@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 {848, title = {Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. The Cardiovascular Health Study Collaborative Research Group.}, journal = {J Clin Epidemiol}, volume = {45}, year = {1992}, month = {1992 Jun}, pages = {683-92}, abstract = {

The Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary heart disease and stroke, recruited 5201 community-dwelling adults aged 65 years or older. To assess the prevalence of medication use at baseline, we used the method of medication inventory and transcribed information about drug names and doses from prescription bottles. Using a specially-written computer program, persons without a knowledge of drug nomenclature coded 10,511 (89\%) of the 11,846 medicines entered. We compared the results of the medication inventory and answers to questions on specific medications for reliability and validity. The use of beta-blockers and beta-agonists assessed by the method of medication inventory, but not by the method of directed recall, was associated with a significant effect on mean heart rate. Among 5197 participants with medication data, 76.1\% were taking at least one medicine, and the mean number of drugs per person was 2.28. Among those with a reported history of high blood pressure, participants with cardiovascular disease (CVD) were more likely to be treated, and they were more likely to be taking beta-blockers and calcium-channel blockers than those without CVD. Daily aspirin use was also more common among those with CVD (30.5\% of women and 43.2\% of men) than among those without CVD (14.0\% of women and 14.0\% of men). The prevalence of post-menopausal estrogen use differed significantly among the four clinical centers (range = 5.5\%-22.5\% of women). We conclude that this method of assessing medications was easy to use and provided estimates of exposure to drugs that may affect risk of cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Cerebrovascular Disorders, Coronary Disease, Data Collection, Drug Utilization, Female, Humans, Male, Prospective Studies, Risk Factors, United States}, issn = {0895-4356}, doi = {10.1016/0895-4356(92)90143-b}, author = {Psaty, B M and Lee, M and Savage, P J and Rutan, G H and German, P S and Lyles, M} } @article {951, title = {Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study.}, journal = {J Am Soc Echocardiogr}, volume = {5}, year = {1992}, month = {1992 Jan-Feb}, pages = {63-72}, abstract = {

The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults.

}, keywords = {Allied Health Personnel, Cerebrovascular Disorders, Coronary Disease, Echocardiography, Echocardiography, Doppler, Humans, Prospective Studies, Quality Control, Risk Factors, United States}, issn = {0894-7317}, doi = {10.1016/s0894-7317(14)80105-3}, author = {Gardin, J M and Wong, N D and Bommer, W and Klopfenstein, H S and Smith, V E and Tabatznik, B and Siscovick, D and Lobodzinski, S and Anton-Culver, H and Manolio, T A} } @article {808, title = {Eligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study.}, journal = {Ann Intern Med}, volume = {116}, year = {1992}, month = {1992 Apr 15}, pages = {641-9}, abstract = {

OBJECTIVES: To assess the proportion of community-dwelling adults aged 65 years or older who are eligible for referral for lipoprotein analysis and intervention according to the National Cholesterol Education Program (NCEP) guidelines.

DESIGN: Cross-sectional study based on examinations and questionnaires collected in 1989 and 1990.

SETTING: Four communities in the U.S. in the Cardiovascular Health Study (CHS), a study of risk factors for heart disease and stroke in older adults.

PARTICIPANTS: A sample of 4810 men and women ages 65 to 100 randomly selected and recruited from Health Care Financing Administration Medicare eligibility lists for the four communities; not institutionalized, not wheelchair-bound, not currently receiving therapy for cancer, not currently taking lipid-lowering medications, and not having eaten in the preceding 9 hours.

MEASUREMENTS: Total cholesterol and lipoprotein analysis measured in all participants.

RESULTS: Total cholesterol levels were less than 5.17 mmol/L (200 mg/dL) in 37\% of participants, 5.17 to 6.19 mmol/L (200 to 239 mg/dL) in 39\%, and 6.20 mmol/L (240 mg/dL) or greater in 24\%. Compared with their counterparts, older participants, especially those over 80 years of age, were more likely to have levels below 5.17 mmol/L, as were men, nonwhites, and those with coronary heart disease or two or more coronary heart disease risk factors (P less than 0.008 for all values). Based on this screening measurement, 2174 participants were eligible for lipoprotein analysis, 80\% were eligible for dietary or drug therapy using NCEP guidelines. Overall, 46\% of CHS participants were eligible for lipoprotein analysis and 36\% for intervention by NCEP guidelines, based on a single cholesterol measurement.

CONCLUSION: A substantial proportion of older adults in this community sample were eligible for lipoprotein analysis and intervention. Prospective studies of elderly persons are needed to determine the risk for incident coronary heart disease according to NCEP classifications and the benefits of lipid-lowering treatments in persons in this age group so that intervention strategies may best be targeted to an appropriately high-risk group.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cerebrovascular Disorders, Cholesterol, LDL, Coronary Disease, Eligibility Determination, Female, Humans, Hypercholesterolemia, Longitudinal Studies, Male, Primary Prevention, Referral and Consultation, Risk Factors, United States}, issn = {0003-4819}, doi = {10.7326/0003-4819-116-8-641}, author = {Manolio, T A and Furberg, C D and Wahl, P W and Tracy, R P and Borhani, N O and Gardin, J M and Fried, L P and O{\textquoteright}Leary, D H and Kuller, L H} } @article {835, title = {Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.}, journal = {Am J Cardiol}, volume = {69}, year = {1992}, month = {1992 May 15}, pages = {1329-35}, abstract = {

Electrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29\% in the entire cohort, 19\% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37\% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2\%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Arrhythmias, Cardiac, Chi-Square Distribution, Electrocardiography, Female, Heart Diseases, Humans, Logistic Models, Male, Prevalence, Risk Factors, Sex Factors, United States}, issn = {0002-9149}, doi = {10.1016/0002-9149(92)91231-r}, author = {Furberg, C D and Manolio, T A and Psaty, B M and Bild, D E and Borhani, N O and Newman, A and Tabatznik, B and Rautaharju, P M} } @article {1448, title = {Smoking and lung function in elderly men and women. The Cardiovascular Health Study.}, journal = {JAMA}, volume = {269}, year = {1993}, month = {1993 Jun 02}, pages = {2741-8}, abstract = {

OBJECTIVE: To investigate relationships between cigarette smoking and pulmonary function in elderly men and women.

DESIGN: Cross-sectional analysis of baseline data from a prospective, population-based study of risk factors, preclinical, and overt cardiovascular and pulmonary disease.

SETTING: Defined communities in Forsyth County, North Carolina; Pittsburgh, Pa; Sacramento County, California; and Washington County, Maryland.

POPULATION: A total of 5201 noninstitutionalized men and women 65 years of age and older.

MAIN OUTCOME MEASURES: Pulmonary function; means of forced expiratory volume in 1 second (FEV1) and forced vital capacity and prevalence of low FEV1 levels.

RESULTS: Prevalence of cigarette smoking was 10\% to 20\% and higher in women than men and in blacks than whites. Forced vital capacity and FEV1 levels were related positively to height and white race and negatively to age and waist girth. Age- and height-adjusted FEV1 means were 23\% and 18\% lower in male and female current smokers, respectively, than in never smokers but not reduced in never smokers currently living with a smoker. Smokers who quit before age 40 years had FEV1 levels similar to never smokers, but FEV1 levels were lower by 7\% and 14\% in smokers who quit at ages 40 to 60 years and older than 60 years, respectively. Lung function was related inversely to pack-years of cigarette use. Prevalence rates of impaired lung function were highest in current smokers and lowest in never smokers. Regression coefficients for the smoking variables were smaller in persons without cardiovascular or respiratory conditions than in the total cohort.

CONCLUSIONS: Cigarette smoking is associated with reduced pulmonary function in elderly men and women. However, smokers who quit, even after age 60 years, have better pulmonary function than continuing smokers.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Anthropometry, Cardiovascular Diseases, Cross-Sectional Studies, European Continental Ancestry Group, Female, Forced Expiratory Volume, Humans, Lung Diseases, Male, Prevalence, Prospective Studies, Reference Values, Respiratory Function Tests, Risk Factors, Smoking, United States, Vital Capacity}, issn = {0098-7484}, author = {Higgins, M W and Enright, P L and Kronmal, R A and Schenker, M B and Anton-Culver, H and Lyles, M} } @article {1429, title = {Temporal patterns of antihypertensive medication use among elderly patients. The Cardiovascular Health Study.}, journal = {JAMA}, volume = {270}, year = {1993}, month = {1993 Oct 20}, pages = {1837-41}, abstract = {

OBJECTIVES: To estimate the incidence of newly treated hypertension and to describe the patterns of antihypertensive medication use among those aged 65 years and older.

DESIGN: Medicare eligibility lists from four US communities (Forsyth County, North Carolina; Washington County, Maryland; Sacramento County, California; and Pittsburgh, Pa) were used to obtain a representative sample of 5201 community-dwelling elderly for the Cardiovascular Health Study, a prospective cohort study of risk factors for coronary heart disease and stroke. Participants were examined at baseline and again 1 year later. The two examinations included standardized questionnaires, blood pressure measurements, and the assessment of medication use by medication inventory. In this cohort analysis, we excluded 231 subjects (4.4\%) who did not return for follow-up, 69 (1.3\%) who had missing data for medications, and another 495 (9.5\%) who were taking "antihypertensive" medications for an indication other than high blood pressure.

INTERVENTIONS: None.

RESULTS: Among the 4406 participants, 1613 used antihypertensive medications at both visits. Between the two visits, 144 started and 115 stopped antihypertensive therapy. Among nonusers at baseline, the annual incidence of newly treated hypertension was 5.2\% in women and 5.6\% in men. Due to the number of participants who stopped therapy, the overall prevalence of antihypertensive treatment increased only slightly, from 40.7\% to 41.1\% in women and from 37.1\% to 38.2\% in men, during 1 year of follow-up. After adjustment for age, systolic blood pressure, number of antihypertensive drugs, diabetes, and cardiovascular disease, the newly treated hypertensives were about half as likely as the previously treated hypertensives to receive diuretics (odds ratio [OR], 0.59; P = .008) or beta-blockers (OR, 0.52; P = .01); and they were about twice as likely to receive calcium channel blockers (OR, 1.88; P < .004) or angiotensin converting enzyme inhibitors (OR, 2.40; P < .001). A similar pattern of within-person changes over time was apparent among the continuous users.

CONCLUSIONS: Between June 1990 and June 1991, physicians were increasingly prescribing angiotensin converting enzyme inhibitors and calcium channel blockers in place of diuretics and beta-blockers for the treatment of hypertension in elderly patients, especially for those just starting therapy.

}, keywords = {Adrenergic beta-Antagonists, Aged, Analysis of Variance, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Calcium Channel Blockers, Cohort Studies, Diuretics, Drug Utilization, Female, Follow-Up Studies, Humans, Hypertension, Linear Models, Logistic Models, Male, Medicare, Practice Patterns, Physicians{\textquoteright}, Recurrence, United States, Vasodilator Agents}, issn = {0098-7484}, author = {Psaty, B M and Savage, P J and Tell, G S and Polak, J F and Hirsch, C H and Gardin, J M and McDonald, R H} } @article {1437, title = {Correlates of blood pressure in community-dwelling older adults. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group.}, journal = {Hypertension}, volume = {23}, year = {1994}, month = {1994 Jan}, pages = {59-67}, abstract = {

Although elevated blood pressure is an important predictor of cardiovascular disease and stroke in the elderly, little information exists on the distribution and risk factor correlates of blood pressure in this group. As part of the Cardiovascular Health Study, a population-based cohort study of 5201 men and women aged 65 to 101 years, we investigated correlates of systolic and diastolic blood pressure. Multiple regression analyses were conducted for all participants and a subgroup of 2482 without coronary heart disease and not on antihypertensive therapy (the "healthier" subgroup). In the total group, independent predictors of diastolic blood pressure included heart rate, aortic root dimension, creatinine, hematocrit, alcohol use, and black race (positive associations) and internal carotid artery wall thickness, mitral early/late peak flow velocity, white blood cell count, cigarette smoking, and age (negative associations). Positive predictors of systolic blood pressure included mitral late peak flow velocity, left ventricular mass, common carotid artery wall thickness, serum albumin, factor VII, diabetes, alcohol use, and age; negative predictors were coronary heart disease, uric acid, height, and smoking. In the healthier subgroup, positive predictors of diastolic blood pressure included heart rate, hematocrit, serum albumin, creatinine, and body weight, whereas mitral early/late peak flow velocity, serum potassium, smoking, and age inversely related to diastolic pressure. For the same group, common carotid artery wall thickness, left ventricular mass, serum albumin, factor VII, high-density lipoprotein cholesterol, and age were directly related to systolic blood pressure, whereas serum potassium was inversely related. Both systolic and diastolic pressures varied considerably by geographic site.(ABSTRACT TRUNCATED AT 250 WORDS)

}, keywords = {Aged, Aged, 80 and over, Aging, Blood Pressure, Cohort Studies, Coronary Disease, Female, Health Surveys, Humans, Hypertrophy, Left Ventricular, Male, Regression Analysis, United States}, issn = {0194-911X}, author = {Tell, G S and Rutan, G H and Kronmal, R A and Bild, D E and Polak, J F and Wong, N D and Borhani, N O} } @article {1420, title = {A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.}, journal = {AJNR Am J Neuroradiol}, volume = {15}, year = {1994}, month = {1994 Oct}, pages = {1625-33}, abstract = {

PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history.

METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9.

RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95\% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77\% of the participants with histories of stroke but was also present in 23\% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm.

CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Diagnosis, Differential, Feasibility Studies, Female, Humans, Image Interpretation, Computer-Assisted, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mass Screening, Observer Variation, Pilot Projects, Prospective Studies, Risk Factors, United States}, issn = {0195-6108}, author = {Bryan, R N and Manolio, T A and Schertz, L D and Jungreis, C and Poirier, V C and Elster, A D and Kronmal, R A} } @article {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 {587, title = {Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study.}, journal = {J Aging Health}, volume = {6}, year = {1994}, month = {1994 Nov}, pages = {419-47}, abstract = {

Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.

}, keywords = {Aged, Cardiovascular Diseases, Data Collection, Female, Forecasting, Geriatric Assessment, Health Status, Humans, Male, Multivariate Analysis, Regression Analysis, Self-Assessment, Sex Factors, United States}, issn = {0898-2643}, doi = {10.1177/089826439400600401}, author = {Schulz, R and Mittelmark, M and Kronmal, R and Polak, J F and Hirsch, C H and German, P and Bookwala, J} } @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 {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 {1449, title = {Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {5}, year = {1995}, month = {1995 Jul}, pages = {270-7}, abstract = {

The objective of this article is to describe the methods of assessing cardiovascular conditions among older adults recruited to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke. Medicare eligibility lists from four US communities were used to obtain a representative sample of 5201 community-dwelling elderly, who answered standardized questionnaires and underwent an extensive clinic examination at baseline. For each cardiovascular condition, self-reports were confirmed by components of the baseline examination or, if necessary, by a validation protocol that included either the review of medical records or surveys of treating physicians. Potential underreporting of a condition was detected either by the review of medical records at baseline for other self-reported conditions or, during prospective follow-up, by the investigation of potential incident events. For myocardial infarction, 75.5\% of the self-reports in men and 60.6\% in women were confirmed. Self-reported congestive heart failure was confirmed in 73.3\% of men and 76.6\% of women; stroke, in 59.6\% of men and 53.8\% of women; and transient ischemic attack, in 41.5\% of men and 37.0\% of women. Underreporting was also common. During prospective follow-up of an average of about 3 years per person, approximately 50\% of men and 38\% of women were hospitalized or investigated for at least one potential incident event; for each cardiovascular condition, about 1 to 4\% of those investigated during prospective follow-up were found to have had the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

}, keywords = {Aged, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Electrocardiography, Epidemiologic Methods, False Negative Reactions, Female, Humans, Male, Population Surveillance, Prevalence, Prospective Studies, Reproducibility of Results, Risk Factors, Self Disclosure, United States}, issn = {1047-2797}, author = {Psaty, B M and Kuller, L H and Bild, D and Burke, G L and Kittner, S J and Mittelmark, M and Price, T R and Rautaharju, P M and Robbins, J} } @article {1450, title = {Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {5}, year = {1995}, month = {1995 Jul}, pages = {278-85}, abstract = {

While previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.

}, keywords = {Aged, Cerebrovascular Disorders, Coronary Disease, Epidemiologic Methods, Female, Hospitalization, Humans, Incidence, Longitudinal Studies, Male, Population Surveillance, Quality Control, United States}, issn = {1047-2797}, author = {Ives, D G and Fitzpatrick, A L and Bild, D E and Psaty, B M and Kuller, L H and Crowley, P M and Cruise, R G and Theroux, S} } @article {1418, title = {Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?}, journal = {JAMA}, volume = {273}, year = {1995}, month = {1995 May 10}, pages = {1436-8}, abstract = {

OBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults.

DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3.

RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9\% in period 2 to 47.5\% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7\% in the prevalence of diuretic use in period 1 abated during period 2 (1.8\% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2\% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7\%) and period 3 (+2.8\%).

CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.

}, keywords = {Aged, Antihypertensive Agents, Clinical Trials as Topic, Data Interpretation, Statistical, Drug Utilization Review, Female, Humans, Hypertension, Male, Practice Patterns, Physicians{\textquoteright}, United States}, issn = {0098-7484}, author = {Psaty, B M and Koepsell, T D and Yanez, N D and Smith, N L and Manolio, T A and Heckbert, S R and Borhani, N O and Gardin, J M and Gottdiener, J S and Rutan, G H} } @article {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 {1465, title = {Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {6}, year = {1996}, month = {1996 Jul}, pages = {314-23}, abstract = {

The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1\% vs. 0\%); OR = 0.61; 95\% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95\% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.

}, keywords = {Aged, Arteriosclerosis, Carotid Arteries, Carotid Stenosis, Cohort Studies, Confidence Intervals, Cross-Sectional Studies, Databases, Factual, Drug Therapy, Combination, Estrogen Replacement Therapy, Estrogens, Female, Health Status Indicators, Humans, Odds Ratio, Progestins, Reproductive History, Ultrasonography, United States, Women{\textquoteright}s Health}, issn = {1047-2797}, author = {Jonas, H A and Kronmal, R A and Psaty, B M and Manolio, T A and Meilahn, E N and Tell, G S and Tracy, R P and Robbins, J A and Anton-Culver, H} } @article {1459, title = {Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {16}, year = {1996}, month = {1996 Aug}, pages = {963-70}, abstract = {

B-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5\% (451/4741) overall, with a prevalence among men of 14.2\% (278/1956) and prevalence among women of 6.2\% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.

}, keywords = {Aged, Anthropometry, Aortic Aneurysm, Abdominal, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Humans, Male, Middle Aged, Pilot Projects, Prevalence, Reproducibility of Results, Risk Factors, Smoking, Ultrasonography, United States}, issn = {1079-5642}, author = {Alcorn, H G and Wolfson, S K and Sutton-Tyrrell, K and Kuller, L H and O{\textquoteright}Leary, D} } @article {1472, title = {Spirometry reference values for healthy elderly blacks. The Cardiovascular Health Study Research Group.}, journal = {Chest}, volume = {110}, year = {1996}, month = {1996 Dec}, pages = {1416-24}, abstract = {

Pulmonary function was assessed by spirometry in 497 black and 2,980 white ambulatory elderly male and female participants of the Cardiovascular Health Study. The quality assurance program prompted technicians to exceed American Thoracic Society recommendations for spirometry. A "healthy" subgroup of 235 black and 1,227 white participants age 65 years and older was identified by excluding current and former smoker, and those with self-reported asthma or emphysema, congestive heart failure, and poor-quality results of spirometry tests, since those factors were associated with a lower FEV1. Reference equations and normal ranges for elderly blacks for measurements of FEV1, FVC, and the FEV1/FVC ratio were then determined from the healthy group. These elderly blacks had an FVC about 6\% lower than elderly whites, even after correcting for standing height, sitting height (trunk length), and age. The popular use of spirometry reference values from studies of middle-aged white subjects by applying a 12\% race correction factor for black patients appears to overestimate predicted values.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, European Continental Ancestry Group, Female, Forced Expiratory Volume, Humans, Male, Reference Values, Spirometry, United States, Vital Capacity}, issn = {0012-3692}, author = {Enright, P L and Arnold, A and Manolio, T A and Kuller, L H} } @article {1456, title = {White blood cell counts in persons aged 65 years or more from the Cardiovascular Health Study. Correlations with baseline clinical and demographic characteristics.}, journal = {Am J Epidemiol}, volume = {143}, year = {1996}, month = {1996 Jun 01}, pages = {1107-15}, abstract = {

A higher white blood cell (WBC) count has been shown to be a risk factor for myocardial infarction and stroke in middle-aged populations. This study evaluated the relation between baseline WBC count and other risk factors, as well as subclinical and prevalent disease, in the Cardiovascular Health Study, an epidemiologic study of coronary heart disease and stroke in 5,201 persons aged 65 years or older. Baseline data were collected over a 12-month period in 1989-1990. WBC counts were statistically significantly higher in people with prevalent and subclinical atherosclerotic cardiovascular disease than in those who were free of disease. WBC counts correlated (p < 0.01) positively with coagulation factors, measures of glucose metabolism, creatinine, smoking, and triglycerides. In contrast, WBC counts correlated negatively with high density lipoprotein cholesterol, forced expiratory volume, forced vital capacity, and height. The correlations between WBC counts and risk factors were similar in both the entire cohort and the subgroup of persons who had never smoked. The authors conclude that WBC counts in the elderly are associated with prevalent and subclinical atherosclerotic cardiovascular disease, as well as its risk factors.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cerebrovascular Disorders, Female, Humans, Leukocyte Count, Leukocytosis, Longitudinal Studies, Male, Myocardial Infarction, Prevalence, Reference Values, Risk Factors, United States}, issn = {0002-9262}, author = {Bovill, E G and Bild, D E and Heiss, G and Kuller, L H and Lee, M H and Rock, R and Wahl, P W} } @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 {1477, title = {Preventive health behaviors among spousal caregivers.}, journal = {Prev Med}, volume = {26}, year = {1997}, month = {1997 Mar-Apr}, pages = {162-9}, abstract = {

BACKGROUND: The physical and emotional burden of caring for a functionally impaired spouse may adversely affect the preventive health behavior of the caregiver. This study explores the relationship between caregiving and lifestyle health behaviors and use of preventive services.

METHODS: The Caregiver Health Effects Study identified spousal caregivers among a sample of more than 3,000 married, community-dwelling older persons, from four counties in the United States, who were enrollees in the Cardiovascular Health Study. High-level caregivers were defined as having a spouse with an ADL impairment (n = 212) and moderate-level caregivers, a spouse with one or more IADL impairments (n = 222). For each caregiver, a control, matched for age and gender, was selected (n = 385). Structured interviews were conducted in the home, following enrollment.

RESULTS: Being a high-level caregiver significantly increased the odds of not getting enough rest, not having enough time to exercise, not having time to rest to recuperate from illness, and forgetting to take prescription medications, compared with noncaregivers. These findings did not hold for moderate-level caregivers. The odds were not significantly different for either level of caregiver compared with noncaregivers for missing meals, missing doctor appointments, missing flu shots, and not refilling medications. Larger proportions of caregivers with a strong sense of control had good preventive health behaviors, compared with caregivers with a weak sense of control.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Caregivers, Case-Control Studies, Chi-Square Distribution, Confidence Intervals, Exercise, Female, Health Behavior, Health Status, Health Surveys, Humans, Internal-External Control, Life Style, Logistic Models, Male, Odds Ratio, Preventive Health Services, Self Care, Social Support, Spouses, United States}, issn = {0091-7435}, doi = {10.1006/pmed.1996.0129}, author = {Burton, L C and Newsom, J T and Schulz, R and Hirsch, C H and German, P S} } @article {1473, title = {Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Jan}, pages = {1-7}, abstract = {

OBJECTIVES: To describe the prevalence of self reported sleep disturbances in older men and women and to describe their relationships with health status and cardiovascular disease (CVD).

DESIGN: Cross-sectional study of sleep disturbance, CVD, general health, psychosocial factors, physical function, and use of psychotropic medications.

SETTING: Participants of the Cardiovascular Health Study, 5201 adults aged 65 and older recruited from a random sample of noninstitutionalized Medicare enrollees in four US communities.

MEASURES: Self-reported sleep disturbances and standardized questionnaires for cardiopulmonary symptoms and diseases, depression, social support, activities of daily living, physical activity, cognitive function, and current medications, spirometry, ECG, echocardiography, and carotid ultrasound.

RESULTS: Women were twice as likely as men to report difficulty falling asleep (30\% vs 14\%). Daytime sleepiness, difficulty falling asleep, and frequent awakenings increased in prevalence with age. All symptoms were related strongly to depression. Symptoms of daytime sleepiness were also related strongly to poor health and limitations in activities of daily living in men and women. In multivariate analysis, men taking benzodiazepines were likely to report difficulty falling asleep and daytime sleepiness, whereas women taking benzodiazepines reported difficulty falling asleep and waking up too early. After accounting for these factors, the only cardiovascular disease independently associated with sleep disturbances was angina. Men and women with confirmed angina were 1.6 times more likely to report trouble falling asleep. Independent relationships between sleep disturbances and cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes were relatively weak and inconsistent, though smokers were less likely to report frequent awakenings.

CONCLUSIONS: Sleep disturbances are relatively common in older men and women and are associated with poor health, depression, angina, limitations in activities of daily living, and the use of benzodiazepines.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cross-Sectional Studies, Depression, Female, Geriatric Assessment, Health Surveys, Humans, Male, Prevalence, Psychotropic Drugs, Random Allocation, Risk Factors, Sex Factors, Sleep Wake Disorders, Social Support, Surveys and Questionnaires, United States}, issn = {0002-8614}, author = {Newman, A B and Enright, P L and Manolio, T A and Haponik, E F and Wahl, P W} } @article {1502, title = {Body mass index and mortality in nonsmoking older adults: the Cardiovascular Health Study.}, journal = {Am J Public Health}, volume = {88}, year = {1998}, month = {1998 Apr}, pages = {623-9}, abstract = {

OBJECTIVES: This study assesses the relationship of body mass index to 5-year mortality in a cohort of 4317 nonsmoking men and women aged 65 to 100 years.

METHODS: Logistic regression analyses were conducted to predict mortality as a function of baseline body mass index, adjusting for demographic, clinical, and laboratory covariates.

RESULTS: There was an inverse relationship between body mass index and mortality; death rates were higher for those who weighed the least. Inclusion of covariates had trivial effects on these results. People who had lost 10\% or more of their body weight since age 50 had a relatively high death rate. When that group was excluded, there was no remaining relationship between body mass index and mortality.

CONCLUSIONS: The association between higher body mass index and mortality often found in middle-aged populations was not observed in this large cohort of older adults. Over-weight does not seem to be a risk factor for 5-year mortality in this age group. Rather, the risks associated with significant weight loss should be the primary concern.

}, keywords = {Age Distribution, Aged, Body Mass Index, Cardiovascular Diseases, Cause of Death, Cohort Studies, Female, Humans, Logistic Models, Male, Mortality, Predictive Value of Tests, Risk Factors, Sex Distribution, Smoking, Survival Analysis, United States, Weight Loss}, issn = {0090-0036}, author = {Diehr, P and Bild, D E and Harris, T B and Duxbury, A and Siscovick, D and Rossi, M} } @article {1509, title = {Brain abnormalities in the elderly: frequency and predictors in the United States (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.}, journal = {J Neural Transm Suppl}, volume = {53}, year = {1998}, month = {1998}, pages = {9-16}, abstract = {

PURPOSE: Characterize brain abnormalities in elderly people using cranial magnetic resonance imaging (MRI).

METHODS: Comprehensive lists of people 65 years and older living in the United States of America were used to obtain a representative sample of 5,888 community-dwelling participants who underwent extensive standardized evaluations. A subset of 3,660 underwent MRI. Without clinical information, neuroradiologists evaluated each scan.

RESULTS: Enlarged ventricles and sulci and prominent white matter changes were relatively common, even in a subset of the healthiest participants. Infarcts 3 mm or greater were present in 31\% of all participants and 28\% of those without a history of stroke. Most infarcts were clinically silent, small, and in the basal ganglia. Among those without a history of stroke, white matter changes were common but mostly of a mild degree. These changes were independently related to greater age, silent stroke, higher systolic blood pressure, lower forced expiratory volume in one second and income less than $50,000 per year. Changes were also associated with dysfunction, especially of cognition and the lower extremities.

CONCLUSION: MRI abnormalities are common in elderly people. Cautious interpretation is appropriate because participants are healthier than the general population and the study{\textquoteright}s design is cross-sectional.

}, keywords = {Aged, Brain, Brain Diseases, Cerebral Infarction, Cerebrovascular Disorders, Humans, Magnetic Resonance Imaging, United States}, issn = {0303-6995}, author = {Longstreth, W T} } @article {1501, title = {Caregiving from the recipient{\textquoteright}s perspective: negative reactions to being helped.}, journal = {Health Psychol}, volume = {17}, year = {1998}, month = {1998 Mar}, pages = {172-81}, abstract = {

This study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40\% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.

}, keywords = {Activities of Daily Living, Aged, Caregivers, Chronic Disease, Depression, Disabled Persons, Factor Analysis, Statistical, Female, Helping Behavior, Humans, Internal-External Control, Longitudinal Studies, Male, Regression Analysis, Self Concept, Spouses, United States}, issn = {0278-6133}, author = {Newsom, J T and Schulz, R} } @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 {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 {1507, title = {Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995.}, journal = {Arch Intern Med}, volume = {158}, year = {1998}, month = {1998 May 25}, pages = {1074-80}, abstract = {

BACKGROUND: Evidence from clinical trials in the past decade has consistently shown that angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in patients with congestive heart failure (CHF). The extent to which clinical practice has adopted ACE inhibitor therapy is unknown.

METHODS: The Cardiovascular Health Study is a prospective observational study of 5201 community-dwelling adults aged 65 years and older. Prevalent CHF cases were identified on study entry (from June 10, 1989, through May 31, 1990) and incident CHF cases were identified throughout 5 years of follow-up. Medication data were collected from annual medication inventories. The percentage of patients with CHF using ACE inhibitors was calculated at each annual examination. Temporal trends in CHF treatment with ACE inhibitors between June 10, 1989, through May 31, 1990, and June 1, 1994, through May 31, 1995, were analyzed.

RESULTS: Use of ACE inhibitors to treat CHF increased slightly over time among prevalent cases at each annual examination: 26\% of prevalent CHF cases were treated in 1989-1990 compared with 36\% of prevalent cases in 1994-1995. This 10\% increase was statistically significant (P<.01). Participants with low ejection fractions were 2 times more likely to be treated with ACE inhibitors than were those with normal ejection fraction and this tendency did not change over time. Among cases newly diagnosed in the year before the 1990-1991 examination, 42\% were using ACE inhibitors; among those newly diagnosed in the year before 1994-1995, 40\% were using ACE inhibitors. This 2\% decrease was not statistically significant (P=.68).

CONCLUSION: These findings suggest that, while the medical management of CHF with ACE inhibitors has increased modestly over time in prevalent cases, these drugs may still be underused, especially among incident cases.

}, keywords = {Aged, Angiotensin-Converting Enzyme Inhibitors, Drug Utilization, Female, Heart Failure, Humans, Logistic Models, Male, Stroke Volume, Treatment Outcome, United States}, issn = {0003-9926}, author = {Smith, N L and Psaty, B M and Pitt, B and Garg, R and Gottdiener, J S and Heckbert, S R} } @article {1513, title = {Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {158}, year = {1998}, month = {1998 Sep 14}, pages = {1761-8}, abstract = {

OBJECTIVES: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older.

SUBJECTS AND METHODS: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit.

RESULTS: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5\% among the men and 5.9\% among the women; these figures increased over the next 6 years to 8.1\% and 10.0\%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9\% of all participants in 1989-1990 to 7.5\% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1\% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20\% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy.

CONCLUSIONS: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.

}, keywords = {Aged, Anticholesteremic Agents, Cholesterol, LDL, Cohort Studies, Female, Humans, Hypercholesterolemia, Male, Prevalence, Risk Factors, United States}, issn = {0003-9926}, author = {Lemaitre, R N and Furberg, C D and Newman, A B and Hulley, S B and Gordon, D J and Gottdiener, J S and McDonald, R H and Psaty, B M} } @article {1516, title = {Utilities for major stroke: results from a survey of preferences among persons at increased risk for stroke.}, journal = {Am Heart J}, volume = {136}, year = {1998}, month = {1998 Oct}, pages = {703-13}, abstract = {

BACKGROUND: Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward hypothetical major stroke.

METHODS AND RESULTS: Respondents were obtained from the Academic Medical Center Consortium (n = 621), the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45\% of respondents considered major stroke to be a worse outcome than death, 15\% were willing to trade off little or no survival to avoid a major stroke.

CONCLUSIONS: Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable.

}, keywords = {Adult, Age Distribution, Aged, Aged, 80 and over, Attitude to Health, Female, Health Status, Humans, Intracranial Embolism and Thrombosis, Male, Middle Aged, Quality of Life, Sex Distribution, Surveys and Questionnaires, United States}, issn = {0002-8703}, author = {Samsa, G P and Matchar, D B and Goldstein, L and Bonito, A and Duncan, P W and Lipscomb, J and Enarson, C and Witter, D and Venus, P and Paul, J E and Weinberger, M} } @article {591, title = {Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.}, journal = {Diabetes Care}, volume = {22}, year = {1999}, month = {1999 May}, pages = {736-42}, abstract = {

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort.

RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes.

RESULTS: A total of 387 (7\%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17\%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48\% (P < 0.001) and from 67 to 50\% (P < 0.003) and insulin use increased from 20 to 33\% (P = 0.001) and from 33 to 37\% (P = 0.603). There were 396 (8\%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7\%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30\% and insulin use reached 6 and 16\% in 1996-1997.

CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80\% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.

}, keywords = {Aged, Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Drug Therapy, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Insulin, Male, Prospective Studies, Risk Factors, Time Factors, United States}, issn = {0149-5992}, doi = {10.2337/diacare.22.5.736}, author = {Smith, N L and Heckbert, S R and Bittner, V A and Savage, P J and Barzilay, J I and Dobs, A S and Psaty, B M} } @article {596, title = {Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.}, journal = {N Engl J Med}, volume = {341}, year = {1999}, month = {1999 Jul 15}, pages = {142-7}, abstract = {

BACKGROUND: Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events.

METHODS: We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke.

RESULTS: There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves.

CONCLUSIONS: Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.

}, keywords = {Aged, Angina Pectoris, Aortic Valve, Calcinosis, Cardiovascular Diseases, Cerebrovascular Disorders, Female, Heart Failure, Heart Valve Diseases, Humans, Male, Mortality, Myocardial Infarction, Prospective Studies, Risk, Risk Factors, Ultrasonography, United States, Ventricular Outflow Obstruction}, issn = {0028-4793}, doi = {10.1056/NEJM199907153410302}, author = {Otto, C M and Lind, B K and Kitzman, D W and Gersh, B J and Siscovick, D S} } @article {600, title = {Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria.}, journal = {Lancet}, volume = {354}, year = {1999}, month = {1999 Aug 21}, pages = {622-5}, abstract = {

BACKGROUND: The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly.

METHODS: We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria.

FINDINGS: There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3\%) than by the WHO criteria (46.8\%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28\% vs 54\%).

INTERPRETATION: The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.

}, keywords = {Age Factors, Aged, Blood Glucose, Cardiovascular Diseases, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Fasting, Female, Glucose Intolerance, Humans, Longitudinal Studies, Male, Prospective Studies, Risk Factors, Sensitivity and Specificity, Societies, Medical, United States, World Health Organization}, issn = {0140-6736}, doi = {10.1016/s0140-6736(98)12030-5}, author = {Barzilay, J I and Spiekerman, C F and Wahl, P W and Kuller, L H and Cushman, M and Furberg, C D and Dobs, A and Polak, J F and Savage, P J} } @article {605, title = {Caregiving as a risk factor for mortality: the Caregiver Health Effects Study.}, journal = {JAMA}, volume = {282}, year = {1999}, month = {1999 Dec 15}, pages = {2215-9}, abstract = {

CONTEXT: There is strong consensus that caring for an elderly individual with disability is burdensome and stressful to many family members and contributes to psychiatric morbidity. Researchers have also suggested that the combination of loss, prolonged distress, the physical demands of caregiving, and biological vulnerabilities of older caregivers may compromise their physiological functioning and increase their risk for physical health problems, leading to increased mortality.

OBJECTIVE: To examine the relationship between caregiving demands among older spousal caregivers and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline.

DESIGN: Prospective population-based cohort study, from 1993 through 1998 with an average of 4.5 years of follow-up.

SETTING: Four US communities.

PARTICIPANTS: A total of 392 caregivers and 427 noncaregivers aged 66 to 96 years who were living with their spouses.

MAIN OUTCOME MEASURE: Four-year mortality, based on level of caregiving: (1) spouse not disabled; (2) spouse disabled and not helping; (3) spouse disabled and helping with no strain reported; or(4) spouse disabled and helping with mental or emotional strain reported.

RESULTS: After 4 years of follow-up, 103 participants (12.6\%) died. After adjusting for sociodemographic factors, prevalent disease, and subclinical cardiovascular disease, participants who were providing care and experiencing caregiver strain had mortality risks that were 63\% higher than noncaregiving controls (relative risk [RR], 1.63; 95\% confidence interval [CI], 1.00-2.65). Participants who were providing care but not experiencing strain (RR, 1.08; 95 \% CI, 0.61-1.90) and those with a disabled spouse who were not providing care (RR, 1.37; 95\% CI, 0.73-2.58) did not have elevated adjusted mortality rates relative to the noncaregiving controls.

CONCLUSIONS: Our study suggests that being a caregiver who is experiencing mental or emotional strain is an independent risk factor for mortality among elderly spousal caregivers. Caregivers who report strain associated with caregiving are more likely to die than noncaregiving controls.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Caregivers, Disabled Persons, Female, Health Status, Home Nursing, Humans, Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, Socioeconomic Factors, Spouses, Stress, Psychological, United States}, issn = {0098-7484}, doi = {10.1001/jama.282.23.2215}, author = {Schulz, R and Beach, S R} } @article {588, title = {Hormone replacement therapy, inflammation, and hemostasis in elderly women.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Apr}, pages = {893-9}, abstract = {

Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the assumed coronary risk reduction associated with therapy. To explore other possible mechanisms, we studied associations of HRT use with inflammation and hemostasis risk markers in women >/=65 years of age. Subjects were selected from 3393 participants in the fourth year examination of the Cardiovascular Health Study, an observational study of vascular disease risk factors. After excluding women with vascular disease, we compared levels of inflammation and hemostasis variables in the 230 women using unopposed estrogen and 60 using estrogen/progestin, with those of 196 nonusers selected as controls. Compared with nonusers, unopposed estrogen use was associated with 59\% higher mean C-reactive protein (P<0.001), but with modestly lower levels of other inflammation indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was 16\% higher among estrogen users (P<0.001), but this was not associated with higher thrombin production (prothrombin fragment 1-2), or increased fibrin breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50\% lower in both using groups (P<0.001) compared with nonusers, and this was associated with higher plasmin-antiplasmin complex: 8\% higher in estrogen and 18\% higher in estrogen/progestin users (P<0. 05). Relationships between the markers and hormone use were less pronounced in estrogen/progestin users, with no association for C-reactive protein except in women in upper 2 tertiles of body mass index (P for interaction, 0.02). The direction and strength of the associations of HRT use with inflammation markers differed depending on the protein, so it is not clear whether HRT confers coronary risk reduction through an inflammation-sensitive mechanism. Associations with hemostasis markers indicated no association with evidence of procoagulation and a possible association with increased fibrinolytic activity.

}, keywords = {Aged, Biomarkers, Case-Control Studies, Cross-Sectional Studies, Estrogens, Female, Hemostasis, Hormone Replacement Therapy, Humans, Inflammation, Progestins, Random Allocation, United Kingdom, United States}, issn = {1079-5642}, doi = {10.1161/01.atv.19.4.893}, author = {Cushman, M and Meilahn, E N and Psaty, B M and Kuller, L H and Dobs, A S and Tracy, R P} } @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 {1524, title = {Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {30}, year = {1999}, month = {1999 Feb}, pages = {383-8}, abstract = {

BACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA.

METHODS: Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA.

RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46\% versus 28\%; P<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95\% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95\% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima-media thickness (P=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis.

CONCLUSIONS: MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cerebral Infarction, Cross-Sectional Studies, Female, Humans, Ischemic Attack, Transient, Magnetic Resonance Imaging, Male, Odds Ratio, Population Surveillance, Predictive Value of Tests, Prevalence, Prospective Studies, Risk Factors, United States}, issn = {0039-2499}, author = {Bhadelia, R A and Anderson, M and Polak, J F and Manolio, T A and Beauchamp, N and Knepper, L and O{\textquoteright}Leary, D H} } @article {603, title = {Stability and change in older adults{\textquoteright} social contact and social support: the Cardiovascular Health Study.}, journal = {J Gerontol B Psychol Sci Soc Sci}, volume = {54}, year = {1999}, month = {1999 Sep}, pages = {S302-11}, abstract = {

OBJECTIVES: The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life.

METHODS: Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time.

RESULTS: Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time.

DISCUSSION: The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cross-Sectional Studies, Educational Status, Family, Female, Health Status, Humans, Interpersonal Relations, Linear Models, Longitudinal Studies, Male, Predictive Value of Tests, Sex Factors, Social Support, Socioeconomic Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1079-5014}, doi = {10.1093/geronb/54b.5.s302}, author = {Martire, L M and Schulz, R and Mittelmark, M B and Newsom, J T} } @article {618, title = {Association between depression and mortality in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {160}, year = {2000}, month = {2000 Jun 26}, pages = {1761-8}, abstract = {

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals.

OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors.

METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality.

RESULTS: Of the 5201 participants, 984 (18.9\%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9\%) than low baseline depression scores (17.7\%) (unadjusted relative risk [RR], 1.41; 95\% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95\% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95\% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95\% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95\% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95\% CI, 1.06-1.46).

CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

}, keywords = {Aged, Alcohol Drinking, Depression, Depressive Disorder, Female, Health Status Indicators, Humans, Male, Motivation, Prevalence, Risk Factors, Smoking, Socioeconomic Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.160.12.1761}, author = {Schulz, R and Beach, S R and Ives, D G and Martire, L M and Ariyo, A A and Kop, W J} } @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 {622, title = {Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group.}, journal = {Circulation}, volume = {102}, year = {2000}, month = {2000 Oct 10}, pages = {1773-9}, abstract = {

BACKGROUND: Several epidemiological studies have associated depressive symptoms with cardiovascular disease. We investigated whether depressive symptoms constituted a risk for coronary heart disease (CHD) and total mortality among an apparently healthy elderly cohort.

METHODS AND RESULTS: In a prospective cohort of 5888 elderly Americans (>/=65 years) who were enrolled in the Cardiovascular Health Study, 4493 participants who were free of cardiovascular disease at baseline provided annual information on their depressive status, which was assessed using the Depression Scale of the Center for Epidemiological Studies. These 4493 subjects were followed for 6 years for the development of CHD and mortality. The cumulative mean depression score was assessed for each participant up to the time of event (maximum 6-year follow-up). Using time-dependent, proportional-hazards models, the unadjusted hazard ratio associated with every 5-unit increase in mean depression score for the development of CHD was 1.15 (P:=0.006); the ratio for all-cause mortality was 1.29 (P:<0.0001). In multivariate analyses adjusted for age, race, sex, education, diabetes, hypertension, cigarette smoking, total cholesterol, triglyceride level, congestive heart failure, and physical inactivity, the hazard ratio for CHD was 1.15 (P:=0.006) and that for all-cause mortality was 1.16 (P:=0.006). Among participants with the highest cumulative mean depression scores, the risk of CHD increased by 40\% and risk of death by 60\% compared with those who had the lowest mean scores.

CONCLUSIONS: Among elderly Americans, depressive symptoms constitute an independent risk factor for the development of CHD and total mortality.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Coronary Disease, Depression, Female, Humans, Male, Prospective Studies, Risk Factors, United States}, issn = {1524-4539}, doi = {10.1161/01.cir.102.15.1773}, author = {Ariyo, A A and Haan, M and Tangen, C M and Rutledge, J C and Cushman, M and Dobs, A and Furberg, C D} } @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 {660, title = {Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {32}, year = {2001}, month = {2001 Sep}, pages = {1939-46}, abstract = {

BACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings.

METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics.

RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007).

CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.

}, keywords = {Aged, Aging, Alcohol Drinking, Atrophy, Brain, Brain Diseases, Cerebral Infarction, Comorbidity, Demography, Female, Health Surveys, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Odds Ratio, Prospective Studies, Sensitivity and Specificity, United States}, issn = {1524-4628}, doi = {10.1161/hs0901.095723}, author = {Mukamal, K J and Longstreth, W T and Mittleman, M A and Crum, R M and Siscovick, D S} } @article {657, title = {Area characteristics and individual-level socioeconomic position indicators in three population-based epidemiologic studies.}, journal = {Ann Epidemiol}, volume = {11}, year = {2001}, month = {2001 Aug}, pages = {395-405}, abstract = {

PURPOSE: There is growing interest in incorporating area indicators into epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual-level data from three epidemiologic studies, we investigated how different area indicators are interrelated, how measures for different sized areas compare, and the relation between area and individual-level social position indicators.

METHODS: The interrelations between 13 area indicators of wealth/income, education, occupation, and other socioenvironmental characteristics were investigated using correlation coefficients and factor analyses. The extent to which block-group measures provide information distinct from census tract measures was investigated using intraclass correlation coefficients. Loglinear models were used to investigate associations between area and individual-level indicators.

RESULTS: Correlations between area measures were generally in the 0.5--0.8 range. In factor analyses, six indicators of income/wealth, education, and occupation loaded on one factor in most geographic sites. Correlations between block-group and census tract measures were high (correlation coefficients 0.85--0.96). Most of the variability in block-group indicators was between census tracts (intraclass correlation coefficients 0.72--0.92). Although individual-level and area indicators were associated, there was evidence of important heterogeneity in area of residence within individual-level income or education categories. The strength of the association between individual and area measures was similar in the three studies and in whites and blacks, but blacks were much more likely to live in more disadvantaged areas than whites.

CONCLUSIONS: Area measures of wealth/income, education, and occupation are moderately to highly correlated. Differences between using census tract or block-group measures in contextual investigations are likely to be relatively small. Area and individual-level indicators are far from perfectly correlated and provide complementary information on living circumstances. Differences in the residential environments of blacks and whites may need to be taken into account in interpreting race differences in epidemiologic studies.

}, keywords = {Adult, Black or African American, Cardiovascular Diseases, Demography, Educational Status, Factor Analysis, Statistical, Humans, Income, Linear Models, Occupations, Risk Factors, Social Class, Social Environment, Socioeconomic Factors, Statistics, Nonparametric, United States, White People}, issn = {1047-2797}, doi = {10.1016/s1047-2797(01)00221-6}, author = {Diez-Roux, A V and Kiefe, C I and Jacobs, D R and Haan, M and Jackson, S A and Nieto, F J and Paton, C C and Schulz, R} } @article {647, title = {Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {161}, year = {2001}, month = {2001 May 14}, pages = {1183-92}, abstract = {

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure.

METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified.

RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95\% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95\% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension.

CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

}, keywords = {Aged, Blood Pressure, Female, Humans, Male, Myocardial Infarction, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.161.9.1183}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Cushman, M and Savage, P J and Levine, D and O{\textquoteright}Leary, D H and Bryan, R N and Anderson, M and Lumley, T} } @article {633, title = {The association of sleep-disordered breathing and sleep symptoms with quality of life in the Sleep Heart Health Study.}, journal = {Sleep}, volume = {24}, year = {2001}, month = {2001 Feb 01}, pages = {96-105}, abstract = {

This study assessed the extent to which sleep-disordered breathing (SDB), difficulty initiating and maintaining sleep (DIMS), and excessive daytime sleepiness (EDS) were associated with impairment of quality of life (QoL) using the SF-36. Participants (n=5,816; mean age=63 years; 52.5\% women) were enrolled in the nation-wide population-based Sleep Heart Health Study (SHHS) implemented to investigate sleep-disordered breathing as a risk factor in the development of cardiovascular disease. Each transformed SF-36 scale was analyzed independently using multiple logistic regression analysis with sleep and other potential confounding variables (e.g., age, ethnicity) included as independent variables. Men (11.6\%) were significantly more likely to have SDB compared to women (5.6\%), while women (42.4\%) were significantly more likely to report DIMS than men (32.5\%). Vitality was the sole SF-36 scale to have a linear association with the clinical categories of SDB (mild, moderate, severe SDB). However, individuals with severe SDB indicated significantly poorer QoL on several SF-36 scales. Both DIMS and EDS were strongly associated with reduced QoL even after adjusting for confounding variables for both sexes. Findings suggest 1) mild to moderate SDB is associated with reduced vitality, while severe SDB is more broadly associated with poorer QoL, 2) subjective sleep symptoms are comprehensively associated with poorer QoL, and 3) SF-36 mean score profiles for SDB and sleep symptoms are equivalent to other chronic diseases in the U.S. general population.

}, keywords = {Adult, Cardiovascular Diseases, Chronic Disease, Circadian Rhythm, Disorders of Excessive Somnolence, Female, Health Status, Humans, Male, Middle Aged, Polysomnography, Population Surveillance, Prevalence, Quality of Life, Risk Factors, Severity of Illness Index, Sleep Apnea Syndromes, United States}, issn = {0161-8105}, doi = {10.1093/sleep/24.1.96}, author = {Baldwin, C M and Griffith, K A and Nieto, F J and O{\textquoteright}Connor, G T and Walsleben, J A and Redline, S} } @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 {630, title = {Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.}, journal = {Ann Intern Med}, volume = {134}, year = {2001}, month = {2001 Feb 06}, pages = {182-90}, abstract = {

BACKGROUND: Persons with abdominal aortic aneurysm are more likely to have a higher prevalence of risk factors for and clinical manifestations of cardiovascular disease. It is unknown whether these factors explain the high mortality rate associated with abdominal aortic aneurysm.

