable analytical variability (CVA < or = 1/2 CVI) for all assays. However, there was a large range of intraindividual variation as a proportion of total variance (2-78%), and adjusting for intraindividual and between individual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays showed a significant increase in intraindividual variation over 6 months (p < 0.05). While these findings suggest that most of these assays have biovariability characteristics similar to cholesterol, there is variation among assays. Some assays may be better suited to epidemiologic studies, and knowledge of an assay's biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.
Keywords: Adult; Aged; Analysis of Variance; Cardiovascular Diseases; Cholesterol; Epidemiology; Female; Fibrinolysis; Hemostasis; Humans; Inflammation; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Risk Factors

Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. - Newman, A B; Shemanski, L; Manolio, T A; Cushman, M; Mittelmark, M; Polak, J F; Powe, N R; Siscovick, D (Arterioscler Thromb Vasc Biol, 1999)
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.
Keywords: Age Distribution; Aged; Aged, 80 and over; Ankle; Arm; Blood Pressure Determination; Cardiovascular Diseases; Cohort Studies; Female; Humans; Hypertension; Male; Predictive Value of Tests; Risk Factors; Sex Distribution; Survival Analysis

Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997. - Smith, N L; Heckbert, S R; Bittner, V A; Savage, P J; Barzilay, J I; Dobs, A S; Psaty, B M (Diabetes Care, 1999)
OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort. RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes. RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997. CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.
Keywords: Aged; Blood Glucose; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Drug Therapy; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin; Male; Prospective Studies; Risk Factors; Time Factors; United States

Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. - Otto, C M; Lind, B K; Kitzman, D W; Gersh, B J; Siscovick, D S (N Engl J Med, 1999)
BACKGROUND: Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events. METHODS: We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke. RESULTS: There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves. CONCLUSIONS: Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.
Keywords: Aged; Angina Pectoris; Aortic Valve; Calcinosis; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Mortality; Myocardial Infarction; Prospective Studies; Risk; Risk Factors; Ultrasonography; United States; Ventricular Outflow Obstruction

Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria. - Barzilay, J I; Spiekerman, C F; Wahl, P W; Kuller, L H; Cushman, M; Furberg, C D; Dobs, A; Polak, J F; Savage, P J (Lancet, 1999)
BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%). INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.
Keywords: Age Factors; Aged; Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Fasting; Female; Glucose Intolerance; Humans; Longitudinal Studies; Male; Prospective Studies; Risk Factors; Sensitivity and Specificity; Societies, Medical; United States; World Health Organization

Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. - Schulz, R; Beach, S R (JAMA, 1999)
CONTEXT: There is strong consensus that caring for an elderly individual with disability is burdensome and stressful to many family members and contributes to psychiatric morbidity. Researchers have also suggested that the combination of loss, prolonged distress, the physical demands of caregiving, and biological vulnerabilities of older caregivers may compromise their physiological functioning and increase their risk for physical health problems, leading to increased mortality. OBJECTIVE: To examine the relationship between caregiving demands among older spousal caregivers and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline. DESIGN: Prospective population-based cohort study, from 1993 through 1998 with an average of 4.5 years of follow-up. SETTING: Four US communities. PARTICIPANTS: A total of 392 caregivers and 427 noncaregivers aged 66 to 96 years who were living with their spouses. MAIN OUTCOME MEASURE: Four-year mortality, based on level of caregiving: (1) spouse not disabled; (2) spouse disabled and not helping; (3) spouse disabled and helping with no strain reported; or(4) spouse disabled and helping with mental or emotional strain reported. RESULTS: After 4 years of follow-up, 103 participants (12.6%) died. After adjusting for sociodemographic factors, prevalent disease, and subclinical cardiovascular disease, participants who were providing care and experiencing caregiver strain had mortality risks that were 63% higher than noncaregiving controls (relative risk [RR], 1.63; 95% confidence interval [CI], 1.00-2.65). Participants who were providing care but not experiencing strain (RR, 1.08; 95 % CI, 0.61-1.90) and those with a disabled spouse who were not providing care (RR, 1.37; 95% CI, 0.73-2.58) did not have elevated adjusted mortality rates relative to the noncaregiving controls. CONCLUSIONS: Our study suggests that being a caregiver who is experiencing mental or emotional strain is an independent risk factor for mortality among elderly spousal caregivers. Caregivers who report strain associated with caregiving are more likely to die than noncaregiving controls.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Caregivers; Disabled Persons; Female; Health Status; Home Nursing; Humans; Male; Mortality; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors; Spouses; Stress, Psychological; United States

Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. - O'Leary, D H; Polak, J F; Kronmal, R A; Manolio, T A; Burke, G L; Wolfson, S K (N Engl J Med, 1999)
BACKGROUND: The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease. METHODS: Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years. RESULTS: The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point. CONCLUSIONS: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.
Keywords: Aged; Carotid Arteries; Cerebrovascular Disorders; Disease-Free Survival; Female; Humans; Incidence; Male; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Factors; Tunica Intima; Tunica Media; Ultrasonography

Cerebrovascular disease and depression symptoms in the cardiovascular health study. - Steffens, D C; Helms, M J; Krishnan, K R; Burke, G L (Stroke, 1999)
BACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study. METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score. RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions. CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.
Keywords: Activities of Daily Living; Aged; Brain; Cardiovascular Diseases; Cerebrovascular Disorders; Cross-Sectional Studies; Depression; Female; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Risk Factors

Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study. - Cushman, M; Lemaitre, R N; Kuller, L H; Psaty, B M; Macy, E M; Sharrett, A R; Tracy, R P (Arterioscler Thromb Vasc Biol, 1999)
Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group.
Keywords: Age Factors; Aged; Angina Pectoris; Biomarkers; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Follow-Up Studies; Heart Arrest; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Risk Factors

Hormone replacement therapy, inflammation, and hemostasis in elderly women. - Cushman, M; Meilahn, E N; Psaty, B M; Kuller, L H; Dobs, A S; Tracy, R P (Arterioscler Thromb Vasc Biol, 1999)
Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.
Keywords: Aged; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Estrogens; Female; Hemostasis; Hormone Replacement Therapy; Humans; Inflammation; Progestins; Random Allocation; United Kingdom; United States

Increased blood glucose and insulin, body size, and incident colorectal cancer. - Schoen, R E; Tangen, C M; Kuller, L H; Burke, G L; Cushman, M; Tracy, R P; Dobs, A; Savage, P J (J Natl Cancer Inst, 1999)
BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer. METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided. RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02). CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.
Keywords: Adipose Tissue; Aged; Blood Glucose; Body Constitution; Cholesterol, HDL; Colorectal Neoplasms; Female; Humans; Incidence; Insulin; Male; Prospective Studies; Risk; Triglycerides; Viscera

Neuroanatomic and functional correlates of depressed mood: the Cardiovascular Health Study. - Sato, R; Bryan, R N; Fried, L P (Am J Epidemiol, 1999)
Although a number of studies suggest an association between stroke and depression, few have examined the relation between magnetic resonance imaging (MRI)-identified lesions and depression among community-dwelling older adults. This cross-sectional study sought to assess the association between MRI infarcts in the basal ganglia and non-basal-ganglia areas, potential functional consequences of these lesions, and depressive symptomatology in 3,371 US men and women aged 65 years or older who participated in the Cardiovascular Health Study between 1992 and 1994. By using multiple linear regression models, the authors found that after adjustment for age, gender, and stroke history, Center for Epidemiologic Studies Depression Scale scores were independently associated with non-basal-ganglia lesions (p = 0.04) but were not independently associated with basal ganglia lesions (p = 0.11). When measures of physical disability and cognitive impairment were added to the models, these measures displaced MRI-identified infarcts in their association with depressive symptoms. In additional models, hemispheric location and size of the basal ganglia lesion were found to have no relation to depression levels. These results suggest that the functional consequences of cerebrovascular disease may be the causal pathway by which basal ganglia and non-basal-ganglia lesions are associated with depressive symptomatology.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Basal Ganglia; Cerebral Infarction; Cognition; Cross-Sectional Studies; Depression; Female; Geriatric Assessment; Humans; Linear Models; Magnetic Resonance Imaging; Male; Psychiatric Status Rating Scales; Risk Factors; United States

Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort. - White, R H; McBurnie, M A; Manolio, T; Furberg, C D; Gardin, J M; Kittner, S J; Bovill, E; Knepper, L (Am J Med, 1999)
PURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation. SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995. RESULTS: In 1995, 172 (4.1%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95% CI 0.2-1.0). CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.
Keywords: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebrovascular Disorders; Cross-Sectional Studies; Female; Humans; Logistic Models; Male; Odds Ratio; Practice Guidelines as Topic; Prospective Studies; Risk; Risk Factors; Warfarin

Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study. - Bhadelia, R A; Anderson, M; Polak, J F; Manolio, T A; Beauchamp, N; Knepper, L; O'Leary, D H (Stroke, 1999)
BACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA. METHODS: Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA. RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%; P<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima-media thickness (P=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis. CONCLUSIONS: MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.
Keywords: Aged; Brain; Cardiovascular Diseases; Cerebral Infarction; Cross-Sectional Studies; Female; Humans; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Odds Ratio; Population Surveillance; Predictive Value of Tests; Prevalence; Prospective Studies; Risk Factors; United States

Relation of education to brain size in normal aging: implications for the reserve hypothesis. - Coffey, C E; Saxton, J A; Ratcliff, G; Bryan, R N; Lucke, J F (Neurology, 1999)
OBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults. BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure. METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained. RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume. CONCLUSIONS: The authors' findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.
Keywords: Aged; Aged, 80 and over; Atrophy; Brain; Cerebral Cortex; Cerebrospinal Fluid; Educational Status; Female; Functional Laterality; Health Status; Humans; Magnetic Resonance Imaging; Male; Mental Status Schedule; Regression Analysis; Sex Characteristics

Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study. - Gottlieb, D J; Whitney, C W; Bonekat, W H; Iber, C; James, G D; Lebowitz, M; Nieto, F J; Rosenberg, C E (Am J Respir Crit Care Med, 1999)
Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.
Keywords: Aged; Cardiovascular Diseases; Cross-Sectional Studies; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Polysomnography; Respiration; Retrospective Studies; Severity of Illness Index; Sleep Apnea Syndromes; Surveys and Questionnaires

The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study. - Tracy, R P; Arnold, A M; Ettinger, W; Fried, L; Meilahn, E; Savage, P (Arterioscler Thromb Vasc Biol, 1999)
Little is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.
Keywords: Aged; Cardiovascular Diseases; Factor VII; Factor VIII; Female; Fibrinogen; Humans; Male; Multivariate Analysis; Risk Factors

Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women. - Sakkinen, P A; Cushman, M; Psaty, B M; Rodriguez, B; Boineau, R; Kuller, L H; Tracy, R P (Arterioscler Thromb Vasc Biol, 1999)
Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, </=0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P</=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.
Keywords: Aged; Aged, 80 and over; alpha-2-Antiplasmin; Antifibrinolytic Agents; Asian Continental Ancestry Group; Cohort Studies; Coronary Disease; Diabetes Mellitus, Type 2; European Continental Ancestry Group; Female; Fibrinolysin; Fibrinolysis; Humans; Insulin Resistance; Male; Multivariate Analysis; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Risk Factors

Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group. - Manolio, T A; Burke, G L; O'Leary, D H; Evans, G; Beauchamp, N; Knepper, L; Ward, B (Arterioscler Thromb Vasc Biol, 1999)
Cerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3%) and measurable carotid plaque in 2745 (75.3%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis.
Keywords: Aged; Arteriosclerosis; Brain; Cardiovascular System; Carotid Artery Diseases; Cerebral Infarction; Cohort Studies; Cross-Sectional Studies; Echoencephalography; Female; Health Status; Humans; Magnetic Resonance Imaging; Male; Prevalence

The reliability of medication inventory methods compared to serum levels of cardiovascular drugs in the elderly. - Smith, N L; Psaty, B M; Heckbert, S R; Tracy, R P; Cornell, E S (J Clin Epidemiol, 1999)
Medication inventory is more reliable than self-report in assessing prescription drug use in elderly populations. It is not known how strongly medication inventory reflects actual medication use as measured by serum drug levels. In the Cardiovascular Health Study, medication data were collected annually by study interviewers from medication containers brought to the clinic visit. At the fourth clinic visit, venipuncture was performed under 12-hour fasting conditions. Participants were told to take medications as usual. Based on medication inventory results, we randomly selected 55 users and 55 non-users of four cardiovascular drugs: aspirin, propranolol, hydrochlorothiazide, and digoxin. All 110 blood samples for each of the four drugs were analyzed; cut points were based on detectable levels given laboratory limitations. Kappa statistics (K) tested degree of agreement between medication inventory findings and serum detection. Assays were completed on 400 samples (91%). Agreement for aspirin (n=102) was poor: K=0.16 (95% CI: 0.0-0.32). Agreement for propranolol (n = 98) was fair: K=0.43 (95% CI: 0.27-0.59). Agreement for hydrochlorothiazide (n=100) was good: K=0.62 (95% CI: 0.53-0.91). Agreement for digoxin (n=100) was excellent: K=0.94 (95% CI: 0.74-1.0). For four all drugs, lack of agreement was confined primarily to participants who reported use but did not have detectable levels. Excluding aspirin users, only one non-user (0.7%) had drug detected in serum. The medication inventory is a reasonably sensitive and a fairly reliable method for ascertaining non-aspirin cardiovascular drug use in the elderly even though this method may overestimate use as assessed by serum level.
Keywords: Aged; Aspirin; Cardiovascular Agents; Digoxin; Humans; Hydrochlorothiazide; Patient Compliance; Propranolol; Reproducibility of Results

The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. - Haan, M N; Shemanski, L; Jagust, W J; Manolio, T A; Kuller, L (JAMA, 1999)
CONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD. OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline. DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study. SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively. MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus. RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele. CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.
Keywords: Aged; Aging; Alleles; Apolipoproteins E; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Diabetes Mellitus; Genotype; Humans; Mental Status Schedule; Prospective Studies; Risk Factors

Stability and change in older adults' social contact and social support: the Cardiovascular Health Study. - Martire, L M; Schulz, R; Mittelmark, M B; Newsom, J T (J Gerontol B Psychol Sci Soc Sci, 1999)
OBJECTIVES: The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life. METHODS: Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time. RESULTS: Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time. DISCUSSION: The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.
Keywords: Age Factors; Aged; Aged, 80 and over; Cross-Sectional Studies; Educational Status; Family; Female; Health Status; Humans; Interpersonal Relations; Linear Models; Longitudinal Studies; Male; Predictive Value of Tests; Sex Factors; Social Support; Socioeconomic Factors; Surveys and Questionnaires; Time Factors; United States

Stroke risk in an elderly population with atrial fibrillation. - Feinberg, W M; Kronmal, R A; Newman, A B; Kraut, M A; Bovill, E G; Cooper, L; Hart, R G (J Gen Intern Med, 1999)
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.
Keywords: Aged; Atrial Fibrillation; Cerebrovascular Disorders; Cohort Studies; Humans; Male; Poisson Distribution; Proportional Hazards Models; Risk Factors

Survival versus years of healthy life: which is more powerful as a study outcome? - Diehr, P; Patrick, D L; Burke, G L; Williamson, J (Control Clin Trials, 1999)
Studies of interventions that are intended to improve patients' health are often evaluated with survival as the primary outcome, even when a measure adjusted for quality of survival, such as years of healthy life (YHL), would seem more appropriate. The purpose of this article is to determine whether studies based on survival are more or less powerful than studies based on YHL in clinical trials where either measure might be appropriate. We used data from the Cardiovascular Health Study (CHS) to estimate the sample size that would be needed in studies of 156 different health conditions, for the two outcome measures. The median sample size for a 5-year study was 687 if survival was the endpoint and 484 for YHL. YHL usually required lower sample sizes than survival, although survival was more powerful for some health conditions. We also found that lengthy studies, and studies with many follow-up measures per person, did not have appreciably higher power than less intensive studies. We conclude that clinical investigations in which the goal is to improve health may often be performed more efficiently with YHL rather than survival as the primary outcome measure. Such studies can be short in duration, with relatively few measures per person of health status.
Keywords: Aged; Angina Pectoris; Female; Follow-Up Studies; Health Status; Humans; Life Expectancy; Male; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Research Design; Sample Size; Survival Analysis; Time Factors; Treatment Outcome

Temporal trends in the use of anticoagulants among older adults with atrial fibrillation. - Smith, N L; Psaty, B M; Furberg, C D; White, R; Lima, J A; Newman, A B; Manolio, T A (Arch Intern Med, 1999)
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.
Keywords: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Therapy; Electrocardiography; Female; Humans; Incidence; Male; Prevalence; Treatment Outcome; Warfarin

Traditional risk factors and subclinical disease measures as predictors of first myocardial infarction in older adults: the Cardiovascular Health Study. - Psaty, B M; Furberg, C D; Kuller, L H; Bild, D E; Rautaharju, P M; Polak, J F; Bovill, E; Gottdiener, J S (Arch Intern Med, 1999)
BACKGROUND: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease. METHODS: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model. RESULTS: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women. CONCLUSIONS: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.
Keywords: Age Distribution; Aged; Female; Follow-Up Studies; Humans; Incidence; Male; Multivariate Analysis; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk; Risk Factors; Sex Distribution

Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group. - Enright, P L; McClelland, R L; Newman, A B; Gottlieb, D J; Lebowitz, M D (Chest, 1999)
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.
Keywords: Age Factors; Aged; Aged, 80 and over; Asthma; Female; Humans; Male; Peak Expiratory Flow Rate; Quality of Life; Risk Factors; Spirometry; Vital Capacity

Association between depression and mortality in older adults: the Cardiovascular Health Study. - Schulz, R; Beach, S R; Ives, D G; Martire, L M; Ariyo, A A; Kop, W J (Arch Intern Med, 2000)
BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.
Keywords: Aged; Alcohol Drinking; Depression; Depressive Disorder; Female; Health Status Indicators; Humans; Male; Motivation; Prevalence; Risk Factors; Smoking; Socioeconomic Factors; United States

Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. - Nieto, F J; Young, T B; Lind, B K; Shahar, E; Samet, J M; Redline, S; D'Agostino, R B; Newman, A B; Lebowitz, M D; Pickering, T G (JAMA, 2000)
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.
Keywords: Adult; Aged; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Logistic Models; Male; Middle Aged; Obesity; Polysomnography; Sleep Apnea Syndromes; Snoring

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study. - Siscovick, D S; Schwartz, S M; Corey, L; Grayston, J T; Ashley, R; Wang, S P; Psaty, B M; Tracy, R P; Kuller, L H; Kronmal, R A (Circulation, 2000)
BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (</=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4). CONCLUSIONS: Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.
Keywords: Adult; Age Factors; Aged; Antibodies, Bacterial; Antibodies, Viral; Case-Control Studies; Chlamydophila pneumoniae; Coronary Disease; Cytomegalovirus; Female; Herpesvirus 1, Human; HIV Antibodies; Humans; Immunoglobulin G; Male; Myocardial Infarction; Risk Factors

Clinical correlates of ventricular and sulcal size on cranial magnetic resonance imaging of 3,301 elderly people. The Cardiovascular Health Study. Collaborative Research Group. - Longstreth, W T; Arnold, A M; Manolio, T A; Burke, G L; Bryan, N; Jungreis, C A; O'Leary, D; Enright, P L; Fried, L (Neuroepidemiology, 2000)
To identify potential risk factors for and clinical manifestations of ventricular and sulcal enlargement on cranial magnetic resonance imaging (MRI), 3,301 community-dwelling people 65 years or older without a history of stroke or transient ischemic attack underwent extensive standardized evaluations and MRI. In the multivariate model, increased age and white matter grade on MRI were the dominant risk factors for ventricular and sulcal grade. For ventricular grade, other than race, for which non-Blacks had higher grades, models for men and women shared no other factors. For sulcal grades, models for men and women shared variables reflecting cigarette smoking and diabetes. Clinical features were correlated more strongly with ventricular than sulcal grade and more strongly for women than men. Significant age-adjusted correlations between ventricular grade and the Digit-Symbol Substitution Test were found for men and women. Prospective studies will be needed to extend findings of this cross-sectional analysis.
Keywords: Age Distribution; Age Factors; Aged; Aging; Cerebral Ventricles; Continental Population Groups; Cross-Sectional Studies; Diabetes Complications; Female; Humans; Hypertrophy; Linear Models; Magnetic Resonance Imaging; Male; Multivariate Analysis; Risk Factors; Severity of Illness Index; Sex Distribution; Sex Factors; Smoking; Stroke

Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. - Sakkinen, P A; Wahl, P; Cushman, M; Lewis, M R; Tracy, R P (Am J Epidemiol, 2000)
The known metabolic cardiovascular disease risk factors associated with insulin resistance syndrome (IRS) do not adequately explain the excess cardiovascular disease risk attributed to this syndrome, and abnormalities in hemostatic variables may contribute to this excess risk. Using data from 322 nondiabetic elderly men and women (aged 65-100 years) participating in the Cardiovascular Health Study during 1989-1990, the authors performed factor analysis on 10 metabolic risk factors associated with IRS and 11 procoagulation, inflammation, and fibrinolysis variables to examine the clustering of the metabolic and hemostatic risk markers. Factor analysis of the metabolic variables confirmed four uncorrelated factors: body mass, insulin/glucose, lipids, and blood pressure. Adding the hemostatic variables yielded three new factors interpreted as inflammation, vitamin K-dependent proteins, and procoagulant activity. Plasminogen activator inhibitor-1 clustered with the body mass factor, supporting the hypothesis that obesity is related to impaired fibrinolysis. Fibrinogen clustered with the inflammation summary factor rather than procoagulant activity, supporting the position that fibrinogen principally reflects underlying inflammation rather than procoagulant potential. The authors conclude that should hemostatic variables be shown to contribute to IRS-related cardiovascular disease, apart from plasminogen activator inhibitor-1, they may do so independently of the established metabolic abnormalities.
Keywords: Aged; Aged, 80 and over; Antigens; Blood Coagulation; Cardiovascular Diseases; Cluster Analysis; Factor Analysis, Statistical; Factor VII; Female; Fibrinogen; Fibrinolysis; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Risk Factors

Cognitive test performance and presence of subclinical cardiovascular disease in the cardiovascular health study. - Saxton, J; Ratcliff, G; Newman, A; Belle, S; Fried, L; Yee, J; Kuller, L (Neuroepidemiology, 2000)
The purpose of the present study was to investigate the relationship between performance on a comprehensive battery of neuropsychological tests and the presence of clinical, subclinical or no cardiovascular disease in an elderly community-dwelling population. The results confirm previous reports of significant associations of age, education and gender with test performance. When performance was examined controlling for these variables, significant associations of disease group were seen with five measures emphasizing speed of performance; Parts A and B of the Trail Making Test, the WAIS-R Digit Symbol and Block Design subtests and category verbal fluency. These results add to the evidence that, in addition to other health implications, cardiovascular disease is related to cognitive functioning in the elderly even at subclinical levels.
Keywords: Aged; Cardiovascular Diseases; Cognition Disorders; Female; Humans; Hypertension; Male; Severity of Illness Index; Wechsler Scales

A comparison of primary stressors, secondary stressors, and depressive symptoms between elderly caregiving husbands and wives: the Caregiver Health Effects Study. - Bookwala, J; Schulz, R (Psychol Aging, 2000)
The present study examined gender differences in the experience of primary and secondary caregiving stressors, depressive symptoms, and their interrelationships using a sample of 283 elderly spouse caregivers (145 women, 138 men). Two primary stressors, two secondary stressors, and depressive symptoms were assessed. In general, t-tests indicated that caregiving husbands experience fewer stressors and depressive symptoms than their female counterparts. Multiple group analysis revealed that the primary stressors were more useful in explaining variance associated with the secondary stressors for women than men and that the path coefficients linking amount of caregiving assistance to caregivers' activity restriction was significantly different across men and women. Other paths linking primary stressors, secondary stressors, and depressive symptoms, however, were statistically equivalent across men and women. Hence, although caregiving women and men may vary in their reports of caregiving stressors, the complexity of the caregiving experience appears to be quite uniform for both groups.
Keywords: Aged; Aging; Caregivers; Depressive Disorder; Female; Health Status; Humans; Male; Spouses; Stress, Psychological

Coronary artery calcification in older adults with minimal clinical or subclinical cardiovascular disease. - Newman, A B; Naydeck, B; Sutton-Tyrrell, K; Edmundowicz, D; Gottdiener, J; Kuller, L H (J Am Geriatr Soc, 2000)
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.
Keywords: Aged; Aging; Analysis of Variance; Calcinosis; Cardiovascular Diseases; Chi-Square Distribution; Coronary Artery Disease; Coronary Disease; Female; Humans; Male; Risk Factors; Statistics, Nonparametric; Tomography, X-Ray Computed

Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group. - Newman, A B; Spiekerman, C F; Enright, P; Lefkowitz, D; Manolio, T; Reynolds, C F; Robbins, J (J Am Geriatr Soc, 2000)
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.
Keywords: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Female; Health Status; Heart Failure; Humans; Incidence; Male; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Risk Factors; Sex Factors; Sleep Apnea Syndromes; Sleep Stages; Sleep Wake Disorders; Snoring; Surveys and Questionnaires; United States

Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group. - Ariyo, A A; Haan, M; Tangen, C M; Rutledge, J C; Cushman, M; Dobs, A; Furberg, C D (Circulation, 2000)
BACKGROUND: Several epidemiological studies have associated depressive symptoms with cardiovascular disease. We investigated whether depressive symptoms constituted a risk for coronary heart disease (CHD) and total mortality among an apparently healthy elderly cohort. METHODS AND RESULTS: In a prospective cohort of 5888 elderly Americans (>/=65 years) who were enrolled in the Cardiovascular Health Study, 4493 participants who were free of cardiovascular disease at baseline provided annual information on their depressive status, which was assessed using the Depression Scale of the Center for Epidemiological Studies. These 4493 subjects were followed for 6 years for the development of CHD and mortality. The cumulative mean depression score was assessed for each participant up to the time of event (maximum 6-year follow-up). Using time-dependent, proportional-hazards models, the unadjusted hazard ratio associated with every 5-unit increase in mean depression score for the development of CHD was 1.15 (P:=0.006); the ratio for all-cause mortality was 1.29 (P:<0.0001). In multivariate analyses adjusted for age, race, sex, education, diabetes, hypertension, cigarette smoking, total cholesterol, triglyceride level, congestive heart failure, and physical inactivity, the hazard ratio for CHD was 1.15 (P:=0.006) and that for all-cause mortality was 1.16 (P:=0.006). Among participants with the highest cumulative mean depression scores, the risk of CHD increased by 40% and risk of death by 60% compared with those who had the lowest mean scores. CONCLUSIONS: Among elderly Americans, depressive symptoms constitute an independent risk factor for the development of CHD and total mortality.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Coronary Disease; Depression; Female; Humans; Male; Prospective Studies; Risk Factors; United States

Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality. - Kuller, L H; Velentgas, P; Barzilay, J; Beauchamp, N J; O'Leary, D H; Savage, P J (Arterioscler Thromb Vasc Biol, 2000)
Previously diagnosed diabetes mellitus, newly diagnosed diabetes mellitus, and impaired glucose tolerance are important determinants of the risk of clinical cardiovascular disease (CVD). We have evaluated the relation of patients with subclinical CVD, diabetes, and impaired glucose tolerance and "normal" subjects and the risk of clinical CVD in the Cardiovascular Health Study. Diabetes (1343), impaired glucose tolerance (1433), and normal (2421) were defined by World Health Organization criteria at baseline in 1989 to 1990. The average follow-up was 6.4 years (mean age 73 years). Diabetics had a higher prevalence of clinical and subclinical CVD at baseline. Compared with diabetes in the absence of subclinical disease, the presence of subclinical CVD and diabetes was associated with significant increased adjusted relative risk of death (1.5, CI 0.93 to 2.41), relative risk of incident coronary heart disease (1.99, CI 1.25 to 3.19), and incident myocardial infarction (1.93, CI 0.96 to 3.91). The risk of clinical events was greater for participants with a history of diabetes compared with newly diagnosed diabetics at baseline. Compared with nondiabetic nonhypertensive subjects without subclinical disease, patients with a combination of diabetes, hypertension, and subclinical disease had a 12-fold increased risk of stroke. Fasting blood glucose levels were a weak predictor of incident coronary heart disease as were most other risk factors. Subclinical CVD was the primary determinant of clinical CVD among diabetics in the Cardiovascular Health Study.
Keywords: Aged; Arteriosclerosis; Coronary Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Incidence; Male; Multivariate Analysis; Myocardial Infarction; Prevalence; Proportional Hazards Models; Risk Factors; Sex Distribution; Stroke

Does snoring predict sleepiness independently of apnea and hypopnea frequency? - Gottlieb, D J; Yao, Q; Redline, S; Ali, T; Mahowald, M W (Am J Respir Crit Care Med, 2000)
Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.
Keywords: Adult; Aged; Arousal; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Polysomnography; Risk Factors; Sleep Apnea, Obstructive; Snoring; Wakefulness

Effects of varying approaches for identifying respiratory disturbances on sleep apnea assessment. - Redline, S; Kapur, V K; Sanders, M H; Quan, S F; Gottlieb, D J; Rapoport, D M; Bonekat, W H; Smith, P L; Kiley, J P; Iber, C (Am J Respir Crit Care Med, 2000)
Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.
Keywords: Adult; Aged; Aged, 80 and over; Arousal; Diagnosis, Differential; Female; Humans; Lung Volume Measurements; Male; Middle Aged; Observer Variation; Oxygen; Oxyhemoglobins; Polysomnography; Risk Factors; Sleep Apnea Syndromes

Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study. - Luoto, R; Manolio, T; Meilahn, E; Bhadelia, R; Furberg, C; Cooper, L; Kraut, M (J Am Geriatr Soc, 2000)
OBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women. DESIGN: A population-based prospective study (Cardiovascular Health Study). SETTING: Four regions in the United States. PARTICIPANTS: A total of 2133 (62.9% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994. MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (> or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates. RESULTS: Current use of ERT was reported by 15% and past use by another 23% of participants; 35% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE. CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear.
Keywords: Aged; Aged, 80 and over; Atrophy; Brain; Brain Infarction; Estrogen Replacement Therapy; Female; Humans; Intelligence Tests; Life Style; Magnetic Resonance Imaging; Population Surveillance; Prevalence; Prospective Studies; Social Class; United States

Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction. - Yaffe, K; Haan, M; Byers, A; Tangen, C; Kuller, L (Neurology, 2000)
OBJECTIVE: APOE-epsilon4 increases the risk of cognitive decline, while elderly women who take estrogen may have less risk of cognitive decline. The authors sought to determine whether estrogen use modifies the association between APOE-epsilon4 and cognitive decline. METHOD: - As part of the Cardiovascular Health Study, 3,393 Medicare-eligible women (> or =65 years) were randomly selected and recruited from Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Pittsburgh, PA. Cognitive testing was administered annually; the authors studied the 2,716 women with cognitive testing on > or =2 visits. They analyzed change in score on the Modified Mini-Mental State Examination (3MS) as a function of estrogen use, APOE genotype, and baseline common and internal carotid artery wall thickening. RESULTS: A total of 297 (11%) women were current estrogen users and 336 (12%) were past estrogen users. Over the 6-year average follow-up, baseline current users declined 1.5 points on the 3MS whereas never users declined 2.7 points (p = 0.023). Compared with epsilon4-negative women, epsilon4-positive women had a greater adjusted hazard ratio of cognitive impairment (3MS < 80), hazard risk [HR] = 1.47; 95% CI, 1.13 to 1.90. There was an interaction between estrogen use and epsilon4 presence (p = 0.037). Among epsilon4-negative women, current estrogen use reduced the risk of adjusted cognitive impairment compared with never users by almost half (HR = 0.59; 95% CI, 0.36 to 0.99), whereas, it did not reduce the risk among epsilon4-positive women (current use, HR = 1.33; 95% CI, 0.74 to 2.42). Compared with never use, current estrogen use was associated with less internal and common carotid wall thickening in epsilon4-negative women but not in epsilon4-positive women (p for interaction < 0.05 for both). Differences remained after adjusting for age, education, race, and stroke. CONCLUSIONS: Estrogen use was associated with less cognitive decline among epsilon4-negative women but not epsilon4-positive women. Potential mechanisms, including carotid atherosclerosis, by which epsilon4 may interact with estrogen and cognition warrant further investigation.
Keywords: Aged; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Carotid Stenosis; Estrogen Replacement Therapy; Female; Genotype; Humans; Mental Status Schedule; Neuropsychological Tests; Risk Factors

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. - Pietropaolo, M; Barinas-Mitchell, E; Pietropaolo, S L; Kuller, L H; Trucco, M (Diabetes, 2000)
In light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.
Keywords: Aged; Aged, 80 and over; Aging; Autoantibodies; Autoantigens; Autoimmunity; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Fibrinogen; Glucose Tolerance Test; Glutamate Decarboxylase; Humans; Islets of Langerhans; Male; Membrane Proteins; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 8

Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study. - Beach, S R; Schulz, R; Yee, J L; Jackson, S (Psychol Aging, 2000)
Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.
Keywords: Aged; Anxiety; Caregivers; Depression; Disabled Persons; Female; Health Behavior; Health Status; Humans; Longitudinal Studies; Male; Mental Health; Risk-Taking; Spouses

Normative data on the Boston Naming Test and two equivalent 30-item short forms. - Saxton, J; Ratcliff, G; Munro, C A; Coffey, E C; Becker, J T; Fried, L; Kuller, L (Clin Neuropsychol, 2000)
Because of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer's disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Female; Humans; Male; Neuropsychological Tests; Population Surveillance; Reference Values

Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. - Gottdiener, J S; Arnold, A M; Aurigemma, G P; Polak, J F; Tracy, R P; Kitzman, D W; Gardin, J M; Rutledge, J E; Boineau, R C (J Am Coll Cardiol, 2000)
OBJECTIVES: We sought to characterize the predictors of incident congestive heart failure (CHF), as determined by central adjudication, in a community-based elderly population. BACKGROUND: The elderly constitute a growing proportion of patients admitted to the hospital with CHF, and CHF is a leading source of morbidity and mortality in this group. Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of 5,888 elderly people >65 years old (average 73 +/- 5, range 65 to 100) at four locations. Multiple laboratory measures of cardiovascular structure and function, blood chemistries and functional assessments were obtained. RESULTS: During an average follow-up of 5.5 years (median 6.3), 597 participants developed incident CHF (rate 19.3/1,000 person-years). The incidence of CHF increased progressively across age groups and was greater in men than in women. On multivariate analysis, other independent predictors included prevalent coronary heart disease, stroke or transient ischemic attack at baseline, diabetes, systolic blood pressure (BP), forced expiratory volume 1 s, creatinine >1.4 mg/dl, C-reactive protein, ankle-arm index <0.9, atrial fibrillation, electrocardiographic (ECG) left ventricular (LV) mass, ECG ST-T segment abnormality, internal carotid artery wall thickness and decreased LV systolic function. Population-attributable risk, determined from predictors of risk and prevalence, was relatively high for prevalent coronary heart disease (13.1%), systolic BP > or =140 mm Hg (12.8%) and a high level of C-reactive protein (9.7%), but was low for subnormal LV function (4.1%) and atrial fibrillation (2.2%). CONCLUSIONS: The incidence of CHF is high in the elderly and is related mainly to age, gender, clinical and subclinical coronary heart disease, systolic BP and inflammation. Despite the high relative risk of subnormal systolic LV function and atrial fibrillation, the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people.
Keywords: Aged; Aged, 80 and over; Coronary Disease; Female; Geriatric Assessment; Heart Failure; Humans; Ischemic Attack, Transient; Male; Prospective Studies; Risk Factors; Survival Rate

Prevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly. - Sheifer, S E; Gersh, B J; Yanez, N D; Ades, P A; Burke, G L; Manolio, T A (J Am Coll Cardiol, 2000)
OBJECTIVES: This study was designed to determine the prevalence of unrecognized myocardial infarction (UMI), as well as risk factors, and to compare prognosis after detection of previously UMI to that after recognized myocardial infarction (RMI). BACKGROUND: Past studies revealed that a significant proportion of MIs escape recognition, and that prognosis after such events is poor, but the epidemiology of UMI has not been reassessed in the contemporary era. METHODS: The Cardiovascular Health Study (CHS) database, composed of individuals > or =65, was queried for participants who, at entry, demonstrated electrocardiographic evidence of a prior Q-wave MI, but who lacked a history of this diagnosis. The features and outcomes of this group were compared to those of individuals with prevalent RMI. RESULTS: Of 5,888 participants, 901 evidenced a past MI, and 201 (22.3%) were previously unrecognized. The independent predictors of UMI were the absence of angina and the absence of congestive heart failure (CHF). Six-year mortality did not significantly differ between the two groups. CONCLUSIONS: 1) In the elderly, UMI continues to represent a significant proportion of all MIs; 2) associations with angina and CHF may reflect complex neurological issues, but they also may represent diagnosis bias; 3) these individuals can otherwise not be distinguished from those with recognized infarctions; and 4) mortality rates after UMI and RMI are similar. Future studies should address screening for UMI, risk stratification after detection of previously UMI, and the role of standard post-MI therapies.
Keywords: Aged; Cause of Death; Coronary Disease; Cross-Sectional Studies; Databases, Factual; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Prognosis; Risk Factors; Stroke; Survival Rate

Race- and sex-specific ECG models for left ventricular mass in older populations. Factors influencing overestimation of left ventricular hypertrophy prevalence by ECG criteria in African-Americans. - Rautaharju, P M; Park, L P; Gottdiener, J S; Siscovick, D; Boineau, R; Smith, V; Powe, N R (J Electrocardiol, 2000)
The validity of the reported high prevalence of left ventricular hypertrophy (LVH) among African-American men and women has been questioned owing to conflicting echocardiographic evidence. We used echocardiographic left ventricular mass (LVM) from M-mode measurements to evaluate associations between LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and African-American men and women 65 years of age and older who were participants of the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were substantially higher in African-Americans, with apparent LVH prevalence 2 to 3 times higher in African American men and women than in white men and women, although there was no significant racial difference in echocardiographic LVM. The higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men is in part owing to smaller lateral chest diameter. In women, reasons for racial differences in ECG LVH prevalence remain largely unexplained although a small part of the excess LVH in African-American women by the Sokolow-Lyon criteria appears to be owing to a larger lateral chest semidiameter in white women. ECG variables alone were too inaccurate for LVM prediction, and it was necessary to incorporate in all ECG models body weight that was properly adjusted for race and sex. This resulted in modest LVM prediction accuracy, with R-square values ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM estimation with an appropriate adjustment for body size differences are expected to facilitate evaluation of LVH status in contrasting racial population groups.
Keywords: African Continental Ancestry Group; Age Factors; Aged; Anthropometry; Electrocardiography; European Continental Ancestry Group; Female; Humans; Hypertrophy, Left Ventricular; Male; Predictive Value of Tests; Prevalence; Sex Factors; Ultrasonography

Rates of sensor loss in unattended home polysomnography: the influence of age, gender, obesity, and sleep-disordered breathing. - Kapur, V K; Rapoport, D M; Sanders, M H; Enright, P; Hill, J; Iber, C; Romaniuk, J (Sleep, 2000)
OBJECTIVES: To evaluate study failure and sensor loss in unattended home polysomnography and their relationship to age, gender, obesity, and severity of sleep-disordered breathing (SDB). DESIGN: A cross-sectional analysis of data gathered prospectively for the Sleep Heart Health Study (SHHS). SETTING: Unattended polysomnography was performed in participants' homes by the staff of the sites that are involved in SHHS. PARTICIPANTS: 6,802 individuals who met the inclusion criteria (age >40 years, no history of treatment of sleep apnea, no tracheostomy, no current home oxygen therapy) for SHHS. RESULTS: A total of 6802 participants had 7151 studies performed. 6161 of 6802 initial studies (90.6%) were acceptable. Obesity was associated with a decreased likelihood of a successful initial study. After one or more attempts, 6440 participants (94.7%) had studies that were judged as acceptable. The mean duration of scorable signals for specific channels ranged from 5.7 to 6.8 hours. The magnitudes of the effects of age, gender, BMI, and RDI on specific signal durations were not clinically significant. CONCLUSION: Unattended home PSG as performed for SHHS was usually successful. Participant characteristics had very weak associations with duration of scorable signal. This study suggests that unattended home PSG, when performed with proper protocols and quality controls, has reasonable success rates and signal quality for the evaluation of SDB in clinical and research settings.
Keywords: Age Factors; Cross-Sectional Studies; Electroencephalography; Electromyography; Electrooculography; Equipment Failure; Female; Humans; Male; Middle Aged; Obesity; Polysomnography; Prospective Studies; Severity of Illness Index; Sex Factors; Sleep Apnea Syndromes

Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population. - Bleyer, A J; Shemanski, L R; Burke, G L; Hansen, K J; Appel, R G (Kidney Int, 2000)
BACKGROUND: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population. METHODS: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase. RESULTS: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness. CONCLUSIONS: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.
Keywords: African Continental Ancestry Group; Aged; Aging; Cohort Studies; Creatinine; European Continental Ancestry Group; Female; Humans; Hypertension; Kidney; Male; Regression Analysis; Retrospective Studies; Risk Factors; Smoking; Vascular Diseases

Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study. - Mukamal, K J; Longstreth, W T; Mittleman, M A; Crum, R M; Siscovick, D S (Stroke, 2001)
BACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings. METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics. RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007). CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.
Keywords: Aged; Aging; Alcohol Drinking; Atrophy; Brain; Brain Diseases; Cerebral Infarction; Comorbidity; Demography; Female; Health Surveys; Humans; Logistic Models; Longitudinal Studies; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Odds Ratio; Prospective Studies; Sensitivity and Specificity; United States

