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

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

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

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

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

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 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

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

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

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

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

Classification accuracy of electrocardiographic criteria for left ventricular hypertrophy in normal weight and overweight older adults: the Cardiovascular Health Study - Rautaharju, PM; Manolio, TA; Siscovick, D; Zhou, SH; Gardin, JM; Furberg, CD; Borhani, NO; Newman, AB (Annals of Noninvasive Electrocardiology, 1996)
BACKGROUND We evaluated classification accuracy of ECG criteria at varying levels of left ventricular hypertrophy (LVH) severity according to echocardiographically measured left ventricular mass (LVM) adjusted body size. METHODS: The test population was derived from the Cardiovascular Health Study (CHS), a population based sample of 5201 men and women aged 65 and older, and consisted of 1844 women and 1119 men with adequate quality ECGs and echocardiograms for LVM determination. The criteria evaluated were Sokolow-Lyon, Cornell Voltage, Cornell product, Framingham modification of Cornell voltage, and the left ventricular mass index (LVMI) of the Novacode ECG program. RESULTS: With LVH thresholds at upper 95% normal limit for weight adjusted LVM for the CHS population and ECG thresholds adjusted for 95% specificity in normal weight and overweight subgroups, the sensitivity of ECG criteria for LVH was relatively low. it was highest (40.8%) for the Novacode LVMI in normal weight men and for the Framingham criteria (30.9%) in normal weight women, but it deteriorated for both of these criteria in the presence of obesity. The overall performance of the Cornell product and Cornell voltage criteria was least influenced by obesity. The Framingham adjustment for the Cornell Voltage criteria for obesity substantially reduced their sensitivity. CONCLUSION: The choice of echocardiographic standard, LVH severity level and overweight in the test groups have a strong influence on ECG evaluation results.
Keywords: Adult; Aged; Body Size; classification; Health; Hypertrophy; methods; Obesity; Population

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Neurologic correlates of infarction-like lesion location on magnetic resonance imaging in the cardiovascular health study - McClelland, RL; Kronmal, RA; Bryan, RN; Manolio, TA; Herskovits, EH; Kuller, LH; O'Leary, DH (J. Stroke Cerebrovascular Disease, 2000)
Objective: To evaluate and quantify the associations of infarction-like lesion location in the brain with cognitive and physical impairment in an elderly population. Methods: Data from magnetic resonance imaging (MRI) scans for 3647 Cardiovascular Health Study participants were analyzed. Associations between infarction-like lesion location and various neurologic and performance-based measurements were assessed by using regression models. Continuous responses were expressed in percentiles. Models excluding participants with a history of stroke were also examined. Results: Brainstem infarction-like lesions were associated with a severely reduced Mini-Mental State Examination score (difference [d] = 15 percentiles, P < .001), reduced digit-symbol score (d = 12 percentiles, P < .01), increased time to walk 15 feet (d = 15 percentiles, P < .001), and increased odds of a history of dizziness (odds ratio [OR] = 2.5, P <.01). Basal ganglia infarctions were associated with an increased prevalence of visual field deficits (OR = 1.8, P <.001), and cerebellar white matter infarction-like lesions with an increased prevalence of a history of coma (OR = 4.0, P < .01). For those with infarction-like lesions in both the cerebral cortex and brainstem, the degree of sleepiness was substantially elevated (d = 34 percentiles, P < .01). No associations with a history of migraines were detected. After exclusion of those with stroke history, all of these associations persisted. Conclusion: The estimated magnitude and statistical significance of these associations relative to those with no infarction-like lesions provides new information. Further investigation for some of the associations, such as the role of the brainstem in cognitive function and the association of basal ganglia infarction-like lesions with visual field deficits, would be worthwhile.
Keywords: basal; Brain; Cerebral Cortex; ganglia; Health; history; Infarction; Magnetic Resonance Imaging; methods; Odds Ratio; Population; Prevalence; Stroke

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

Orthostatic Hypotension in the Elderly: Contributions of Impaired LV Filling and Altered Sympathovagal Balance. - Gottdiener, John S.; Yanez, David; Rautaharju, Penttii; Gardin, Julius M.; Bild, Diane E.; Lima, Joao; Newman, Anne B. (Am J Geriatr Cardiol, 2000)
Orthostatic hypotension, which occurs in 5%-18% of the elderly, may contribute to age-related disability. While autonomic dysfunction and alterations of cardiac structure and function likely to impair postural maintenance of blood pressure are common in the elderly, these have not been jointly studied in large cohorts. The authors evaluated the association of orthostatic hypotension with echocardiographic measures of cardiac structure and function, and with autonomic function determined by analysis of heart rate variability, in a large population of community-dwelling elderly. A total of 5201 men and women, aged 65-100 years and living in four geographically separate communities, were recruited from Medicare eligibility lists. In this prospective, observational cohort study, measurements included clinical questionnaires, standing and supine blood pressures, mini-glucose tolerance testing, echocardiography, and 24-hour Holter recording for assessment of heart rate variability. Orthostatic hypotension, defined as a decrease in standing systolic blood pressure of 20 mm Hg or more, was positively associated in bivariate analyses with left ventricular wall thickness, peak velocity of late diastolic filling, vagal tone on heart rate variability analysis, supine systolic pressure, supine diastolic pressure, age, and diabetes, and inversely associated with body weight. After statistical adjustment for the presence of myocardial infarction, stroke, and use of antihypertensive medication, the associations were maintained, and a previous trend toward an association with decreased left ventricular cavity size became statistically significant. The data suggest that in elderly, community-based individuals, orthostatic hypotension is associated with increased blood pressure and decreased weight; it possibly acts mechanistically via altered sympathovagal balance, increased left ventricular wall thickness, decreased left ventricular preload, and alterations of left ventricular diastolic filling. (c) 2000 by CVRR, Inc.

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

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

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 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

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

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

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

Predictors of loss of lung function in the elderly: the Cardiovascular Health Study. - Griffith, K A; Sherrill, D L; Siegel, E M; Manolio, T A; Bonekat, H W; Enright, P L (Am J Respir Crit Care Med, 2001)
Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.
Keywords: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Forced Expiratory Volume; Humans; Longitudinal Studies; Lung; Lung Volume Measurements; Male

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study. - Barzilay, J I; Spiekerman, C F; Kuller, L H; Burke, G L; Bittner, V; Gottdiener, J S; Brancati, F L; Orchard, T J; O'Leary, D H; Savage, P J (Diabetes Care, 2001)
OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.
Keywords: Aged; Angina Pectoris; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Electrocardiography; Female; Glucose Intolerance; Heart Diseases; Humans; Male; Peripheral Vascular Diseases; Prevalence; United States

The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. - Barzilay, J I; Abraham, L; Heckbert, S R; Cushman, M; Kuller, L H; Resnick, H E; Tracy, R P (Diabetes, 2001)
Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.
Keywords: Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus; Female; Humans; Hypoglycemia; Inflammation; Longitudinal Studies; Male; Reference Values; Risk Factors

Silent MRI infarcts and the risk of future stroke: the cardiovascular health study. - Bernick, C; Kuller, L; Dulberg, C; Longstreth, W T; Manolio, T; Beauchamp, N; Price, T (Neurology, 2001)
BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly. OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors. METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts. RESULTS: Approximately 28% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes). CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.
Keywords: Aged; Cerebral Infarction; Cohort Studies; Female; Follow-Up Studies; Humans; Incidence; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Risk Factors; Stroke

Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. - Shahar, E; Whitney, C W; Redline, S; Lee, E T; Newman, A B; Nieto, F J; O'Connor, G T; Boland, L L; Schwartz, J E; Samet, J M (Am J Respir Crit Care Med, 2001)
Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Sleep Apnea Syndromes

The aging and dying processes and the health of older adults. - Diehr, Paula; Williamson, Jeff; Burke, Gregory L; Psaty, Bruce M (J Clin Epidemiol, 2002)
It is difficult to distinguish changes in health due to aging from those related to dying, because the two processes are highly related. Some potentially treatable conditions may mistakenly be dismissed as due to old age. The goal of this article was to examine the relationships of aging and of dying to changes in 10 health-related variables: self-rated health, depression, ADLs, IADLs, minimental state examination, body mass index, blocks walked per week, bed days, hospitalization, and walking speed (all coded so that higher values were better). We used longitudinal data from the Cardiovascular Health Study to estimate the changes in the variables associated with 5 years of aging and also in the 5 years before death, controlling for years from death and for age, respectively. All 10 health variables declined as death approached, and most of them also declined with age. The "effect" of the dying process was usually significantly larger than the effect of aging. Large declines in these health measures are probably not due to aging, and should be taken seriously by patients and their providers.
Keywords: Aged; Aging; Death; Female; Health Status Indicators; Humans; Linear Models; Longitudinal Studies; Male; Muscular Atrophy

Cardiovascular disease risk status in elderly persons with renal insufficiency. - Shlipak, Michael G; Fried, Linda F; Crump, Casey; Bleyer, Anthony J; Manolio, Teri A; Tracy, Russell P; Furberg, Curt D; Psaty, Bruce M (Kidney Int, 2002)
BACKGROUND: Renal insufficiency has been independently associated with incident cardiovascular disease events in some, but not all, prospective studies. We determined the prevalence of elevated cardiovascular disease risk status among elderly persons with renal insufficiency. METHODS: This study is a cross-sectional analysis using data collected at the baseline visit of the Cardiovascular Health Study, which enrolled 5888 community dwelling adults aged 65 years or older from four clinical centers in the United States. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. The outcomes of this study included prevalent cardiovascular disease [prior coronary heart disease (CHD) or stroke], subclinical cardiovascular disease (abnormal values of ankle-arm index, carotid ultrasound, and echocardiography) and elevated cardiovascular risk based upon a diagnosis of diabetes and the Framingham equations. The association between renal insufficiency and cardiovascular risk status was estimated with and without adjustment for other cardiovascular predictors. RESULTS: Among the 5808 participants with creatinine levels measured at entry, 15.9% of men (N = 394), and 7.6% of women (N = 254) had renal insufficiency. The prevalence of either clinical or subclinical cardiovascular disease was 64% in persons with renal insufficiency compared with 43% in those without it [odds ratio (OR) 2.34; 95% confidence interval (95% CI), 1.96, 2.80]. After adjustment for other cardiovascular risk factors, renal insufficiency remained significantly associated with clinical and subclinical cardiovascular disease (adjusted OR 1.43; 95% CI, 1.18, 1.75), but the magnitude of association was substantially reduced. After combining clinical and subclinical cardiovascular disease, diabetes, and an estimated risk>20% by the Framingham equations, 78% of men and 61% of women with renal insufficiency had elevated cardiovascular risk status. CONCLUSIONS: Renal insufficiency is a marker for elevated cardiovascular disease risk in community dwelling elderly adults.
Keywords: Age Distribution; Aged; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Creatinine; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Male; Prevalence; Prospective Studies; Risk Factors

Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study. - Steffens, David C; Krishnan, K Ranga Rama; Crump, Casey; Burke, Gregory L (Stroke, 2002)
BACKGROUND AND PURPOSE: Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms. METHODS: The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently. RESULTS: After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions. CONCLUSIONS: These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.
Keywords: Aged; Aged, 80 and over; Basal Ganglia Cerebrovascular Disease; Brain; Cerebrovascular Disorders; Cohort Studies; Comorbidity; Depression; Disease Progression; Female; Health Surveys; Humans; Incidence; Logistic Models; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Odds Ratio; United States

Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study. - Smith, Nicholas L; Barzilay, Joshua I; Shaffer, Douglas; Savage, Peter J; Heckbert, Susan R; Kuller, Lewis H; Kronmal, Richard A; Resnick, Helaine E; Psaty, Bruce M (Arch Intern Med, 2002)
BACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk. METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk. RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk. CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.
Keywords: Aged; Blood Glucose; Cardiovascular Diseases; Fasting; Female; Glucose Tolerance Test; Humans; Male; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Stroke

Glucose, blood pressure, and lipid control in older people with and without diabetes mellitus: the Cardiovascular Health Study. - Smith, Nicholas L; Savage, Peter J; Heckbert, Susan R; Barzilay, Joshua I; Bittner, Vera A; Kuller, Lewis H; Psaty, Bruce M (J Am Geriatr Soc, 2002)
OBJECTIVES: To determine the prevalence of cardiovascular risk-factor treatment and control in older adults with normal fasting glucose, impaired fasting glucose, and diabetes mellitus and whether those with diabetes mellitus had better risk factor control than older adults with normal fasting glucose. DESIGN: Secondary analysis of data from population-based, prospective cohort study of risk factors for cardio-vascular and cerebrovascular disease in older people (Cardiovascular Health Study). SETTING: Community-based. PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: Fasting plasma glucose, serum cholesterol and its subfractions, systolic and diastolic blood pressures, and body mass index. RESULTS: There were 579 (18%) cohort members with diabetes mellitus (77% receiving antidiabetic medication, 23% with fasting glucose > or =126 mg/dL and no treatment), 213 (6%) with impaired fasting glucose, and 2,582 (77%)with normal fasting glucose. Of diabetic participants, 12% had recommended fasting glucose levels of less than 110 mg/dL. Of participants with hypertension, a larger proportion of diabetic participants than nondiabetic participants (89% versus 75%, P < .01) was treated with antihypertensive agents, but a smaller proportion of diabetic participants had recommended blood pressure levels of 129/85 mmHg or lower than nondiabetic participants had recommended blood pressure levels of 139/89 mmHg or lower (27% vs 48%, P < .01). Diabetic dyslipidemic participants were treated less often with lipid-lowering therapy (26% versus 55%, P < .01) and achieved recommended low-density lipoprotein goals less often (8%versus 54%, P < .01) than nondiabetic dyslipidemic participants. CONCLUSIONS: Overall, treatment and control of cardiovascular risk factors were suboptimal in this older population, especially among those with diabetes mellitus. Optimizing risk-factor control can improve health outcomes in older adults with and without diabetes mellitus.
Keywords: Age Factors; Aged; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Prevalence; Prospective Studies; Risk Factors

Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. - Longstreth, W T; Dulberg, Corinne; Manolio, Teri A; Lewis, Michael R; Beauchamp, Norman J; O'Leary, Daniel; Carr, Jeff; Furberg, Curt D (Stroke, 2002)
BACKGROUND AND PURPOSE: MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts. METHODS: The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged > or =65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI. RESULTS: On follow-up MRI, 254 participants (17.7%) had 1 or more infarcts. Most were single (75.6%), subcortical (79.9%), and small (3 to 20 mm in 87.0%). Only 11.4% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index. CONCLUSIONS: Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.
Keywords: Aged; Brain Infarction; California; Cohort Studies; Creatinine; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Magnetic Resonance Imaging; Maryland; Multivariate Analysis; Neuropsychological Tests; North Carolina; Odds Ratio; Pennsylvania; Predictive Value of Tests; Risk Factors

Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study. - Boland, Lori L; Shahar, Eyal; Iber, Conrad; Knopman, David S; Kuo, Tracy F; Nieto, F Javier (J Sleep Res, 2002)
Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.
Keywords: Aged; Body Mass Index; Brain; Cognition Disorders; Cohort Studies; Female; Humans; Hypoxia; Male; Middle Aged; Neuropsychological Tests; Oxygen; Polysomnography; Severity of Illness Index; Sleep Apnea, Central

Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. - Kuller, Lewis; Arnold, Alice; Tracy, Russell; Otvos, James; Burke, Greg; Psaty, Bruce; Siscovick, David; Freedman, David S; Kronmal, Richard (Arterioscler Thromb Vasc Biol, 2002)
OBJECTIVES: Relationships between incident cardiovascular disease and lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy were evaluated in the Cardiovascular Health Study (CHS) in a nested case-cohort analysis. METHODS AND RESULTS: The case group consisted of 434 participants with incident myocardial infarction (MI) and angina diagnosed after entry to the study (1990 to 1995) and the comparison group, 249 "healthy" participants with no prevalent clinical or subclinical disease. By univariate analysis, the median levels for healthy participants versus participants with incident MI and angina were 0 versus 7 mg% for small low density lipoprotein (LDL), 1501 versus 1680 nmol/L for the number of LDL particles, and 21.6 versus 21.3 for LDL size, and these values were significantly different between "healthy" participants and those with incident MI and angina for women but not men. The levels of less dense LDL, which is most of the total LDL cholesterol among women, was not related to incident MI and angina. For women, large high density lipoprotein cholesterol (HDLc), but not small HDLc, levels were significantly higher for healthy participants compared with levels for participants with MI and angina. For men and women, levels of total and very low density lipoprotein triglycerides were higher for the case group than for the healthy group. In multivariate models for women that included triglycerides and HDLc, the number of LDL particles (but not LDL size) remained significantly related to MI and angina. CONCLUSIONS: Small LDL, the size of LDL particles, and the greater number of LDL particles are related to incident coronary heart disease among older women.
Keywords: Aged; Aging; Cardiovascular System; Case-Control Studies; Cohort Studies; Coronary Disease; Female; Health Status; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Magnetic Resonance Spectroscopy; Male; Nuclear Magnetic Resonance, Biomolecular; Risk Factors; Sex Factors

Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. - Lyketsos, Constantine G; Lopez, Oscar; Jones, Beverly; Fitzpatrick, Annette L; Breitner, John; DeKosky, Steven (JAMA, 2002)
CONTEXT: Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI. OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study. DESIGN: Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia. MAIN OUTCOME MEASURE: Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms. RESULTS: Of the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P =.02). CONCLUSIONS: Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.
Keywords: Aged; Aggression; Anxiety; Behavioral Symptoms; Cognition Disorders; Comorbidity; Cross-Sectional Studies; Delusions; Dementia; Depression; Feeding and Eating Disorders; Female; Humans; Longitudinal Studies; Male; Neuropsychological Tests; Prevalence; Sleep Wake Disorders

Prevalence of renovascular disease in the elderly: a population-based study. - Hansen, Kimberley J; Edwards, Matthew S; Craven, Timothy E; Cherr, Gregory S; Jackson, Sharon A; Appel, Richard G; Burke, Gregory L; Dean, Richard H (J Vasc Surg, 2002)
PURPOSE: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as > or = 60% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with chi(2) and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis. RESULTS: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 +/- 4.9 years and consisted of 63% women and 37% men. Participant race was 76% white and 23% African American. The overall prevalence rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral disease and seven (12%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1 +/- 4.9 years (P =.018). RVD was present in 5.5% of women and 9.1% of men (P =.053). RVD was present in 6.9% of white participants and 6.7% of African American participants (P =.933). Multivariate analysis revealed increasing participant age (P =.028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63; 95% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio, 1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD. CONCLUSION: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure.
Keywords: Age Factors; Aged; Aged, 80 and over; Cohort Studies; Ethnic Groups; Female; Humans; Longitudinal Studies; Male; Prevalence; Prospective Studies; Renal Artery; Renal Artery Obstruction; Risk Factors; Sex Factors; Ultrasonography, Doppler, Duplex

A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. - Folsom, Aaron R; Cushman, Mary; Tsai, Michael Y; Aleksic, Nena; Heckbert, Susan R; Boland, Lori L; Tsai, Albert W; Yanez, N David; Rosamond, Wayne D (Blood, 2002)
The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR = 1.05; 95% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden.
Keywords: Activated Protein C Resistance; Aged; Cohort Studies; Continental Population Groups; Factor V; Genotype; Haplotypes; Humans; Incidence; Longitudinal Studies; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Thromboembolism; Venous Thrombosis