OBJECTIVE: To describe the risk for mortality, cardiovascular mortality, and cardiovascular morbidity in persons screened for abdominal aortic aneurysm.

DESIGN: Longitudinal cohort study.

SETTING: Four communities in the United States.

PARTICIPANTS: 4734 men and women older than 65 years of age recruited from Medicare eligibility lists.

MEASUREMENTS: Abdominal ultrasonography was used to measure the aortic diameter and the ratio of infrarenal to suprarenal measurement of aortic diameter in 1992-1993. Abdominal aortic aneurysm was defined as aortic diameter of 3 cm or greater or infrarenal-to-suprarenal ratio of 1.2 or greater. Mortality, cardiovascular disease mortality, incident cardiovascular disease, and repair or rupture were assessed after 4.5 years.

RESULTS: The prevalence of aneurysm was 8.8\%, and 87.7\% of aneurysms were 3.5 cm or less in diameter. Rates of total mortality (65.1 vs. 32.8 per 1000 person-years), cardiovascular mortality (34.3 vs. 13.8 per 1000 person-years), and incident cardiovascular disease (47.3 vs. 31.0 per 1000 person-years) were higher in participants with aneurysm than in those without aneurysm; after adjustment for age, risk factors, and presence of other cardiovascular disease, the respective relative risks were 1.32, 1.36, and 1.57. Rates of repair and rupture were low.

CONCLUSIONS: Rates of total mortality, cardiovascular disease mortality, and incident cardiovascular disease were higher in participants with abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease, and extent of atherosclerosis detected by noninvasive testing. Persons with smaller aneurysms detected by ultrasonography should be advised to modify risk factors for cardiovascular disease while under surveillance for increase in the size of the aneurysm.

}, keywords = {Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal, Aortic Rupture, Cardiovascular Diseases, Disease Progression, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Proportional Hazards Models, Risk Factors, Ultrasonography, United States}, issn = {0003-4819}, doi = {10.7326/0003-4819-134-3-200102060-00008}, author = {Newman, A B and Arnold, A M and Burke, G L and O{\textquoteright}Leary, D H and Manolio, T A} } @article {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 {629, title = {Frequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study.}, journal = {Neurology}, volume = {56}, year = {2001}, month = {2001 Feb 13}, pages = {368-75}, abstract = {

BACKGROUND: Few population-based studies have examined in detail issues of stroke-related deaths in elderly people.

METHODS: Participants in the Cardiovascular Health Study (CHS) are 65 years of age or older, have had extensive baseline evaluations, and have been followed-up for fatal and nonfatal cardiovascular and cerebrovascular disease outcomes. Investigators adjudicated these outcomes and classified strokes by types and subtypes.

RESULTS: Over 7 years, 1,310 (22.2\%) of 5,888 participants died, and 455 (7.7\%) experienced incident stroke. For the 5,888, stroke mortality was 3.2 per 1,000 person-years. For the 455, it was 36.1 per 1,000 person-years, with the most lethal type being hemorrhagic and the ischemic subtype being cardioembolic. After controlling for age and stroke type, the only other independent predictor of death after any stroke was poor performance on a timed walk measured before the incident stroke. Considering only ischemic stroke, the independent predictors of death were African American race and poor performance on timed walk.

CONCLUSION: In CHS, death attributable to stroke is common. As in other studies, the most lethal stroke type was hemorrhagic, and ischemic stroke subtype, cardioembolic. Slow walking, possibly a measure of frailty, was associated with an increased risk of death of stroke. Finally, African Americans faced a greater risk of death than others after an ischemic stroke.

}, keywords = {Aged, Aged, 80 and over, Clinical Trials as Topic, Female, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Stroke, Survival Analysis, United States}, issn = {0028-3878}, doi = {10.1212/wnl.56.3.368}, author = {Longstreth, W T and Bernick, C and Fitzpatrick, A and Cushman, M and Knepper, L and Lima, J and Furberg, C D} } @article {666, title = {Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.}, journal = {Ann Epidemiol}, volume = {11}, year = {2001}, month = {2001 Nov}, pages = {534-42}, abstract = {

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth.

METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants.

RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95\% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95\% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk.

CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

}, keywords = {Aged, Antihypertensive Agents, Cohort Studies, Heart Rate, Humans, Hypertension, Incidence, Male, Proportional Hazards Models, Prostatic Neoplasms, Risk, United States}, issn = {1047-2797}, doi = {10.1016/s1047-2797(01)00246-0}, author = {Fitzpatrick, A L and Daling, J R and Furberg, C D and Kronmal, R A and Weissfeld, J L} } @article {632, title = {Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study.}, journal = {Am J Cardiol}, volume = {87}, year = {2001}, month = {2001 Feb 15}, pages = {413-9}, abstract = {

Although congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8\% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6\%) to age > or = 85 years (14\%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55\% of subjects with CHF had normal left ventricular systolic function and 80\% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67\% vs 42\%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Chi-Square Distribution, Echocardiography, Doppler, Female, Health Status, Heart Failure, Humans, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Surveys and Questionnaires, United States, Ventricular Function, Left}, issn = {0002-9149}, doi = {10.1016/s0002-9149(00)01393-x}, author = {Kitzman, D W and Gardin, J M and Gottdiener, J S and Arnold, A and Boineau, R and Aurigemma, G and Marino, E K and Lyles, M and Cushman, M and Enright, P L} } @article {652, title = {Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.}, journal = {Diabetes Care}, volume = {24}, year = {2001}, month = {2001 Jul}, pages = {1233-9}, abstract = {

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes.

RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease.

RESULTS: Approximately 30\% of the cohort had clinical disease, and approximately 60\% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75\% of men and 66\% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88\% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes.

CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

}, keywords = {Aged, Angina Pectoris, Cardiovascular Diseases, Cerebrovascular Disorders, Cohort Studies, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Electrocardiography, Female, Glucose Intolerance, Heart Diseases, Humans, Male, Peripheral Vascular Diseases, Prevalence, United States}, issn = {0149-5992}, doi = {10.2337/diacare.24.7.1233}, author = {Barzilay, J I and Spiekerman, C F and Kuller, L H and Burke, G L and Bittner, V and Gottdiener, J S and Brancati, F L and Orchard, T J and O{\textquoteright}Leary, D H and Savage, P J} } @article {654, title = {Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.}, journal = {Am J Epidemiol}, volume = {154}, year = {2001}, month = {2001 Jul 01}, pages = {50-9}, abstract = {

Associations between sleep-disordered breathing and cardiovascular disease (CVD) may be mediated by higher cardiovascular risk factor levels in those with sleep-disordered breathing. The authors examined these relations in the Sleep Heart Health Study, a multiethnic cohort of 6,440 men and women over age 40 years conducted from October 1995 to February 1998 and characterized by home polysomnography. In 4,991 participants who were free of self-reported CVD at the time of the sleep study, moderate levels of sleep-disordered breathing were common, with a median Respiratory Disturbance Index (RDI) of 4.0 (interquartile range, 1.25-10.7). The level of RDI was associated cross-sectionally with age, body mass index, waist-to-hip ratio, hypertension, diabetes, and lipid levels. These relations were more pronounced in those under age 65 years than in those over age 65. Women under age 65 years with RDI in the higher quartiles were more obese than men with similar RDI. Although the pattern of associations was consistent with greater obesity in those with higher RDI, higher body mass index did not explain all of these associations. If sleep-disordered breathing is shown in future follow-up to increase the risk for incident CVD events, part of the risk is likely to be due to the higher cardiovascular risk factors in those with higher RDI.

}, keywords = {Adult, Aged, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Polysomnography, Risk Factors, Sleep Apnea Syndromes, United States}, issn = {0002-9262}, doi = {10.1093/aje/154.1.50}, author = {Newman, A B and Nieto, F J and Guidry, U and Lind, B K and Redline, S and Pickering, T G and Quan, S F} } @article {635, title = {Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Feb}, pages = {126-33}, abstract = {

OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors.

DESIGN: Prospective cohort study.

SETTING: The Cardiovascular Health Study (CHS).

PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS.

MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up.

RESULTS: Among CHS participants (mean baseline age 73.3 years, 42\% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95\% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95\% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95\% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 \% CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease.

CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.

}, keywords = {Activities of Daily Living, Age Distribution, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Anticoagulants, Aspirin, Cardiovascular Diseases, Female, Gastrointestinal Hemorrhage, Hospitalization, Humans, Incidence, Male, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Smoking, United States}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49032.x}, author = {Kaplan, R C and Heckbert, S R and Koepsell, T D and Furberg, C D and Polak, J F and Schoen, R E and Psaty, B M} } @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 {711, title = {Angiotensin II type 1 receptor polymorphisms in the cardiovascular health study: relation to blood pressure, ethnicity, and cardiovascular events.}, journal = {Am J Hypertens}, volume = {15}, year = {2002}, month = {2002 Dec}, pages = {1050-6}, abstract = {

BACKGROUND: The angiotensin II type 1 receptor A1166C polymorphism has been associated with increased risks of hypertension and myocardial infarction in several small studies. We examined the association between this polymorphism and new-onset hypertension, blood pressure (BP) control, and incident cardiovascular events in a large population-based cohort of older adults.

METHODS: Eight hundred self-identified African Americans and 1,371 randomly selected white participants in the Cardiovascular Health Study were genotyped. The median duration of follow-up was 8.1 years.

RESULTS: The A1166C polymorphism was not associated with new-onset hypertension, with BP control, or with incident cardiovascular events in the overall population. In white participants, the CC genotype was associated with higher baseline systolic BP and pulse pressure, compared to the AC or AA genotype. In whites with treated hypertension at baseline, compared to the AA genotype, the CC genotype was associated with increased risks of incident congestive heart failure (hazard ratio = 2.5, 95\% confidence interval [CI] 1.3-4.9) and incident ischemic stroke (hazard ratio = 2.6, 95\% CI 1.1-6.0). These associations were not observed among white participants without treated hypertension, but the interaction of genotype with treated hypertension on ischemic stroke and heart failure was only marginally significant.

CONCLUSIONS: On the whole, in this large cohort of older adults, the A1166C polymorphism was not associated with BP control or incident cardiovascular events. The subgroup findings in treated hypertensives need to be confirmed in additional studies.

}, keywords = {African Continental Ancestry Group, Aged, Blood Pressure, Cardiovascular Diseases, European Continental Ancestry Group, Female, Gene Frequency, Humans, Hypertension, Male, Polymorphism, Genetic, Receptor, Angiotensin, Type 1, Receptors, Angiotensin, United States}, issn = {0895-7061}, doi = {10.1016/s0895-7061(02)03063-7}, author = {Hindorff, Lucia A and Heckbert, Susan R and Tracy, Russell and Tang, Zhonghua and Psaty, Bruce M and Edwards, Karen L and Siscovick, David S and Kronmal, Richard A and Nazar-Stewart, Valle} } @article {691, title = {Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 May 27}, pages = {1182-9}, abstract = {

BACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.

METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.

RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95\% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95\% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95\% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95\% CI, 1.0-2.1]).

CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.

}, keywords = {Aged, Arteriosclerosis, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Pulmonary Embolism, Risk Factors, United States, Venous Thrombosis}, issn = {0003-9926}, doi = {10.1001/archinte.162.10.1182}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Polak, Joseph F and Folsom, Aaron R} } @article {692, title = {Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Jun}, pages = {1636-44}, abstract = {

BACKGROUND AND PURPOSE: Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms.

METHODS: The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently.

RESULTS: After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions.

CONCLUSIONS: These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.

}, keywords = {Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Depression, Disease Progression, Female, Health Surveys, Humans, Incidence, Logistic Models, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Odds Ratio, United States}, issn = {1524-4628}, doi = {10.1161/01.str.0000018405.59799.d5}, author = {Steffens, David C and Krishnan, K Ranga Rama and Crump, Casey and Burke, Gregory L} } @article {710, title = {Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism.}, journal = {Am J Hematol}, volume = {71}, year = {2002}, month = {2002 Dec}, pages = {285-90}, abstract = {

Case-control studies have indicated increased risk of venous thrombosis associated with the prothrombin gene G20210A polymorphism and with elevated plasma prothrombin levels. We sought to confirm these results in a prospective population-based study of 21,690 persons. We measured G20210A and prothrombin antigen on pre-event blood samples of 302 participants who developed venous thromboembolism (VTE) and 626 participants who remained free of VTE. Approximately 4.0\% of cases and 2.4\% of controls carried the G20210A polymorphism, but only one of 137 African Americans did. The odds ratio in whites was 1.87 (95\% CI = 0.85, 4.11)--higher for those who reported a prior history of VTE (OR = 5.44) than those reporting no VTE history (OR = 1.41) and in those with idiopathic VTE (OR = 2.51) than those with secondary VTE (OR = 1.38). There was no association between venous thromboembolism and plasma prothrombin antigen level. We estimated that the G20210A polymorphism may account for approximately 2.5\% of venous thromboembolism events in United States whites.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Case-Control Studies, European Continental Ancestry Group, Genotype, Humans, Incidence, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Prothrombin, Recurrence, Research Design, Risk Factors, Thromboembolism, United States}, issn = {0361-8609}, doi = {10.1002/ajh.10229}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Heckbert, Susan R and Aleksic, Nena} } @article {676, title = {A stroke prediction score in the elderly: validation and Web-based application.}, journal = {J Clin Epidemiol}, volume = {55}, year = {2002}, month = {2002 Feb}, pages = {129-36}, abstract = {

The objective of this study was to construct a prediction model for predicting stroke in an elderly U.S. population, and to assess the accuracy in this population of other previously published prediction models. The subjects were participants in the Cardiovascular Health Study: 2,495 men and 3,393 women age 65 years and older at baseline, and followed for 6.3 years. Among 5,711 participants free of baseline stroke, 399 strokes occurred. Sex-specific prediction equations were constructed using study variables that were most importantly related to incident stroke: age, systolic blood pressure, diabetes, ECG diagnosis of atrial fibrillation or left ventricular hypertrophy, confirmed history of cardiovascular disease, diabetes, time to walk 15 ft, and serum creatinine. The prediction rule was implemented as a risk score and in a Web-based interactive Java applet. Overall, the model predicted 5-year stroke risks ranging from less than 1 to 59\%. The 20\% of subjects in the highest predicted risk group had a 5-year actual stroke incidence rate of 15\%, while the 20\% lowest risk group had a 1\% incidence. Risk scores from two other studies performed well in these study participants. Effective discrimination between low and high stroke risk in the elderly was possible in this cohort with data that are easy to obtain. Evaluation of the generalizability and clinical usefulness of this prediction model requires further research.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Female, Follow-Up Studies, Humans, Incidence, Male, Models, Cardiovascular, Predictive Value of Tests, Risk Factors, ROC Curve, Stroke, United States}, issn = {0895-4356}, doi = {10.1016/s0895-4356(01)00434-6}, author = {Lumley, Thomas and Kronmal, Richard A and Cushman, Mary and Manolio, Teri A and Goldstein, Steven} } @article {695, title = {Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Jun 24}, pages = {1395-400}, abstract = {

BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol.

METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years{\textquoteright} follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95\% confidence intervals (CIs), adjusted for confounding variables.

RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95\% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95\% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline.

CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.

}, keywords = {Aged, Cholesterol, LDL, Coronary Disease, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hypolipidemic Agents, Incidence, Male, Multivariate Analysis, Proportional Hazards Models, Risk Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.162.12.1395}, author = {Lemaitre, Rozenn N and Psaty, Bruce M and Heckbert, Susan R and Kronmal, Richard A and Newman, Anne B and Burke, Gregory L} } @article {694, title = {Underdiagnosis of sleep apnea syndrome in U.S. communities.}, journal = {Sleep Breath}, volume = {6}, year = {2002}, month = {2002 Jun}, pages = {49-54}, abstract = {

We hypothesize that clinical recognition rates for obstructive sleep apnea-hypoapnea syndrome (OSAHS) are influenced by comorbidity and demographic factors. Data on medical disorders, symptoms of sleep disorders, and cardiovascular risk factors gathered from 15,699 individuals in the Sleep Heart Health Study were compared. Participants were classified into three groups: those with a self-reported physician diagnosis of OSAHS, those with self-reported physician-diagnosed and -treated OSAHS, and those reporting both frequent snoring and daytime sleepiness (two-symptom group). Among all participants, 4.1\% reported two symptoms (range across sites: 1.55 to 7.23\%), whereas 1.6\% reported a physician diagnosis of OSAHS (range: 0.66 to 2.88\%) and 0.6\% reported physician diagnosis and treatment (range: 0.11 to 0.88\%). Recognized OSAHS groups were similar to the two-symptom group in age, having a sleeping partner, measured blood pressure, total cholesterol, and race. In a logistic model that included age along with characteristics found to vary significantly among the three groups (gender, body mass index [BMI], high-density lipoprotein cholesterol levels, hypertension), only male gender and BMI were increased in those with physician-diagnosed and -treated OSAHS. We conclude that disparities (especially in women and in those with lower BMI) exist between current recognition rates for OSAHS and the estimated prevalence by symptom report across the United States.

}, keywords = {Diagnosis, Differential, Diagnostic Errors, Female, Humans, Male, Middle Aged, Prevalence, Sleep Apnea Syndromes, United States}, issn = {1520-9512}, doi = {10.1007/s11325-002-0049-5}, author = {Kapur, Vishesh and Strohl, Kingman P and Redline, Susan and Iber, Conrad and O{\textquoteright}Connor, George and Nieto, Javier} } @article {725, title = {The 6-min walk test: a quick measure of functional status in elderly adults.}, journal = {Chest}, volume = {123}, year = {2003}, month = {2003 Feb}, pages = {387-98}, abstract = {

OBJECTIVES: To determine the correlates of the total 6-min walk distance (6MWD) in a population sample of adults > or = 68 years old.

METHODS: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular Health Study cohort during their seventh annual examination.

RESULTS: Of the 3,333 participants with a clinic visit, 2,281 subjects (68\%) performed the 6MWT. There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general correlates of a shorter 6MWD in linear regression models in women and men included the following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression, and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV(1) in women; and the use of digitalis in men. Approximately 30\% of the variance in 6MWD was explained by the linear regression models. Newly described bivariate associations of a shorter 6MWD included impaired activities of daily living; self-reported poor health; less education; nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes; and higher levels of C-reactive protein, fibrinogen, or WBC count.

CONCLUSIONS: Most community-dwelling elderly persons can quickly and safely perform this functional status test in the outpatient clinic setting. The test may be used clinically to measure the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis, diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older adults. Expected values should be adjusted for the patient{\textquoteright}s age, gender, height, and weight.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Exercise Test, Female, Humans, Ischemic Attack, Transient, Linear Models, Male, Mass Screening, Sensitivity and Specificity, Stroke, United States, Walking}, issn = {0012-3692}, doi = {10.1378/chest.123.2.387}, author = {Enright, Paul L and McBurnie, Mary Ann and Bittner, Vera and Tracy, Russell P and McNamara, Robert and Arnold, Alice and Newman, Anne B} } @article {761, title = {The association between the length of the QT interval and mortality in the Cardiovascular Health Study.}, journal = {Am J Med}, volume = {115}, year = {2003}, month = {2003 Dec 15}, pages = {689-94}, abstract = {

PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain.

METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett{\textquoteright}s rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors.

RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95\% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95\% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95\% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95\% CI: 1.1 to 3.7).

CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.

}, keywords = {Aged, Arrhythmias, Cardiac, Cause of Death, Coronary Disease, Electrocardiography, Female, Follow-Up Studies, Heart Rate, Humans, Male, Randomized Controlled Trials as Topic, Risk Factors, Statistics as Topic, Survival Analysis, United States}, issn = {0002-9343}, doi = {10.1016/j.amjmed.2003.07.014}, author = {Robbins, John and Nelson, Jennifer Clark and Rautaharju, Pentti M and Gottdiener, John S} } @article {733, title = {Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Apr 22}, pages = {2021-4}, abstract = {

BACKGROUND: Genetic polymorphisms at codons 16 and 27 of the beta2-adrenergic receptor have been associated with altered response to sympathetic stimulation. We examined these polymorphisms in relation to cardiovascular event risk in the Cardiovascular Health Study.

METHODS AND RESULTS: A total of 808 black and 4441 white participants (mean age, 73 years) were genotyped for the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenergic receptor. There were 702 incident coronary events, 438 ischemic strokes, and 1136 combined cardiovascular events during 7 to 10 years of follow-up. Allele frequencies differed by race but not by age or hypertension status. Glu27 carriers had a lower risk of coronary events than Gln27 homozygotes (hazard ratio, 0.82; 95\% CI, 0.70 to 0.95), and there was a suggestion of decreased risk among Gly16 carriers compared with Arg16 homozygotes (hazard ratio, 0.88; 95\% CI, 0.72 to 1.07). There was no association of beta2-adrenergic receptor genotype with ischemic stroke or combined cardiovascular events.

CONCLUSIONS: The Glu27 allele of the beta2-adrenergic receptor was associated with a lower risk of incident coronary events in this elderly population.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Brain Ischemia, Cardiovascular Diseases, Cohort Studies, Comorbidity, Coronary Disease, European Continental Ancestry Group, Follow-Up Studies, Gene Frequency, Humans, Incidence, Linkage Disequilibrium, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Assessment, Stroke, United States}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000065231.07729.92}, author = {Heckbert, Susan R and Hindorff, Lucia A and Edwards, Karen L and Psaty, Bruce M and Lumley, Thomas and Siscovick, David S and Tang, Zhonghua and Durda, J Peter and Kronmal, Richard A and Tracy, Russell P} } @article {721, title = {Hormone replacement therapy and sleep-disordered breathing.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 May 01}, pages = {1186-92}, abstract = {

Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index) was determined by unattended, single-night polysomnography at the participant{\textquoteright}s home. The prevalence of sleep-disordered breathing (apnea-hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95\% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95\% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.

}, keywords = {Age Distribution, Aged, Body Mass Index, Causality, Cohort Studies, Confidence Intervals, Estrogen Replacement Therapy, Female, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Odds Ratio, Polysomnography, Postmenopause, Prevalence, Sensitivity and Specificity, Severity of Illness Index, Sleep Apnea Syndromes, Sleep Stages, United States}, issn = {1073-449X}, doi = {10.1164/rccm.200210-1238OC}, author = {Shahar, Eyal and Redline, Susan and Young, Terry and Boland, Lori L and Baldwin, Carol M and Nieto, F Javier and O{\textquoteright}Connor, George T and Rapoport, David M and Robbins, John A} } @article {740, title = {Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.}, journal = {J Womens Health (Larchmt)}, volume = {12}, year = {2003}, month = {2003 May}, pages = {341-50}, abstract = {

BACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.

METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).

RESULTS: At baseline, 62\% were never users, 26\% were past users, and 12\% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95\% confidence interval [95\% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).

CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Heart Failure, Humans, Incidence, Life Style, Middle Aged, Multivariate Analysis, Obesity, Osteoporosis, Postmenopausal, Proportional Hazards Models, Prospective Studies, Risk, Risk Factors, United States, Women{\textquoteright}s Health}, issn = {1540-9996}, doi = {10.1089/154099903765448853}, author = {Rea, Thomas D and Psaty, Bruce M and Heckbert, Susan R and Cushman, Mary and Meilahn, Elaine and Olson, Jean L and Lemaitre, Rozenn N and Smith, Nicholas L and Sotoodehnia, Nona and Chaves, Paulo H M} } @article {754, title = {Imputation of missing longitudinal data: a comparison of methods.}, journal = {J Clin Epidemiol}, volume = {56}, year = {2003}, month = {2003 Oct}, pages = {968-76}, abstract = {

BACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal studies, and can result in biased estimates and a loss of power. One approach to this problem is to impute the missing data to yield a more complete data set. Our goal was to compare the performance of 14 methods of imputing missing data on depression, weight, cognitive functioning, and self-rated health in a longitudinal cohort of older adults.

METHODS: We identified situations where a person had a known value following one or more missing values, and treated the known value as a "missing value." This "missing value" was imputed using each method and compared to the observed value. Methods were compared on the root mean square error, mean absolute deviation, bias, and relative variance of the estimates.

RESULTS: Most imputation methods were biased toward estimating the "missing value" as too healthy, and most estimates had a variance that was too low. Imputed values based on a person{\textquoteright}s values before and after the "missing value" were superior to other methods, followed by imputations based on a person{\textquoteright}s values before the "missing value." Imputations that used no information specific to the person, such as using the sample mean, had the worst performance.

CONCLUSIONS: We conclude that, in longitudinal studies where the overall trend is for worse health over time and where missing data can be assumed to be primarily related to worse health, missing data in a longitudinal sequence should be imputed from the available longitudinal data for that person.

}, keywords = {Aged, Analysis of Variance, Bias, Coronary Disease, Data Interpretation, Statistical, Depression, Female, Health Status, Humans, Longitudinal Studies, Male, Research Design, Risk Factors, Stroke, United States}, issn = {0895-4356}, doi = {10.1016/s0895-4356(03)00170-7}, author = {Engels, Jean Mundahl and Diehr, Paula} } @article {759, title = {Lp(a) lipoprotein, vascular disease, and mortality in the elderly.}, journal = {N Engl J Med}, volume = {349}, year = {2003}, month = {2003 Nov 27}, pages = {2108-15}, abstract = {

BACKGROUND: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults.

METHODS: In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line.

RESULTS: Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation.

CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.

}, keywords = {Aged, Coronary Disease, Female, Humans, Incidence, Lipoprotein(a), Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, Stroke, Survival Analysis, United States, Vascular Diseases}, issn = {1533-4406}, doi = {10.1056/NEJMoa001066}, author = {Ariyo, Abraham A and Thach, Chau and Tracy, Russell} } @article {717, title = {Multiple imputation of baseline data in the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {157}, year = {2003}, month = {2003 Jan 01}, pages = {74-84}, abstract = {

Most epidemiologic studies will encounter missing covariate data. Software packages typically used for analyzing data delete any cases with a missing covariate to perform a complete case analysis. The deletion of cases complicates variable selection when different variables are missing on different cases, reduces power, and creates the potential for bias in the resulting estimates. Recently, software has become available for producing multiple imputations of missing data that account for the between-imputation variability. The implementation of the software to impute missing baseline data in the setting of the Cardiovascular Health Study, a large, observational study, is described. Results of exploratory analyses using the imputed data were largely consistent with results using only complete cases, even in a situation where one third of the cases were excluded from the complete case analysis. There were few differences in the exploratory results across three imputations, and the combined results from the multiple imputations were very similar to results from a single imputation. An increase in power was evident and variable selection simplified when using the imputed data sets.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Cause of Death, Cohort Studies, Data Collection, Data Interpretation, Statistical, Epidemiologic Studies, Female, Humans, Linear Models, Male, Mathematical Computing, Models, Statistical, Predictive Value of Tests, Proportional Hazards Models, Risk Factors, Software, Survival Analysis, United States, Ventricular Remodeling}, issn = {0002-9262}, doi = {10.1093/aje/kwf156}, author = {Arnold, Alice M and Kronmal, Richard A} } @article {734, title = {The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study.}, journal = {Ophthalmology}, volume = {110}, year = {2003}, month = {2003 Apr}, pages = {658-66}, abstract = {

PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons.

DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities.

METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations.

MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis.

RESULTS: The prevalence of retinal microvascular abnormalities was 8.3\% for retinopathy, 9.6\% for focal arteriolar narrowing, and 7.7\% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis.

CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Coronary Artery Disease, Cross-Sectional Studies, Female, Humans, Hypertension, Male, Prevalence, Retinal Diseases, Retinal Vessels, Risk Factors, United States}, issn = {0161-6420}, doi = {10.1016/S0161-6420(02)01931-0}, author = {Wong, Tien Yin and Klein, Ronald and Sharrett, A Richey and Manolio, Teri A and Hubbard, Larry D and Marino, Emily K and Kuller, Lewis and Burke, Gregory and Tracy, Russell P and Polak, Joseph F and Gottdiener, John S and Siscovick, David S} } @article {736, title = {Recruitment of healthy adults into a study of overnight sleep monitoring in the home: experience of the Sleep Heart Health Study.}, journal = {Sleep Breath}, volume = {7}, year = {2003}, month = {2003 Mar}, pages = {13-24}, abstract = {

The Sleep Heart Health Study (SHHS) is a prospective cohort study using participants from several ongoing cardiovascular and respiratory disease research projects to investigate the relationship between sleep-disordered breathing and cardiovascular disease. This study design required unusual and different recruiting techniques to meet the study{\textquoteright}s enrollment goal of between 6000 and 6600 participants. Individuals were recruited to undergo an overnight home polysomnogram, completion of several questionnaires, and collection of a small amount of physical examination data. This article describes the methods used to recruit these participants and how these procedures influenced the final participation rate and the representativeness of SHHS to its parent cohorts. Of 30,773 people eligible for recruitment into SHHS, attempts were made to enroll 11,145 (36\%). Of those contacted, 6441 ultimately agreed to participate (58\%). Recruitment rates (38 to 91\%) varied among sites. SHHS participants were slightly younger (63.0 vs. 65.0 years, p < 0.001), had more years of education (14.1 vs. 13.7, p < 0.001), more likely to snore (34\% vs. 23\%, p < 0.001), had higher Epworth sleepiness scores (7.7 vs. 6.5, p < 0.001), slightly higher higher systolic and diastolic blood pressures (127.6/73.9 vs. 127.2/72.1, p < 0.001 for diastolic only), and a slightly higher body mass index (BMI) (28.5 vs. 27.5, p < 0.001). We conclude that it is feasible to recruit existing participants from one large-scale epidemiologic study into another with a high degree of success. However, the characteristics of the new cohort may vary in several respects from their original cohorts and therefore interpretation of study results will have to consider these differences.

}, keywords = {Adult, Body Mass Index, Cardiovascular Diseases, Catchment Area, Health, Circadian Rhythm, Cohort Studies, Disorders of Excessive Somnolence, Health Status, Home Care Services, Humans, Hypertension, Patient Selection, Polysomnography, Prospective Studies, Severity of Illness Index, Sleep Apnea Syndromes, Surveys and Questionnaires, United States}, issn = {1520-9512}, doi = {10.1007/s11325-003-0013-z}, author = {Lind, Bonnie K and Goodwin, James L and Hill, Joel G and Ali, Tauqeer and Redline, Susan and Quan, Stuart F} } @article {750, title = {Regional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States.}, journal = {Mov Disord}, volume = {18}, year = {2003}, month = {2003 Sep}, pages = {1035-40}, abstract = {

For reasons that are unclear, prevalence estimates of essential tremor (ET) differ considerably across the United States. Separate communities have never been sampled within the framework of the same study to substantiate these differences. We estimated the prevalence of physician-diagnosed ET in the elderly in four communities in the United States in whom the same screening questions were used, and examined whether this prevalence differed between Caucasians and African Americans. The Cardiovascular Health Study recruited a sample of Medicare beneficiaries >/=65 years of age from four communities in different regions of the United States. In 1998 to 1999, 3,494 participants (mean age, 80.0 years; range, 70-103 years) answered a 12-question screen for ET, including the question, "has a doctor diagnosed you as having familial tremor or benign essential tremor?" Fifty-four participants reported that a doctor had diagnosed them as having ET (1.5\%; 95\% confidence interval, [CI], 1.1-2.0\%). Prevalence was similar across the four communities (1.1-2.0\%). A larger proportion of Caucasians than African Americans reported a diagnosis of ET (1.7\% vs. 0.4\%; odds ratio = 4.9; 95\% CI, 1.2-20.2; P = 0.028). In a logistic regression analysis, physician-diagnosed ET was associated with Caucasian ethnicity (P = 0.038) but not with age, gender, education, mental status or depression scores, income, smoking status, or alcohol consumption. When a standardized screening question was used, the proportion of participants with physician-diagnosed ET was similar across four communities, suggesting that the prevalence of this condition may be less variable than is often reported. Caucasians were five times more likely to have physician-diagnosed ET than were African Americans. This study does not provide an explanation for this difference, which deserves further study.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Essential Tremor, European Continental Ancestry Group, Female, Humans, Male, Physicians, Prevalence, United States}, issn = {0885-3185}, doi = {10.1002/mds.10492}, author = {Louis, Elan D and Fried, Linda P and Fitzpatrick, Annette L and Longstreth, William T and Newman, Anne B} } @article {803, title = {The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1639-47}, abstract = {

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults.

DESIGN: A prospective population-based study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later.

MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.

RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95\% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality.

CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.

}, keywords = {African Americans, African Continental Ancestry Group, Aged, Female, Health Surveys, Humans, Incidence, Lipids, Male, Mortality, Myocardial Infarction, Population Surveillance, Prospective Studies, Risk Factors, Stroke, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52455.x}, author = {Psaty, Bruce M and Anderson, Melissa and Kronmal, Richard A and Tracy, Russell P and Orchard, Trevor and Fried, Linda P and Lumley, Thomas and Robbins, John and Burke, Greg and Newman, Anne B and Furberg, Curt D} } @article {765, title = {Associations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study.}, journal = {Vasc Endovascular Surg}, volume = {38}, year = {2004}, month = {2004 Jan-Feb}, pages = {25-35}, abstract = {

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

}, keywords = {Aged, Arteriosclerosis, Cardiovascular Diseases, Cohort Studies, Humans, Hypertension, Renovascular, Longitudinal Studies, Male, Multivariate Analysis, Prevalence, Prospective Studies, Renal Artery Obstruction, Ultrasonography, United States}, issn = {1538-5744}, doi = {10.1177/153857440403800103}, author = {Edwards, Matthew S and Hansen, Kimberley J and Craven, Timothy E and Bleyer, Anthony J and Burke, Gregory L and Levy, Pavel J and Dean, Richard H} } @article {805, title = {Barriers to health care access among the elderly and who perceives them.}, journal = {Am J Public Health}, volume = {94}, year = {2004}, month = {2004 Oct}, pages = {1788-94}, abstract = {

OBJECTIVES: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries.

METHODS: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study.

RESULTS: The questionnaires were completed by 4889 (91.1\%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor{\textquoteright}s lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors.

CONCLUSIONS: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.

}, keywords = {Aged, Aged, 80 and over, Chi-Square Distribution, Female, Health Behavior, Health Services Accessibility, Humans, Logistic Models, Male, Medicare, Patients, Surveys and Questionnaires, United States}, issn = {0090-0036}, doi = {10.2105/ajph.94.10.1788}, author = {Fitzpatrick, Annette L and Powe, Neil R and Cooper, Lawton S and Ives, Diane G and Robbins, John A} } @article {767, title = {Concurrent and long-term predictors of older adults{\textquoteright} use of community-based long-term care services: the Caregiver Health Effects Study.}, journal = {J Aging Health}, volume = {16}, year = {2004}, month = {2004 Feb}, pages = {88-115}, abstract = {

OBJECTIVE: This study examined concurrent and long-term associations between caregiver-related characteristics and the use of community long-term care services in a sample of 186 older adults caring for a disabled spouse.

METHOD: We used two waves of data from the Caregiver Health Effects Study, an ancillary study of the Cardiovascular Health Study. Caregiver-related need variables as predictors of service use were of primary interest and included caregiving demands, caregiver mental and physical health, and mastery. Their contribution to service use was examined after controlling for known predictors of service use.

RESULTS: At Time 1, more caregiver depressive symptoms predicted greater service use; at Time 2, more caregiver activity restriction and depressive symptoms predicted greater formal service use; increases in caregiver activity restriction and depressive symptomatology over time predicted increases in service use.

DISCUSSION: Caregiver-related need variables play a significant role in defining utilization patterns of community-based long-term care services among older adults.

}, keywords = {Aged, Caregivers, Community Health Services, Disabled Persons, Forecasting, Health Services for the Aged, Humans, Long-Term Care, Regression Analysis, Spouses, United States}, issn = {0898-2643}, doi = {10.1177/0898264303260448}, author = {Bookwala, Jamila and Zdaniuk, Bozena and Burton, Lynda and Lind, Bonnie and Jackson, Sharon and Schulz, Richard} } @article {771, title = {Congestive heart failure in the elderly: the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {61-8}, abstract = {

Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Atrial Natriuretic Factor, Blood Pressure, Diagnosis, Differential, Female, Geriatric Assessment, Heart Atria, Heart Failure, Heart Rate, Humans, Incidence, Male, Prevalence, Risk Factors, Stroke Volume, United States, Ventricular Dysfunction, Left}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02121.x}, author = {Mathew, Sunil T and Gottdiener, John S and Kitzman, Dalane and Aurigemma, Gerard} } @article {762, title = {Incidence and prevalence of dementia in the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Feb}, pages = {195-204}, abstract = {

OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer{\textquoteright}s disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort.

DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia.

SETTING: Four U.S. communities.

PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years.

MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria for AD and Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Center{\textquoteright}s State of California criteria for VaD.

RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0\%) than men (14.7\%).

CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.

}, keywords = {African Americans, Age Distribution, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Dementia, Dementia, Vascular, Education, European Continental Ancestry Group, Female, Humans, Incidence, Longitudinal Studies, Male, Prevalence, Proportional Hazards Models, Risk Factors, Sex Distribution, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52058.x}, author = {Fitzpatrick, Annette L and Kuller, Lewis H and Ives, Diane G and Lopez, Oscar L and Jagust, William and Breitner, John C S and Jones, Beverly and Lyketsos, Constantine and Dulberg, Corinne} } @article {809, title = {Neighbourhood environments and mortality in an elderly cohort: results from the cardiovascular health study.}, journal = {J Epidemiol Community Health}, volume = {58}, year = {2004}, month = {2004 Nov}, pages = {917-23}, abstract = {

BACKGROUND: It has been postulated that neighbourhood conditions are related to the health of the elderly population but longitudinal studies are rare and confounding by individual level variables remains a possibility.

METHODS: Data were obtained from the cardiovascular health study, a population based study of adults aged 65 years and older. Census block groups were used as proxies for neighbourhoods. A summary score was used to characterise the neighbourhood socioeconomic environment. Information on personal socioeconomic indicators, cardiovascular disease prevalence, and cardiovascular risk factors was obtained from the baseline examination. Proportional hazards regression and propensity score matching were used to control for individual level variables.

RESULTS: Over the eight year follow up there were 1346 deaths among the 5074 participants, of which 43\% were attributable to cardiovascular disease. Among white participants, living in the most disadvantaged neighbourhood group was associated with higher rates of cardiovascular death, after adjustment for income, education, and occupation (hazard ratio (HR) 1.5, 95\% confidence intervals (CI) 1.2 to 1.9). No neighbourhood differences were observed for non-cardiovascular deaths. Estimates for black participants were 1.3 (95\% CI 0.7 to 2.3) for cardiovascular deaths and 1.4 (95\% CI 0.8 to 2.4) for non-cardiovascular deaths, but sample size was small. In white participants, associations of neighbourhood characteristics with cardiovascular mortality persisted after adjustment for prevalent baseline disease and cardiovascular risk factors. The use of propensity score matching led to similar results (HR for the lowest compared with the highest neighbourhood score group: 1.6 95\% CI 1.1 to 2.5, controlling for personal socioeconomic indicators).

CONCLUSION: Neighbourhood disadvantage is related to rates of cardiovascular death in elderly white adults.

}, keywords = {African Americans, Aged, Cardiovascular Diseases, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Income, Male, Poverty Areas, Residence Characteristics, Risk Factors, Socioeconomic Factors, United States}, issn = {0143-005X}, doi = {10.1136/jech.2003.019596}, author = {Diez Roux, Ana V and Borrell, Luisa N and Haan, Mary and Jackson, Sharon A and Schultz, Richard} } @article {787, title = {Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {14}, year = {2004}, month = {2004 May}, pages = {325-31}, abstract = {

PURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline.

METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997.

RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change.

CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.

}, keywords = {African Americans, Age Factors, Aged, Cardiovascular Diseases, Cholesterol, European Continental Ancestry Group, Female, Forecasting, Health Status, Humans, Male, Medicare, Prospective Studies, Risk Factors, Sex Distribution, Sex Factors, United States}, issn = {1047-2797}, doi = {10.1016/j.annepidem.2003.09.006}, author = {Manolio, Teri A and Cushman, Mary and Gottdiener, John S and Dobs, Adrian and Kuller, Lewis H and Kronmal, Richard A} } @article {775, title = {The presence of frailty in elderly persons with chronic renal insufficiency.}, journal = {Am J Kidney Dis}, volume = {43}, year = {2004}, month = {2004 May}, pages = {861-7}, abstract = {

BACKGROUND: Frailty has been defined as a tool to define individuals who lack functional reserve and are at risk for functional decline. We hypothesized that chronic renal insufficiency (CRI) would be associated with a greater prevalence of frailty and disability in the elderly.

METHODS: This cross-sectional analysis used baseline data collected from the Cardiovascular Health Study, which enrolled 5,888 community-dwelling adults aged 65 years or older from 4 clinical centers in the United States. Renal insufficiency is defined as a serum creatinine level of 1.3 mg/dL or greater (> or =115 micromol/L) in women and 1.5 mg/dL or greater (> or =133 micromol/L) in men. Frailty is defined by the presence of 3 of the following abnormalities: unintentional weight loss, self-reported exhaustion, measured weakness, slow walking speed, and low physical activity. Disability is defined as any self-reported difficulty with activities of daily living.

RESULTS: Among 5,808 participants with creatinine levels measured at entry, 15.9\% of men (n = 394) and 7.6\% of women (n = 254) had CRI. Prevalences of frailty (15\% versus 6\%; P < 0.001) and disability (12\% versus 7\%; P = 0.001) were greater in participants with CRI compared with those with normal renal function. After multivariate adjustment for comorbidity, CRI remained significantly associated with frailty (odds ratio, 1.76; 95\% confidence interval, 1.28 to 2.41), but not disability (odds ratio, 1.26; 95\% confidence interval, 0.94 to 1.69).

CONCLUSION: Elderly persons with CRI have a high prevalence of frailty, which may signal their risk for progression to adverse health outcomes. If confirmed in other studies, identification of frailty in patients with CRI may warrant special interventions to preserve their independence, quality of life, and survival.

}, keywords = {Activities of Daily Living, Aged, Cross-Sectional Studies, Female, Frail Elderly, Humans, Kidney Failure, Chronic, Male, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2003.12.049}, author = {Shlipak, Michael G and Stehman-Breen, Catherine and Fried, Linda F and Song, Xiao and Siscovick, David and Fried, Linda P and Psaty, Bruce M and Newman, Anne B} } @article {804, title = {Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1648-54}, abstract = {

OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.

DESIGN: Prospective cohort study.

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

PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.

MEASUREMENTS: Adjudicated incident CHF.

RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22\% of men and 8\% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95\% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5\% used alpha antagonists during follow-up, with no observed increase in CHF risk.

CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.

}, keywords = {Adrenergic alpha-Antagonists, Aged, Antihypertensive Agents, Benzothiadiazines, Blood Pressure, Cohort Studies, Diuretics, Female, Heart Failure, Humans, Hypertension, Male, Risk Factors, Sodium Chloride Symporter Inhibitors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52456.x}, author = {Bryson, Chris L and Smith, Nicholas L and Kuller, Lewis H and Chaves, Paulo H M and Manolio, Teri A and Lewis, William and Boyko, Edward J and Furberg, Curt D and Psaty, Bruce M} } @article {792, title = {Self-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Jul}, pages = {1174-9}, abstract = {

OBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults.

DESIGN: Cross-sectional and longitudinal analyses.

SETTING: Four U.S. communities.

PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated.

MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline.

RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95\% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25\% higher risk in consumers of 14 or more drinks per week (95\% CI=3-52\%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity.

CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.

}, keywords = {Accidental Falls, Aged, Alcohol Drinking, Chi-Square Distribution, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Regression Analysis, Risk Factors, Self Disclosure, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52318.x}, author = {Mukamal, Kenneth J and Mittleman, Murray A and Longstreth, W T and Newman, Anne B and Fried, Linda P and Siscovick, David S} } @article {801, title = {Stroke risk factors and loss of high cognitive function.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Sep 14}, pages = {793-9}, abstract = {

BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition.

METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS).

RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95\% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95\% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction).

CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.

}, keywords = {Aged, Aged, 80 and over, Aging, Cognition Disorders, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Higher Nervous Activity, Humans, Incidence, Male, Risk Assessment, Risk Factors, Sampling Studies, Sensitivity and Specificity, Severity of Illness Index, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000137014.36689.7f}, author = {Elkins, J S and O{\textquoteright}Meara, E S and Longstreth, W T and Carlson, M C and Manolio, T A and Johnston, S C} } @article {772, title = {Traditional and novel risk factors in older adults: cardiovascular risk assessment late in life.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {69-80}, abstract = {

As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.

}, keywords = {Aged, Blood Coagulation Factors, Cardiovascular Diseases, Cohort Studies, Diabetes Complications, Female, Genetic Predisposition to Disease, Humans, Hypertension, Infections, Inflammation, Lipids, Longitudinal Studies, Male, Obesity, Predictive Value of Tests, Risk Factors, Smoking, United States}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02123.x}, author = {Mukamal, Kenneth J and Kronmal, Richard A and Tracy, Russell P and Cushman, Mary and Siscovick, David S} } @article {834, title = {Association of sleep time with diabetes mellitus and impaired glucose tolerance.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Apr 25}, pages = {863-7}, abstract = {

BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing.

METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index.

RESULTS: The median sleep time was 7 hours per night, with 27.1\% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95\% confidence interval, 1.57-4.02) and 1.66 (95\% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95\% confidence interval, 0.83-2.15) and 1.58 (95\% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded.

CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Blood Glucose, Diabetes Mellitus, Disease Progression, Female, Glucose Intolerance, Humans, Male, Middle Aged, Odds Ratio, Prevalence, Prospective Studies, Sleep, Surveys and Questionnaires, Time Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.8.863}, author = {Gottlieb, Daniel J and Punjabi, Naresh M and Newman, Ann B and Resnick, Helaine E and Redline, Susan and Baldwin, Carol M and Nieto, F Javier} } @article {837, title = {Classification of vascular dementia in the Cardiovascular Health Study Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1539-47}, abstract = {

OBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study.

METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI.

RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l{\textquoteright}Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD).

CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Arteries, Cohort Studies, Dementia, Vascular, Diagnosis, Differential, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000159860.19413.C4}, author = {Lopez, O L and Kuller, L H and Becker, J T and Jagust, W J and DeKosky, S T and Fitzpatrick, A and Breitner, J and Lyketsos, C and Kawas, C and Carlson, M} } @article {829, title = {Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {609-15}, abstract = {

OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment).

DESIGN: Cross-sectional.

SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults.

PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS.

MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status.

RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status.

CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.

}, keywords = {Aged, Brain, Calcinosis, Cognition Disorders, Coronary Artery Disease, Cross-Sectional Studies, Dementia, Female, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53208.x}, author = {Rosano, Caterina and Naydeck, Barbara and Kuller, Lewis H and Longstreth, William T and Newman, Anne B} } @article {828, title = {The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {569-75}, abstract = {

OBJECTIVES: To examine the relationship between persistently high depressive symptoms and long-term changes in functional disability in elderly persons.

DESIGN: A community-based, prospective, observational study.

SETTING: Participant data from the Cardiovascular Health Study.

PARTICIPANTS: From the overall sample of 5,888 subjects, three types of participants were identified for this study: (1) persistently depressed individuals, who experienced an onset of depressive symptoms that persisted over 4 years (n=119); (2) temporarily depressed individuals, who experienced an onset of depressive symptoms that resolved over time (n=259); and (3) nondepressed individuals, with persistently low depressive symptoms throughout the follow-up period who were matched on baseline activity of daily living (ADL) scores, sex, and age to the previous two groups combined (n=378).

MEASUREMENTS: Four consecutive years of data were assessed: validated measures of depression (10-item CES-D), functional disability (10-item ADL/instrumental ADL measure), physical performance, medical illness, and cognition.

RESULTS: The persistently depressed group showed a greater linear increase in functional disability ratings than the temporarily depressed and nondepressed groups. This association between persistent depression and functional disability was robust even when controlling for baseline demographic and clinical/performance measures, including cognition. The persistently depressed group had an adjusted odds ratio (OR) of 5.27 (95\% confidence interval (CI) 3.03-9.16) for increased functional disability compared with the nondepressed group over 3 years of follow-up, whereas the temporarily depressed group had an adjusted OR of 2.39 (95\% CI=1.55-3.69) compared with the nondepressed group.

CONCLUSION: Persistently elevated depressive symptoms in elderly persons are associated with a steep trajectory of worsening functional disability, generating the hypothesis that treatments for late-life depression need to be assessed on their efficacy in maintaining long-term functional status as well as remission of depressive symptoms. These results also demonstrate the need for studies to differentiate between persistent and temporary depressive symptoms when examining their relationship to disability.

}, keywords = {Activities of Daily Living, Aged, Case-Control Studies, Depressive Disorder, Disabled Persons, Female, Humans, Longitudinal Studies, Male, Multivariate Analysis, Risk, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53202.x}, author = {Lenze, Eric J and Schulz, Richard and Martire, Lynn M and Zdaniuk, Bozena and Glass, Thomas and Kop, Willem J and Jackson, Sharon A and Reynolds, Charles F} } @article {873, title = {Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Dec 12-26}, pages = {2666-70}, abstract = {

BACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined.

METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR).

RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43\% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21\% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95\% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses.

CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.

}, keywords = {Aged, Cohort Studies, Cystatin C, Cystatins, Female, Health Surveys, Humans, Longitudinal Studies, Male, Peripheral Vascular Diseases, Predictive Value of Tests, Risk Factors, ROC Curve, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.22.2666}, author = {O{\textquoteright}Hare, Ann M and Newman, Anne B and Katz, Ronit and Fried, Linda F and Stehman-Breen, Catherine O and Seliger, Stephen L and Siscovick, David S and Shlipak, Michael G} } @article {827, title = {Cystatin C concentration as a risk factor for heart failure in older adults.}, journal = {Ann Intern Med}, volume = {142}, year = {2005}, month = {2005 Apr 05}, pages = {497-505}, abstract = {

BACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.

OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.

DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.

SETTING: Adults 65 years of age or older from 4 communities in the United States.

PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.

MEASUREMENTS: Incident heart failure.

RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17\%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95\% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).

LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.

CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.

