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

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

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

Respondent Burden in Studies of the Elderly: Experience from the Cardiovascular Health Study (CHS) - Manolio, TA; Hermanson, B; Hill, J; Meyer, M; Cruise, G; Anton-Culver, H (ACC, 1992)
ACC Workshop entitled "Inclusion of Elderly Individuals in Clinical Trials" September 15-16, 1992
Keywords: Health; respondent burden

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

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

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

Cardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study. - Manolio, T A; Furberg, C D; Rautaharju, P M; Siscovick, D; Newman, A B; Borhani, N O; Gardin, J M; Tabatznik, B (J Am Coll Cardiol, 1994)
OBJECTIVES: This study describes the prevalence and correlates of cardiac arrhythmias in older persons. BACKGROUND: Cardiac arrhythmias are frequent in selected samples of elderly persons, but their prevalence and association with cardiovascular disease and its risk factors have not been examined in a large population-based sample. METHODS: In 1,372 participants in the Cardiovascular Health Study, a population-based study of cardiovascular disease risk factors, 24-h ambulatory electrocardiography was performed. RESULTS: Serious arrhythmias, such as sustained ventricular tachycardia and complete atrioventricular block, were uncommon, but brief episodes of ventricular tachycardia (> or = 3 consecutive ventricular depolarizations) were detected in 4.3% of women and 10.3% of men. Ventricular arrhythmias as a group (excluding ectopic beats < 15/h) were more common in men than in women but were not significantly associated with age. The same patterns were true for bradycardia/conduction blocks. Supraventricular arrhythmias as a group (excluding ectopic beats < 15/h), in contrast, did not differ by gender but were strongly associated with increased age. Multivariate analyses showed associations with arrhythmias to differ by gender, with only one association (increased age and supraventricular arrhythmias) present in both women and men. Ventricular arrhythmias, particularly in men, were associated with a higher prevalence of cardiovascular disease and its risk factors and with subclinical disease, as measured by increased left ventricular mass and impaired left ventricular function. CONCLUSIONS: Arrhythmias are common in the elderly, and their association with cardiovascular disease differs by gender. Although risk related to arrhythmias can only be determined by prospective study, such studies should have adequate power to examine potential gender differences in associations.
Keywords: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Diseases; Circadian Rhythm; Electrocardiography, Ambulatory; Female; Humans; Logistic Models; Longitudinal Studies; Male; Prevalence; Risk Factors; Sex Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prevalence and correlates of snoring and observed apneas in 5,201 older adults. - Enright, P L; Newman, A B; Wahl, P W; Manolio, T A; Haponik, E F; Boyle, P J (Sleep, 1996)
The objectives of this study were to describe the prevalence of snoring, observed apneas, and daytime sleepiness in older men and women, and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases (CVD). A cross-sectional design was employed to study sleep problems, CVD, general health, psychosocial factors, and medication use. The subjects were participants in the Cardiovascular Health Study, which included 5,201 adults, aged 65 and older, who were recruited from a random sample of Medicare enrollees in four U.S. communities. Study measures employed were sleep questions, echocardiography, carotid ultrasound, resting electrocardiogram, cognitive function, cardiopulmonary symptoms and diseases, depression, independent activities of daily living (IADLs), and benzodiazepine use. Thirty-three percent of the men and 19% of the women reported loud snoring, which was less frequent in those over age 75. Snoring was positively associated with younger age, marital status, and alcohol use in men, and obesity, diabetes, and arthritis in women. Snoring was not associated, however, with cardiovascular risk factors or clinical CVD in men or women. Observed apneas were reported much less frequently (13% of men and 4% women) than snoring, and they were associated with alcohol use, chronic bronchitis, and marital status in men. Observed apneas were associated with depression and diabetes in women. In both men and women, daytime sleepiness was associated with poor health, advanced age, and IADL limitations. The conclusions of the study were that loud snoring, observed apneas, and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons.
Keywords: Activities of Daily Living; Age Factors; Aged; Cardiovascular Diseases; Comorbidity; Female; Humans; Incidence; Lung Diseases; Male; Narcolepsy; Prevalence; Random Allocation; Sex Factors; Sleep Apnea Syndromes; Snoring

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study. - Newman, A B; Enright, P L; Manolio, T A; Haponik, E F; Wahl, P W (J Am Geriatr Soc, 1997)
OBJECTIVES: To describe the prevalence of self reported sleep disturbances in older men and women and to describe their relationships with health status and cardiovascular disease (CVD). DESIGN: Cross-sectional study of sleep disturbance, CVD, general health, psychosocial factors, physical function, and use of psychotropic medications. SETTING: Participants of the Cardiovascular Health Study, 5201 adults aged 65 and older recruited from a random sample of noninstitutionalized Medicare enrollees in four US communities. MEASURES: Self-reported sleep disturbances and standardized questionnaires for cardiopulmonary symptoms and diseases, depression, social support, activities of daily living, physical activity, cognitive function, and current medications, spirometry, ECG, echocardiography, and carotid ultrasound. RESULTS: Women were twice as likely as men to report difficulty falling asleep (30% vs 14%). Daytime sleepiness, difficulty falling asleep, and frequent awakenings increased in prevalence with age. All symptoms were related strongly to depression. Symptoms of daytime sleepiness were also related strongly to poor health and limitations in activities of daily living in men and women. In multivariate analysis, men taking benzodiazepines were likely to report difficulty falling asleep and daytime sleepiness, whereas women taking benzodiazepines reported difficulty falling asleep and waking up too early. After accounting for these factors, the only cardiovascular disease independently associated with sleep disturbances was angina. Men and women with confirmed angina were 1.6 times more likely to report trouble falling asleep. Independent relationships between sleep disturbances and cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes were relatively weak and inconsistent, though smokers were less likely to report frequent awakenings. CONCLUSIONS: Sleep disturbances are relatively common in older men and women and are associated with poor health, depression, angina, limitations in activities of daily living, and the use of benzodiazepines.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cross-Sectional Studies; Depression; Female; Geriatric Assessment; Health Surveys; Humans; Male; Prevalence; Psychotropic Drugs; Random Allocation; Risk Factors; Sex Factors; Sleep Wake Disorders; Social Support; Surveys and Questionnaires; United States

Tumor necrosis factor-alpha-angiotensin interactions and regulation of blood pressure. - Ferreri, N R; Zhao, Y; Takizawa, H; McGiff, J C (J Hypertens, 1997)
OBJECTIVES: To compare the levels of tumor necrosis factor-alpha (TNF) produced by medullary thick ascending limb tubules (MTAL) obtained from normotensive and angiotensin II (Ang II)-dependent hypertensive rats and determine whether TNF participates in a mechanism that opposes elevation of blood pressure by Ang II. DESIGN: We have previously demonstrated that in-vitro administration of Ang II increases production of TNF and prostaglandin E2 (PGE2) by the MTAL. We hypothesize that production of TNF and PGE2 by the MTAL is elevated in in-vivo models of Ang II-dependent hypertension and acts to modulate the pressor effects of Ang II. Thus, inhibition of TNF should disclose whether this cytokine acts to modulate Ang II-induced hypertension. METHODS: MTAL tubules obtained from normotensive and Ang II-dependent hypertensive rats were isolated by enzymatic digestion and sieving. Tubules were cultured in the absence of exogenous Ang II. TNF and PGE2 levels were measured by enzyme-linked immunosorbent assay. Anti-TNF antiserum was administered intravenously to normotensive and Ang II-dependent hypertensive rats and their mean arterial pressures were measured. RESULTS: Production of TNF and PGE2 was significantly greater in MTAL tubules isolated from Ang II hypertensive rats than it was in those from normotensive controls. Administration of anti-TNF antiserum exacerbated the Ang II-mediated increase in mean arterial pressure. CONCLUSIONS: The higher levels of production of TNF and PGE2 by MTAL tubules isolated from Ang II hypertensive rats compared with those of normotensive controls are consistent with results of in-vitro experiments showing that administration of Ang II increases production of TNF and PGE2 by the MTAL. TNF and PGE2 participate in a counter-regulatory mechanism that opposes the pressor actions of Ang II.
Keywords: Angiotensin II; Animals; Blood Pressure; Dinoprostone; Drug Interactions; Hypertension; Immune Sera; In Vitro Techniques; Kidney Medulla; Loop of Henle; Male; Rats; Rats, Sprague-Dawley; Reference Values; Tumor Necrosis Factor-alpha

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

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

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

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

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

Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study. - Lemaitre, R N; Furberg, C D; Newman, A B; Hulley, S B; Gordon, D J; Gottdiener, J S; McDonald, R H; Psaty, B M (Arch Intern Med, 1998)
OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.
Keywords: Aged; Anticholesteremic Agents; Cholesterol, LDL; Cohort Studies; Female; Humans; Hypercholesterolemia; Male; Prevalence; Risk Factors; United States

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

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

Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. - Newman, A B; Shemanski, L; Manolio, T A; Cushman, M; Mittelmark, M; Polak, J F; Powe, N R; Siscovick, D (Arterioscler Thromb Vasc Biol, 1999)
Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.
Keywords: Age Distribution; Aged; Aged, 80 and over; Ankle; Arm; Blood Pressure Determination; Cardiovascular Diseases; Cohort Studies; Female; Humans; Hypertension; Male; Predictive Value of Tests; Risk Factors; Sex Distribution; Survival Analysis

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

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

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

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

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

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

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

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

Temporal trends in the use of anticoagulants among older adults with atrial fibrillation. - Smith, N L; Psaty, B M; Furberg, C D; White, R; Lima, J A; Newman, A B; Manolio, T A (Arch Intern Med, 1999)
BACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation. METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996. RESULTS: The use of warfarin increased 4-fold from 13% in 1990 to 50% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age. CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.
Keywords: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Drug Therapy; Electrocardiography; Female; Humans; Incidence; Male; Prevalence; Treatment Outcome; Warfarin

Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group. - Enright, P L; McClelland, R L; Newman, A B; Gottlieb, D J; Lebowitz, M D (Chest, 1999)
OBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons. PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study. MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow. RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40% were taking a sympathomimetic bronchodilator, 30% inhaled corticosteroids, 21% theophylline, and 18% oral corticosteroids; 39% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not. CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.
Keywords: Age Factors; Aged; Aged, 80 and over; Asthma; Female; Humans; Male; Peak Expiratory Flow Rate; Quality of Life; Risk Factors; Spirometry; Vital Capacity

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

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

Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group. - Newman, A B; Spiekerman, C F; Enright, P; Lefkowitz, D; Manolio, T; Reynolds, C F; Robbins, J (J Am Geriatr Soc, 2000)
INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD. SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease. METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure. RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95% CI = 1.03, 1.76) in men and was 1.66 (95% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95% CI, 1.12- 1.98) and in women, was 2.21 (95% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men. CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.
Keywords: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Female; Health Status; Heart Failure; Humans; Incidence; Male; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Risk Factors; Sex Factors; Sleep Apnea Syndromes; Sleep Stages; Sleep Wake Disorders; Snoring; Surveys and Questionnaires; United States

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

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

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

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

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

Associations of subclinical cardiovascular disease with frailty. - Newman, A B; Gottdiener, J S; McBurnie, M A; Hirsch, C H; Kop, W J; Tracy, R; Walston, J D; Fried, L P (J Gerontol A Biol Sci Med Sci, 2001)
BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology. METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing. RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05). CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.
Keywords: Aged; Ankle; Arm; Black or African American; Blood Pressure; Brain; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Infarction; Cerebrovascular Disorders; Cohort Studies; Echocardiography; Electrocardiography; Frail Elderly; Health Status; Heart Failure; Humans; Magnetic Resonance Imaging; United States; Vascular Diseases