The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study. - Klein, Ronald; Marino, Emily K; Kuller, Lewis H; Polak, Joseph F; Tracy, Russell P; Gottdiener, John S; Burke, Gregory L; Hubbard, Larry D; Boineau, Robin (Br J Ophthalmol, 2002)
AIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes. METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system. RESULTS: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86). CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.
Keywords: Age of Onset; Aged; Aged, 80 and over; Arteriosclerosis; Black People; Blood Pressure; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Longitudinal Studies; Male; Odds Ratio; Prospective Studies; Regression Analysis; Risk Factors; Time Factors; White People

Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults. - Newman, Anne B; Naydeck, Barbara L; Sutton-Tyrrell, Kim; Edmundowicz, Daniel; O'Leary, Daniel; Kronmal, Richard; Burke, Gregory L; Kuller, Lewis H (Arterioscler Thromb Vasc Biol, 2002)
BACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown. METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures. CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.
Keywords: Aged; Aged, 80 and over; Calcinosis; Cardiovascular Diseases; Carotid Stenosis; Cohort Studies; Coronary Artery Disease; Demography; Female; Humans; Male; Prevalence; Risk Factors; Sensitivity and Specificity; Sex Factors; Tomography, X-Ray Computed; Tunica Intima; Tunica Media

Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study. - Wong, T Y; Hubbard, L D; Klein, R; Marino, E K; Kronmal, R; Sharrett, A R; Siscovick, D S; Burke, G; Tielsch, J M (Br J Ophthalmol, 2002)
AIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people. METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised. RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes. CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Cohort Studies; Diabetic Retinopathy; Eye; Female; Humans; Male; Microcirculation; Prospective Studies; Retina; Retinal Diseases

Serum potassium level and dietary potassium intake as risk factors for stroke. - Green, D M; Ropper, A H; Kronmal, R A; Psaty, B M; Burke, G L (Neurology, 2002)
BACKGROUND: Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. METHODS: The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. RESULTS: Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. CONCLUSIONS: A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.
Keywords: Aged; Cohort Studies; Confidence Intervals; Diuretics; Humans; Linear Models; Male; Potassium; Potassium, Dietary; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke

Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study. - Lemaitre, Rozenn N; Psaty, Bruce M; Heckbert, Susan R; Kronmal, Richard A; Newman, Anne B; Burke, Gregory L (Arch Intern Med, 2002)
BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol. METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years' follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding variables. RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline. CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.
Keywords: Aged; Cholesterol, LDL; Coronary Disease; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Incidence; Male; Multivariate Analysis; Proportional Hazards Models; Risk Factors; United States

Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study. - Psaty, Bruce M; Manolio, Teri A; Smith, Nicholas L; Heckbert, Susan R; Gottdiener, John S; Burke, Gregory L; Weissfeld, Joel; Enright, Paul; Lumley, Thomas; Powe, Neil; Furberg, Curt D (Arch Intern Med, 2002)
BACKGROUND: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention. OBJECTIVE: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications. RESULTS: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37% at baseline to 49% in 1999. The 51% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5% in 1990 to 51.1% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased. CONCLUSIONS: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers--the preferred agents since 1993 according to the recommendations of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure--remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure.
Keywords: Age Factors; Aged; Antihypertensive Agents; Awareness; Cohort Studies; Drug Therapy; Female; Health Knowledge, Attitudes, Practice; Humans; Hypertension; Male; Prospective Studies; Time Factors

The 6-min walk test: a quick measure of functional status in elderly adults. - Enright, Paul L; McBurnie, Mary Ann; Bittner, Vera; Tracy, Russell P; McNamara, Robert; Arnold, Alice; Newman, Anne B (Chest, 2003)
OBJECTIVES: To determine the correlates of the total 6-min walk distance (6MWD) in a population sample of adults > or = 68 years old. METHODS: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular Health Study cohort during their seventh annual examination. RESULTS: Of the 3,333 participants with a clinic visit, 2,281 subjects (68%) performed the 6MWT. There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general correlates of a shorter 6MWD in linear regression models in women and men included the following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression, and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV(1) in women; and the use of digitalis in men. Approximately 30% of the variance in 6MWD was explained by the linear regression models. Newly described bivariate associations of a shorter 6MWD included impaired activities of daily living; self-reported poor health; less education; nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes; and higher levels of C-reactive protein, fibrinogen, or WBC count. CONCLUSIONS: Most community-dwelling elderly persons can quickly and safely perform this functional status test in the outpatient clinic setting. The test may be used clinically to measure the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis, diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older adults. Expected values should be adjusted for the patient's age, gender, height, and weight.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Exercise Test; Female; Humans; Ischemic Attack, Transient; Linear Models; Male; Mass Screening; Sensitivity and Specificity; Stroke; United States; Walking

Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. - Mozaffarian, Dariush; Lemaitre, Rozenn N; Kuller, Lewis H; Burke, Gregory L; Tracy, Russell P; Siscovick, David S (Circulation, 2003)
BACKGROUND: Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk. METHODS AND RESULTS: In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged > or =65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years' mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk. CONCLUSIONS: Among adults aged > or =65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.
Keywords: Aged; Animals; Arrhythmias, Cardiac; Diet; Eating; Fatty Acids, Omega-3; Female; Fishes; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Risk; Tuna

Cereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals. - Mozaffarian, Dariush; Kumanyika, Shiriki K; Lemaitre, Rozenn N; Olson, Jean L; Burke, Gregory L; Siscovick, David S (JAMA, 2003)
CONTEXT: People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population. OBJECTIVE: To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons. DESIGN: Prospective cohort study conducted from 1989 to June 2000. SETTING AND PARTICIPANTS: Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire. MAIN OUTCOME MEASURE: Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction). RESULTS: During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend =.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend =.98) nor vegetable fiber intake (P for trend =.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources. CONCLUSIONS: Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber.
Keywords: Aged; Cardiovascular Diseases; Dietary Fiber; Edible Grain; Female; Fruit; Humans; Male; Nutrition Assessment; Prospective Studies; Risk; Vegetables

Early age-related maculopathy in the cardiovascular health study. - Klein, Ronald; Klein, Barbara E K; Marino, Emily K; Kuller, Lewis H; Furberg, Curt; Burke, Gregory L; Hubbard, Larry D (Ophthalmology, 2003)
OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes. DESIGN: Population-based cohort study. PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998. METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Early ARM. RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites (18.2%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM. CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Arteriosclerosis; Blood Pressure; C-Reactive Protein; California; Cohort Studies; Diet; European Continental Ancestry Group; Female; Humans; Hypertension; Leukocyte Count; Longitudinal Studies; Macular Degeneration; Male; Mid-Atlantic Region; North Carolina; Prevalence; Prospective Studies; Risk Factors; Serum Albumin

Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. - Shlipak, Michael G; Fried, Linda F; Crump, Casey; Bleyer, Anthony J; Manolio, Teri A; Tracy, Russell P; Furberg, Curt D; Psaty, Bruce M (Circulation, 2003)
BACKGROUND: Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. METHODS AND RESULTS: The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar. CONCLUSION: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.
Keywords: Aged; alpha-2-Antiplasmin; Biomarkers; Blood Coagulation Factors; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Creatinine; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Humans; Inflammation; Interleukin-6; Male; Prospective Studies; Renal Insufficiency; Risk Factors

Evaluation of dementia in the cardiovascular health cognition study. - Lopez, Oscar L; Kuller, Lewis H; Fitzpatrick, Annette; Ives, Diane; Becker, James T; Beauchamp, Norman (Neuroepidemiology, 2003)
OBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS). METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists. RESULTS: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer's disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women. CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.
Keywords: Age Distribution; Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Dementia; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Prevalence; Risk Factors; Sex Distribution

Hormone replacement therapy and sleep-disordered breathing. - Shahar, Eyal; Redline, Susan; Young, Terry; Boland, Lori L; Baldwin, Carol M; Nieto, F Javier; O'Connor, George T; Rapoport, David M; Robbins, John A (Am J Respir Crit Care Med, 2003)
Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant's home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.
Keywords: Age Distribution; Aged; Body Mass Index; Causality; Cohort Studies; Confidence Intervals; Estrogen Replacement Therapy; Female; Humans; Logistic Models; Middle Aged; Multivariate Analysis; Odds Ratio; Polysomnography; Postmenopause; Prevalence; Sensitivity and Specificity; Severity of Illness Index; Sleep Apnea Syndromes; Sleep Stages; United States

Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. - Lopez, Oscar L; Jagust, William J; DeKosky, Steven T; Becker, James T; Fitzpatrick, Annette; Dulberg, Corinne; Breitner, John; Lyketsos, Constantine; Jones, Beverly; Kawas, Claudia; Carlson, Michelle; Kuller, Lewis H (Arch Neurol, 2003)
OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study. DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort. SETTING: Multicenter population study. PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI. MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type. RESULTS: The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%. CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Dementia; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Memory Disorders; Neuropsychological Tests; Pennsylvania; Population; Psychiatric Status Rating Scales

The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study. - Wong, Tien Yin; Klein, Ronald; Sharrett, A Richey; Manolio, Teri A; Hubbard, Larry D; Marino, Emily K; Kuller, Lewis; Burke, Gregory; Tracy, Russell P; Polak, Joseph F; Gottdiener, John S; Siscovick, David S (Ophthalmology, 2003)
PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons. DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities. METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations. MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis. RESULTS: The prevalence of retinal microvascular abnormalities was 8.3% for retinopathy, 9.6% for focal arteriolar narrowing, and 7.7% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis. CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Prevalence; Retinal Diseases; Retinal Vessels; Risk Factors; United States