Area characteristics and individual-level socioeconomic position indicators in three population-based epidemiologic studies. - Diez-Roux, A V; Kiefe, C I; Jacobs, D R; Haan, M; Jackson, S A; Nieto, F J; Paton, C C; Schulz, R (Ann Epidemiol, 2001)
PURPOSE: There is growing interest in incorporating area indicators into epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual-level data from three epidemiologic studies, we investigated how different area indicators are interrelated, how measures for different sized areas compare, and the relation between area and individual-level social position indicators. METHODS: The interrelations between 13 area indicators of wealth/income, education, occupation, and other socioenvironmental characteristics were investigated using correlation coefficients and factor analyses. The extent to which block-group measures provide information distinct from census tract measures was investigated using intraclass correlation coefficients. Loglinear models were used to investigate associations between area and individual-level indicators. RESULTS: Correlations between area measures were generally in the 0.5--0.8 range. In factor analyses, six indicators of income/wealth, education, and occupation loaded on one factor in most geographic sites. Correlations between block-group and census tract measures were high (correlation coefficients 0.85--0.96). Most of the variability in block-group indicators was between census tracts (intraclass correlation coefficients 0.72--0.92). Although individual-level and area indicators were associated, there was evidence of important heterogeneity in area of residence within individual-level income or education categories. The strength of the association between individual and area measures was similar in the three studies and in whites and blacks, but blacks were much more likely to live in more disadvantaged areas than whites. CONCLUSIONS: Area measures of wealth/income, education, and occupation are moderately to highly correlated. Differences between using census tract or block-group measures in contextual investigations are likely to be relatively small. Area and individual-level indicators are far from perfectly correlated and provide complementary information on living circumstances. Differences in the residential environments of blacks and whites may need to be taken into account in interpreting race differences in epidemiologic studies.
Keywords: Adult; Black or African American; Cardiovascular Diseases; Demography; Educational Status; Factor Analysis, Statistical; Humans; Income; Linear Models; Occupations; Risk Factors; Social Class; Social Environment; Socioeconomic Factors; Statistics, Nonparametric; United States; White People

Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. - Psaty, B M; Furberg, C D; Kuller, L H; Cushman, M; Savage, P J; Levine, D; O'Leary, D H; Bryan, R N; Anderson, M; Lumley, T (Arch Intern Med, 2001)
BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified. RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension. CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.
Keywords: Aged; Blood Pressure; Female; Humans; Male; Myocardial Infarction; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Survival Rate; United States

Association between physical activity and markers of inflammation in a healthy elderly population. - Geffken, D F; Cushman, M; Burke, G L; Polak, J F; Sakkinen, P A; Tracy, R P (Am J Epidemiol, 2001)
Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.
Keywords: Aged; Analysis of Variance; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Factor VIII; Female; Fibrinogen; Humans; Inflammation; Leukocyte Count; Male; Physical Exertion; Sex Factors; Smoking

The association of bone mineral density and depression in an older population. - Robbins, J; Hirsch, C; Whitmer, R; Cauley, J; Harris, T (J Am Geriatr Soc, 2001)
OBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population. DESIGN: Population-based, cross-sectional study. SETTING: Study subjects were participants in the Cardiovascular Health Study (CHS), a longitudinal, long-term, follow-up study, at the University of California Davis (Sacramento, California) and the University of Pittsburgh (Pittsburgh, Pennsylvania) clinical centers. PARTICIPANTS: A random sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS. MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry (DEXA), after adjustment for multiple covariates, was compared with depression evaluated with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for osteoporosis were compared in depressed and nondepressed participants. Potential correlates were entered into a regression model. Depression scores were compared in normal, osteopenic, and osteoporotic individuals. RESULTS: Sixteen percent of participants were clinically depressed; 9% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm2 lower in those with clinical depression. High CES-Dm scores were associated with lower BMD (P < .001) when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen use, gender, race, smoking and drinking. When stratified by race, this remained true for all Caucasians (P < .01), all African Americans (P < .05), and when stratified by race and gender the association remained only for all Caucasian women (P < .001). In women and Caucasian men there was an increase in depression scores among individuals with osteoporotic-range BMDs. CONCLUSIONS: A significant association was found between BMD and depressive symptoms after adjustment for osteoporosis risk factors. In Caucasians, depressive symptoms were associated with both osteoporotic and osteopenic levels of BMD. Causality cannot be ascribed, with only one measurement of BMD. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression.
Keywords: Absorptiometry, Photon; Aged; Analysis of Variance; Black People; Body Mass Index; Bone Density; Bone Diseases, Metabolic; California; Cross-Sectional Studies; Depression; Energy Metabolism; Exercise; Female; Follow-Up Studies; Fractures, Bone; Humans; Linear Models; Male; Osteoporosis; Pennsylvania; Population Surveillance; Psychiatric Status Rating Scales; Radionuclide Imaging; Risk Factors; Sex Distribution; Single-Blind Method; White People

The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study. - Baldwin, C M; Griffith, K A; Nieto, F J; O'Connor, G T; Walsleben, J A; Redline, S (Sleep, 2001)
This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6%) were significantly more likely to have SDB compared to women (5.6%), while women (42.4%) were significantly more likely to report DIMS than men (32.5%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.
Keywords: Adult; Cardiovascular Diseases; Chronic Disease; Circadian Rhythm; Disorders of Excessive Somnolence; Female; Health Status; Humans; Male; Middle Aged; Polysomnography; Population Surveillance; Prevalence; Quality of Life; Risk Factors; Severity of Illness Index; Sleep Apnea Syndromes; United States

Associations of subclinical cardiovascular disease with frailty. - Newman, A B; Gottdiener, J S; McBurnie, M A; Hirsch, C H; Kop, W J; Tracy, R; Walston, J D; Fried, L P (J Gerontol A Biol Sci Med Sci, 2001)
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.
Keywords: Aged; Ankle; Arm; Black or African American; Blood Pressure; Brain; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Infarction; Cerebrovascular Disorders; Cohort Studies; Echocardiography; Electrocardiography; Frail Elderly; Health Status; Heart Failure; Humans; Magnetic Resonance Imaging; United States; Vascular Diseases

Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter. - Herrington, D M; Fan, L; Drum, M; Riley, W A; Pusser, B E; Crouse, J R; Burke, G L; McBurnie, M A; Morgan, T M; Espeland, M A (J Cardiovasc Risk, 2001)
BACKGROUND: Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform. METHODS: We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4,040 ultrasound examinations from subjects aged 14 to 98 years. RESULTS: Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 +/- 0.10% (mean +/- standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 +/- 0.87 mm and 0.15 +/- 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P< 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2,315) had significantly larger per cent change in diameter than men (n=1,725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001). CONCLUSIONS: Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.
Keywords: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Blood Circulation; Brachial Artery; Female; Humans; Male; Middle Aged; Observer Variation; Population Surveillance; Reproducibility of Results; Sex Factors; Vasodilation; Vasodilator Agents

Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study. - Newman, A B; Arnold, A M; Burke, G L; O'Leary, D H; Manolio, T A (Ann Intern Med, 2001)
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.
Keywords: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Diseases; Disease Progression; Female; Humans; Incidence; Longitudinal Studies; Male; Mortality; Proportional Hazards Models; Risk Factors; Ultrasonography; United States

Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study. - Longstreth, W T; Diehr, P; Manolio, T A; Beauchamp, N J; Jungreis, C A; Lefkowitz, D (Arch Neurol, 2001)
OBJECTIVE: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis. SUBJECTS AND METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations. RESULTS: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected. CONCLUSIONS: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.
Keywords: Aged; Brain; Cerebral Infarction; Cerebrovascular Disorders; Cluster Analysis; Cohort Studies; Discriminant Analysis; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Risk Factors

Coronary artery calcification in older adults to age 99: prevalence and risk factors. - Newman, A B; Naydeck, B L; Sutton-Tyrrell, K; Feldman, A; Edmundowicz, D; Kuller, L H (Circulation, 2001)
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.
Keywords: Age Distribution; Age Factors; Aged; Aged, 80 and over; Black People; Calcinosis; Calcium; Cohort Studies; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Demography; Female; Humans; Logistic Models; Male; Predictive Value of Tests; Prevalence; Risk Factors; Sex Distribution; Sex Factors; Tomography, X-Ray Computed; White People

Correlates of peak expiratory flow lability in elderly persons. - Enright, P L; McClelland, R L; Buist, A S; Lebowitz, M D (Chest, 2001)
OBJECTIVE: To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly. METHODS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study completed an asthma questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum - PEF minimum)/mean PEF. RESULTS: Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18% in those with current asthma (n = 165) vs 12% in healthy nonsmokers (upper limit of normal, 29%). Approximately 26% of those with asthma and 14% of the other participants had abnormally high PEF lability (> 29%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability. CONCLUSIONS: Measurement of PEF lability at home is highly successful in elderly persons. PEF lability > or = 30% is abnormal in the elderly and is associated with asthma.
Keywords: Aged; Aged, 80 and over; Aging; Asthma; Female; Heart Failure; Humans; Male; Monitoring, Ambulatory; Peak Expiratory Flow Rate; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Reference Values; Rhinitis, Allergic, Seasonal; Risk Factors; Signal Processing, Computer-Assisted; Spirometry

