@article {897, title = {The Cardiovascular Health Study: design and rationale.}, journal = {Ann Epidemiol}, volume = {1}, year = {1991}, month = {1991 Feb}, pages = {263-76}, abstract = {

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}, issn = {1047-2797}, doi = {10.1016/1047-2797(91)90005-w}, author = {Fried, L P and Borhani, N O and Enright, P and Furberg, C D and Gardin, J M and Kronmal, R A and Kuller, L H and Manolio, T A and Mittelmark, M B and Newman, A} } @article {1082, title = {Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Stroke}, volume = {22}, year = {1991}, month = {1991 Sep}, pages = {1155-63}, abstract = {

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}, issn = {0039-2499}, doi = {10.1161/01.str.22.9.1155}, author = {O{\textquoteright}Leary, D H and Polak, J F and Wolfson, S K and Bond, M G and Bommer, W and Sheth, S and Psaty, B M and Sharrett, A R and Manolio, T A} } @article {808, title = {Eligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study.}, journal = {Ann Intern Med}, volume = {116}, year = {1992}, month = {1992 Apr 15}, pages = {641-9}, abstract = {

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}, issn = {0003-4819}, doi = {10.7326/0003-4819-116-8-641}, author = {Manolio, T A and Furberg, C D and Wahl, P W and Tracy, R P and Borhani, N O and Gardin, J M and Fried, L P and O{\textquoteright}Leary, D H and Kuller, L H} } @article {781, title = {Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group.}, journal = {Circulation}, volume = {86}, year = {1992}, month = {1992 Sep}, pages = {858-69}, abstract = {

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}, issn = {0009-7322}, doi = {10.1161/01.cir.86.3.858}, author = {Ettinger, W H and Wahl, P W and Kuller, L H and Bush, T L and Tracy, R P and Manolio, T A and Borhani, N O and Wong, N D and O{\textquoteright}Leary, D H} } @article {835, title = {Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.}, journal = {Am J Cardiol}, volume = {69}, year = {1992}, month = {1992 May 15}, pages = {1329-35}, abstract = {

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}, issn = {0002-9149}, doi = {10.1016/0002-9149(92)91231-r}, author = {Furberg, C D and Manolio, T A and Psaty, B M and Bild, D E and Borhani, N O and Newman, A and Tabatznik, B and Rautaharju, P M} } @article {1441, title = {Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.}, journal = {Circulation}, volume = {88}, year = {1993}, month = {1993 Sep}, pages = {837-45}, abstract = {

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}, issn = {0009-7322}, author = {Newman, A B and Siscovick, D S and Manolio, T A and Polak, J and Fried, L P and Borhani, N O and Wolfson, S K} } @article {1435, title = {Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group.}, journal = {Circulation}, volume = {88}, year = {1993}, month = {1993 Nov}, pages = {2163-71}, abstract = {

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}, issn = {0009-7322}, author = {Manolio, T A and Furberg, C D and Shemanski, L and Psaty, B M and O{\textquoteright}Leary, D H and Tracy, R P and Bush, T L} } @article {1445, title = {Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study.}, journal = {Circulation}, volume = {87}, year = {1993}, month = {1993 Mar}, pages = {728-37}, abstract = {

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}, issn = {0009-7322}, author = {Manolio, T A and Ettinger, W H and Tracy, R P and Kuller, L H and Borhani, N O and Lynch, J C and Fried, L P} } @article {1447, title = {Properties of the random zero sphygmomanometer.}, journal = {Hypertension}, volume = {21}, year = {1993}, month = {1993 May}, pages = {632-7}, abstract = {

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{\textquoteright}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{\textquoteright}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}, issn = {0194-911X}, author = {Kronmal, R A and Rutan, G H and Manolio, T A and Borhani, N O} } @article {1436, title = {Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {3}, year = {1993}, month = {1993 Jul}, pages = {358-66}, abstract = {

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{\textquoteright}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}, issn = {1047-2797}, author = {Tell, G S and Fried, L P and Hermanson, B and Manolio, T A and Newman, A B and Borhani, N O} } @article {1430, title = {Cardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {23}, year = {1994}, month = {1994 Mar 15}, pages = {916-25}, abstract = {

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}, issn = {0735-1097}, author = {Manolio, T A and Furberg, C D and Rautaharju, P M and Siscovick, D and Newman, A B and Borhani, N O and Gardin, J M and Tabatznik, B} } @article {1433, title = {Correlates of QT prolongation in older adults (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.}, journal = {Am J Cardiol}, volume = {73}, year = {1994}, month = {1994 May 15}, pages = {999-1002}, keywords = {Aged, Aged, 80 and over, Female, Humans, Logistic Models, Long QT Syndrome, Longitudinal Studies, Male, Sex Factors}, issn = {0002-9149}, author = {Rautaharju, P M and Manolio, T A and Psaty, B M and Borhani, N O and Furberg, C D} } @article {1438, title = {Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {25}, year = {1994}, month = {1994 Feb}, pages = {318-27}, abstract = {

