@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 {747, title = {The distribution of coagulation factors VII and VIII and fibrinogen in adults over 65 years. Results from the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {2}, year = {1992}, month = {1992 Jul}, pages = {509-19}, abstract = {

The Cardiovascular Health Study (CHS) was designed to examine cardiovascular disease and its risk factors in older adults. We report here the distributions of the coagulation factors fibrinogen, factor VII, and factor VIII in a population-based cohort of men and women 65 years or older. In other studies of middle-aged individuals, these factors were shown to be associated with cardiovascular risk. In the CHS cohort, all three factors were elevated, compared to levels reported in middle-aged individuals, and fibrinogen and factor VIII values were higher in each successive age group; factor VII values, in contrast, declined slightly with age in the CHS cohort. Compared to white subjects, blacks had higher values for fibrinogen and factor VIII and lower values for factor VII. While women had markedly higher values for factor VII and factor VIII than men at all ages in the CHS, mean fibrinogen values were not different between men and women.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Cardiovascular Diseases, Cohort Studies, Factor VII, Factor VIII, Female, Fibrinogen, Humans, Male, Middle Aged, Risk Factors}, issn = {1047-2797}, doi = {10.1016/1047-2797(92)90100-5}, author = {Tracy, R P and Bovill, E G and Fried, L P and Heiss, G and Lee, M H and Polak, J F and Psaty, B M and Savage, P J} } @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 {748, title = {Isolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study.}, journal = {JAMA}, volume = {268}, year = {1992}, month = {1992 Sep 09}, pages = {1287-91}, abstract = {

OBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above.

DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg.

MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis.

RESULTS: Among the 2189 men and women in this analysis, 195 (9\%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23\%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001).

CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.

}, keywords = {Aged, Aged, 80 and over, Cardiomegaly, Cardiovascular Diseases, Carotid Artery Diseases, Cerebrovascular Disorders, Coronary Disease, Cross-Sectional Studies, Echocardiography, Electrocardiography, Female, Humans, Hypertension, Male, Myocardial Infarction, Prospective Studies, Risk Factors, Systole}, issn = {0098-7484}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Borhani, N O and Rautaharju, P M and O{\textquoteright}Leary, D H and Bild, D E and Robbins, J and Fried, L P and Reid, C} } @article {1442, title = {Age-related trends in cardiovascular morbidity and physical functioning in the elderly: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {41}, year = {1993}, month = {1993 Oct}, pages = {1047-56}, abstract = {

OBJECTIVE: To describe relationships between age and sub-clinical cardiovascular disease, manifest chronic disease, and physical functioning and limitations among persons aged 65 years and older, with emphasis on the "oldest old," those 85 years and older.

DESIGN: Observational population-based study.

SETTING: Four U.S. communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania.

PARTICIPANTS: 5,201 men and women aged 65 years and older.

MEASUREMENTS: Demographic data; histories of cardiovascular disease (CVD), chronic lung disease, arthritis, diabetes, and hypertension; measures of subclinical disease including arm and ankle blood pressures, internal carotid wall thickness and stenosis, ejection fraction, left ventricular mass, fractional shortening, and diastolic function, electrocardiographic left ventricular hypertrophy and cardiac injury score, forced expiratory flow and volume; functional status including self-reported physical functioning, hearing and sight limitations and health status, and performance-based measures of function. These variables were examined among men and women in three age groups: 65-74 years, 75-84 years, and 85 + years. Subgroups of participants with and without manifest CVD were also examined.

MAIN RESULTS: In women, the prevalence of CVD and other chronic conditions increased with age, and the highest rates occurred among those 85 years and older. In men, prevalence rates increased between the two younger groups, but the oldest group had lower than expected rates for coronary heart disease, cerebrovascular disease, hypertension, and chronic lung disease. In contrast, there were strong age-related linear trends in most of the subclinical measures of blood pressure, atherosclerosis and pulmonary function and in virtually all measures of functional status in both gender groups across the age range. There was a particularly marked decline in functional status between the two older age groups. While subclinical disease was greater and functional status was poorer among those with manifest CVD, with few exceptions, age-related trends were not significantly different between the two groups.