A prospective analysis of risk factors for white matter disease in the brain stem: the Cardiovascular Health Study. - Ding, Jingzhong; Nieto, F Javier; Beauchamp, Norman J; Longstreth, W T; Manolio, Teri A; Hetmanski, Jacqueline B; Fried, Linda P (Neuroepidemiology, 2003)
BACKGROUND AND PURPOSE: White matter disease (WMD) in the brain stem may be a predictor of poor clinical outcome, independent of WMD in the periventricular and subcortical areas of the brain. Many cardiovascular risk factors such as older age, hypertension, and smoking have been suggested as risk factors for WMD in the periventricular and subcortical areas of the brain. However, no epidemiologic study has examined the associations between cardiovascular risk factors and WMD in the brain stem. METHODS: A total of 789 participants, aged 65 years or older, from the Cardiovascular Health Study constituted the present study population. WMD, defined as hyperintensive lesions on magnetic resonance imaging (MRI), in the brain stem was measured in 1992/1993 and 1997/1998. RESULTS: Of the 789 participants, 212 (26.9%) had WMD in the brain stem in 1997/1998. In multivariate logistic regression analysis, the presence of WMD in the brain stem in 1997/1998 was significantly associated with several variables measured in 1992/1993: an increase by 5 years of age (OR = 1.51, 95% CI: 1.25-1.83), a 10-pack-years increase in smoking (OR = 1.12, 95% CI: 1.04-1.21), a 0.1-liter increase in first-second forced expiratory volume (OR = 0.95, 95% CI: 0.92-0.99), a 1 micromol/l increase in fibrinogen level (OR = 1.13, 95% CI: 1.03-1.23), and MRI infarction (OR = 2.58, 95% CI: 1.78-3.74). Excluding those (n = 167) with WMD in the brain stem in 1992/1993, the pattern remained. Hypertension was not associated with WMD in the brain stem. CONCLUSIONS: Increased age, smoking, lower forced expiratory volume, increased fibrinogen level, and MRI infarction, but not hypertension, may be independent risk factors for WMD in the brain stem in older adults.
Keywords: Age Factors; Aged; Brain Diseases; Brain Infarction; Brain Stem; Cardiovascular Diseases; Female; Fibrinogen; Forced Expiratory Volume; Humans; Magnetic Resonance Imaging; Male; Prospective Studies; Regression Analysis; Risk Factors; Smoking

The relation of dietary patterns to future survival, health, and cardiovascular events in older adults. - Diehr, Paula; Beresford, Shirley A A (J Clin Epidemiol, 2003)
BACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns. METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later. RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large. CONCLUSIONS: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes.
Keywords: Aged; Cardiovascular Diseases; Cluster Analysis; Diet; Energy Intake; Female; Follow-Up Studies; Health Status; Humans; Incidence; Linear Models; Male; Nutritional Physiological Phenomena; Survival Rate

Relationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study. - Edwards, Matthew S; Hansen, Kimberley J; Craven, Timothy E; Cherr, Gregory S; Bleyer, Anthony J; Burke, Gregory L; Dean, Richard H (Am J Kidney Dis, 2003)
BACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination. RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041). CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.
Keywords: Aged; Blood Pressure; Female; Humans; Hypertension; Kidney; Kidney Diseases; Male; Prospective Studies; Ultrasonography, Doppler, Duplex; Vascular Diseases

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. - Fried, Linda F; Shlipak, Michael G; Crump, Casey; Bleyer, Anthony J; Gottdiener, John S; Kronmal, Richard A; Kuller, Lewis H; Newman, Anne B (J Am Coll Cardiol, 2003)
OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women. RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.
Keywords: Aged; Cardiovascular Diseases; Confidence Intervals; Creatinine; Female; Heart Failure; Humans; Intermittent Claudication; Kidney Failure, Chronic; Male; Odds Ratio; Predictive Value of Tests; Survival Analysis

Risk factors for dementia in the cardiovascular health cognition study. - Kuller, Lewis H; Lopez, Oscar L; Newman, Anne; Beauchamp, Norman J; Burke, Greg; Dulberg, Corinne; Fitzpatrick, Annette; Fried, Linda; Haan, Mary N (Neuroepidemiology, 2003)
BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.
Keywords: Aged; Aged, 80 and over; Apolipoproteins E; Cardiovascular Diseases; Cognition Disorders; Dementia; Female; Genotype; Humans; Magnetic Resonance Imaging; Male; Odds Ratio; Predictive Value of Tests; Proportional Hazards Models; Risk Factors

Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. - Lopez, Oscar L; Jagust, William J; Dulberg, Corinne; Becker, James T; DeKosky, Steven T; Fitzpatrick, Annette; Breitner, John; Lyketsos, Constantine; Jones, Beverly; Kawas, Claudia; Carlson, Michelle; Kuller, Lewis H (Arch Neurol, 2003)
OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.
Keywords: Aged; Apolipoprotein E4; Apolipoproteins E; Brain; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Depressive Disorder; Female; Humans; Logistic Models; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mood Disorders; Pennsylvania; Population; Risk Factors

"Successful aging": effect of subclinical cardiovascular disease. - Newman, Anne B; Arnold, Alice M; Naydeck, Barbara L; Fried, Linda P; Burke, Gregory L; Enright, Paul; Gottdiener, John; Hirsch, Calvin; O'Leary, Daniel; Tracy, Russell (Arch Intern Med, 2003)
BACKGROUND: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined. METHODS: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning. RESULTS: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself. CONCLUSIONS: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.
Keywords: Aged; Aged, 80 and over; Aging; C-Reactive Protein; Cardiovascular Diseases; Female; Health Status; Humans; Longitudinal Studies; Male; Quality of Life; Regression Analysis; Risk Factors

Transitions in spousal caregiving. - Burton, Lynda C; Zdaniuk, Bozena; Schulz, Richard; Jackson, Sharon; Hirsch, Calvin (Gerontologist, 2003)
PURPOSE: This study describes transitions over 5 years among community-dwelling elderly spouses into and within caregiving roles and associated health outcomes. DESIGN AND METHODS: Participants in the Caregiver Health Effects Study (n = 818) were interviewed four times over 5 years with changes in their caregiving status described. Analyses of the effect on health outcomes of transitions were performed on those for whom four observations were available (n = 428). RESULTS: Only half (49.5%) of noncaregivers at baseline remained noncaregivers at 5-year follow-up. The remainder experienced one or more transitions, including moving into the caregiving role, their own or their spouse's death, or placement of their spouse in a long-term care facility. The trajectory of health outcomes associated with caregiving was generally downward. Those who transitioned to heavy caregiving had more symptoms of depression, and poorer self-reported health and health behaviors. IMPLICATIONS: Transitions into and within the caregiving role should be monitored for adverse health effects on the caregiver, with interventions tailored to the individual's location in the caregiving trajectory.
Keywords: Adaptation, Psychological; Aged; Aged, 80 and over; Caregivers; Female; Health Behavior; Health Status; Humans; Long-Term Care; Male; Residence Characteristics; Spouses; Stress, Psychological; Time Factors

Variation in symptoms of sleep-disordered breathing with race and ethnicity: the Sleep Heart Health Study. - O'Connor, George T; Lind, Bonnie K; Lee, Elisa T; Nieto, F Javier; Redline, Susan; Samet, Jonathan M; Boland, Lori L; Walsleben, Joyce A; Foster, Gregory L (Sleep, 2003)
STUDY OBJECTIVES: To examine the relation of sleep-related symptoms to race and ethnicity in a diverse sample of middle-aged and older men and women. DESIGN: Cross-sectional questionnaire survey. SETTING: In the initial phase of the Sleep Heart Health Study, men and women enrolled in participating epidemiologic cohort studies were surveyed. PARTICIPANTS: 13,194 men and women 40 years of age and older, including 11,517 non-Hispanic white, 648 black, 643 American Indian, 296 Hispanic, and 90 Asian-Pacific Islander. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: After adjustment for BMI and other factors, frequent snoring was more common among Hispanic women (odds ratio (OR) = 2.25, 95% confidence interval (CI) = 1.48, 3.42) and black women (OR = 1.55, 95% Ci = 1.13, 2.13) than among non-Hispanic white women. Hispanic men were significantly more likely to report frequent snoring than non-Hispanic white men (OR = 2.30, 95% CI = 1.43, 3.69). Black, American Indian, and Asian men did not differ significantly from white men in snoring prevalence. American Indian women were significantly more likely to report breathing pauses during sleep than their white, non-Hispanic counterparts (OR = 1.52, 95% CI 1.03, 2.24), although polysomnography data on a subset of the sample suggested that the association between this symptom reported on questionnaire and objective evidence of sleep-disordered breathing may be weaker among American Indians than among other groups. Mean Epworth Sleepiness Scale scores were slightly higher in black men and women than in their white, non-hispanic counterparts. CONCLUSIONS: Frequent snoring was more common among black and Hispanic women and Hispanic men than among their white non-Hispanic counterparts, even after adjusting for BMI and other factors. Further research including polysomnography and objective measurements of sleepiness is needed to assess the physiologic and clinical significance of these findings.
Keywords: Adult; Cross-Sectional Studies; Electroencephalography; Electrooculography; Ethnic Groups; Female; Heart Rate; Humans; Male; Polysomnography; Severity of Illness Index; Sleep Apnea Syndromes; Snoring; Surveys and Questionnaires

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study. - Psaty, Bruce M; Anderson, Melissa; Kronmal, Richard A; Tracy, Russell P; Orchard, Trevor; Fried, Linda P; Lumley, Thomas; Robbins, John; Burke, Greg; Newman, Anne B; Furberg, Curt D (J Am Geriatr Soc, 2004)
OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.
Keywords: African Americans; African Continental Ancestry Group; Aged; Female; Health Surveys; Humans; Incidence; Lipids; Male; Mortality; Myocardial Infarction; Population Surveillance; Prospective Studies; Risk Factors; Stroke; United States