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}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and Poirier, V and O{\textquoteright}Leary, D H and Gardin, J M and Fried, L P and Steinberg, E P and Bryan, R N} } @article {1420, title = {A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.}, journal = {AJNR Am J Neuroradiol}, volume = {15}, year = {1994}, month = {1994 Oct}, pages = {1625-33}, abstract = {

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}, issn = {0195-6108}, author = {Bryan, R N and Manolio, T A and Schertz, L D and Jungreis, C and Poirier, V C and Elster, A D and Kronmal, R A} } @article {1427, title = {Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {74}, year = {1994}, month = {1994 Aug 01}, pages = {236-41}, abstract = {

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}, issn = {0002-9149}, author = {Furberg, C D and Psaty, B M and Manolio, T A and Gardin, J M and Smith, V E and Rautaharju, P M} } @article {1439, title = {Respiratory muscle strength in the elderly. Correlates and reference values. Cardiovascular Health Study Research Group.}, journal = {Am J Respir Crit Care Med}, volume = {149}, year = {1994}, month = {1994 Feb}, pages = {430-8}, abstract = {

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}, issn = {1073-449X}, doi = {10.1164/ajrccm.149.2.8306041}, author = {Enright, P L and Kronmal, R A and Manolio, T A and Schenker, M B and Hyatt, R E} } @article {1414, title = {Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {J Clin Epidemiol}, volume = {48}, year = {1995}, month = {1995 Sep}, pages = {1141-52}, abstract = {

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}, issn = {0895-4356}, author = {Manolio, T A and Burke, G L and Psaty, B M and Newman, A B and Haan, M and Powe, N and Tracy, R P and O{\textquoteright}Leary, D H} } @article {1451, title = {Ischemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the Cardiovascular Health Study.}, journal = {Int J Cardiol}, volume = {51}, year = {1995}, month = {1995 Sep}, pages = {165-75}, abstract = {

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}, issn = {0167-5273}, author = {Rautaharju, P M and Manolio, T A and Furberg, C D and Siscovick, D and Newman, A B and Borhani, N O and Gardin, J M} } @article {1419, title = {Reduced vital capacity in elderly persons with hypertension, coronary heart disease, or left ventricular hypertrophy. The Cardiovascular Health Study.}, journal = {Chest}, volume = {107}, year = {1995}, month = {1995 Jan}, pages = {28-35}, abstract = {

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}, issn = {0012-3692}, author = {Enright, P L and Kronmal, R A and Smith, V E and Gardin, J M and Schenker, M B and Manolio, T A} } @article {1422, title = {Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study.}, journal = {Circulation}, volume = {91}, year = {1995}, month = {1995 Mar 15}, pages = {1739-48}, abstract = {

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}, issn = {0009-7322}, author = {Gardin, J M and Siscovick, D and Anton-Culver, H and Lynch, J C and Smith, V E and Klopfenstein, H S and Bommer, W J and Fried, L and O{\textquoteright}Leary, D and Manolio, T A} } @article {1418, title = {Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?}, journal = {JAMA}, volume = {273}, year = {1995}, month = {1995 May 10}, pages = {1436-8}, abstract = {

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{\textquoteright}, United States}, issn = {0098-7484}, author = {Psaty, B M and Koepsell, T D and Yanez, N D and Smith, N L and Manolio, T A and Heckbert, S R and Borhani, N O and Gardin, J M and Gottdiener, J S and Rutan, G H} } @article {1454, title = {Carotid artery measures are strongly associated with left ventricular mass in older adults (a report from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {77}, year = {1996}, month = {1996 Mar 15}, pages = {628-33}, abstract = {

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}, issn = {0002-9149}, author = {Kronmal, R A and Smith, V E and O{\textquoteright}Leary, D H and Polak, J F and Gardin, J M and Manolio, T A} } @article {1460, title = {Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {27}, year = {1996}, month = {1996 Aug}, pages = {1274-82}, abstract = {

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}, issn = {0039-2499}, author = {Longstreth, W T and Manolio, T A and Arnold, A and Burke, G L and Bryan, N and Jungreis, C A and Enright, P L and O{\textquoteright}Leary, D and Fried, L} } @article {1465, title = {Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {6}, year = {1996}, month = {1996 Jul}, pages = {314-23}, abstract = {