}, keywords = {Aged, Biomarkers, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney, Kidney Function Tests, Male, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-142-7-200504050-00008}, author = {Sarnak, Mark J and Katz, Ronit and Stehman-Breen, Catherine O and Fried, Linda F and Jenny, Nancy Swords and Psaty, Bruce M and Newman, Anne B and Siscovick, David and Shlipak, Michael G} } @article {818, title = {Fish consumption and stroke risk in elderly individuals: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {200-6}, abstract = {

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential.

METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained.

RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27\% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95\% confidence interval [CI], 0.55-0.98) and 30\% lower risk with intake of 5 or more times per week (HR, 0.70; 95\% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44\% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95\% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke.

CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Animals, Cohort Studies, Confidence Intervals, Diet, Fatty Acids, Omega-3, Female, Fish Oils, Fishes, Humans, Incidence, Male, Multivariate Analysis, Probability, Proportional Hazards Models, Risk Assessment, Seafood, Sensitivity and Specificity, Sex Distribution, Stroke, Surveys and Questionnaires, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.200}, author = {Mozaffarian, Dariush and Longstreth, W T and Lemaitre, Rozenn N and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Siscovick, David S} } @article {843, title = {Fish intake and risk of incident heart failure.}, journal = {J Am Coll Cardiol}, volume = {45}, year = {2005}, month = {2005 Jun 21}, pages = {2015-21}, abstract = {

OBJECTIVES: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF).

BACKGROUND: The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown.

METHODS: Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated.

RESULTS: During 12 years{\textquoteright} follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20\% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95\% confidence interval [CI] = 0.64 to 0.99), 31\% lower risk with intake 3 to 4 times/week (HR = 0.69, 95\% CI = 0.52 to 0.91), and 32\% lower risk with intake > or =5 times/week (HR = 0.68, 95\% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37\% lower risk in the highest quintile of intake (HR = 0.73, 95\% CI = 0.57 to 0.94) compared with the lowest.

CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.

}, keywords = {Aged, Animals, Cohort Studies, Cooking, Diet, Diet Surveys, Disease-Free Survival, Female, Fishes, Heart Failure, Humans, Incidence, Male, Risk Factors, United States}, issn = {0735-1097}, doi = {10.1016/j.jacc.2005.03.038}, author = {Mozaffarian, Dariush and Bryson, Chris L and Lemaitre, Rozenn N and Burke, Gregory L and Siscovick, David S} } @article {820, title = {Incidence of cardiovascular disease in older Americans: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Feb}, pages = {211-8}, abstract = {

OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans.

DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events.

SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS).

PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American).

MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD.

RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95\% confidence interval (CI)=36.4-43.1) in men and 22.3 (95\% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95\% CI=13.0-16.6) and 13.7 (95\% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9\% with each year of age over 65 and was greater than 6\% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians.

CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.

}, keywords = {African Americans, Age Distribution, Aged, Aged, 80 and over, Cardiovascular Diseases, European Continental Ancestry Group, Female, Geriatric Assessment, Humans, Incidence, Longitudinal Studies, Male, Sex Distribution, Survival Rate, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53105.x}, author = {Arnold, Alice M and Psaty, Bruce M and Kuller, Lewis H and Burke, Gregory L and Manolio, Teri A and Fried, Linda P and Robbins, John A and Kronmal, Richard A} } @article {865, title = {Kidney function as a predictor of noncardiovascular mortality.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3728-35}, abstract = {

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95\% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Cohort Studies, Confidence Intervals, Creatinine, Cystatin C, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Longitudinal Studies, Male, Probability, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Survival Analysis, United States}, issn = {1046-6673}, doi = {10.1681/ASN.2005040384}, author = {Fried, Linda F and Katz, Ronit and Sarnak, Mark J and Shlipak, Michael G and Chaves, Paulo H M and Jenny, Nancy Swords and Stehman-Breen, Catherine and Gillen, Dan and Bleyer, Anthony J and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {824, title = {Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.}, journal = {Am J Epidemiol}, volume = {161}, year = {2005}, month = {2005 Apr 01}, pages = {639-51}, abstract = {

Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer{\textquoteright}s disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95\% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95\% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer{\textquoteright}s disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Dementia, Dementia, Vascular, Female, Genotype, Humans, Male, Motor Activity, Proportional Hazards Models, Prospective Studies, Risk Factors, United States}, issn = {0002-9262}, doi = {10.1093/aje/kwi092}, author = {Podewils, Laura Jean and Guallar, Eliseo and Kuller, Lewis H and Fried, Linda P and Lopez, Oscar L and Carlson, Michelle and Lyketsos, Constantine G} } @article {871, title = {Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Nov 14}, pages = {2408-13}, abstract = {

BACKGROUND: The relationship of weight changes to the incidence, progression, and remission of sleep-disordered breathing (SDB) is not well defined. This study aims to determine the relationship between change in weight and progression or remission of SDB by polysomnography.

METHODS: We performed a longitudinal cohort study of the cardiovascular consequences of sleep apnea in diverse US communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5 years apart.

RESULTS: A total of 2968 men and women (mean age, 62 years) participated in the study. Men were more likely to have an increase in Respiratory Disturbance Index (RDI) with a given increase in weight than were women, and this was not explained by differences in starting weight, waist circumference, age, or ethnicity. In a linear regression analysis, both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss. In a categorical analysis of larger degrees of change, this sex difference was also evident. Associations were similar in diverse ethnic groups. However, SDB progressed over time, even in those with stable weight.

CONCLUSION: Modest changes in weight were related to an increase or decrease in SDB, and this association was stronger in men than in women.

}, keywords = {Body Weights and Measures, Causality, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Linear Models, Male, Middle Aged, Obesity, Odds Ratio, Sex Distribution, Sleep Apnea Syndromes, United States, Weight Gain, Weight Loss}, issn = {0003-9926}, doi = {10.1001/archinte.165.20.2408}, author = {Newman, Anne B and Foster, Greg and Givelber, Rachel and Nieto, F Javier and Redline, Susan and Young, Terry} } @article {836, title = {Renal duplex parameters, blood pressure, and renal function in elderly people.}, journal = {Am J Kidney Dis}, volume = {45}, year = {2005}, month = {2005 May}, pages = {842-50}, abstract = {

BACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans.

METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37\% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques.

RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7\% decrease in inverse serum creatinine.

CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.

}, keywords = {African Americans, Aged, Aging, Arteriosclerosis, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Creatinine, Cross-Sectional Studies, Diastole, Disease Progression, European Continental Ancestry Group, Female, Humans, Hypertension, Renovascular, Kidney, Kidney Diseases, Kidney Function Tests, Male, Renal Artery, Renal Artery Obstruction, Renal Circulation, Risk Factors, Sampling Studies, Systole, Ultrasonography, Doppler, Duplex, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2005.01.028}, author = {Pearce, Jeffrey D and Edwards, Matthew S and Craven, Timothy E and English, William P and Mondi, Matthew M and Reavis, Scott W and Hansen, Kimberley J} } @article {819, title = {Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {207-13}, abstract = {

BACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans.

METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization.

RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95\% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure.

CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cohort Studies, Comorbidity, Coronary Disease, Female, Geriatric Assessment, Heart Function Tests, Humans, Hypertension, Renovascular, Incidence, Kidney Function Tests, Male, Multivariate Analysis, Probability, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate, Ultrasonography, Doppler, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.207}, author = {Edwards, Matthew S and Craven, Timothy E and Burke, Gregory L and Dean, Richard H and Hansen, Kimberley J} } @article {859, title = {Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses.}, journal = {J Cardiovasc Electrophysiol}, volume = {16}, year = {2005}, month = {2005 Sep}, pages = {954-9}, abstract = {

OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly.

METHODS: Hourly Poincar{\'e} plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7\% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100\% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality.

RESULTS: Of 5,815 eligible hourly plots, 64.4\% were normal, 14.5\% borderline, and 21.1\% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04).

CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Arrhythmia, Sinus, Cohort Studies, Diagnosis, Computer-Assisted, Electrocardiography, Female, Heart Rate, Humans, Male, Models, Cardiovascular, Nonlinear Dynamics, Numerical Analysis, Computer-Assisted, Prevalence, Proportional Hazards Models, Reproducibility of Results, Risk Assessment, Risk Factors, Sensitivity and Specificity, United States}, issn = {1045-3873}, doi = {10.1111/j.1540-8167.2005.40788.x}, author = {Stein, Phyllis K and Domitrovich, Peter P and Hui, Nelson and Rautaharju, Pentti and Gottdiener, John} } @article {830, title = {Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {649-54}, abstract = {

OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance.

DESIGN: Longitudinal analysis, average follow-up time: 4.0 years.

SETTING: Cardiovascular Health Study (CHS).

PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4).

MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand).

RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35\% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22\% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26\% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed.

CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Brain, Female, Follow-Up Studies, Gait, Humans, Incidence, Magnetic Resonance Imaging, Male, Proportional Hazards Models, Psychomotor Disorders, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53214.x}, author = {Rosano, Caterina and Kuller, Lewis H and Chung, Hyoju and Arnold, Alice M and Longstreth, William T and Newman, Anne B} } @article {868, title = {Weight loss, muscle strength, and angiotensin-converting enzyme inhibitors in older adults with congestive heart failure or hypertension.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Nov}, pages = {1996-2000}, abstract = {

OBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor use may be associated with weight maintenance and sustained muscle strength (measured by grip strength) in older adults.

DESIGN: Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used.

SETTING: Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001.

PARTICIPANTS: CHS participants with congestive heart failure (CHF) or treated hypertension.

MEASUREMENTS: The exposure, current ACE inhibitor use, was ascertained by medication inventory at annual clinic visits; the outcomes were weight change and grip-strength change during the following year. Multivariate linear regression was used, accounting for correlations between observations on the same participant over time.

RESULTS: The average annual weight change was -0.38 kg in 2,834 participants (14,443 person-years) with treated hypertension and -0.62 kg in 342 participants (980 person-years) with CHF. ACE inhibitor use was associated with less annual weight loss after adjustment for potential confounders: a difference of 0.17 kg (95\% confidence interval (CI)=0.05-0.29) in those with treated hypertension and 0.29 kg (95\% CI=-0.25-0.83) in those with CHF. There was no evidence of association between ACE inhibitor use and grip-strength change.

CONCLUSION: ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.

}, keywords = {Aged, Aged, 80 and over, Angiotensin-Converting Enzyme Inhibitors, Female, Hand Strength, Heart Failure, Humans, Hypertension, Male, Multivariate Analysis, Outcome Assessment, Health Care, Prospective Studies, Statistics as Topic, United States, Weight Loss}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53568.x}, author = {Schellenbaum, Gina D and Smith, Nicholas L and Heckbert, Susan R and Lumley, Thomas and Rea, Thomas D and Furberg, Curt D and Lyles, Mary F and Psaty, Bruce M} } @article {878, title = {10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {71-8}, abstract = {

BACKGROUND: The incidence of coronary heart disease (CHD) is very high among individuals 65 years or older.

METHODS: We evaluated the relationships between measurements of subclinical disease at baseline (1989-1990) and at the third-year follow-up examination (1992-1993) and subsequent incidence of cardiovascular disease and total mortality as of June 2001. Approximately 61\% of the participants without clinical cardiovascular disease at baseline had subclinical disease based on our previously described criteria from the Cardiovascular Health Study.

RESULTS: The incidence of CHD was substantially increased for participants with subclinical disease compared with those who had no subclinical disease: 30.5 per 1000 person-years with and 16.3 per 1000 person-years without for white individuals, and 31.2 per 1000 person-years with and 12.5 per 1000 person-years without for black individuals. The risk persisted over the entire follow-up period. Incidence rates were higher for men than for women with or without subclinical disease, but there was little difference in rates for black individuals and white individuals.

CONCLUSIONS: In multivariable models, subclinical disease at baseline remained a significant predictor of CHD in both men and women; the hazard ratios (95\% confidence intervals) of their relative risks were 1.64 (1.30-2.06) and 1.49 (1.21-1.84), respectively. The presence of subclinical disease substantially increased the risk of subsequent CHD for participants with hypertension, diabetes mellitus, or elevated C-reactive protein. In summary, subclinical disease is very prevalent among older individuals, is independently associated with risk of CHD even over a 10-year follow-up period, and substantially increases the risk of CHD among participants with hypertension or diabetes mellitus.

}, keywords = {African Continental Ancestry Group, Aged, Blood Chemical Analysis, Cardiovascular Diseases, Comorbidity, Coronary Disease, Echocardiography, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Multivariate Analysis, Prevalence, Proportional Hazards Models, Regression Analysis, Risk Factors, Sex Distribution, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.71}, author = {Kuller, Lewis H and Arnold, Alice M and Psaty, Bruce M and Robbins, John A and O{\textquoteright}Leary, Daniel H and Tracy, Russell P and Burke, Gregory L and Manolio, Teri A and Chaves, Paolo H M} } @article {934, title = {Adjusted mortality after hip fracture: From the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Dec}, pages = {1885-91}, abstract = {

OBJECTIVES: To estimate the risk of death associated with hip fracture (HFx), stratifying by sex and time since fracture.

DESIGN: Prospective cohort study compared participants with and without hip fracture, matched on sex, age, race, recruitment period, and time since enrollment.

SETTING: The Cardiovascular Health Study, a more-than-15-year longitudinal study of 5,888 older individuals from four U.S. sites.

PARTICIPANTS: Three hundred seventy-nine individuals with HFx were compared with 1,134 without HFx.

MEASUREMENTS: Extended Cox models were used to estimate mortality hazard ratios (HRs) for different periods after fracture, adjusting for prefracture health.

RESULTS: Age- and race-adjusted excess mortality was 9\% in women and 24\% in men 1 year after fracture, and 24\% in women and 26\% men 5 years postfracture. Multivariable-adjusted HRs of mortality associated with HFx in women were 7.1 (95\% confidence interval (CI) = 2.3-21.5), 2.1 (95\% CI = 1.0-4.1), 1.4 (95\% CI = 1.1-2.0), and 1.0 (95\% CI = 0.6-1.5) for 0 to 1 months, 2 to 6 months, 7 months to 4 years, and 5 to 8 years, respectively, after index date. In men, respective HRs for the same time periods were 39.9 (95\% CI = 5.2-308.7), 3.8 (95\% CI = 1.4-10.3), 1.1 (95\% CI = 0.7-1.8), and 1.0 (95\% CI = 0.3-2.7). HRs adjusted for age and race were 20\% to 40\% higher.

CONCLUSION: The risk of mortality was highest in the first 6 months after HFx. In men, the risk of death approximated that of men without HFx after 6 months; in women, a moderately greater risk persisted through the fourth year. Although the mortality pattern was different in women and men, excess mortality 5 years postfracture was similar for both sexes.

}, keywords = {Aged, Cohort Studies, Female, Health Status, Health Surveys, Hip Fractures, Humans, Male, Mortality, Multicenter Studies as Topic, Proportional Hazards Models, Sex Distribution, Time Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00985.x}, author = {Robbins, John A and Biggs, Mary L and Cauley, Jane} } @article {881, title = {Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Jan}, pages = {30-7}, abstract = {

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome.

DESIGN: Prospective cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline.

MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly.

RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95\% confidence interval (CI)=0.71-1.14), 0.93 (95\% CI=0.73-1.20), 0.76 (95\% CI=0.53-1.10), and 0.58 (95\% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9\% to 10\% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele.

CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Beer, Cohort Studies, Coronary Disease, Female, Genotype, Health Behavior, Humans, Incidence, Male, Residence Characteristics, Risk Assessment, Socioeconomic Factors, United States, Wine}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.00561.x}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Psaty, Bruce M and Siscovick, David S} } @article {941, title = {Alcohol consumption in older adults and Medicare costs.}, journal = {Health Care Financ Rev}, volume = {27}, year = {2006}, month = {2006 Spring}, pages = {49-61}, abstract = {

We determined the relationship of alcohol consumption and Medicare costs among 4,392 participants in the Cardiovascular Health Study (CHS), a longitudinal, population-based cohort study of adults age 65 or over in four U.S. communities. We assessed 5-year Parts A and B costs and self-reported intake of beer, wine, and liquor at baseline. Among both sexes, total costs were approximately $2,000 lower among consumers of > 1-6 drinks per week than abstainers. The lower costs associated with moderate drinking were most apparent among participants with cardiovascular disease (CVD) and for hospitalization costs for CVD among healthy participants. Former drinkers had the highest costs.

}, keywords = {Aged, Alcohol Drinking, Cardiovascular Diseases, Female, Health Expenditures, Hospitalization, Humans, Longitudinal Studies, Male, Medicare, United States}, issn = {0195-8631}, author = {Mukamal, Kenneth J and Lumley, Thomas and Luepker, Russell V and Lapin, Pauline and Mittleman, Murray A and McBean, A Marshall and Crum, Rosa M and Siscovick, David S} } @article {863, title = {The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {187}, year = {2006}, month = {2006 Aug}, pages = {372-7}, abstract = {

PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events.

METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33\%), those with hypertension (52\%) and those with diabetes, with or without hypertension (15\%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass.

RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95\% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95\% CI 1.08, 2.30]) or diabetes (OR 2.51 [95\% CI 1.27, 4.94]).

CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Atherosclerosis, Cardiovascular Diseases, Coronary Disease, Diabetes Mellitus, Female, Humans, Hypertension, Male, Peripheral Vascular Diseases, Prevalence, Risk Factors, Stroke, United States}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2005.09.015}, author = {Cao, Jie J and Barzilay, Joshua I and Peterson, Do and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis and Wexler, Jason and Bleyer, Anthony J and Cushman, Mary} } @article {877, title = {The association of race with frailty: the cardiovascular health study.}, journal = {Ann Epidemiol}, volume = {16}, year = {2006}, month = {2006 Jul}, pages = {545-53}, abstract = {

PURPOSE: Frailty, which has been conceptualized as a state of decreased physiologic reserve contributing to functional decline, has a prevalence among older African Americans that is twice that in older whites. This study assesses the independent contribution of race to frailty.

METHODS: We evaluated 786 African-American and 4491 white participants of the Cardiovascular Health Study (CHS). Frailty is defined as meeting three or more of five criteria derived from CHS measures: lowest quintile for grip strength, self-reported exhaustion, unintentional weight loss of 10 lbs or greater in 1 year, slowest quintile for gait speed, and lowest quintile for physical activity. Controlling for age, sex, comorbidity, socioeconomic factors, and race, multinomial logistic regression estimated the odds ratio (OR) of prefrail (one or two criteria) to not frail and frail to not frail.

RESULTS: Among African Americans, 8.7\% of men and 15.0\% of women were frail compared with 4.6\% and 6.8\% of white men and women, respectively. In adjusted models, nonobese African Americans had a fourfold greater odds of frailty compared with whites. The increased OR of frailty associated with African-American race was less pronounced among those who were obese or disabled.

CONCLUSION: African-American race is associated independently with frailty.

}, keywords = {African Americans, Aged, Asthenia, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, European Continental Ancestry Group, Female, Frail Elderly, Health Status, Humans, Male, Middle Aged, Motor Activity, Odds Ratio, United States, Weight Loss}, issn = {1047-2797}, doi = {10.1016/j.annepidem.2005.10.003}, author = {Hirsch, Calvin and Anderson, Melissa L and Newman, Anne and Kop, Willem and Jackson, Sharon and Gottdiener, John and Tracy, Russell and Fried, Linda P} } @article {913, title = {Body mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS.}, journal = {J Clin Densitom}, volume = {9}, year = {2006}, month = {2006 Jul-Sep}, pages = {329-34}, abstract = {

Body mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women{\textquoteright}s Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.

}, keywords = {Absorptiometry, Photon, Aged, Aged, 80 and over, Biometry, Body Height, Body Mass Index, Body Weight, Bone Density, Female, France, Humans, Male, United States}, issn = {1094-6950}, doi = {10.1016/j.jocd.2006.02.005}, author = {Robbins, John and Schott, Anne-Marie and Azari, Rahman and Kronmal, Richard} } @article {895, title = {Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {97}, year = {2006}, month = {2006 May 01}, pages = {1281-6}, abstract = {

In the elderly, mitral annular calcification (MAC) and aortic valve sclerosis (AVS) are associated with increased cardiovascular morbidity and mortality. Aortic annular calcification (AAC) commonly occurs with MAC. However, the prognostic value of AAC, singly or in combination with MAC and AVS, for incident cardiovascular disease and mortality is unknown. From the Cardiovascular Health Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60\% women) who had an echocardiogram at the 1994 to 1995 examination and who were prospectively followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification categories were associated with incident congestive heart failure (MAC: hazard ratio [HR] 1.71, 95\% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95\% CI 1.28 to 2.06, and AVS: HR 1.50, 95\% CI 1.19 to 1.89) and death. A stronger association with incident cardiovascular disease and mortality was observed with a larger number of calcification categories and with increased MAC severity. Moreover, in the participants with prevalent cardiovascular disease at echocardiographic examination (n = 1,054), MAC and AAC were still associated with cardiovascular mortality (MAC: HR 1.91, 95\% CI 1.04 to 3.50; AAC: HR 2.11, 95\% CI 1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are associated with a significant risk of incident congestive heart failure, cardiovascular and all-cause mortalities, and worse outcome in older patients with preexisting cardiovascular disease. Elderly patients with these findings represent a high-risk group and may require close medical attention.

}, keywords = {Aged, Aortic Valve, Calcinosis, Echocardiography, Female, Follow-Up Studies, Heart Failure, Heart Valve Diseases, Humans, Male, Mitral Valve, Prospective Studies, Risk Factors, Sclerosis, Severity of Illness Index, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2005.11.065}, author = {Barasch, Eddy and Gottdiener, John S and Marino Larsen, Emily K and Chaves, Paulo H M and Newman, Anne B} } @article {896, title = {Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {113}, year = {2006}, month = {2006 May 09}, pages = {2177-85}, abstract = {

BACKGROUND: Although >80\% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described.

METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30\% were fatal. Case fatality decreased slightly over time, ranging from 28\% to 30\% per year in the early 1990s versus 23\% by 2000-2001; with adjustment for age at MI and gender, there was a 6\% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95\% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95\% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95\% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95\% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95\% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups.

CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Carotid Artery, Common, Cohort Studies, Comorbidity, Coronary Disease, Diabetes Mellitus, Electrocardiography, Female, Follow-Up Studies, Forecasting, Heart Failure, Heart Ventricles, Hospitalization, Humans, Hyperlipidemias, Hypertension, Male, Multivariate Analysis, Myocardial Infarction, Organ Size, Predictive Value of Tests, Risk Factors, Sampling Studies, Tunica Intima, Tunica Media, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.105.610352}, author = {Pearte, Camille A and Furberg, Curt D and O{\textquoteright}Meara, Ellen S and Psaty, Bruce M and Kuller, Lewis and Powe, Neil R and Manolio, Teri} } @article {904, title = {Cigarette smoking and nocturnal sleep architecture.}, journal = {Am J Epidemiol}, volume = {164}, year = {2006}, month = {2006 Sep 15}, pages = {529-37}, abstract = {

Cigarette smoking has been associated with a high prevalence of sleep-related complaints. However, its effects on sleep architecture have not been fully examined. The primary objective of this investigation was to assess the impact of cigarette smoking on sleep architecture. Polysomnography was used to characterize sleep architecture among 6,400 participants of the Sleep Heart Health Study (United States, 1994-1999). Sleep parameters included total sleep time, latency to sleep onset, sleep efficiency, and percentage of time in each sleep stage. The study sample consisted of 2,916 never smokers, 2,705 former smokers, and 779 current smokers. Compared with never smokers, current smokers had a longer initial sleep latency (5.4 minutes, 95\% confidence interval (CI): 2.9, 7.9) and less total sleep time (14.0 minutes, 95\% CI: 6.4, 21.7). Furthermore, relative to never smokers, current smokers also had more stage 1 sleep (relative proportion = 1.24, 95\% CI: 1.14, 1.33) and less slow wave sleep (relative proportion = 0.86, 95\% CI: 0.78, 0.95). Finally, no differences in sleep architecture were noted between former and never smokers. The results of this study show that cigarette smoking is independently associated with disturbances in sleep architecture, including a longer latency to sleep onset and a shift toward lighter stages of sleep. Nicotine in cigarette smoke and acute withdrawal from it may contribute to disturbances in sleep architecture.

}, keywords = {Aged, Arousal, Chi-Square Distribution, Female, Humans, Male, Middle Aged, Polysomnography, Prevalence, Regression Analysis, Risk Factors, Sleep Stages, Sleep Wake Disorders, Smoking, United States}, issn = {0002-9262}, doi = {10.1093/aje/kwj231}, author = {Zhang, Lin and Samet, Jonathan and Caffo, Brian and Punjabi, Naresh M} } @article {879, title = {Costs for heart failure with normal vs reduced ejection fraction.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {112-8}, abstract = {

BACKGROUND: Among the elderly population, heart failure (HF) with normal ejection fraction (EF) is more common than classic HF with low EF. However, there are few data regarding the costs of HF with normal EF. In a prospective, population-based cohort of elderly participants, we compared the costs and resource use of patients with HF and normal and reduced EF.

METHODS: A total of 4549 participants (84.5\% white; 40.6\% male) in the National Heart, Lung, and Blood Institute Cardiovascular Health Study were linked to Medicare claims from 1992 through 1998. By protocol echo examinations or clinical EF assessments, 881 participants with HF were characterized as having abnormal or normal EF. We applied semiparametric estimators to calculate mean costs per subject for a 5-year period.

RESULTS: There were 495 HF participants with normal EF (186 prevalent at study entry and 309 incident during the study period) and 386 participants with abnormal EF (166 prevalent and 220 incident). Participants with abnormal EF had more cardiology encounters and cardiac procedures. However, compared with abnormal EF participants, the 5-year costs for normal EF participants were similar in both the prevalent ($33,023 with abnormal EF and $32,580 with normal EF; P=.93) and incident ($49,128 with abnormal EF and $45,604 with normal EF; P=.55) groups. In models accounting for comorbid conditions, the costs with normal and abnormal EF remained similar.

CONCLUSIONS: Over a 5-year period, patients with HF and normal EF consume as many health care resources as those with reduced EF. These data highlight the substantial financial burden of HF with normal EF among the elderly population.

}, keywords = {Aged, Aged, 80 and over, Comorbidity, Echocardiography, Health Care Costs, Heart Failure, Humans, Incidence, Medicare, Prevalence, Prospective Studies, Regression Analysis, Statistics, Nonparametric, Stroke Volume, Systole, United States, Ventricular Function, Left}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.112}, author = {Liao, Lawrence and Jollis, James G and Anstrom, Kevin J and Whellan, David J and Kitzman, Dalane W and Aurigemma, Gerard P and Mark, Daniel B and Schulman, Kevin A and Gottdiener, John S} } @article {899, title = {Education, cognitive test scores, and black-white differences in dementia risk.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Jun}, pages = {898-905}, abstract = {

OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups.

DESIGN: Longitudinal, 6-year follow-up.

PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study.

MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes.

RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95\% confidence interval (CI)=1.5-2.4 and 95\% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95\% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95\% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95\% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE.

CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

}, keywords = {African Continental Ancestry Group, Aged, Cognition, Dementia, Educational Status, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Psychological Tests, Retrospective Studies, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00747.x}, author = {Shadlen, Marie-Florence and Siscovick, David and Fitzpatrick, Annette L and Dulberg, Corinne and Kuller, Lewis H and Jackson, Sharon} } @article {883, title = {Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States).}, journal = {Cancer Causes Control}, volume = {17}, year = {2006}, month = {2006 Mar}, pages = {187-97}, abstract = {

OBJECTIVE: To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk.

METHODS: We conducted a case-control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989-2000. We genotyped 193 cases and 391 controls for the PSA -252 G/A and -158 G/A SNPs and the AR CAG microsatellite, and developed methods to directly determine proximal PSA promoter haplotypes. Exact logistic regression was used to estimate odds ratios and significance levels.

RESULTS: No significant associations were observed between PSA diplotype and prostate cancer overall. Short (< 20) AR CAG repeat lengths were associated with modest increases in the risk of prostate cancer (OR, 1.46; 95\% CI, 0.97-2.19; p = 0.071) that were significant for advanced disease (OR, 1.82; 95\% CI, 1.02-3.26; p = 0.044). Men who possessed two copies of the PSA*2 (-252G/-158G) haplotype and short AR CAG repeat lengths had a 4-fold (95\% CI, 1.05-20.75; exact p = 0.040) increased risk of prostate cancer, and a 7-fold (95\% CI, 1.25-39.78; exact p = 0.026) increased risk of advanced disease.

CONCLUSIONS: We found evidence that the PSA*2*2 diplotype in combination with short AR CAG alleles increases a man{\textquoteright}s risk of developing prostate cancer. These findings support an etiologic role in prostate cancer of genetic interactions between polymorphisms that increase AR transactivation strength and those that alter the regulatory regions of target genes such as PSA that are responsive to androgen stimulation.

}, keywords = {Aged, Biomarkers, Tumor, Case-Control Studies, Cohort Studies, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Polymorphism, Genetic, Prostate-Specific Antigen, Prostatic Neoplasms, Receptors, Androgen, United States}, issn = {0957-5243}, doi = {10.1007/s10552-005-0454-8}, author = {Sieh, Weiva and Edwards, Karen L and Fitzpatrick, Annette L and Srinouanprachanh, Sengkeo L and Farin, Fred M and Monks, Stephanie A and Kronmal, Richard A and Eaton, David L} } @article {872, title = {Lipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation.}, journal = {Metabolism}, volume = {55}, year = {2006}, month = {2006 Jan}, pages = {96-102}, abstract = {

Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.

}, keywords = {Adult, African Americans, Age Factors, Aged, Alleles, Body Mass Index, Cardiovascular Diseases, Caribbean Region, Cohort Studies, DNA, European Continental Ancestry Group, Gene Frequency, Genetic Variation, Humans, Lipase, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Liver, Longitudinal Studies, Male, Middle Aged, Particle Size, Trinidad and Tobago, United States}, issn = {0026-0495}, doi = {10.1016/j.metabol.2005.07.011}, author = {Miljkovic-Gacic, Iva and Bunker, Clareann H and Ferrell, Robert E and Kammerer, Candace M and Evans, Rhobert W and Patrick, Alan L and Kuller, Lewis H} } @article {903, title = {Plasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {114}, year = {2006}, month = {2006 Jul 18}, pages = {209-15}, abstract = {

BACKGROUND: Intake of trans fatty acids is associated with increased risk of coronary heart disease. Whether different classes of trans fatty acids show similar associations is unclear. We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids. To extend these findings, we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease (IHD) and sudden cardiac death.

METHODS AND RESULTS: We conducted a case-control study nested in the Cardiovascular Health Study. We identified 214 cases of fatal IHD (fatal myocardial infarction and coronary heart disease death) between 1992 and 1998. We randomly selected 214 controls, matched to cases on demographics, prevalent cardiovascular disease, and timing of blood draw. Plasma phospholipid fatty acids were assessed in blood samples collected earlier. Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD (odds ratio [OR] for interquintile range 1.68, 95\% confidence interval [CI] 1.21 to 2.33) after adjustment for risk factors and trans-18:1 levels. Trans-18:1 levels above the 20th percentile were associated with lower risk (OR 0.34, 95\% CI 0.18 to 0.63). In analyses limited to cases of sudden cardiac death (n=95), higher levels of trans-18:2 fatty acids were associated with higher risk (OR 2.34, 95\% CI 1.27 to 4.31) and higher trans-18:1 with lower risk (OR 0.18, 95\% CI 0.06 to 0.54).

CONCLUSIONS: Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death. If confirmed, these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Case-Control Studies, Coronary Disease, Death, Sudden, Cardiac, Female, Humans, Male, Myocardial Ischemia, Phospholipids, Trans Fatty Acids, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.620336}, author = {Lemaitre, Rozenn N and King, Irena B and Mozaffarian, Dariush and Sotoodehnia, Nona and Rea, Thomas D and Kuller, Lewis H and Tracy, Russel P and Siscovick, David S} } @article {866, title = {Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {26}, year = {2006}, month = {2006}, pages = {52-60}, abstract = {

Abnormal gait in high-functioning older adults may indicate underlying subtle structural brain abnormalities. We tested the hypothesis that temporal and spatial parameters of gait, including speed, stride length and double support time, are cross-sectionally associated with white matter hyperintensity, subcortical infarcts or brain atrophy on brain MRI. We examined 321 men and women (mean age = 78.3) participating to the Cardiovascular Health Study who were free of dementia or stroke at the time of the gait assessment. Analyses were set with gait as independent variable and brain MRIs as dependent variables. Gait measures were determined from the footfalls recorded on a 4-meter-long instrumented walking surface, the GaitMat II. Brain MRIs were examined for the presence of white matter hyperintensity (WMG, graded from 0 to 9), brain infarcts (predominantly subcortical) and ventricular enlargement (graded from 0 to 9). Slower gait, shorter stride length and longer double support times were associated with greater prevalence of white matter grade > or =3 (p = 0.02), and at least 1 brain infarct (p = 0.04) independent of age. In multivariate logistic regression models adjusted for demographics and clinical cardiovascular diseases, those with gait speed <1.02 m/s were more likely to have WMG > or =3 and at least 1 brain infarct, compared with those with faster gait - odds ratio (OR): 2.85, 95\% confidence interval (95\% CI): 1.35, 6.02, and OR: 2.09, 95\% CI: 1.04, 4.19. Shorter stride length was also associated with greater probability of having at least 1 brain infarct (gait stride <0.88 vs. >1.10 m: OR: 3.20, 95\% CI: 1.49, 6.88), while longer double support times were associated with a greater probability of having WMG > or =3 (double support time >0.19 vs. <0.14 s: OR: 2.3, 95\% CI: 1.1, 4.7) independent of demographics and clinical cardiovascular diseases. Gait parameters were not significantly associated with ventricular grade. In summary, in this group of high-functioning older adults, poorer gait speed, shorter stride and longer double support time are associated with high white matter disease and subclinical strokes.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Dementia, Female, Gait, Gait Disorders, Neurologic, Humans, Hypertension, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Stroke, United States}, issn = {0251-5350}, doi = {10.1159/000089240}, author = {Rosano, Caterina and Brach, Jennifer and Longstreth, William T and Newman, Anne B} } @article {929, title = {Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Nov 27}, pages = {2388-94}, abstract = {

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons.

METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods.

RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7\%; 95\% confidence interval [CI], 8.7\%-15.8\%, vs 8.1\%; 95\% CI, 5.7\%-11.6\%), comparing largest with smallest venular caliber quartiles, and stroke (8.4\%; 95\% CI, 6.0-11.7, vs 5.8\%; 95\% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95\% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95\% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95\% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95\% CI, 0.5-2.2; P = .73).

CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cardiovascular Diseases, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Incidence, Male, Photography, Prospective Studies, Retinal Diseases, Retinal Vein, Retinal Vessels, Risk Factors, Stroke, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.21.2388}, author = {Wong, Tien Yin and Kamineni, Aruna and Klein, Ronald and Sharrett, A Richey and Klein, Barbara E and Siscovick, David S and Cushman, Mary and Duncan, Bruce B} } @article {971, title = {Alcohol consumption and type 2 diabetes among older adults: the Cardiovascular Health Study.}, journal = {Obesity (Silver Spring)}, volume = {15}, year = {2007}, month = {2007 Jul}, pages = {1758-65}, abstract = {

OBJECTIVE: The objective was to examine the role of total and beverage-specific alcohol consumption on the incidence of type 2 diabetes mellitus (DM) among elderly men and women.

RESEARCH METHODS AND PROCEDURES: We studied prospectively 4655 participants of the Cardiovascular Health Study who were free of DM at baseline. Alcohol consumption was obtained at baseline and during follow-up examinations. DM was defined using fasting glucose and/or use of hypoglycemic medications. We used Cox proportional hazard models to estimate adjusted relative risks of diabetes across alcohol categories.

RESULTS: During a mean follow-up of 6.3 years, 234 incident cases of DM were documented. Compared with never drinkers, hazard ratios [95\% confidence interval (CI)] for DM were 0.7 (0.3 to 1.4), 0.5 (0.3 to 0.9), 0.6 (0.4 to 1.1), and 0.8 (0.4 to 1.3) for former drinkers and current drinkers of <1, 1 to 6, and 7+ drinks per week, respectively, for men after adjustment for age, BMI, education, and smoking. Corresponding values for women were 1.2 (0.6 to 2.3), 0.7 (0.4 to 1.1), 0.6 (0.3 to 1.1), and 0.4 (0.2 to 1.0), respectively. A reduced risk of DM was observed with all types of beverage consumed. Similar findings were observed when we repeated the above analyses using simple or weighted cumulative alcohol update and covariates over time.

DISCUSSION: Light to moderate alcohol consumption was associated with a lower incidence of DM among elderly people, irrespective of the type of beverage consumed.

}, keywords = {Aged, Aged, 80 and over, Alcohol Drinking, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Medicare, Middle Aged, Risk, Smoking, Temperance, United States}, issn = {1930-7381}, doi = {10.1038/oby.2007.209}, author = {Djouss{\'e}, Luc and Biggs, Mary L and Mukamal, Kenneth J and Siscovick, David S} } @article {944, title = {Alcohol consumption, bone density, and hip fracture among older adults: the cardiovascular health study.}, journal = {Osteoporos Int}, volume = {18}, year = {2007}, month = {2007 May}, pages = {593-602}, abstract = {

INTRODUCTION: Previous studies have found inconsistent relationships of alcohol consumption with risk of hip fracture, and the importance of bone mineral density and risk of falls in mediating such a relationship has not been determined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort study of adults aged 65 years and older from four U.S. communities, 5,865 participants reported their use of beer, wine, and liquor yearly. We identified cases of hip fracture unrelated to malignancy or motor vehicle accidents using hospitalization discharge diagnoses. A subgroup of 1,567 participants in two communities underwent dual-energy x-ray absorptiometry scans to assess bone mineral density.

RESULTS: A total of 412 cases of hip fracture occurred during an average of 12 years of follow-up. There was a significant U-shaped relationship between alcohol intake and risk of hip fracture (p quadratic 0.02). Compared with long-term abstainers, the adjusted hazard ratios for hip fracture were 0.78 (95\% confidence interval [CI], 0.61-1.00) among consumers of up to 14 drinks per week and 1.18 (95\% CI, 0.77-1.81) among consumers of 14 or more drinks per week. Alcohol intake was associated with bone mineral density of the total hip and femoral neck in a stepwise manner, with approximately 5\% (95\% CI, 1\%-9\%) higher bone density among consumers of 14 or more drinks per week than among abstainers. These relationships were all similar among men and women.

CONCLUSIONS: Among older adults, moderate alcohol consumption has a U-shaped relationship with risk of hip fracture, but a graded positive relationship with bone mineral density at the hip.

}, keywords = {Absorptiometry, Photon, Aged, Alcohol Drinking, Alcoholic Beverages, Apolipoproteins E, Bone Density, Female, Femur Neck, Genotype, Hip, Hip Fractures, Humans, Longitudinal Studies, Male, Risk Assessment, Risk Factors, Sex Distribution, United States}, issn = {0937-941X}, doi = {10.1007/s00198-006-0287-7}, author = {Mukamal, K J and Robbins, J A and Cauley, J A and Kern, L M and Siscovick, D S} } @article {949, title = {Are microvascular abnormalities in the retina associated with depression symptoms? The Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {15}, year = {2007}, month = {2007 Apr}, pages = {335-43}, abstract = {

OBJECTIVE: Depression has been linked with vascular risk factors and stroke. The authors examined the relationship between retinal microvascular abnormalities and depression symptoms in an elderly population.

METHODS: The Cardiovascular Health Study is a population-based study conducted in four U.S. communities initiated in 1989-1990. A total of 2,420 persons aged 65 years and older were included in the current analyses. During the 1997-1998 examination, retinal photographs were performed and assessed for retinal microvascular abnormalities (retinopathy, focal arteriolar narrowing, arteriovenous nicking, generalized retinal arteriolar narrowing, and generalized retinal venular dilation) according to standardized methods. Depression symptoms were assessed by a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989 through 1997-1998 and was defined as a CES-D score of >9.

RESULTS: Participants with retinal microvascular abnormalities were not more likely to have depression symptoms, with adjusted odds ratio (OR) (95\% confidence intervals) of 1.08 (0.71-1.65) for retinopathy, OR 1.09 (0.71-1.68) for focal arteriolar narrowing, OR 0.85 (0.52-1.40) for arteriovenous nicking, OR 0.97 (0.70-1.34) for generalized arteriolar narrowing, and OR 0.79 (0.56-1.12) for generalized venular dilation. Retinal microvascular abnormalities were not related to depression symptoms in multinomial logistic regression comparing the three top quartiles of the depression CES-D scores with the lowest quartile.

CONCLUSIONS: Our study did not find an association between retinal microvascular abnormalities and depression symptoms in older people.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Comorbidity, Cross-Sectional Studies, Depression, Female, Fluorescein Angiography, Humans, Male, Microcirculation, Personality Inventory, Retinal Artery Occlusion, Retinal Diseases, Retinal Vein Occlusion, Risk Factors, Statistics as Topic, United States}, issn = {1064-7481}, doi = {10.1097/01.JGP.0000247161.98311.0f}, author = {Sun, Cong and Tikellis, Gabriella and Klein, Ronald and Steffens, David C and Larsen, Emily K Marino and Siscovick, David S and Klein, Barbara E K and Wong, Tien Y} } @article {967, title = {Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {116}, year = {2007}, month = {2007 Jul 03}, pages = {32-8}, abstract = {

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72\% (95\% CI, 1.46 to 2.01) increased risk for CVD death and a 52\% (95\% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54\% for CVD death and 79\% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {979, title = {Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the fibrinogen studies collab}, journal = {Am J Epidemiol}, volume = {166}, year = {2007}, month = {2007 Oct 15}, pages = {867-79}, abstract = {

Long-term increases in plasma fibrinogen levels of 1 g/liter are associated with an approximate doubling of risk of major cardiovascular disease outcomes, but causality remains uncertain. To quantify cross-sectional associations of fibrinogen levels with established risk factors and other characteristics, the investigators combined individual data on 154,211 apparently healthy adults from 31 prospective studies conducted between 1967 and 2003, using a linear mixed model that included random effects at the cohort level. Fibrinogen levels increased with age and showed continuous, approximately linear relations with several risk markers and slightly curvilinear associations with log triglycerides, albumin, and tobacco and alcohol consumption. Female sex, Black ethnicity, lower socioeconomic status, and alcohol abstinence were each associated with modestly higher fibrinogen levels. Approximately one third of the variation in fibrinogen levels was explained by cohort, age, and sex. An additional 7\% was explained by established risk factors (notably, positive associations with smoking and body mass index and an inverse association with high density lipoprotein cholesterol), and a further 10\% was explained by inflammatory markers (notably, a positive association with C-reactive protein). The association with body mass index was twice as strong in women as in men, whereas the association with smoking was much stronger in men. These findings substantially advance understanding of the correlates and possible determinants of fibrinogen levels.

}, keywords = {Adult, African Americans, Age Factors, Biomarkers, Body Mass Index, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Female, Fibrinogen, Humans, Linear Models, Male, Prospective Studies, Risk Factors, Sex Factors, Smoking, Social Class, United States}, issn = {0002-9262}, doi = {10.1093/aje/kwm191}, author = {Kaptoge, S and White, I R and Thompson, S G and Wood, A M and Lewington, S and Lowe, G D O and Danesh, J} } @article {962, title = {Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {115}, year = {2007}, month = {2007 May 08}, pages = {2390-7}, abstract = {

BACKGROUND: The relationship between impaired brachial flow-mediated dilation (FMD) and subsequent clinical cardiovascular events is not well established, especially in older adults whose FMD is often diminished. We assessed the hypothesis that FMD predicts incident cardiovascular events in a population-based cohort of older adults.

METHODS AND RESULTS: FMD was measured at the 1997 to 1998 Cardiovascular Health Study clinic visit in 2792 adults aged 72 to 98 years (82.7\% white, 58.6\% women) recruited at 4 clinic sites in the United States. Log-rank test and Cox proportional hazard models were used to examine the association between FMD and adjudicated cardiovascular events. A total of 674 subjects (24.1\%) had an adjudicated event over the 5-year follow-up period. Event-free survival rates for cardiovascular events were significantly higher in subjects with FMD greater than the sex-specific medians than in subjects with FMD less than or equal to the sex-specific medians (78.3\% versus 73.6\%, log-rank P=0.006). FMD remained a significant predictor of cardiovascular events after adjustment for age, gender, diabetes mellitus, cigarette smoking, systolic and diastolic blood pressure, baseline cardiovascular disease status, and total cholesterol (hazard ratio, 0.91 [95\% CI, 0.83 to 0.99], P=0.02 per unit SD of FMD) but added only approximately 1\% to the prognostic accuracy of the best Cox model. Brachial artery diameter was also predictive of CV events in the adjusted Cox proportional hazard model (hazard ratio, 1.12 [95\% CI, 1.02 to 1.28], P=0.025) and also added approximately 1\% to the accuracy of our best Cox model.

CONCLUSIONS: FMD is a predictor of future cardiovascular events but adds very little to the prognostic accuracy of traditional cardiovascular risk scores/factors in older adults. FMD and brachial artery diameter may have similar predictive values for cardiovascular events in older adults.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Brachial Artery, Cardiovascular Diseases, Cohort Studies, Disease-Free Survival, Endothelium, Vascular, Female, Hemorheology, Humans, Hyperemia, Male, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Reproducibility of Results, Risk Factors, Stress, Mechanical, Tourniquets, Ultrasonography, United States, Vasodilation}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.678276}, author = {Yeboah, Joseph and Crouse, John R and Hsu, Fang-Chi and Burke, Gregory L and Herrington, David M} } @article {969, title = {Costs of the metabolic syndrome in elderly individuals: findings from the Cardiovascular Health Study.}, journal = {Diabetes Care}, volume = {30}, year = {2007}, month = {2007 Oct}, pages = {2553-8}, abstract = {

OBJECTIVE: The cardiovascular consequences of the metabolic syndrome and its component risk factors have been documented in elderly individuals. Little is known about how the metabolic syndrome and its individual components translate into long-term medical costs.

RESEARCH DESIGN AND METHODS: We used log-linear regression models to assess the independent contributions of the metabolic syndrome and its individual components to 10-year medical costs among 3,789 individuals aged > or = 65 years in the Cardiovascular Health Study.

RESULTS: As defined by the National Cholesterol Education Program Third Adult Treatment Panel report, the metabolic syndrome was present in 47\% of the sample. Total costs to Medicare were 20\% higher among participants with the metabolic syndrome ($40,873 vs. $33,010; P < 0.001). Controlling for age, sex, race/ethnicity, and other covariates, we found that abdominal obesity, low HDL cholesterol, and elevated blood pressure were associated with 15\% (95\% CI 4.3-26.7), 16\% (1.7-31.8), and 20\% (10.1-31.7) higher costs, respectively. When added to the model, the metabolic syndrome composite variable did not contribute significantly (P = 0.32).

CONCLUSIONS: Abdominal obesity, low HDL cholesterol, and hypertension but not the metabolic syndrome per se are important predictors of long-term costs in the Medicare population.

}, keywords = {Aged, Aged, 80 and over, Cholesterol, HDL, Continental Population Groups, Cost of Illness, Diabetic Angiopathies, Female, Humans, Hypertension, Interviews as Topic, Male, Medicare, Metabolic Syndrome, Multivariate Analysis, Obesity, Patient Education as Topic, Prospective Studies, Regression Analysis, United States}, issn = {1935-5548}, doi = {10.2337/dc07-0460}, author = {Curtis, Lesley H and Hammill, Bradley G and Bethel, M Angelyn and Anstrom, Kevin J and Gottdiener, John S and Schulman, Kevin A} } @article {968, title = {Depressive symptoms and age-related macular degeneration in older people: the cardiovascular health study.}, journal = {Ophthalmic Epidemiol}, volume = {14}, year = {2007}, month = {2007 May-Jun}, pages = {127-33}, abstract = {

PURPOSE: To examine the association between age-related macular degeneration (AMD) and depressive symptoms.

METHODS: Population-based, cross-sectional study. A total of 2,194 persons aged 69-97 years were included in the current analyses. During the 1997-1998 examination, retinal photography from one randomly selected eye was graded for presence of early and late AMD using a modified Wisconsin AMD by Grading System. Depressive symptoms were assessed via a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989 through 1997-1998. Depressive symptoms were defined as a CES-D score of >9 (top quartile of CES-D score) at the 1997-1998 examination.

RESULTS: There were 338 (15.6\%) individuals with early AMD and 29 (1.3\%) with late AMD. Among them, 368 (16.8\%) persons had depressive symptoms at the 1997-1998 examination. Depressive symptoms were not associated with early AMD (multivariable adjusted odds ratio [OR]: 0.97; 95\% confidence intervals [CI]: 0.69-1.36) or late AMD (OR: 1.15; 95\% CI: 0.38-3.46). Including persons using anti-depressive medications did not alter these associations (OR: 0.98; 95\% CI: 0.74-1.32 for early AMD and OR: 0.97; 95\% CI: 0.35-2.67 for late AMD). There was no association in multinomial logistic regression models of increasing quartiles of the CES-D scores with early or late AMD status.

CONCLUSIONS: Our study did not find an association between early AMD and depressive symptoms in older people.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cross-Sectional Studies, Depressive Disorder, Female, Health Surveys, Humans, Intelligence Tests, Macular Degeneration, Male, Photography, United States}, issn = {0928-6586}, doi = {10.1080/09286580601186742}, author = {Sun, Cong and Tikellis, Gabriella and Klein, Ronald and Steffens, David C and Larsen, Emily K Marino and Wong, Tien Y} } @article {992, title = {Depressive symptoms, inflammation, and ischemic stroke in older adults: a prospective analysis in the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {55}, year = {2007}, month = {2007 Nov}, pages = {1825-30}, abstract = {

OBJECTIVES: To investigate the mediator role of inflammation in any relationship between depressive symptoms and ischemic stroke.

DESIGN: Longitudinal prospective study.

SETTING: Review of medical records, death certificates, and the Medicare healthcare utilization database for hospitalizations.

PARTICIPANTS: Total of 5,525 elderly men and women aged 65 and older who were prospectively followed from 1989 to 2000 as participants in the Cardiovascular Health Study.