The association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study. - Barzilay, Joshua I; Kronmal, Richard A; Gottdiener, John S; Smith, Nicholas L; Burke, Gregory L; Tracy, Russell; Savage, Peter J; Carlson, Michelle (J Am Coll Cardiol, 2004)
OBJECTIVES: The purpose of this study was to determine if fasting glucose levels are an independent risk factor for congestive heart failure (CHF) in elderly individuals with diabetes mellitus (DM) with or without coronary heart disease (CHD). BACKGROUND: Diabetes mellitus and CHF frequently coexist in the elderly. It is not clear whether fasting glucose levels in the setting of DM are a risk factor for incident CHF in the elderly. METHODS: A cohort of 829 diabetic participants, age > or =65 years, without prevalent CHF, was followed for five to eight years. The Cox proportional hazards modeling was used to determine the risk of CHF by fasting glucose levels. The cohort was categorized by the presence or absence of prevalent CHD. RESULTS: For a 1 standard deviation (60.6 mg/dl) increase in fasting glucose, the adjusted hazard ratios for incident CHF among participants without CHD at baseline, with or without an incident myocardial infarction (MI) or CHD event on follow-up, was 1.41 (95% confidence interval 1.24 to 1.61; p < 0.0001). Among those with prevalent CHD at baseline, with or without another incident MI or CHD event on follow-up, the corresponding adjusted hazard ratio was 1.27 (95% confidence interval 1.02 to 1.58; p < 0.05). CONCLUSIONS: Among older adults with DM, elevated fasting glucose levels are a risk factor for incident CHF. The relationship of fasting glucose to CHF differs somewhat by the presence or absence of prevalent CHD.
Keywords: Aged; Biomarkers; Blood Glucose; Blood Pressure; Coronary Disease; Diabetes Mellitus; Diabetic Angiopathies; Fasting; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Proportional Hazards Models; Risk Factors; Statistics as Topic; Stroke Volume; Ventricular Function, Left

Associations between gender and measures of daytime somnolence in the Sleep Heart Health Study. - Baldwin, Carol M; Kapur, Vishesh K; Holberg, Catharine J; Rosen, Carol; Nieto, F Javier (Sleep, 2004)
STUDY OBJECTIVES: To examine the relationship of gender to subjective measures of sleepiness, including the Epworth Sleepiness Scale (ESS), in a community-based population. DESIGN: A cross-sectional study. SETTING/PARTICIPANTS: Multicenter Sleep Heart Health Study participants (N = 6.440, 52% women) recruited from ongoing cohort studies. INTERVENTIONS: N/A. MEASUREMENTS: Scores from the ESS, Sleep Heart Health Study daytime sleepiness and feeling unrested questions, polysomnography results (respiratory disturbance index at 4% desaturation), as well as data on difficulty initiating and maintaining sleep, insufficient sleep, sedative use, alcohol use, cardiovascular or respiratory disease, frequent awakening due to leg cramps. RESULTS: Women reported feeling sleepy as often as men did (odds ratio [OR] = 1.06; confidence interval [CI], 0.86-1.32), but women were less likely to have an ESS score > 10 (adjusted OR = 0.77; CI, 0.66-0.90) and more likely to report feeling unrested (adjusted OR = 1.39; CI, 1.14-1.69) than men. In men, the ESS score was more strongly correlated with reports of feeling unrested or sleepy compared to women. CONCLUSIONS: Men and women answer questions on sleepiness differently. Findings indicate that using the ESS to detect subjective sleepiness is more likely to identify men with sleepiness. Since the ESS is more strongly related to other subjective measures in men, the ESS may be a more sensitive measure of subjective sleepiness in men than in women.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Disorders of Excessive Somnolence; Female; Health Status; Humans; Hypertension; Male; Middle Aged; Polysomnography; Severity of Illness Index; Sex Factors

Associations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study. - Edwards, Matthew S; Hansen, Kimberley J; Craven, Timothy E; Bleyer, Anthony J; Burke, Gregory L; Levy, Pavel J; Dean, Richard H (Vasc Endovascular Surg, 2004)
Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity >/= 1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African-Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/-4.9 years underwent RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p = 0.002), previous myocardial infarction (p < 0.001), >/= 25% diameter-reducing internal carotid artery stenosis (p = 0.010), increased carotid intimal medial thickness (p = 0.003), and major electrocardiographic abnormalities (p = 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.
Keywords: Aged; Arteriosclerosis; Cardiovascular Diseases; Cohort Studies; Humans; Hypertension, Renovascular; Longitudinal Studies; Male; Multivariate Analysis; Prevalence; Prospective Studies; Renal Artery Obstruction; Ultrasonography; United States

Concurrent and long-term predictors of older adults' use of community-based long-term care services: the Caregiver Health Effects Study. - Bookwala, Jamila; Zdaniuk, Bozena; Burton, Lynda; Lind, Bonnie; Jackson, Sharon; Schulz, Richard (J Aging Health, 2004)
OBJECTIVE: This study examined concurrent and long-term associations between caregiver-related characteristics and the use of community long-term care services in a sample of 186 older adults caring for a disabled spouse. METHOD: We used two waves of data from the Caregiver Health Effects Study, an ancillary study of the Cardiovascular Health Study. Caregiver-related need variables as predictors of service use were of primary interest and included caregiving demands, caregiver mental and physical health, and mastery. Their contribution to service use was examined after controlling for known predictors of service use. RESULTS: At Time 1, more caregiver depressive symptoms predicted greater service use; at Time 2, more caregiver activity restriction and depressive symptoms predicted greater formal service use; increases in caregiver activity restriction and depressive symptomatology over time predicted increases in service use. DISCUSSION: Caregiver-related need variables play a significant role in defining utilization patterns of community-based long-term care services among older adults.
Keywords: Aged; Caregivers; Community Health Services; Disabled Persons; Forecasting; Health Services for the Aged; Humans; Long-Term Care; Regression Analysis; Spouses; United States

Fish intake and risk of incident atrial fibrillation. - Mozaffarian, Dariush; Psaty, Bruce M; Rimm, Eric B; Lemaitre, Rozenn N; Burke, Gregory L; Lyles, Mary F; Lefkowitz, David; Siscovick, David S (Circulation, 2004)
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is particularly common in the elderly. Although effects of fish intake, including potential antiarrhythmic effects, may favorably influence risk of AF, relationships between fish intake and AF incidence have not been evaluated. METHODS AND RESULTS: In a prospective, population-based cohort of 4815 adults > or =age 65 years, usual dietary intake was assessed at baseline in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. AF incidence was prospectively ascertained on the basis of hospital discharge records and annual electrocardiograms. During 12 years' follow-up, 980 cases of incident AF were diagnosed. In multivariate analyses, consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF, with 28% lower risk with intake 1 to 4 times per week (HR=0.72, 95% CI=0.58 to 0.91, P=0.005), and 31% lower risk with intake > or =5 times per week (HR=0.69, 95% CI=0.52 to 0.91, P=0.008), compared with <1 time per month (P trend=0.004). Results were not materially different after adjustment for preceding myocardial infarction or congestive heart failure. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of AF. CONCLUSIONS: Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF. Fish intake may influence risk of this common cardiac arrhythmia.
Keywords: Aged; Animals; Atrial Fibrillation; Cardiotonic Agents; Cohort Studies; Cooking; Diet; Dietary Fats; Fatty Acids, Omega-3; Fish Oils; Fishes; Follow-Up Studies; Humans; Incidence; Massachusetts; Proportional Hazards Models; Prospective Studies; Risk; Seafood; Tuna

Incidence and prevalence of dementia in the Cardiovascular Health Study. - Fitzpatrick, Annette L; Kuller, Lewis H; Ives, Diane G; Lopez, Oscar L; Jagust, William; Breitner, John C S; Jones, Beverly; Lyketsos, Constantine; Dulberg, Corinne (J Am Geriatr Soc, 2004)
OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. SETTING: Four U.S. communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.
Keywords: African Americans; Age Distribution; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Dementia; Dementia, Vascular; Education; European Continental Ancestry Group; Female; Humans; Incidence; Longitudinal Studies; Male; Prevalence; Proportional Hazards Models; Risk Factors; Sex Distribution; United States

Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. - Fried, Linda; Solomon, Cam; Shlipak, Michael; Seliger, Stephen; Stehman-Breen, Catherine; Bleyer, Anthony J; Chaves, Paolo; Furberg, Curt; Kuller, Lewis; Newman, Anne (J Am Soc Nephrol, 2004)
Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.
Keywords: Aged; Biomarkers; C-Reactive Protein; Creatinine; Factor VII; Female; Fibrinogen; Follow-Up Studies; Glomerular Filtration Rate; Hemoglobins; Humans; Leukocyte Count; Linear Models; Longitudinal Studies; Male; Predictive Value of Tests; Prospective Studies; Renal Insufficiency; Serum Albumin; Thrombosis

Lifestyles of older adults: can we influence cardiovascular risk in older adults? - Mozaffarian, Dariush; Fried, Linda P; Burke, Gregory L; Fitzpatrick, Annette; Siscovick, David S (Am J Geriatr Cardiol, 2004)
Influences of lifestyle habits on cardiovascular disease risk among older adults are not well established. The authors present evidence from the Cardiovascular Health Study that dietary, physical activity, and smoking habits assessed late in life are associated with cardiovascular disease risk among adults aged 65 years or older. Persons consuming fatty fish twice per week had a 47% lower risk of coronary death compared with those who consumed fatty fish less than once per month, while cereal fiber intake (about two whole-grain bread slices per day) was associated with a 14% lower risk of myocardial infarction or stroke. Modest alcohol intake (1-6 drinks per week) predicted the fewest subclinical cerebrovascular abnormalities. Compared with little activity, moderate and high leisure-time activity predicted 28% and 44% lower mortality, respectively, while compared with nonexercisers, low, moderate, and high exercise intensity predicted 30%, 37%, and 53% more years of healthy life, respectively. Former and current smokers had 25% and 44% fewer years of healthy life than those who never smoked; lifetime smoking (pack-years) predicted higher mortality. Clinical practice and public health implications, gaps in knowledge, and future research directions are summarized.
Keywords: Aged; Alcohol Drinking; Cardiovascular Diseases; Diet Fads; Dietary Fiber; Exercise; Feeding Behavior; Humans; Life Style; Predictive Value of Tests; Risk Factors; Smoking