CONCLUSIONS: Lower than expected prevalence rates of CVD among those aged 85 years and older, particularly among men, in this study of community-dwelling elderly may represent selection bias or a real plateauing in disease prevalence with age. However, subclinical disease appears to increase and functional status to decline across the age range in both men and women regardless of the presence of CVD. The apparent increase in subclinical disease with age indicates potential for CVD prevention after age 65.

}, keywords = {Activities of Daily Living, Age Distribution, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Humans, Male, Prevalence, Sex Distribution, Socioeconomic Factors}, issn = {0002-8614}, author = {Bild, D E and Fitzpatrick, A and Fried, L P and Wong, N D and Haan, M N and Lyles, M and Bovill, E and Polak, J F and Schulz, R} } @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 {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 {1446, title = {Prevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {137}, year = {1993}, month = {1993 Feb 01}, pages = {311-7}, abstract = {

The Cardiovascular Health Study is a population-based longitudinal study of 5,201 adults aged 65 years and older. Prevalences of myocardial infarction, angina pectoris, congestive heart failure, peripheral artery disease, stroke, and transient ischemic attack were ascertained between June 1989 and May 1990 in participants recruited from Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pennsylvania. A medical history was taken to obtain self-reports of prevalent disease. For all participants, use of nitrates was ascertained to document angina, electrocardiograms were used to document prevalent myocardial infarction, and ankle-arm blood pressure studies were used to document peripheral artery disease. Self-reports of disease that were not confirmed by examination findings were further investigated by examination of medical records. Reported disease that was confirmed by examination findings or by medical records was classified as "definite." Disease that was documented by examination, but not reported by the participant, was classified as "unreported." The prevalence rates of definite myocardial infarction and angina were 11\% and 15\%, respectively, among men aged 65-69 years, 18\% and 17\% among men aged 80-84 years, 4\% and 8\% among women aged 65-69 years, and 3\% and 13\% among women aged 80-84 years. Twenty-three percent of men and 38\% of women with electrocardiographic evidence of myocardial infarction did not report it. These results suggest that prevalent disease estimates based only on self-report may underestimate the prevalence of cardiovascular diseases in older Americans.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Bias, California, Cardiovascular Diseases, Electrocardiography, Female, Health Surveys, Humans, Longitudinal Studies, Male, Maryland, Mass Screening, North Carolina, Pennsylvania, Population Surveillance, Prevalence, Reproducibility of Results}, issn = {0002-9262}, author = {Mittelmark, M B and Psaty, B M and Rautaharju, P M and Fried, L P and Borhani, N O and Tracy, R P and Gardin, J M and O{\textquoteright}Leary, D H} } @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 {1432, title = {High density lipoprotein cholesterol subfractions in older people.}, journal = {J Gerontol}, volume = {49}, year = {1994}, month = {1994 May}, pages = {M116-22}, abstract = {

BACKGROUND: High density lipoprotein (HDL) may be an important risk factor for cardiovascular disease in older people. HDL is heterogeneous with several subfractions. This article describes the distribution and correlates of HDL2 cholesterol (C) and HDL3-C in older people.

METHODS: HDL subfraction cholesterols were measured in 1,127 females and 825 males > or = 65 years old who participated in the Cardiovascular Health Study. Distributions of HDL subfraction cholesterols and bivariate and multivariate relationships were determined in cross-sectional analyses.

RESULTS: Mean (+/- SD) concentrations of HDL subfractions were: HDL3-C (M .98 +/- .25, F 1.2 +/- .29 mmol/l), HDL2-C (M .09 +/- .08, F .13 +/- .09 mmol/l). HDL2-C, but not HDL3-C, was slightly higher with age. Using multivariate analysis, both HDL2-C and HDL3-C (in females) were inversely correlated with triglyceride, body weight, and fasting insulin; HDL3-C was inversely correlated with central fat distribution in women. Both HDL2-C and HDL3-C were lower in participants with prevalent cardiovascular disease. However, only HDL3-C was significantly inversely related to carotid stenosis, as measured by ultrasound.