MEASUREMENTS: Depression symptom scores, inflammatory markers.

RESULTS: Greater depressive symptoms were associated with risk of ischemic stroke (unadjusted hazard ratio (HR)=1.32, 95\% confidence interval (CI)=1.09-1.59; HR=1.26, 95\% CI=1.03-1.54, adjusted for traditional risk factors). When a term for inflammation (C-reactive protein (CRP)) was introduced in the model, the HRs were not appreciably altered (unadjusted HR=1.31, 95\% CI=1.08-1.58; adjusted HR=1.25, 95\% CI=1.02-1.53), indicating that CRP at baseline was not a mediator in this relationship. In analyses stratified according to CRP levels, a J-shaped relationship between depressive symptoms and stroke was evident in the unadjusted analyses; in the fully adjusted model, only CRP in the highest tertile was associated with a higher risk for stroke in the presence of higher depressive symptoms scores.

CONCLUSION: The analyses from this prospective study provide evidence of a positive association between depressive symptoms and risk of incident stroke. Inflammation, as measured according to CRP at baseline, did not appear to mediate the relationship between depressive symptoms and stroke.

}, keywords = {Aged, C-Reactive Protein, Cardiovascular Diseases, Cerebral Infarction, Cohort Studies, Depression, Female, Geriatric Assessment, Humans, Inflammation, Kaplan-Meier Estimate, Longitudinal Studies, Male, Multivariate Analysis, Personality Assessment, Proportional Hazards Models, Prospective Studies, Psychoneuroimmunology, Risk Factors, Socioeconomic Factors, Statistics as Topic, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01393.x}, author = {Arbelaez, Jose J and Ariyo, Abraham A and Crum, Rosa M and Fried, Linda P and Ford, Daniel E} } @article {953, title = {The effect of different public health interventions on longevity, morbidity, and years of healthy life.}, journal = {BMC Public Health}, volume = {7}, year = {2007}, month = {2007 Apr 05}, pages = {52}, abstract = {

BACKGROUND: Choosing cost-effective strategies for improving the health of the public is difficult because the relative effects of different types of interventions are not well understood. The benefits of one-shot interventions may be different from the benefits of interventions that permanently change the probability of getting sick, recovering, or dying. Here, we compare the benefits of such types of public health interventions.

METHODS: We used multi-state life table methods to estimate the impact of five types of interventions on mortality, morbidity (years of life in fair or poor health), and years of healthy life (years in excellent, very good, or good health).

RESULTS: A one-shot intervention that makes all the sick persons healthy at baseline would increase life expectancy by 3 months and increase years of healthy life by 6 months, in a cohort beginning at age 65. An equivalent amount of improvement can be obtained from an intervention that either decreases the probability of getting sick each year by 12\%, increases the probability of a sick person recovering by 16\%, decreases the probability that a sick person dies by 15\%, or decreases the probability that a healthy person dies by 14\%. Interventions aimed at keeping persons healthy increased longevity and years of healthy life, while decreasing morbidity and medical expenditures. Interventions focused on preventing mortality had a greater effect on longevity, but had higher future morbidity and medical expenditures. Results differed for older and younger cohorts and depended on the value to society of an additional year of sick life.

CONCLUSION: Interventions that promote health and prevent disease performed well, but other types of intervention were sometimes better. The value to society of interventions that increase longevity but also increase morbidity needs further research. More comprehensive screening and treatment of new Medicare enrollees might improve their health and longevity without increasing future medical expenditures.

}, keywords = {Actuarial Analysis, Cost-Benefit Analysis, Disease Management, Health Priorities, Health Promotion, Health Services, Health Status, Humans, Life Expectancy, Medicare, Models, Biological, Morbidity, United States, United States Public Health Service}, issn = {1471-2458}, doi = {10.1186/1471-2458-7-52}, author = {Diehr, Paula and Derleth, Ann and Cai, Liming and Newman, Anne B} } @article {948, title = {Ethnic-specific prevalence of peripheral arterial disease in the United States.}, journal = {Am J Prev Med}, volume = {32}, year = {2007}, month = {2007 Apr}, pages = {328-33}, abstract = {

BACKGROUND: Individuals diagnosed with peripheral arterial disease (PAD) are at increased risk for future functional limitations as well as cardiovascular morbidity and mortality. The aim of this study was to estimate the age-, gender-, and ethnic-specific burden of PAD in the United States for the year 2000.

METHODS: Data were collected from seven community-based studies that assessed subjects for the presence of PAD using the ankle-brachial index (ABI). Using standardized weighting criteria, age-, gender-, and ethnic-specific prevalence rates were computed and then multiplied by the corresponding 2000 Census population totals to estimate the burden of PAD in the United States for that year. Evidence-based adjustments for studies which did not consider possible subclavian stenosis, prior revascularization for PAD, or both were employed.

RESULTS: In 2000, it is conservatively estimated that at least 6.8 million (5.8\%) individuals aged 40 years or older had PAD based on an ABI of less than 0.9 or previous revascularization for PAD, and that that there are an additional 1.7 million Americans with PAD but "normal" ABIs. Including this group gives a total of 8.5 million (7.2\%) individuals with PAD.

CONCLUSIONS: Roughly one in 16 individuals residing in the United States in 2000 who were aged 40 years and older had PAD. Clinicians are encouraged to screen for the presence of PAD using the ABI.

}, keywords = {Adult, Aged, Aged, 80 and over, Databases as Topic, Female, Humans, Male, Middle Aged, Peripheral Vascular Diseases, United States}, issn = {0749-3797}, doi = {10.1016/j.amepre.2006.12.010}, author = {Allison, Matthew A and Ho, Elena and Denenberg, Julie O and Langer, Robert D and Newman, Anne B and Fabsitz, Richard R and Criqui, Michael H} } @article {960, title = {Focal atrophy and cerebrovascular disease increase dementia risk among cognitively normal older adults.}, journal = {J Neuroimaging}, volume = {17}, year = {2007}, month = {2007 Apr}, pages = {148-55}, abstract = {

BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer{\textquoteright}s disease (AD) among cognitively normal older adults.

METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60\% women, 81\% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD.

RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95\% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95\% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions.

CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.

}, keywords = {Aged, Alzheimer Disease, Analysis of Variance, Atrophy, Cerebrovascular Disorders, Cognition, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Temporal Lobe, United States}, issn = {1051-2284}, doi = {10.1111/j.1552-6569.2007.00093.x}, author = {Rosano, Caterina and Aizenstein, Howard J and Wu, Minjie and Newman, Anne B and Becker, James T and Lopez, Oscar L and Kuller, Lewis H} } @article {942, title = {Frailty and risk of venous thromboembolism in older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Jan}, pages = {79-82}, abstract = {

BACKGROUND: Frailty is a common risk factor for morbidity and mortality in elderly persons. Recent evidence links frailty to activation of coagulation and inflammatory pathways. We aimed to determine whether frailty in community-dwelling older adults is a risk factor for venous thromboembolism (VTE).

METHODS: We conducted a prospective cohort study in four U.S. communities involving 4859 participants 65 years old and older. At baseline, in 1989-1993, we assessed frailty based on weight loss, grip strength, feelings of exhaustion, walk time, and physical activity. Incident VTE (deep vein thrombosis or pulmonary embolus) through 2002 was identified by review of hospital records.

RESULTS: Fifty-two percent of the sample was classified as having intermediate or definite frailty. After adjustment for age, race, sex, body mass index, and diabetes, the relative risk of total VTE (n = 150) for people who were frail compared with no frailty was 1.31 (95\% confidence interval [CI], 0.93-1.84). The comparably adjusted relative risk for idiopathic VTE (n = 58) was 1.79 (95\% CI, 1.02-3.13).

CONCLUSIONS: The incidence rates of idiopathic VTE was higher in community-dwelling older adults with baseline frailty compared with no frailty. Further studies of the clotting process in frailty may allow the development of an improved strategy to determine VTE risk in this vulnerable subset of older adults.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Frail Elderly, Humans, Male, Morbidity, Motor Activity, Prospective Studies, Risk Factors, Thromboembolism, United States, Venous Thrombosis}, issn = {1079-5006}, doi = {10.1093/gerona/62.1.79}, author = {Folsom, Aaron R and Boland, Lori L and Cushman, Mary and Heckbert, Susan R and Rosamond, Wayne D and Walston, Jeremy D} } @article {1002, title = {Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {29}, year = {2007}, month = {2007}, pages = {193-200}, abstract = {

BACKGROUND: Gait variability is an index of how much gait parameters, such as step length, change from one step to the next. Gait variability increases with age and in individuals affected by cortical and subcortical neurodegenerative conditions, and it is associated with falls and incident mobility disability. The brain anatomical correlates of gait variability have not been studied in high-functioning community-dwelling older adults.

METHODS: Gait variability and brain MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free from stroke, dementia or Parkinson{\textquoteright}s disease. Gait variability was computed for spatial parameters (step length and step width) and for temporal parameters (stance time). Subclinical brain vascular abnormalities were measured on brain MRIs as infarcts and white matter hyperintensities.

RESULTS: Greater variability of step length was associated with greater prevalence of infarcts, including infarcts in the basal ganglia, and with greater white matter hyperintensities severity, independent of age, gender, cognitive function and cardiovascular disease. Weaker associations were found between the other variability measures and the MRI measures.

CONCLUSION: In this group of older adults free from neurodegenerative diseases, a greater variability of step length was associated with greater burden of subclinical brain vascular abnormalities as defined by MRI.

}, keywords = {Accidental Falls, Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebral Infarction, Comorbidity, Female, Gait Disorders, Neurologic, Geriatric Assessment, Health Surveys, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mobility Limitation, Neurodegenerative Diseases, Neurologic Examination, Risk Factors, United States}, issn = {1423-0208}, doi = {10.1159/000111582}, author = {Rosano, Caterina and Brach, Jennifer and Studenski, Stephanie and Longstreth, W T and Newman, Anne B} } @article {964, title = {Individual and neighborhood socioeconomic status and progressive chronic kidney disease in an elderly population: The Cardiovascular Health Study.}, journal = {Soc Sci Med}, volume = {65}, year = {2007}, month = {2007 Aug}, pages = {809-21}, abstract = {

Few studies have focused on the association between socioeconomic status (SES) and progressive chronic kidney disease (pCKD) in an elderly population. We conducted a cohort study of 4735 Cardiovascular Health Study participants, ages 65 and older and living in 4 US communities, to examine the independent risk of pCKD associated with income, education and living in a low SES area. pCKD was defined as creatinine elevation 0.4 mg/dL (35 micromol/L) over a 4-7 year follow-up or CKD hospitalization. Area SES was characterized using measures of income, wealth, education and occupation for 1990 (corresponding to time of enrollment) US Census block groups of residence. Age and study site-adjusted incidence rates (per 1000 person years) of pCKD by quartiles of area-level SES score, income and education showed decreasing rates with increasing SES. Cox proportional hazards models showed that living in the lowest SES area quartile, as opposed to the highest, was associated with 50\% greater risk of pCKD, after adjusting for age, gender, study site, baseline creatinine, and individual-level SES. This increased risk and trend persisted after adjusting for lifestyle risk factors, diabetes and hypertension. We found no significant independent associations between pCKD and individual-level income or education (after adjusting for all other SES factors). As such, living in a low SES area is associated with greater risk of pCKD in an elderly US population.

}, keywords = {Age Factors, Aged, Cohort Studies, Female, Humans, Incidence, Kidney Failure, Chronic, Male, Proportional Hazards Models, Residence Characteristics, Risk Factors, Sex Factors, Social Class, United States}, issn = {0277-9536}, doi = {10.1016/j.socscimed.2007.04.011}, author = {Merkin, Sharon Stein and Diez Roux, Ana V and Coresh, Josef and Fried, Linda F and Jackson, Sharon A and Powe, Neil R} } @article {936, title = {Inflammation biomarkers and near-term death in older men.}, journal = {Am J Epidemiol}, volume = {165}, year = {2007}, month = {2007 Mar 15}, pages = {684-95}, abstract = {

Associations of C-reactive protein (CRP) and fibrinogen with death may weaken over time. Combining both markers may improve prediction of death in older adults. In 5,828 Cardiovascular Health Study participants (United States, 1989-2000), 383 deaths (183 cardiovascular disease (CVD)) in years 1-3 (early) and 914 deaths (396 CVD) in years 4-8 (late) occurred. For men, when comparing highest to lowest quartiles, hazard ratios for early death were 4.1 (95\% confidence interval (CI): 2.7, 6.3) for CRP and 4.1 (95\% CI: 2.7, 6.4) for fibrinogen in models adjusted for CVD risk. For early CVD death, hazard ratios were 4.3 (95\% CI: 2.2, 8.4) and 3.4 (95\% CI: 1.8, 6.3), respectively. When comparing men in the highest quartiles of both biomarkers with those in the lowest, hazard ratios were 9.6 (95\% CI: 4.3, 21.1) for early death and 13.5 (95\% CI: 3.2, 56.5) for early CVD death. Associations were weaker for late deaths. For women, CRP (hazard ratio = 2.3, 95\% CI: 1.4, 3.9), but not fibrinogen (hazard ratio = 1.3, 95\% CI: 0.8, 2.2), was associated with early death. Results were similar for CVD death. Neither was associated with late deaths. CRP and fibrinogen were more strongly associated with death in older men than women and more strongly associated with early than late death. Combining both markers may identify older men at greatest risk of near-term death.

}, keywords = {Age Distribution, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Diabetes Complications, Epidemiologic Studies, Female, Fibrinogen, Follow-Up Studies, Humans, Hypercholesterolemia, Hypertension, Inflammation, Male, Middle Aged, Obesity, Population Surveillance, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Risk Factors, Sex Distribution, Smoking, Time Factors, United States}, issn = {0002-9262}, doi = {10.1093/aje/kwk057}, author = {Jenny, Nancy Swords and Yanez, N David and Psaty, Bruce M and Kuller, Lewis H and Hirsch, Calvin H and Tracy, Russell P} } @article {954, title = {Physical activity and white matter lesion progression: assessment using MRI.}, journal = {Neurology}, volume = {68}, year = {2007}, month = {2007 Apr 10}, pages = {1223-6}, abstract = {

We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.

}, keywords = {Activities of Daily Living, Aged, Alzheimer Disease, Cognition Disorders, Cohort Studies, Demyelinating Diseases, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Motor Activity, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000259063.50219.3e}, author = {Podewils, L J and Guallar, E and Beauchamp, N and Lyketsos, C G and Kuller, L H and Scheltens, P} } @article {963, title = {Socioeconomic position and incident mobility impairment in the Cardiovascular Health Study.}, journal = {BMC Geriatr}, volume = {7}, year = {2007}, month = {2007 May 10}, pages = {11}, abstract = {

BACKGROUND: We investigated if personal socioeconomic position (SEP) factors and neighborhood characteristics were associated with incident mobility impairment in the elderly.

METHODS: We used data from the Cardiovascular Health Study, a longitudinal, population-based examination of coronary heart disease and stroke among persons aged 65 and older in the United States.

RESULTS: Among 3,684 persons without baseline mobility impairment, lower baseline SEP was associated with increased risk of incident mobility disability during the 10-year follow-up period, although the strengths of these associations varied by socioeconomic indicator and race/sex group.

CONCLUSION: Among independent-living elderly, SEP affected development of mobility impairment into later life. Particular effort should be made to prevent or delay its onset among the elderly with low income, education, and/or who live in economically disadvantaged neighborhoods.

}, keywords = {Aged, Aged, 80 and over, Coronary Disease, Disabled Persons, Education, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Mobility Limitation, Residence Characteristics, Social Class, Stroke, United States}, issn = {1471-2318}, doi = {10.1186/1471-2318-7-11}, author = {Nordstrom, Cheryl K and Diez Roux, Ana V and Schulz, Richard and Haan, Mary N and Jackson, Sharon A and Balfour, Jennifer L} } @article {985, title = {USF1 gene variants, cardiovascular risk, and mortality in European Americans: analysis of two US cohort studies.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {27}, year = {2007}, month = {2007 Dec}, pages = {2736-42}, abstract = {

OBJECTIVE: A common haplotype of the upstream transcription factor 1 gene (USF1) has been associated with decreased susceptibility to familial combined hyperlipidemia (FCHL) and, paradoxically, with increased risk of cardiovascular disease (CVD) and all-cause mortality.

METHODS AND RESULTS: We assessed associations between USF1 tagSNPs, CVD risk factors, and aging-related phenotypes using data from 2 large population-based cohorts, Coronary Artery Risk Development in Young Adults (CARDIA) and the Cardiovascular Health Study (CHS), comprising younger and older adults, respectively. In CARDIA, each additional copy of the FCHL low-risk allele was associated with 2.4 mg/dL lower levels of LDL cholesterol (P=0.01) and decreased risk of subclinical atherosclerosis as assessed by coronary artery calcium (odds ratio 0.79; 95\%CI 0.63 to 0.98). Whereas there was little association between USF1 genotype and metabolic or CVD traits in older adults from CHS, the USF1 low-risk dyslipidemia allele was associated with higher plasma C-reactive protein and interleukin (IL)-6 levels and with increased risk of mortality, particularly attributable to noncardiovascular causes.

CONCLUSIONS: There appears to be a complex and possibly age-dependent relationship between USF1 genotype, atherosclerosis phenotypes, and CVD risk. USF1 may influence mortality through pathways distinct from atherosclerosis. Alternatively, linkage disequilibrium with neighboring polymorphisms in other genes such as F11R may be responsible for the observed USF1 genotype-phenotype associations in older adults.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Blood Glucose, C-Reactive Protein, Calcium, Cardiovascular Diseases, Carotid Artery, Common, Cohort Studies, Coronary Artery Disease, Coronary Vessels, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Hyperlipidemia, Familial Combined, Insulin, Interleukin-6, Linkage Disequilibrium, Lipids, Male, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Upstream Stimulatory Factors}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.107.154559}, author = {Reiner, Alexander P and Carlson, Christopher S and Jenny, Nancy S and Durda, J Peter and Siscovick, David S and Nickerson, Deborah A and Tracy, Russell P} } @article {946, title = {Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {49}, year = {2007}, month = {2007 Mar 06}, pages = {972-81}, abstract = {

OBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample.

BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures.

METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167).

RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively.

CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly.

}, keywords = {Age Distribution, Aged, Body Size, Case-Control Studies, Cohort Studies, Comorbidity, Continental Population Groups, Echocardiography, Female, Heart Failure, Heart Ventricles, Humans, Hypertension, Longitudinal Studies, Male, Multivariate Analysis, Prevalence, Regression Analysis, Risk Factors, Sex Distribution, Stroke Volume, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2006.10.061}, author = {Maurer, Mathew S and Burkhoff, Daniel and Fried, Linda P and Gottdiener, John and King, Donald L and Kitzman, Dalane W} } @article {994, title = {Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {167}, year = {2008}, month = {2008 Jan 01}, pages = {34-41}, abstract = {

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95\% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95\% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95\% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

}, keywords = {Aged, Alcohol Drinking, Female, Follow-Up Studies, Health Surveys, Humans, Intermittent Claudication, Male, Prevalence, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwm274}, author = {Mukamal, Kenneth J and Kennedy, Margaret and Cushman, Mary and Kuller, Lewis H and Newman, Anne B and Polak, Joseph and Criqui, Michael H and Siscovick, David S} } @article {995, title = {Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {28}, year = {2008}, month = {2008 Jan}, pages = {173-9}, abstract = {

OBJECTIVE: We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.

METHODS AND RESULTS: Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided P<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HR=1.29; 90\%CI 1.1 to 1.52), VAMP8 (HR=1.2; 90\%CI 1.02 to 1.41), TAS2R50 (HR=1.13; 90\%CI 1 to 1.27), and LPA (HR=1.62; 90\%CI 1.09 to 2.42).

CONCLUSIONS: Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.

}, keywords = {African Americans, Aged, Aged, 80 and over, Coronary Disease, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Myocardial Infarction, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Proportional Hazards Models, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.107.153981}, author = {Shiffman, Dov and O{\textquoteright}Meara, Ellen S and Bare, Lance A and Rowland, Charles M and Louie, Judy Z and Arellano, Andre R and Lumley, Thomas and Rice, Kenneth and Iakoubova, Olga and Luke, May M and Young, Bradford A and Malloy, Mary J and Kane, John P and Ellis, Stephen G and Tracy, Russell P and Devlin, James J and Psaty, Bruce M} } @article {1019, title = {Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study.}, journal = {Thromb Haemost}, volume = {99}, year = {2008}, month = {2008 Feb}, pages = {388-95}, abstract = {

Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5\% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European- (EA) and African-descent (AA) adults (> or = 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807, FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437; each additional copy of the minor allele was associated with 13 mg/dl (95\%CI: 9-16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR = 1.9 (95\%CI: 1.3-2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.

}, keywords = {African Americans, Age Factors, Aged, Brain Ischemia, Cardiovascular Diseases, Carotid Artery Diseases, European Continental Ancestry Group, Female, Fibrinogen, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Myocardial Infarction, Polymorphism, Single Nucleotide, Population Surveillance, Proportional Hazards Models, Prospective Studies, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Stroke, United States}, issn = {0340-6245}, doi = {10.1160/TH07-08-0523}, author = {Carty, Cara L and Cushman, Mary and Jones, Daniel and Lange, Leslie A and Hindorff, Lucia A and Rice, Kenneth and Jenny, Nancy S and Durda, J Peter and Walston, Jeremy and Carlson, Christopher S and Nickerson, Debbie and Tracy, Russell P and Reiner, Alex P} } @article {1011, title = {Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adults.}, journal = {J Thromb Haemost}, volume = {6}, year = {2008}, month = {2008 Apr}, pages = {654-9}, abstract = {

BACKGROUND AND OBJECTIVES: D-dimer is a hemostasis marker that reflects ongoing fibrin formation and degradation. There is significant inter-individual and inter-population variability in D-dimer concentration, but whether genetic factors underlie these differences is largely unknown. We hypothesized that common coagulation gene variants contribute to differences in circulating D-dimer concentration.

METHODS: The setting was European-American (EA; n = 1858) and African-American (AA; n = 327) unrelated older adults from the Cardiovascular Health Study (CHS), in which we genotyped SNPs in 42 genes related to blood coagulation and fibrinolysis.

RESULTS: Several fibrinogen gene polymorphisms, including the Thr312Ala Aalpha chain variant and the FGG-10034 C/T variant, were associated with approximately 20\% higher plasma D-dimer levels in EA (false discovery rate < 5\% for covariate-adjusted model). There was also some evidence that a Pro41Leu variant of the PLAU gene encoding urinary plasminogen activator and non-coding polymorphism of the plasminogen activator inhibitor type 1 gene (SERPINE1) were associated with higher plasma D-dimer in EA. There were no significant associations between the studied coagulation or fibrinolysis gene SNPs and plasma D-dimer levels in the smaller AA sample. However, each standard deviation increase in European ancestry assessed by ancestry-informative gene markers was associated with approximately 10\% lower mean D-dimer levels in AA.

CONCLUSIONS: Together, common coagulation/fibrinolysis gene SNPs explained only approximately 2\% of the variance in plasma D-dimer levels in EA. These findings suggest that the association of D-dimer with risk of vascular outcomes may be mediated largely by environmental factors, other genes, and/or genetic interactions.

}, keywords = {Africa, African Americans, Aged, Aged, 80 and over, Blood Coagulation, Europe, European Continental Ancestry Group, Female, Fibrin Fibrinogen Degradation Products, Fibrinogen, Fibrinolysis, Genotype, Humans, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, Prospective Studies, United States, Urokinase-Type Plasminogen Activator}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2008.02906.x}, author = {Lange, L A and Reiner, A P and Carty, C L and Jenny, N S and Cushman, M and Lange, E M} } @article {986, title = {Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {197}, year = {2008}, month = {2008 Apr}, pages = {922-30}, abstract = {

Common polymorphisms in the CRP gene are associated with plasma CRP levels in population-based studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, noncardiovascular (non-CV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality. CRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of non-CV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95\% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and non-CV mortality in older adults, particularly in self-identified blacks.

}, keywords = {African Americans, Aged, C-Reactive Protein, Cardiovascular Diseases, Cause of Death, Cohort Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Linear Models, Longevity, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2007.08.012}, author = {Hindorff, Lucia A and Rice, Kenneth M and Lange, Leslie A and Diehr, Paula and Halder, Indrani and Walston, Jeremy and Kwok, Pui and Ziv, Elad and Nievergelt, Caroline and Cummings, Steven R and Newman, Anne B and Tracy, Russell P and Psaty, Bruce M and Reiner, Alexander P} } @article {1006, title = {Coronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old.}, journal = {Am J Cardiol}, volume = {101}, year = {2008}, month = {2008 Jan 15}, pages = {186-92}, abstract = {

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95\% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95\% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

}, keywords = {Aged, Aged, 80 and over, Carotid Artery Diseases, Carotid Artery, Common, Carotid Artery, Internal, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, ROC Curve, Severity of Illness Index, Survival Analysis, Ultrasonography, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2007.07.075}, author = {Newman, Anne B and Naydeck, Barbara L and Ives, Diane G and Boudreau, Robert M and Sutton-Tyrrell, Kim and O{\textquoteright}Leary, Daniel H and Kuller, Lewis H} } @article {1020, title = {Dietary fish and omega-3 fatty acid consumption and heart rate variability in US adults.}, journal = {Circulation}, volume = {117}, year = {2008}, month = {2008 Mar 04}, pages = {1130-7}, abstract = {

BACKGROUND: Fish and omega-3 fatty acid consumption reduce risk of cardiac death, but mechanisms are not well established. Heart rate variability (HRV) predicts cardiac death and reflects specific electrophysiological pathways and influences. We hypothesized that habitual consumption of fish and marine omega-3 fatty acids would be associated with more favorable HRV, elucidating electrophysiological influences and supporting effects on clinical risk.

METHODS AND RESULTS: In a population-based cohort of older US adults, we evaluated cross-sectional associations of usual dietary fish and omega-3 consumption during the prior year and ECG-derived (n=4263) and 24-hour Holter monitor-derived (n=1152) HRV. After multivariable adjustment, consumption of tuna or other broiled/baked fish was associated with specific HRV components, including indices suggesting greater vagal predominance and moderated baroreceptor responses (eg, higher root mean square successive differences of normal-to-normal intervals [P=0.001]; higher normalized high-frequency power [P=0.008]; and lower low-frequency/high-frequency ratio [P=0.03]) and less erratic sinoatrial node firing (eg, lower Poincar{\'e} ratio [P=0.02] and higher short-term fractal scaling exponent [P=0.005]) but not measures of circadian fluctuations (eg, 24-hour standard deviation of normal-to-normal intervals). Findings were similar for estimated dietary consumption of marine omega-3 fatty acids. For magnitudes of observed differences in HRV comparing the highest to lowest category of fish intake, differences in relative risk of cardiac death during 10.8 years of follow-up ranged from 1.1\% (for difference in standard deviation of normal-to-normal intervals) to 5.9\% and 8.4\% (for differences in Poincar{\'e} ratio and short-term fractal scaling exponent) lower risk.

CONCLUSIONS: Habitual tuna/other fish and marine omega-3 consumption are associated with specific HRV components in older adults, particularly indices of vagal activity, baroreceptor responses, and sinoatrial node function. Cellular mechanisms and implications for clinical risk deserve further investigation.

}, keywords = {Aged, Aged, 80 and over, Animals, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Electrocardiography, Fatty Acids, Omega-3, Female, Fishes, Heart Rate, Humans, Male, Risk Factors, Seafood, Tuna, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.107.732826}, author = {Mozaffarian, Dariush and Stein, Phyllis K and Prineas, Ronald J and Siscovick, David S} } @article {1036, title = {Hemostatic and inflammatory risk factors for intracerebral hemorrhage in a pooled cohort.}, journal = {Stroke}, volume = {39}, year = {2008}, month = {2008 Aug}, pages = {2268-73}, abstract = {

BACKGROUND AND PURPOSE: The purpose of this study was to identify novel risk factors for intracerebral hemorrhagic stroke (ICH).

METHODS: Risk factors were assessed at baseline in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) involving 21,680 adults aged 45 or over. Over 263,489 person-years of follow-up, we identified 135 incident ICH events.

RESULTS: In multivariable models, for each SD higher baseline level of fibrinogen, the relative rate of incident ICH increased 35\% (95\% CI, 17\% to 55\%). Fibrinogen was more strongly related to ICH in ARIC than in CHS. In multivariable models, those with von Willebrand factor levels above the median were 1.72 (95\% CI, 0.97 to 3.03) times more likely to have an incident ICH as those below the median. Factor VIII was significantly positively related to ICH in ARIC (relative rate per standard deviation of 1.31; 95\% CI, 1.07 to 1.62), but not in CHS. There was no relation in multivariable models between lipoprotein (a), Factor VII, white blood cell count, or C-reactive protein and ICH.

CONCLUSIONS: Greater plasma fibrinogen and, to some degree, von Willebrand factor were associated with increased rates of ICH in these prospective studies, whereas Factor VIII was related to ICH in younger ARIC study participants only.

}, keywords = {Age Distribution, Aged, Biomarkers, C-Reactive Protein, Cerebral Hemorrhage, Cohort Studies, Factor VIII, Female, Fibrinogen, Follow-Up Studies, Humans, Leukocyte Count, Lipoprotein(a), Male, Middle Aged, Multivariate Analysis, Prevalence, Risk Factors, Stroke, United States, Vasculitis, von Willebrand Factor}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.505800}, author = {Sturgeon, Jared D and Folsom, Aaron R and Longstreth, W T and Shahar, Eyal and Rosamond, Wayne D and Cushman, Mary} } @article {1040, title = {High-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Blood}, volume = {112}, year = {2008}, month = {2008 Oct 01}, pages = {2675-80}, abstract = {

We determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL(2), HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.

}, keywords = {Aged, Apolipoprotein A-I, Cholesterol, HDL, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, United States, Venous Thromboembolism}, issn = {1528-0020}, doi = {10.1182/blood-2008-05-157412}, author = {Chamberlain, Alanna M and Folsom, Aaron R and Heckbert, Susan R and Rosamond, Wayne D and Cushman, Mary} } @article {1024, title = {Incident physical disability in people with lower extremity peripheral arterial disease: the role of cardiovascular disease.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Jun}, pages = {1037-44}, abstract = {

OBJECTIVES: To evaluate the risk of incident physical disability and the decline in gait speed over a 6-year follow-up associated with a low ankle-arm index (AAI) in older adults.

DESIGN: Observational cohort study.

SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.

PARTICIPANTS: Four thousand seven hundred five older adults, 58\% women and 17.6\% black, participating in the Cardiovascular Health Study.

MEASUREMENTS: AAI was measured in 1992/93 (baseline). Self-reported mobility, activity of daily living (ADL), and instrumental activity of daily living (IADL) disability and gait speed were recorded at baseline and at 1-year intervals over 6 years of follow-up. Mobility disability was defined as any difficulty walking half a mile and ADL and IADL disability was defined as any difficulty with 11 specific ADL and IADL tasks. Individuals with mobility, ADL, or IADL disability at baseline were excluded from the respective incident disability analyses.

RESULTS: Lower baseline AAI values were associated with increased risk of mobility disability and ADL/IADL disability. Clinical cardiovascular disease (CVD), diabetes mellitus, and interim CVD events partially explained these associations for mobility disability and clinical CVD and diabetes mellitus partially explained these associations for ADL and IADL disability. Individuals with an AAI less than 0.9 had on average a mean decrease in gait speed of 0.02 m/s per year, or a decline of 0.12 m/s over the 6-year follow-up. Prevalent CVD partly explained this decrease but interim CVD events did not further attenuate it.

CONCLUSION: Low AAI serves as marker of future disability risk. Reduction of disability risk in patients with a low AAI should consider cardiovascular comorbidity and the prevention of additional disabling CVD events.

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Cohort Studies, Comorbidity, Disability Evaluation, Female, Gait, Geriatric Assessment, Humans, Lower Extremity, Male, Mobility Limitation, Peripheral Vascular Diseases, Proportional Hazards Models, Risk Assessment, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01719.x}, author = {Brach, Jennifer S and Solomon, Cam and Naydeck, Barbara L and Sutton-Tyrrell, Kim and Enright, Paul L and Jenny, Nancy Swords and Chaves, Paulo M and Newman, Anne B} } @article {1033, title = {Metabolic syndrome and mortality in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {168}, year = {2008}, month = {2008 May 12}, pages = {969-78}, abstract = {

BACKGROUND: The utility of metabolic syndrome (MetS) for predicting mortality among older adults, the highest-risk population, is not well established. In addition, few studies have compared the predictive utility of MetS to that of its individual risk factors.

METHODS: We evaluated relationships of MetS (as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III (ATPIII)], International Diabetes Foundation [IDF], and World Health Organization [WHO]) and individual MetS criteria with mortality between 1989 and 2004 among 4258 US adults 65 years or older and free of prevalent cardiovascular disease (CVD) in the Cardiovascular Health Study, a multicenter, population-based, prospective cohort. Total, CVD, and non-CVD mortality were evaluated. Cox proportional hazards models were used to estimate the mortality hazard ratio (relative risk [RR]) predicted by MetS.

RESULTS: At baseline (mean age, 73 years), 31\% of men and 38\% of women had MetS (ATPIII). During 15 years of follow-up, 2116 deaths occurred. After multivariable adjustment, compared with persons without MetS, those with MetS had a 22\% higher mortality (RR, 1.22; 95\% confidence interval [CI], 1.11-1.34). Higher risk with MetS was confined to persons having elevated fasting glucose level (EFG) (defined as > or = 110 mg/dL [> or = 6.1 mmol/L] or treated diabetes mellitus) (RR, 1.41; 95\% CI, 1.27-1.57) or hypertension (RR, 1.26; 95\% CI, 1.15-1.39) as one of the criteria; persons having MetS without EFG (RR, 0.97; 95\% CI, 0.85-1.11) or MetS without hypertension (RR, 0.92; 95\% CI, 0.71-1.19) did not have higher risk. Evaluating MetS criteria individually, we found that only hypertension and EFG predicted higher mortality; persons having both hypertension and EFG had 82\% higher mortality (RR, 1.82; 95\% CI, 1.58-109). Substantially higher proportions of deaths were attributable to EFG and hypertension (population attributable risk fraction [PAR\%], 22.2\%) than to MetS (PAR\%, 6.3\%). Results were similar when we used WHO or IDF criteria, when we evaluated different cut points of each individual criterion, and when we evaluated CVD mortality.

CONCLUSION: These findings suggest limited utility of MetS for predicting total or CVD mortality in older adults compared with assessment of fasting glucose and blood pressure alone.

}, keywords = {Aged, Aged, 80 and over, Blood Glucose, Fasting, Female, Follow-Up Studies, Humans, Hypertension, Male, Metabolic Syndrome, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Assessment, United States}, issn = {1538-3679}, doi = {10.1001/archinte.168.9.969}, author = {Mozaffarian, Dariush and Kamineni, Aruna and Prineas, Ronald J and Siscovick, David S} } @article {1007, title = {The relationship between exercise and risk of venous thrombosis in elderly people.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Mar}, pages = {517-22}, abstract = {

OBJECTIVES: To study whether exercise is associated with the risk of venous thrombosis in elderly people.

DESIGN: Observational study with a median follow-up of 11.6 years.

SETTING: The Cardiovascular Health Study in four U.S. communities.

PARTICIPANTS: People aged 65 and older without prior venous thrombosis (deep venous thrombosis or pulmonary embolism).

MEASUREMENTS: Self-reported exercise was measured two or three times during follow-up and was defined as expending more than 500 kcal/wk on exercise, including walking for exercise. Venous thrombosis cases were verified using medical record review.

RESULTS: Of 5,534 participants, 171 developed a first venous thrombosis. Self-reported exercise at baseline was not related to the risk of venous thrombosis after adjustment for sex, age, race, self-reported health, and body mass index (adjusted hazard ratio (HR(adj))=1.16, 95\% confidence interval (CI)=0.84-1.61), although with exercise modeled as a time-varying exposure, overall results were in the direction of greater risk of venous thrombosis (HR(adj)=1.38, 95\% CI=0.99-1.91). For mild-intensity exercise, such as walking, there was a nonsignificant finding in the direction of benefit (HR(adj)=0.75, 95\% CI=0.49-1.16), but strenuous exercise, such as jogging, was associated with greater risk of venous thrombosis (HR(adj)=1.75, 95\% CI=1.08-2.83) than no exercise at all.

CONCLUSION: In elderly people, strenuous exercise was associated with a higher risk of venous thrombosis than no exercise at all. Future studies are needed to explain this unexpected higher risk.

}, keywords = {Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Energy Metabolism, Exercise, Female, Humans, Male, Prevalence, Risk Factors, United States, Venous Thrombosis}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01588.x}, author = {van Stralen, Karlijn J and Doggen, Carine J M and Lumley, Thomas and Cushman, Mary and Folsom, Aaron R and Psaty, Bruce M and Siscovick, David and Rosendaal, Frits R and Heckbert, Susan R} } @article {1051, title = {Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association?}, journal = {Sleep}, volume = {31}, year = {2008}, month = {2008 Aug}, pages = {1127-32}, abstract = {

STUDY OBJECTIVES: Epidemiologic studies that demonstrate increased risk of hypertension in persons with sleep disordered breathing indicate that only a minority of these persons report significant subjective sleepiness. Studies also suggest that presence of self-reported sleepiness may identify a subset of persons with sleep disordered breathing who are at greatest risk of cardiovascular sequelae, including hypertension. We explore whether self-reported sleepiness modifies the relationship between sleep disordered breathing and prevalent hypertension.

DESIGN: Cross-sectional.

SETTING: Multicenter study.

PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study.

MEASUREMENTS: Polysomnography, systolic and diastolic blood pressure, antihypertensive medication use, questionnaire determined excessive sleepiness and Epworth Sleepiness Scale, and covariates.

RESULTS: The odds of hypertension at higher apnea hypopnea index categories were larger in participants identified as sleepy based on responses to a frequency of sleepiness question or the Epworth score. For example, for those with AHI > or =30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or =5 days per month, but only 1.22 (0.89-1.68) among those reporting less frequent daytime sleepiness. In adjusted logistic regression models, there was statistical evidence for effect modification by frequency of sleepiness (P = 0.033) of the association between apnea hypopnea index and hypertension. In adjusted models that included the Epworth score as a continuous variable, the interaction term fell slightly short of statistical significance (beta = 0.010, P = 0.07).

CONCLUSION: This study finds that the association of sleep disordered breathing with hypertension is stronger in individuals who report daytime sleepiness than in those who do not.

}, keywords = {Aged, Antihypertensive Agents, Comorbidity, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Health Surveys, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Oxygen, Polysomnography, Sleep Apnea, Obstructive, United States}, issn = {0161-8105}, author = {Kapur, Vishesh K and Resnick, Helaine E and Gottlieb, Daniel J} } @article {1021, title = {Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Apr}, pages = {652-60}, abstract = {

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults.

DESIGN: Cohort study.

SETTING/PARTICIPANTS: One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study.

MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality.

RESULTS: Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95\% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95\% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties.

CONCLUSION: In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Enzyme-Linked Immunosorbent Assay, Fasting, Female, Follow-Up Studies, Hand Strength, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Survival Rate, United States, Walking}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01637.x}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Xue, XiaoNan and Kritchevsky, Stephen B and Newman, Anne B and Psaty, Bruce M} } @article {1000, title = {Weight, mortality, years of healthy life, and active life expectancy in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Jan}, pages = {76-83}, abstract = {

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults.

DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults.

SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.

PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline.

MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated.

RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes.

CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a "healthy" weight may be much higher than currently believed.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Body Mass Index, Body Weight, Female, Health Status Indicators, Humans, Life Expectancy, Life Style, Male, Prognosis, Risk Factors, Sex Factors, Survival Rate, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01500.x}, author = {Diehr, Paula and O{\textquoteright}Meara, Ellen S and Fitzpatrick, Annette and Newman, Anne B and Kuller, Lewis and Burke, Gregory} } @article {1111, title = {Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study.}, journal = {Ophthalmology}, volume = {116}, year = {2009}, month = {2009 Oct}, pages = {1913-9}, abstract = {

PURPOSE: To examine the associations of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and stroke in the Cardiovascular Health Study.

DESIGN: Population-based prospective cohort study.

PARTICIPANTS: A total of 1786 white and African-American participants free of CHD or 2228 participants free of stroke, aged 69 to 97 years.

METHODS: AMD was evaluated from photographs taken in 1997 and 1998.

MAIN OUTCOME MEASURES: Incident CHD and stroke ascertained using standardized methods.

RESULTS: Of the 1786 persons free of CHD, 303 developed incident CHD over 7 years. Participants with early AMD (n = 277) had a higher cumulative incidence of CHD than participants without early AMD (25.8\% vs. 18.9\%, P = 0.001). By adjusting for age, gender, race, systolic and diastolic blood pressure, hypertension status, fasting glucose, triglyceride, low-density lipoprotein cholesterol, cigarette smoking, pack years of smoking, and C-reactive protein, the presence of early AMD was associated with an increased risk of incident CHD (hazard ratio 1.57; 95\% confidence interval, 1.17-2.22). Late AMD (n = 25) was not associated with incident CHD (hazard ratio 0.78; 95\% confidence interval, 0.25-2.48). Among 2228 persons at risk, 198 developed incident stroke; neither early nor late AMD was associated with incident stroke.

CONCLUSIONS: This study suggests persons with early AMD have a higher risk of CHD but not stroke in a population aged 69 to 97 years. This provides further support that AMD is associated with underlying systemic vascular disease.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Blood Pressure, Cholesterol, LDL, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Macular Degeneration, Male, Prospective Studies, Risk Factors, Sex Factors, Stroke, Triglycerides, United States}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2009.03.046}, author = {Sun, Cong and Klein, Ronald and Wong, Tien Y} } @article {1072, title = {Associations of pentraxin 3 with cardiovascular disease and all-cause death: the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {29}, year = {2009}, month = {2009 Apr}, pages = {594-9}, abstract = {

OBJECTIVE: We examined associations of pentraxin 3 (PTX3), a vascular inflammation marker, with incident cardiovascular disease (CVD) and all-cause death.

METHODS AND RESULTS: 1583 Cardiovascular Health Study participants free of prevalent CVD were included. Nonexclusive case groups were angina (n=476), myocardial infarction (MI; n=237), stroke (n=310), CVD death (n=282), and all-cause death (n=772). 535 participants had no events. PTX3 levels were higher in those with subclinical CVD (1.90+/-1.89 ng/mL) than those without (1.71+/-1.88 ng/mL; P=0.001). Using Cox regression adjusted for age, sex, and ethnicity, a standard deviation increase in PTX3 (1.89 ng/mL) was associated with CVD death (hazard ratio 1.11; 95\% confidence interval 1.02 to 1.21) and all-cause death (1.08; 1.02 to 1.15). PTX3 was not associated with angina (1.09; 0.98 to 1.20), MI (0.96; 0.81 to 1.12), or stroke (1.06; 0.95 to 1.18). Adding C-reactive protein (CRP) or CVD risk factors to the models had no significant effects on associations.

CONCLUSIONS: In these older adults, PTX3 was associated with CVD and all-cause death independent of CRP and CVD risk factors. PTX3 likely reflects different aspects of inflammation than CRP and may provide insight into vascular health in aging and chronic diseases of aging that lead to death.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Case-Control Studies, Female, Health Surveys, Humans, Inflammation Mediators, Linear Models, Male, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Serum Amyloid P-Component, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.108.178947}, author = {Jenny, Nancy Swords and Arnold, Alice M and Kuller, Lewis H and Tracy, Russell P and Psaty, Bruce M} } @article {1057, title = {Clinical and subclinical cardiovascular disease and kidney function decline in the elderly.}, journal = {Atherosclerosis}, volume = {204}, year = {2009}, month = {2009 May}, pages = {298-303}, abstract = {

OBJECTIVE: Kidney function decline in elderly persons may be the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline.

METHODS: This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >or=65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration rate (eGFR(creat)) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m(2). Predictors of rapid kidney decline included prevalent and subclinical measures of CVD.

RESULTS: Mean decline in eGFR(creat) was 0.4+/-2.6/year; 714 (16\%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95\% CI: 1.55, 1.16-2.08) and heart failure (OR, 95\% CI: 1.80, 1.40-2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle-arm index <0.9 (OR, 95\% CI: 1.67, 1.25-2.24), common carotid intima-media thickness (>or=1.14 mm) (OR, 95\% CI: 1.52, 1.12-2.06) and internal carotid intima-media thickness (>1.82 mm) (OR, 95\% CI: 1.50, 1.12-2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C.

CONCLUSION: Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis.

}, keywords = {Age Factors, Aged, Atherosclerosis, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Failure, Humans, Kidney, Kidney Diseases, Linear Models, Longitudinal Studies, Male, Odds Ratio, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2008.08.016}, author = {Shlipak, Michael G and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda F and Siscovick, David and Sarnak, Mark J} } @article {1100, title = {Early age-related macular degeneration, cognitive function, and dementia: the Cardiovascular Health Study.}, journal = {Arch Ophthalmol}, volume = {127}, year = {2009}, month = {2009 May}, pages = {667-73}, abstract = {

OBJECTIVE: To describe the association of cognitive function and dementia with early age-related macular degeneration (AMD) in older individuals.

METHODS: This population-based study included 2,088 persons aged 69 to 97 years who participated in the Cardiovascular Health Study. The AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and the Modified Mini-Mental State Examination. Participants were also evaluated for dementia using detailed neuropsychological testing.

RESULTS: After controlling for age, sex, race, and study center, persons with low DSST scores (lowest quartile of scores, < or =30) were more likely to have early AMD (odds ratio, 1.38; 95\% confidence interval, 1.03-1.85) than were persons with higher DSST scores. In analyses further controlling for education, systolic blood pressure, total cholesterol level, diabetes mellitus, smoking status, and apolipoprotein E genotype, this association was stronger (odds ratio, 2.00; 95\% confidence interval, 1.29-3.10). There was no association of low Modified Mini-Mental State Examination scores, dementia, or Alzheimer disease with early AMD.

CONCLUSIONS: In this older population, cognitive impairment may share common age-related pathogenesis and risk factors with early AMD.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition Disorders, Dementia, Female, Humans, Intelligence Tests, Macular Degeneration, Male, Neuropsychological Tests, Odds Ratio, Prospective Studies, Risk Factors, United States}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2009.30}, author = {Baker, Michelle L and Wang, Jie Jin and Rogers, Sophie and Klein, Ronald and Kuller, Lewis H and Larsen, Emily K and Wong, Tien Yin} } @article {1113, title = {External validity of the cardiovascular health study: a comparison with the Medicare population.}, journal = {Med Care}, volume = {47}, year = {2009}, month = {2009 Aug}, pages = {916-23}, abstract = {

BACKGROUND: The Cardiovascular Health Study (CHS), a population-based prospective cohort study, has been used to identify major risk factors associated with cardiovascular disease and stroke in the elderly.

OBJECTIVE: To assess the external validity of the CHS.

RESEARCH DESIGN: Comparison of the CHS cohort to a national cohort of Medicare beneficiaries and to Medicare beneficiaries residing in the CHS geographic regions.

SUBJECTS: CHS participants and a 5\% sample of Medicare beneficiaries.

MEASURES: Demographic and administrative characteristics, comorbid conditions, resource use, and mortality.

RESULTS: Compared with both Medicare cohorts, the CHS cohort was older and included more men and African American participants. CHS participants were more likely to be enrolled in Medicare managed care than beneficiaries in the national Medicare cohort. Compared with the Medicare cohorts, mortality in the CHS was more than 40\% lower at 1 year, approximately 25\% lower at 5 years, and approximately 15\% lower at 10 years. There were minimal differences in comorbid conditions and health care resource use.

CONCLUSION: The CHS cohort is comparable with the Medicare population, particularly with regard to comorbid conditions and resource use, but had lower mortality. The difference in mortality may reflect the CHS recruitment strategy or volunteer bias. These findings suggest it may not be appropriate to project absolute rates of disease and outcomes based on CHS data to the entire Medicare population. However, there is no reason to expect that the relative risks associated with physiologic processes identified by CHS data would differ for nonparticipants.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Humans, Male, Medicare, Randomized Controlled Trials as Topic, Reproducibility of Results, Socioeconomic Factors, United States}, issn = {1537-1948}, doi = {10.1097/MLR.0b013e318197b104}, author = {DiMartino, Lisa D and Hammill, Bradley G and Curtis, Lesley H and Gottdiener, John S and Manolio, Teri A and Powe, Neil R and Schulman, Kevin A} } @article {1064, title = {Gene variants associated with ischemic stroke: the cardiovascular health study.}, journal = {Stroke}, volume = {40}, year = {2009}, month = {2009 Feb}, pages = {363-8}, abstract = {

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.

METHODS: Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).

RESULTS: In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90\% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90\% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10\% versus 6\%) and black (12\% versus 3\%) participants of CHS.

CONCLUSIONS: The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Brain Ischemia, Cardiovascular Diseases, Coronary Disease, Ethnic Groups, European Continental Ancestry Group, Female, Gene Frequency, Genetic Variation, Humans, Kaplan-Meier Estimate, Male, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.108.521328}, author = {Luke, May M and O{\textquoteright}Meara, Ellen S and Rowland, Charles M and Shiffman, Dov and Bare, Lance A and Arellano, Andre R and Longstreth, W T and Lumley, Thomas and Rice, Kenneth and Tracy, Russell P and Devlin, James J and Psaty, Bruce M} } @article {1076, title = {Insomnia did not predict incident hypertension in older adults in the cardiovascular health study.}, journal = {Sleep}, volume = {32}, year = {2009}, month = {2009 Jan}, pages = {65-72}, abstract = {

STUDY OBJECTIVE: We hypothesized that the sleep complaints of insomnia predict incident hypertension, particularly in African Americans. The purpose of this study was to analyze insomnia complaints as predictors of incident hypertension in the Cardiovascular Health Study (CHS), stratifying by gender and allowing for race and sleep variable interaction.

DESIGN: This is a prospective cohort study over a 6-year period of follow-up.

SETTING: This is a community-based study of participants in Forsyth County, North Carolina; Pittsburgh, Pennsylvania; Sacramento County, California; and Washington County, Maryland.