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{\textquoteright}s Health}, issn = {1047-2797}, author = {Jonas, H A and Kronmal, R A and Psaty, B M and Manolio, T A and Meilahn, E N and Tell, G S and Tracy, R P and Robbins, J A and Anton-Culver, H} } @article {1467, title = {Prevalence and correlates of snoring and observed apneas in 5,201 older adults.}, journal = {Sleep}, volume = {19}, year = {1996}, month = {1996 Sep}, pages = {531-8}, abstract = {

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}, issn = {0161-8105}, author = {Enright, P L and Newman, A B and Wahl, P W and Manolio, T A and Haponik, E F and Boyle, P J} } @article {1463, title = {Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {27}, year = {1996}, month = {1996 Sep}, pages = {1479-86}, abstract = {

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}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and O{\textquoteright}Leary, D H and Price, T R} } @article {1472, title = {Spirometry reference values for healthy elderly blacks. The Cardiovascular Health Study Research Group.}, journal = {Chest}, volume = {110}, year = {1996}, month = {1996 Dec}, pages = {1416-24}, abstract = {

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}, issn = {0012-3692}, author = {Enright, P L and Arnold, A and Manolio, T A and Kuller, L H} } @article {1458, title = {Utility of new electrocardiographic models for left ventricular mass in older adults. The Cardiovascular Health Study Collaborative Research Group.}, journal = {Hypertension}, volume = {28}, year = {1996}, month = {1996 Jul}, pages = {8-15}, abstract = {

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}, issn = {0194-911X}, author = {Rautaharju, P M and Manolio, T A and Siscovick, D and Zhou, S H and Gardin, J M and Kronmal, R and Furberg, C D and Borhani, N O and Newman, A} } @article {1486, title = {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.}, journal = {Stroke}, volume = {28}, year = {1997}, month = {1997 Sep}, pages = {1693-701}, abstract = {

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}, issn = {0039-2499}, author = {Howard, G and Manolio, T A and Burke, G L and Wolfson, S K and O{\textquoteright}Leary, D H} } @article {1488, title = {Incidence of and risk factors for atrial fibrillation in older adults.}, journal = {Circulation}, volume = {96}, year = {1997}, month = {1997 Oct 07}, pages = {2455-61}, abstract = {

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}, issn = {0009-7322}, author = {Psaty, B M and Manolio, T A and Kuller, L H and Kronmal, R A and Cushman, M and Fried, L P and White, R and Furberg, C D and Rautaharju, P M} } @article {1471, title = {Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {47-54}, abstract = {

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}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988191}, author = {Bryan, R N and Wells, S W and Miller, T J and Elster, A D and Jungreis, C A and Poirier, V C and Lind, B K and Manolio, T A} } @article {1483, title = {Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Stroke}, volume = {28}, year = {1997}, month = {1997 Jun}, pages = {1158-64}, abstract = {

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}, issn = {0039-2499}, author = {Price, T R and Manolio, T A and Kronmal, R A and Kittner, S J and Yue, N C and Robbins, J and Anton-Culver, H and O{\textquoteright}Leary, D H} } @article {1473, title = {Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Jan}, pages = {1-7}, abstract = {

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}, issn = {0002-8614}, author = {Newman, A B and Enright, P L and Manolio, T A and Haponik, E F and Wahl, P W} } @article {1504, title = {Aspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group.}, journal = {Stroke}, volume = {29}, year = {1998}, month = {1998 May}, pages = {887-94}, abstract = {

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}, issn = {0039-2499}, author = {Kronmal, R A and Hart, R G and Manolio, T A and Talbert, R L and Beauchamp, N J and Newman, A} } @article {1514, title = {Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {55}, year = {1998}, month = {1998 Sep}, pages = {1217-25}, abstract = {

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}, issn = {0003-9942}, author = {Longstreth, W T and Bernick, C and Manolio, T A and Bryan, N and Jungreis, C A and Price, T R} } @article {586, title = {Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Mar}, pages = {538-45}, abstract = {

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}, issn = {1079-5642}, doi = {10.1161/01.atv.19.3.538}, author = {Newman, A B and Shemanski, L and Manolio, T A and Cushman, M and Mittelmark, M and Polak, J F and Powe, N R and Siscovick, D} } @article {1520, title = {Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.}, journal = {N Engl J Med}, volume = {340}, year = {1999}, month = {1999 Jan 07}, pages = {14-22}, abstract = {

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}, issn = {0028-4793}, doi = {10.1056/NEJM199901073400103}, author = {O{\textquoteright}Leary, D H and Polak, J F and Kronmal, R A and Manolio, T A and Burke, G L and Wolfson, S K} } @article {1524, title = {Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {30}, year = {1999}, month = {1999 Feb}, pages = {383-8}, abstract = {

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}, issn = {0039-2499}, author = {Bhadelia, R A and Anderson, M and Polak, J F and Manolio, T A and Beauchamp, N and Knepper, L and O{\textquoteright}Leary, D H} } @article {1525, title = {Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Feb}, pages = {356-65}, abstract = {