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

Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study. - Newman, A B; Arnold, A M; Burke, G L; O'Leary, D H; Manolio, T A (Ann Intern Med, 2001)
BACKGROUND: Persons with abdominal aortic aneurysm are more likely to have a higher prevalence of risk factors for and clinical manifestations of cardiovascular disease. It is unknown whether these factors explain the high mortality rate associated with abdominal aortic aneurysm. OBJECTIVE: To describe the risk for mortality, cardiovascular mortality, and cardiovascular morbidity in persons screened for abdominal aortic aneurysm. DESIGN: Longitudinal cohort study. SETTING: Four communities in the United States. PARTICIPANTS: 4734 men and women older than 65 years of age recruited from Medicare eligibility lists. MEASUREMENTS: Abdominal ultrasonography was used to measure the aortic diameter and the ratio of infrarenal to suprarenal measurement of aortic diameter in 1992-1993. Abdominal aortic aneurysm was defined as aortic diameter of 3 cm or greater or infrarenal-to-suprarenal ratio of 1.2 or greater. Mortality, cardiovascular disease mortality, incident cardiovascular disease, and repair or rupture were assessed after 4.5 years. RESULTS: The prevalence of aneurysm was 8.8%, and 87.7% of aneurysms were 3.5 cm or less in diameter. Rates of total mortality (65.1 vs. 32.8 per 1000 person-years), cardiovascular mortality (34.3 vs. 13.8 per 1000 person-years), and incident cardiovascular disease (47.3 vs. 31.0 per 1000 person-years) were higher in participants with aneurysm than in those without aneurysm; after adjustment for age, risk factors, and presence of other cardiovascular disease, the respective relative risks were 1.32, 1.36, and 1.57. Rates of repair and rupture were low. CONCLUSIONS: Rates of total mortality, cardiovascular disease mortality, and incident cardiovascular disease were higher in participants with abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease, and extent of atherosclerosis detected by noninvasive testing. Persons with smaller aneurysms detected by ultrasonography should be advised to modify risk factors for cardiovascular disease while under surveillance for increase in the size of the aneurysm.
Keywords: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiovascular Diseases; Disease Progression; Female; Humans; Incidence; Longitudinal Studies; Male; Mortality; Proportional Hazards Models; Risk Factors; Ultrasonography; United States

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

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

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

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

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

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

Relation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study. - de Simone, G; McClelland, R; Gottdiener, J S; Celentano, A; Kronmal, R A; Gardin, J M (J Hypertens, 2001)
OBJECTIVE: To investigate the interaction between left ventricular (LV) geometry, carotid structure and arterial compliance in relation to hemodynamic stimuli and risk factors (plasma cholesterol, body mass index, insulin resistance, smoking habit, age, sex and race). DESIGN: Cross-sectional. METHODS: Echocardiography and carotid ultrasound were performed in 2375 elderly subjects without signs or history of prevalent cardiovascular disease, diabetes or renal disease (795 men; 298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health Study. Arterial compliance was estimated by the prognostically validated ratio of stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from the value predicted by individual age, heart rate and body weight. RESULTS: Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH) in normotensive and hypertensive subjects and was greatest in the presence of concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the presence of LVH (and was greatest with eccentric LVH, in association with relatively high values for stroke volume). After adjusting for blood pressure, maximum carotid lumen diameter was directly correlated with stroke volume, and IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum carotid lumen diameter, independently of prevalent risk factors (P < 0.001). SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P < 0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not affect these associations in normotensives, but made them insignificant in hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P < 0.001), independently of risk factors, whereas no significant relation was found in hypertensives. CONCLUSIONS: The magnitudes of carotid intima-medial thickness and lumen diameter parallel levels of LV mass and geometry, and are directly related to stroke volume and arterial stiffness; this interaction is most evident in the presence of normal blood pressure, whereas it is affected by other cardiovascular risk factors when arterial hypertension is present.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Carotid Arteries; Compliance; Cross-Sectional Studies; Echocardiography; Female; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Reference Values; Risk Factors; Stroke Volume; Tunica Intima; Tunica Media; Ventricular Function, Left

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

Transforming self-rated health and the SF-36 scales to include death and improve interpretability. - Diehr, P; Patrick, D L; Spertus, J; Kiefe, C I; McDonell, M; Fihn, S D (Med Care, 2001)
BACKGROUND: Most measures of health-related quality of life are undefined for people who die. Longitudinal analyses are often limited to a healthier cohort (survivors) that cannot be identified prospectively, and that may have had little change in health. OBJECTIVE: To develop and evaluate methods to transform a single self-rated health item (excellent to poor; EVGGFP) and the physical component score of the SF-36 (PCS) to new variables that include a defensible value for death. METHODS: Using longitudinal data from two large studies of older adults, health variables were transformed to the probability of being healthy in the future, conditional on the current observed value; death then has the value of 0. For EVGGFP, the new transformations were compared with some that were published earlier, based on different data. For the PCS, how well three different transformations, based on different definitions of being healthy, discriminated among groups of patients, and detected change in time were assessed. RESULTS: The new transformation for EVGGFP was similar to that published previously. Coding the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended. The three transformations of the PCS detected group differences and change at least as well as the standard PCS. CONCLUSION: These easily interpretable transformed variables permit keeping persons who die in the analyses. Using the transformed variables for longitudinal analyses of health when deaths occur, either for secondary or primary analysis, is recommended. This approach can be applied to other measures of health.
Keywords: Aged; Data Interpretation, Statistical; Death; Decision Making; Female; Health Status; Humans; Logistic Models; Longitudinal Studies; Male; Models, Statistical; Quality of Life; ROC Curve; Surveys and Questionnaires

Usefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (the Cardiovascular Health Study). - Rautaharju, P M; Nelson, J C; Kronmal, R A; Zhang, Z M; Robbins, J; Gottdiener, J S; Furberg, C D; Manolio, T; Fried, L (Am J Cardiol, 2001)
T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (> or =45 degrees ) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.
Keywords: Aged; Algorithms; Cohort Studies; Coronary Disease; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Prevalence; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; Survival Analysis

Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study. - Runchey, Shauna S; Folsom, Aaron R; Tsai, Michael Y; Cushman, Mary; McGovern, Paul D (Br J Haematol, 2002)
Anticardiolipin antibodies, one of the family of 'antiphospholipid' antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.
Keywords: Aged; Aged, 80 and over; Antibodies, Anticardiolipin; Case-Control Studies; Female; Humans; Immunoglobulin G; Immunoglobulin M; Longitudinal Studies; Male; Middle Aged; Odds Ratio; Prospective Studies; Reference Values; Risk Factors; Thromboembolism; Venous Thrombosis

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

Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study. - Mackey, Rachel H; Sutton-Tyrrell, Kim; Vaitkevicius, Peter V; Sakkinen, Pamela A; Lyles, Mary F; Spurgeon, Harold A; Lakatta, Edward G; Kuller, Lewis H (Am J Hypertens, 2002)
BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals. METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998. RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993. CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.
Keywords: Aged; Aged, 80 and over; Aging; Aorta; Female; Heart Rate; Humans; Hypertension; Insulin Resistance; Longitudinal Studies; Male; Pulsatile Flow; Risk Factors; Sex Distribution

Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. - Walston, Jeremy; McBurnie, Mary Ann; Newman, Anne; Tracy, Russell P; Kop, Willem J; Hirsch, Calvin H; Gottdiener, John; Fried, Linda P (Arch Intern Med, 2002)
BACKGROUND: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness. OBJECTIVE: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus. METHODS: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson chi2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures. RESULTS: Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean +/- SD levels of C-reactive protein (5.5 +/- 9.8 vs 2.7 +/- 4.0 mg/L), factor VIII (13 790 +/- 4480 vs 11 860 +/- 3460 mg/dL), and, in a smaller subset, D dimer (647 +/- 1033 vs 224 +/- 258 ng/mL) (P< or =.001 for all, chi2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race. CONCLUSIONS: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.
Keywords: Aged; Aged, 80 and over; Blood Coagulation Disorders; Cardiovascular Diseases; Cohort Studies; Diabetes Complications; Diabetes Mellitus; Female; Frail Elderly; Geriatric Assessment; Humans; Inflammation; Longitudinal Studies; Male

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

Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. - Kop, Willem J; Gottdiener, John S; Tangen, Catherine M; Fried, Linda P; McBurnie, Mary Ann; Walston, Jeremy; Newman, Anne; Hirsch, Calvin; Tracy, Russell P (Am J Cardiol, 2002)
Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.
Keywords: Aged; Blood Chemical Analysis; Blood Coagulation Factors; Cardiovascular Diseases; Depression; Female; Humans; Inflammation; Male; Risk Factors

Left atrial dimensions determined by M-mode echocardiography in black and white older (> or =65 years) adults (The Cardiovascular Health Study). - Manolio, Teri A; Gottdiener, John S; Tsang, Teresa S M; Gardin, Julius M (Am J Cardiol, 2002)
Stroke and atrial fibrillation are common and serious illnesses in the elderly, the risks of which are substantially increased by left atrial (LA) enlargement. Despite growing recognition of the importance of LA enlargement, the distribution and correlates of LA dimension in the elderly have not been well defined. A total of 3,882 women and men aged >65 years were studied. Increased LA dimension was independently associated with increased weight, mitral annular calcium, regional wall motion abnormalities, mitral early peak inflow velocity, and left ventricular (LV) fractional shortening. Increased LA dimension was negatively associated with aortic leaflet thickening. The relation with LV fractional shortening was curvilinear with a nadir at 35% to 40%. LA dimension in black men was approximately 1.9 mm less than in white men in multivariate analyses. Adjustment for spirometric lung volumes and chest dimensions appeared to diminish the race-LA dimension relation. Thus, LA dimension is strongly associated with weight and with several echocardiographic valvular abnormalities; its relation with LV fractional shortening is U-shaped with a nadir at the borderline of LV functional impairment.
Keywords: African Continental Ancestry Group; Age Factors; Aged; Blood Flow Velocity; Body Weight; Cardiovascular Diseases; Echocardiography; Electrocardiography; European Continental Ancestry Group; Evidence-Based Medicine; Female; Heart Atria; Heart Ventricles; Humans; Male; Multivariate Analysis; Prospective Studies; Risk Factors; Statistics as Topic; Ventricular Function, Left

Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study. - Gottdiener, John S; McClelland, Robyn L; Marshall, Robert; Shemanski, Lynn; Furberg, Curt D; Kitzman, Dalane W; Cushman, Mary; Polak, Joseph; Gardin, Julius M; Gersh, Bernard J; Aurigemma, Gerard P; Manolio, Teri A (Ann Intern Med, 2002)
BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function. OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons. DESIGN: Population-based longitudinal study of coronary heart disease and stroke. SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland. PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community. MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality. RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category. CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.
Keywords: Aged; Cause of Death; Echocardiography; Female; Heart Failure; Humans; Longitudinal Studies; Male; Myocardial Infarction; Prevalence; Prognosis; Risk Factors; Stroke; Ventricular Dysfunction, Right; Ventricular Function, Left

Regression-based variable clustering for data reduction. - McClelland, R L; Kronmal, R A (Stat Med, 2002)
In many studies it is of interest to cluster states, counties or other small regions in order to obtain improved estimates of disease rates or other summary measures, and a more parsimonious representation of the country as a whole. This may be the case if there are too many to summarize concisely, and/or many regions with a small number of cases. By merging the regions into larger geographic areas, we obtain more cases within each area (and hence lower standard errors for parameter estimates), as well as fewer areas to summarize in terms of disease rates. The resulting clusters should be such that regions within the same cluster are similar in terms of their disease rates. In this paper we present a clustering algorithm which uses data at the subject-specific level in order to cluster the original regions into a reduced set of larger areas. The proposed clustering algorithm expresses the clustering goals in terms of a regression framework. This formulation of the problem allows the regions to be clustered in terms of their association with the response, and confounding variables measured at the subject-specific level may be easily incorporated during the clustering process. Additionally, this framework allows estimation and testing of the association between the areas and the response. The statistical properties and performance of the algorithm were evaluated via simulation studies, and the results are promising. Additional simulations illustrate the importance of controlling for confounding variables during the clustering process, rather than after the clusters are determined. The algorithm is illustrated with data from the Cardiovascular Health Study. Although developed with a specific application in mind, the method is applicable to a wide range of problems.
Keywords: Aged; Algorithms; Cardiovascular Diseases; Cluster Analysis; Cognition; Computer Simulation; Humans; Infarction; Magnetic Resonance Imaging; Models, Statistical; Regression Analysis

