@article {1434, title = {Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {139}, year = {1994}, month = {1994 Jun 15}, pages = {1164-79}, abstract = {

The prevalence of subclinical atherosclerosis and cardiovascular disease was evaluated among the 5,201 adults aged > or = 65 years in four communities participating in the Cardiovascular Health Study from June 1989 through May 1990. A combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication defined subclinical disease. The prevalence of subclinical disease was 36\% in women and 38.7\% in men and increased with age. Among women, low-density lipoprotein cholesterol, systolic blood pressure, blood glucose, and cigarette smoking were positively associated, and high-density lipoprotein cholesterol negatively associated, with subclinical disease. In men, systolic blood pressure, blood glucose, and cigarette smoking were independent risk factors in multiple logistic regression analyses. The risk factors for subclinical disease are, therefore, similar to those for clinical disease at younger ages, especially among women. It is possible that older individuals with subclinical disease are at very high risk of developing clinical disease and that more aggressive interventions to prevent clinical disease should be oriented to individuals with subclinical disease.

}, keywords = {Aged, Aged, 80 and over, Arteriosclerosis, Cardiovascular Diseases, Female, Humans, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, United States}, issn = {0002-9262}, author = {Kuller, L and Borhani, N and Furberg, C and Gardin, J and Manolio, T and O{\textquoteright}Leary, D and Psaty, B and Robbins, J} } @article {1496, title = {Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {18}, year = {1998}, month = {1998 Feb}, pages = {283-93}, abstract = {

A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged > or =65 years) was 41.3\% for white women, 39.7\% for black women, 41.9\% for white men, and 43.7\% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease.

}, keywords = {African Americans, Aged, Cardiovascular Physiological Phenomena, Cohort Studies, European Continental Ancestry Group, Female, Health Status, Humans, Male, Multivariate Analysis, Prevalence, Regression Analysis, Risk Factors, Vascular Diseases}, issn = {1079-5642}, author = {Kuller, L and Fisher, L and McClelland, R and Fried, L and Cushman, M and Jackson, S and Manolio, T} } @article {1494, title = {Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study.}, journal = {Stroke}, volume = {29}, year = {1998}, month = {1998 Feb}, pages = {388-98}, abstract = {

BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores.

METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years.

RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2\% for participants without and 20.4\% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]).

CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.

}, keywords = {African Continental Ancestry Group, Aged, Apolipoproteins E, Brain, Cardiovascular Diseases, Cerebral Infarction, Cognition, Cognition Disorders, European Continental Ancestry Group, Female, Genotype, Health Status, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Polymerase Chain Reaction, Risk Factors, Sex Factors, United States}, issn = {0039-2499}, author = {Kuller, L H and Shemanski, L and Manolio, T and Haan, M and Fried, L and Bryan, N and Burke, G L and Tracy, R and Bhadelia, R} } @article {590, title = {Oral anticoagulation in patients with atrial fibrillation: adherence with guidelines in an elderly cohort.}, journal = {Am J Med}, volume = {106}, year = {1999}, month = {1999 Feb}, pages = {165-71}, abstract = {

PURPOSE: To determine adherence with practice guidelines in a population-based cohort of elderly persons aged 70 years or older with atrial fibrillation.

SUBJECTS AND METHODS: This was a cross-sectional analysis of a subgroup of participants in the Cardiovascular Health Study, a prospective observational study involving four communities in the United States. Subjects were participants with atrial fibrillation on electrocardiogram at one or more yearly examinations from 1993 to 1995. The outcome measure was self-reported use of warfarin in 1995.

RESULTS: In 1995, 172 (4.1\%) participants had atrial fibrillation together with information regarding warfarin use and no preexisting indication for its use. Warfarin was used by 63 (37\%) of these participants. Of the 109 participants not reporting warfarin use, 92 (84\%) had at least one of the clinical risk factors (aside from age) associated with stroke in patients with atrial fibrillation. Among participants not taking warfarin, 47\% were taking aspirin. Several characteristics were independently associated with warfarin use, including age [odds ratio (OR) = 0.6 per 5-year increment, 95\% CI 0.5-0.9], a modified mini-mental examination score <85 points [OR = 0.3, 95\% confidence interval (CI) 0.1-0.9], and among patients without prior stroke, female sex (OR = 0.5, 95\% CI 0.2-1.0).

CONCLUSIONS: Despite widely publicized practice guidelines to treat patients who have atrial fibrillation with warfarin, most participants who had atrial fibrillation were at high risk for stroke but were not treated with warfarin. More studies are needed to determine why elderly patients with atrial fibrillation are not being treated with warfarin.

}, keywords = {Administration, Oral, Aged, Anticoagulants, Atrial Fibrillation, Cerebrovascular Disorders, Cross-Sectional Studies, Female, Humans, Logistic Models, Male, Odds Ratio, Practice Guidelines as Topic, Prospective Studies, Risk, Risk Factors, Warfarin}, issn = {0002-9343}, doi = {10.1016/s0002-9343(98)00389-1}, author = {White, R H and McBurnie, M A and Manolio, T and Furberg, C D and Gardin, J M and Kittner, S J and Bovill, E and Knepper, L} } @article {610, title = {Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 Feb}, pages = {115-23}, abstract = {

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD.

SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease.

METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure.

RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95\% CI = 1.03, 1.76) in men and was 1.66 (95\% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95\% CI, 1.12- 1.98) and in women, was 2.21 (95\% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95\% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men.

CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Heart Failure, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Odds Ratio, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Stages, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb03901.x}, author = {Newman, A B and Spiekerman, C F and Enright, P and Lefkowitz, D and Manolio, T and Reynolds, C F and Robbins, J} } @article {616, title = {Estrogen replacement therapy and MRI-demonstrated cerebral infarcts, white matter changes, and brain atrophy in older women: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 May}, pages = {467-72}, abstract = {

OBJECTIVE: We studied the relationship between the use of estrogen replacement therapy (ERT) and cerebral magnetic resonance imaging (MRI) abnormalities among older women.

DESIGN: A population-based prospective study (Cardiovascular Health Study).

SETTING: Four regions in the United States.

PARTICIPANTS: A total of 2133 (62.9\% of the eligible) women aged 65 to 95 years (mean age 74.8), on whom MRI was performed in 1992-1994.

MEASUREMENTS: Presence of global brain atrophy, white matter changes, small infarct-like lesion (ILL) (<3 mm), MRI infarcts (> or =3 mm, mostly small and asymptomatic), and cognitive function as measured by Mini-Mental State Exam (MMSE), and by ERT use (current/past/never), adjusted for a number of socioeconomic, lifestyle, and reproductive covariates.

RESULTS: Current use of ERT was reported by 15\% and past use by another 23\% of participants; 35\% of all women had MRI infarcts. The prevalence of MRI infarcts did not differ in current or past users from those who had never used ERT (nonusers). Bifrontal distance, the largest distance between frontal horns, and the size of ventricles were larger among current ERT users compared to past users or nonusers (P (trend) = .01), adjusted for all other covariates, but no dose-response relationship to current or past ERT use was found. Duration of estrogen use was not associated with any atrophy measure. Cortical atrophy measure, sulcal widening, or white matter disease did not differ significantly by ERT use or duration of use. Central measures of atrophy, bifrontal distance, and ventricular size were significantly associated with cognition as measured by MMSE.

CONCLUSIONS: Current ERT users had much more clinically significant central atrophy than nonusers, but the implications remained unclear.

}, keywords = {Aged, Aged, 80 and over, Atrophy, Brain, Brain Infarction, Estrogen Replacement Therapy, Female, Humans, Intelligence Tests, Life Style, Magnetic Resonance Imaging, Population Surveillance, Prevalence, Prospective Studies, Social Class, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb04990.x}, author = {Luoto, R and Manolio, T and Meilahn, E and Bhadelia, R and Furberg, C and Cooper, L and Kraut, M} } @article {663, title = {Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.}, journal = {Neurology}, volume = {57}, year = {2001}, month = {2001 Oct 09}, pages = {1222-9}, abstract = {

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly.

OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors.

METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts.

RESULTS: Approximately 28\% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes).

CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

}, keywords = {Aged, Cerebral Infarction, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Risk Factors, Stroke}, issn = {0028-3878}, doi = {10.1212/wnl.57.7.1222}, author = {Bernick, C and Kuller, L and Dulberg, C and Longstreth, W T and Manolio, T and Beauchamp, N and Price, T} } @article {655, title = {Usefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {88}, year = {2001}, month = {2001 Jul 15}, pages = {118-23}, abstract = {

T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (> or =45 degrees ) was 12\%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50\% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.

}, keywords = {Aged, Algorithms, Cohort Studies, Coronary Disease, Electrocardiography, Female, Follow-Up Studies, Humans, Male, Prevalence, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Survival Analysis}, issn = {0002-9149}, doi = {10.1016/s0002-9149(01)01604-6}, author = {Rautaharju, P M and Nelson, J C and Kronmal, R A and Zhang, Z M and Robbins, J and Gottdiener, J S and Furberg, C D and Manolio, T and Fried, L} } @article {745, title = {Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.}, journal = {J Thromb Haemost}, volume = {1}, year = {2003}, month = {2003 Aug}, pages = {1799-804}, abstract = {

Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22\%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, European Continental Ancestry Group, Female, Genotype, Homozygote, Humans, Male, Myocardial Infarction, Plasminogen Activator Inhibitor 1, Polymorphism, Genetic, Promoter Regions, Genetic, Risk}, issn = {1538-7933}, doi = {10.1046/j.1538-7836.2003.00255.x}, author = {Crainich, P and Jenny, N S and Tang, Z and Arnold, A M and Kuller, L H and Manolio, T and Sharrett, A R and Tracy, R P} }