Echocardiographic features of the right heart in sleep-disordered breathing: the Framingham Heart Study. - Guidry, U C; Mendes, L A; Evans, J C; Levy, D; O'Connor, G T; Larson, M G; Gottlieb, D J; Benjamin, E J (Am J Respir Crit Care Med, 2001)
The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.
Keywords: Adult; Age Factors; Aged; Cohort Studies; Cross-Sectional Studies; Data Interpretation, Statistical; Echocardiography; Female; Forced Expiratory Volume; Humans; Hypertrophy, Right Ventricular; Linear Models; Male; Middle Aged; Obesity; Observer Variation; Polysomnography; Prospective Studies; Sex Factors; Sleep Apnea Syndromes; Ventricular Function, Right; Vital Capacity

Estrogen replacement and brachial artery flow-mediated vasodilation in older women. - Herrington, D M; Espeland, M A; Crouse, J R; Robertson, J; Riley, W A; McBurnie, M A; Burke, G L (Arterioscler Thromb Vasc Biol, 2001)
It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Brachial Artery; Cardiovascular Diseases; Drug Therapy, Combination; Estrogen Replacement Therapy; Estrogens; Female; Humans; Longitudinal Studies; Progestins; Risk Factors; Ultrasonography; Vasodilation

Factors associated with healthy aging: the cardiovascular health study. - Burke, G L; Arnold, A M; Bild, D E; Cushman, M; Fried, L P; Newman, A; Nunn, C; Robbins, J (J Am Geriatr Soc, 2001)
OBJECTIVES: To identify factors associated with remaining healthy in older adults. DESIGN: Longitudinal cohort study. SETTING: Data were collected at the four Cardiovascular Health Study field centers. PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study. MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes. RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults. CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.
Keywords: Aged; Aged, 80 and over; Aging; Cardiovascular Diseases; Cohort Studies; Diet; Exercise; Female; Health Status; Humans; Incidence; Life Style; Longitudinal Studies; Lung Diseases, Obstructive; Male; Neoplasms; Probability; Reference Values; Risk Factors; Sex Distribution; Socioeconomic Factors; Survival Rate; United States

Frailty in older adults: evidence for a phenotype. - Fried, L P; Tangen, C M; Walston, J; Newman, A B; Hirsch, C; Gottdiener, J; Seeman, T; Tracy, R; Kop, W J; Burke, G; McBurnie, M A (J Gerontol A Biol Sci Med Sci, 2001)
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.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Disabled Persons; Fatigue; Female; Frail Elderly; Humans; Incidence; Male; Muscle Weakness; Phenotype; Prevalence; Sex Distribution; United States; Weight Loss

Frequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study. - Longstreth, W T; Bernick, C; Fitzpatrick, A; Cushman, M; Knepper, L; Lima, J; Furberg, C D (Neurology, 2001)
BACKGROUND: Few population-based studies have examined in detail issues of stroke-related deaths in elderly people. METHODS: Participants in the Cardiovascular Health Study (CHS) are 65 years of age or older, have had extensive baseline evaluations, and have been followed-up for fatal and nonfatal cardiovascular and cerebrovascular disease outcomes. Investigators adjudicated these outcomes and classified strokes by types and subtypes. RESULTS: Over 7 years, 1,310 (22.2%) of 5,888 participants died, and 455 (7.7%) experienced incident stroke. For the 5,888, stroke mortality was 3.2 per 1,000 person-years. For the 455, it was 36.1 per 1,000 person-years, with the most lethal type being hemorrhagic and the ischemic subtype being cardioembolic. After controlling for age and stroke type, the only other independent predictor of death after any stroke was poor performance on a timed walk measured before the incident stroke. Considering only ischemic stroke, the independent predictors of death were African American race and poor performance on timed walk. CONCLUSION: In CHS, death attributable to stroke is common. As in other studies, the most lethal stroke type was hemorrhagic, and ischemic stroke subtype, cardioembolic. Slow walking, possibly a measure of frailty, was associated with an increased risk of death of stroke. Finally, African Americans faced a greater risk of death than others after an ischemic stroke.
Keywords: Aged; Aged, 80 and over; Clinical Trials as Topic; Female; Humans; Longitudinal Studies; Male; Predictive Value of Tests; Stroke; Survival Analysis; United States

Gait variability in community-dwelling older adults. - Brach, J S; Berthold, R; Craik, R; VanSwearingen, J M; Newman, A B (J Am Geriatr Soc, 2001)
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.
Keywords: Aged; Aged, 80 and over; Aging; Body Height; Body Weight; Cross-Sectional Studies; Disability Evaluation; Female; Gait; Humans; Male; Residence Characteristics; Risk Factors; Time Factors; Walking

Hormone replacement therapy is associated with higher FEV1 in elderly women. - Carlson, C L; Cushman, M; Enright, P L; Cauley, J A; Newman, A B (Am J Respir Crit Care Med, 2001)
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.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Estrogen Replacement Therapy; Female; Forced Expiratory Volume; Humans; Longitudinal Studies; Spirometry; Vital Capacity

Hypertension, heart rate, use of antihypertensives, and incident prostate cancer. - Fitzpatrick, A L; Daling, J R; Furberg, C D; Kronmal, R A; Weissfeld, J L (Ann Epidemiol, 2001)
PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth. METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants. RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk. CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.
Keywords: Aged; Antihypertensive Agents; Cohort Studies; Heart Rate; Humans; Hypertension; Incidence; Male; Proportional Hazards Models; Prostatic Neoplasms; Risk; United States

Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. - Kitzman, D W; Gardin, J M; Gottdiener, J S; Arnold, A; Boineau, R; Aurigemma, G; Marino, E K; Lyles, M; Cushman, M; Enright, P L (Am J Cardiol, 2001)
Although congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6%) to age > or = 85 years (14%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55% of subjects with CHF had normal left ventricular systolic function and 80% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67% vs 42%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Chi-Square Distribution; Echocardiography, Doppler; Female; Health Status; Heart Failure; Humans; Logistic Models; Longitudinal Studies; Male; Prevalence; Risk Factors; Surveys and Questionnaires; United States; Ventricular Function, Left

Incidence and predictors of coronary heart disease among older African Americans--the Cardiovascular Health Study. - Jackson, S A; Burke, G L; Thach, C; Cushman, M; Ives, D; Powe, N; Manolio, T A (J Natl Med Assoc, 2001)
Although coronary heart disease (CHD) is the leading cause of death and morbidity in older African Americans, relatively little is known about the incidence and predictors of CHD in this population. This study was undertaken to determine the incidence and predictors of CHD in African-American men and women aged 65 years and older. The participants in this study included a total of 924 African-American men and women aged 65 years of age and older who participated in the Cardiovascular Health Study (CHS). The overall CHD incidence was 26.6 per 1,000 person-years of risk. Rates were higher in men than women (35.3 vs. 21.6) and in those 75 years or older than in those less than 75 years (31.3 vs. 24.5). In multivariate analysis, factors associated with higher risk of incident disease were male gender [relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.1, 2.7], diabetes mellitus (RR = 1.9, 95% CI = 1.2, 2.9), total cholesterol (RR for 40 mg/dL increment = 1.3, 95% CI = 1.0, 1.5), and low (i.e., <0.9) ankle-arm index (RR = 2.1, 95% CI = 1.3, 3.4) after adjusting for age. Within this cohort of older African Americans, male gender, diabetes mellitus, total cholesterol, and low ankle-arm index and were independently predictive of incident events. These results suggest that the ankle-arm index, a measure of advanced atherosclerosis, should be further evaluated for its efficacy in identifying older African Americans at risk for incident clinical events.
Keywords: Age Distribution; Aged; Black or African American; Coronary Disease; Female; Health Status; Humans; Incidence; Male; Predictive Value of Tests