Mesenteric artery disease in the elderly. - Hansen, Kimberley J; Wilson, David B; Craven, Timothy E; Pearce, Jeffrey D; English, William P; Edwards, Matthew S; Ayerdi, Juan; Burke, Gregory L (J Vasc Surg, 2004)
PURPOSE: The purpose of this study was to estimate the population-based prevalence of mesenteric artery stenosis (MAS) and occlusion among independent elderly Americans. METHOD: As part of an ancillary investigation to the Cardiovascular Health Study (CHS), participants in the Forsyth County, NC cohort had visceral duplex sonography of the celiac arteries and superior mesenteric arteries (SMAs). Critical MAS was defined by celiac peak systolic velocity >or=2.0 m/s and/or SMA peak systolic velocity >or=2.7 m/s. Occlusion of either vessel was defined by lack of a Doppler-shifted signal within the imaged artery. Demographic data, blood pressures, and blood lipid levels were collected as part of the baseline CHS examination. Participants' weights were measured at baseline and before the duplex exam. Univariate tests of association were performed with two-way contingency tables, Student t tests, and Fisher exact tests. Multivariate associations were examined with logistic regression analysis. RESULTS: A total of 553 CHS participants had visceral duplex sonography technically adequate to define the presence or absence of MAS. The study group had a mean age of 77.2 +/- 4.9 years and comprised 63% women and 37% men. Participant race was 76% white and 23% African-American. Ninety-seven participants (17.5%) had MAS. There was no significant difference in age, race, gender, body mass index, blood pressure, cholesterol, or low-density lipoproteins for participants with or without MAS. Forward stepwise variable selection found renal artery stenosis (P =.008; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.31, 6.21) and high-density lipoprotein >40 (P =.02; OR, 3.03; 95% CI, 1.17, 7.81) significantly associated with MAS in a multivariate logistic regression model. Eighty-three of the 97 participants with MAS (15.0% of the cohort) had isolated celiac stenosis. Seven participants (1.3% of the cohort) had combined celiac and SMA stenosis. Five participants (0.9% of the cohort) had isolated SMA stenosis. Two participants (0.4% of the cohort) had celiac occlusion. Considering all participants with MAS, there was no association with weight change. However, SMA stenosis and celiac occlusion demonstrated an independent association with annualized weight loss (P =.028; OR, 1.54; 95% CI, 1.05, 2.26) and with renal artery stenosis (P =.001; OR, 9.48; 95% CI, 2.62, 34.47). CONCLUSION: This investigation provides the first population-based estimate of the prevalence of MAS among independent elderly Americans. MAS existed in 17.5% of the study cohort. The majority had isolated celiac disease. SMA stenosis and celiac artery occlusion demonstrated a significant and independent association with weight loss and concurrent renal artery disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Arteriosclerosis; Celiac Artery; Cohort Studies; Female; Humans; Male; Mesenteric Arteries; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Prevalence; Ultrasonography, Doppler, Duplex; Weight Loss

Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. - Seliger, Stephen L; Siscovick, David S; Stehman-Breen, Catherine O; Gillen, Daniel L; Fitzpatrick, Annette; Bleyer, Anthony; Kuller, Lew H (J Am Soc Nephrol, 2004)
Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.
Keywords: Aged; Alzheimer Disease; Cardiovascular Diseases; Creatinine; Dementia; Dementia, Vascular; Female; Humans; Kidney; Kidney Diseases; Male; Muscles; Proportional Hazards Models

Neighbourhood environments and mortality in an elderly cohort: results from the cardiovascular health study. - Diez Roux, Ana V; Borrell, Luisa N; Haan, Mary; Jackson, Sharon A; Schultz, Richard (J Epidemiol Community Health, 2004)
BACKGROUND: It has been postulated that neighbourhood conditions are related to the health of the elderly population but longitudinal studies are rare and confounding by individual level variables remains a possibility. METHODS: Data were obtained from the cardiovascular health study, a population based study of adults aged 65 years and older. Census block groups were used as proxies for neighbourhoods. A summary score was used to characterise the neighbourhood socioeconomic environment. Information on personal socioeconomic indicators, cardiovascular disease prevalence, and cardiovascular risk factors was obtained from the baseline examination. Proportional hazards regression and propensity score matching were used to control for individual level variables. RESULTS: Over the eight year follow up there were 1346 deaths among the 5074 participants, of which 43% were attributable to cardiovascular disease. Among white participants, living in the most disadvantaged neighbourhood group was associated with higher rates of cardiovascular death, after adjustment for income, education, and occupation (hazard ratio (HR) 1.5, 95% confidence intervals (CI) 1.2 to 1.9). No neighbourhood differences were observed for non-cardiovascular deaths. Estimates for black participants were 1.3 (95% CI 0.7 to 2.3) for cardiovascular deaths and 1.4 (95% CI 0.8 to 2.4) for non-cardiovascular deaths, but sample size was small. In white participants, associations of neighbourhood characteristics with cardiovascular mortality persisted after adjustment for prevalent baseline disease and cardiovascular risk factors. The use of propensity score matching led to similar results (HR for the lowest compared with the highest neighbourhood score group: 1.6 95% CI 1.1 to 2.5, controlling for personal socioeconomic indicators). CONCLUSION: Neighbourhood disadvantage is related to rates of cardiovascular death in elderly white adults.
Keywords: African Americans; Aged; Cardiovascular Diseases; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Income; Male; Poverty Areas; Residence Characteristics; Risk Factors; Socioeconomic Factors; United States

Plasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons: the Cardiovascular Health Study. - Longstreth, W T; Katz, Ronit; Olson, Jean; Bernick, Charles; Carr, J Jeffrey; Malinow, M René; Hess, David L; Cushman, Mary; Schwartz, Stephen M (Arch Neurol, 2004)
BACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI). DESIGN: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype. RESULTS: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P =.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P =.07 for linear trend). CONCLUSION: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.
Keywords: Aged; Aging; Brain; Brain Infarction; Female; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Odds Ratio; Radiography; Risk Factors

Progressive cognitive impairment after stroke. - Toole, James F; Bhadelia, Rafeeque; Williamson, Jeff D; Veltkamp, Roland (J Stroke Cerebrovasc Dis, 2004)
OBJECTIVE: We examined the putative relationship between stroke and cognitive function in the population-based prospective cohort of the Cardiovascular Health Study (CHS). METHODS: Of the 5888 participants of the CHS aged 65 years or older, there were 5364 with more than one modified mini-mental (3MS) examination between 1992 and 1998. To determine the effect of baseline stroke before first and subsequent (stroke between two consecutive examinations) 3MS examination on cognitive function, linear regression models were computed with potential confounders entered as additional independent variables. Stroke was divided into right and left hemispheres or posterior circulation on the basis of the clinical and/or imaging information by the hospital that treated the event and subsequent adjudication by CHS committee. RESULTS: Participants with baseline stroke had an average 3MS decline of 1.2 (95% confidence interval [CI]: -0.7 - -1.7) points per year more than those without one. Those with a history of subsequent stroke had an average first year 3MS decline of 6.2 (CI -8.7 - -3.7) for left hemisphere, 3.5 (CI -5.3 - -1.8) for right hemisphere, and 1.1 (CI -3.9 - 1.6) for posterior circulation more than those without stroke. The effect of stroke on the rate of cognitive decline appeared to ameliorate after the first year (test for linear trend among those with stroke, P = .003). CONCLUSION: Results from this prospective population-based data study show that stroke in the left hemisphere results in a more pronounced decline in cognition than that in the right hemisphere and that cognitive loss because of stroke appears to attenuate over time, perhaps as a result of relearning.

Racial differences in endothelial function in postmenopausal women. - Loehr, Laura R; Espeland, Mark A; Sutton-Tyrrell, Kim; Burke, Gregory L; Crouse, John R; Herrington, David M (Am Heart J, 2004)
OBJECTIVE: Racial differences in cardiovascular mortality among women remain largely unexplained. Preliminary data suggest that African American and Caucasian differences in endothelial function may parallel differential cardiovascular disease (CVD) risk in women. To further study differences in endothelial function between African American and Caucasian women, we analyzed measures of brachial artery flow-mediated dilation (FMD) in women enrolled in the Cardiovascular Health Study (CHS). METHODS AND RESULTS: Brachial artery FMD was measured in the fasting state using established ultrasound techniques in 1330 Caucasian and 297 African American female participants in CHS (mean age 78.4 +/- 4.4 years). General linear models were used to compare FMD between African American and Caucasian women after adjusting for baseline brachial diameter, hypertension, diabetes, smoking, cholesterol, systolic blood pressure, body mass index, waist/hip ratio, age, education, income level; use of angiotensin-converting enzyme inhibitors, beta-blockers, nitroglycerin, estrogens and lipid-lowering drugs; and presence of clinical or subclinical disease. Adjusted absolute change and percent change in brachial artery diameter was significantly reduced in African American women compared with Caucasian women (P <.0001 and P =.0002, respectively). Similar results were found when the women were stratified by history of CVD (- CVD, P =.02; + CVD, P =.001) and CVD or subclinical vascular disease (- disease, P =.01, + disease, P =.03). CONCLUSIONS: In this cohort, brachial artery FMD was lower in African American women compared to Caucasian women, and this difference persisted after adjustment by multivariable analysis. The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health.
Keywords: African Continental Ancestry Group; Aged; Brachial Artery; Cohort Studies; Endothelium, Vascular; European Continental Ancestry Group; Female; Humans; Multivariate Analysis; Postmenopause; Risk Factors; Vasodilation