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

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

A stroke prediction score in the elderly: validation and Web-based application. - Lumley, Thomas; Kronmal, Richard A; Cushman, Mary; Manolio, Teri A; Goldstein, Steven (J Clin Epidemiol, 2002)
The objective of this study was to construct a prediction model for predicting stroke in an elderly U.S. population, and to assess the accuracy in this population of other previously published prediction models. The subjects were participants in the Cardiovascular Health Study: 2,495 men and 3,393 women age 65 years and older at baseline, and followed for 6.3 years. Among 5,711 participants free of baseline stroke, 399 strokes occurred. Sex-specific prediction equations were constructed using study variables that were most importantly related to incident stroke: age, systolic blood pressure, diabetes, ECG diagnosis of atrial fibrillation or left ventricular hypertrophy, confirmed history of cardiovascular disease, diabetes, time to walk 15 ft, and serum creatinine. The prediction rule was implemented as a risk score and in a Web-based interactive Java applet. Overall, the model predicted 5-year stroke risks ranging from less than 1 to 59%. The 20% of subjects in the highest predicted risk group had a 5-year actual stroke incidence rate of 15%, while the 20% lowest risk group had a 1% incidence. Risk scores from two other studies performed well in these study participants. Effective discrimination between low and high stroke risk in the elderly was possible in this cohort with data that are easy to obtain. Evaluation of the generalizability and clinical usefulness of this prediction model requires further research.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Female; Follow-Up Studies; Humans; Incidence; Male; Models, Cardiovascular; Predictive Value of Tests; Risk Factors; ROC Curve; Stroke; 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

Alcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Kronmal, Richard A; Mittleman, Murray A; O'Leary, Daniel H; Polak, Joseph F; Cushman, Mary; Siscovick, David S (Arterioscler Thromb Vasc Biol, 2003)
OBJECTIVE: The association of alcohol use with atherosclerosis is inconsistent in previous studies. METHODS AND RESULTS: For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07+/-0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07+/-0.05-mm higher IMT than abstainers (P quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24+/-0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22%. CONCLUSIONS: Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.
Keywords: Aged; Alcohol Drinking; Cardiovascular Diseases; Carotid Artery Diseases; Cross-Sectional Studies; Female; Health Surveys; Humans; Longitudinal Studies; Male; Prospective Studies

Body composition in the elderly: the influence of nutritional factors and physical activity. - Mitchell, D; Haan, M N; Steinberg, F M; Visser, M (J Nutr Health Aging, 2003)
BACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio. OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue. DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition. RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes. CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.
Keywords: Absorptiometry, Photon; Aged; Aged, 80 and over; Aging; Body Composition; Cohort Studies; Cross-Sectional Studies; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Exercise; Female; Humans; Male; 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

C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. - Cao, Jie J; Thach, Chau; Manolio, Teri A; Psaty, Bruce M; Kuller, Lewis H; Chaves, Paulo H M; Polak, Joseph F; Sutton-Tyrrell, Kim; Herrington, David M; Price, Thomas R; Cushman, Mary (Circulation, 2003)
BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT. METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95% CI 0.92 to 1.53), 1.05 (95% CI 0.81 to 1.37), and 1.60 (95% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT. CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.
Keywords: Aged; Brain Ischemia; C-Reactive Protein; California; Carotid Arteries; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Maryland; North Carolina; Odds Ratio; Pennsylvania; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Tunica Intima; Tunica Media; Ultrasonography

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

Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study. - Rea, Thomas D; Psaty, Bruce M; Heckbert, Susan R; Cushman, Mary; Meilahn, Elaine; Olson, Jean L; Lemaitre, Rozenn N; Smith, Nicholas L; Sotoodehnia, Nona; Chaves, Paulo H M (J Womens Health (Larchmt), 2003)
BACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF. METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223). RESULTS: At baseline, 62% were never users, 26% were past users, and 12% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction). CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.
Keywords: Aged; Aged, 80 and over; Body Mass Index; Cohort Studies; Estrogen Replacement Therapy; Female; Heart Failure; Humans; Incidence; Life Style; Middle Aged; Multivariate Analysis; Obesity; Osteoporosis, Postmenopausal; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; United States; Women's Health

Inflammation as a risk factor for atrial fibrillation. - Aviles, Ronnier J; Martin, David O; Apperson-Hansen, Carolyn; Houghtaling, Penny L; Rautaharju, Pentti; Kronmal, Richard A; Tracy, Russell P; Van Wagoner, David R; Psaty, Bruce M; Lauer, Michael S; Chung, Mina K (Circulation, 2003)
BACKGROUND: The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort. METHODS AND RESULTS: CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9+/-1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P=0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P=0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P<0.001). CONCLUSIONS: CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.
Keywords: Aged; Atrial Fibrillation; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Inflammation; Longitudinal Studies; Male; Risk Factors

Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly. - Crainich, P; Jenny, N S; Tang, Z; Arnold, A M; Kuller, L H; Manolio, T; Sharrett, A R; Tracy, R P (J Thromb Haemost, 2003)
Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.
Keywords: African Continental Ancestry Group; Aged; Alleles; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; European Continental Ancestry Group; Female; Genotype; Homozygote; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Promoter Regions, Genetic; Risk

n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. - Lemaitre, Rozenn N; King, Irena B; Mozaffarian, Dariush; Kuller, Lewis H; Tracy, Russell P; Siscovick, David S (Am J Clin Nutr, 2003)
BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.
Keywords: Aged; alpha-Linolenic Acid; Biomarkers; Case-Control Studies; Cohort Studies; Coronary Disease; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Incidence; Male; Myocardial Infarction; Odds Ratio; Phospholipids; Prevalence; Prospective Studies; Risk Factors

Perceptions and implications of received spousal care: evidence from the Caregiver Health Effects Study. - Martire, Lynn M; Schulz, Richard; Wrosch, Carsten; Newsom, Jason T (Psychol Aging, 2003)
The experiences of older care recipients have received far less theoretical and empirical attention than those of their family caregivers. In this study of 91 care recipients, the authors assessed perceptions of the amount, timing, and manner of spousal assistance; the amount of strain experienced from receiving care; and psychological well-being. Although female care recipients were more likely to report dissatisfaction with the manner in which assistance was provided, there were few gender differences in perceptions of care overall. In a stringent test of the hypothesis that perceived quality of spousal care affects recipient well-being, the authors found that poorer quality of care was related to increased depressive symptoms and a decreased sense of mastery 1 year later. These longitudinal effects were independent of the recipient's physical disability, marital quality, and care-receiving strain as well as the caregiver's well-being. These findings argue for a comprehensive assessment of the care-receiving experience that includes both care-recipient and caregiver perspectives.
Keywords: Aged; Caregivers; Chronic Disease; Disabled Persons; Family Health; Female; Health Status; Humans; Longitudinal Studies; Male; Mental Health; Quality of Health Care; Research Design; Spouses

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

Prospective study of alcohol consumption and risk of dementia in older adults. - Mukamal, Kenneth J; Kuller, Lewis H; Fitzpatrick, Annette L; Longstreth, W T; Mittleman, Murray A; Siscovick, David S (JAMA, 2003)
CONTEXT: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. OBJECTIVE: To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. MAIN OUTCOME MEASURES: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. RESULTS: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term =.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. CONCLUSIONS: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.
Keywords: Aged; Alcohol Drinking; Apolipoprotein E4; Apolipoproteins E; Brain; Case-Control Studies; Dementia; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prospective Studies; Risk

Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Cushman, Mary; Mittleman, Murray A; Tracy, Russell P; Siscovick, David S (Atherosclerosis, 2004)
OBJECTIVE: We sought to determine the relation of alcohol intake and systemic inflammation in a population-based sample of older adults. METHODS AND RESULTS: As part of the Cardiovascular Health Study (CHS), 5865 adults aged 65 years and older reported their intake of beer, wine, and liquor. We determined white blood cell count (WBC), factor VIII coagulant activity (factor VIIIc), and levels of C-reactive protein (CRP), fibrinogen, and albumin as markers of systemic inflammation. Among participants without confirmed cardiovascular disease, alcohol consumption was inversely associated with WBC, factor VIIIc, and fibrinogen level, and positively associated with albumin concentration in multivariate analyses. We found no consistent modification of these results by sex, obesity, or beverage type. The relation of alcohol use and CRP levels was significantly modified by apoE genotype (P interaction 0.03), with a positive association among participants with an apoE4 allele (P = 0.05), but a trend toward an inverse association among those without an apoE4 allele (P = 0.15). CONCLUSIONS: Alcohol intake is associated with lower levels of inflammatory markers in older adults free of cardiovascular disease.
Keywords: Aged; Aged, 80 and over; Alcohol Drinking; Apolipoproteins E; C-Reactive Protein; Coronary Artery Disease; Female; Fibrinogen; Geriatric Assessment; Humans; Inflammation Mediators; Leukocyte Count; Logistic Models; Longitudinal Studies; Male; Probability; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. - Gottlieb, D J; DeStefano, A L; Foley, D J; Mignot, E; Redline, S; Givelber, R J; Young, T (Neurology, 2004)
BACKGROUND: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association. METHODS: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship. RESULTS: At least one APOE epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without. CONCLUSION: The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.
Keywords: Adult; Age Distribution; Aged; Aged, 80 and over; Alleles; Apolipoprotein E4; Apolipoproteins E; Cardiovascular Diseases; Cohort Studies; Comorbidity; Female; Genetic Predisposition to Disease; Genotype; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Polysomnography; Sleep Apnea, Obstructive; Smoking

Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. - Johnston, S Claiborne; O'Meara, Ellen S; Manolio, Teri A; Lefkowitz, David; O'Leary, Daniel H; Goldstein, Steven; Carlson, Michelle C; Fried, Linda P; Longstreth, W T (Ann Intern Med, 2004)
BACKGROUND: Whether carotid artery disease is a cause of cognitive impairment in persons who have not had stroke is unknown. If this is the case, diminished performance on the Modified Mini-Mental State Examination should be more common in persons with left carotid artery disease than in those with right carotid artery disease. OBJECTIVE: To determine whether left carotid artery disease is associated with cognitive impairment. DESIGN: Cross-sectional and cohort study. SETTING: Four U.S. communities participating in the Cardiovascular Health Study. PATIENTS: 4006 right-handed men and women 65 years of age or older without history of stroke, transient ischemic attack, or carotid endarterectomy. MEASUREMENTS: Internal carotid artery stenosis and intima-media thickness of the common carotid artery were assessed by using duplex ultrasonography. Cognitive impairment was defined as a score less than 80 on the Modified Mini-Mental State Examination, and cognitive decline was defined as an average decrease of more than 1 point annually in Modified Mini-Mental State Examination score during up to 5 years of follow-up. Multivariate logistic regression models were used to estimate the risk for cognitive impairment and decline associated with left internal carotid artery stenosis and intima-media thickness, after adjustment for measures of right-sided disease and risk factors for vascular disease. RESULTS: After adjustment for right-sided stenosis, high-grade (> or =75% narrowing of diameter) stenosis of the left internal carotid artery (32 patients) was associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1] compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to 6.3]). Intima-media thickness of the left common carotid artery was associated with cognitive impairment and decline in univariate analysis, but this effect did not persist after adjustment. CONCLUSIONS: Cognitive impairment and decline are associated with asymptomatic high-grade stenosis of the left internal carotid artery. The persistence of the association after adjustment for right-sided stenosis indicates that the association is not due to underlying vascular risk factors or atherosclerosis in general.
Keywords: Aged; Carotid Stenosis; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Neuropsychological Tests; Odds Ratio; Risk Factors; Tunica Intima

Congestive heart failure in the elderly: the Cardiovascular Health Study. - Mathew, Sunil T; Gottdiener, John S; Kitzman, Dalane; Aurigemma, Gerard (Am J Geriatr Cardiol, 2004)
Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.
Keywords: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Diagnosis, Differential; Female; Geriatric Assessment; Heart Atria; Heart Failure; Heart Rate; Humans; Incidence; Male; Prevalence; Risk Factors; Stroke Volume; United States; Ventricular Dysfunction, Left