CONCLUSIONS: The slight increase in HDL-C with age appears to be due to an increase in the HDL2-C subfraction. HDL-C subfractions are independently related to triglyceride levels, body weight, and insulin concentrations in older people, all potentially modifiable risk factors. Both HDL2-C and HDL3-C are lower in older people with prevalent cardiovascular disease, although only HDL3-C was correlated with carotid atherosclerosis. These findings are consistent with the hypothesis that HDL subfractions are important risk factors for atherosclerotic cardiovascular disease in the elderly.

}, keywords = {Aged, Aged, 80 and over, Alcohol Drinking, Body Weight, Carotid Stenosis, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Drug Therapy, Female, Humans, Insulin, Lipoproteins, HDL, Lipoproteins, HDL2, Lipoproteins, HDL3, Male, Sex Factors, Socioeconomic Factors}, issn = {0022-1422}, author = {Ettinger, W H and Verdery, R B and Wahl, P W and Fried, L P} } @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 {1417, title = {Physical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.}, journal = {J Clin Epidemiol}, volume = {47}, year = {1994}, month = {1994 Jul}, pages = {747-60}, abstract = {

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

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Chronic Disease, Disabled Persons, Factor Analysis, Statistical, Female, Geriatric Assessment, Humans, Logistic Models, Male, Outcome Assessment (Health Care), Risk Factors, Sex Factors, Socioeconomic Factors, United States}, issn = {0895-4356}, author = {Fried, L P and Ettinger, W H and Lind, B and Newman, A B and Gardin, J} } @article {1424, title = {Self-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {J Am Geriatr Soc}, volume = {42}, year = {1994}, month = {1994 Oct}, pages = {1035-44}, abstract = {

OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self-report of diseases given as the causes of the difficulty in functioning, in community-dwelling older people.

DESIGN: Cross sectional analyses of data obtained in an observational cohort study.

SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA.

PARTICIPANTS: 5201 community-dwelling people > or = 65 years old.

RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0\% of the participants reporting difficulty in any task, followed by heart disease (13.7\%), injury (12.0\%), old age (11.7\%), lung disease (6.0\%), and stroke (2.9\%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91\%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85\% in men and 71\% in women, and varied according to type of disease and the individual{\textquoteright}s cognitive status and health status.

CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Arthritis, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Disabled Persons, Female, Health Status, Health Surveys, Heart Diseases, Humans, Lung Diseases, Male, Observer Variation, Reproducibility of Results, Risk Factors, Sex Factors, United States}, issn = {0002-8614}, author = {Ettinger, W H and Fried, L P and Harris, T and Shemanski, L and Schulz, R and Robbins, J} } @article {1416, title = {Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly. Results from The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {15}, year = {1995}, month = {1995 Sep}, pages = {1269-79}, abstract = {

No studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, fibrinogen was significantly associated with carotid artery stenosis, internal (but not common) carotid artery wall thickness, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Carotid Stenosis, Cohort Studies, Factor VII, Factor VIII, Fibrinogen, Humans, Multivariate Analysis, Prospective Studies, Regression Analysis, Risk Factors}, issn = {1079-5642}, author = {Tracy, R P and Bovill, E G and Yanez, D and Psaty, B M and Fried, L P and Heiss, G and Lee, M and Polak, J F and Savage, P J} } @article {1457, title = {Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators.}, journal = {Am J Epidemiol}, volume = {143}, year = {1996}, month = {1996 Apr 01}, pages = {665-76}, abstract = {