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}, issn = {1079-5642}, author = {Manolio, T A and Burke, G L and O{\textquoteright}Leary, D H and Evans, G and Beauchamp, N and Knepper, L and Ward, B} } @article {597, title = {The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.}, journal = {JAMA}, volume = {282}, year = {1999}, month = {1999 Jul 07}, pages = {40-6}, abstract = {

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}, issn = {0098-7484}, doi = {10.1001/jama.282.1.40}, author = {Haan, M N and Shemanski, L and Jagust, W J and Manolio, T A and Kuller, L} } @article {599, title = {Temporal trends in the use of anticoagulants among older adults with atrial fibrillation.}, journal = {Arch Intern Med}, volume = {159}, year = {1999}, month = {1999 Jul 26}, pages = {1574-8}, abstract = {

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}, issn = {0003-9926}, doi = {10.1001/archinte.159.14.1574}, author = {Smith, N L and Psaty, B M and Furberg, C D and White, R and Lima, J A and Newman, A B and Manolio, T A} } @article {608, title = {Clinical correlates of ventricular and sulcal size on cranial magnetic resonance imaging of 3,301 elderly people. The Cardiovascular Health Study. Collaborative Research Group.}, journal = {Neuroepidemiology}, volume = {19}, year = {2000}, month = {2000 Jan-Feb}, pages = {30-42}, abstract = {

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}, issn = {0251-5350}, doi = {10.1159/000026235}, author = {Longstreth, W T and Arnold, A M and Manolio, T A and Burke, G L and Bryan, N and Jungreis, C A and O{\textquoteright}Leary, D and Enright, P L and Fried, L} } @article {607, title = {Prevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly.}, journal = {J Am Coll Cardiol}, volume = {35}, year = {2000}, month = {2000 Jan}, pages = {119-26}, abstract = {

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}, issn = {0735-1097}, doi = {10.1016/s0735-1097(99)00524-0}, author = {Sheifer, S E and Gersh, B J and Yanez, N D and Ades, P A and Burke, G L and Manolio, T A} } @article {630, title = {Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.}, journal = {Ann Intern Med}, volume = {134}, year = {2001}, month = {2001 Feb 06}, pages = {182-90}, abstract = {

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}, issn = {0003-4819}, doi = {10.7326/0003-4819-134-3-200102060-00008}, author = {Newman, A B and Arnold, A M and Burke, G L and O{\textquoteright}Leary, D H and Manolio, T A} } @article {644, title = {Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {58}, year = {2001}, month = {2001 Apr}, pages = {635-40}, abstract = {

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}, issn = {0003-9942}, doi = {10.1001/archneur.58.4.635}, author = {Longstreth, W T and Diehr, P and Manolio, T A and Beauchamp, N J and Jungreis, C A and Lefkowitz, D} } @article {668, title = {Incidence and predictors of coronary heart disease among older African Americans--the Cardiovascular Health Study.}, journal = {J Natl Med Assoc}, volume = {93}, year = {2001}, month = {2001 Nov}, pages = {423-9}, abstract = {

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}, issn = {0027-9684}, author = {Jackson, S A and Burke, G L and Thach, C and Cushman, M and Ives, D and Powe, N and Manolio, T A} } @article {669, title = {Patterns on cranial magnetic resonance imaging in elderly people and vascular disease outcomes.}, journal = {Arch Neurol}, volume = {58}, year = {2001}, month = {2001 Dec}, pages = {2074}, keywords = {Aged, Brain, Cardiovascular Diseases, Cluster Analysis, Humans, Magnetic Resonance Imaging}, issn = {0003-9942}, doi = {10.1001/archneur.58.12.2074}, author = {Longstreth, W T and Diehr, P and Beauchamp, N J and Manolio, T A} } @article {637, title = {Predictors of loss of lung function in the elderly: the Cardiovascular Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Jan}, pages = {61-8}, abstract = {

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}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.1.9906089}, author = {Griffith, K A and Sherrill, D L and Siegel, E M and Manolio, T A and Bonekat, H W and Enright, P L} } @article {801, title = {Stroke risk factors and loss of high cognitive function.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Sep 14}, pages = {793-9}, abstract = {

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}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000137014.36689.7f}, author = {Elkins, J S and O{\textquoteright}Meara, E S and Longstreth, W T and Carlson, M C and Manolio, T A and Johnston, S C} } @article {860, title = {Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Sep 27}, pages = {835-42}, abstract = {

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}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000176058.09848.bb}, author = {Kaplan, R C and Tirschwell, D L and Longstreth, W T and Manolio, T A and Heckbert, S R and Lefkowitz, D and El-Saed, A and Psaty, B M} }