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

Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. - Drazner, Mark H; Rame, J Eduardo; Marino, Emily K; Gottdiener, John S; Kitzman, Dalane W; Gardin, Julius M; Manolio, Teri A; Dries, Daniel L; Siscovick, David S (J Am Coll Cardiol, 2004)
OBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF). BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF. METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF. RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8% in quartile 1, 4.4% in quartile 2, 7.5% in quartile 3, and 14.1% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF. CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.
Keywords: Aged; Body Surface Area; Coronary Artery Disease; Diastole; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Longitudinal Studies; Male; Multivariate Analysis; Prospective Studies; Risk Factors; Sensitivity and Specificity; Statistics as Topic; Stroke Volume; Ventricular Dysfunction, Left

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

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

Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study. - Manolio, Teri A; Cushman, Mary; Gottdiener, John S; Dobs, Adrian; Kuller, Lewis H; Kronmal, Richard A (Ann Epidemiol, 2004)
PURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline. METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997. RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change. CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.
Keywords: African Americans; Age Factors; Aged; Cardiovascular Diseases; Cholesterol; European Continental Ancestry Group; Female; Forecasting; Health Status; Humans; Male; Medicare; Prospective Studies; Risk Factors; Sex Distribution; Sex Factors; United States

Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131). - Scuteri, Angelo; Manolio, Teri A; Marino, Emily K; Arnold, Alice M; Lakatta, Edward G (J Am Coll Cardiol, 2004)
OBJECTIVES: We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT). BACKGROUND: Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease. METHOD: Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM). RESULTS: Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95% confidence interval [CI] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95% CI 1.16 to 1.75) compared with CGP1 (normal). CONCLUSIONS: Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT.
Keywords: Aged; Cardiovascular Diseases; Carotid Arteries; Female; Humans; Hypertrophy; Incidence; Male; Predictive Value of Tests; Prevalence; Prospective Studies; Ultrasonography

Respiratory muscle strength and the risk of incident cardiovascular events. - van der Palen, J; Rea, T D; Manolio, T A; Lumley, T; Newman, A B; Tracy, R P; Enright, P L; Psaty, B M (Thorax, 2004)
BACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained. METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke. RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly. CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.
Keywords: Cardiovascular Diseases; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Maximal Voluntary Ventilation; Prospective Studies; Respiratory Muscles; Risk Factors; Vital Capacity

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

Self-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study. - Mukamal, Kenneth J; Mittleman, Murray A; Longstreth, W T; Newman, Anne B; Fried, Linda P; Siscovick, David S (J Am Geriatr Soc, 2004)
OBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Four U.S. communities. PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated. MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline. RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25% higher risk in consumers of 14 or more drinks per week (95% CI=3-52%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity. CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.
Keywords: Accidental Falls; Aged; Alcohol Drinking; Chi-Square Distribution; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Regression Analysis; Risk Factors; Self Disclosure; United States

Stroke risk factors and loss of high cognitive function. - Elkins, J S; O'Meara, E S; Longstreth, W T; Carlson, M C; Manolio, T A; Johnston, S C (Neurology, 2004)
BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition. METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS). RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction). CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.
Keywords: Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Higher Nervous Activity; Humans; Incidence; Male; Risk Assessment; Risk Factors; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Stroke; United States

Subclinical cardiovascular disease in older adults: insights from the Cardiovascular Health Study. - Chaves, Paulo H M; Kuller, Lewis H; O'Leary, Daniel H; Manolio, Teri A; Newman, Anne B (Am J Geriatr Cardiol, 2004)
Knowledge about the epidemiology of subclinical cardiovascular disease (SCVD) in older adults may hold the key for improved opportunities for primary prevention of cardiovascular disease (CVD), a top clinical and public health priority. This review reports findings on the prevalence of SCVD and the ability of SCVD measures to predict incident and adverse outcomes from one of the largest (N=5888) and most comprehensive prospective observational studies on SCVD in older adults, the Cardiovascular Health Study. According to a composite index that combined SCVD measures from different vascular beds, the overall prevalence of SCVD was 37%, making it as common as clinically overt CVD in older adults. SCVD measures strongly predicted incident CVD, stroke, mortality, frailty, and physical and cognitive decline, even after adjustment for traditional CVD risk factors. Ongoing research will address the potential use of SCVD for clinical decision making in older adults.
Keywords: Aged; Cardiovascular Diseases; Coronary Artery Disease; Heart Failure; Humans; Longitudinal Studies; Prevalence; Risk Assessment; Risk Factors

Traditional and novel risk factors in older adults: cardiovascular risk assessment late in life. - Mukamal, Kenneth J; Kronmal, Richard A; Tracy, Russell P; Cushman, Mary; Siscovick, David S (Am J Geriatr Cardiol, 2004)
As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.
Keywords: Aged; Blood Coagulation Factors; Cardiovascular Diseases; Cohort Studies; Diabetes Complications; Female; Genetic Predisposition to Disease; Humans; Hypertension; Infections; Inflammation; Lipids; Longitudinal Studies; Male; Obesity; Predictive Value of Tests; Risk Factors; Smoking; United States

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

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

Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies. - Wong, Tien Yin; Larsen, Emily K Marino; Klein, Ronald; Mitchell, Paul; Couper, David J; Klein, Barbara E K; Hubbard, Larry D; Siscovick, David S; Sharrett, A Richey (Ophthalmology, 2005)
OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years). METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli. RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3% (n = 39 cases) and 0.2% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95% CI, 2.60-12.16), body mass index (OR, 3.88; 95% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95% CI, 1.44-6.84), systolic BP (OR, 3.46; 95% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound. CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.
Keywords: Aged; Aged, 80 and over; Arterioles; Blood Pressure; Cardiovascular Diseases; Carotid Stenosis; Coronary Artery Disease; Cross-Sectional Studies; Embolism; Female; Fibrinogen; Humans; Hypertension; Lipoprotein(a); Male; Meta-Analysis as Topic; Middle Aged; Retinal Artery; Retinal Vein Occlusion; Risk Factors

The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study. - Lenze, Eric J; Schulz, Richard; Martire, Lynn M; Zdaniuk, Bozena; Glass, Thomas; Kop, Willem J; Jackson, Sharon A; Reynolds, Charles F (J Am Geriatr Soc, 2005)
OBJECTIVES: To examine the relationship between persistently high depressive symptoms and long-term changes in functional disability in elderly persons. DESIGN: A community-based, prospective, observational study. SETTING: Participant data from the Cardiovascular Health Study. PARTICIPANTS: From the overall sample of 5,888 subjects, three types of participants were identified for this study: (1) persistently depressed individuals, who experienced an onset of depressive symptoms that persisted over 4 years (n=119); (2) temporarily depressed individuals, who experienced an onset of depressive symptoms that resolved over time (n=259); and (3) nondepressed individuals, with persistently low depressive symptoms throughout the follow-up period who were matched on baseline activity of daily living (ADL) scores, sex, and age to the previous two groups combined (n=378). MEASUREMENTS: Four consecutive years of data were assessed: validated measures of depression (10-item CES-D), functional disability (10-item ADL/instrumental ADL measure), physical performance, medical illness, and cognition. RESULTS: The persistently depressed group showed a greater linear increase in functional disability ratings than the temporarily depressed and nondepressed groups. This association between persistent depression and functional disability was robust even when controlling for baseline demographic and clinical/performance measures, including cognition. The persistently depressed group had an adjusted odds ratio (OR) of 5.27 (95% confidence interval (CI) 3.03-9.16) for increased functional disability compared with the nondepressed group over 3 years of follow-up, whereas the temporarily depressed group had an adjusted OR of 2.39 (95% CI=1.55-3.69) compared with the nondepressed group. CONCLUSION: Persistently elevated depressive symptoms in elderly persons are associated with a steep trajectory of worsening functional disability, generating the hypothesis that treatments for late-life depression need to be assessed on their efficacy in maintaining long-term functional status as well as remission of depressive symptoms. These results also demonstrate the need for studies to differentiate between persistent and temporary depressive symptoms when examining their relationship to disability.
Keywords: Activities of Daily Living; Aged; Case-Control Studies; Depressive Disorder; Disabled Persons; Female; Humans; Longitudinal Studies; Male; Multivariate Analysis; Risk; United States

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

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

Haptoglobin phenotype, sleep-disordered breathing, and the prevalence of cardiovascular disease: the Sleep Heart Health Study. - Levy, Andrew P; Zhang, Lin; Miller-Lotan, Rachel; Redline, Susan; O'Connor, George T; Quan, Stuart F; Resnick, Helaine E (Sleep, 2005)
BACKGROUND: Diabetes is an independent risk factor for cardiovascular disease, and there is growing evidence that sleep-disordered breathing also may increase the risk of cardiovascular disease. The mechanism responsible for increased susceptibility of people with diabetes to cardiovascular disease is thought to share several features with sleep-disordered breathing, notably increased oxidative stress. We recently demonstrated that a particular haptoglobin phenotype that is associated with differential antioxidant activity is an independent risk factor for cardiovascular disease in individuals with diabetes. We therefore sought to determine whether sleep-disordered breathing and cardiovascular disease are more strongly associated among people with the unfavorable haptoglobin phenotype. METHODS: We tested this hypothesis in 2612 middle-aged and older participants from the Sleep Heart Health Study. Haptoglobin phenotyping was performed by gel electrophoresis. Respiratory disturbance index was assessed by standard methods. Logistic regression analysis was performed to estimate the association between haptoglobin phenotype and cardiovascular disease, adjusting for known cardiovascular risk factors (age, sex, diabetes, smoking, lipid levels, and hypertension). Possible modification by haptoglobin phenotype of the association of sleep-disordered breathing with cardiovascular disease prevalence was explored by examining interaction terms. RESULTS: We found no significant association between haptoglobin phenotype and prevalent cardiovascular disease in this cohort, nor were significant interactions found between haptoglobin phenotype and sleep-disordered breathing on the prevalence of cardiovascular disease. CONCLUSIONS: Sleep-disordered breathing did not appear to interact with haptoglobin phenotype in modifying the association with prevalent cardiovascular disease in the Sleep Heart Health Study. These findings could be due to the absence of association or to survivor bias in these cross-sectional analyses.
Keywords: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Cross-Sectional Studies; Female; Haptoglobins; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Phenotype; Polysomnography; Prevalence; Sleep Apnea Syndromes

Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. - Longstreth, W T; Arnold, Alice M; Beauchamp, Norman J; Manolio, Teri A; Lefkowitz, David; Jungreis, Charles; Hirsch, Calvin H; O'Leary, Daniel H; Furberg, Curt D (Stroke, 2005)
BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade. RESULTS: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk. CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.
Keywords: Aged; Brain; Cardiovascular Diseases; Cognition Disorders; Female; Humans; Incidence; Leukoaraiosis; Longitudinal Studies; Magnetic Resonance Imaging; Male; Risk Factors; Stroke

Incidence of cardiovascular disease in older Americans: the cardiovascular health study. - Arnold, Alice M; Psaty, Bruce M; Kuller, Lewis H; Burke, Gregory L; Manolio, Teri A; Fried, Linda P; Robbins, John A; Kronmal, Richard A (J Am Geriatr Soc, 2005)
OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans. DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events. SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS). PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American). MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD. RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95% confidence interval (CI)=36.4-43.1) in men and 22.3 (95% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95% CI=13.0-16.6) and 13.7 (95% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9% with each year of age over 65 and was greater than 6% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians. CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.
Keywords: African Americans; Age Distribution; Aged; Aged, 80 and over; Cardiovascular Diseases; European Continental Ancestry Group; Female; Geriatric Assessment; Humans; Incidence; Longitudinal Studies; Male; Sex Distribution; Survival Rate; United States