The cross-sectional correlates of three hemostatic factors--fibrinogen, factor VII, and factor VIII--were examined in the Cardiovascular Health Study, a population-based cohort study of 5,201 subjects over age 65 years. Subjects were recruited in 1989-1990 in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. In multivariate linear regression models, cardiac risk factors significantly associated with fibrinogen were current smoking, race, lipids, and white blood count. In women, alcohol use, obesity, physical activity, and insulin level were also significant, while in men hypertension was correlated. The significant correlates of factor VII were lipids and white blood count in men and estrogen use, alcohol use, race, lipids, insulin level, white blood count, and obesity in women. The independent correlates of factor VIII were insulin, glucose, and race in both sexes; low density lipoprotein cholesterol, white blood count, and diuretic use in men; and alcohol use in women. In multivariate models, factors known to be modifiable risk factors for cardiovascular disease accounted for more of the population variance of these hemostatic factors in women than in men, especially for factor VII. The hemostatic factors may mediate some effects of risk factors on disease, and this should be considered in longitudinal studies.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Cohort Studies, Factor VII, Factor VIII, Female, Fibrinogen, Humans, Linear Models, Logistic Models, Male, Prevalence, Risk Factors, Sex Distribution, United States}, issn = {0002-9262}, author = {Cushman, M and Yanez, D and Psaty, B M and Fried, L P and Heiss, G and Lee, M and Polak, J F and Savage, P J and Tracy, R P} } @article {1485, title = {Correlates of performance-based measures of muscle function in the elderly: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {52}, year = {1997}, month = {1997 Jul}, pages = {M192-200}, abstract = {

BACKGROUND: It is unknown how much age-related changes in muscle performance represent normal aging versus the effects of chronic disease and life style. We examined the correlates of four performance measures-gait speed, timed chair stands (TCS), grip strength, and maximal inspiratory pressure (MIP)-using baseline data from the Cardiovascular Health Study (CHS), a population-based study of risk factors for heart disease and stroke in persons > or = age 65.

METHODS: We analyzed data from the 5,201 CHS participants. Variables were arranged into nine categories: Personal Characteristics, Anthropometry, Physical Condition, Reported Functional Status, Subjective Health, Psychological Factors, Symptoms, Cognitive Status, Habits and Lifestyle, and Prevalent Disease. Independent correlates were identified using stepwise linear regression.

RESULTS: The regression models explained 17.7-25.4\% of the observed variability. Although age significantly correlated with each measure, it explained little of the variability (< or = 5.7\%). Anthropometric features plus physical condition explained 14.0-17.4\% of the variability for grip strength and MIP, but 2.8-12.9\% of the variability for gait speed and the log of TCS. Subjective health and psychological factors explained 1.8-9.4\% of the variability in gait speed and the log of TCS, but < or = 1.2\% of the variability in grip strength and MIP. Variables for prevalent disease explained < or = 1.3\% of the variability in each measure.

CONCLUSIONS: After age 64, age explained little of the variability in muscle performance in a large sample of mostly functionally intact, community-dwelling older persons. Complex measures such as gait speed were more associated with subjective factors than were direct measures of strength. Prevalent disease contributed surprisingly little to muscle performance.

}, keywords = {Aging, Anthropometry, Cardiovascular Physiological Phenomena, Female, Gait, Hand Strength, Health Status, Humans, Male, Middle Aged, Motor Activity, Muscles, Pressure, Regression Analysis, Respiration}, issn = {1079-5006}, author = {Hirsch, C H and Fried, L P and Harris, T and Fitzpatrick, A and Enright, P and Schulz, R} } @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 {1480, title = {Left ventricular mass in the elderly. The Cardiovascular Health Study.}, journal = {Hypertension}, volume = {29}, year = {1997}, month = {1997 May}, pages = {1095-103}, abstract = {

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

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Body Weight, Cardiovascular Diseases, Cohort Studies, Echocardiography, Female, Humans, Hypertrophy, Left Ventricular, Male, Prospective Studies, Risk Factors, Ventricular Function, Left}, issn = {0194-911X}, author = {Gardin, J M and Arnold, A and Gottdiener, J S and Wong, N D and Fried, L P and Klopfenstein, H S and O{\textquoteright}Leary, D H and Tracy, R and Kronmal, R} } @article {1498, title = {Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study.}, journal = {JAMA}, volume = {279}, year = {1998}, month = {1998 Feb 25}, pages = {585-92}, abstract = {

CONTEXT: Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known.

OBJECTIVE: To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older.

DESIGN: Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up.