PARTICIPANTS: The study analyzed data from 1419 older individuals (baseline mean age 73.4 +/- 4.4 years) from the Cardiovascular Health Study who were not hypertensive at baseline.

INTERVENTIONS: none.

MEASUREMENTS: We constructed relative risks of incident hypertension over a 6-year period for insomnia complaints singly and in combination.

RESULTS: Difficulty falling asleep, singly or in combination with other sleep complaints, predicted a statistically significant reduction of risk for incident hypertension for non-African American men in 6 years of follow-up. Insomnia complaints did not predict incident hypertension in 6 years of follow-up in women or in African Americans, although there may not have been enough power to show a significant association for African Americans.

CONCLUSIONS: Insomnia did not predict hypertension in this older cohort which was free of hypertension at baseline. Difficulty falling asleep was associated with reduced risk of hypertension in non-African American men.

}, keywords = {African Americans, Aged, Cohort Studies, Comorbidity, European Continental Ancestry Group, Female, Follow-Up Studies, Health Surveys, Humans, Hypertension, Male, Prospective Studies, Risk Factors, Sleep Initiation and Maintenance Disorders, United States}, issn = {0161-8105}, author = {Phillips, Barbara and B{\r u}zkov{\'a}, Petra and Enright, Paul} } @article {1136, title = {Left atrial volume and geometry in healthy aging: the Cardiovascular Health Study.}, journal = {Circ Cardiovasc Imaging}, volume = {2}, year = {2009}, month = {2009 Jul}, pages = {282-9}, abstract = {

BACKGROUND: The left atrium is a validated marker of clinical and subclinical cardiovascular disease. Left atrial enlargement is often seen among older individuals; however, there are few population-based data regarding normal left atrial size among older persons, especially from those who are healthy, and from women. Furthermore, because the left atrium is a 3D structure, the commonly used parasternal long-axis diastolic diameter often underdiagnoses left atrial enlargement.

METHODS AND RESULTS: We evaluated left atrial size in 230 healthy participants (mean age, 76+/-5 years) free of prevalent cardiac disease, rhythm abnormality, hypertension, and diabetes selected from the Cardiovascular Health Study, a prospective community-based study of risk factors for cardiovascular disease in 5888 elderly participants. In addition to the standard long-axis measurement, we obtained left atrial superoinferior and lateral diameters and used these dimensions to estimate left atrial volume. These measurements were used to generate reference ranges for determining left atrial enlargement in older men and women, based on the 95\% percentiles of the left atrial dimensions in healthy participants, both unadjusted, and after adjustment for age, height, and weight. In healthy elderly subjects, indices of left atrial size do not correlate with age or height but with weight and other measures of body build.

CONCLUSIONS: These data provide normative reference values for left atrial size in healthy older women and men. The results should be useful for refining diagnostic criteria for left atrial dilation in the older population and may be relevant for cardiovascular risk stratification.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Atrial Function, Left, Body Size, Body Surface Area, Echocardiography, Three-Dimensional, Female, Heart Atria, Humans, Linear Models, Male, Models, Biological, Organ Size, Population Surveillance, Prospective Studies, Reference Values, Sex Factors, United States}, issn = {1942-0080}, doi = {10.1161/CIRCIMAGING.108.826602}, author = {Aurigemma, Gerard P and Gottdiener, John S and Arnold, Alice M and Chinali, Marcello and Hill, Jeffrey C and Kitzman, Dalane} } @article {1095, title = {Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Apr 27}, pages = {798-807}, abstract = {

BACKGROUND: The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults.

METHODS: We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989-1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73 [6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels.

RESULTS: During 34,539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35\% lower (relative risk, 0.65; 95\% confidence interval, 0.59-0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82\% lower incidence of diabetes (relative risk, 0.18; 95\% confidence interval, 0.06-0.56) compared with all other participants. When absence of adiposity (either body mass index <25 or waist circumference < or =88/92 cm for women/men) was added to the other 4 low-risk lifestyle factors, incidence of diabetes was 89\% lower (relative risk, 0.11; 95\% confidence interval, 0.01-0.76). Overall, 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors. Associations were slightly attenuated, but still highly significant, for incident diabetes defined by medication use or glucose level.

CONCLUSION: Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus.

}, keywords = {Age of Onset, Aged, Aged, 80 and over, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Life Style, Male, National Heart, Lung, and Blood Institute (U.S.), Prospective Studies, Risk Factors, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.21}, author = {Mozaffarian, Dariush and Kamineni, Aruna and Carnethon, Mercedes and Djouss{\'e}, Luc and Mukamal, Kenneth J and Siscovick, David} } @article {1135, title = {Lipoprotein-associated phospholipase A(2) and risk of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {2}, year = {2009}, month = {2009 Sep}, pages = {429-36}, abstract = {

BACKGROUND: Inflammation may be a causative factor in congestive heart failure (CHF). Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammation marker associated with vascular risk. One previous study showed an association of Lp-PLA(2) activity with CHF risk, but there were only 94 CHF cases and Lp-PLA(2) antigen, which is available clinically in the United States, was not measured.

METHODS AND RESULTS: We measured baseline Lp-PLA(2) antigen and activity in 3991 men and women without baseline CHF or cardiovascular disease who were participating in the Cardiovascular Health Study, a prospective observational study of adults 65 years or older. Cox proportional hazards models adjusted for age, sex, clinic site, race, low-density and high-density lipoprotein cholesterol, body mass index, systolic and diastolic blood pressure, hypertension, smoking status, pack-years, and diabetes were used to calculate hazard ratios and 95\% CIs for incident CHF. Further models adjusted for coronary disease events during follow-up and C-reactive protein. Eight hundred twenty-nine participants developed CHF during 12.1 years. Adjusted hazard ratios for CHF with Lp-PLA(2) in the fourth compared with the first quartile were 1.44 (95\% CI, 1.16 to 1.79) for Lp-PLA(2) antigen and 1.06 (95\% CI, 0.84 to 1.32) for activity. Adjustment for incident coronary disease attenuated the hazard ratio for Lp-PLA(2) antigen to 1.26 (95\% CI, 1.02 to 1.57), adjustment for C-reactive protein had minimal impact.

CONCLUSIONS: Lp-PLA(2) antigen was associated with risk of future CHF in older people, independent of CHF and coronary risk factors, and partly mediated by coronary disease events. Further clinical and basic research is needed to better understand the role of Lp-PLA(2) in CHF.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Biomarkers, C-Reactive Protein, Female, Fibrinogen, Heart Failure, Humans, Incidence, Inflammation Mediators, Interleukin-6, Kaplan-Meier Estimate, Male, Population Surveillance, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.108.839613}, author = {Suzuki, Takeki and Solomon, Cam and Jenny, Nancy Swords and Tracy, Russell and Nelson, Jeanenne J and Psaty, Bruce M and Furberg, Curt and Cushman, Mary} } @article {1075, title = {Long-term function in an older cohort--the cardiovascular health study all stars study.}, journal = {J Am Geriatr Soc}, volume = {57}, year = {2009}, month = {2009 Mar}, pages = {432-40}, abstract = {

OBJECTIVES: To evaluate shared and unique risk factors for maintaining physical and cognitive function into the ninth decade and beyond.

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: One thousand six hundred seventy-seven participants in the Cardiovascular Health Study All Stars Study, assessed in 2005/06. Median age was 85 (range 77-102), 66.5\% were women, and 16.6\% were black.

MEASUREMENTS: Intact function was defined as no difficulty with any activities of daily living and a score of 80 or higher on the Modified Mini-Mental State Examination. Baseline characteristics assessed in 1992/93 included demographics, behavioral health factors, chronic disease history, subclinical disease markers, cardiovascular risk factors, and inflammatory markers. Multinomial logistic regression was used to compare risk for physical disability, cognitive impairment,and combined impairments with no functional impairment.

RESULTS: Of the 1,677 participants evaluated in both domains, 891 (53\%) were functionally intact. Continuous measures of function, including the Digit Symbol Substitution Test and gait speed, showed that all groups, including the most functional, had declined over time. The functional group had less decline but also tended to have higher starting values. Functional individuals had a higher baseline health profile than those with either or cognitive impairment or both impairments combined. Women and individuals with greater weight had higher rates of physical impairment but not cognitive impairment. Risk factors common to both types of impairment included cardiovascular disease and hypertension.

CONCLUSION: Intact function was found in only approximately half of these older adults in the ninth decade and beyond. High baseline function and low vascular disease risk characterized functional aging.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Attention, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Comorbidity, Cross-Sectional Studies, Female, Follow-Up Studies, Gait, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Male, Memory, Short-Term, Mental Status Schedule, Proportional Hazards Models, Psychometrics, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.02152.x}, author = {Newman, Anne B and Arnold, Alice M and Sachs, Michael C and Ives, Diane G and Cushman, Mary and Strotmeyer, Elsa S and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Fried, Linda P and Robbins, John} } @article {1119, title = {Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 Oct}, pages = {1639-48}, abstract = {

BACKGROUND: Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin.

OBJECTIVES: We evaluated the relationship of basal peak thrombin generation with the risk of future venous thromboembolism (VTE), and determined whether associations were independent of other coagulation markers.

METHODS: The Longitudinal Investigation of Thromboembolism Etiology (LITE) study investigated VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case-control sample (434 cases and 1004 controls). Logistic regression was used to estimate the relationship of peak thrombin generation with VTE, adjusted for age, sex, race, center, and body mass index. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer.

RESULTS: Relative to the first quartile of peak thrombin generation, the odds ratio (OR) of VTE for those above the median was 1.74 [95\% confidence interval (CI) 1.28-2.37]. The association was modestly attenuated by adjustment for FVIII and D-dimer (OR 1.47, 95\% CI 1.05-2.05). Associations appeared to be stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with FV Leiden or low activated partial thromboplastin time.

CONCLUSIONS: In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independently of established VTE risk factors.

}, keywords = {Adult, Aged, Biomarkers, Blood Coagulation Factors, Case-Control Studies, Ethnic Groups, Factor VIII, Female, Fibrin Fibrinogen Degradation Products, Humans, Male, Middle Aged, Partial Thromboplastin Time, Prospective Studies, Risk Factors, Thrombin, United States, Venous Thromboembolism}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2009.03561.x}, author = {Lutsey, P L and Folsom, A R and Heckbert, S R and Cushman, M} } @article {1093, title = {Prevalence of hearing loss in Black and White elders: results of the Cardiovascular Health Study.}, journal = {J Speech Lang Hear Res}, volume = {52}, year = {2009}, month = {2009 Aug}, pages = {973-89}, abstract = {

PURPOSE: The goal of this study was to determine the impact of age, gender, and race on the prevalence and severity of hearing loss in elder adults, aged 72-96 years, after accounting for income, education, smoking, and clinical and subclinical cardiovascular disease. Methods Air-conduction thresholds for standard and extended high-frequency pure-tones were obtained from a cohort of 548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and cardiovascular disease histories were obtained from the CHS database and were included as factors.

RESULTS: Hearing loss was more common and more severe for the participants in their 80s than for those in their 70s-the men more than the women and the White participants more than the Black participants. The inclusion of education, income, smoking, and cardiovascular disease (clinical and subclinical) histories as factors did not substantively impact the overall results.

CONCLUSION: Although the data reported in this article were cross-sectional and a cohort phenomenon might have been operational, they suggested that hearing loss is more substantive in the 8th than the 7th decade of life and that race and gender influence this decline in audition. Given the high prevalence in the aging population and the differences across groups, there is a clear need to understand the nature and causes of hearing loss across various groups in order to improve prevention and develop appropriate interventions.

}, keywords = {African Americans, Aged, Aged, 80 and over, Aging, Auditory Threshold, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, European Continental Ancestry Group, Female, Hearing Loss, Hearing Tests, Humans, Male, Occupations, Prevalence, Sex Characteristics, Smoking, Socioeconomic Factors, United States}, issn = {1092-4388}, doi = {10.1044/1092-4388(2009/08-0026)}, author = {Pratt, Sheila R and Kuller, Lewis and Talbott, Evelyn O and McHugh-Pemu, Kathleen and Buhari, Alhaji M and Xu, Xiaohui} } @article {1083, title = {Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {179}, year = {2009}, month = {2009 Jun 15}, pages = {1159-64}, abstract = {

RATIONALE: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.

OBJECTIVES: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.

METHODS: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.

MEASUREMENTS AND MAIN RESULTS: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95\% confidence interval, 0.93-2.47) does not exclude the possibility of a modest association.

CONCLUSIONS: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded.

}, keywords = {Adult, Blood Pressure, Confidence Intervals, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Middle Aged, Odds Ratio, Polysomnography, Prognosis, Prospective Studies, Risk Factors, Sleep Apnea Syndromes, Time Factors, United States}, issn = {1535-4970}, doi = {10.1164/rccm.200712-1809OC}, author = {O{\textquoteright}Connor, George T and Caffo, Brian and Newman, Anne B and Quan, Stuart F and Rapoport, David M and Redline, Susan and Resnick, Helaine E and Samet, Jonathan and Shahar, Eyal} } @article {1090, title = {Race, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {103}, year = {2009}, month = {2009 Apr 15}, pages = {1120-7}, abstract = {

In patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults > or =65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15\% to 20\% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Continental Population Groups, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Male, Proportional Hazards Models, Sex Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2008.12.043}, author = {Parashar, Susmita and Katz, Ronit and Smith, Nicholas L and Arnold, Alice M and Vaccarino, Viola and Wenger, Nanette K and Gottdiener, John S} } @article {1144, title = {Rapid decline of kidney function increases cardiovascular risk in the elderly.}, journal = {J Am Soc Nephrol}, volume = {20}, year = {2009}, month = {2009 Dec}, pages = {2625-30}, abstract = {

Chronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C-based estimated GFR as >3 ml/min per 1.73 m(2)/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24\%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95\% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95\% CI 1.21 to 1.83), and PAD (HR 1.67; 95\% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95\% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Failure, Humans, Longitudinal Studies, Male, Myocardial Infarction, Peripheral Vascular Diseases, Renal Insufficiency, Chronic, Risk Factors, Stroke, Time Factors, United States}, issn = {1533-3450}, doi = {10.1681/ASN.2009050546}, author = {Shlipak, Michael G and Katz, Ronit and Kestenbaum, Bryan and Siscovick, David and Fried, Linda and Newman, Anne and Rifkin, Dena and Sarnak, Mark J} } @article {1146, title = {Sibling history of myocardial infarction or stroke and risk of cardiovascular disease in the elderly: the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {19}, year = {2009}, month = {2009 Dec}, pages = {858-66}, abstract = {

PURPOSE: To assess the relationship between sibling history of myocardial infarction (MI) or stroke with cardiovascular disease (CVD) and risk factors in older adults.

METHODS: Prospective cohort study of 5,888 older adults participating in the Cardiovascular Health Study (CHS). History of MI and stroke in siblings was obtained by self-report. Participants with positive sibling histories were compared to those with negative histories to determine if prevalent or incident disease (coronary heart disease [CHD], MI, stroke, angina), subclinical CVD (carotid wall thickness, left ventricular mass, hypertension, diabetes, ankle-brachial index), CVD risk factors differed between groups.

RESULTS: More than 91\% (n = 5,383) of CHS participants reported at least one sibling. Sibling history of MI was associated with increased disease prevalence (CHD, MI, angina) and incidence (CHD, angina). Sibling history of stroke was associated with increased disease prevalence (CHD, angina). Sibling history of either MI or stroke was associated with increased disease prevalence and incidence for CHD, MI and angina, more subclinical disease, and a higher CVD risk profile.

CONCLUSIONS: Sibling history of MI and stroke were markers of higher CVD risk status even in older adults. Of clinical importance, participants with positive sibling history have numerous risk factors amenable to intervention.

}, keywords = {Aged, Atherosclerosis, Female, Genetic Predisposition to Disease, Humans, Incidence, Male, Myocardial Infarction, Odds Ratio, Prevalence, Prospective Studies, Risk Factors, Siblings, Stroke, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2009.07.095}, author = {Yanez, N David and Burke, Gregory L and Manolio, Teri and Gardin, Julius M and Polak, Joseph} } @article {1124, title = {Total and cause-specific mortality in the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Dec}, pages = {1251-61}, abstract = {

BACKGROUND: Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.

METHODS: A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.

RESULTS: Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E epsilon4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.

CONCLUSIONS: In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cause of Death, Chronic Disease, Cohort Studies, Female, Geriatric Assessment, Health Surveys, Humans, Kaplan-Meier Estimate, Male, Probability, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp127}, author = {Newman, Anne B and Sachs, Michael C and Arnold, Alice M and Fried, Linda P and Kronmal, Richard and Cushman, Mary and Psaty, Bruce M and Harris, Tamara B and Robbins, John A and Burke, Gregory L and Kuller, Lewis H and Lumley, Thomas} } @article {1123, title = {Trajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Dec}, pages = {1268-74}, abstract = {

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual{\textquoteright}s ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging.

METHODS: Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged >or=65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points.

RESULTS: Overall, there was a slight decline in DHEAS levels over time (-0.013 microg/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p < .001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32-2.33) and extreme variability (HR 1.89, CI 1.47-2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88-1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p < .001).

CONCLUSIONS: Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Cardiovascular Diseases, Cause of Death, Cohort Studies, Dehydroepiandrosterone Sulfate, Female, Geriatric Assessment, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp129}, author = {Cappola, Anne R and O{\textquoteright}Meara, Ellen S and Guo, Wensheng and Bartz, Traci M and Fried, Linda P and Newman, Anne B} } @article {1097, title = {Using telephone and informant assessments to estimate missing Modified Mini-Mental State Exam scores and rates of cognitive decline. The cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {33}, year = {2009}, month = {2009}, pages = {55-65}, abstract = {

AIM: To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores.

METHODS: Comparability study on a subset of 405 participants, aged >or=70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants.

RESULTS: The TICS explained 67\% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered.

CONCLUSIONS: 3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Interviews as Topic, Longitudinal Studies, Male, Predictive Value of Tests, Psychiatric Status Rating Scales, Regression Analysis, Risk Factors, ROC Curve, United States}, issn = {1423-0208}, doi = {10.1159/000215830}, author = {Arnold, Alice M and Newman, Anne B and Dermond, Norma and Haan, Mary and Fitzpatrick, Annette} } @article {1210, title = {Association between adiposity in midlife and older age and risk of diabetes in older adults.}, journal = {JAMA}, volume = {303}, year = {2010}, month = {2010 Jun 23}, pages = {2504-12}, abstract = {

CONTEXT: Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults.

OBJECTIVE: To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older.

DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later.

MAIN OUTCOME MEASURE: Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater.

RESULTS: Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95\% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95\% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95\% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95\% CI, 2.8-6.4) for weight, 4.0 (95\% CI, 2.6-6.0) for fat mass, 4.2 (95\% CI, 2.8-6.2) for waist circumference, 2.4 (95\% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95\% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (+/-2 kg), those who gained the most weight from 50 years of age to baseline (> or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95\% CI, 1.9-4.3) and 2.0 (95\% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95\% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less.

CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes.

}, keywords = {Adiposity, Age Factors, Aged, Body Mass Index, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States, Weight Gain}, issn = {1538-3598}, doi = {10.1001/jama.2010.843}, author = {Biggs, Mary L and Mukamal, Kenneth J and Luchsinger, Jos{\'e} A and Ix, Joachim H and Carnethon, Mercedes R and Newman, Anne B and de Boer, Ian H and Strotmeyer, Elsa S and Mozaffarian, Dariush and Siscovick, David S} } @article {1162, title = {Association of Holter-based measures including T-wave alternans with risk of sudden cardiac death in the community-dwelling elderly: the Cardiovascular Health Study.}, journal = {J Electrocardiol}, volume = {43}, year = {2010}, month = {2010 May-Jun}, pages = {251-9}, abstract = {

BACKGROUND: Sudden cardiac death (SCD) can be the first manifestation of cardiovascular disease. Development of screening methods for higher/lower risk is critical.

METHODS: The Cardiovascular Health Study is a population-based study of risk factors for coronary heart disease and stroke those 65 years or older. Forty-nine (of 1649) with usable Holters and in normal sinus rhythm had SCD during follow-up and were matched with 2 controls, alive at the time of death of the case and not experiencing SCD on follow-up. Univariate and multivariate conditional logistic regression determined the association of Holter-based information and SCD.

RESULTS: In univariate models, the upper half of ventricular premature contraction (VPC) counts, abnormal heart rate turbulence, decreased normalized low-frequency power, increased T-wave alternans (TWA), and decreased the short-term fractal scaling exponent (DFA(1)) were associated with SCD, but time domain heart rate variability was not. In multivariate models, the upper half of VPC counts (odds ratio [OR], 6.6) and having TWA of 37 muV or greater on channel 2 (OR, 4.8) were independently associated with SCD. Also, the upper half of VPC counts (OR, 6.9) and having a DFA(1) of less than 1.05 (OR, 5.0) were independently associated with SCD. When additive effects were explored, having both higher VPCs and higher TWA was associated with an OR of 8.2 for SCD compared with 2.6 for having either. Also, having both higher VPCs and lower DFA(1) was associated with an OR of 9.6 for SCD compared with 3.1 for having either.

CONCLUSIONS: Results support a potential role for 24-hour Holter recordings to identify older adults at increased or lower risk of SCD.

}, keywords = {Comorbidity, Coronary Artery Disease, Death, Sudden, Cardiac, Electrocardiography, Ambulatory, Female, Humans, Male, Prevalence, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sensitivity and Specificity, Survival Analysis, Survival Rate, United States, Ventricular Premature Complexes}, issn = {1532-8430}, doi = {10.1016/j.jelectrocard.2009.12.009}, author = {Stein, Phyllis K and Sanghavi, Devang and Sotoodehnia, Nona and Siscovick, David S and Gottdiener, John} } @article {1245, title = {Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.}, journal = {JAMA}, volume = {304}, year = {2010}, month = {2010 Dec 08}, pages = {2494-502}, abstract = {

CONTEXT: Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk for hospitalization or death.

OBJECTIVES: To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death.

DESIGN, SETTING, AND PARTICIPANTS: A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n = 2918).

MAIN OUTCOME MEASURES: New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors.

RESULTS: Cardiac troponin T was detectable (>=3.00 pg/mL) in 2794 participants (66.2\%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95\% confidence interval [CI], 5.8-7.2; adjusted hazard ratio [aHR], 2.48; 95\% CI, 2.04-3.00) for HF and an incidence rate of 4.8 (95\% CI, 4.3-5.4; aHR, 2.91; 95\% CI, 2.37-3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95\% CI, 1.4-1.8 and 1.1; 95\% CI, 0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50\% (n = 393, 22\%) was associated with a greater risk for HF (aHR, 1.61; 95\% CI, 1.32-1.97) and cardiovascular death (aHR, 1.65; 95\% CI, 1.35-2.03) and a decrease of more than 50\% (n = 247, 14\%) was associated with a lower risk for HF (aHR, 0.73; 95\% CI, 0.54-0.97) and cardiovascular death (aHR, 0.71; 95\% CI, 0.52-0.97) compared with participants with 50\% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death.

CONCLUSION: In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Heart Failure, Humans, Incidence, Male, Predictive Value of Tests, Risk, Sensitivity and Specificity, Troponin T, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1708}, author = {deFilippi, Christopher R and de Lemos, James A and Christenson, Robert H and Gottdiener, John S and Kop, Willem J and Zhan, Min and Seliger, Stephen L} } @article {1202, title = {Associations of PM10 with sleep and sleep-disordered breathing in adults from seven U.S. urban areas.}, journal = {Am J Respir Crit Care Med}, volume = {182}, year = {2010}, month = {2010 Sep 15}, pages = {819-25}, abstract = {

RATIONALE: Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17\% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood.

OBJECTIVES: We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older.

METHODS: Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90\% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects).

MEASUREMENTS AND MAIN RESULTS: In summer, increases in RDI or percentage of sleep time at less than 90\% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5\% (95\% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5{\textdegree}F) in temperature.

CONCLUSIONS: Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk.

}, keywords = {Adult, Aged, Aged, 80 and over, Air Pollutants, Air Pollution, Cities, Cohort Studies, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Particle Size, Particulate Matter, Polysomnography, Seasons, Severity of Illness Index, Sleep, Sleep Apnea Syndromes, Temperature, United States, Urban Health}, issn = {1535-4970}, doi = {10.1164/rccm.200912-1797OC}, author = {Zanobetti, Antonella and Redline, Susan and Schwartz, Joel and Rosen, Dennis and Patel, Sanjay and O{\textquoteright}Connor, George T and Lebowitz, Michael and Coull, Brent A and Gold, Diane R} } @article {1094, title = {Body weight dynamics and their association with physical function and mortality in older adults: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Jan}, pages = {63-70}, abstract = {

BACKGROUND: To estimate the associations of weight dynamics with physical functioning and mortality in older adults.

METHODS: Longitudinal cohort study using prospectively collected data on weight, physical function, and health status in four U.S. Communities in the Cardiovascular Health Study. Included were 3,278 participants (2,013 women and 541 African Americans), aged 65 or older at enrollment, who had at least five weight measurements. Weight was measured at annual clinic visits between 1992 and 1999, and summary measures of mean weight, coefficient of variation, average annual weight change, and episodes of loss and gain (cycling) were calculated. Participants were followed from 1999 to 2006 for activities of daily living (ADL) difficulty, incident mobility limitations, and mortality.

RESULTS: Higher mean weight, weight variability, and weight cycling increased the risk of new onset of ADL difficulties and mobility limitations. After adjustment for risk factors, the hazard ratio (95\% confidence interval) for weight cycling for incident ADL impairment was 1.28 (1.12, 1.47), similar to that for several comorbidities in our model, including cancer and diabetes. Lower weight, weight loss, higher variability, and weight cycling were all risk factors for mortality, after adjustment for demographic risk factors, height, self-report health status, and comorbidities.

CONCLUSIONS: Variations in weight are important indicators of future physical limitations and mortality in the elderly and may reflect difficulties in maintaining homeostasis throughout older ages. Monitoring the weight of an older person for fluctuations or episodes of both loss and gain is an important aspect of geriatric care.

}, keywords = {Activities of Daily Living, Age Factors, Aged, 80 and over, Body Weight, Cardiovascular Diseases, Female, Follow-Up Studies, Health Status, Humans, Longevity, Male, Prospective Studies, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp050}, author = {Arnold, Alice M and Newman, Anne B and Cushman, Mary and Ding, Jingzhong and Kritchevsky, Stephen} } @article {1168, title = {Cardiovascular disease is associated with greater incident dehydroepiandrosterone sulfate decline in the oldest old: the cardiovascular health study all stars study.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Mar}, pages = {421-6}, abstract = {

OBJECTIVES: To describe cross-sectional and longitudinal associations with dehydroepiandrosterone sulfate (DHEAS) and change in DHEAS with age.

DESIGN: Longitudinal cohort study.

SETTING: Pittsburgh, Pennsylvania.

PARTICIPANTS: Cardiovascular Health Study All Stars study participants assessed in 2005/06 (N=989, mean age 85.2, 63.5\% women, 16.5\% African American).

MEASUREMENTS: Health characteristics were assessed in 2005/06 according to DHEAS level, mean DHEAS and DHEAS change across age categories were tested, and linear and logistic regression was used to identify factors present in 1996/97 associated with continuous and categorical DHEAS change.

RESULTS: Mean +/- standard deviation DHEAS was 0.555 +/- 0.414 microg/mL in 1996/97 and 0.482 +/- 0.449 microg/mL in 2005/06 for women and 0.845 +/- 0.520 microg/mL in 1996/97 and 0.658 +/- 0.516 microg/mL in 2005/06 for men. In 2005/06, DHEAS was lower in women and subjects with cardiovascular disease (CVD) and chronic pulmonary disease and higher for African Americans and subjects with hypertension and high cholesterol. Mean DHEAS change was greater in men (-0.200 microg/mL) than in women (-0.078 microg/mL) (P<.001). Each 1-year increase in age attenuated the effect of male sex by 0.01 microg/mL (P=.009), abolishing the sex difference in DHEAS change by age 79. Presence of CVD before the study period was associated with greater absolute DHEAS change (beta=-0.04 microg/mL, P=.04) and with the fourth quartile of DHEAS change versus the first to third quartiles (odds ratio=1.46, 95\% confidence interval=1.03-2.05).

CONCLUSION: DHEAS change continues into very old age, is not homogenous, is affected by sex, and is associated with prevalent CVD. Future studies should investigate factors that might accelerate DHEAS decline.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Dehydroepiandrosterone Sulfate, Female, Humans, Longitudinal Studies, Male, Multivariate Analysis, Regression Analysis, Sex Distribution, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.02724.x}, author = {Sanders, Jason L and Boudreau, Robert M and Cappola, Anne R and Arnold, Alice M and Robbins, John and Cushman, Mary and Newman, Anne B} } @article {1214, title = {Change in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Nov}, pages = {1208-14}, abstract = {

BACKGROUND: Cross-sectional studies show that adiponectin is higher in older than in younger adults but long-term change in adiponectin, its determinants, and its relationship to functional decline or survival in the elderly population have not been evaluated.

METHODS: We investigated predictors of longitudinal change in adiponectin, and the association of this adipokine or its antecedent change with physical deterioration and all-cause mortality in 988 participants in a population-based study who completed examinations in 1996-1997 and 2005-2006, had serial adiponectin measurements and underwent follow-up through June 2009.

RESULTS: Adiponectin level rose significantly during follow-up, but the increase was smaller in blacks, was associated with declining weight or fasting glucose and, in men, lower albumin, and was affected by medications. Adiponectin was independently associated with greater physical decline, but the relationship for adiponectin change was driven by concomitant weight decrease. Both adiponectin and its change independently predicted mortality, even after adjustment for weight change. The association for adiponectin and mortality was observed in whites but not in blacks and only for levels in the upper range (hazard ratio = 1.85, 95\% confidence interval = 1.36-2.52 per SD >= 20 mg/L), whereas that for adiponectin change was linear throughout in both racial groups (hazard ratio = 1.30, 95\% confidence interval = 1.10-1.52 per SD).

CONCLUSIONS: Adiponectin levels increase over time in long-lived adults and are associated with greater physical disability and mortality. Such increases may occur in response to age-related homeostatic dysregulation. Additional investigation is required to define the underlying mechanisms and whether this represents a marker or causal factor for mortality in this age group.

}, keywords = {Adiponectin, Age Factors, Aged, Aging, Analysis of Variance, Cardiovascular Diseases, Cause of Death, Chi-Square Distribution, Cohort Studies, Cross-Sectional Studies, Female, Health Status, Humans, Linear Models, Male, Physical Fitness, Proportional Hazards Models, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glq122}, author = {Kizer, Jorge R and Arnold, Alice M and Strotmeyer, Elsa S and Ives, Diane G and Cushman, Mary and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Hirsch, Calvin H and Newman, Anne B} } @article {1145, title = {Combined association of lipids and blood pressure in relation to incident cardiovascular disease in the elderly: the cardiovascular health study.}, journal = {Am J Hypertens}, volume = {23}, year = {2010}, month = {2010 Feb}, pages = {161-7}, abstract = {

BACKGROUND: Hypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events.

METHODS: We studied 4,311 participants aged 65-98 (61.2\% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years.

RESULTS: CVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >or=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl and 2.1 when BP >or=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP.

CONCLUSION: Increased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Female, Health Surveys, Humans, Likelihood Functions, Lipids, Male, Proportional Hazards Models, Sex Factors, Smoking, Socioeconomic Factors, United States}, issn = {1941-7225}, doi = {10.1038/ajh.2009.216}, author = {Wong, Nathan D and Lopez, Victor A and Roberts, Craig S and Solomon, Henry A and Burke, Gregory L and Kuller, Lewis and Tracy, Russell and Yanez, David and Psaty, Bruce M} } @article {1178, title = {Commentary on "Developing a national strategy to prevent dementia: Leon Thal Symposium 2009." Dementia risk indices: A framework for identifying individuals with a high dementia risk.}, journal = {Alzheimers Dement}, volume = {6}, year = {2010}, month = {2010 Mar}, pages = {138-41}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Diagnosis, Differential, Disability Evaluation, Early Diagnosis, Humans, National Health Programs, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.01.005}, author = {Barnes, Deborah E and Covinsky, Kenneth E and Whitmer, Rachel A and Kuller, Lewis H and Lopez, Oscar L and Yaffe, Kristine} } @article {1204, title = {Common genetic determinants of vitamin D insufficiency: a genome-wide association study.}, journal = {Lancet}, volume = {376}, year = {2010}, month = {2010 Jul 17}, pages = {180-8}, abstract = {

BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency.

METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants.

FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95\% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile.

INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency.

FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

}, keywords = {Canada, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 4, Cohort Studies, Dietary Supplements, Europe, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Homozygote, Humans, Immunoassay, International Cooperation, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Seasons, United States, Vitamin D, Vitamin D Deficiency}, issn = {1474-547X}, doi = {10.1016/S0140-6736(10)60588-0}, author = {Wang, Thomas J and Zhang, Feng and Richards, J Brent and Kestenbaum, Bryan and van Meurs, Joyce B and Berry, Diane and Kiel, Douglas P and Streeten, Elizabeth A and Ohlsson, Claes and Koller, Daniel L and Peltonen, Leena and Cooper, Jason D and O{\textquoteright}Reilly, Paul F and Houston, Denise K and Glazer, Nicole L and Vandenput, Liesbeth and Peacock, Munro and Shi, Julia and Rivadeneira, Fernando and McCarthy, Mark I and Anneli, Pouta and de Boer, Ian H and Mangino, Massimo and Kato, Bernet and Smyth, Deborah J and Booth, Sarah L and Jacques, Paul F and Burke, Greg L and Goodarzi, Mark and Cheung, Ching-Lung and Wolf, Myles and Rice, Kenneth and Goltzman, David and Hidiroglou, Nick and Ladouceur, Martin and Wareham, Nicholas J and Hocking, Lynne J and Hart, Deborah and Arden, Nigel K and Cooper, Cyrus and Malik, Suneil and Fraser, William D and Hartikainen, Anna-Liisa and Zhai, Guangju and Macdonald, Helen M and Forouhi, Nita G and Loos, Ruth J F and Reid, David M and Hakim, Alan and Dennison, Elaine and Liu, Yongmei and Power, Chris and Stevens, Helen E and Jaana, Laitinen and Vasan, Ramachandran S and Soranzo, Nicole and Bojunga, J{\"o}rg and Psaty, Bruce M and Lorentzon, Mattias and Foroud, Tatiana and Harris, Tamara B and Hofman, Albert and Jansson, John-Olov and Cauley, Jane A and Uitterlinden, Andr{\'e} G and Gibson, Quince and Jarvelin, Marjo-Riitta and Karasik, David and Siscovick, David S and Econs, Michael J and Kritchevsky, Stephen B and Florez, Jose C and Todd, John A and Dupuis, Jos{\'e}e and Hypp{\"o}nen, Elina and Spector, Timothy D} } @article {1200, title = {Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Sep}, pages = {976-81}, abstract = {

INTRODUCTION: The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging.

METHODS: DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5\% women and 16.5\% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline.

RESULTS: After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline.

CONCLUSIONS: In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

}, keywords = {Aged, 80 and over, Biomarkers, Cognition, Cohort Studies, Dehydroepiandrosterone Sulfate, Female, Gait, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Sex Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glq072}, author = {Sanders, J L and Cappola, A R and Arnold, A M and Boudreau, R M and Chaves, P H and Robbins, J and Cushman, M and Newman, A B} } @article {1177, title = {Cystatin C and sudden cardiac death risk in the elderly.}, journal = {Circ Cardiovasc Qual Outcomes}, volume = {3}, year = {2010}, month = {2010 Mar}, pages = {159-64}, abstract = {

BACKGROUND: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease.

METHODS AND RESULTS: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95\% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95\% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.

CONCLUSIONS: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease.

}, keywords = {Age Factors, Aged, Biomarkers, Chi-Square Distribution, Creatinine, Cystatin C, Death, Sudden, Cardiac, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney Diseases, Longitudinal Studies, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1941-7705}, doi = {10.1161/CIRCOUTCOMES.109.875369}, author = {Deo, Rajat and Sotoodehnia, Nona and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and Kestenbaum, Bryan and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1207, title = {Diabetes and coronary heart disease as risk factors for mortality in older adults.}, journal = {Am J Med}, volume = {123}, year = {2010}, month = {2010 Jun}, pages = {556.e1-9}, abstract = {

BACKGROUND: Type 2 diabetes has been described as a coronary heart disease (CHD) "risk equivalent." We tested whether cardiovascular and all-cause mortality rates were similar between participants with prevalent CHD vs diabetes in an older adult population in whom both glucose disorders and preexisting atherosclerosis are common.

METHODS: The Cardiovascular Health Study is a longitudinal study of men and women (n=5784) aged > or =65 years at baseline who were followed from baseline (1989/1992-1993) through 2005 for mortality. Diabetes was defined by fasting plasma glucose > or =7.0 mmol/L or use of diabetes control medications. Prevalent CHD was determined by confirmed history of myocardial infarction, angina, or coronary revascularization.

RESULTS: Following multivariable adjustment for other cardiovascular disease risk factors and subclinical atherosclerosis, CHD mortality risk was similar between participants with CHD alone vs diabetes alone (hazard ratio [HR] 1.04, 95\% confidence interval [CI], 0.83-1.30). The proportion of mortality attributable to prevalent diabetes (population-attributable risk percent=8.4\%) and prevalent CHD (6.7\%) was similar in women, but the proportion of mortality attributable to CHD (16.5\%) as compared with diabetes (6.4\%) was markedly higher in men. Patterns were similar for cardiovascular disease mortality. By contrast, the adjusted relative hazard of total mortality was lower among participants with CHD alone (HR 0.85, 95\% CI, 0.75-0.96) as compared with those who had diabetes alone.

CONCLUSIONS: Among older adults, diabetes alone confers a risk for cardiovascular mortality similar to that from established clinical CHD. The public health burden of both diabetes and CHD is substantial, particularly among women.

}, keywords = {Aged, Coronary Disease, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Male, Prevalence, Risk Factors, Sex Distribution, Survival Rate, Time Factors, United States}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2009.11.023}, author = {Carnethon, Mercedes R and Biggs, Mary L and Barzilay, Joshua and Kuller, Lewis H and Mozaffarian, Dariush and Mukamal, Kenneth and Smith, Nicholas L and Siscovick, David} } @article {1164, title = {Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing.}, journal = {J Am Coll Cardiol}, volume = {55}, year = {2010}, month = {2010 Feb 02}, pages = {441-50}, abstract = {

OBJECTIVES: This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people would provide additional prognostic information to that from traditional risk factors.

BACKGROUND: Accurate cardiovascular risk stratification is challenging in elderly people.

METHODS: NT-proBNP was measured at baseline and 2 to 3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal CHS (Cardiovascular Health Study). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.

RESULTS: NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR]: 3.05; 95\% confidence interval [CI]: 2.46 to 3.78) and cardiovascular death (HR: 3.02; 95\% CI: 2.36 to 3.86) compared with the lowest quintile (<47.5 pg/ml). The inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among participants with initially low NT-proBNP (<190 pg/ml), those who developed a >25\% increase on follow-up to >190 pg/ml (21\%) were at greater adjusted risk of HF (HR: 2.13; 95\% CI: 1.68 to 2.71) and cardiovascular death (HR: 1.91; 95\% CI: 1.43 to 2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25\% increase (40\%) were at higher risk of HF (HR: 2.06; 95\% CI: 1.56 to 2.72) and cardiovascular death (HR: 1.88; 95\% CI: 1.37 to 2.57), whereas those who developed a >25\% decrease to

CONCLUSIONS: NT-proBNP levels independently predict heart failure and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk.

}, keywords = {Aged, Biomarkers, Female, Heart Failure, Humans, Male, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2009.07.069}, author = {deFilippi, Christopher R and Christenson, Robert H and Gottdiener, John S and Kop, Willem J and Seliger, Stephen L} } @article {1232, title = {Geriatric impairments and disability: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Sep}, pages = {1686-92}, abstract = {

OBJECTIVES: To determine the relative importance of geriatric impairments (in muscle strength, physical capacity, cognition, vision, hearing, and psychological status) and chronic diseases in predicting subsequent functional disability in longitudinal analyses.

DESIGN: Longitudinal data from the Cardiovascular Health Study were analyzed. Multivariable Cox hazards regression modeling was used to analyze associations between time-dependent predictors and onset of disability in activities of daily living (ADLs) and mobility.

SETTING: Four communities across the United States (Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Allegheny County, PA).

PARTICIPANTS: Five thousand eight hundred eighty-eight elderly persons.

MEASUREMENTS: Data were collected annually through in-person examinations.

RESULTS: ADL disability developed in 15\% of participants and mobility disability in 30\%. A single multivariable model was developed that included demographics, marital status, body mass index, and number of impairments and diseases. The hazard ratios (HRs) of having one, two, and three or more geriatric impairments (vs none) for the outcome of ADL disability were 2.12 (95\% confidence interval (CI)=1.63-2.75), 4.25 (95\% CI=3.30-5.48), and 7.87 (95\% CI=6.10-10.17), respectively, and for having one, two, and three or more chronic diseases were 1.75 (95\% CI=1.41-2.19), 2.45 (95\% CI=1.95-3.07), and 3.26 (95\% CI=2.53-4.19), respectively. Similarly, the HRs of having one, two, and three or more impairments for the outcome of mobility disability were 1.48 (95\% CI=1.27-1.73), 2.08 (95\% CI=1.77-2.45), and 3.70 (95\% CI=3.09-4.42), respectively, and for having one, two, and three or more diseases were 2.06 (95\% CI=1.76-2.40), 2.80 (95\% CI=2.36-3.31), and 4.20 (95\% CI=3.44-5.14), respectively.

CONCLUSION: Number of geriatric impairments was more strongly associated than number of chronic diseases with subsequent ADL disability and nearly as strongly associated with the subsequent mobility disability.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Cardiac Rehabilitation, Cardiovascular Diseases, Disabled Persons, Female, Follow-Up Studies, Geriatric Assessment, Health Status, Humans, Male, Morbidity, Retrospective Studies, Risk Factors, Time Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03022.x}, author = {Chaudhry, Sarwat I and McAvay, Gail and Ning, Yuming and Allore, Heather G and Newman, Anne B and Gill, Thomas M} } @article {1091, title = {Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.}, journal = {Nutr Metab Cardiovasc Dis}, volume = {20}, year = {2010}, month = {2010 Jan}, pages = {15-21}, abstract = {

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults.

METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4\% per year, 4.3\% per year and 4.6\% per year for tertile 1 (< or =5.6\%), tertile 2 (5.61-6.20\%) and tertile 3 (> or =6.21\%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95\% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95\% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest).

CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Glycated Hemoglobin A, Health Surveys, Heart Failure, Humans, Incidence, Male, Myocardial Infarction, Risk Factors, Statistics as Topic, Stroke, United States}, issn = {1590-3729}, doi = {10.1016/j.numecd.2009.02.007}, author = {Chonchol, M and Katz, R and Fried, L F and Sarnak, M J and Siscovick, D S and Newman, A B and Strotmeyer, E S and Bertoni, A and Shlipak, M G} } @article {1143, title = {Hip fractures and heart failure: findings from the Cardiovascular Health Study.}, journal = {Eur Heart J}, volume = {31}, year = {2010}, month = {2010 Jan}, pages = {77-84}, abstract = {

AIMS: The aim of the study was to find the epidemiology of hip fractures in heart failure. The increasing survival rate for patients with heart failure places them at risk for other diseases of ageing, including osteoporosis.

METHODS AND RESULTS: We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95\% CI 1.2-2.93) and 1.59 (95\% CI 0.93-2.72), respectively. Respective HRs for women were 1.75 (95\% CI 1.27-2.4) and 1.41 (95\% CI 0.98-2.03). Mortality hazard was approximately 2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone.

CONCLUSION: Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure.

}, keywords = {Aged, Female, Heart Failure, Hip Fractures, Humans, Incidence, Male, Risk Factors, United States}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehp483}, author = {Carbone, Laura and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Lee, Jennifer S and Chen, Zhao and Ahmed, Ali and Parashar, Susmita and Robbins, John R} } @article {1173, title = {Intravenous tissue plasminogen activator and stroke in the elderly.}, journal = {Am J Emerg Med}, volume = {28}, year = {2010}, month = {2010 Mar}, pages = {359-63}, abstract = {

OBJECTIVE: Since publication in 1995 of the National Institute of Neurological Disorders and Stroke (NINDS) trial of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke, the benefit and frequency of use of IV tPA in the elderly have remained uncertain.

METHODS: We obtained data from the NINDS trial to summarize outcomes for randomized subjects older than 80 years. We used data from the Cardiovascular Health Study, a cohort study of 5888 elderly participants from 4 US communities followed longitudinally for stroke since 1989 to estimate the use of and hospital outcome after IV tPA in older adults following publication of the trial in 1995.

RESULTS: In the NINDS trial, 44 subjects older than 80 years were randomized, and their 3-month functional outcomes were not significantly improved with IV tPA. Of 25 randomized to IV tPA, 4 experienced symptomatic intracranial hemorrhages within 36 hours of treatment. Compared with younger patients, older patients were 2.87 times more likely to experience a symptomatic intracranial hemorrhage within 36 hours of IV tPA (95\% confidence interval, 1.04-7.93). Of 227 Cardiovascular Health Study participants hospitalized for ischemic stroke between 1995 and 2002, seven, whose mean age was 84 years, were treated with IV tPA (3.1\%; 95\% confidence interval 1.2-6.2). Two had symptomatic intracranial hemorrhages, 3 failed to improve, and 2 of the 7 had good outcomes.

CONCLUSIONS: These data highlight the need to clarify the risk-benefit profile of IV tPA in ischemic stroke victims who are older than 80 years.

}, keywords = {Aged, 80 and over, Female, Fibrinolytic Agents, Humans, Longitudinal Studies, Male, Placebos, Randomized Controlled Trials as Topic, Stroke, Tissue Plasminogen Activator, Treatment Outcome, United States}, issn = {1532-8171}, doi = {10.1016/j.ajem.2009.01.025}, author = {Longstreth, W T and Katz, Ronit and Tirschwell, David L and Cushman, Mary and Psaty, Bruce M} } @article {1185, title = {Long-term retention of older adults in the Cardiovascular Health Study: implications for studies of the oldest old.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Apr}, pages = {696-701}, abstract = {

OBJECTIVES: To describe retention according to age and visit type (clinic, home, telephone) and to determine characteristics associated with visit types for a longitudinal epidemiological study in older adults.

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. clinical sites.

PARTICIPANTS: Five thousand eight hundred eighty-eight Cardiovascular Health Study (CHS) participants aged 65 to 100 at 1989/90 or 1992/93 enrollment (58.6\% female; 15.7\% black). CHS participants were contacted every 6 months, with annual assessments through 1999 and in 2005/06 for the All Stars Study visit of the CHS cohort (aged 77-102; 66.5\% female; 16.6\% black).

MEASUREMENTS: All annual contacts through 1999 (n=43,772) and for the 2005/06 visit (n=1,942).

RESULTS: CHS had 43,772 total participant contacts from 1989 to 1999: 34,582 clinic visits (79.0\%), 2,238 refusals (5.1\%), 4,401 telephone visits (10.1\%), 1,811 home visits (4.1\%), and 740 other types (1.7\%). In 2005/06, the All Stars participants of the CHS cohort had 36.6\% clinic, 22.3\% home, and 41.1\% telephone visits. Compared with participants aged 65 to 69, odds ratios of not attending a CHS clinic visit were 1.82 (95\% confidence interval (CI)=1.54-2.13), 2.94 (95\% CI=2.45-3.57), 4.55 (95\% CI=3.70-5.56), and 9.09 (95\% CI=7.69-11.11) for those aged 70 to 74, 75 to 79, 80 to 84, and 85 and older, respectively, in sex-adjusted regression. In multivariable regression, participants with a 2005/06 clinic visit were younger, more likely to be male and in good health, and had had better cognitive and physical function 7 years earlier than participants with other visit types. Participants with home, telephone, and missing visits were similar on characteristics measured 7 years earlier.

CONCLUSION: Offering home, telephone, and proxy visits are essential to optimizing follow-up of aging cohorts. Home visits increased in-person retention from 36.5\% to 58.8\% and diversified the cohort with respect to age, health, and physical functioning.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Ambulatory Care Facilities, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Epidemiologic Studies, Female, Geriatric Assessment, House Calls, Humans, Logistic Models, Longitudinal Studies, Male, Multivariate Analysis, Patient Dropouts, Patient Selection, Research Subjects, Telephone, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.02770.x}, author = {Strotmeyer, Elsa S and Arnold, Alice M and Boudreau, Robert M and Ives, Diane G and Cushman, Mary and Robbins, John A and Harris, Tamara B and Newman, Anne B} } @article {1233, title = {Post hoc Parkinson{\textquoteright}s disease: identifying an uncommon disease in the Cardiovascular Health Study.}, journal = {Neuroepidemiology}, volume = {35}, year = {2010}, month = {2010}, pages = {241-9}, abstract = {

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson{\textquoteright}s disease (PD), they typically have limited information for clinical diagnosis.

METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.

RESULTS: We identified 60 cases with prevalent PD (1.0\%; 95\% confidence interval, CI = 0.8-1.3\%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95\% CI = 0.26-0.95) and for those who smoked >=50 pack-years (OR = 0.53; 95\% CI = 0.29-0.96). Estimates for smoking were similar when >=2 data sources were required. Estimates for self-report alone were attenuated towards null.

CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cohort Studies, Female, Health Status, Humans, Incidence, Male, Odds Ratio, Parkinson Disease, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1423-0208}, doi = {10.1159/000319895}, author = {Ton, T G and Jain, S and Boudreau, R and Thacker, E L and Strotmeyer, E S and Newman, A B and Longstreth, W T and Checkoway, H} } @article {1175, title = {Reproductive history, hormone replacement, and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.}, journal = {Br J Haematol}, volume = {149}, year = {2010}, month = {2010 May}, pages = {606-12}, abstract = {

Numerous studies have established that hormone replacement therapy increases the risk of venous thromboembolism (VTE), but an association of endogenous oestrogen exposure with the incidence of VTE is not fully established. Using a prospective design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, we studied the 12-year risk of VTE in relation to hormone replacement therapy use, age at menopause, parity number, and type of menopause in 8236 post-menopausal women. There were no significant associations of age at menopause, parity number, or type of menopause with incidence of VTE. Women currently using hormone replacement had a 1.6-times higher multivariate-adjusted rate ratio (RR) of VTE compared with those without hormone use in the time-dependent model (RR=1.60, 95\% confidence interval [CI], 1.06-2.36; Population attributable fraction=6.7\%, 95\%CI, 1.0-10.3). When we excluded women with 1-year or more duration of hormone therapy at baseline, the association was stronger (RR=2.02, 95\%CI, 1.31-3.12). The multivariate-adjusted RRs of VTE for current users tended to be higher in those with idiopathic VTE (RR=2.40, 95\%CI, 1.40-4.12) than those with secondary VTE (RR=1.08, 95\%CI, 0.63-1.85). Hormone replacement therapy is associated with increased risk of VTE, but reproductive history markers of endogenous oestrogen exposure were not associated with VTE.

}, keywords = {Age Factors, Aged, Epidemiologic Methods, Estrogen Replacement Therapy, Female, Humans, Male, Middle Aged, Parity, Pregnancy, Reproductive History, United States, Venous Thromboembolism}, issn = {1365-2141}, doi = {10.1111/j.1365-2141.2010.08128.x}, author = {Ohira, Tetsuya and Folsom, Aaron R and Cushman, Mary and White, Richard H and Hannan, Peter J and Rosamond, Wayne D and Heckbert, Susan R} } @article {1184, title = {Serum albumin and risk of venous thromboembolism.}, journal = {Thromb Haemost}, volume = {104}, year = {2010}, month = {2010 Jul}, pages = {100-4}, abstract = {

The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95\% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95\% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95\% CI = 0.90, 1.84) in ARIC and 1.80 (95\% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study.

}, keywords = {Aged, Biomarkers, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Risk Factors, Serum Albumin, United States, Venous Thromboembolism}, issn = {2567-689X}, doi = {10.1160/TH09-12-0856}, author = {Folsom, Aaron R and Lutsey, Pamela L and Heckbert, Susan R and Cushman, Mary} } @article {1189, title = {Sleep disturbances, quality of life, and ethnicity: the Sleep Heart Health Study.}, journal = {J Clin Sleep Med}, volume = {6}, year = {2010}, month = {2010 Apr 15}, pages = {176-83}, abstract = {

STUDY OBJECTIVES: To compare health-related quality of life (HR-QOL) across subgroups defined by sleep disturbances and ethnicity.

METHODS: Men (47\%) and women (53\%) Sleep Heart Health Study participants age 40 and older (N = 5237) underwent overnight polysomnography and completed self-report questionnaires on symptoms of sleep disturbances. The physical and mental composite scales (PCS and MCS) of the Medical Outcomes Study 36-item short form survey assessed HR-QOL and were compared to sleep data.

RESULTS: Participants self-identified as Caucasian/White (n = 4482, 86\%), African American/Black (n = 490, 9\%), or Hispanic/Mexican American (n = 265, 5\%). The prevalence of obstructive sleep apnea (OSA) was 17\%, frequent snoring was 34\%, difficulty initiating or maintaining sleep (DIMS; insomnia symptoms) was 30\%, and excessive daytime sleepiness (EDS) was 25\%. African American participants with frequent snoring, insomnia symptoms, or EDS had significantly poorer physical health compared to Caucasians (p < 0.001). Hispanics with frequent snoring, insomnia symptoms, or EDS had significantly poorer mental health than Caucasian participants (p <0.001). Neither PCS nor MCS scores differed significantly across ethnic subgroups for participants with moderate to severe OSA (respiratory disturbance index > 15, 4\% desaturation).

CONCLUSIONS: Across ethnic/racial subgroups, sleep disturbances are associated with worse physical and better mental HR-QOL than the U.S. norm, but this relationship may be moderated by comorbid health conditions. This study replicates and extends prior research indicating differences among minority and non-minority participants and highlights the need for future studies of sleep disturbances with larger samples of minorities that control for comorbid health conditions.

}, keywords = {African Americans, Cohort Studies, Ethnic Groups, European Continental Ancestry Group, Female, Health Status, Heart Diseases, Hispanic Americans, Humans, Longitudinal Studies, Male, Mental Health, Middle Aged, Polysomnography, Prevalence, Quality of Life, Sleep Apnea, Obstructive, Sleep Initiation and Maintenance Disorders, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {1550-9389}, author = {Baldwin, Carol M and Ervin, Ann-Margret and Mays, Mary Z and Robbins, John and Shafazand, Shirin and Walsleben, Joyce and Weaver, Terri} } @article {1246, title = {Subclinical thyroid dysfunction and incident hip fracture in older adults.}, journal = {Arch Intern Med}, volume = {170}, year = {2010}, month = {2010 Nov 22}, pages = {1876-83}, abstract = {

BACKGROUND: Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture.

METHODS: Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95\% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline.

RESULTS: During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95\% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95\% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women.

CONCLUSIONS: Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

}, keywords = {Aged, Female, Follow-Up Studies, Hip Fractures, Humans, Hyperthyroidism, Hypothyroidism, Incidence, Male, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Distribution, Thyrotropin, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2010.424}, author = {Lee, Jennifer S and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Vu, Joseph and Carbone, Laura and Chen, Zhao and Cauley, Jane and Bauer, Doug C and Cappola, Anne R and Robbins, John} } @article {1257, title = {Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.}, journal = {Ann Intern Med}, volume = {153}, year = {2010}, month = {2010 Dec 21}, pages = {790-9}, abstract = {

BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.

OBJECTIVE: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.

DESIGN: Prospective cohort study from 1992 to 2006.

SETTING: Four U.S. communities.

PATIENTS: 3736 adults in the Cardiovascular Health Study.

MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.

RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9\% across quintiles; P = 0.040), lower triglyceride levels (-19.0\%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7\%; P < 0.001), lower C-reactive protein levels (-13.8\%; P = 0.05), and lower insulin resistance (-16.7\%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95\% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.

LIMITATION: Results could be affected by measurement error or residual confounding.

CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

}, keywords = {Adiposity, Aged, C-Reactive Protein, Cholesterol, Cholesterol, HDL, Dairy Products, Diabetes Mellitus, Type 2, Fatty Acids, Monounsaturated, Feeding Behavior, Female, Humans, Incidence, Insulin Resistance, Male, Prospective Studies, Risk Factors, Triglycerides, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-153-12-201012210-00005}, author = {Mozaffarian, Dariush and Cao, Haiming and King, Irena B and Lemaitre, Rozenn N and Song, Xiaoling and Siscovick, David S and Hotamisligil, G{\"o}khan S} } @article {1247, title = {Validation of an atrial fibrillation risk algorithm in whites and African Americans.}, journal = {Arch Intern Med}, volume = {170}, year = {2010}, month = {2010 Nov 22}, pages = {1909-17}, abstract = {

BACKGROUND: We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups.

METHODS: We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts in the age range 45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study) (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874 [16.2\%] were African Americans). The risk algorithm included age, sex, body mass index, systolic blood pressure, electrocardiographic PR interval, hypertension treatment, and heart failure.

RESULTS: We found 1359 incident AF events in 100 074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years; and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4 cases/1000 person-years). The strongest risk factors in all samples were age and heart failure. The relative risks for incident AF associated with risk factors were comparable across cohorts and race groups. After recalibration for baseline incidence and risk factor distribution, the Framingham algorithm, reported in C statistic, performed reasonably well in all samples: AGES, 0.67 (95\% confidence interval [CI], 0.64-0.71); CHS whites, 0.68 (95\% CI, 0.66-0.70); and CHS African Americans, 0.66 (95\% CI, 0.61-0.71). Risk factors combined in the algorithm explained between 47.0\% (AGES) and 63.6\% (FHS) of the population-attributable risk.

CONCLUSIONS: Risk of incident AF in community-dwelling whites and African Americans can be assessed reliably by routinely available and potentially modifiable clinical variables. Seven risk factors accounted for up to 64\% of risk.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Algorithms, Atrial Fibrillation, Blood Pressure, Body Mass Index, Cohort Studies, Electrocardiography, Europe, European Continental Ancestry Group, Female, Follow-Up Studies, Heart Failure, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Sex Factors, Systole, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2010.434}, author = {Schnabel, Renate B and Aspelund, Thor and Li, Guo and Sullivan, Lisa M and Suchy-Dicey, Astrid and Harris, Tamara B and Pencina, Michael J and D{\textquoteright}Agostino, Ralph B and Levy, Daniel and Kannel, William B and Wang, Thomas J and Kronmal, Richard A and Wolf, Philip A and Burke, Gregory L and Launer, Lenore J and Vasan, Ramachandran S and Psaty, Bruce M and Benjamin, Emelia J and Gudnason, Vilmundur and Heckbert, Susan R} } @article {1194, title = {Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {3}, year = {2010}, month = {2010 Jul}, pages = {495-502}, abstract = {

BACKGROUND: The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.

METHODS AND RESULTS: Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5\%) participants developed heart failure over 5 years versus 364 (6.8\%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2\% versus 2.8\%, 9.0\% versus 7.0\%, 15.9\% versus 13.7\%, and 24.6\% versus 30.8\% for the <5\%, 5\% to 10\%, 10\% to 20\%, and >20\% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95\% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5\% to 10\% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.

CONCLUSIONS: The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Confidence Intervals, Disease Progression, Echocardiography, Doppler, Female, Heart Failure, Humans, Incidence, Male, Models, Statistical, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Survival Analysis, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.109.904300}, author = {Kalogeropoulos, Andreas and Psaty, Bruce M and Vasan, Ramachandran S and Georgiopoulou, Vasiliki and Smith, Andrew L and Smith, Nicholas L and Kritchevsky, Stephen B and Wilson, Peter W F and Newman, Anne B and Harris, Tamara B and Butler, Javed} } @article {1326, title = {Association of body mass index with peripheral arterial disease in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {174}, year = {2011}, month = {2011 Nov 01}, pages = {1036-43}, abstract = {

The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)(2)) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged >= 65 years at baseline (1989-1990 or 1992-1993). Ankle brachial index was measured, and participants reported their history of PAD procedures. Participants were followed longitudinally for adjudicated incident PAD events. At baseline, mean BMI was 26.6 (standard deviation, 4.6), and 776 participants (14\%) had prevalent PAD. During 13.2 (median) years of follow-up through June 30, 2007, 276 incident PAD events occurred. In cross-sectional analysis, each 5-unit increase in BMI was inversely associated with PAD (prevalence ratio (PR) = 0.92, 95\% confidence interval (CI): 0.85, 1.00). However, among persons in good health who had never smoked, the direction of association was opposite (PR = 1.20, 95\% CI: 0.94, 1.52). Similar results were observed between BMI calculated using weight at age 50 years and PAD prevalence (PR = 1.30, 95\% CI: 1.11, 1.51) and between BMI at baseline and incident PAD events occurring during follow-up (hazard ratio = 1.32, 95\% CI: 1.00, 1.76) among never smokers in good health. Greater BMI is associated with PAD in older persons who remain healthy and have never smoked. Normal weight maintenance may decrease PAD incidence and associated comorbidity in older age.

}, keywords = {Aged, Ankle Brachial Index, Body Mass Index, Cross-Sectional Studies, Health Status, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Obesity, Peripheral Arterial Disease, Prevalence, Sex Factors, Smoking, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwr228}, author = {Ix, Joachim H and Biggs, Mary L and Kizer, Jorge R and Mukamal, Kenneth J and Djouss{\'e}, Luc and Zieman, Susan J and de Boer, Ian H and Nelson, Tracy L and Newman, Anne B and Criqui, Michael H and Siscovick, David S} } @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} } @article {1286, title = {Chronic kidney disease in octogenarians.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Jun}, pages = {1410-7}, abstract = {

BACKGROUND AND OBJECTIVES: There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.

RESULTS: Mean age was 86 years, 64\% were women, 86\% were Caucasians, 14\% had diabetes, and 39\% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51\%, 46\%, and 33\% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95\% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95\% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95\% CI, 1.55, 2.83).

CONCLUSIONS: Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.

}, keywords = {Age Factors, Aged, 80 and over, Analysis of Variance, Biomarkers, Cardiovascular Diseases, Chi-Square Distribution, Chronic Disease, Creatinine, Cross-Sectional Studies, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Logistic Models, Male, Models, Biological, Prevalence, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.08801010}, author = {Shastri, Shani and Tighiouart, Hocine and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1270, title = {Depressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study.}, journal = {Heart}, volume = {97}, year = {2011}, month = {2011 Mar}, pages = {500-5}, abstract = {

BACKGROUND: Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality.

METHODS: A cohort of 5888 individuals (mean 72.8 {\textpm} 5.6 years, 58\% female, 16\% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables.

RESULTS: At baseline, 20\% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8\%), of which 1176 (20.1\%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all p < 0.001). Individuals with both depressive symptoms and physical inactivity had greater cardiovascular mortality than those with either individually (p < 0.001, log rank test). Physical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26\% after adjustment. This was similar for persons with (25\%) and without (23\%) established coronary heart disease.

CONCLUSIONS: Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Depression, Epidemiologic Methods, Female, Humans, Male, Motor Activity, Psychiatric Status Rating Scales, United States}, issn = {1468-201X}, doi = {10.1136/hrt.2010.209767}, author = {Win, Sithu and Parakh, Kapil and Eze-Nliam, Chete M and Gottdiener, John S and Kop, Willem J and Ziegelstein, Roy C} } @article {1306, title = {Electrocardiographic and clinical predictors separating atherosclerotic sudden cardiac death from incident coronary heart disease.}, journal = {Heart}, volume = {97}, year = {2011}, month = {2011 Oct}, pages = {1597-601}, abstract = {

OBJECTIVE: To identify specific ECG and clinical predictors that separate atherosclerotic sudden cardiac death (SCD) from incident coronary heart disease (CHD) (non-fatal events and non-sudden death) in the combined cohorts of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study.

METHODS: This analysis included 18,497 participants (58\% females, 24\% black individuals, mean age 58 years) who were initially free of clinical CHD. A competing risk analysis was conducted to examine the prognostic significance of baseline clinical characteristics and an extensive electronic database of ECG measurements for prediction of 229 cases of SCD as a first event versus 2297 incident CHD cases (2122 non-fatal events and 175 non-sudden death) that occurred during a median follow-up time of 13 years in the Cardiovascular Health Study and 14 years in the Atherosclerosis Risk in Communities study.

RESULTS: After adjusting for common CHD risk factors, a number of clinical characteristics and ECG measurements were independently predictive of SCD and CHD. However, the risk of SCD versus incident CHD was significantly different for race/ethnicity, hypertension, body mass index (BMI), heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2. Black race/ethnicity (compared to non-black) was predictive of high SCD risk but less risk of incident CHD (p value for differences in the risk (HR) for SCD versus CHD <0.0001). Hypertension, increased heart rate, prolongation of QTc and abnormally inverted T wave were stronger predictors of high SCD risk compared to CHD (p value=0.0460, 0.0398, 0.0158 and 0.0265, respectively). BMI was not predictive of incident CHD but was predictive of high SCD risk in a quadratic fashion (p value=0.0220). On the other hand, elevated ST height as measured at the J point and that measured at 60 ms after the J point in V2 were not predictive of SCD but were predictive of high incident CHD risk (p value=0.0251 and 0.0155, respectively).

CONCLUSIONS: SCD and CHD have many risk factors in common. Hypertension, race/ethnicity, BMI, heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2 have the potential to separate between the risks of SCD and CHD. These results need to be validated in another cohort.

}, keywords = {Adult, Aged, Aged, 80 and over, Body Mass Index, Continental Population Groups, Coronary Disease, Death, Sudden, Cardiac, Electrocardiography, Ethnic Groups, Female, Heart Rate, Humans, Hypertension, Male, Middle Aged, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Risk Adjustment, Risk Factors, Time Factors, United States}, issn = {1468-201X}, doi = {10.1136/hrt.2010.215871}, author = {Soliman, Elsayed Z and Prineas, Ronald J and Case, L Douglas and Russell, Gregory and Rosamond, Wayne and Rea, Thomas and Sotoodehnia, Nona and Post, Wendy S and Siscovick, David and Psaty, Bruce M and Burke, Gregory L} } @article {1259, title = {Gait speed and survival in older adults.}, journal = {JAMA}, volume = {305}, year = {2011}, month = {2011 Jan 05}, pages = {50-8}, abstract = {

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates.

OBJECTIVE: To evaluate the relationship between gait speed and survival.

DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6\%, women; and 79.8\%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s.

MAIN OUTCOME MEASURES: Survival rates and life expectancy.

RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8\% (confidence interval [CI], 79.6\%-88.8\%) and 10-year survival rate was 59.7\% (95\% CI, 46.5\%-70.6\%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95\% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19\% to 87\% in men and from 35\% to 91\% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization.

CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

}, keywords = {Aged, Cohort Studies, Female, Gait, Geriatric Assessment, Humans, Life Expectancy, Male, Survival Analysis, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1923}, author = {Studenski, Stephanie and Perera, Subashan and Patel, Kushang and Rosano, Caterina and Faulkner, Kimberly and Inzitari, Marco and Brach, Jennifer and Chandler, Julie and Cawthon, Peggy and Connor, Elizabeth Barrett and Nevitt, Michael and Visser, Marjolein and Kritchevsky, Stephen and Badinelli, Stefania and Harris, Tamara and Newman, Anne B and Cauley, Jane and Ferrucci, Luigi and Guralnik, Jack} } @article {1262, title = {Gender differences between the Minnesota code and Novacode electrocardiographic prognostication of coronary heart disease in the cardiovascular health study.}, journal = {Am J Cardiol}, volume = {107}, year = {2011}, month = {2011 Mar 15}, pages = {817-820.e1}, abstract = {

The Minnesota Code (MC) and Novacode (Nova) are the most widely used electrocardiographic (ECG) classification systems. The comparative strengths of their classifications for Q- and ST-T-wave abnormalities in predicting coronary heart disease (CHD) events and total mortality have not been evaluated separately by gender. We studied standard 12-lead electrocardiograms at rest from 4,988 participants in the Cardiovascular Health Study. Average age at baseline was 73 years, 60\% of participants were women 85\% were white, and 22\% had a history of cardiovascular disease or presence of ECG myocardial infarction by MC or Nova. Starting in 1989 with an average 17-year follow-up, 65\% of participants died and 33\% had incident CHD in a cohort free of cardiovascular disease at baseline. Of these, electrocardiograms with major Q-wave or major ST-T abnormalities by MC or Nova predicted increased risk for CHD events and total mortality with no significant differences in predictability between men and women. The study also found that women had fewer major Q-wave changes but more major ST-T abnormalities than men. However, there were no gender differences in predicting CHD events and total mortality. In conclusion, ECG classification systems for myocardial infarction/ischemia abnormalities by MC or Nova are valuable and useful for men and women in clinical trials and epidemiologic studies.

}, keywords = {Aged, Coronary Disease, Electrocardiography, Female, Humans, Incidence, Male, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2010.11.004}, author = {Zhang, Zhu-Ming and Prineas, Ronald J and Case, Doug and Psaty, Bruce M and Suzuki, Takeki and Burke, Gregory L} } @article {1316, title = {Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource (CARe) project.}, journal = {Circ Cardiovasc Genet}, volume = {4}, year = {2011}, month = {2011 Oct}, pages = {557-64}, abstract = {

BACKGROUND: The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated.

METHODS AND RESULTS: We examined a panel of approximately 50,000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18,524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute{\textquoteright}s Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident ischemic stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology Stroke Consortium (n=19,602 whites, 1544 incident strokes). SNP rs4845625 in the IL6R gene was associated with AF (relative risk [RR] C allele, 0.90; 95\% confidence interval [CI], 0.85-0.95; P=0.0005) in whites but did not reach statistical significance in African Americans (RR, 0.86; 95\% CI, 0.72-1.03; P=0.09). The results were comparable in the German AF Network replication, (RR, 0.71; 95\% CI, 0.57-0.89; P=0.003). No association between rs4845625 and stroke was observed in whites. The known chromosome 4 locus near PITX2 in whites also was associated with AF in African Americans (rs4611994; hazard ratio, 1.40; 95\% CI, 1.16-1.69; P=0.0005).

CONCLUSIONS: In a community-based cohort meta-analysis, we identified genetic association in IL6R with AF in whites. Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans.

}, keywords = {African Americans, Aged, Alleles, Atrial Fibrillation, Chromosomes, Human, Pair 4, Cohort Studies, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Polymorphism, Single Nucleotide, Receptors, Interleukin-6, Risk Factors, Stroke, United States}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.110.959197}, author = {Schnabel, Renate B and Kerr, Kathleen F and Lubitz, Steven A and Alkylbekova, Ermeg L and Marcus, Gregory M and Sinner, Moritz F and Magnani, Jared W and Wolf, Philip A and Deo, Rajat and Lloyd-Jones, Donald M and Lunetta, Kathryn L and Mehra, Reena and Levy, Daniel and Fox, Ervin R and Arking, Dan E and Mosley, Thomas H and M{\"u}ller-Nurasyid, Martina and Young, Taylor R and Wichmann, H-Erich and Seshadri, Sudha and Farlow, Deborah N and Rotter, Jerome I and Soliman, Elsayed Z and Glazer, Nicole L and Wilson, James G and Breteler, Monique M B and Sotoodehnia, Nona and Newton-Cheh, Christopher and K{\"a}{\"a}b, Stefan and Ellinor, Patrick T and Alonso, Alvaro and Benjamin, Emelia J and Heckbert, Susan R} } @article {1295, title = {Longer legs are associated with greater risk of incident venous thromboembolism independent of total body height. The Longitudinal Study of Thromboembolism Etiology (LITE).}, journal = {Thromb Haemost}, volume = {106}, year = {2011}, month = {2011 Jul}, pages = {113-20}, abstract = {

Several studies have reported that taller individuals are at greater risk of venous thromboembolism (VTE). We hypothesised that longer leg length would be positively associated with incident VTE, and would explain the height association. LITE ascertained VTE in a prospective population-based sample of 21,860 individuals aged 45 and older. Leg length was measured as standing height minus torso length. Cox regression models were adjusted for age, race, sex, waist circumference, diabetes, and factor VIII. To evaluate whether leg length was associated with VTE risk independent of height, we standardised leg length and height per 1 standard deviation (SD), and then included them simultaneously in Cox regression models. A total of 641 incident VTE cases accrued over a median follow-up of 16 years. Participants in the highest quintile of leg length were at 59\% (95\% CI: 22\%-108\%) greater risk of VTE, relative to the lowest quintile. For height, risk was 45\% (12\%-88\%) greater for those in the highest quintile, compared to the lowest. When leg length and height were modelled simultaneously leg length remained associated with VTE risk (HR per 1 SD: 1.21 (1.04-1.40) while height was unrelated (HR per 1 SD: 1.00 (0.86-1.16). To conclude, participants with longer legs were at greater risk of incident VTE, and leg length explained the relation of height to VTE. It remains to be established whether this finding is due to greater venous surface area, a larger number of venous valves, or greater hydrostatic pressure among individuals with longer legs.

}, keywords = {Adult, Aged, Anthropometry, Body Height, Female, Follow-Up Studies, Humans, Leg, Male, Middle Aged, Population Groups, Prospective Studies, Risk Factors, United States, Venous Thromboembolism}, issn = {2567-689X}, doi = {10.1160/TH11-02-0100}, author = {Lutsey, Pamela L and Cushman, Mary and Heckbert, Susan R and Tang, Weihong and Folsom, Aaron R} } @article {1296, title = {Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Oct}, pages = {1100-7}, abstract = {

BACKGROUND: Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.

METHODS: We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).

RESULTS: Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95\% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels >=20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p = .55), as compared with smaller changes for both.

CONCLUSION: Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

}, keywords = {Adiponectin, Aged, 80 and over, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Chi-Square Distribution, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Interleukin-6, Male, Mortality, Predictive Value of Tests, Risk Factors, Sensitivity and Specificity, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glr098}, author = {Kizer, Jorge R and Arnold, Alice M and Jenny, Nancy S and Cushman, Mary and Strotmeyer, Elsa S and Ives, Diane G and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Hirsch, Calvin H and Newman, Anne B} } @article {1254, title = {Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women.}, journal = {Am J Epidemiol}, volume = {173}, year = {2011}, month = {2011 Jan 01}, pages = {10-25}, abstract = {

The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (>= 30 kg/m{\texttwosuperior}) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints for obesity, although BMI-defined overweight (25-29.9 kg/m{\texttwosuperior} was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95\% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95\% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Brain Ischemia, Coronary Disease, Female, Humans, Incidence, Male, Middle Aged, Obesity, Prevalence, Retrospective Studies, Risk Factors, Sex Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwq311}, author = {Kizer, Jorge R and Biggs, Mary L and Ix, Joachim H and Mukamal, Kenneth J and Zieman, Susan J and de Boer, Ian H and Mozaffarian, Dariush and Barzilay, Joshua I and Strotmeyer, Elsa S and Luchsinger, Jos{\'e} A and Elkind, Mitchell S V and Longstreth, W T and Kuller, Lewis H and Siscovick, David S} } @article {1313, title = {The Next PAGE in understanding complex traits: design for the analysis of Population Architecture Using Genetics and Epidemiology (PAGE) Study.}, journal = {Am J Epidemiol}, volume = {174}, year = {2011}, month = {2011 Oct 01}, pages = {849-59}, abstract = {

Genetic studies have identified thousands of variants associated with complex traits. However, most association studies are limited to populations of European descent and a single phenotype. The Population Architecture using Genomics and Epidemiology (PAGE) Study was initiated in 2008 by the National Human Genome Research Institute to investigate the epidemiologic architecture of well-replicated genetic variants associated with complex diseases in several large, ethnically diverse population-based studies. Combining DNA samples and hundreds of phenotypes from multiple cohorts, PAGE is well-suited to address generalization of associations and variability of effects in diverse populations; identify genetic and environmental modifiers; evaluate disease subtypes, intermediate phenotypes, and biomarkers; and investigate associations with novel phenotypes. PAGE investigators harmonize phenotypes across studies where possible and perform coordinated cohort-specific analyses and meta-analyses. PAGE researchers are genotyping thousands of genetic variants in up to 121,000 DNA samples from African-American, white, Hispanic/Latino, Asian/Pacific Islander, and American Indian participants. Initial analyses will focus on single nucleotide polymorphisms (SNPs) associated with obesity, lipids, cardiovascular disease, type 2 diabetes, inflammation, various cancers, and related biomarkers. PAGE SNPs are also assessed for pleiotropy using the "phenome-wide association study" approach, testing each SNP for associations with hundreds of phenotypes. PAGE data will be deposited into the National Center for Biotechnology Information{\textquoteright}s Database of Genotypes and Phenotypes and made available via a custom browser.

}, keywords = {Epidemiologic Methods, Epidemiologic Research Design, Ethnic Groups, Genetic Association Studies, Genetics, Population, Genome-Wide Association Study, Humans, Interinstitutional Relations, Multifactorial Inheritance, National Human Genome Research Institute (U.S.), Phenotype, Pilot Projects, Research Design, Risk Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwr160}, author = {Matise, Tara C and Ambite, Jose Luis and Buyske, Steven and Carlson, Christopher S and Cole, Shelley A and Crawford, Dana C and Haiman, Christopher A and Heiss, Gerardo and Kooperberg, Charles and Marchand, Loic Le and Manolio, Teri A and North, Kari E and Peters, Ulrike and Ritchie, Marylyn D and Hindorff, Lucia A and Haines, Jonathan L} } @article {1242, title = {N-terminal pro-B-type natriuretic peptide is associated with sudden cardiac death risk: the Cardiovascular Health Study.}, journal = {Heart Rhythm}, volume = {8}, year = {2011}, month = {2011 Feb}, pages = {228-33}, abstract = {

BACKGROUND: Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality as well as with sudden death in women.

OBJECTIVE: The purpose of this study was to examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.

METHODS: The risk of SCD associated with baseline NT-proBNP was examined in 5,447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP.

RESULTS: Over a median follow-up of 12.5 years (maximum 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95\% confidence interval [2.9, 6.1]; P <.001) in the highest quintile compared with in the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the fifth versus the first quintile of 2.5 (95\% confidence interval [1.6, 3.8]; P <.001).

CONCLUSION: NT-proBNP provides information regarding the risk of SCD in a community-based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions.

}, keywords = {Age Distribution, Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Confidence Intervals, Death, Sudden, Cardiac, Female, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sex Distribution, Time Factors, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2010.10.038}, author = {Patton, Kristen K and Sotoodehnia, Nona and DeFilippi, Christopher and Siscovick, David S and Gottdiener, John S and Kronmal, Richard A} } @article {1264, title = {Patterns and predictors of recovery from exhaustion in older adults: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Feb}, pages = {207-13}, abstract = {

OBJECTIVES: To estimate the likelihood of, and factors associated with, recovery from exhaustion in older adults.

DESIGN: Secondary analysis of a cohort study.

SETTING: Six annual examinations in four U.S. communities.

PARTICIPANTS: Four thousand five hundred eighty-four men and women aged 69 and older.

MEASUREMENTS: Exhaustion was considered present when a participant responded "a moderate amount" or "most of the time" to either of two questions: "How often have you had a hard time getting going?" and "How often does everything seem an effort?"

RESULTS: Of the 964 participants who originally reported exhaustion, 634 (65.8\%) were exhaustion free at least once during follow-up. When data from all time points were considered, 48\% of those who reported exhaustion were exhaustion free the following year. After adjustment for age, sex, race, education, and marital status, 1-year recovery was less likely in individuals with worse self-rated health and in those who were taking six or more medications or were obese, depressed, or had musculoskeletal pain or history of stroke. In proportional hazards models, the following risk factors were associated with more persistent exhaustion over 5 years: poor self-rated health, six or more medications, obesity, and depression. Recovery was not less likely in participants with a history of cancer or heart disease.

CONCLUSION: Exhaustion is common in old age but is dynamic, even in those with a history of cancer and congestive heart failure. Recovery is especially likely in seniors who have a positive perception of their overall health, take few medications, and are not obese or depressed. These findings support the notion that resiliency is associated with physical and psychological well-being.

}, keywords = {Aged, Aging, Cardiovascular Physiological Phenomena, Exercise Test, Exercise Tolerance, Female, Follow-Up Studies, Geriatric Assessment, Health Status, Humans, Male, Predictive Value of Tests, Recovery of Function, Retrospective Studies, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03238.x}, author = {Whitson, Heather E and Thielke, Stephen and Diehr, Paula and O{\textquoteright}Hare, Ann M and Chaves, Paulo H M and Zakai, Neil A and Arnold, Alice and Chaudhry, Sarwat and Ives, Diane and Newman, Anne B} } @article {1268, title = {Predictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality.}, journal = {Am J Cardiol}, volume = {107}, year = {2011}, month = {2011 Mar 01}, pages = {723-9}, abstract = {

Depression and natriuretic peptides predict heart failure (HF) progression, but the unique contributions of depression and biomarkers associated with HF outcomes are not known. The present study determined the additive predictive value of depression and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) for new-onset HF in HF-free subjects and mortality in patients with HF. The participants in the Cardiovascular Health Study were assessed for depressive symptoms using the Center for Epidemiologic Studies Depression Scale and NT-proBNP using an electrochemiluminescence immunoassay. The validated cutoff values for depression (Center for Epidemiologic Studies Depression Scale >=8) and NT-proBNP (>=190 pg/ml) were used. The risks of incident HF and mortality (cardiovascular disease-related and all-cause) were examined during a median follow-up of 11 years, adjusting for demographics, clinical factors, and health behaviors. In patients with HF (n = 208), depression was associated with an elevated risk of cardiovascular disease mortality (hazard ratios [HR] 2.07, 95\% confidence interval [CI] 1.31 to 3.27) and all-cause mortality (HR 1.49, 95\% CI 1.05 to 2.11), independent of the NT-proBNP level and covariates. The combined presence of depression and elevated NT-proBNP was associated with substantially elevated covariate-adjusted risks of cardiovascular disease mortality (HR 5.42, 95\% CI 2.38 to 12.36) and all-cause mortality (HR 3.72, 95\% CI 2.20 to 6.37). In the 4,114 HF-free subjects, new-onset HF was independently predicted by an elevated NT-proBNP level (HR 2.27, 95\% CI 1.97 to 2.62) but not depression (HR 1.08, 95\% CI 0.92 to 1.26) in covariate-adjusted analysis. In conclusion, depression and NT-proBNP displayed additive predictive value for mortality in patients with HF. These associations can be explained by complementary pathophysiologic mechanisms. The presence of both elevated depression and NT-proBNP levels might improve the identification of patients with HF with a high risk of mortality.

}, keywords = {Aged, Depression, Disease Progression, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Natriuretic Peptide, Brain, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2010.10.055}, author = {van den Broek, Krista C and deFilippi, Christopher R and Christenson, Robert H and Seliger, Stephen L and Gottdiener, John S and Kop, Willem J} } @article {1293, title = {Predictors of thyroid hormone initiation in older adults: results from the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Jul}, pages = {809-14}, abstract = {

BACKGROUND: Despite widespread use, there are no data on initiation of thyroid hormone use in older people. We report the prevalence of thyroid hormone use and predictors of thyroid hormone initiation in a population of older men and women.

METHODS: Thyroid hormone medication data were collected annually from 1989 to 2006 in community-dwelling individuals aged 65 years and older enrolled in the Cardiovascular Health Study (N = 5,888). Associations of age, sex, race, body mass index, education, and coronary heart disease with initiation were evaluated using discrete-time survival analysis.

RESULTS: In 1989-1990, 8.9\% (95\% confidence interval 8.1\%-9.7\%) of participants were taking a thyroid hormone preparation, increasing to 20.0\% (95\% confidence interval 8.2\%-21.8\%) over 16 years. The average initiation rate was 1\% per year. The initiation rate was nonlinear with age, and those aged 85 years and older initiated thyroid hormone more than twice as frequently as those aged 65-69 years (hazard ratio = 2.34; 95\% confidence interval 1.43-3.85). White women were more likely to initiate thyroid hormone than any other race and sex group. Higher body mass index was independently associated with higher risk for initiation (p = .002) as was greater education (p = .02) and prevalent coronary heart disease (p = .03).

CONCLUSIONS: Thyroid hormone use is common in older people. The indications and benefits of thyroid hormone use in older individuals with the highest rate of thyroid hormone initiation-the oldest old, overweight and obese individuals, and those with coronary heart disease-should be investigated.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Hypothyroidism, Incidence, Male, Prevalence, Prognosis, Retrospective Studies, Risk Factors, Sex Factors, Thyroid Hormones, Thyroxine, Time Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glr063}, author = {Somwaru, Lily L and Arnold, Alice M and Cappola, Anne R} } @article {1255, title = {Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults.}, journal = {J Cardiovasc Electrophysiol}, volume = {22}, year = {2011}, month = {2011 Feb}, pages = {122-7}, abstract = {

INTRODUCTION: We examined whether heart rate turbulence (HRT) and C-reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk.

METHODS AND RESULTS: One thousand two hundred and seventy-two individuals, age >= 65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low-risk group [HR 7.9, 95\% confidence interval (CI) 2.8-22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95\% CI 1.5-4.0, P = 0.016] and [HR 2.7, 95\% CI 1.2-5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low-risk individuals [HR 2.5, 95\% CI 1.3-5.1, P = 0.009]. Among low risk, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT.

CONCLUSIONS: Abnormal HRT independently adds to risk stratification of low, intermediate and high-risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk.

}, keywords = {Aged, C-Reactive Protein, Cardiovascular Diseases, Comorbidity, Electrocardiography, Ambulatory, Female, Humans, Incidence, Male, Risk Assessment, Risk Factors, Statistics as Topic, Survival Analysis, Survival Rate, United States, Ventricular Premature Complexes}, issn = {1540-8167}, doi = {10.1111/j.1540-8167.2010.01967.x}, author = {Stein, Phyllis K and Barzilay, Joshua I} } @article {1352, title = {Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Oct}, pages = {1793-801}, abstract = {

OBJECTIVES: To examine the association between 25-hydroxyvitamin D (25(OH)D) and physical function in adults of advanced age.

DESIGN: Cross-sectional and longitudinal analysis of physical function over 3~years of follow-up in the Cardiovascular Health Study All Stars.

SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.

PARTICIPANTS: Community-dwelling adults aged 77 to 100 (N~=~988).

MEASUREMENTS: Serum 25-hydroxyvitamin D 25(OH)D), Short Physical Performance Battery (SPPB), and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADLs) disability were assessed at baseline and every 6~months over 3~years of follow-up.

RESULTS: Almost one-third (30.8\%) of participants were deficient in 25(OH)D (<20~ng/mL). SPPB scores were lower in those with deficient 25(OH)D (mean (standard error) 6.53~(0.24)) than in those with sufficient 25(OH)D (>=30~ng/mL) (7.15~(0.25)) after adjusting for sociodemographic characteristics, season, health behaviors, and chronic conditions (P~=~.006). Grip strength adjusted for body size was also lower in those with deficient 25(OH)D than in those with sufficient 25(OH)D (24.7~(0.6)~kg vs 26.0~(0.6)~kg, P~=~.02). Participants with deficient 25(OH)D were more likely to have prevalent mobility (OR~=~1.44, 95\% confidence interval (CI))~=~0.96-2.14) and ADL disability (OR~=~1.51, 95\% CI~=~1.01-2.25) at baseline than those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at greater risk of incident mobility disability over 3~years of follow-up (hazard ratio~=~1.56, 95\% CI~=~1.06-2.30).

CONCLUSION: Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability in community-dwelling older adults. Moreover, vitamin D deficiency predicted incident mobility disability.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Female, Follow-Up Studies, Geriatric Assessment, Health Surveys, Humans, Male, Mobility Limitation, Muscle Strength, Physical Fitness, Proportional Hazards Models, Reference Values, United States, Vitamin D, Vitamin D Deficiency}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2011.03601.x}, author = {Houston, Denise K and Tooze, Janet A and Davis, Cralen C and Chaves, Paulo H M and Hirsch, Calvin H and Robbins, John A and Arnold, Alice M and Newman, Anne B and Kritchevsky, Stephen B} } @article {1350, title = {Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {58}, year = {2011}, month = {2011 Dec}, pages = {1021-8}, abstract = {

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >=20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >=65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7\% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95\% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.

}, keywords = {Aged, Cardiovascular Diseases, Comorbidity, Death, Sudden, Cardiac, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Kidney, Male, Middle Aged, Minerals, Parathyroid Hormone, Proportional Hazards Models, Risk Factors, Socioeconomic Factors, United States, Vitamin D}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.111.179135}, author = {Deo, Rajat and Katz, Ronit and Shlipak, Michael G and Sotoodehnia, Nona and Psaty, Bruce M and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and de Boer, Ian H and Enquobahrie, Daniel and Siscovick, David and Kestenbaum, Bryan} } @article {1344, title = {Adiposity and incident heart failure in older adults: the cardiovascular health study.}, journal = {Obesity (Silver Spring)}, volume = {20}, year = {2012}, month = {2012 Sep}, pages = {1936-41}, abstract = {

While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5\% were men and 15.3\% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14\% increased risk of HF (95\% CI: 3\%-26\%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95\% CI: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95\% CI: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women.

}, keywords = {Adiposity, Aged, Aging, Body Fat Distribution, Body Mass Index, Female, Heart Failure, Humans, Incidence, Independent Living, Male, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, United States, Waist Circumference}, issn = {1930-739X}, doi = {10.1038/oby.2011.320}, author = {Djouss{\'e}, Luc and Bartz, Traci M and Ix, Joachim H and Zieman, Susan J and Delaney, Joseph A and Mukamal, Kenneth J and Gottdiener, John S and Siscovick, David S and Kizer, Jorge R} } @article {1402, title = {Association of weight status with mortality in adults with incident diabetes.}, journal = {JAMA}, volume = {308}, year = {2012}, month = {2012 Aug 08}, pages = {581-90}, abstract = {

CONTEXT: Type 2 diabetes in normal-weight adults (body mass index [BMI] <25) is a representation of the metabolically obese normal-weight phenotype with unknown mortality consequences.

OBJECTIVE: To test the association of weight status with mortality in adults with new-onset diabetes in order to minimize the influence of diabetes duration and voluntary weight loss on mortality.

DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011. A total of 2625 participants with incident diabetes contributed 27,125 person-years of follow-up. Included were men and women (age >40 years) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI. Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater.

MAIN OUTCOME MEASURES: Total, cardiovascular, and noncardiovascular mortality.

RESULTS: The proportion of adults who were normal weight at the time of incident diabetes ranged from 9\% to 21\% (overall 12\%). During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes (18 were not classified). The rates of total, cardiovascular, and noncardiovascular mortality were higher in normal-weight participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively) than in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and noncardiovascular mortality were 2.08 (95\% CI, 1.52-2.85), 1.52 (95\% CI, 0.89-2.58), and 2.32 (95\% CI, 1.55-3.48), respectively.

CONCLUSION: Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese.

}, keywords = {Adult, Aged, Aged, 80 and over, Body Mass Index, Body Weight, Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Type 2, Female, Humans, Longitudinal Studies, Male, Middle Aged, Obesity, Overweight, United States}, issn = {1538-3598}, doi = {10.1001/jama.2012.9282}, author = {Carnethon, Mercedes R and De Chavez, Peter John D and Biggs, Mary L and Lewis, Cora E and Pankow, James S and Bertoni, Alain G and Golden, Sherita H and Liu, Kiang and Mukamal, Kenneth J and Campbell-Jenkins, Brenda and Dyer, Alan R} } @article {1368, title = {Chronic kidney disease, insulin resistance, and incident diabetes in older adults.}, journal = {Clin J Am Soc Nephrol}, volume = {7}, year = {2012}, month = {2012 Apr}, pages = {588-94}, abstract = {

BACKGROUND AND OBJECTIVES: Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic β cell, effects on glucose tolerance, and risk of diabetes are not clear.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, β cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose >=126 mg/dl, nonfasting glucose >=200 mg/dl, or use of glucose-lowering medications.

RESULTS: Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2\% higher fasting insulin concentration (95\% confidence interval [CI], 1.4\%, 2.9\%; P<0.001) and a 1.1\% lower insulin sensitivity index (95\% CI, 0.03\%, 2.2\%; P=0.04). Surprisingly, eGFR was associated with an augmented β cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years{\textquoteright} follow-up, 437 participants (9.3\%) developed diabetes. eGFR was not associated with the risk of incident diabetes.

CONCLUSIONS: Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Chronic Disease, Creatinine, Diabetes Mellitus, Female, Glomerular Filtration Rate, Glucose Tolerance Test, Health Surveys, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin Resistance, Insulin-Secreting Cells, Kidney, Kidney Diseases, Linear Models, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.11861111}, author = {Pham, Hien and Robinson-Cohen, Cassianne and Biggs, Mary L and Ix, Joachim H and Mukamal, Kenneth J and Fried, Linda F and Kestenbaum, Bryan and Siscovick, David S and de Boer, Ian H} } @article {1396, title = {Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Aug}, pages = {269-74}, abstract = {

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged >=65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95\% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95\% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

}, keywords = {Aged, Alcohol Drinking, alpha-Linolenic Acid, Biomarkers, Body Mass Index, Cardiovascular Diseases, Diet, Fatty Acid Desaturases, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.037960}, author = {Lemaitre, Rozenn N and Sitlani, Colleen and Song, Xiaoling and King, Irena B and McKnight, Barbara and Spiegelman, Donna and Sacks, Frank M and Djouss{\'e}, Luc and Rimm, Eric B and Siscovick, David S and Mozaffarian, Dariush} } @article {1408, title = {Development and validation of a coronary risk prediction model for older U.S. and European persons in the Cardiovascular Health Study and the Rotterdam Study.}, journal = {Ann Intern Med}, volume = {157}, year = {2012}, month = {2012 Sep 18}, pages = {389-97}, abstract = {

BACKGROUND: Risk scores for prediction of coronary heart disease (CHD) in older adults are needed.

OBJECTIVE: To develop a sex-specific CHD risk prediction model for older adults that accounts for competing risks for death.

DESIGN: 2 observational cohort studies, using data from 4946 participants in the Cardiovascular Health Study (CHS) and 4303 participants in the Rotterdam Study (RS).

SETTING: Community settings in the United States (CHS) and Rotterdam, the Netherlands (RS).

PARTICIPANTS: Persons aged 65 years or older who were free of cardiovascular disease.

MEASUREMENTS: A composite of nonfatal myocardial infarction and coronary death.

RESULTS: During a median follow-up of 16.5 and 14.9 years, 1166 CHS and 698 RS participants had CHD events, respectively. Deaths from noncoronary causes largely exceeded the number of CHD events, complicating accurate CHD risk predictions. The prediction model had moderate ability to discriminate between events and nonevents (c-statistic, 0.63 in both U.S. and European men and 0.67 and 0.68 in U.S. and European women). The model was well-calibrated; predicted risks were in good agreement with observed risks. Compared with the Framingham point scores, the prediction model classified elderly U.S. persons into higher risk categories but elderly European persons into lower risk categories. Differences in classification accuracy were not consistent and depended on cohort and sex. Adding newer cardiovascular risk markers to the model did not substantially improve performance.

LIMITATION: The model may be less applicable in nonwhite populations, and the comparison Framingham model was not designed for adults older than 79 years.

CONCLUSION: A CHD risk prediction model that accounts for deaths from noncoronary causes among older adults provided well-calibrated risk estimates but was not substantially more accurate than Framingham point scores. Moreover, adding newer risk markers did not improve accuracy. These findings emphasize the difficulties of predicting CHD risk in elderly persons and the need to improve these predictions.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; The Netherlands Organisation for Scientific Research; and the Netherlands Organisation for Health Research and Development.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cause of Death, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Male, Models, Statistical, Multivariate Analysis, Netherlands, Prospective Studies, Risk Assessment, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-157-6-201209180-00002}, author = {Koller, Michael T and Leening, Maarten J G and Wolbers, Marcel and Steyerberg, Ewout W and Hunink, M G Myriam and Schoop, Rotraut and Hofman, Albert and Bucher, Heiner C and Psaty, Bruce M and Lloyd-Jones, Donald M and Witteman, Jacqueline C M} } @article {1337, title = {Echocardiographic diastolic parameters and risk of atrial fibrillation: the Cardiovascular Health Study.}, journal = {Eur Heart J}, volume = {33}, year = {2012}, month = {2012 Apr}, pages = {904-12}, abstract = {

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly, and shares several risk factors with diastolic dysfunction, including hypertension and advanced age. The purpose of this study is to examine diastolic dysfunction as a risk for incident AF.

METHODS AND RESULTS: We examined the association of echocardiographic parameters of diastolic function with the incidence of AF in 4480 participants enrolled in the Cardiovascular Health Study, an ongoing cohort of community-dwelling older adults from four US communities. Participants underwent baseline echocardiography in 1989-1990 and were followed for incident AF on routine follow-up and hospitalizations. After 50 941 person-years of follow-up (median follow-up time 12.1 years), 1219 participants developed AF. In multivariable-adjusted age-stratified Cox models, diastolic echocardiographic parameters were significantly associated with the risk of incident AF. The most significant parameters were the Doppler peak E-wave velocity and left atrial diameter, which demonstrated a positive nonlinear association [HR 1.5 (CI 1.3-1.9) and HR 1.7 (CI 1.4-2.1) for highest vs. lowest quintile, respectively], and Doppler A-wave velocity time integral, which displayed a U-shaped relationship with the risk of AF [HR 0.7 (CI 0.6-0.9) for middle vs. lowest quintile]. Each diastolic parameter displayed a significant association with adjusted NT-proBNP levels, although the nature of the association did not entirely parallel the risk of AF. Further cluster analysis revealed unique patterns of diastolic function that may identify patients at risk for AF.

CONCLUSION: In a community-based population of older adults, echocardiographic measures of diastolic function are significantly associated with an increased risk of AF.

}, keywords = {Aged, Atrial Fibrillation, Blood Flow Velocity, Diastole, Echocardiography, Doppler, Female, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Risk Factors, United States, Ventricular Dysfunction, Left}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehr378}, author = {Rosenberg, Michael A and Gottdiener, John S and Heckbert, Susan R and Mukamal, Kenneth J} } @article {1392, title = {Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {60}, year = {2012}, month = {2012 Jul 17}, pages = {200-7}, abstract = {

OBJECTIVES: This study sought to determine the association of fibroblast growth factor (FGF)-23 with death, heart failure (HF), and cardiovascular disease (CVD) in the general population, as well as the influence of chronic kidney disease (CKD) in this setting.

BACKGROUND: FGF-23 increases renal phosphorus excretion and inhibits vitamin D activation. In end-stage renal disease, high FGF-23 levels are associated with mortality. The association of FGF-23 with death, HF, and CVD in the general population, and the influence of CKD in this setting, are unknown.

METHODS: Plasma FGF-23 was measured in 3,107 community-living persons >= 65 years of age in 1996 and 1997, and participants were followed through 2008. HF and CVD events were adjudicated by a panel of experts. Associations of FGF-23 with each outcome were evaluated using Cox proportional hazards models, and we tested whether associations differed by CKD status.

RESULTS: Both lower estimated glomerular filtration rate and higher urine albumin to creatinine ratios were associated with high FGF-23 at baseline. During 10.5 years (median) follow-up, there were 1,730 deaths, 697 incident HF events, and 797 incident CVD events. Although high FGF-23 concentrations were associated with each outcome in combined analyses, the associations were consistently stronger for those with CKD (p interactions all <0.006). In the CKD group (n = 1,128), the highest FGF-23 quartile had adjusted hazards ratios (HR) of 1.87 (95\% confidence interval [CI]: 1.47 to 2.38) for all-cause death, 1.94 (95\% CI: 1.32 to 2.83) for incident HF, and 1.49 (95\% CI: 1.02 to 2.18) for incident CVD events compared with the lowest quartile. Corresponding HRs in those without CKD (n = 1,979) were 1.29 (95\% CI: 1.05 to 1.59), 1.37 (95\% CI: 0.99 to 1.89), and 1.07 (95\% CI: 0.79 to 1.45).