Polysomnographic predictors of blood pressure and hypertension: is one index best? - Redline, Susan; Min, Nancy I; Shahar, Eyal; Rapoport, David; O'Connor, George (Sleep, 2005)
STUDY OBJECTIVES: Numerous indexes derived from polysomnography are available to characterize sleep-disordered breathing, with no consensus over which measures best predict clinical outcomes. This study addresses the relative merits of using alternative polysomnography indexes by characterizing the consistency and strength of the association of each index with blood pressure and hypertension. DESIGN: Cross-sectional analyses of the association of alternative polysomnography indexes with blood pressure and hypertension were performed in construction and validation data sets. Linear and logistic regression models were used to identify the best variable sets. PATIENTS: Data were obtained from 6433 men and women (age 62.9 +/- 11.0 years, 52.8% women) who participated in the Sleep Heart Health Study. RESULTS: In multivariable models, most indexes showed weak linear associations with systolic, with slightly stronger associations for diastolic blood pressure, and the log odds of hypertension. No single index showed consistent superiority over others. Systolic blood pressure, diastolic blood pressure, and hypertension each were associated with distinct sets of polysomnography variables. Slightly more-consistent associations were demonstrated for indexes that included hypopneas that were linked with either a 3% or 4% desaturation level than indexes that did not require hypopneas to have linked desaturation. For indexes that combined apneas and hypopneas, there was no evidence that linking obstructive apneas to desaturation or arousal altered prediction compared with counting all apneas. CONCLUSION: In summary, using a rigorous cross-validation assessment, we did not identify a clear superiority of any single index for blood pressure or hypertension prediction. Detailed analyses of alternative definitions of the respiratory disturbance index support current scoring guidelines, where desaturation criteria are recommended for hypopneas but not apneas.
Keywords: Blood Pressure; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Middle Aged; Polysomnography; Predictive Value of Tests; Reproducibility of Results; Severity of Illness Index; Sleep Apnea, Obstructive

Renal duplex parameters, blood pressure, and renal function in elderly people. - Pearce, Jeffrey D; Edwards, Matthew S; Craven, Timothy E; English, William P; Mondi, Matthew M; Reavis, Scott W; Hansen, Kimberley J (Am J Kidney Dis, 2005)
BACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans. METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques. RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine. CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.
Keywords: African Americans; Aged; Aging; Arteriosclerosis; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Creatinine; Cross-Sectional Studies; Diastole; Disease Progression; European Continental Ancestry Group; Female; Humans; Hypertension, Renovascular; Kidney; Kidney Diseases; Kidney Function Tests; Male; Renal Artery; Renal Artery Obstruction; Renal Circulation; Risk Factors; Sampling Studies; Systole; Ultrasonography, Doppler, Duplex; United States

Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. - Kennedy, Margaret; Solomon, Cam; Manolio, Teri A; Criqui, Michael H; Newman, Anne B; Polak, Joseph F; Burke, Gregory L; Enright, Paul; Cushman, Mary (Arch Intern Med, 2005)
BACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population. METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI. RESULTS: The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89). CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.
Keywords: Aged; Aged, 80 and over; Ankle; Brachial Artery; Cardiovascular Diseases; Female; Humans; Male; Peripheral Vascular Diseases; Risk Assessment; Risk Factors

Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly. - Kaplan, R C; Tirschwell, D L; Longstreth, W T; Manolio, T A; Heckbert, S R; Lefkowitz, D; El-Saed, A; Psaty, B M (Neurology, 2005)
BACKGROUND: The authors studied mortality, vascular events, and preventive therapies following ischemic stroke among adults aged > or =65 years. METHODS: The authors identified 546 subjects with first ischemic stroke during 1989 to 2001 among Cardiovascular Health Study participants. Deaths, recurrent strokes, and coronary heart disease (CHD) events were identified over 3.2 years (median) follow-up. RESULTS: During the first year of follow-up, rates were 105.4/1,000 for recurrent stroke and 59.3/1,000 for CHD. After the first year, the stroke rate was 52.0/1,000 and the CHD rate was 46.5/1,000. Cardioembolic strokes had the highest mortality (185.4/1,000) and recurrence rates (86.6/1,000). Lacunar strokes had the lowest mortality (119.3/1,000) and recurrence rates (43.0/1,000). Age and male sex predicted death and CHD, but not recurrence. Outcomes did not differ by race. Following stroke, 47.8% used aspirin and 13.5% used other antiplatelet agents; 52.6% of patients with atrial fibrillation used warfarin; 31.3% of hyperlipidemic subjects, 57.0% of diabetic patients, and 81.5% of hypertensive patients were drug-treated; and 40.0% of hypertensive patients had blood pressure (BP) <140/90 mm Hg. Older subjects were less likely to use lipid-lowering therapy, women were less likely to have BP <140/90 mm Hg, and low-income subjects were less likely to use diabetes medications. CONCLUSIONS: Recurrent strokes were nearly twice as frequent as coronary heart disease (CHD) events during the first year after initial stroke, but stroke and CHD rates were similar after the first year. Preventive drug therapies were underused, which may reflect clinical uncertainty due to the lack of clinical trials among the elderly. Utilization was lower among the oldest patients, women, and low-income individuals.
Keywords: Age Factors; Aged; Aged, 80 and over; Aging; Anticoagulants; Antihypertensive Agents; Brain Ischemia; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Utilization; Female; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Male; Mortality; Prospective Studies; Recurrence; Sex Factors; Stroke; Treatment Outcome

10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study. - Kuller, Lewis H; Arnold, Alice M; Psaty, Bruce M; Robbins, John A; O'Leary, Daniel H; Tracy, Russell P; Burke, Gregory L; Manolio, Teri A; Chaves, Paolo H M (Arch Intern Med, 2006)
BACKGROUND: The incidence of coronary heart disease (CHD) is very high among individuals 65 years or older. METHODS: We evaluated the relationships between measurements of subclinical disease at baseline (1989-1990) and at the third-year follow-up examination (1992-1993) and subsequent incidence of cardiovascular disease and total mortality as of June 2001. Approximately 61% of the participants without clinical cardiovascular disease at baseline had subclinical disease based on our previously described criteria from the Cardiovascular Health Study. RESULTS: The incidence of CHD was substantially increased for participants with subclinical disease compared with those who had no subclinical disease: 30.5 per 1000 person-years with and 16.3 per 1000 person-years without for white individuals, and 31.2 per 1000 person-years with and 12.5 per 1000 person-years without for black individuals. The risk persisted over the entire follow-up period. Incidence rates were higher for men than for women with or without subclinical disease, but there was little difference in rates for black individuals and white individuals. CONCLUSIONS: In multivariable models, subclinical disease at baseline remained a significant predictor of CHD in both men and women; the hazard ratios (95% confidence intervals) of their relative risks were 1.64 (1.30-2.06) and 1.49 (1.21-1.84), respectively. The presence of subclinical disease substantially increased the risk of subsequent CHD for participants with hypertension, diabetes mellitus, or elevated C-reactive protein. In summary, subclinical disease is very prevalent among older individuals, is independently associated with risk of CHD even over a 10-year follow-up period, and substantially increases the risk of CHD among participants with hypertension or diabetes mellitus.
Keywords: African Continental Ancestry Group; Aged; Blood Chemical Analysis; Cardiovascular Diseases; Comorbidity; Coronary Disease; Echocardiography; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Incidence; Male; Multivariate Analysis; Prevalence; Proportional Hazards Models; Regression Analysis; Risk Factors; Sex Distribution; United States

Alcohol consumption and risk of coronary heart disease in 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; Psaty, Bruce M; Siscovick, David S (J Am Geriatr Soc, 2006)
OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76 (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.
Keywords: Aged; Alcohol Drinking; Apolipoproteins E; Beer; Cohort Studies; Coronary Disease; Female; Genotype; Health Behavior; Humans; Incidence; Male; Residence Characteristics; Risk Assessment; Socioeconomic Factors; United States; Wine

Alcohol consumption in older adults and Medicare costs. - Mukamal, Kenneth J; Lumley, Thomas; Luepker, Russell V; Lapin, Pauline; Mittleman, Murray A; McBean, A Marshall; Crum, Rosa M; Siscovick, David S (Health Care Financ Rev, 2006)
We determined the relationship of alcohol consumption and Medicare costs among 4,392 participants in the Cardiovascular Health Study (CHS), a longitudinal, population-based cohort study of adults age 65 or over in four U.S. communities. We assessed 5-year Parts A and B costs and self-reported intake of beer, wine, and liquor at baseline. Among both sexes, total costs were approximately $2,000 lower among consumers of > 1-6 drinks per week than abstainers. The lower costs associated with moderate drinking were most apparent among participants with cardiovascular disease (CVD) and for hospitalization costs for CVD among healthy participants. Former drinkers had the highest costs.
Keywords: Aged; Alcohol Drinking; Cardiovascular Diseases; Female; Health Expenditures; Hospitalization; Humans; Longitudinal Studies; Male; Medicare; United States

The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. - Bryson, Chris L; Mukamal, Kenneth J; Mittleman, Murray A; Fried, Linda P; Hirsch, Calvin H; Kitzman, Dalane W; Siscovick, David S (J Am Coll Cardiol, 2006)
OBJECTIVES: We investigated the association between alcohol consumption and incident congestive heart failure (CHF) both overall and after adjusting for incident myocardial infarction (MI). BACKGROUND: Moderate alcohol consumption has been associated with lower risk of CHF and MI. METHODS: The Cardiovascular Health study, a prospective cohort study of cardiovascular disease risk factors and outcomes, followed 5,888 subjects > or =65 years old for 7 to 10 years. Cox models were used to estimate the adjusted risk of CHF by reported alcohol consumption. RESULTS: There were 5,595 subjects at baseline at risk for incident CHF with alcohol data and 1,056 events during follow-up. Compared with abstainers, the adjusted risk of CHF was lower among subjects who reported consuming 1 to 6 drinks per week (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67 to 1.00, p = 0.05) and 7 to 13 drinks per week (HR 0.66, 95% CI 0.47 to 0.91, p = 0.01). Time-dependent adjustment for incident MI altered only slightly the association between moderate alcohol consumption and CHF (for 1 to 6 drinks per week, HR 0.84, 95% CI 0.65 to 1.04; for 7 to 13 drinks per week, HR 0.69, 95% CI 0.49 to 0.99). Baseline former drinkers had a higher risk of CHF than abstainers (HR 1.51, p < 0.01), but those who quit during the study did not have a higher risk (HR 0.83, 95% CI 0.66 to 1.03). CONCLUSIONS: Moderate alcohol use is associated with a lower risk of incident CHF among older adults, even after accounting for incident MI and other factors.
Keywords: Aged; Alcohol Drinking; Chi-Square Distribution; Comorbidity; Female; Heart Failure; Humans; Life Style; Male; Multicenter Studies as Topic; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Smoking

The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study. - Cao, Jie J; Barzilay, Joshua I; Peterson, Do; Manolio, Teri A; Psaty, Bruce M; Kuller, Lewis; Wexler, Jason; Bleyer, Anthony J; Cushman, Mary (Atherosclerosis, 2006)
PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events. METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass. RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]). CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.
Keywords: Aged; Aged, 80 and over; Albuminuria; Atherosclerosis; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Female; Humans; Hypertension; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Stroke; United States

Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. - Mehra, Reena; Benjamin, Emelia J; Shahar, Eyal; Gottlieb, Daniel J; Nawabit, Rawan; Kirchner, H Lester; Sahadevan, Jayakumar; Redline, Susan (Am J Respir Crit Care Med, 2006)
RATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development. OBJECTIVE: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing. METHODS: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5). RESULTS: Atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome. CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.
Keywords: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Circadian Rhythm; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Polysomnography; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; Sleep; Sleep Apnea, Obstructive

Blood pressure level and outcomes in adults aged 65 and older with prior ischemic stroke. - Kaplan, Robert C; Tirschwell, David L; Longstreth, W T; Manolio, Teri A; Heckbert, Susan R; LeValley, Aaron J; Lefkowitz, David; El-Saed, Aiman; Psaty, Bruce M (J Am Geriatr Soc, 2006)
OBJECTIVES: To examine the association between blood pressure (BP) levels and long-term stroke outcomes in elderly stroke survivors. DESIGN: Observational study. SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling adults. PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age 78.6) who sustained a nonfatal first ischemic stroke. MEASUREMENTS: BP levels assessed at prestroke and poststroke CHS visits were examined as predictors of stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs), and mortality. RESULTS: Higher poststroke BP level, assessed 261.6 days (mean) after stroke, was associated with higher risk of stroke recurrence over 5.4 years (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence was 1.42 (95% confidence interval (CI) = 1.03-1.99) per standard deviation (SD) of systolic BP (P = .04) and 1.39 (95% CI = 1.01-1.91) per SD of diastolic BP (P = .04). Mortality was significantly greater in patients with low or high poststroke BP than in those with intermediate BP. Poststroke BP was not associated with risk of CHD or CVE, although further analyses suggested that high systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP did not predict poststroke outcomes. CONCLUSION: In this observational study of adults aged 65 and older assessed approximately 8 months after stroke, low BP was associated with favorable risk of recurrent stroke, although high and low poststroke BP levels were associated with greater mortality. Long-term antihypertensive trials in older stroke survivors would increase knowledge about the benefits of lowering BP in this population.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Brain Ischemia; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Prospective Studies; Recurrence; Stroke; Survival Rate

CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. - Conley, Yvette P; Jakobsdottir, Johanna; Mah, Tammy; Weeks, Daniel E; Klein, Ronald; Kuller, Lewis; Ferrell, Robert E; Gorin, Michael B (Hum Mol Genet, 2006)
Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P</=0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.
Keywords: Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Complement Factor H; Eye Proteins; Female; Genetic Predisposition to Disease; Humans; Intracellular Signaling Peptides and Proteins; Macular Degeneration; Male; Membrane Proteins; Proteins

Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study. - Pearte, Camille A; Furberg, Curt D; O'Meara, Ellen S; Psaty, Bruce M; Kuller, Lewis; Powe, Neil R; Manolio, Teri (Circulation, 2006)
BACKGROUND: Although >80% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described. METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups. CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.
Keywords: Age Factors; Aged; Aged, 80 and over; Carotid Artery, Common; Cohort Studies; Comorbidity; Coronary Disease; Diabetes Mellitus; Electrocardiography; Female; Follow-Up Studies; Forecasting; Heart Failure; Heart Ventricles; Hospitalization; Humans; Hyperlipidemias; Hypertension; Male; Multivariate Analysis; Myocardial Infarction; Organ Size; Predictive Value of Tests; Risk Factors; Sampling Studies; Tunica Intima; Tunica Media; United States

Clinical course of mesenteric artery stenosis in elderly americans. - Wilson, David B; Mostafavi, Kian; Craven, Timothy E; Ayerdi, Juan; Edwards, Matthew S; Hansen, Kimberley J (Arch Intern Med, 2006)
BACKGROUND: To examine prospectively the relationship between stenosis or occlusion of the celiac and superior mesenteric arteries and symptoms of chronic intestinal ischemia in free-living elderly patients in the United States. METHODS: As part of an ancillary study to the Cardiovascular Health Study, participants in the Forsyth County (North Carolina) cohort underwent visceral duplex ultrasonography of the celiac and superior mesenteric arteries. Critical mesenteric artery stenosis (MAS) or occlusion was defined by Doppler flow ultrasound-derived criteria. Clinical outcomes were assessed at annual follow-up examinations and review of death certificates. Multivariate associations between the presence of MAS and all-cause mortality and adverse cardiovascular events were analyzed. Participants with MAS were contacted to determine the presence of symptoms consistent with chronic intestinal ischemia. RESULTS: Of 553 participants who underwent visceral duplex ultrasonography, 97 (17.5%) had disease of the celiac or superior mesenteric artery. At a mean follow-up of 6(1/2) years, 20 participants with MAS (20.6%) and 93 without MAS (20.4%) had died (relative risk, 1.01; 95% confidence interval, 0.66-1.55). No deaths were attributed to intestinal infarction. No association existed between the presence of MAS and prevalent cardiovascular disease, all-cause mortality, or adverse cardiovascular events. A questionnaire was completed by 71% of the surviving participants with MAS. No participant reported symptoms or weight loss consistent with chronic intestinal ischemia. CONCLUSIONS: Mesenteric artery stenosis was a common finding in free-living elderly patients. At long-term follow-up, the presence of asymptomatic MAS was not associated with death or adverse cardiovascular events. Participants with asymptomatic MAS by duplex ultrasonographic criteria did not experience intestinal infarction or develop chronic intestinal ischemia.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Comorbidity; Female; Humans; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Proportional Hazards Models; Prospective Studies; Radiography; Risk Factors; Surveys and Questionnaires; Ultrasonography

Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS). - Barasch, Eddy; Gottdiener, John S; Larsen, Emily K Marino; Chaves, Paulo H M; Newman, Anne B; Manolio, Teri A (Am Heart J, 2006)
BACKGROUND: Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population. METHODS: We used 2-dimensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons. RESULTS: Mitral annular calcification was found in 1640 (42 %) subjects, AAC in 1710 (44 %), AVS in 2114 (54 %), and all 3 combined in 662 (17 %). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC. CONCLUSIONS: In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile.
Keywords: Aged; Aortic Valve; Calcinosis; Female; Heart Valve Diseases; Humans; Male; Mitral Valve; Prevalence; Prospective Studies; Risk Factors; Sclerosis; Ultrasonography

Costs for heart failure with normal vs reduced ejection fraction. - Liao, Lawrence; Jollis, James G; Anstrom, Kevin J; Whellan, David J; Kitzman, Dalane W; Aurigemma, Gerard P; Mark, Daniel B; Schulman, Kevin A; Gottdiener, John S (Arch Intern Med, 2006)
BACKGROUND: Among the elderly population, heart failure (HF) with normal ejection fraction (EF) is more common than classic HF with low EF. However, there are few data regarding the costs of HF with normal EF. In a prospective, population-based cohort of elderly participants, we compared the costs and resource use of patients with HF and normal and reduced EF. METHODS: A total of 4549 participants (84.5% white; 40.6% male) in the National Heart, Lung, and Blood Institute Cardiovascular Health Study were linked to Medicare claims from 1992 through 1998. By protocol echo examinations or clinical EF assessments, 881 participants with HF were characterized as having abnormal or normal EF. We applied semiparametric estimators to calculate mean costs per subject for a 5-year period. RESULTS: There were 495 HF participants with normal EF (186 prevalent at study entry and 309 incident during the study period) and 386 participants with abnormal EF (166 prevalent and 220 incident). Participants with abnormal EF had more cardiology encounters and cardiac procedures. However, compared with abnormal EF participants, the 5-year costs for normal EF participants were similar in both the prevalent ($33,023 with abnormal EF and $32,580 with normal EF; P=.93) and incident ($49,128 with abnormal EF and $45,604 with normal EF; P=.55) groups. In models accounting for comorbid conditions, the costs with normal and abnormal EF remained similar. CONCLUSIONS: Over a 5-year period, patients with HF and normal EF consume as many health care resources as those with reduced EF. These data highlight the substantial financial burden of HF with normal EF among the elderly population.
Keywords: Aged; Aged, 80 and over; Comorbidity; Echocardiography; Health Care Costs; Heart Failure; Humans; Incidence; Medicare; Prevalence; Prospective Studies; Regression Analysis; Statistics, Nonparametric; Stroke Volume; Systole; United States; Ventricular Function, Left

Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. - Mozaffarian, Dariush; Prineas, Ronald J; Stein, Phyllis K; Siscovick, David S (J Am Coll Cardiol, 2006)
OBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk. BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects. METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories. RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88). CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.
Keywords: Aged; Animals; Atrioventricular Node; Cross-Sectional Studies; Diet; Electrocardiography; Fatty Acids, Omega-3; Female; Fishes; Heart; Heart Rate; Humans; Male; Ventricular Function

Education and the cognitive decline associated with MRI-defined brain infarct. - Elkins, J S; Longstreth, W T; Manolio, T A; Newman, A B; Bhadelia, R A; Johnston, S C (Neurology, 2006)
OBJECTIVE: To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. RESULTS: In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct. CONCLUSIONS: Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.
Keywords: Cerebral Infarction; Cognition Disorders; Cross-Sectional Studies; Educational Status; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Neuropsychological Tests

Factors associated with geographic variations in stroke incidence among older populations in four US communities. - El-Saed, Aiman; Kuller, Lewis H; Newman, Anne B; Lopez, Oscar; Costantino, Joseph; McTigue, Kathleen; Cushman, Mary; Kronmal, Richard (Stroke, 2006)
BACKGROUND AND PURPOSE: In the Cardiovascular Health Study (CHS), we previously observed lower stroke incidence in Allegheny County, PA compared with the other 3 study sites. The purpose of this study was to study possible reasons for the lower stroke incidence in Allegheny County. METHODS: CHS participants 65 years or older who were stroke-free at baseline (n=5639) were followed between 1989 to 1990 and 2000 for the development of stroke. Risk factors at baseline and their subsequent control were compared among both groups. Site-specific hazard ratios for stroke incidence were calculated using Cox regression models. RESULTS: The unadjusted hazard ratio for total stroke incidence in Forsyth County, NC; Sacramento County, CA; and Washington County, MD combined compared with Allegheny County, PA was 1.74 (95% CI: 1.42, 2.14). After adjustment for age and other traditional risk factors, there was modest reduction of the excess hazard in non-Allegheny sites compared with Allegheny County (hazard ratio=1.52, 95% CI: 1.17, 1.98). Between baseline and the seventh-year visits, control of hypertension, diabetes, lipids, smoking, atrial fibrillation and transient ischemic attack were similar across sites. White matter grade > or = 3 on the baseline brain MRI was less common in Allegheny County (25.8% versus 36.3%, respectively; P<0.001) and accounted for 25% of the excess hazard in non-Allegheny sites compared with Allegheny County. CONCLUSIONS: Site differences in stroke risk factors at baseline and subsequent control only partially explain site differences in stroke incidence. White matter grade as a possible integrated measure of exposure and control of risk factors may help in explaining geographic variations in stroke incidence.
Keywords: Aged; Brain; California; Female; Humans; Incidence; Magnetic Resonance Imaging; Male; Maryland; North Carolina; Pennsylvania; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke

Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States). - Sieh, Weiva; Edwards, Karen L; Fitzpatrick, Annette L; Srinouanprachanh, Sengkeo L; Farin, Fred M; Monks, Stephanie A; Kronmal, Richard A; Eaton, David L (Cancer Causes Control, 2006)
OBJECTIVE: To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk. METHODS: We conducted a case-control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989-2000. We genotyped 193 cases and 391 controls for the PSA -252 G/A and -158 G/A SNPs and the AR CAG microsatellite, and developed methods to directly determine proximal PSA promoter haplotypes. Exact logistic regression was used to estimate odds ratios and significance levels. RESULTS: No significant associations were observed between PSA diplotype and prostate cancer overall. Short (< 20) AR CAG repeat lengths were associated with modest increases in the risk of prostate cancer (OR, 1.46; 95% CI, 0.97-2.19; p = 0.071) that were significant for advanced disease (OR, 1.82; 95% CI, 1.02-3.26; p = 0.044). Men who possessed two copies of the PSA*2 (-252G/-158G) haplotype and short AR CAG repeat lengths had a 4-fold (95% CI, 1.05-20.75; exact p = 0.040) increased risk of prostate cancer, and a 7-fold (95% CI, 1.25-39.78; exact p = 0.026) increased risk of advanced disease. CONCLUSIONS: We found evidence that the PSA*2*2 diplotype in combination with short AR CAG alleles increases a man's risk of developing prostate cancer. These findings support an etiologic role in prostate cancer of genetic interactions between polymorphisms that increase AR transactivation strength and those that alter the regulatory regions of target genes such as PSA that are responsive to androgen stimulation.
Keywords: Aged; Biomarkers, Tumor; Case-Control Studies; Cohort Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Polymorphism, Genetic; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; United States

Geographic variations in stroke incidence and mortality among older populations in four US communities. - El-Saed, Aiman; Kuller, Lewis H; Newman, Anne B; Lopez, Oscar; Costantino, Joseph; McTigue, Kathleen; Cushman, Mary; Kronmal, Richard (Stroke, 2006)
BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability in the US. There is limited data on geographic variations in stroke incidence among older US populations who experience the majority of stroke burden. The purpose of this study was to compare stroke incidence and mortality rates in 4 US communities. METHODS: Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n=5639) were followed for 10 or 7 years in predominantly white (n=5002) and black (n=637) participants, respectively. Incident stroke was validated by a stroke adjudication committee after ascertainment at annual visits, interim telephone contacts, and review of Medicare hospitalization data. RESULTS: The 2000 US population age and sex standardized total stroke incidence rate for all CHS participants was 17.7 per 1000 person-years (95% CI: 15.9, 19.5). The rate was significantly lower in Allegheny County, Pennsylvania 9.6/1000 person-years (95% CI: 7.7, 11.5) than Forsyth County, North Carolina 19.2/1000 person-years (95% CI: 15.6, 22.8), Sacramento County, California 20.7/1000 person-years (95% CI: 16.9, 24.5), and Washington County, Maryland 19.8/1000 person-years (95% CI: 16.1, 23.5). The lower stroke incidence rate in Allegheny County was consistent in gender, race, and age groups. Though not statistically significant, stroke mortality was also lower in Allegheny County than other 3 sites. The 1-month case fatality rate was similar in the 4 sites for all strokes, and by stroke types. CONCLUSIONS: Understanding geographic variations in stroke incidence may be an important step in improving preventive practices of stroke.
Keywords: Aged; Aged, 80 and over; California; Female; Humans; Incidence; Male; Maryland; North Carolina; Pennsylvania; Stroke