SETTING: Four US communities.

PARTICIPANTS: A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively.

MAIN OUTCOME MEASURES: Five-year mortality.

RESULTS: In the main cohort, 646 deaths (12\%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (< or = 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (< or = 37 g/L), elevated creatinine level (> or = 106 micromol/L [1.2 mg/dL]), low forced vital capacity (< or = 2.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2\% to 39\% and 0\% to 26\% for the 2 cohorts.

CONCLUSIONS: Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Health Surveys, Humans, Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, United States}, issn = {0098-7484}, author = {Fried, L P and Kronmal, R A and Newman, A B and Bild, D E and Mittelmark, M B and Polak, J F and Robbins, J A and Gardin, J M} } @article {604, title = {Neuroanatomic and functional correlates of depressed mood: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {150}, year = {1999}, month = {1999 Nov 01}, pages = {919-29}, abstract = {

Although a number of studies suggest an association between stroke and depression, few have examined the relation between magnetic resonance imaging (MRI)-identified lesions and depression among community-dwelling older adults. This cross-sectional study sought to assess the association between MRI infarcts in the basal ganglia and non-basal-ganglia areas, potential functional consequences of these lesions, and depressive symptomatology in 3,371 US men and women aged 65 years or older who participated in the Cardiovascular Health Study between 1992 and 1994. By using multiple linear regression models, the authors found that after adjustment for age, gender, and stroke history, Center for Epidemiologic Studies Depression Scale scores were independently associated with non-basal-ganglia lesions (p = 0.04) but were not independently associated with basal ganglia lesions (p = 0.11). When measures of physical disability and cognitive impairment were added to the models, these measures displaced MRI-identified infarcts in their association with depressive symptoms. In additional models, hemispheric location and size of the basal ganglia lesion were found to have no relation to depression levels. These results suggest that the functional consequences of cerebrovascular disease may be the causal pathway by which basal ganglia and non-basal-ganglia lesions are associated with depressive symptomatology.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia, Cerebral Infarction, Cognition, Cross-Sectional Studies, Depression, Female, Geriatric Assessment, Humans, Linear Models, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Risk Factors, United States}, issn = {0002-9262}, doi = {10.1093/oxfordjournals.aje.a010100}, author = {Sato, R and Bryan, R N and Fried, L P} } @article {640, title = {Associations of subclinical cardiovascular disease with frailty.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M158-66}, abstract = {

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology.

METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing.

RESULTS: Of 4,735 eligible participants, 2,289 (48\%) were not frail, 299 (6\%) were frail, and 2.147 (45\%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95\% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75\% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05).

CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

}, keywords = {Aged, Ankle, Arm, Black or African American, Blood Pressure, Brain, Cardiovascular Diseases, Carotid Artery Diseases, Cerebral Infarction, Cerebrovascular Disorders, Cohort Studies, Echocardiography, Electrocardiography, Frail Elderly, Health Status, Heart Failure, Humans, Magnetic Resonance Imaging, United States, Vascular Diseases}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m158}, author = {Newman, A B and Gottdiener, J S and McBurnie, M A and Hirsch, C H and Kop, W J and Tracy, R and Walston, J D and Fried, L P} } @article {646, title = {Factors associated with healthy aging: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Mar}, pages = {254-62}, abstract = {

OBJECTIVES: To identify factors associated with remaining healthy in older adults.

DESIGN: Longitudinal cohort study.

SETTING: Data were collected at the four Cardiovascular Health Study field centers.

PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study.

MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes.

RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults.

CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cohort Studies, Diet, Exercise, Female, Health Status, Humans, Incidence, Life Style, Longitudinal Studies, Lung Diseases, Obstructive, Male, Neoplasms, Probability, Reference Values, Risk Factors, Sex Distribution, Socioeconomic Factors, Survival Rate, United States}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.4930254.x}, author = {Burke, G L and Arnold, A M and Bild, D E and Cushman, M and Fried, L P and Newman, A and Nunn, C and Robbins, J} } @article {639, title = {Frailty in older adults: evidence for a phenotype.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M146-56}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Disabled Persons, Fatigue, Female, Frail Elderly, Humans, Incidence, Male, Muscle Weakness, Phenotype, Prevalence, Sex Distribution, United States, Weight Loss}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m146}, author = {Fried, L P and Tangen, C M and Walston, J and Newman, A B and Hirsch, C and Gottdiener, J and Seeman, T and Tracy, R and Kop, W J and Burke, G and McBurnie, M A} } @article {683, title = {Weight change in old age and its association with mortality.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Oct}, pages = {1309-18}, abstract = {

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

DESIGN: Longitudinal observational cohort study.

SETTING: Four U.S. communities.

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

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

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

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

}, keywords = {Aged, Analysis of Variance, Body Weight, Chi-Square Distribution, Female, Health Status, Humans, Longitudinal Studies, Male, Mortality, Proportional Hazards Models, Risk Factors, United States, Weight Gain, Weight Loss}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49258.x}, author = {Newman, A B and Yanez, D and Harris, T and Duxbury, A and Enright, P L and Fried, L P} } @article {815, title = {Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Dec 28}, pages = {2341-7}, abstract = {

OBJECTIVE: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset.

METHODS: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years).

RESULTS: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later.

CONCLUSIONS: Cognitive changes can be detected well before onset of Alzheimer disease.

}, keywords = {Age of Onset, Alzheimer Disease, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Confounding Factors, Epidemiologic, Disease Progression, Early Diagnosis, Educational Status, Female, Follow-Up Studies, Humans, Male, Memory Disorders, Neuropsychological Tests, Predictive Value of Tests, Proportional Hazards Models, Risk, Sensitivity and Specificity, Time Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000147470.58328.50}, author = {Saxton, J and Lopez, O L and Ratcliff, G and Dulberg, C and Fried, L P and Carlson, M C and Newman, A B and Kuller, L} } @article {870, title = {Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1409-14}, abstract = {

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician{\textquoteright}s assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28\% (95\% CI: 0.51 to 1.02), and AD by 41\% (95\% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Dietary Fats, Unsaturated, Fatty Acids, Omega-3, Feeding Behavior, Female, Fish Oils, Fish Products, Food, Formulated, Genetic Predisposition to Disease, Humans, Incidence, Male, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000183148.34197.2e}, author = {Huang, T L and Zandi, P P and Tucker, K L and Fitzpatrick, A L and Kuller, L H and Fried, L P and Burke, G L and Carlson, M C} } @article {888, title = {A cross-sectional study of vitamin C and cognitive function in older adults: the differential effects of gender.}, journal = {J Nutr Health Aging}, volume = {10}, year = {2006}, month = {2006 Jan-Feb}, pages = {37-44}, abstract = {

Previous studies have suggested that vitamin C status may be associated with cognitive function in community-dwelling populations. However, this has not been consistent across all studies due to methodological differences. This cross-sectional study assessed the association between vitamin C and cognitive function in 544 community-dwelling older adults aged 65 or older who participated in both the Cardiovascular Health Study (CHS) and the CLUE II study in 1989. Three percent of the subjects had low plasma vitamin C concentrations (< 40 mg/dL) and 15\% had low total vitamin C intake (< 60 mg/day). Most participants (96.7 percent) had normal cognitive function. In the unadjusted analyses, the highest fifth of plasma vitamin C concentration was associated with better Digit Symbol Substitution Test (DSST) scores and marginally associated with Mini-Mental State Examination (MMSE) compared to the lowest fifth. Total vitamin C intake, measured by Block{\textquoteright}s food frequency questionnaire, was generally associated with higher MMSE scores, though it was not significant. Adjusting for numerous factors did not substantially change results. In a stratified analysis by gender, higher plasma concentrations or intake were associated with higher MMSE scores for men but not for women. These mixed results do not provide strong evidence of an association between vitamin C concentrations or intake and cognitive function.