The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the cardiovascular health study. - Barzilay, Joshua I; Peterson, Do; Cushman, Mary; Heckbert, Susan R; Cao, Jie J; Blaum, Caroline; Tracy, Russell P; Klein, Ronald; Herrington, David M (Am J Kidney Dis, 2004)
BACKGROUND: Microalbuminuria is a risk factor for coronary heart disease (CHD). It occurs most commonly in the settings of diabetes and hypertension. The mechanisms by which it increases CHD risk are uncertain. METHODS: We examined the cross-sectional association of microalbuminuria with a broad range of CHD risk factors in 3 groups of adults aged 65 years or older with and without microalbuminuria: those with (1) no diabetes or hypertension (n = 1,098), (2) hypertension only (n = 1,450), and (3) diabetes with or without hypertension (n = 465). RESULTS: Three factors were related to microalbuminuria in all 3 groups: age, elevated systolic blood pressure, and markers of systemic inflammation. In patients with neither diabetes nor hypertension, increasing C-reactive protein levels were associated with microalbuminuria (odds ratio per 1-mg/L increase, 1.46; 95% confidence interval [CI], 1.15 to 1.84). Among those with diabetes, an increase in white blood cell (WBC) count was associated with microalbuminuria (odds ratio per 1,000-cell/mL increase, 2.57; 95% CI, 1.12 to 5.89). Among those with hypertension, an increase in WBC count (odds ratio per 1,000-cell/mL increase, 1.83; 95% CI, 1.04 to 3.23) and fibrinogen level (odds ratio per 10-mg/dL increase, 1.02; 95% CI, 1.00 to 1.05) were significantly associated with microalbuminuria. In all 3 groups, prevalent CHD was related to an elevated WBC count. In none of the 3 groups was brachial artery reactivity to ischemia, an in vivo marker of endothelial function, related to microalbuminuria. CONCLUSION: Microalbuminuria is associated with age, systolic blood pressure, and markers of inflammation. These associations reflect potential mechanisms by which microalbuminuria is related to CHD risk.
Keywords: Age Distribution; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Brachial Artery; Comorbidity; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypertension; Inflammation; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Risk Factors; Smoking; Ultrasonography

The relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort. - Kronmal, Richard A; Barzilay, Joshua I; Tracy, Russell P; Savage, Peter J; Orchard, Trevor J; Burke, Gregory L (J Clin Endocrinol Metab, 2004)
It is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6-9 yr. All were free of CHD at baseline. There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43-150 microU/ml (258-900 pmol/liter)] had an adjusted 30% increased relative risk (95% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 microU/ml (<120 pmol/liter)]. Those in the fourth interval [151-400 microU/ml (906-2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3-13.1; P < 0.0001). Approximately 15% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels. Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.
Keywords: Aged; Cohort Studies; Coronary Disease; Diabetes Mellitus, Type 1; Fasting; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Male; Radioimmunoassay; Risk Factors

Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists. - Bryson, Chris L; Smith, Nicholas L; Kuller, Lewis H; Chaves, Paulo H M; Manolio, Teri A; Lewis, William; Boyko, Edward J; Furberg, Curt D; Psaty, Bruce M (J Am Geriatr Soc, 2004)
OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists. DESIGN: Prospective cohort study. SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina. PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older. MEASUREMENTS: Adjudicated incident CHF. RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk. CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.
Keywords: Adrenergic alpha-Antagonists; Aged; Antihypertensive Agents; Benzothiadiazines; Blood Pressure; Cohort Studies; Diuretics; Female; Heart Failure; Humans; Hypertension; Male; Risk Factors; Sodium Chloride Symporter Inhibitors; United States

Sleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study. - Walsleben, Joyce A; Kapur, Vishesh K; Newman, Anne B; Shahar, Eyal; Bootzin, Richard R; Rosenberg, Carl E; O'Connor, George; Nieto, F Javier (Sleep, 2004)
STUDY OBJECTIVES: To describe the distribution of nocturnal sleep characteristics and reports of daytime sleepiness in a large well-defined group of healthy adults. DESIGN: The Sleep Heart Health Study is a multicenter study examining sleep and cardiopulmonary parameters through nocturnal polysomnography in adults enrolled in geographically distinct cardiovascular cohorts. SETTING: Community setting. PARTICIPANTS: 470 subjects enrolled in the Sleep Heart Health Study (n = 6440) were selected as a 'normative' group based on screening of health conditions and daily habits that could interfere with sleep. MEASUREMENTS AND RESULTS: Home-based nocturnal polysomnography was obtained on all participants and centrally scored for sleep and respiratory parameters. Demographic and health-related data were obtained and updated at the time of the home visit. Sleep efficiency decreased by 1.6% for each 10 years of increased age. Sleep time decreased by 0.1 hours (6.0 minutes) for each 10-year age increase and was longer in women. The arousal index increased by 0.8 for each 10-year increase in age and was lower by 1.4 in women. Women had a lower mean percentage of stage 1 and stage 2 sleep. Mean percentage of slow-wave sleep was higher in women (by 6.7%). Percentage of slow-wave sleep decreased with increased age for men only (by 1.9% for each 10-year age change). CONCLUSIONS: Data suggest a clear lessening in the quantity and quality of sleep with age that appears to be more rapid in males compared to females.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Circadian Rhythm; Cohort Studies; Disorders of Excessive Somnolence; Female; Health Status; Humans; Male; Middle Aged; Polysomnography; Sleep; Sleep Stages; Surveys and Questionnaires

Sleep apnea and markers of vascular endothelial function in a large community sample of older adults. - Nieto, F Javier; Herrington, David M; Redline, Susan; Benjamin, Emelia J; Robbins, John A (Am J Respir Crit Care Med, 2004)
Clinical studies have suggested that sleep apnea is associated with impaired brachial artery flow-mediated dilation, a surrogate of endothelial dysfunction. We examined this question among older participants in the baseline examination of the Sleep Heart Health/Cardiovascular Health Study cohort (n = 1,037, age 68 years or older, 56% female). Indices of sleep apnea, derived from 12-channel home polysomnography, were the apnea-hypopnea index (average number of apneas/hypopneas per hour) and the hypoxemia index (percentage of time below 90% O2 saturation). Baseline arterial diameter and percentage of flow-mediated dilation were measured by ultrasound. Sleep apnea measures were associated with baseline diameter and the percentage of flow-mediated dilation, although these associations were weakened after adjustment for other cardiovascular risk factors, particularly body mass index. However, a statistically significant linear association between the hypoxemia index and baseline diameter was observed even after adjustment for body mass index and other confounders (p < 0.01). The associations were stronger among participants who were younger than 80 years and among those who with hypertension. This study adds to the growing body of evidence linking sleep apnea with vascular dysfunction in older subjects. Whether these relationships are entirely independent of obesity is unclear. This association might be one of the mechanisms explaining the relationship between sleep apnea, hypertension, and cardiovascular disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Brachial Artery; Cardiovascular Diseases; Cohort Studies; Comorbidity; Endothelium, Vascular; Female; Humans; Hypertension; Linear Models; Male; Polysomnography; Prevalence; Probability; Residence Characteristics; Risk Assessment; Sampling Studies; Severity of Illness Index; Sleep Apnea Syndromes; Ultrasonography, Doppler

Sleep-disordered breathing and white matter disease in the brainstem in older adults. - Ding, Jingzhong; Nieto, F Javier; Beauchamp, Norman J; Harris, Tamara B; Robbins, John A; Hetmanski, Jacqueline B; Fried, Linda P; Redline, Susan (Sleep, 2004)
STUDY OBJECTIVES: To examine whether sleep-disordered breathing is associated with white matter disease in the brainstem. DESIGN: A population-based longitudinal study. SETTING: Allegheny County, PA; Sacramento County, CA; and Washington County, MD. PATIENTS OR PARTICIPANTS: A total of 789 individuals, aged 68 years or older, drawn from the Sleep Heart Health Study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The participants underwent home polysomnography in 1995-1998 and cerebral magnetic resonance imaging in both 1992-1993 and 1997-1998. The apnea-hypopnea index was not associated with white matter disease in the brainstem, with or without adjusting for age, sex, race, community, body mass index, smoking status, alcohol use, systolic blood pressure, and the use of antihypertensive medication. In contrast, the arousal index (number of arousals per hour of sleep) was inversely associated with brainstem white matter disease (odds ratio = 0.75 for a SD increase in the arousal index, 95% confidence interval: 0.62, 0.92). CONCLUSIONS: The frequency of apneas and hypopneas was not associated with brainstem white matter disease in these older adults. A unique relationship with arousal frequency suggests that ischemic changes in the brainstem may be associated with arousals during sleep.
Keywords: Aged; Arousal; Brain; Brain Stem; Cerebrovascular Disorders; Electrooculography; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Polysomnography; Population Surveillance; Severity of Illness Index; Sleep Apnea Syndromes; Sleep Stages