Intake of tuna or other broiled or baked fish versus fried fish and cardiac structure, function, and hemodynamics. - Mozaffarian, Dariush; Gottdiener, John S; Siscovick, David S (Am J Cardiol, 2006)
Fish intake is associated with improved cardiovascular health, including a lower risk of arrhythmic death, atrial fibrillation, and heart failure. However, the physiologic effects that may produce these cardiovascular benefits are not well-established. We investigated the cross-sectional associations between a usual dietary intake of fish during the previous year and cardiac structure, function, and hemodynamics as determined by physical examination and 2-dimensional, Doppler, and M-mode transthoracic echocardiography among 5,073 older adults enrolled in the Cardiovascular Health Study. On multivariate-adjusted analyses, consumption of tuna or other broiled or baked fish was associated with a lower heart rate (p < 0.001), lower systemic vascular resistance (p = 0.002), and greater stroke volume (p < 0.001). Tuna/other fish intake was also associated with a higher E/A ratio (p = 0.004), a measure of more normal diastolic function. In contrast, fried fish or fish sandwich (fish burger) intake was associated with left ventricular wall motion abnormalities (p = 0.02), a reduced ejection fraction (p < 0.001), lower cardiac output (p = 0.04), a trend toward a larger left ventricular diastolic dimension (p = 0.07), and higher systemic vascular resistance (p = 0.003). In conclusion, in this large population-based study, the intake of tuna or other broiled or baked fish was associated with improved cardiac hemodynamics, but fried fish intake was associated with structural abnormalities indicative of systolic dysfunction and potential coronary atherosclerosis. These findings suggest potential specific physiologic mechanisms that may, in part, account for the effects of fish intake on cardiovascular health.
Keywords: Animals; Blood Pressure; Cardiac Output; Confounding Factors, Epidemiologic; Cooking; Heart Rate; Hemodynamics; Humans; Seafood; Tuna; Vascular Resistance

Kidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study. - Fried, Linda F; Shlipak, Michael G; Stehman-Breen, Catherine; Mittalhenkle, Anuja; Seliger, Stephen; Sarnak, Mark; Robbins, John; Siscovick, David; Harris, Tamara B; Newman, Anne B; Cauley, Jane A (J Gerontol A Biol Sci Med Sci, 2006)
BACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old. METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women. RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women. CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.
Keywords: Absorptiometry, Photon; Aged; Bone Density; Creatinine; Cystatin C; Cystatins; Female; Hip; Humans; Kidney Diseases; Kidney Function Tests; Linear Models; Longitudinal Studies; Male; Osteoporosis; Predictive Value of Tests

Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons > or =65 years of age (the cardiovascular health study). - Gottdiener, John S; Kitzman, Dalane W; Aurigemma, Gerard P; Arnold, Alice M; Manolio, Teri A (Am J Cardiol, 2006)
The left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects > or =65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction.
Keywords: Aged; Atrial Function, Left; Case-Control Studies; Diastole; Echocardiography; Female; Heart Atria; Heart Failure; Humans; Male; Multivariate Analysis; Systole

Lipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation. - Miljkovic-Gacic, Iva; Bunker, Clareann H; Ferrell, Robert E; Kammerer, Candace M; Evans, Rhobert W; Patrick, Alan L; Kuller, Lewis H (Metabolism, 2006)
Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.
Keywords: Adult; African Americans; Age Factors; Aged; Alleles; Body Mass Index; Cardiovascular Diseases; Caribbean Region; Cohort Studies; DNA; European Continental Ancestry Group; Gene Frequency; Genetic Variation; Humans; Lipase; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Liver; Longitudinal Studies; Male; Middle Aged; Particle Size; Trinidad and Tobago; United States

Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study. - McNeill, Ann Marie; Katz, Ronit; Girman, Cynthia J; Rosamond, Wayne D; Wagenknecht, Lynne E; Barzilay, Joshua I; Tracy, Russell P; Savage, Peter J; Jackson, Sharon A (J Am Geriatr Soc, 2006)
OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD. DESIGN: Prospective cohort study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62% female, 14% black). MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L). RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95% confidence interval (CI) = 1.07-1.57), 0.94 (95% CI = 0.73-1.21), and 1.40 (95% CI = 1.12-1.76) for women and 1.35 (95% CI = 1.10-1.66), 1.51 (95% CI = 1.08-2.12), and 1.47 (95% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20% to 30% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16% to 46%) and an additional 9% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD. CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.
Keywords: African Americans; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Diseases; Cohort Studies; European Continental Ancestry Group; Fasting; Female; Humans; Incidence; Male; Metabolic Syndrome; Risk Factors; Sex Factors

Plasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: the cardiovascular health study. - Lemaitre, Rozenn N; King, Irena B; Mozaffarian, Dariush; Sotoodehnia, Nona; Rea, Thomas D; Kuller, Lewis H; Tracy, Russel P; Siscovick, David S (Circulation, 2006)
BACKGROUND: Intake of trans fatty acids is associated with increased risk of coronary heart disease. Whether different classes of trans fatty acids show similar associations is unclear. We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids. To extend these findings, we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease (IHD) and sudden cardiac death. METHODS AND RESULTS: We conducted a case-control study nested in the Cardiovascular Health Study. We identified 214 cases of fatal IHD (fatal myocardial infarction and coronary heart disease death) between 1992 and 1998. We randomly selected 214 controls, matched to cases on demographics, prevalent cardiovascular disease, and timing of blood draw. Plasma phospholipid fatty acids were assessed in blood samples collected earlier. Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD (odds ratio [OR] for interquintile range 1.68, 95% confidence interval [CI] 1.21 to 2.33) after adjustment for risk factors and trans-18:1 levels. Trans-18:1 levels above the 20th percentile were associated with lower risk (OR 0.34, 95% CI 0.18 to 0.63). In analyses limited to cases of sudden cardiac death (n=95), higher levels of trans-18:2 fatty acids were associated with higher risk (OR 2.34, 95% CI 1.27 to 4.31) and higher trans-18:1 with lower risk (OR 0.18, 95% CI 0.06 to 0.54). CONCLUSIONS: Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death. If confirmed, these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content.
Keywords: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Coronary Disease; Death, Sudden, Cardiac; Female; Humans; Male; Myocardial Ischemia; Phospholipids; Trans Fatty Acids; United States

Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study. - Carmichael, Owen T; Kuller, L H; Lopez, O L; Thompson, P M; Dutton, R A; Lu, A; Lee, S E; Lee, J Y; Aizenstein, H J; Meltzer, C C; Liu, Y; Toga, A W; et al. (Neurobiol Aging, 2007)
Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.
Keywords: Aged; Analysis of Variance; Cardiovascular Diseases; Cerebral Ventricles; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Reference Values; Retrospective Studies; Sex Factors; Time Factors

Alcohol consumption and lipoprotein subclasses in older adults. - Mukamal, Kenneth J; Mackey, Rachel H; Kuller, Lewis H; Tracy, Russell P; Kronmal, Richard A; Mittleman, Murray A; Siscovick, David S (J Clin Endocrinol Metab, 2007)
CONTEXT: Limited evidence suggests that alcohol intake may be associated with lipoprotein subclass distribution, which could mediate its relationship with coronary heart disease. OBJECTIVES: The objective was to determine the relationship of alcohol intake with lipoprotein particle subclasses. DESIGN, SETTING, AND PARTICIPANTS: The study included a cross-sectional analysis of 1850 participants of the Cardiovascular Health Study aged 65 yr and older and free of clinical cardiovascular disease. MAIN OUTCOME MEASURE: Lipoprotein subclass distribution was measured with nuclear magnetic resonance spectroscopy, according to self-reported alcohol intake. RESULTS: Alcohol intake was associated with total low-density lipoprotein (LDL) particles in a U-shaped manner. Consumers of one or more drinks per week had the highest number of large LDL particles, whereas consumers of 7-13 drinks per week had the lowest number of small LDL particles. Alcohol intake was strongly positively associated with large- and medium-sized high-density lipoprotein (HDL) particles but had an inverse relationship with concentrations of small HDL particles and small- and medium-sized very-low-density lipoprotein particles. Average particle sizes of all three lipoproteins were positively associated with alcohol intake. Associations were generally stronger among women than men but in similar directions. Beverage type did not consistently modify these findings. CONCLUSIONS: Alcohol intake is associated with less total LDL particles, lower levels of small LDL, HDL, and very-low-density lipoprotein particles, and higher levels of large LDL and medium- and large-sized HDL particles in older adults free of prevalent clinical cardiovascular disease.
Keywords: Aged; Alcohol Drinking; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Coronary Disease; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Spectroscopy; Male; Prevalence; Risk Factors

Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Psaty, Bruce M; Rautaharju, Pentti M; Furberg, Curt D; Kuller, Lewis H; Mittleman, Murray A; Gottdiener, John S; Siscovick, David S (Am Heart J, 2007)
BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined. METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations. RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95% CI, 1.02-1.54) among former drinkers, 1.09 (95% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95% CI, 1.06-1.52) among former drinkers, 0.94 (95% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12). CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.
Keywords: Aged; Alcohol Drinking; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Prognosis; Risk Factors

Alcohol consumption and type 2 diabetes among older adults: the Cardiovascular Health Study. - Djoussé, Luc; Biggs, Mary L; Mukamal, Kenneth J; Siscovick, David S (Obesity (Silver Spring), 2007)
OBJECTIVE: The objective was to examine the role of total and beverage-specific alcohol consumption on the incidence of type 2 diabetes mellitus (DM) among elderly men and women. RESEARCH METHODS AND PROCEDURES: We studied prospectively 4655 participants of the Cardiovascular Health Study who were free of DM at baseline. Alcohol consumption was obtained at baseline and during follow-up examinations. DM was defined using fasting glucose and/or use of hypoglycemic medications. We used Cox proportional hazard models to estimate adjusted relative risks of diabetes across alcohol categories. RESULTS: During a mean follow-up of 6.3 years, 234 incident cases of DM were documented. Compared with never drinkers, hazard ratios [95% confidence interval (CI)] for DM were 0.7 (0.3 to 1.4), 0.5 (0.3 to 0.9), 0.6 (0.4 to 1.1), and 0.8 (0.4 to 1.3) for former drinkers and current drinkers of <1, 1 to 6, and 7+ drinks per week, respectively, for men after adjustment for age, BMI, education, and smoking. Corresponding values for women were 1.2 (0.6 to 2.3), 0.7 (0.4 to 1.1), 0.6 (0.3 to 1.1), and 0.4 (0.2 to 1.0), respectively. A reduced risk of DM was observed with all types of beverage consumed. Similar findings were observed when we repeated the above analyses using simple or weighted cumulative alcohol update and covariates over time. DISCUSSION: Light to moderate alcohol consumption was associated with a lower incidence of DM among elderly people, irrespective of the type of beverage consumed.
Keywords: Aged; Aged, 80 and over; Alcohol Drinking; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Medicare; Middle Aged; Risk; Smoking; Temperance; United States