}, keywords = {Aged, Aging, Ascorbic Acid, Cognition, Cross-Sectional Studies, Diet, Female, Health Surveys, Humans, Male, Mental Status Schedule, Nutrition Surveys, Nutritional Requirements, Sex Factors, Surveys and Questionnaires}, issn = {1279-7707}, author = {Sato, R and Helzlsouer, K J and Comstock, G W and Hoffman, S C and Norkus, E P and Fried, L P} } @article {880, title = {Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.}, journal = {J Thromb Haemost}, volume = {4}, year = {2006}, month = {2006 Jan}, pages = {107-13}, abstract = {

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression.

OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study.

METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up.

RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95\% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events.

CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

}, keywords = {Aged, Aged, 80 and over, Angina Pectoris, Biomarkers, Cardiovascular Diseases, Female, Humans, Incidence, Intercellular Adhesion Molecule-1, Male, Mortality, Myocardial Infarction, Regression Analysis, Risk Factors, Sex Factors, Solubility, Stroke}, issn = {1538-7933}, doi = {10.1111/j.1538-7836.2005.01678.x}, author = {Jenny, N S and Arnold, A M and Kuller, L H and Sharrett, A R and Fried, L P and Psaty, B M and Tracy, R P} } @article {1031, title = {Knee height and arm span: a reflection of early life environment and risk of dementia.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 May 06}, pages = {1818-26}, abstract = {

OBJECTIVES: To determine if anthropometric measures, as markers of early life environment, are associated with risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).

METHODS: A total of 2,798 subjects were followed as part of the Cardiovascular Health Cognition Study for an average of 5.4 years; 480 developed dementia. Knee height was measured 3 years prior to and arm span 4 years after the study{\textquoteright}s baseline. Cox proportional hazard models were used to examine their association with subsequent risk of dementia, AD, and VaD.

RESULTS: Among women, greater knee height and arm span were associated with lower risks of dementia (knee height: HR per 1-inch increase 0.84; 95\% CI 0.74-0.96; arm span: HR per 1-inch increase 0.93; 95\% CI 0.88-0.98) and AD (knee height: HR per 1-inch increase 0.78; 95\% CI 0.65-0.93; arm span: HR per 1-inch increase 0.90; 95\% CI 0.85-0.96). Women in the lowest quartile of arm span had approximately 1.5 times greater risk of dementia (HR 1.45; 95\% CI 1.03-2.05) and AD (HR 1.70; 95\% CI 1.10-2.62) than other women. Among men, only arm span was associated with lower risks of dementia (HR per 1-inch increase 0.94; 95\% CI 0.89-1.00) and AD (HR per 1-inch increase 0.92; 95\% CI 0.84-1.00). For each gender, knee height was not associated with VaD, while arm span was associated with a nonsignificant lower risk of VaD.

CONCLUSIONS: Our findings with knee height and arm span are consistent with previous reports and suggest early life environment may play an important role in the determination of future dementia risk.

}, keywords = {Aged, Aged, 80 and over, Aging, Anthropometry, Arm, Body Height, Brain, Child, Child, Preschool, Dementia, Environment, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Knee, Male, Middle Aged, Prospective Studies, Risk Factors, Sex Characteristics, Skeleton}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000311444.20490.98}, author = {Huang, T L and Carlson, M C and Fitzpatrick, A L and Kuller, L H and Fried, L P and Zandi, P P} } @article {1335, title = {The association of genetic variants in interleukin-1 genes with cognition: findings from the cardiovascular health study.}, journal = {Exp Gerontol}, volume = {46}, year = {2011}, month = {2011 Dec}, pages = {1010-9}, abstract = {

The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer{\textquoteright}s, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95\%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95\%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95\%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95\%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95\%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cognition, Cognition Disorders, Dementia, Educational Status, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Interleukin 1 Receptor Antagonist Protein, Interleukin-1alpha, Interleukin-1beta, Linkage Disequilibrium, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, United States}, issn = {1873-6815}, doi = {10.1016/j.exger.2011.09.005}, author = {Benke, K S and Carlson, M C and Doan, B Q and Walston, J D and Xue, Q L and Reiner, A P and Fried, L P and Arking, D E and Chakravarti, A and Fallin, M D} }