CONCLUSIONS: FGF-23, a hormone involved in phosphorous and vitamin D homeostasis, is independently associated with all-cause death and incident HF in community-living older persons. These associations appear stronger in persons with CKD.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Female, Fibroblast Growth Factors, Heart Failure, Humans, Kidney Function Tests, Male, Mortality, Renal Insufficiency, Chronic, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2012.03.040}, author = {Ix, Joachim H and Katz, Ronit and Kestenbaum, Bryan R and de Boer, Ian H and Chonchol, Michel and Mukamal, Kenneth J and Rifkin, Dena and Siscovick, David S and Sarnak, Mark J and Shlipak, Michael G} } @article {6083, title = {Fine-mapping and initial characterization of QT interval loci in African Americans.}, journal = {PLoS Genet}, volume = {8}, year = {2012}, month = {2012}, pages = {e1002870}, abstract = {

The QT interval (QT) is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE) studies: the Atherosclerosis Risk in Communities study and Women{\textquoteright}s Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P<=1.20{\texttimes}10(-4)): ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P<=1.37{\texttimes}10(-5)): one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD) patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT across multiple populations, that novel signals exist in African Americans, and that the SNPs identified as strong candidates for functional evaluation implicate gene regulatory dysfunction in QT prolongation.

}, keywords = {African Americans, Aged, Computational Biology, Electrocardiography, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Metagenomics, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Risk Factors, Tachycardia, United States}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002870}, author = {Avery, Christy L and Sethupathy, Praveen and Buyske, Steven and He, Qianchuan and Lin, Dan-Yu and Arking, Dan E and Carty, Cara L and Duggan, David and Fesinmeyer, Megan D and Hindorff, Lucia A and Jeff, Janina M and Klein, Liviu and Patton, Kristen K and Peters, Ulrike and Shohet, Ralph V and Sotoodehnia, Nona and Young, Alicia M and Kooperberg, Charles and Haiman, Christopher A and Mohlke, Karen L and Whitsel, Eric A and North, Kari E} } @article {1407, title = {The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study.}, journal = {Eur Heart J}, volume = {33}, year = {2012}, month = {2012 Nov}, pages = {2709-17}, abstract = {

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice.

METHODS AND RESULTS: We examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6\%) and 568 (27.1\%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height.

CONCLUSION: Independent from sex, increased height is significantly associated with the risk of AF.

}, keywords = {Aged, Atrial Fibrillation, Body Height, Epidemiologic Methods, Female, Humans, Male, Sex Factors, United States}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehs301}, author = {Rosenberg, Michael A and Patton, Kristen K and Sotoodehnia, Nona and Karas, Maria G and Kizer, Jorge R and Zimetbaum, Peter J and Chang, James D and Siscovick, David and Gottdiener, John S and Kronmal, Richard A and Heckbert, Susan R and Mukamal, Kenneth J} } @article {1370, title = {Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.}, journal = {Vasc Med}, volume = {17}, year = {2012}, month = {2012 Apr}, pages = {85-93}, abstract = {

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95\% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95\% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Fasting, Female, Health Surveys, Humans, Incidence, Insulin, Insulin Resistance, Logistic Models, Longitudinal Studies, Male, Odds Ratio, Peripheral Arterial Disease, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1477-0377}, doi = {10.1177/1358863X11436195}, author = {Britton, Kathryn A and Mukamal, Kenneth J and Ix, Joachim H and Siscovick, David S and Newman, Anne B and de Boer, Ian H and Thacker, Evan L and Biggs, Mary L and Gaziano, J Michael and Djouss{\'e}, Luc} } @article {1395, title = {Kidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {60}, year = {2012}, month = {2012 Jul}, pages = {1201-7}, abstract = {

OBJECTIVES: To examine the association between kidney function and all-cause mortality in octogenarians.

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: Community.

PARTICIPANTS: Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.

MEASUREMENTS: Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.

RESULTS: Mean age of the participants was 85, 64\% were female, 66\% had hypertension, 14\% had diabetes mellitus, and 39\% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (>= 75 mL/min per 1.73 m(2) ) and lowest (<= 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95\% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95\% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95\% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).

CONCLUSION: Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

}, keywords = {Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Creatinine, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Diseases, Male, Prevalence, Proportional Hazards Models, Retrospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2012.04046.x}, author = {Shastri, Shani and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Odden, Michelle C and Peralta, Carmen A and Chonchol, Michel and Siscovick, David and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1541, title = {Lifetime risks of cardiovascular disease.}, journal = {N Engl J Med}, volume = {366}, year = {2012}, month = {2012 Jan 26}, pages = {321-9}, abstract = {

BACKGROUND: The lifetime risks of cardiovascular disease have not been reported across the age spectrum in black adults and white adults.

METHODS: We conducted a meta-analysis at the individual level using data from 18 cohort studies involving a total of 257,384 black men and women and white men and women whose risk factors for cardiovascular disease were measured at the ages of 45, 55, 65, and 75 years. Blood pressure, cholesterol level, smoking status, and diabetes status were used to stratify participants according to risk factors into five mutually exclusive categories. The remaining lifetime risks of cardiovascular events were estimated for participants in each category at each age, with death free of cardiovascular disease treated as a competing event.

RESULTS: We observed marked differences in the lifetime risks of cardiovascular disease across risk-factor strata. Among participants who were 55 years of age, those with an optimal risk-factor profile (total cholesterol level, <180 mg per deciliter [4.7 mmol per liter]; blood pressure, <120 mm Hg systolic and 80 mm Hg diastolic; nonsmoking status; and nondiabetic status) had substantially lower risks of death from cardiovascular disease through the age of 80 years than participants with two or more major risk factors (4.7\% vs. 29.6\% among men, 6.4\% vs. 20.5\% among women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal coronary heart disease or nonfatal myocardial infarction (3.6\% vs. 37.5\% among men, <1\% vs. 18.3\% among women) and fatal or nonfatal stroke (2.3\% vs. 8.3\% among men, 5.3\% vs. 10.7\% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts.

CONCLUSIONS: Differences in risk-factor burden translate into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. (Funded by the National Heart, Lung, and Blood Institute.).

}, keywords = {Adult, African Americans, Aged, Cardiovascular Diseases, Cohort Effect, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Risk, Risk Assessment, Risk Factors, United States}, issn = {1533-4406}, doi = {10.1056/NEJMoa1012848}, author = {Berry, Jarett D and Dyer, Alan and Cai, Xuan and Garside, Daniel B and Ning, Hongyan and Thomas, Avis and Greenland, Philip and Van Horn, Linda and Tracy, Russell P and Lloyd-Jones, Donald M} } @article {1400, title = {Modification of the association between ambient air pollution and lung function by frailty status among older adults in the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {176}, year = {2012}, month = {2012 Aug 01}, pages = {214-23}, abstract = {

The susceptibility of older adults to the health effects of air pollution is well-recognized. Advanced age may act as a partial surrogate for conditions associated with aging. The authors investigated whether gerontologic frailty (a clinical health status metric) modified the association between ambient level of ozone or particulate matter with an aerodynamic diameter less than 10 {\textmu}m and lung function in 3,382 older adults using 7 years of follow-up data (1990-1997) from the Cardiovascular Health Study and its Environmental Factors Ancillary Study. Monthly average pollution and annual frailty assessments were related to up to 3 repeated measurements of lung function using cumulative summaries of pollution and frailty histories that accounted for duration as well as concentration. Frailty history was found to modify long-term associations of pollutants with forced vital capacity. For example, the decrease in forced vital capacity associated with a 70-ppb/month greater cumulative sum of monthly average ozone exposure was 12.3 mL (95\% confidence interval: 10.4, 14.2) for a woman who had spent the prior 7 years prefrail or frail as compared with 4.7 mL (95\% confidence interval: 3.8, 5.6) for a similar woman who was robust during all 7 years (interaction P < 0.001).

}, keywords = {Aged, Air Pollution, Cardiovascular Diseases, Female, Forced Expiratory Volume, Frail Elderly, Geriatric Assessment, Humans, Male, Prospective Studies, Respiratory Function Tests, Sex Factors, Smoking, Time Factors, United States, Vital Capacity}, issn = {1476-6256}, doi = {10.1093/aje/kws001}, author = {Eckel, Sandrah P and Louis, Thomas A and Chaves, Paulo H M and Fried, Linda P and Margolis, And Helene G} } @article {1410, title = {Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Dec}, pages = {1252-61}, abstract = {

BACKGROUND: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk.

OBJECTIVES: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort.

DESIGN: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis.

RESULTS: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95\% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95\% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05).

CONCLUSIONS: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Coronary Artery Disease, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Myocardial Ischemia, Principal Component Analysis, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Trans Fatty Acids, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.039990}, author = {Imamura, Fumiaki and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Lichtenstein, Alice H and Matthan, Nirupa R and Herrington, David M and Siscovick, David S and Mozaffarian, Dariush} } @article {1379, title = {Plasma free fatty acids and risk of atrial fibrillation (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {110}, year = {2012}, month = {2012 Jul 15}, pages = {212-6}, abstract = {

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women >=65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 {\textpm} 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95\% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults.

}, keywords = {Aged, Atrial Fibrillation, C-Reactive Protein, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Lipoproteins, HDL, Lipoproteins, LDL, Male, Natriuretic Peptide, Brain, Obesity, Peptide Fragments, Prospective Studies, Sex Factors, Triglycerides, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2012.03.010}, author = {Khawaja, Owais and Bartz, Traci M and Ix, Joachim H and Heckbert, Susan R and Kizer, Jorge R and Zieman, Susan J and Mukamal, Kenneth J and Tracy, Russell P and Siscovick, David S and Djouss{\'e}, Luc} } @article {1357, title = {Predicting late-life disability and death by the rate of decline in physical performance measures.}, journal = {Age Ageing}, volume = {41}, year = {2012}, month = {2012 Mar}, pages = {155-61}, abstract = {

BACKGROUND: the rate of performance decline may influence the risk of disability or death.

METHODS: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998-99, and the rate of performance change between 1992-93 and 1998-99, to the risk of death or disability in 2005-06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992-93 and 1998-99.

RESULTS: participants{\textquoteright} age averaged 79.4 in 1998-99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95\% CI: 1.16 -1.96) and a 1.27 RR of death (95\% CI: 1.07 -1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35\% (95\% CI: 1.13 -1.61) and death by 31\% (95\% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF.

CONCLUSION: performance trajectories independently predict death and disability.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Aging, Disability Evaluation, Disabled Persons, Female, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Linear Models, Male, Mobility Limitation, Mortality, Motor Skills, Predictive Value of Tests, Risk Assessment, Risk Factors, Survival Analysis, Time Factors, United States, Upper Extremity, Walking}, issn = {1468-2834}, doi = {10.1093/ageing/afr151}, author = {Hirsch, Calvin Hayes and B{\r u}zkov{\'a}, Petra and Robbins, John A and Patel, Kushang V and Newman, Anne B} } @article {1384, title = {Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study.}, journal = {Ann Intern Med}, volume = {156}, year = {2012}, month = {2012 May 01}, pages = {627-34}, abstract = {

BACKGROUND: Circulating concentrations of 25-hydroxyvitamin D [25-(OH)D] are used to define vitamin D deficiency. Current clinical 25-(OH)D targets based on associations with intermediate markers of bone metabolism may not reflect optimal levels for other chronic diseases and do not account for known seasonal variation in 25-(OH)D concentration.

OBJECTIVE: To evaluate the relationship of 25-(OH)D concentration with the incidence of major clinical disease events that are pathophysiologically relevant to vitamin D.

DESIGN: Cohort study.

SETTING: The Cardiovascular Health Study conducted in 4 U.S. communities. Data from 1992 to 2006 were included in this analysis.

PARTICIPANTS: 1621 white older adults.

MEASUREMENTS: Serum 25-(OH)D concentration (using a high-performance liquid chromatography-tandem mass spectrometry assay that conforms to National Institute of Standards and Technology reference standards) and associations with time to a composite outcome of incident hip fracture, myocardial infarction, cancer, or death.

RESULTS: Over a median 11-year follow-up, the composite outcome occurred in 1018 participants (63\%). Defining events included 137 hip fractures, 186 myocardial infarctions, 335 incidences of cancer, and 360 deaths. The association of low 25-(OH)D concentration with risk for the composite outcome varied by season (P = 0.057). A concentration lower than a season-specific Z score of -0.54 best discriminated risk for the composite outcome and was associated with a 24\% higher risk in adjusted analyses (95\% CI, 9\% to 42\%). Corresponding season-specific 25-(OH)D concentrations were 43, 50, 61, and 55 nmol/L (17, 20, 24, and 22 ng/mL) in winter, spring, summer, and autumn, respectively.

LIMITATION: The observational study was restricted to white participants.

CONCLUSION: Threshold concentrations of 25-(OH)D associated with increased risk for relevant clinical disease events center near 50 nmol/L (20 ng/mL). Season-specific targets for 25-(OH)D concentration may be more appropriate than static targets when evaluating health risk.

PRIMARY FUNDING SOURCE: National Institutes of Health.

}, keywords = {Aged, Cause of Death, Female, Follow-Up Studies, Hip Fractures, Humans, Male, Myocardial Infarction, Neoplasms, Proportional Hazards Models, Risk Assessment, Risk Factors, Seasons, United States, Vitamin D, Vitamin D Deficiency}, issn = {1539-3704}, doi = {10.7326/0003-4819-156-9-201205010-00004}, author = {de Boer, Ian H and Levin, Gregory and Robinson-Cohen, Cassianne and Biggs, Mary L and Hoofnagle, Andy N and Siscovick, David S and Kestenbaum, Bryan} } @article {1397, title = {Trans-fatty acid consumption and heart rate variability in 2 separate cohorts of older and younger adults.}, journal = {Circ Arrhythm Electrophysiol}, volume = {5}, year = {2012}, month = {2012 Aug 01}, pages = {728-38}, abstract = {

BACKGROUND: Trans-fatty acid (TFA) consumption is associated with risk of coronary heart disease, and trans-18:2, but not trans-18:1, in red blood cell membranes has been associated with sudden cardiac arrest. Abnormal heart rate variability (HRV) reflects autonomic dysfunction and predicts cardiac death. Relationships between TFA consumption and HRV remain understudied. We determined whether total TFA consumption, as well as trans-18:1 and trans-18:2 TFA consumption, was independently associated with HRV in 2 independent cohorts in the United States and Portugal.

METHODS AND RESULTS: In 2 independent cohorts of older US adults (Cardiovascular Health Study [CHS], age 72{\textpm}5 years, 1989/1995) and young Portuguese adults (Porto, age 19{\textpm}2 years, 2008/2010), we assessed habitual TFA intake by food frequency questionnaires in CHS (separately estimating trans-18:1 and trans-18:2) and multiple 24-hour recalls in Porto (estimating total TFA only, which in a subset correlated with circulating trans-18:2 but not trans-18:1, suggesting that we captured the former). HRV was assessed using 24-hour Holters in CHS (n=1076) and repeated short-term (5-minute) ECGs in Porto (n=160). We used multivariate-adjusted linear regression to relate TFA consumption to HRV cross-sectionally (CHS, Porto) and longitudinally (CHS). In CHS, higher trans-18:2 consumption was associated with lower 24-hour SD of all normal-to-normal intervals both cross-sectionally (-12\%; 95\% CI, -19\% to -6\%; P=0.001) and longitudinally (-15\%; 95\% CI, -25\% to -4\%; P= 0.009) and lower 24-hour SD of 5-minute average N-N intervals and mean of the 5-minute SD of N-N intervals calculated over 24 hours (P<0.05 each). Higher trans-18:1 consumption in CHS was associated with more favorable 24-hour HRV in particular time-domain indices (24-hour SD of all normal-to-normal intervals, SD of 5-minute average N-N intervals, mean of the 5-minute SD of N-N intervals calculated over 24 hours; P<0.05 each). In Porto, each higher SD TFA consumption was associated with 4\% lower 5-minute 24-hour SD of all normal-to-normal intervals (95\% CI, -8\% to -1\%; P=0.04) and 7\% lower 5-minute square root of the mean of the squares of successive N-N differences (95\% CI, -13\% to -1\%; P=0.04).

CONCLUSIONS: Trans-18:2 consumption is associated with specific, less favorable indices of HRV in both older and young adults. Trans-18:1 consumption is associated with more favorable HRV indices in older adults. Our results support the need to investigate potential HRV-related mechanisms, whereby trans-18:2 may increase arrhythmic risk.

}, keywords = {Adolescent, Age Factors, Aged, Aging, Arrhythmias, Cardiac, Cohort Studies, Cross-Sectional Studies, Dietary Fats, Electrocardiography, Ambulatory, Feeding Behavior, Female, Heart Rate, Humans, Linear Models, Longitudinal Studies, Male, Multivariate Analysis, Portugal, Predictive Value of Tests, Prospective Studies, Risk Assessment, Risk Factors, Surveys and Questionnaires, Trans Fatty Acids, United States, Young Adult}, issn = {1941-3084}, doi = {10.1161/CIRCEP.111.966259}, author = {Soares-Miranda, Luisa and Stein, Phyllis K and Imamura, Fumiaki and Sattelmair, Jacob and Lemaitre, Rozenn N and Siscovick, David S and Mota, Jorge and Mozaffarian, Dariush} } @article {1403, title = {Transforming growth factor beta-1 and incidence of heart failure in older adults: the Cardiovascular Health Study.}, journal = {Cytokine}, volume = {60}, year = {2012}, month = {2012 Nov}, pages = {341-5}, abstract = {

CONTEXT: Transforming growth factor-beta1 (TGF-B1) is a highly pleiotropic cytokine whose functions include a central role in the induction of fibrosis.

OBJECTIVE: To investigate the hypothesis that elevated plasma levels of TGF-B1 are positively associated with incident heart failure (HF).

PARTICIPANTS AND METHODS: The hypotheses were tested using a two-phase case-control study design, ancillary to the Cardiovascular Health Study - a longitudinal, population-based cohort study. Cases were defined as having an incident HF event after their 1992-1993 exam and controls were free of HF at follow-up. TGF-B1 was measured using plasma collected in 1992-1993 and data from 89 cases and 128 controls were used for analysis. The association between TGF-B1 and risk of HF was evaluated using the weighted likelihood method, and odds ratios (OR) for risk of HF were calculated for TGF-B1 as a continuous linear variable and across quartiles of TGF-B1.

RESULTS: The OR for HF was 1.88 (95\% confidence intervals [CI] 1.26-2.81) for each nanogram increase in TGF-B1, and the OR for the highest quartile (compared to the lowest) of TGF-B1 was 5.79 (95\% CI 1.65-20.34), after adjustment for age, sex, C-reactive protein, platelet count and digoxin use. Further adjustment with other covariates did not change the results.

CONCLUSIONS: Higher levels of plasma TGF-B1 were associated with an increased risk of incident heart failure among older adults. However, further study is needed in larger samples to confirm these findings.

}, keywords = {Aged, Case-Control Studies, Health, Heart Failure, Humans, Incidence, Transforming Growth Factor beta1, United States}, issn = {1096-0023}, doi = {10.1016/j.cyto.2012.07.013}, author = {Glazer, Nicole L and Macy, Elizabeth M and Lumley, Thomas and Smith, Nicholas L and Reiner, Alex P and Psaty, Bruce M and King, George L and Tracy, Russell P and Siscovick, David S} } @article {6059, title = {Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study.}, journal = {Osteoporos Int}, volume = {24}, year = {2013}, month = {2013 Dec}, pages = {2993-3000}, abstract = {

UNLABELLED: The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78~years). We find a small independent association in women but not in men.

INTRODUCTION: The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30~mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78~years.

METHODS: From the Cardiovascular Health Study (41~\% male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5~years. BMD was performed in a subset of 1,208 participants.

RESULTS: There were 313 hip fractures during follow-up (7.7~\% of men; 11.7~\% of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95~\% CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009~g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women.

CONCLUSIONS: In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Bone Density, Female, Follow-Up Studies, Hip Fractures, Hip Joint, Humans, Incidence, Kaplan-Meier Estimate, Male, Osteoporotic Fractures, Risk Factors, Sex Factors, United States}, issn = {1433-2965}, doi = {10.1007/s00198-013-2389-3}, author = {Barzilay, J I and B{\r u}{\v z}kov{\'a}, P and Chen, Z and de Boer, I H and Carbone, L and Rassouli, N N and Fink, H A and Robbins, J A} } @article {6827, title = {Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with serum uric acid and gout in 4 US populations: the PAGE Study.}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, month = {2013 May 1}, pages = {923-32}, abstract = {

A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 {\texttimes} 10(-67), P = 3.98 {\texttimes} 10(-5), P = 6.97 {\texttimes} 10(-9), and P = 5.33 {\texttimes} 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 {\texttimes} 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 {\texttimes} 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 {\texttimes} 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout.

}, keywords = {Adult, African Americans, Age Distribution, ATP-Binding Cassette Transporters, Comorbidity, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetics, Population, Genome-Wide Association Study, Gout, Hormone Replacement Therapy, Humans, Indians, North American, Male, Mexican Americans, Middle Aged, Neoplasm Proteins, Polymorphism, Genetic, Postmenopause, Sex Distribution, United States, Uric Acid}, issn = {1476-6256}, doi = {10.1093/aje/kws330}, author = {Zhang, Lili and Spencer, Kylee L and Voruganti, V Saroja and Jorgensen, Neal W and Fornage, Myriam and Best, Lyle G and Brown-Gentry, Kristin D and Cole, Shelley A and Crawford, Dana C and Deelman, Ewa and Franceschini, Nora and Gaffo, Angelo L and Glenn, Kimberly R and Heiss, Gerardo and Jenny, Nancy S and K{\"o}ttgen, Anna and Li, Qiong and Liu, Kiang and Matise, Tara C and North, Kari E and Umans, Jason G and Kao, W H Linda} } @article {6061, title = {Association of heat shock proteins with all-cause mortality.}, journal = {Age (Dordr)}, volume = {35}, year = {2013}, month = {2013 Aug}, pages = {1367-76}, abstract = {

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

}, keywords = {Aged, 80 and over, Aging, Cause of Death, Forecasting, Genotype, Heat-Shock Proteins, Humans, Longevity, Promoter Regions, Genetic, Retrospective Studies, Transcription, Genetic, United States}, issn = {1574-4647}, doi = {10.1007/s11357-012-9417-7}, author = {Broer, L and Demerath, E W and Garcia, M E and Homuth, G and Kaplan, R C and Lunetta, K L and Tanaka, T and Tranah, G J and Walter, S and Arnold, A M and Atzmon, G and Harris, T B and Hoffmann, W and Karasik, D and Kiel, D P and Kocher, T and Launer, L J and Lohman, K K and Rotter, J I and Tiemeier, H and Uitterlinden, A G and Wallaschofski, H and Bandinelli, S and D{\"o}rr, M and Ferrucci, L and Franceschini, N and Gudnason, V and Hofman, A and Liu, Y and Murabito, J M and Newman, A B and Oostra, B A and Psaty, B M and Smith, A V and van Duijn, C M} } @article {5846, title = {Associations of plasma phospholipid and dietary alpha linolenic acid with incident atrial fibrillation in older adults: the Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {2}, year = {2013}, month = {2013 Jan 31}, pages = {e003814}, abstract = {

BACKGROUND: Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF).

METHODS AND RESULTS: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95\% CI, 0.90 to 1.37), 1.09 (95\% CI, 0.88 to 1.35), and 0.92 (95\% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar.

CONCLUSIONS: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

}, keywords = {Age Factors, Aged, Aged, 80 and over, alpha-Linolenic Acid, Atrial Fibrillation, Biomarkers, Diet, Female, Humans, Incidence, Linear Models, Longitudinal Studies, Male, Nutritional Status, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.112.003814}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Heckbert, Susan R and McKnight, Barbara and King, Irena B and Rimm, Eric B and Psaty, Bruce M and Sacks, Frank M and Song, Xiaoling and Spiegelman, Donna and Lemaitre, Rozenn N} } @article {5850, title = {Atrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study.}, journal = {JAMA Intern Med}, volume = {173}, year = {2013}, month = {2013 Jan 14}, pages = {29-35}, abstract = {

BACKGROUND: It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.

METHODS: In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2\% women; and 26.6\% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, >=65 years; 58.2\% women; and 15.4\% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.

RESULTS: In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95\% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95\% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95\% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively.

CONCLUSIONS: Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.

}, keywords = {Aged, Atrial Fibrillation, Cardiovascular Diseases, Death, Sudden, Cardiac, Demography, Ethnic Groups, Female, Humans, Incidence, Male, Middle Aged, Proportional Hazards Models, Risk Assessment, Risk Factors, Sex Factors, United States}, issn = {2168-6114}, doi = {10.1001/2013.jamainternmed.744}, author = {Chen, Lin Y and Sotoodehnia, Nona and B{\r u}zkov{\'a}, Petra and Lopez, Faye L and Yee, Laura M and Heckbert, Susan R and Prineas, Ronald and Soliman, Elsayed Z and Adabag, Selcuk and Konety, Suma and Folsom, Aaron R and Siscovick, David and Alonso, Alvaro} } @article {6001, title = {Blood pressure variability and the risk of all-cause mortality, incident myocardial infarction, and incident stroke in the cardiovascular health study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Oct}, pages = {1210-7}, abstract = {

BACKGROUND: Recent reports have linked variability in visit-to-visit systolic blood pressure (SBP) to risk of mortality and stroke, independent of the effect of mean SBP level. This study aimed to evaluate whether variability in SBP is associated with all-cause mortality, incident myocardial infarction (MI), and incident stroke, independent of mean SBP or trends in SBP levels over time.

METHODS: The Cardiovascular Health Study is a longitudinal cohort study of vascular risk factors and disease in the elderly. Participants who attended their first 5 annual clinic visits and experienced no event before the 5th visit were eligible (n = 3,852). Primary analyses were restricted to participants not using antihypertensive medications throughout the first 5 clinic visits (n = 1,642). Intraindividual SBP variables were defined using each participant{\textquoteright}s 5-visit blood pressure measures. Cox proportional hazards models estimated adjusted hazard ratios (HRs) per SD increase in intraindividual SBP variability, adjusted for intraindividual SBP mean and change over time.

RESULTS: Over a mean follow-up of 9.9 years, there were 844 deaths, 203 MIs, and 195 strokes. Intraindividual SBP variability was significantly associated with increased risk of mortality (HR = 1.13; 95\% confidence interval (CI) = 1.05-1.21) and of incident MI (HR = 1.20; 95\%CI = 1.06-1.36), independent of the effect from adjustment factors. Intraindividual SBP variability was not associated with risk of stroke (HR = 1.03; 95\% CI = 0.89-1.21).

CONCLUSIONS: Long-term visit-to-visit SBP variability was independently associated with a higher risk of subsequent mortality and MI but not stroke. More research is needed to determine the relationship of BP variability with cardiovascular risk and the clinical implications.

}, keywords = {Aged, Blood Pressure, Cohort Studies, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Myocardial Infarction, Risk, Stroke, United States}, issn = {1941-7225}, doi = {10.1093/ajh/hpt092}, author = {Suchy-Dicey, Astrid M and Wallace, Erin R and Mitchell, S V Elkind and Aguilar, Maria and Gottesman, Rebecca F and Rice, Kenneth and Kronmal, Richard and Psaty, Bruce M and Longstreth, W T} } @article {6030, title = {The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium as a model of collaborative science.}, journal = {Epidemiology}, volume = {24}, year = {2013}, month = {2013 May}, pages = {346-8}, keywords = {Aging, Cohort Studies, Cooperative Behavior, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Multicenter Studies as Topic, Myocardial Infarction, Research Support as Topic, Stroke, United States}, issn = {1531-5487}, doi = {10.1097/EDE.0b013e31828b2cbb}, author = {Psaty, Bruce M and Sitlani, Colleen} } @article {6063, title = {Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Mar}, pages = {401-8}, abstract = {

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.

OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans.

METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P<=2.5{\texttimes}10(-8)).

RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98{\texttimes}10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.

CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

}, keywords = {Adult, African Americans, Aged, Arrhythmias, Cardiac, Connexin 43, Electrocardiography, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Rest, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2012.11.014}, author = {Deo, R and Nalls, M A and Avery, C L and Smith, J G and Evans, D S and Keller, M F and Butler, A M and Buxbaum, S G and Li, G and Miguel Quibrera, P and Smith, E N and Tanaka, T and Akylbekova, E L and Alonso, A and Arking, D E and Benjamin, E J and Berenson, G S and Bis, J C and Chen, L Y and Chen, W and Cummings, S R and Ellinor, P T and Evans, M K and Ferrucci, L and Fox, E R and Heckbert, S R and Heiss, G and Hsueh, W C and Kerr, K F and Limacher, M C and Liu, Y and Lubitz, S A and Magnani, J W and Mehra, R and Marcus, G M and Murray, S S and Newman, A B and Njajou, O and North, K E and Paltoo, D N and Psaty, B M and Redline, S S and Reiner, A P and Robinson, J G and Rotter, J I and Samdarshi, T E and Schnabel, R B and Schork, N J and Singleton, A B and Siscovick, D and Soliman, E Z and Sotoodehnia, N and Srinivasan, S R and Taylor, H A and Trevisan, M and Zhang, Z and Zonderman, A B and Newton-Cheh, C and Whitsel, E A} } @article {5992, title = {Decline in health for older adults: five-year change in 13 key measures of standardized health.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {68}, year = {2013}, month = {2013 Sep}, pages = {1059-67}, abstract = {

BACKGROUND: The health of older adults declines over time, but there are many ways of measuring health. It is unclear whether all health measures decline at the same rate or whether some aspects of health are less sensitive to aging than others.

METHODS: We compared the decline in 13 measures of physical, mental, and functional health from the Cardiovascular Health Study: hospitalization, bed days, cognition, extremity strength, feelings about life as a whole, satisfaction with the purpose of life, self-rated health, depression, digit symbol substitution test, grip strength, activities of daily living, instrumental activities of daily living, and gait speed. Each measure was standardized against self-rated health. We compared the 5-year change to see which of the 13 measures declined the fastest and the slowest.

RESULTS: The 5-year change in standardized health varied from a decline of 12 points (out of 100) for hospitalization to a decline of 17 points for gait speed. In most comparisons, standardized health from hospitalization and bed days declined the least, whereas health measured by activities of daily living, instrumental activities of daily living, and gait speed declined the most. These rankings were independent of age, sex, mortality patterns, and the method of standardization.

CONCLUSIONS: All of the health variables declined, on average, with advancing age, but at significantly different rates. Standardized measures of mental health, cognition, quality of life, and hospital utilization did not decline as fast as gait speed, activities of daily living, and instrumental activities of daily living. Public health interventions to address problems with gait speed, activities of daily living, and instrumental activities of daily living may help older adults to remain healthier in all dimensions.

}, keywords = {Activities of Daily Living, Aged, Aging, Cohort Studies, Female, Gait, Health Status, Health Status Indicators, Hospitalization, Humans, Longitudinal Studies, Male, Mental Health, Quality of Life, Self Report, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt038}, author = {Diehr, Paula H and Thielke, Stephen M and Newman, Anne B and Hirsch, Calvin and Tracy, Russell} } @article {6095, title = {Evaluating subject-level incremental values of new markers for risk classification rule.}, journal = {Lifetime Data Anal}, volume = {19}, year = {2013}, month = {2013 Oct}, pages = {547-67}, abstract = {

Suppose that we need to classify a population of subjects into several well-defined ordered risk categories for disease prevention or management with their "baseline" risk factors/markers. In this article, we present a systematic approach to identify subjects using their conventional risk factors/markers who would benefit from a new set of risk markers for more accurate classification. Specifically for each subgroup of individuals with the same conventional risk estimate, we present inference procedures for the reclassification and the corresponding correct re-categorization rates with the new markers. We then apply these new tools to analyze the data from the Cardiovascular Health Study sponsored by the US National Heart, Lung, and Blood Institute. We used Framingham risk factors plus the information of baseline anti-hypertensive drug usage to identify adult American women who may benefit from the measurement of a new blood biomarker, CRP, for better risk classification in order to intensify prevention of coronary heart disease for the subsequent 10 years.

}, keywords = {Aged, Antihypertensive Agents, Biomarkers, Biostatistics, C-Reactive Protein, Confidence Intervals, Coronary Disease, Female, Humans, Risk, Risk Factors, Statistics, Nonparametric, United States}, issn = {1572-9249}, doi = {10.1007/s10985-013-9272-6}, author = {Cai, T and Tian, L and Lloyd-Jones, D and Wei, L J} } @article {5856, title = {Exploring psychosocial pathways between neighbourhood characteristics and stroke in older adults: the cardiovascular health study.}, journal = {Age Ageing}, volume = {42}, year = {2013}, month = {2013 May}, pages = {391-7}, abstract = {

OBJECTIVES: to investigate whether psychosocial pathways mediate the association between neighbourhood socioeconomic disadvantage and stroke.

METHODS: prospective cohort study with a follow-up of 11.5 years.

SETTING: the Cardiovascular Health Study, a longitudinal population-based cohort study of older adults >=65 years.

MEASUREMENTS: the primary outcome was adjudicated incident ischaemic stroke. Neighbourhood socioeconomic status (NSES) was measured using a composite of six census-tract variables. Psychosocial factors were assessed with standard measures for depression, social support and social networks.

RESULTS: of the 3,834 white participants with no prior stroke, 548 had an incident ischaemic stroke over the 11.5-year follow-up. Among whites, the incident stroke hazard ratio (HR) associated with living in the lowest relative to highest NSES quartile was 1.32 (95\% CI = 1.01-1.73), in models adjusted for individual SES. Additional adjustment for psychosocial factors had a minimal effect on hazard of incident stroke (HR = 1.31, CI = 1.00-1.71). Associations between NSES and stroke incidence were not found among African-Americans (n = 785) in either partially or fully adjusted models.

CONCLUSIONS: psychosocial factors played a minimal role in mediating the effect of NSES on stroke incidence among white older adults.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Aging, Brain Ischemia, Depression, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Linear Models, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Residence Characteristics, Risk Assessment, Risk Factors, Social Support, Socioeconomic Factors, Stroke, Time Factors, United States, Vulnerable Populations}, issn = {1468-2834}, doi = {10.1093/ageing/afs179}, author = {Yan, Tingjian and Escarce, Jos{\'e} J and Liang, Li-Jung and Longstreth, W T and Merkin, Sharon Stein and Ovbiagele, Bruce and Vassar, Stefanie D and Seeman, Teresa and Sarkisian, Catherine and Brown, Arleen F} } @article {1565, title = {Fatty acid-binding protein 4 and incident heart failure: the Cardiovascular Health Study.}, journal = {Eur J Heart Fail}, volume = {15}, year = {2013}, month = {2013 Apr}, pages = {394-9}, chapter = {394}, abstract = {

AIM: To examine the association of plasma fatty acid-binding protein 4 (FABP4) with incident heart failure.

METHODS AND RESULTS: In a prospective study of 4179 participants from the Cardiovascular Health Study, we measured plasma FABP4 on blood specimens collected between 1992 and 1993. Incident heart failure was adjudicated by an endpoint committee and we used a Cox proportional hazards model to calculate hazard ratios (HRs) of heart failure. The average age at baseline was 75 years. During a median follow-up of 10.7 years, 1182 cases of incident heart failure occurred. We observed a positive association between FABP4 and heart failure in the minimally adjusted models [HR 1.32, 95\% confidence interval (CI) 1.25-1.38 per 1 SD higher FABP4] that was attenuated upon adjustment for potential confounders, mostly kidney function and body mass index (corresponding HR 1.09, 95\% CI 1.01-1.17). In a subsample of heart failure cases with available data on LV systolic function, FABP4 was not associated with heart failure with or without preserved LV systolic function. Exclusion of people with unintentional weight loss and self-reported fair/poor health status did not alter the conclusion.

CONCLUSION: An elevated plasma concentration of FABP4 was associated with a modestly higher risk of heart failure in older adults in the USA after adjustment for confounding factors.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Fatty Acid-Binding Proteins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Male, Proportional Hazards Models, Prospective Studies, Risk Factors, United States, Ventricular Function, Left}, issn = {1879-0844}, doi = {10.1093/eurjhf/hfs196}, author = {Djouss{\'e}, Luc and Bartz, Traci M and Ix, Joachim H and Kochar, Jinesh and Kizer, Jorge R and Gottdiener, John S and Tracy, Russell P and Mozaffarian, Dariush and Siscovick, David S and Mukamal, Kenneth J and Zieman, Susan J} } @article {1358, title = {Height and risk of incident intraparenchymal hemorrhage: Atherosclerosis Risk in Communities and Cardiovascular Health study cohorts.}, journal = {J Stroke Cerebrovasc Dis}, volume = {22}, year = {2013}, month = {2013 May}, pages = {323-8}, abstract = {

BACKGROUND: Height is inversely associated with incident coronary disease and total stroke, but few studies have examined the association between height and intraparenchymal hemorrhage (IPH). We hypothesized that height would be inversely associated with incident IPH in the combined cohorts of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study.

METHODS: Data on Caucasian and African American participants were used to estimate the association of height at baseline with incident IPH verified by clinician review of medical records and imaging reports. Sex-specific Cox proportional hazards regression models were used to calculate hazard ratios.

RESULTS: A total of 20,983 participants initially free of stroke (11,788 women and 9195 men) were followed for an average of 15.9 years (standard deviation [SD] 5.1 years). Incident IPH occurred in 115 women and 73 men. Sex, but not age, race, study, or blood pressure, modified the association (P = .03). After adjustment for risk factors (age, systolic blood pressure, triglycerides, low-density lipoprotein cholesterol, fibrinogen, and race), among women, height was significantly inversely associated with incident IPH (hazard ratio [HR] per SD [6.3 cm] was 0.81; 95\% confidence interval [CI] 0.66-0.99; P = .04). The HR for tertile 3 vs 1 in women was 0.63 (95\% CI 0.37-1.08). Among men, height was not linearly associated with incident IPH (HR per SD [6.7 cm] was 1.09; 95\% CI 0.84-1.40; P = .52).

CONCLUSIONS: This large prospective study provides evidence that shorter height may be a risk factor for incident IPH in women.

}, keywords = {African Americans, Aged, Body Height, Cerebral Hemorrhage, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1532-8511}, doi = {10.1016/j.jstrokecerebrovasdis.2011.09.004}, author = {Smith, Lindsay G and Yatsuya, Hiroshi and Psaty, Bruce M and Longstreth, W T and Folsom, Aaron R} } @article {5854, title = {Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.}, journal = {Ann Epidemiol}, volume = {23}, year = {2013}, month = {2013 Mar}, pages = {106-11}, abstract = {

PURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age.

METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.

RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95\% confidence interval [CI], 0.1, 4.4), 5.1 (95\% CI, 4.1, 6.1), and 6.9 (95\%~CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80~years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95\% CI, 3.5, 6.3), 7.1 (95\% CI, 6.0, 8.3), 8.9 (95\% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.

CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Causality, Cholesterol, LDL, Cohort Studies, Comorbidity, Cross-Sectional Studies, Cystatin C, Female, Humans, Hypertension, Kidney Function Tests, Male, Netherlands, Obesity, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Smoking, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2012.12.004}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Fried, Linda F and Newman, Anne B and Katz, Ronit and Satterfield, Suzanne and Harris, Tamara B and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {6630, title = {The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: the PAGE study.}, journal = {Diabetes}, volume = {62}, year = {2013}, month = {2013 May}, pages = {1763-7}, abstract = {

Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages >=70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m{\texttwosuperior}, respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Aging, Body Mass Index, Cohort Studies, Cross-Sectional Studies, European Continental Ancestry Group, Female, Genetic Association Studies, Health Surveys, Humans, Male, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Proteins, United States, Young Adult}, issn = {1939-327X}, doi = {10.2337/db12-0863}, author = {Graff, Mariaelisa and Gordon-Larsen, Penny and Lim, Unhee and Fowke, Jay H and Love, Shelly-Ann and Fesinmeyer, Megan and Wilkens, Lynne R and Vertilus, Shawyntee and Ritchie, Marilyn D and Prentice, Ross L and Pankow, Jim and Monroe, Kristine and Manson, JoAnn E and Le Marchand, Lo{\"\i}c and Kuller, Lewis H and Kolonel, Laurence N and Hong, Ching P and Henderson, Brian E and Haessler, Jeff and Gross, Myron D and Goodloe, Robert and Franceschini, Nora and Carlson, Christopher S and Buyske, Steven and B{\r u}zkov{\'a}, Petra and Hindorff, Lucia A and Matise, Tara C and Crawford, Dana C and Haiman, Christopher A and Peters, Ulrike and North, Kari E} } @article {6136, title = {Kidney function and prevalent and incident frailty.}, journal = {Clin J Am Soc Nephrol}, volume = {8}, year = {2013}, month = {2013 Dec}, pages = {2091-9}, abstract = {

BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: CHS enrolled community-dwelling adults age >=65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.

RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24\% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) >=90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95\% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95\% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95\% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95\% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95\% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95\% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.

CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Creatinine, Cross-Sectional Studies, Cystatin C, Fatigue, Female, Frail Elderly, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Independent Living, Kidney, Kidney Diseases, Logistic Models, Male, Motor Activity, Multivariate Analysis, Muscle Weakness, Odds Ratio, Phenotype, Prevalence, Prospective Studies, Risk Factors, Time Factors, United States, Weight Loss}, issn = {1555-905X}, doi = {10.2215/CJN.02870313}, author = {Dalrymple, Lorien S and Katz, Ronit and Rifkin, Dena E and Siscovick, David and Newman, Anne B and Fried, Linda F and Sarnak, Mark J and Odden, Michelle C and Shlipak, Michael G} } @article {6094, title = {Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four US populations: the Population Architecture using Genomics and Epidemiology (PAGE) study.}, journal = {Atherosclerosis}, volume = {228}, year = {2013}, month = {2013 Jun}, pages = {390-9}, abstract = {

BACKGROUND: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque.

METHODS: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model.

RESULTS: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR~=~1.32, 95\% confidence interval: 1.17, 1.49, P~=~1.08~{\texttimes}~10(-5)), but not in the other populations (P~=~0.90 in EA and P~=~0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR~=~1.07, P~=~0.02) and in AI (OR~=~1.10, P~=~0.05).

CONCLUSIONS: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.

}, keywords = {African Americans, Aged, Ankle Brachial Index, Asymptomatic Diseases, Carotid Artery Diseases, Carotid Intima-Media Thickness, Coronary Disease, European Continental Ancestry Group, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Indians, North American, Linear Models, Logistic Models, Male, Mexican Americans, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Risk Assessment, Risk Factors, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.02.038}, author = {Zhang, Lili and B{\r u}zkov{\'a}, Petra and Wassel, Christina L and Roman, Mary J and North, Kari E and Crawford, Dana C and Boston, Jonathan and Brown-Gentry, Kristin D and Cole, Shelley A and Deelman, Ewa and Goodloe, Robert and Wilson, Sarah and Heiss, Gerardo and Jenny, Nancy S and Jorgensen, Neal W and Matise, Tara C and McClellan, Bob E and Nato, Alejandro Q and Ritchie, Marylyn D and Franceschini, Nora and Kao, W H Linda} } @article {5847, title = {Lifetime risk for heart failure among white and black Americans: cardiovascular lifetime risk pooling project.}, journal = {J Am Coll Cardiol}, volume = {61}, year = {2013}, month = {2013 Apr 09}, pages = {1510-7}, chapter = {1510}, abstract = {

OBJECTIVES: This study sought to estimate lifetime risk for heart failure (HF) by sex and race.

BACKGROUND: Prior estimates of lifetime risk for developing HF range from 20\% to 33\% in predominantly white cohorts. Short-term risks for HF appear higher for blacks than whites, but only limited comparisons of lifetime risk for HF have been made.

METHODS: Using public-release and internal datasets from National Heart, Lung, and Blood Institute-sponsored cohorts, we estimated lifetime risks for developing HF to age 95 years, with death free of HF as the competing event, among participants in the CHA (Chicago Heart Association Detection Project in Industry), ARIC (Atherosclerosis Risk in Communities), and CHS (Cardiovascular Health Study) cohorts.

RESULTS: There were 39,578 participants (33,652 [85\%] white; 5,926 [15\%] black) followed for 716,976 person-years; 5,983 participants developed HF. At age 45 years, lifetime risks for HF through age 95 years in CHA and CHS were 30\% to 42\% in white men, 20\% to 29\% in black men, 32\% to 39\% in white women, and 24\% to 46\% in black women. Results for ARIC demonstrated similar lifetime risks for HF in blacks and whites through age 75 years (limit of follow-up). Lifetime risk for HF was higher with higher blood pressure and body mass index at all ages in both blacks and whites, and did not diminish substantially with advancing index age.

CONCLUSIONS: These are among the first data to compare lifetime risks for HF between blacks and whites. Lifetime risks for HF are high and appear similar for black and white women, yet are somewhat lower for black compared with white men due to competing risks.

}, keywords = {Adolescent, Adult, African Americans, Age Factors, Aged, Anthropometry, Body Mass Index, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Female, Health Surveys, Heart Failure, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, Time Factors, United States, Young Adult}, issn = {1558-3597}, doi = {10.1016/j.jacc.2013.01.022}, author = {Huffman, Mark D and Berry, Jarett D and Ning, Hongyan and Dyer, Alan R and Garside, Daniel B and Cai, Xuan and Daviglus, Martha L and Lloyd-Jones, Donald M} } @article {6281, title = {Lipoprotein receptor-related protein 1 variants and dietary fatty acids: meta-analysis of European origin and African American studies.}, journal = {Int J Obes (Lond)}, volume = {37}, year = {2013}, month = {2013 Sep}, pages = {1211-20}, abstract = {

OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.

DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).

RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed.

CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.

}, keywords = {Adipose Tissue, Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Body Mass Index, Europe, European Continental Ancestry Group, Fatty Acids, Female, Gene Frequency, Gene-Environment Interaction, Genetic Predisposition to Disease, Genotype, Humans, Low Density Lipoprotein Receptor-Related Protein-1, Male, Middle Aged, Obesity, Phenotype, Polymorphism, Single Nucleotide, Prevalence, United States}, issn = {1476-5497}, doi = {10.1038/ijo.2012.215}, author = {Smith, C E and Ngwa, J and Tanaka, T and Qi, Q and Wojczynski, M K and Lemaitre, R N and Anderson, J S and Manichaikul, A and Mikkil{\"a}, V and van Rooij, F J A and Ye, Z and Bandinelli, S and Frazier-Wood, A C and Houston, D K and Hu, F and Langenberg, C and McKeown, N M and Mozaffarian, D and North, K E and Viikari, J and Zillikens, M C and Djouss{\'e}, L and Hofman, A and K{\"a}h{\"o}nen, M and Kabagambe, E K and Loos, R J F and Saylor, G B and Forouhi, N G and Liu, Y and Mukamal, K J and Chen, Y-D I and Tsai, M Y and Uitterlinden, A G and Raitakari, O and van Duijn, C M and Arnett, D K and Borecki, I B and Cupples, L A and Ferrucci, L and Kritchevsky, S B and Lehtim{\"a}ki, T and Qi, Lu and Rotter, J I and Siscovick, D S and Wareham, N J and Witteman, J C M and Ordov{\'a}s, J M and Nettleton, J A} } @article {6064, title = {Plasma free fatty acids and risk of heart failure: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {6}, year = {2013}, month = {2013 Sep 01}, pages = {964-9}, abstract = {

BACKGROUND: Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes mellitus and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF).

METHODS AND RESULTS: To test the hypothesis that plasma concentration of FFAs is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and >65 years old from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per SD of FFAs. During a median follow-up of 10.5 years, a total of 1286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12\% (95\% confidence interval, 6\%-19\%) higher risk of HF. Controlling for time-varying diabetes mellitus and coronary heart disease did not change the results (hazard ratio per SD, 1.16 [95\% confidence interval, 1.09-1.23]).

CONCLUSIONS: A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biological mechanisms by which FFAs may influence the risk of HF and determine whether FFAs could serve as a novel pharmacological target for HF prevention.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Fatty Acids, Nonesterified, Female, Heart Failure, Humans, Incidence, Kaplan-Meier Estimate, Linear Models, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.113.000521}, author = {Djouss{\'e}, Luc and Benkeser, David and Arnold, Alice and Kizer, Jorge R and Zieman, Susan J and Lemaitre, Rozenn N and Tracy, Russell P and Gottdiener, John S and Mozaffarian, Dariush and Siscovick, David S and Mukamal, Kenneth J and Ix, Joachim H} } @article {5852, title = {Racial differences in the incidence of and risk factors for atrial fibrillation in older adults: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {61}, year = {2013}, month = {2013 Feb}, pages = {276-80}, abstract = {

This study examined whether different associations between risk factors and atrial fibrillation (AF) according to race could explain the lower incidence of AF in blacks. Baseline risk factor information was obtained from interviews, clinical examinations, and echocardiography in 4,774 white and 911 black Cardiovascular Health Study participants aged 65 and older without a history of AF at baseline in 1989/90 or 1992/93. Incident AF was determined according to hospital discharge diagnosis or annual study electrocardiogram. Cox regression was used to assess associations between risk factors and race and incident AF. During a mean 11.2 years of follow-up, 1,403 whites and 182 blacks had incident AF. Associations between all examined risk factors were similar in both races, except left ventricular posterior wall thickness, which was more strongly associated with AF in blacks (per 0.2 cm, blacks: hazard ratio (HR) = 1.72, 95\% confidence interval (CI) = 1.44-2.06; whites: HR = 1.30, 95\% CI = 1.18-1.43). Overall, the relative risk of AF was 25\% lower in blacks than whites after adjustment for age and sex (HR = 0.75, 95\% CI = 0.64-0.87) and 45\% lower after adjustment for all considered risk factors (HR = 0.55, 95\% CI = 0.35-0.88). Different associations of the considered risk factors and incident AF by race do not explain the lower incidence of AF in blacks.

}, keywords = {Aged, Atrial Fibrillation, Continental Population Groups, Female, Follow-Up Studies, Humans, Incidence, Male, Prevalence, Risk Assessment, Risk Factors, Stroke, United States}, issn = {1532-5415}, doi = {10.1111/jgs.12085}, author = {Jensen, Paul N and Thacker, Evan L and Dublin, Sascha and Psaty, Bruce M and Heckbert, Susan R} } @article {1559, title = {Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {111}, year = {2013}, month = {2013 Feb 01}, pages = {418-24}, abstract = {

Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 {\textpm} 4.9 years, 69.7\% were women, and 21\% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 {\textpm} 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels >=65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95\% confidence interval 36.1 to 204), 5.2 pg/ml (95\% confidence interval 3.0 to 7.4), and 17 g (95\% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.