Involvement in caregiving and adjustment to death of a spouse: findings from the caregiver health effects study. - Schulz, R; Beach, S R; Lind, B; Martire, L M; Zdaniuk, B; Hirsch, C; Jackson, S; Burton, L (JAMA, 2001)
CONTEXT: Most deaths in the United States occur among older persons who have 1 or more disabling conditions. As a result, many deaths are preceded by an extended period during which family members provide care to their disabled relative. OBJECTIVE: To better understand the effect of bereavement on family caregivers by examining predeath vs postdeath changes in self-reported and objective health outcomes among elderly persons providing varying levels of care prior to their spouse's death. DESIGN AND SETTING: Prospective, population-based cohort study conducted in 4 US communities between 1993 and 1998. PARTICIPANTS: One hundred twenty-nine individuals aged 66 to 96 years whose spouse died during an average 4-year follow-up. Individuals were classified as noncaregivers (n = 40), caregivers who reported no strain (n = 37), or strained caregivers (n = 52). MAIN OUTCOME MEASURES: Changes in depression symptoms (assessed by the 10-item Center for Epidemiological Studies-Depression [CES-D] scale), antidepressant medication use, 6 health risk behaviors, and weight among the 3 groups of participants. RESULTS: Controlling for age, sex, race, education, prevalent cardiovascular disease at baseline, and interval between predeath and postdeath assessments, CES-D scores remained high but did not change among strained caregivers (9.44 vs 9.19; P =.76), while these scores increased for both noncaregivers (4.74 vs 8.25; F(1,116) = 14.33; P<.001) and nonstrained caregivers (4.94 vs 7.13; F(1,116) = 4.35; P =.04). Noncaregivers were significantly more likely to be using nontricyclic antidepressant medications following the death than the nonstrained caregiver group (odds ratio [OR], 12.85; 95% confidence interval [CI], 1.02-162.13; P =.05). The strained caregiver group experienced significant improvement in health risk behaviors following the death of their spouse (1.47 vs 0.66 behaviors; F(1,118) = 20.23; P<.001), while the noncaregiver and nonstrained caregiver groups showed little change (0.27 vs 0.27 [P =.99] and 0.46 vs 0.27 [P =.39] behaviors, respectively). Noncaregivers experienced significant weight loss following the death (149.1 vs 145.3 lb [67.1 vs 65.4 kg]; F(1,101) = 8.12; P =.005), while the strained and nonstrained caregiving groups did not show significant weight change (156.2 vs 155.2 lb [70.3 vs 69.8 kg] [P =.41] and 156.2 vs 154.0 lb [70.3 vs 69.3 kg] [P =.12], respectively). CONCLUSIONS: These data indicate that the impact of losing one's spouse among older persons varies as a function of the caregiving experiences that precede the death. Among individuals who are already strained prior to the death of their spouse, the death itself does not increase their level of distress. Instead, they show reductions in health risk behaviors. Among noncaregivers, losing one's spouse results in increased depression and weight loss.
Keywords: Aged; Aged, 80 and over; Antidepressive Agents; Bereavement; Caregivers; Death; Depression; Female; Follow-Up Studies; Health Behavior; Humans; Male; Socioeconomic Factors; Spouses; Weight Loss

M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study). - Gardin, J M; McClelland, R; Kitzman, D; Lima, J A; Bommer, W; Klopfenstein, H S; Wong, N D; Smith, V E; Gottdiener, J (Am J Cardiol, 2001)
Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86% vs 97%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.
Keywords: Aged; Aged, 80 and over; Analysis of Variance; Coronary Disease; Echocardiography, Doppler; Female; Heart Failure; Humans; Incidence; Male; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke

Patterns of self-rated health in older adults before and after sentinel health events. - Diehr, P; Williamson, J; Patrick, D L; Bild, D E; Burke, G L (J Am Geriatr Soc, 2001)
OBJECTIVES: To describe and compare patterns of change in self-rated health for older adults before death and before and after stroke, myocardial infarction, congestive heart failure, cardiac procedure, hospital admission for cancer, and hip fracture. DESIGN: "Event cohort," measuring time in months before and after the event. SETTING: Four U.S. communities. PARTICIPANTS: 5888 participants in the Cardiovascular Health Study (CHS), sampled from Medicare rolls and followed up to 8 years. Mean age at baseline was 73. MEASUREMENTS: Self-rated health, including a category for death, assessed at 6-month intervals, and ascertainment of events. METHODS: We examined the percentage that was healthy each month in the 5 years before death and in the 2 years before and after the other events, and compared the patterns to a "no event" group and to one another, using graphs and linear regression. RESULTS: For people who died, health status declined slowly until about 9 months before death, when it dropped steeply. Comparing persons equally far from death, health was unrelated to age, but men and whites were healthier than women and blacks. Health for other events declined before the event, dropped steeply at the event, showed some recovery, and then declined further after the event. About 65% to 80% of the subjects were healthy 2 years before their event, but only 35% to 65% were healthy two years afterwards. Patterns were similar although less extreme for the "no event" group. CONCLUSION: Visualizing trajectories of health helps us understand how serious health events changes health. Conclusions about change must be drawn with care because of a variety of possible biases. We have described the trajectories in detail. Work is now needed to explain, predict, and possibly prevent such changes in health.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Death; Female; Follow-Up Studies; Health Status; Health Status Indicators; Hip Fractures; Hospitalization; Humans; Linear Models; Longitudinal Studies; Male; Random Allocation; Time Factors

Patterns on cranial magnetic resonance imaging in elderly people and vascular disease outcomes. - Longstreth, W T; Diehr, P; Beauchamp, N J; Manolio, T A (Arch Neurol, 2001)
Keywords: Aged; Brain; Cardiovascular Diseases; Cluster Analysis; Humans; Magnetic Resonance Imaging

Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women. - Cushman, M; Psaty, B M; Meilahn, E N; Dobs, A S; Kuller, L H (Br J Haematol, 2001)
The effects of post-menopausal hormone therapy (HRT) on blood coagulation in elderly women are not well defined. We studied associations of HRT use with levels of natural anticoagulant proteins in a cross-sectional study of 3393 women > or = 65 years of age participating in the Cardiovascular Health Study. Protein C antigen and antithrombin were measured in all users (n = 230 unopposed oestrogen; 60 oestrogen/progestin) and a comparison group of 196 age- and race-matched non-users. Compared with non-users, oestrogen use was associated with higher protein C (4.80 vs. 4.30 microg/ml, P < 0.01). Results were similar for oestrogen/progestin (P > 0.05). In both user groups, antithrombin was lower than in non-users (109% for each vs. 115% in non-users, P < 0.001). Adjustment for factors related to prescription of HRT and to anticoagulant protein levels had little impact on the results. For antithrombin, associations with HRT were larger for thinner Caucasian women and black women. Venous thrombosis from HRT may be mediated partly by alterations in antithrombin, but not protein C concentrations. This study extends previous observations to older women, the group at highest risk of venous thromboembolism. Studies of HRT-induced alterations in anticoagulant function in relation to the occurrence of thrombosis with HRT are required.
Keywords: Aged; Antithrombins; Black People; Body Mass Index; Cross-Sectional Studies; Estrogen Replacement Therapy; Female; Humans; Logistic Models; Postmenopause; Progestins; Protein C; Risk Factors; Venous Thrombosis; White People

Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study. - Aurigemma, G P; Gottdiener, J S; Shemanski, L; Gardin, J; Kitzman, D (J Am Coll Cardiol, 2001)
OBJECTIVES: We sought to assess the ability of echocardiographic indices of systolic and diastolic function to predict incident congestive heart failure (CHF). BACKGROUND: Noninvasive indices of subclinical systolic and/or diastolic dysfunction that can be used to identify patients in a transition phase between normal cardiac function and clinical CHF would be valuable. Though midwall shortening and Doppler mitral inflow patterns are seemingly well suited to predict subsequent CHF, the predictive value of these indices has not been investigated. METHODS: We studied 2,671 participants in the Cardiovascular Health Study who were free of coronary heart disease, CHF or atrial fibrillation. Clinical and quantitative echocardiographic data were obtained in all participants. RESULTS: At a mean follow-up of 5.2 years (range 0 to 6 years), 170 participants (6.4% of the cohort) developed CHF. Although 96% of these participants had normal or borderline ejection fraction (EF) at baseline, only 57% had normal or borderline EF at the time of hospitalization. In multivariate modeling, fractional shortening at the endocardium (relative risk [RR] 1.85 per 10-unit decrease, confidence interval [CI] 1.27 to 2.39), fractional shortening at the midwall (RR 1.29 per five-unit decrease, 95% CI 1.11-1.51) and peak Doppler peak E (RR 1.15 for each 0.1 M/s increment; CI 1.02 to 1.21) independently predicted incident CHF. Both high and low Doppler E/A ratios were predictive of incident CHF. CONCLUSIONS: Roughly half the occurrences of CHF in this population are associated with normal or borderline EF. Echocardiographic findings suggestive of subclinical contractile dysfunction and diastolic filling abnormalities are both predictive of subsequent CHF. The standard (FSendo) and refined (FSmw) parameters of systolic function performed similarly in this regard, though subjects with left ventricular hypertrophy and depressed FSmw are at particularly high risk for subsequent CHF.
Keywords: Age Factors; Aged; Aged, 80 and over; Diastole; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Multivariate Analysis; Myocardial Contraction; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Systole