Alcohol consumption, bone density, and hip fracture among older adults: the cardiovascular health study. - Mukamal, K J; Robbins, J A; Cauley, J A; Kern, L M; Siscovick, D S (Osteoporos Int, 2007)
INTRODUCTION: Previous studies have found inconsistent relationships of alcohol consumption with risk of hip fracture, and the importance of bone mineral density and risk of falls in mediating such a relationship has not been determined. METHODS: As part of the Cardiovascular Health Study, a population-based cohort study of adults aged 65 years and older from four U.S. communities, 5,865 participants reported their use of beer, wine, and liquor yearly. We identified cases of hip fracture unrelated to malignancy or motor vehicle accidents using hospitalization discharge diagnoses. A subgroup of 1,567 participants in two communities underwent dual-energy x-ray absorptiometry scans to assess bone mineral density. RESULTS: A total of 412 cases of hip fracture occurred during an average of 12 years of follow-up. There was a significant U-shaped relationship between alcohol intake and risk of hip fracture (p quadratic 0.02). Compared with long-term abstainers, the adjusted hazard ratios for hip fracture were 0.78 (95% confidence interval [CI], 0.61-1.00) among consumers of up to 14 drinks per week and 1.18 (95% CI, 0.77-1.81) among consumers of 14 or more drinks per week. Alcohol intake was associated with bone mineral density of the total hip and femoral neck in a stepwise manner, with approximately 5% (95% CI, 1%-9%) higher bone density among consumers of 14 or more drinks per week than among abstainers. These relationships were all similar among men and women. CONCLUSIONS: Among older adults, moderate alcohol consumption has a U-shaped relationship with risk of hip fracture, but a graded positive relationship with bone mineral density at the hip.
Keywords: Absorptiometry, Photon; Aged; Alcohol Drinking; Alcoholic Beverages; Apolipoproteins E; Bone Density; Female; Femur Neck; Genotype; Hip; Hip Fractures; Humans; Longitudinal Studies; Male; Risk Assessment; Risk Factors; Sex Distribution; United States

Alcohol consumption, interleukin-6 and apolipoprotein E genotypes, and concentrations of interleukin-6 and serum amyloid P in older adults. - Mukamal, Kenneth J; Jenny, Nancy S; Tracy, Russell P; Siscovick, David S (Am J Clin Nutr, 2007)
BACKGROUND: Whether alcohol intake is associated with concentrations of interleukin-6 (IL-6) and serum amyloid P (SAP) is uncertain. OBJECTIVE: We determined how alcohol intake and apolipoprotein E (apo E) and IL-6 promoter (IL-6 -174G-->C) polymorphisms interact for concentrations of IL-6 and SAP. DESIGN: In the Cardiovascular Health Study, 2454 older adults reported their intake of beer, wine, and liquor and underwent measurements of circulating IL-6 and SAP. RESULTS: Alcohol intake was not associated with IL-6 concentrations among apo E4-negative or IL-6C-positive participants but was positively associated among both apo E4-positive and IL-6C-negative participants (P for trend = 0.02 for both). The corresponding interactions on SAP were not significant for alcohol overall but were similar for liquor intake. CONCLUSIONS: Among older adults free of clinical cardiovascular disease, specific IL-6 promoter and apo E alleles appeared to confer positive associations of alcohol consumption with IL-6 concentrations. Genetic heterogeneity should be considered in understanding the cardiovascular effects of alcohol intake.
Keywords: Aged; Alcohol Drinking; Apolipoprotein E4; Apolipoproteins E; Blood Glucose; C-Reactive Protein; Cohort Studies; Female; Genotype; Humans; Interleukin-6; Male; Promoter Regions, Genetic; Serum Amyloid P-Component

Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study. - Cao, Jie J; Arnold, Alice M; Manolio, Teri A; Polak, Joseph F; Psaty, Bruce M; Hirsch, Calvin H; Kuller, Lewis H; Cushman, Mary (Circulation, 2007)
BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction. METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic. CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.
Keywords: African Americans; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Artery Diseases; Cohort Studies; Comorbidity; Diabetes Mellitus; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Hyperlipidemias; Hypertension; Incidence; Inflammation; Kaplan-Meier Estimate; Male; Mass Screening; Mortality; Myocardial Infarction; Obesity; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Smoking; Stroke; Survival Analysis; Tunica Intima; Tunica Media; Ultrasonography; United States

Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke. - Kaplan, Robert C; McGinn, Aileen P; Pollak, Michael N; Kuller, Lewis H; Strickler, Howard D; Rohan, Tom E; Cappola, Anne R; Xue, XiaoNan; Psaty, Bruce M (J Clin Endocrinol Metab, 2007)
CONTEXT: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults. OBJECTIVE: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke. DESIGN AND PARTICIPANTS: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study. MAIN OUTCOME MEASURES: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study. RESULTS: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease. CONCLUSION: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.
Keywords: Aged; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Disease; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Multivariate Analysis; Risk Factors; Stroke

Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study. - Longstreth, Wt; Larsen, Emily K Marino; Klein, Ronald; Wong, Tien Yin; Sharrett, A Richey; Lefkowitz, David; Manolio, Teri A (Am J Epidemiol, 2007)
Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.
Keywords: Age Factors; Aged; Aged, 80 and over; Arteriosclerosis; Cerebral Infarction; Female; Humans; Leukoaraiosis; Longitudinal Studies; Magnetic Resonance Imaging; Male; Microcirculation; Photography; Retina; Retinal Diseases; Retinal Vessels; Risk Assessment; Risk Factors

Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia. - Carmichael, Owen T; Kuller, Lewis H; Lopez, Oscar L; Thompson, Paul M; Dutton, Rebecca A; Lu, Allen; Lee, Sharon E; Lee, Jessica Y; Aizenstein, Howard J; Meltzer, Carolyn C; Liu, Yanxi; Toga, Arthur W; et al. (Alzheimer Dis Assoc Disord, 2007)
Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.
Keywords: Aged; Aged, 80 and over; Case-Control Studies; Cerebral Ventricles; Cognition Disorders; Dementia; Disease Progression; Female; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Magnetic Resonance Imaging; Male; Risk Factors; Severity of Illness Index; Time Factors

Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases. - Ballantyne, C; Cushman, M; Psaty, B; Furberg, C; Khaw, K T; Sandhu, M; Oldgren, J; Rossi, G P; Maiolino, G; Cesari, M; Lenzini, L; James, S K; et al. (Eur J Cardiovasc Prev Rehabil, 2007)
BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
Keywords: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Cardiovascular Diseases; Humans; Phospholipases A2

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases. - Danesh, J; Erqou, S; Walker, M; Thompson, S G; Tipping, R; Ford, C; Pressel, S; Walldius, G; Jungner, I; Folsom, A R; Chambless, L E; Knuiman, M; et al. (Eur J Epidemiol, 2007)
Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
Keywords: Albumins; Biomarkers; Cardiovascular Diseases; Databases, Factual; Far East; Humans; Inflammation; Leukocyte Count; Lipids; Lipoproteins, HDL; Prospective Studies; Risk Factors; Triglycerides

Individual and neighborhood socioeconomic status and progressive chronic kidney disease in an elderly population: The Cardiovascular Health Study. - Merkin, Sharon Stein; Diez Roux, Ana V; Coresh, Josef; Fried, Linda F; Jackson, Sharon A; Powe, Neil R (Soc Sci Med, 2007)
Few studies have focused on the association between socioeconomic status (SES) and progressive chronic kidney disease (pCKD) in an elderly population. We conducted a cohort study of 4735 Cardiovascular Health Study participants, ages 65 and older and living in 4 US communities, to examine the independent risk of pCKD associated with income, education and living in a low SES area. pCKD was defined as creatinine elevation 0.4 mg/dL (35 micromol/L) over a 4-7 year follow-up or CKD hospitalization. Area SES was characterized using measures of income, wealth, education and occupation for 1990 (corresponding to time of enrollment) US Census block groups of residence. Age and study site-adjusted incidence rates (per 1000 person years) of pCKD by quartiles of area-level SES score, income and education showed decreasing rates with increasing SES. Cox proportional hazards models showed that living in the lowest SES area quartile, as opposed to the highest, was associated with 50% greater risk of pCKD, after adjusting for age, gender, study site, baseline creatinine, and individual-level SES. This increased risk and trend persisted after adjusting for lifestyle risk factors, diabetes and hypertension. We found no significant independent associations between pCKD and individual-level income or education (after adjusting for all other SES factors). As such, living in a low SES area is associated with greater risk of pCKD in an elderly US population.
Keywords: Age Factors; Aged; Cohort Studies; Female; Humans; Incidence; Kidney Failure, Chronic; Male; Proportional Hazards Models; Residence Characteristics; Risk Factors; Sex Factors; Social Class; United States

Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. - Barzilay, Joshua I; Blaum, Caroline; Moore, Tisha; Xue, Qian Li; Hirsch, Calvin H; Walston, Jeremy D; Fried, Linda P (Arch Intern Med, 2007)
BACKGROUND: Our research group has previously shown that the geriatric syndrome of frailty is associated with features of the metabolic syndrome (MetS) on cross-sectional analysis. METHODS: To test whether MetS and its physiologic determinants-insulin resistance as measured by homeostasis model assessment score (IR-HOMA), increased inflammation and coagulation factor levels, and elevated blood pressure-are associated with incident frailty, we studied a subcohort of participants from the Cardiovascular Health Study observed from 1989/1990 through 1998/1999: 3141 community-dwelling adults, aged 69 to 74 years, without frailty and illnesses that increase inflammation markers or mimic frailty. The association of baseline MetS, IR-HOMA, levels of inflammation and coagulation factors, and systolic blood pressure (SBP) with time to onset of frailty was adjusted for demographic and psychosocial factors and incident events. Our main outcome measure was incident frailty. RESULTS: Metabolic syndrome was not significantly associated with incident frailty (hazard ratio, 1.16 (95% confidence interval [CI], 0.85-1.57). On the other hand, IR-HOMA and C-reactive protein levels were associated with incident frailty: for every standard deviation increment the hazard ratio for frailty was 1.15 (95% CI, 1.02-1.31) and 1.16 (95% CI, 1.02-1.32), respectively. The white blood cell count and factor VIIIc levels had a borderline association. Elevated systolic blood pressure had no association. Similar trends were found for incident prefrailty, a condition that precedes frailty. CONCLUSIONS: Two physiologic components of MetS- IR-HOMA and inflammation-are associated with incident frailty. Based on these results, IR-HOMA can be considered part of a larger process that leads to generalized decline.
Keywords: Aged; Aged, 80 and over; Female; Frail Elderly; Geriatrics; Humans; Inflammation; Insulin Resistance; Male; Metabolic Syndrome; Prospective Studies

Long-term costs and resource use in elderly participants with congestive heart failure in the Cardiovascular Health Study. - Liao, Lawrence; Anstrom, Kevin J; Gottdiener, John S; Pappas, Paul A; Whellan, David J; Kitzman, Dalane W; Aurigemma, Gerard P; Mark, Daniel B; Schulman, Kevin A; Jollis, James G (Am Heart J, 2007)
BACKGROUND: Although heart failure (HF) afflicts nearly 5 million Americans, the long-term cost of HF care has not been described previously. In a prospective, longitudinal cohort of community-dwelling elderly from 4 regions, we examined the long-term costs and resource use of elderly patients with HF. METHODS: We linked 4860 elderly participants in the National Heart, Lung, and Blood Institute Cardiovascular Health Study to Medicare part A and part B claims from 1992 to 2003. Costs were calculated from Medicare payments and discounted at 3% annually. We applied nonparametric estimators to calculate mean costs and resource use per patient for a 10-year period. To describe the relationship between patient characteristics and long-term costs, we constructed censoring-adjusted regression models. RESULTS: There were 343 participants (84.8% white; 50.1% men; mean age, 78.2 years) with prevalent HF and 4517 participants without HF at study entry. Mean follow-up was 6.7 years (median, 6.4 years). The 10-year survival rates were 33% and 63% for the prevalent HF and nonprevalent HF groups (P < .001), respectively. The mean 10-year medical costs were significantly higher for the prevalent HF cohort (54,704 dollars vs 41 dollars,780, P < .001). The higher costs associated with HF were also reflected in greater resource use with more hospitalizations (P < .05) and more intensive care unit days (P < .05). Participants with HF had more physician visits (P < .05), with most of these encounters involving noncardiology physicians. However, in multivariate models, prevalent HF was not an independent predictor of higher costs. CONCLUSION: Patients with HF consume substantially more health care resources than their elderly peers, and these higher costs persist through 10 years of follow-up. Many of these costs may be related to other comorbid conditions.
Keywords: Aged; Costs and Cost Analysis; Female; Health Resources; Heart Failure; Humans; Male; Medicare; Prospective Studies; Time Factors