Sleep-disordered breathing is not associated with the presence of retinal microvascular abnormalities: the Sleep Heart Health Study. - Boland, Lori L; Shahar, Eyal; Wong, Tien Y; Klein, Ronald; Punjabi, Naresh; Robbins, John A; Newman, Anne B (Sleep, 2004)
STUDY OBJECTIVE: Sleep apnea and milder forms of sleep-disordered breathing (SDB) have been associated with overt clinical cardiovascular disease, but it is unknown whether SDB is associated with arterial microvascular pathology. We examined the relation between SDB and retinal microvascular abnormalities. DESIGN: Cross-sectional study. PARTICIPANTS: Subjects were 2,927 men and women, aged 51 to 97 years, who participated in the Sleep Heart Health Study and had retinal photographs taken within approximately 3 years of overnight, unattended, at-home polysomnography. MEASUREMENTS AND RESULTS: A respiratory disturbance index (RDI), calculated as the average number of apneas and hypopneas per hour of sleep, was used as an indicator of SDB in analysis. The overall prevalence of retinopathy was slightly higher in people with higher RDI values (5.4%, 4.9%, 8.6%, and 7.6%, respectively, in increasing quartiles of RDI), but after adjustment for age, body-mass index, hypertension, diabetes, and other factors, the presence of retinopathy was not associated with SDB. With the possible exceptions of microaneurysms and generalized arteriolar narrowing, as measured by lower arteriole-to-venule ratio, specific retinal abnormalities were not associated consistently with the RDI. Relative to the first quartile of RDI, the adjusted odds ratios (95% confidence interval) for the presence of microaneurysm in the second, third, and fourth quartiles of RDI were 1.05 (0.44-2.55), 1.97 (0.89-4.37), and 1.79 (0.78-4.10), respectively. An increase of RDI from 0 to 10 was associated with a predicted decrease in arteriole-to-venule ratio of 0.01. Results were similar when analyses were conducted in normotensive and nondiabetic persons separately. CONCLUSIONS: These data do not demonstrate a notable relation between SDB and retinal abnormalities. However, since this is the first investigation of a link between retinopathy and SDB, similar studies should be conducted in other population samples to demonstrate either consistency or inconsistency of our findings across studies.
Keywords: Aged; Aged, 80 and over; Body Mass Index; Coronary Disease; Cross-Sectional Studies; Female; Humans; Hypoxia; Middle Aged; Polysomnography; Positive-Pressure Respiration; Retina; Retinal Vessels; Sleep Apnea Syndromes

White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. - Kuller, Lewis H; Longstreth, W T; Arnold, Alice M; Bernick, Charles; Bryan, R Nick; Beauchamp, Norman J (Stroke, 2004)
BACKGROUND AND PURPOSE: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors. METHODS: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.
Keywords: Aged; Brain; Female; Humans; Leukoaraiosis; Magnetic Resonance Imaging; Male; Radiography; Risk Factors; Stroke

Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study. - Mukamal, Kenneth J; Chung, Hyoju; Jenny, Nancy S; Kuller, Lewis H; Longstreth, W T; Mittleman, Murray A; Burke, Gregory L; Cushman, Mary; Beauchamp, Norman J; Siscovick, David S (Stroke, 2005)
BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype. METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly. RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors. CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.
Keywords: Aged; Alcohol Drinking; Apolipoproteins E; Brain Infarction; Brain Ischemia; Cohort Studies; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Inflammation; Ischemia; Lipids; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Prospective Studies; Risk; Risk Factors; Stroke; Substance-Related Disorders; Thrombosis; Time Factors; Vascular Diseases

Association of sleep time with diabetes mellitus and impaired glucose tolerance. - Gottlieb, Daniel J; Punjabi, Naresh M; Newman, Ann B; Resnick, Helaine E; Redline, Susan; Baldwin, Carol M; Nieto, F Javier (Arch Intern Med, 2005)
BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index. RESULTS: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded. CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.
Keywords: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus; Disease Progression; Female; Glucose Intolerance; Humans; Male; Middle Aged; Odds Ratio; Prevalence; Prospective Studies; Sleep; Surveys and Questionnaires; Time Factors; United States

Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study. - Edwards, Matthew S; Wilson, David B; Craven, Timothy E; Stafford, Jeanette; Fried, Linda F; Wong, Tien Y; Klein, Ronald; Burke, Gregory L; Hansen, Kimberley J (Am J Kidney Dis, 2005)
BACKGROUND: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. RESULTS: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. CONCLUSION: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.
Keywords: African Americans; Aged; Aged, 80 and over; Aging; Antihypertensive Agents; Capillaries; Cohort Studies; Comorbidity; Creatinine; Diabetes Mellitus; Disease Progression; European Continental Ancestry Group; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Photography; Prospective Studies; Proteinuria; Retina; Retinal Diseases; Retinal Vessels

Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4. - Huang, T L; Zandi, P P; Tucker, K L; Fitzpatrick, A L; Kuller, L H; Fried, L P; Burke, G L; Carlson, M C (Neurology, 2005)
OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.
Keywords: Aged; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Cohort Studies; Dementia; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Feeding Behavior; Female; Fish Oils; Fish Products; Food, Formulated; Genetic Predisposition to Disease; Humans; Incidence; Male; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires

Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. - Shlipak, Michael G; Fried, Linda F; Cushman, Mary; Manolio, Teri A; Peterson, Do; Stehman-Breen, Catherine; Bleyer, Anthony; Newman, Anne; Siscovick, David; Psaty, Bruce (JAMA, 2005)
CONTEXT: Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown. OBJECTIVE: To compare traditional and novel risk factors as predictors of cardiovascular mortality. DESIGN, SETTING, AND PATIENTS: A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years. MAIN OUTCOME MEASURES: Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2. RESULTS: Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference = .15). CONCLUSIONS: Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.
Keywords: Aged; Cardiovascular Diseases; Chronic Disease; Humans; Kidney Diseases; Longitudinal Studies; Risk Factors

Classification of vascular dementia in the Cardiovascular Health Study Cognition Study. - Lopez, O L; Kuller, L H; Becker, J T; Jagust, W J; DeKosky, S T; Fitzpatrick, A; Breitner, J; Lyketsos, C; Kawas, C; Carlson, M (Neurology, 2005)
OBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study. METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI. RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer's Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD). CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebral Arteries; Cohort Studies; Dementia, Vascular; Diagnosis, Differential; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Stroke; United States

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study. - Reiner, Alexander P; Diehr, Paula; Browner, Warren S; Humphries, Stephen E; Jenny, Nancy S; Cushman, Mary; Tracy, Russell P; Walston, Jeremy; Lumley, Thomas; Newman, Anne B; Kuller, Lewis H; Psaty, Bruce M (Atherosclerosis, 2005)
Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.
Keywords: Aged; Aging; Carboxypeptidase B2; Cause of Death; Cohort Studies; Female; Genotype; Health Status; Humans; Inflammation; Longevity; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Thrombosis

C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. - Cushman, Mary; Arnold, Alice M; Psaty, Bruce M; Manolio, Teri A; Kuller, Lewis H; Burke, Gregory L; Polak, Joseph F; Tracy, Russell P (Circulation, 2005)
BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available. METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33% in men and 17% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20%; the incidences were 31% and 10% for elevated and normal CRP levels, respectively. CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Coronary Disease; Female; Humans; Incidence; Inflammation; Male; Myocardial Infarction; Predictive Value of Tests; Risk Factors

Cystatin C and subclinical brain infarction. - Seliger, Stephen L; Longstreth, W T; Katz, Ronit; Manolio, Teri; Fried, Linda F; Shlipak, Michael; Stehman-Breen, Catherine O; Newman, Anne; Sarnak, Mark; Gillen, Daniel L; Bleyer, Anthony; Siscovick, David S (J Am Soc Nephrol, 2005)
Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; Brain Infarction; Confidence Intervals; Creatinine; Cross-Sectional Studies; Cystatin C; Cystatins; Disease Progression; Female; Geriatric Assessment; Humans; Incidence; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Survival Analysis

Determinants of vascular dementia in the Cardiovascular Health Cognition Study. - Kuller, L H; Lopez, O L; Jagust, W J; Becker, J T; DeKosky, S T; Lyketsos, C; Kawas, C; Breitner, J C S; Fitzpatrick, A; Dulberg, C (Neurology, 2005)
OBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia. METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. RESULTS: Approximately 44% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke. CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.
Keywords: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Cardiovascular Diseases; Cerebral Arteries; Cerebral Infarction; Cohort Studies; Comorbidity; Continental Population Groups; Dementia, Vascular; Female; Humans; Lateral Ventricles; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Neuropsychological Tests; Risk Factors; Sex Factors

Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study. - Quan, Stuart F; Katz, Ronit; Olson, Jean; Bonekat, William; Enright, Paul L; Young, Terry; Newman, Anne (Am J Med Sci, 2005)
BACKGROUND: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well. METHODS: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination 1 to 4 years later. RESULTS: Annualized incidence and nonremission rates were the following: TFA (2.8% and 15.4%), FA (12.3% and 22.7%), and EDS (4.4% and 13.4%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining nonremission was much more limited. CONCLUSIONS: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Depression; Female; Health Status; Humans; Incidence; Logistic Models; Male; Odds Ratio; Prevalence; Risk Factors; Sex Factors; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires

Fish consumption and stroke risk in elderly individuals: the cardiovascular health study. - Mozaffarian, Dariush; Longstreth, W T; Lemaitre, Rozenn N; Manolio, Teri A; Kuller, Lewis H; Burke, Gregory L; Siscovick, David S (Arch Intern Med, 2005)
BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.
Keywords: Age Distribution; Aged; Aged, 80 and over; Animals; Cohort Studies; Confidence Intervals; Diet; Fatty Acids, Omega-3; Female; Fish Oils; Fishes; Humans; Incidence; Male; Multivariate Analysis; Probability; Proportional Hazards Models; Risk Assessment; Seafood; Sensitivity and Specificity; Sex Distribution; Stroke; Surveys and Questionnaires; Survival Rate; United States

Fish intake and risk of incident heart failure. - Mozaffarian, Dariush; Bryson, Chris L; Lemaitre, Rozenn N; Burke, Gregory L; Siscovick, David S (J Am Coll Cardiol, 2005)
OBJECTIVES: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF). BACKGROUND: The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown. METHODS: Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated. RESULTS: During 12 years' follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to 0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% CI = 0.52 to 0.91), and 32% lower risk with intake > or =5 times/week (HR = 0.68, 95% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37% lower risk in the highest quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest. CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.
Keywords: Aged; Animals; Cohort Studies; Cooking; Diet; Diet Surveys; Disease-Free Survival; Female; Fishes; Heart Failure; Humans; Incidence; Male; Risk Factors; United States