}, keywords = {Adult, Aged, Biomarkers, Cardiovascular Diseases, Echocardiography, Electrocardiography, Female, Follow-Up Studies, Heart Ventricles, Humans, Incidence, Male, Mass Spectrometry, Middle Aged, Parathyroid Hormone, Prospective Studies, United States, Vitamin D}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2012.10.021}, author = {van Ballegooijen, Adriana J and Visser, Marjolein and Kestenbaum, Bryan and Siscovick, David S and de Boer, Ian H and Gottdiener, John S and deFilippi, Christopher R and Brouwer, Ingeborg A} } @article {5851, title = {Risk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {61}, year = {2013}, month = {2013 Feb 12}, pages = {635-42}, chapter = {635}, abstract = {

OBJECTIVES: This study sought to identify risk factors for the occurrence of all-cause hospital admissions among older persons after heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors for admission when evaluated in the context of other relevant clinical data.

BACKGROUND: Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk for hospital admission after heart failure diagnosis. With the aging of the population with heart failure, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common.

METHODS: The study population included participants with a new diagnosis of heart failure in the Cardiovascular Health Study, a longitudinal study of community-living older persons. Data were collected through annual examinations and medical-record reviews. Geriatric conditions assessed were slow gait, muscle weakness (defined as weak grip), cognitive impairment, and depressive symptoms. Anderson-Gill regression modeling was used to determine the predictors of hospital admission after heart failure diagnosis.

RESULTS: Of the 758 participants with a new diagnosis of heart failure, the mean rate of hospital admission was 7.9 per 10 person-years (95\% CI: 7.4 to 8.4). Independent risk factors for hospital admission included diabetes mellitus (HR: 1.36; 95\% CI: 1.13 to 1.64), New York Heart Association functional class III or IV (HR: 1.32; 95\% CI: 1.11 to 1.57), chronic kidney disease (HR: 1.32; 95\% CI: 1.14 to 1.53), slow gait (HR: 1.28; 95\% CI: 1.06 to 1.55), depressed ejection fraction (HR: 1.25; 95\% CI: 1.04 to 1.51), depression (HR: 1.23; 95\% CI: 1.05 to 1.45), and muscle weakness (HR: 1.19; 95\% CI: 1.00 to 1.42).

CONCLUSIONS: Geriatric conditions are important, and potentially modifiable, risk factors for hospital admission in heart failure that should be routinely assessed at the time of heart failure diagnosis.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Comorbidity, Effect Modifier, Epidemiologic, Female, Geriatric Assessment, Health Surveys, Heart Failure, Hospitalization, Humans, Longitudinal Studies, Male, Mental Competency, Risk Assessment, Risk Factors, Severity of Illness Index, Stroke Volume, Time-to-Treatment, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2012.11.027}, author = {Chaudhry, Sarwat I and McAvay, Gail and Chen, Shu and Whitson, Heather and Newman, Anne B and Krumholz, Harlan M and Gill, Thomas M} } @article {5994, title = {Risk factors for type 2 diabetes mellitus preceded by β-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, month = {2013 Jun 15}, pages = {1418-29}, chapter = {1418}, abstract = {

Insulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). We tested whether risk factors would differ for DM that was preceded predominantly by IR, β-cell dysfunction, or both among 4,384 older adults (mean age, 72.7 (standard deviation, 5.6) years) in the Cardiovascular Health Study, which was conducted in North Carolina, California, Maryland, and Pennsylvania (1989-2007). When evaluating established risk factors, we found older age, greater adiposity, higher systolic blood pressure, a lower high-density lipoprotein cholesterol level, a higher triglyceride level, and a lower alcohol intake to be independently associated with greater IR but, conversely, with better β-cell function (P < 0.001). The prospective associations between some risk factors and incident DM varied significantly depending on whether DM was preceded predominantly by IR, β-cell dysfunction, or both. For example, obesity and lower high-density lipoprotein cholesterol levels were positively associated with DM preceded predominantly by IR (hazard ratio (HR) = 5.02, 95\% confidence interval (CI): 2.81, 9.00; and HR = 1.97, 95\% CI: 1.32, 2.93, respectively), with a significant association with and an insignificant trend toward a lower risk of DM preceded predominantly by β-cell dysfunction (HR = 0.33, 95\% CI: 0.14, 0.80; and HR = 0.78, 95\% CI: 0.43, 1.39, respectively). In conclusion, among older adults, DM risk factors were differentially associated with DM preceded predominantly by IR or β-cell dysfunction. Biologic and clinical implications of putative subtypes of DM require further investigation.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Aging, Alcohol Drinking, Blood Pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Insulin Resistance, Insulin-Secreting Cells, Lipids, Male, Prospective Studies, Risk Factors, Socioeconomic Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kws440}, author = {Imamura, Fumiaki and Mukamal, Kenneth J and Meigs, James B and Luchsinger, Jos{\'e} A and Ix, Joachim H and Siscovick, David S and Mozaffarian, Dariush} } @article {5878, title = {Simple risk model predicts incidence of atrial fibrillation in a racially and geographically diverse population: the CHARGE-AF consortium.}, journal = {J Am Heart Assoc}, volume = {2}, year = {2013}, month = {2013 Mar 18}, pages = {e000102}, abstract = {

BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors.

METHODS AND RESULTS: Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19\% African Americans, 81\% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95\% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95\% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95\% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95\% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95\% CI, 0.664 to 0.747) and calibration was adequate.

CONCLUSION: A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cohort Studies, Diabetes Mellitus, European Continental Ancestry Group, Female, Heart Failure, Humans, Hypertension, Iceland, Incidence, Male, Middle Aged, Myocardial Infarction, Netherlands, Proportional Hazards Models, Risk Assessment, Smoking, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.112.000102}, author = {Alonso, Alvaro and Krijthe, Bouwe P and Aspelund, Thor and Stepas, Katherine A and Pencina, Michael J and Moser, Carlee B and Sinner, Moritz F and Sotoodehnia, Nona and Fontes, Jo{\~a}o D and Janssens, A Cecile J W and Kronmal, Richard A and Magnani, Jared W and Witteman, Jacqueline C and Chamberlain, Alanna M and Lubitz, Steven A and Schnabel, Renate B and Agarwal, Sunil K and McManus, David D and Ellinor, Patrick T and Larson, Martin G and Burke, Gregory L and Launer, Lenore J and Hofman, Albert and Levy, Daniel and Gottdiener, John S and K{\"a}{\"a}b, Stefan and Couper, David and Harris, Tamara B and Soliman, Elsayed Z and Stricker, Bruno H C and Gudnason, Vilmundur and Heckbert, Susan R and Benjamin, Emelia J} } @article {6189, title = {Sleep and insulin-like growth factors in the Cardiovascular Health Study.}, journal = {J Clin Sleep Med}, volume = {9}, year = {2013}, month = {2013 Dec 15}, pages = {1245-51}, abstract = {

STUDY OBJECTIVES: Sleep and sleep disordered breathing (obstructive sleep apnea [OSA]) are known to affect the growth hormone/insulin-like growth factor (GH/IGF) axis. There are few relevant population studies in this area, particularly in the elderly. We conducted this study to investigate the relationship between sleep (architecture and OSA) and circulating IGF-I (insulin-like growth factor-1), IGFBP-1 (insulin-like growth factor binding protein-1), and IGFBP-3 (insulin-like growth factor binding protein-3) levels in an elderly population.

DESIGN SETTING: Cross-sectional analysis of participants from the year 9 visit of the Cardiovascular Health Study (CHS) who were enrolled in the Sleep Heart Health Study (SHHS).

PATIENTS OR PARTICIPANTS: 1,233 elderly participants from the CHS and SHHS.

MEASUREMENTS AND RESULTS: The mean age of males (n = 526) and females (n = 697) was 77 years. The mean value of IGF-I (ng/mL) in males was 112.4 vs. 97.1 in females (p < 0.01). Mean IGFBP-1 and IGFBP-3 levels were higher in females than males (p < 0.01). As expected, slow wave sleep was better preserved in females compared to males (22\% total sleep time vs. 9\% total sleep time, p < 0.01). Furthermore, as expected, OSA (apneahypopnea index [AHI] >= 5/h) was more prevalent in males compared to females (60\% vs. 46\%, p < 0.01). Multivariable linear regression was used to determine the relationship between objective sleep parameters and circulating IGF-I, IGFBP-1, and IGFBP-3 levels, with adjustment for age, sex, race, BMI, diabetes, estrogen use, progestin use, and physical activity. We did not detect a significant association between slow wave sleep (SWS) (per 5 min) and IGF-I, IGFBP-1, and IGFBP-3 levels (ng/mL). We found no significant linear association between OSA (AHI >= 5/h) and IGF-I, IGFBP-1, and IGFBP-3 levels. Gender-stratification of the entire cohort did not alter these findings. Sensitivity analyses excluding diabetics revealed that moderate OSA (AHI >= 5 and < 15) is inversely associated with IGFBP-3 levels in women. Conclusions The relationship between SWS and GH/IGF system is not significant in the elderly. Furthermore, OSA does not appear to adversely influence the GH/IGF axis, as reported in younger individuals. Whether our study findings are due to diminished GH/IGF-I axis activity in elderly needs further investigation by replication in other large population based elderly cohorts.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Geriatric Assessment, Health Surveys, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Sex Distribution, Sleep, Sleep Apnea, Obstructive, Somatomedins, United States}, issn = {1550-9397}, doi = {10.5664/jcsm.3260}, author = {Shah, Neomi and Rice, Tom and Tracy, Daniel and Rohan, Thomas and B{\r u}zkov{\'a}, Petra and Newman, Anne and Kaplan, Robert C} } @article {1564, title = {Soluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {33}, year = {2013}, month = {2013 Jan}, pages = {158-64}, abstract = {

OBJECTIVE: CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.

METHODS AND RESULTS: We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.

CONCLUSIONS: CD14 independently predicts risk mortality in older adults.

}, keywords = {African Americans, Age Factors, Aged, Biomarkers, Cardiovascular Diseases, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Hexosyltransferases, Humans, Incidence, Inflammation Mediators, Linear Models, Lipopolysaccharide Receptors, Logistic Models, Male, Membrane Proteins, Multivariate Analysis, Phenotype, Polymorphism, Single Nucleotide, Principal Component Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.112.300421}, author = {Reiner, Alex P and Lange, Ethan M and Jenny, Nancy S and Chaves, Paulo H M and Ellis, Jaclyn and Li, Jin and Walston, Jeremy and Lange, Leslie A and Cushman, Mary and Tracy, Russell P} } @article {7628, title = {Use of antihypertensive medications and breast cancer risk.}, journal = {Cancer Causes Control}, volume = {24}, year = {2013}, month = {2013 Feb}, pages = {365-71}, abstract = {

PURPOSE: Use of specific antihypertensive medications (AHTs) has been hypothesized to increase breast cancer risk, but results across published studies are inconsistent.

METHODS: We re-evaluated the relationship between AHT use and breast cancer risk in a prospective cohort of 3,201 women >=65 years of age at recruitment now with more than double the length of follow-up (12 vs. 5 years) and substantially more breast cancer diagnoses (188 compared with 75 cases). We estimated the association between AHT use overall as well as use of specific formulations (based on data collected annually) and breast cancer risk using multivariate-adjusted Cox regression.

RESULTS: Compared with women who reported no use of AHTs, women who had used calcium channel blockers (CCB) within the past two years had a 1.6-fold increased risk of breast cancer (95 \% confidence interval (CI): 1.0-2.5), and in particular, recent users of immediate-release CCBs had a 2.4-fold increased risk (95 \% CI: 1.3-4.5). Neither ever nor recent use of any other type of AHT was associated with breast cancer risk.

CONCLUSIONS: While the observed association between immediate-release CCBs and breast cancer risk is based on a small sample size and needs to be interpreted cautiously, this result is consistent with others in the literature. However, given declines in use of these preparations in favor of sustained-release CCBs, which was not related to risk, the potential clinical and public health impact of this association is limited. This study also adds to the evidence that other commonly used AHTs are not strongly related to breast cancer risk.

}, keywords = {Aged, Aged, 80 and over, Antihypertensive Agents, Breast Neoplasms, Cohort Studies, Female, Humans, Proportional Hazards Models, Prospective Studies, Risk Factors, United States}, issn = {1573-7225}, doi = {10.1007/s10552-012-0122-8}, author = {Saltzman, Babette S and Weiss, Noel S and Sieh, Weiva and Fitzpatrick, Annette L and McTiernan, Anne and Daling, Janet R and Li, Christopher I} } @article {6424, title = {Association of kidney disease measures with ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective community-based cohorts.}, journal = {Stroke}, volume = {45}, year = {2014}, month = {2014 Jul}, pages = {1925-31}, abstract = {

BACKGROUND AND PURPOSE: Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke.

METHODS: We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression.

RESULTS: Among 29,595 participants (mean age, 61 [SD 12.5] years; 46\% men; 17\% black), 1261 developed stroke (12\% hemorrhagic) during 280,549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95\% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure.

CONCLUSIONS: Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations.

}, keywords = {Aged, Albuminuria, Brain Ischemia, Comorbidity, Female, Glomerular Filtration Rate, Humans, Intracranial Hemorrhages, Kidney Diseases, Male, Middle Aged, Netherlands, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.114.004900}, author = {Mahmoodi, Bakhtawar K and Yatsuya, Hiroshi and Matsushita, Kunihiro and Sang, Yinying and Gottesman, Rebecca F and Astor, Brad C and Woodward, Mark and Longstreth, W T and Psaty, Bruce M and Shlipak, Michael G and Folsom, Aaron R and Gansevoort, Ron T and Coresh, Josef} } @article {6581, title = {Brain imaging findings in elderly adults and years of life, healthy life, and able life over the ensuing 16 years: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {62}, year = {2014}, month = {2014 Oct}, pages = {1838-43}, abstract = {

OBJECTIVES: To determine whether elderly people with different patterns of magnetic resonance imaging (MRI) findings have different long-term outcomes.

DESIGN: Longitudinal cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals aged 65 and older were recruited (N = 5,888); 3,660 of these underwent MRI, and 3,230 without a stroke before MRI were included in these analyses.

MEASUREMENTS: Cluster analysis of brain MRI findings was previously used to define five clusters: normal, atrophy, simple infarct, leukoaraiosis, and complex infarct. Participants were subsequently classified as healthy if they rated their health as excellent, very good, or good and as able if they did not report any limitations in activities of daily living (ADLs). Mean years of life (YoL), years of healthy life (YHL), and years of able life (YAL) were calculated over 16 years after the MRI and compared between clusters using unadjusted and adjusted regression analyses.

RESULTS: Mean age of participants was 75.0. With 16 years of follow-up, mean YoL was 11.3; YHL, 8.0; and YAL, 8.4. Outcomes differed significantly between clusters. With or without adjustments, outcomes were all significantly better in the normal than complex infarct cluster. The three remaining clusters had intermediate results, significantly different from the normal and complex infarct clusters but not usually from one another. Over 16 years of follow-up, participants in the complex infarct cluster (n = 368) spent the largest percentage of their 8.4 years alive being sick (38\%) and not able (38\%).

CONCLUSION: Findings on MRI scans in elderly adults are associated not only with long-term survival, but also with long-term self-rated health and limitation in ADLs. The combination of infarcts and leukoaraiosis carried the worst prognosis, presumably reflecting small vessel disease.

}, keywords = {Activities of Daily Living, Aged, Atrophy, Brain, Brain Infarction, Cohort Studies, Disability Evaluation, Female, Health Status, Humans, Leukoaraiosis, Longevity, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prognosis, Regression Analysis, United States}, issn = {1532-5415}, doi = {10.1111/jgs.13068}, author = {Longstreth, W T and Diehr, Paula H and Yee, Laura M and Newman, Anne B and Beauchamp, Norman J} } @article {6601, title = {B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies.}, journal = {Europace}, volume = {16}, year = {2014}, month = {2014 Oct}, pages = {1426-33}, abstract = {

AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information.

METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95\% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95\% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95\% CI, 0.022-0.032), a relative IDI of 41.5\%, and a continuous NRI of 0.389 (95\% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS.

CONCLUSION: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, C-Reactive Protein, Europe, Female, Humans, Incidence, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Risk Assessment, Risk Factors, United States}, issn = {1532-2092}, doi = {10.1093/europace/euu175}, author = {Sinner, Moritz F and Stepas, Katherine A and Moser, Carlee B and Krijthe, Bouwe P and Aspelund, Thor and Sotoodehnia, Nona and Fontes, Jo{\~a}o D and Janssens, A Cecile J W and Kronmal, Richard A and Magnani, Jared W and Witteman, Jacqueline C and Chamberlain, Alanna M and Lubitz, Steven A and Schnabel, Renate B and Vasan, Ramachandran S and Wang, Thomas J and Agarwal, Sunil K and McManus, David D and Franco, Oscar H and Yin, Xiaoyan and Larson, Martin G and Burke, Gregory L and Launer, Lenore J and Hofman, Albert and Levy, Daniel and Gottdiener, John S and K{\"a}{\"a}b, Stefan and Couper, David and Harris, Tamara B and Astor, Brad C and Ballantyne, Christie M and Hoogeveen, Ron C and Arai, Andrew E and Soliman, Elsayed Z and Ellinor, Patrick T and Stricker, Bruno H C and Gudnason, Vilmundur and Heckbert, Susan R and Pencina, Michael J and Benjamin, Emelia J and Alonso, Alvaro} } @article {6337, title = {Circulating fibrosis biomarkers and risk of atrial fibrillation: The Cardiovascular Health Study (CHS).}, journal = {Am Heart J}, volume = {167}, year = {2014}, month = {2014 May}, pages = {723-8.e2}, abstract = {

BACKGROUND: Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited.

METHODS: We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor β1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years.

RESULTS: Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 μg/L), adjusted hazard ratios (95\% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor β1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk.

CONCLUSION: In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Cardiomyopathies, Electrocardiography, Enzyme-Linked Immunosorbent Assay, Female, Fibrosis, Follow-Up Studies, Humans, Incidence, Male, Peptide Fragments, Procollagen, Prospective Studies, Risk Factors, Time Factors, Transforming Growth Factor beta1, United States}, issn = {1097-6744}, doi = {10.1016/j.ahj.2014.01.010}, author = {Rosenberg, Michael A and Maziarz, Marlena and Tan, Alex Y and Glazer, Nicole L and Zieman, Susan J and Kizer, Jorge R and Ix, Joachim H and Djouss{\'e}, Luc and Siscovick, David S and Heckbert, Susan R and Mukamal, Kenneth J} } @article {6613, title = {Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Oct 7}, pages = {1245-53}, abstract = {

BACKGROUND: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.

METHODS AND RESULTS: Among 2792 participants(aged >=65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95\% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95\% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.

CONCLUSIONS: High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.

}, keywords = {Aged, Arachidonic Acid, Biomarkers, Cohort Studies, Coronary Disease, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Fatty Acids, Unsaturated, Female, Follow-Up Studies, Humans, Linoleic Acid, Male, Prospective Studies, Regression Analysis, Risk Factors, Stroke, Survival Rate, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.114.011590}, author = {Wu, Jason H Y and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Psaty, Bruce M and Siscovick, David S and Mozaffarian, Dariush} } @article {6366, title = {Coronary heart disease risks associated with high levels of HDL cholesterol.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Mar 13}, pages = {e000519}, abstract = {

BACKGROUND: The association between high-density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) events is not well described in individuals with very high levels of HDL-C (>80 mg/dL).

METHODS AND RESULTS: Using pooled data from 6 community-based cohorts we examined CHD and total mortality risks across a broad range of HDL-C, including values in excess of 80 mg/dL. We used Cox proportional hazards models with penalized splines to assess multivariable, adjusted, sex-stratified associations of HDL-C with the hazard for CHD events and total mortality, using HDL-C 45 mg/dL and 55 mg/dL as the referent in men and women, respectively. Analyses included 11 515 men and 12 925 women yielding 307 245 person-years of follow-up. In men, the association between HDL-C and CHD events was inverse and linear across most HDL-C values; however at HDL-C values >90 mg/dL there was a plateau effect in the pattern of association. In women, the association between HDL-C and CHD events was inverse and linear across lower values of HDL-C, however at HDL-C values >75 mg/dL there were no further reductions in the hazard ratio point estimates for CHD. In unadjusted models there were increased total mortality risks in men with very high HDL-C, however mortality risks observed in participants with very high HDL-C were attenuated after adjustment for traditional risk factors.

CONCLUSIONS: We did not observe further reductions in CHD risk with HDL-C values higher than 90 mg/dL in men and 75 mg/dL in women.

}, keywords = {Aged, Biomarkers, Cholesterol, HDL, Coronary Disease, Female, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {2047-9980}, doi = {10.1161/JAHA.113.000519}, author = {Wilkins, John T and Ning, Hongyan and Stone, Neil J and Criqui, Michael H and Zhao, Lihui and Greenland, Philip and Lloyd-Jones, Donald M} } @article {6803, title = {Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.}, journal = {Eur J Prev Cardiol}, volume = {21}, year = {2014}, month = {2014 Mar}, pages = {310-20}, abstract = {

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.

DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.

METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.

RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95\% CI 0.599 to 0.737) in men and 0.578 (95\% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95\% CI 0.612 to 0.749) and large increase in women to 0.690 (95\% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3\% (95\% CI 0.0 to 7.6\%, p = 0.050) and 9.6\% (95\% CI 6.1 to 16.4\%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19\% resulted in higher NRI of 15.9\% (95\% CI 6.1 to 20.6\%, p < 0.001) in men and 23.3\% (95\% CI 13.8 to 62.5\%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0\% (95\% CI 2.3 to 4.2\%, p = 0.567) in men and 1.1\% (95\% CI 1.9 to 4.0\%, p = 0.483) in women.

CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

}, keywords = {Adult, Aged, Aged, 80 and over, Ankle Brachial Index, Cardiovascular Diseases, Europe, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Models, Statistical, Predictive Value of Tests, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States, Young Adult}, issn = {2047-4881}, doi = {10.1177/2047487313516564}, author = {Fowkes, F G R and Murray, G D and Butcher, I and Folsom, A R and Hirsch, A T and Couper, D J and deBacker, G and Kornitzer, M and Newman, A B and Sutton-Tyrrell, K C and Cushman, M and Lee, A J and Price, J F and D{\textquoteright}Agostino, R B and Murabito, J M and Norman, Pe and Masaki, K H and Bouter, L M and Heine, R J and Stehouwer, C D A and McDermott, M M and Stoffers, H E J H and Knottnerus, J A and Ogren, M and Hedblad, B and Koenig, W and Meisinger, C and Cauley, J A and Franco, Oh and Hunink, M G M and Hofman, A and Witteman, J C and Criqui, M H and Langer, R D and Hiatt, W R and Hamman, R F} } @article {6560, title = {Disability and recovery of independent function in obstructive lung disease: the cardiovascular health study.}, journal = {Respiration}, volume = {88}, year = {2014}, month = {2014}, pages = {329-38}, abstract = {

BACKGROUND: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time.

OBJECTIVE: To identify factors associated with transition between states of disability and independent function in obstructive lung disease.

METHODS: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in >=1 instrumental activity of daily living (IADL) or >=1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression.

RESULTS: The prevalence of IADL impairment was higher with moderate (23.9\%) and severe (36.9\%) airflow obstruction compared to normal spirometry (22.5\%; p < 0.001). Among participants with severe airflow obstruction, 23.5\% recovered independence in IADLs and 40.5\% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95\% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked >=28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95\% CI 0.69-0.86 and <7 blocks: RR 0.73 and 95\% CI 0.61-0.86). Increased strength (RR 1.16 and 95\% CI 1.05-1.29) was associated with resolving IADL impairment.

CONCLUSIONS: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability.

}, keywords = {Activities of Daily Living, Aged, Cardiac Rehabilitation, Cardiovascular Diseases, Disability Evaluation, Exercise Test, Female, Humans, Independent Living, Longitudinal Studies, Male, Motor Activity, Muscle Strength, Outcome Assessment (Health Care), Pulmonary Disease, Chronic Obstructive, Recovery of Function, Risk Assessment, Severity of Illness Index, Spirometry, United States}, issn = {1423-0356}, doi = {10.1159/000363772}, author = {Fan, Vincent S and Locke, Emily R and Diehr, Paula and Wilsdon, Anthony and Enright, Paul and Yende, Sachin and Avdalovic, Mark and Barr, Graham and Kapur, Vishesh K and Thomas, Rachel and Krishnan, Jerry A and Lovasi, Gina and Thielke, Stephen} } @article {6188, title = {Enhancing case ascertainment of Parkinson{\textquoteright}s disease using Medicare claims data in a population-based cohort: the Cardiovascular Health Study.}, journal = {Pharmacoepidemiol Drug Saf}, volume = {23}, year = {2014}, month = {2014 Feb}, pages = {119-27}, abstract = {

PURPOSE: We sought to improve a previous algorithm to ascertain Parkinson{\textquoteright}s disease (PD) in the Cardiovascular Health Study by incorporating additional data from Medicare outpatient claims. We compared our results to the previous algorithm in terms of baseline prevalence and incidence of PD, as well as associations with baseline smoking characteristics.

METHODS: Our original case ascertainment used self-reported diagnosis, antiparkinsonian medication, and hospitalization discharge International Classification of Diseases-Ninth version code. In this study, we incorporated additional data from fee-for-service Medicare claims, extended follow-up time, review of hospitalization records, and adjudicated cause of death. Two movement disorders specialists adjudicated final PD status. We used logistic regression models and controlled for age, sex, African American race, and education.

RESULTS: We identified 75 additional cases but reclassified 80 previously identified cases as not having PD. We observed significant inverse association with smoking status (odds ratio = 0.42; 95\% confidence interval (CI) = 0.22, 0.79), and inverse linear trends with pack-years (p = 0.005), and cigarettes per day (p = 0.019) with incident PD. All estimates were stronger than those from the previous algorithm.

CONCLUSIONS: Our enhanced method did not alter prevalence and incidence estimates compared with our previous algorithm. However, our enhanced method provided stronger estimates of association, potentially due to reduced level of disease misclassification.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Antiparkinson Agents, Cohort Studies, Databases, Factual, Female, Hospitalization, Humans, Incidence, Logistic Models, Male, Medicare, Parkinson Disease, Prevalence, Prospective Studies, Smoking, Time Factors, United States}, issn = {1099-1557}, doi = {10.1002/pds.3552}, author = {Ton, Thanh G N and Biggs, Mary Lou and Comer, Diane and Curtis, Lesley and Hu, Shu-Ching and Thacker, Evan L and Searles Nielsen, Susan and Delaney, Joseph A and Landsittel, Douglas and Longstreth, William T and Checkoway, Harvey and Jain, Samay} } @article {6399, title = {Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Jul 22}, pages = {298-307}, abstract = {

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.

METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41\% higher risk of incident AF in MESA (hazard ratio, 1.41; 95\% confidence interval, 1.13-1.76; P=0.003) and a 30\% higher risk of incident AF in CHS (hazard ratio, 1.30; 95\% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95\% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.

CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Comorbidity, Ethnic Groups, Female, Fibroblast Growth Factor 3, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Hypertrophy, Left Ventricular, Male, Middle Aged, Phosphates, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors, United States, Ventricular Dysfunction, Left, Ventricular Remodeling, Vitamin D}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.005499}, author = {Mathew, Jehu S and Sachs, Michael C and Katz, Ronit and Patton, Kristen K and Heckbert, Susan R and Hoofnagle, Andrew N and Alonso, Alvaro and Chonchol, Michel and Deo, Rajat and Ix, Joachim H and Siscovick, David S and Kestenbaum, Bryan and de Boer, Ian H} } @article {6541, title = {Fibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study.}, journal = {Circ Arrhythm Electrophysiol}, volume = {7}, year = {2014}, month = {2014 Aug}, pages = {583-9}, abstract = {

BACKGROUND: Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown.

METHODS AND RESULTS: We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β{\textquoteright}s pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95\% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05).

CONCLUSIONS: Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Female, Fibrosis, Heart Failure, Humans, Incidence, Male, Myocardial Infarction, Peptide Fragments, Procollagen, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Time Factors, Transforming Growth Factor beta, United States}, issn = {1941-3084}, doi = {10.1161/CIRCEP.114.001610}, author = {Agarwal, Isha and Glazer, Nicole L and Barasch, Eddy and Biggs, Mary L and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Gottdiener, John S and Ix, Joachim H and Kizer, Jorge R and Rimm, Eric B and Sicovick, David S and Tracy, Russell P and Mukamal, Kenneth J} } @article {7019, title = {Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.}, journal = {Invest Ophthalmol Vis Sci}, volume = {55}, year = {2014}, month = {2014 Sep 9}, pages = {6839-50}, abstract = {

PURPOSE: Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci.

METHODS: Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study.

RESULTS: Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05{\texttimes}10(-8) and P=6.36{\texttimes}10(-6), respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value<0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing.

CONCLUSIONS: While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.

}, keywords = {Adult, Aged, Aged, 80 and over, Complement Factor H, DNA, Ethnic Groups, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Macular Degeneration, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Proteins, Risk Factors, United States}, issn = {1552-5783}, doi = {10.1167/iovs.14-14246}, author = {Restrepo, Nicole A and Spencer, Kylee L and Goodloe, Robert and Garrett, Tiana A and Heiss, Gerardo and B{\r u}zkov{\'a}, Petra and Jorgensen, Neal and Jensen, Richard A and Matise, Tara C and Hindorff, Lucia A and Klein, Barbara E K and Klein, Ronald and Wong, Tien Y and Cheng, Ching-Yu and Cornes, Belinda K and Tai, E-Shyong and Ritchie, Marylyn D and Haines, Jonathan L and Crawford, Dana C} } @article {6367, title = {Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {34}, year = {2014}, month = {2014 May}, pages = {1093-101}, abstract = {

OBJECTIVE: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.

APPROACH AND RESULTS: Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0{\texttimes}10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9{\texttimes}10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3{\texttimes}10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0{\texttimes}10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0{\texttimes}10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke.

CONCLUSIONS: We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.

}, keywords = {Aged, Cells, Cultured, Coronary Artery Disease, Endothelial Cells, Europe, Female, Gene Expression Regulation, Gene Silencing, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Nerve Tissue Proteins, Phenotype, Polymorphism, Single Nucleotide, R-SNARE Proteins, Risk Factors, Stroke, Syntaxin 1, Tissue Plasminogen Activator, Transfection, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.113.302088}, author = {Huang, Jie and Huffman, Jennifer E and Yamakuchi, Munekazu and Yamkauchi, Munekazu and Trompet, Stella and Asselbergs, Folkert W and Sabater-Lleal, Maria and Tr{\'e}gou{\"e}t, David-Alexandre and Chen, Wei-Min and Smith, Nicholas L and Kleber, Marcus E and Shin, So-Youn and Becker, Diane M and Tang, Weihong and Dehghan, Abbas and Johnson, Andrew D and Truong, Vinh and Folkersen, Lasse and Yang, Qiong and Oudot-Mellkah, Tiphaine and Buckley, Brendan M and Moore, Jason H and Williams, Frances M K and Campbell, Harry and Silbernagel, G{\"u}nther and Vitart, Veronique and Rudan, Igor and Tofler, Geoffrey H and Navis, Gerjan J and DeStefano, Anita and Wright, Alan F and Chen, Ming-Huei and de Craen, Anton J M and Worrall, Bradford B and Rudnicka, Alicja R and Rumley, Ann and Bookman, Ebony B and Psaty, Bruce M and Chen, Fang and Keene, Keith L and Franco, Oscar H and B{\"o}hm, Bernhard O and Uitterlinden, Andr{\'e} G and Carter, Angela M and Jukema, J Wouter and Sattar, Naveed and Bis, Joshua C and Ikram, Mohammad A and Sale, Mich{\`e}le M and McKnight, Barbara and Fornage, Myriam and Ford, Ian and Taylor, Kent and Slagboom, P Eline and McArdle, Wendy L and Hsu, Fang-Chi and Franco-Cereceda, Anders and Goodall, Alison H and Yanek, Lisa R and Furie, Karen L and Cushman, Mary and Hofman, Albert and Witteman, Jacqueline C M and Folsom, Aaron R and Basu, Saonli and Matijevic, Nena and van Gilst, Wiek H and Wilson, James F and Westendorp, Rudi G J and Kathiresan, Sekar and Reilly, Muredach P and Tracy, Russell P and Polasek, Ozren and Winkelmann, Bernhard R and Grant, Peter J and Hillege, Hans L and Cambien, Francois and Stott, David J and Lowe, Gordon D and Spector, Timothy D and Meigs, James B and M{\"a}rz, Winfried and Eriksson, Per and Becker, Lewis C and Morange, Pierre-Emmanuel and Soranzo, Nicole and Williams, Scott M and Hayward, Caroline and van der Harst, Pim and Hamsten, Anders and Lowenstein, Charles J and Strachan, David P and O{\textquoteright}Donnell, Christopher J} } @article {6280, title = {Heritability of and mortality prediction with a longevity phenotype: the healthy aging index.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Apr}, pages = {479-85}, abstract = {

BACKGROUND: Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI{\textquoteright}s association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study.

METHODS: The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model.

RESULTS: Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95\% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95\% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95\% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95\% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring.

CONCLUSION: The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.

}, keywords = {Aged, Aging, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genotype, Health Behavior, Humans, Longevity, Male, Phenotype, Retrospective Studies, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt117}, author = {Sanders, Jason L and Minster, Ryan L and Barmada, M Michael and Matteini, Amy M and Boudreau, Robert M and Christensen, Kaare and Mayeux, Richard and Borecki, Ingrid B and Zhang, Qunyuan and Perls, Thomas and Newman, Anne B} } @article {6552, title = {Meta-analysis of loci associated with age at natural menopause in African-American women.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 Jun 15}, pages = {3327-42}, abstract = {

Age at menopause marks the end of a woman{\textquoteright}s reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied. We therefore sought to uncover additional menopause loci and investigate the relevance of European menopause loci by performing a GWAS meta-analysis in 6510 women with African ancestry derived from 11 studies across the USA. We did not identify any additional loci significantly associated with age at menopause in African Americans. We replicated the associations between six loci and age at menopause (P-value < 0.05): AMHR2, RHBLD2, PRIM1, HK3/UMC1, BRSK1/TMEM150B and MCM8. In addition, associations of 14 loci are directionally consistent with previous reports. We provide evidence that genetic variants influencing reproductive traits identified in European populations are also important in women of African ancestry residing in USA.

}, keywords = {African Americans, Age Factors, Chromosomes, Human, European Continental Ancestry Group, Female, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Menopause, United States}, issn = {1460-2083}, doi = {10.1093/hmg/ddu041}, author = {Chen, Christina T L and Liu, Ching-Ti and Chen, Gary K and Andrews, Jeanette S and Arnold, Alice M and Dreyfus, Jill and Franceschini, Nora and Garcia, Melissa E and Kerr, Kathleen F and Li, Guo and Lohman, Kurt K and Musani, Solomon K and Nalls, Michael A and Raffel, Leslie J and Smith, Jennifer and Ambrosone, Christine B and Bandera, Elisa V and Bernstein, Leslie and Britton, Angela and Brzyski, Robert G and Cappola, Anne and Carlson, Christopher S and Couper, David and Deming, Sandra L and Goodarzi, Mark O and Heiss, Gerardo and John, Esther M and Lu, Xiaoning and Le Marchand, Lo{\"\i}c and Marciante, Kristin and McKnight, Barbara and Millikan, Robert and Nock, Nora L and Olshan, Andrew F and Press, Michael F and Vaiyda, Dhananjay and Woods, Nancy F and Taylor, Herman A and Zhao, Wei and Zheng, Wei and Evans, Michele K and Harris, Tamara B and Henderson, Brian E and Kardia, Sharon L R and Kooperberg, Charles and Liu, Yongmei and Mosley, Thomas H and Psaty, Bruce and Wellons, Melissa and Windham, Beverly G and Zonderman, Alan B and Cupples, L Adrienne and Demerath, Ellen W and Haiman, Christopher and Murabito, Joanne M and Rajkovic, Aleksandar} } @article {6360, title = {Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.}, journal = {Circ Cardiovasc Genet}, volume = {7}, year = {2014}, month = {2014 Apr}, pages = {178-88}, abstract = {

BACKGROUND: C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP.

METHODS AND RESULTS: We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P<3.1{\texttimes}10(-3) for replication, P<2.0{\texttimes}10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0{\texttimes}10(-6)) and rs646776 (P=3.1{\texttimes}10(-5)).

CONCLUSIONS: We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes.

}, keywords = {Adult, African Continental Ancestry Group, Aged, Asian Continental Ancestry Group, C-Reactive Protein, Female, Genetic Variation, Genome-Wide Association Study, Hispanic Americans, Humans, Indians, North American, Inflammation, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, Young Adult}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.113.000173}, author = {Kocarnik, Jonathan M and Pendergrass, Sarah A and Carty, Cara L and Pankow, James S and Schumacher, Fredrick R and Cheng, Iona and Durda, Peter and Ambite, Jose Luis and Deelman, Ewa and Cook, Nancy R and Liu, Simin and Wactawski-Wende, Jean and Hutter, Carolyn and Brown-Gentry, Kristin and Wilson, Sarah and Best, Lyle G and Pankratz, Nathan and Hong, Ching-Ping and Cole, Shelley A and Voruganti, V Saroja and B{\r u}zkov{\'a}, Petra and Jorgensen, Neal W and Jenny, Nancy S and Wilkens, Lynne R and Haiman, Christopher A and Kolonel, Laurence N and LaCroix, Andrea and North, Kari and Jackson, Rebecca and Le Marchand, Lo{\"\i}c and Hindorff, Lucia A and Crawford, Dana C and Gross, Myron and Peters, Ulrike} } @article {6562, title = {Plasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study.}, journal = {Br J Nutr}, volume = {112}, year = {2014}, month = {2014 Oct 14}, pages = {1206-13}, abstract = {

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18~:~3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged >=~65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0{\textperiodcentered}73 (95~\% CI 0{\textperiodcentered}61, 0{\textperiodcentered}88) and 0{\textperiodcentered}64 (95~\% CI 0{\textperiodcentered}52, 0{\textperiodcentered}80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.

}, keywords = {Aged, alpha-Linolenic Acid, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Diet, Female, Humans, Male, Mortality, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1475-2662}, doi = {10.1017/S0007114514001925}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Sitlani, Colleen and Psaty, Bruce M and Rimm, Eric B and Song, Xiaoling and McKnight, Barbara and Spiegelman, Donna and King, Irena B and Lemaitre, Rozenn N} } @article {6397, title = {Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Jun 26}, pages = {e000889}, abstract = {

BACKGROUND: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF.

METHODS AND RESULTS: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95\% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95\% CI) for AF in the top and bottom quartiles were 0.76 (95\% CI: 0.61, 0.95) for 18:0; 0.78 (95\% CI: 0.63, 0.97) for 20:0; 0.62 (95\% CI: 0.50, 0.78) for 22:0; and 0.68 (95\% CI: 0.55, 0.85) for 24:0.

CONCLUSIONS: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Eicosanoic Acids, Fatty Acids, Female, Humans, Longitudinal Studies, Male, Palmitic Acid, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Factors, Stearic Acids, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.114.000889}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Djouss{\'e}, Luc and Heckbert, Susan R and King, Irena B and McKnight, Barbara and Sitlani, Colleen and Sacks, Frank M and Song, Xiaoling and Sotoodehnia, Nona and Spiegelman, Donna and Wallace, Erin R and Lemaitre, Rozenn N} } @article {6584, title = {Plasma-free fatty acids, fatty acid-binding protein 4, and mortality in older adults (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {114}, year = {2014}, month = {2014 Sep 15}, pages = {843-8}, abstract = {

Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes, but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the Cardiovascular Health Study, an observational cohort of community-dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14, 95\% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04, 95\% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death because of cardiovascular disease, dementia, infection, and respiratory causes but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality differentially in men and women (HR 1.17, 95\% CI 1.08 to 1.26 for men; HR 1.02, 95\% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a cohort of community-dwelling older subjects, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and noncardiovascular mortality.

}, keywords = {Age Distribution, Age Factors, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cause of Death, Fatty Acid-Binding Proteins, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Health Status, Humans, Male, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, Time Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2014.06.012}, author = {Miedema, Michael D and Maziarz, Marlena and Biggs, Mary L and Zieman, Susan J and Kizer, Jorge R and Ix, Joachim H and Mozaffarian, Dariush and Tracy, Russell P and Psaty, Bruce M and Siscovick, David S and Mukamal, Kenneth J and Djouss{\'e}, Luc} } @article {6240, title = {Racial and regional differences in venous thromboembolism in the United States in 3 cohorts.}, journal = {Circulation}, volume = {129}, year = {2014}, month = {2014 Apr 08}, pages = {1502-9}, abstract = {

BACKGROUND: Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope.

METHODS AND RESULTS: We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor-adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95\% confidence interval, 1.20-2.73) but not ARIC (hazard ratio, 1.21; 95\% confidence interval, 0.96-1.54). In REGARDS, there was a significant region-by-race interaction (P=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95\% confidence interval, 1.08-2.48) that was not seen in whites (hazard ratio, 0.83; 95\% confidence interval, 0.61-1.14).

CONCLUSIONS: The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.

}, keywords = {African Continental Ancestry Group, Aged, Cohort Studies, European Continental Ancestry Group, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prevalence, Proportional Hazards Models, Prospective Studies, Residence Characteristics, Risk Factors, United States, Venous Thromboembolism}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.006472}, author = {Zakai, Neil A and McClure, Leslie A and Judd, Suzanne E and Safford, Monika M and Folsom, Aaron R and Lutsey, Pamela L and Cushman, Mary} } @article {6137, title = {Relations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults >=65 years of age (from the Cardiovascular Health study).}, journal = {Am J Cardiol}, volume = {113}, year = {2014}, month = {2014 Jan 15}, pages = {328-34}, abstract = {

Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine{\textquoteright}s association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged >=65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95\% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95\% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.

}, keywords = {Adiponectin, Age of Onset, Aged, Biomarkers, Cross-Sectional Studies, Echocardiography, Doppler, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Prognosis, Prospective Studies, Recurrence, Severity of Illness Index, United States, Ventricular Function, Left}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2013.09.027}, author = {Karas, Maria G and Benkeser, David and Arnold, Alice M and Bartz, Traci M and Djouss{\'e}, Luc and Mukamal, Kenneth J and Ix, Joachim H and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Mantzoros, Christos S and Gottdiener, John S and deFilippi, Christopher R and Kizer, Jorge R} } @article {6335, title = {Residential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.}, journal = {J Environ Public Health}, volume = {2014}, year = {2014}, month = {2014}, pages = {951971}, abstract = {

OBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address.

METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period.

RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95\% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95\% CI: 1.2-3.3), angina (OR: 1.6, 95\% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95\% CI: 1.0-2.1).

CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations.

}, keywords = {Aged, Cardiovascular Diseases, Cross-Over Studies, Female, Humans, Incidence, Life Change Events, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Residence Characteristics, United States}, issn = {1687-9813}, doi = {10.1155/2014/951971}, author = {Lovasi, Gina S and Richardson, John M and Rodriguez, Carlos J and Kop, Willem J and Ahmed, Ali and Brown, Arleen F and Greenlee, Heather and Siscovick, David S} } @article {6243, title = {Serum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Jun}, pages = {710-6}, abstract = {

BACKGROUND: Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.

METHODS: In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 {\textpm} 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.

RESULTS: Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95\% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95\% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.

CONCLUSIONS: Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML{\textquoteright}s value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Biomarkers, Cardiac Rehabilitation, Cardiovascular Diseases, Disabled Persons, Female, Follow-Up Studies, Frail Elderly, Health Status, Humans, Incidence, Lysine, Male, Prevalence, Prognosis, Retrospective Studies, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt155}, author = {Whitson, Heather E and Arnold, Alice M and Yee, Laura M and Mukamal, Kenneth J and Kizer, Jorge R and Djouss{\'e}, Luc and Ix, Joachim H and Siscovick, David and Tracy, Russell P and Thielke, Stephen M and Hirsch, Calvin and Newman, Anne B and Zieman, Susan} } @article {6270, title = {Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.}, journal = {Diabetologia}, volume = {57}, year = {2014}, month = {2014 Feb}, pages = {339-46}, abstract = {

AIMS/HYPOTHESIS: Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits.

METHODS: We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (<=5~h or >=9~h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene {\texttimes} behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk.

RESULTS: Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95\% CI 1.08, 1.61; p = 0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).

CONCLUSIONS/INTERPRETATION: Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes.

}, keywords = {Blood Glucose, Body Composition, Body Mass Index, Cross-Sectional Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Glucose Intolerance, Glycated Hemoglobin A, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Sleep, Surveys and Questionnaires, Time Factors, United States}, issn = {1432-0428}, doi = {10.1007/s00125-013-3110-y}, author = {Tare, Archana and Lane, Jacqueline M and Cade, Brian E and Grant, Struan F A and Chen, Ting-Hsu and Punjabi, Naresh M and Lauderdale, Diane S and Zee, Phyllis C and Gharib, Sina A and Gottlieb, Daniel J and Scheer, Frank A J L and Redline, Susan and Saxena, Richa} } @article {6589, title = {Subclinical vascular disease burden and longer survival.}, journal = {J Am Geriatr Soc}, volume = {62}, year = {2014}, month = {2014 Sep}, pages = {1692-8}, abstract = {

OBJECTIVES: To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer.

DESIGN: Cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals born between June 30, 1918, and June 30, 1921 (N~=~2,082; aged 70-75 at baseline (1992-93)).

MEASUREMENTS: A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older.

RESULTS: A 1-point lower SVD score was associated with 1.22 greater odds (95\% confidence interval~=~1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking.

CONCLUSION: A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival.

}, keywords = {Aged, Aged, 80 and over, C-Reactive Protein, Carotid Intima-Media Thickness, Cohort Studies, Cystatin C, Depression, Diabetes Mellitus, Electrocardiography, Female, Humans, Inflammation, Kidney Diseases, Male, Smoking, Survival Analysis, United States, Vascular Diseases}, issn = {1532-5415}, doi = {10.1111/jgs.13018}, author = {Odden, Michelle C and Yee, Laura M and Arnold, Alice M and Sanders, Jason L and Hirsch, Calvin and DeFilippi, Christopher and Kizer, Jorge R and Inzitari, Marco and Newman, Anne B} } @article {7017, title = {Vitamin D and the risk of dementia and Alzheimer disease.}, journal = {Neurology}, volume = {83}, year = {2014}, month = {2014 Sep 2}, pages = {920-8}, abstract = {

OBJECTIVE: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.

METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria.

RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95\% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (>=25 to <50 nmol/L) were 2.25 (95\% CI: 1.23-4.13) and 1.53 (95\% CI: 1.06-2.21) compared to participants with sufficient concentrations (>=50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95\% CI: 1.02-4.83) and 1.69 (95\% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

CONCLUSION: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.

}, keywords = {Aged, Alzheimer Disease, Dementia, Female, Follow-Up Studies, Humans, Incidence, Male, Proportional Hazards Models, Risk Factors, United States, Vitamin D, Vitamin D Deficiency}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000000755}, author = {Littlejohns, Thomas J and Henley, William E and Lang, Iain A and Annweiler, Cedric and Beauchet, Olivier and Chaves, Paulo H M and Fried, Linda and Kestenbaum, Bryan R and Kuller, Lewis H and Langa, Kenneth M and Lopez, Oscar L and Kos, Katarina and Soni, Maya and Llewellyn, David J} } @article {6545, title = {Association of mitochondrial DNA levels with frailty and all-cause mortality.}, journal = {J Mol Med (Berl)}, volume = {93}, year = {2015}, month = {2015 Feb}, pages = {177-186}, abstract = {

Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3\% men) from CHS and 11,509 participants (44.9\% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95\% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95\% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population.

}, keywords = {African Americans, Aged, Aged, 80 and over, Aging, DNA, Mitochondrial, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Dosage, Geriatric Assessment, Humans, Kaplan-Meier Estimate, Male, Mortality, Odds Ratio, Population Surveillance, Prospective Studies, Surveys and Questionnaires, United States}, issn = {1432-1440}, doi = {10.1007/s00109-014-1233-3}, author = {Ashar, Foram N and Moes, Anna and Moore, Ann Z and Grove, Megan L and Chaves, Paulo H M and Coresh, Josef and Newman, Anne B and Matteini, Amy M and Bandeen-Roche, Karen and Boerwinkle, Eric and Walston, Jeremy D and Arking, Dan E} } @article {6935, title = {Cardiovascular and Mortality Outcomes in the Elderly With Impaired Cardiac and Pulmonary Function: The Cardiovascular Health Study (CHS).}, journal = {J Am Heart Assoc}, volume = {4}, year = {2015}, month = {2015 Dec}, abstract = {

BACKGROUND: Impaired pulmonary function (IPF) and left ventricular systolic dysfunction (LVSD) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of IPF and LVSD with heart failure, cardiovascular mortality and all-cause mortality, and their impact on risk classification using a continuous net reclassification index.

METHODS AND RESULTS: We followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years. LVSD was defined as LV ejection fraction <55\%. IPF was defined as: forced expiratory volume in 1 second:forced vital capacity <70\%, and predicted forced expiratory volume in 1 second <80\%. Outcomes included heart failure hospitalization, cardiovascular mortality, all-cause mortality, and composite outcome. LVSD was detected in 128 subjects (6\%), IPF in 441 (19\%) and both in 38 (2\%). Compared to those without LVSD or IPF, there was a significantly increased cardiovascular risk for groups of LVSD only, IPF only, and LVSD plus IPF, adjusted hazard ratio (95\% CI) 2.1 (1.5-3.0), 1.7 (1.4-2.1), and 3.2 (2.0-5.1) for HF; 1.8 (1.2-2.6), 1.4 (1.1-1.8), and 2.8 (1.7-4.7) for cardiovascular mortality; 1.3 (1.0-1.8), 1.7 (1.4-1.9), and 2.1 (1.5-3.0) for all-cause mortality, and 1.6 (1.3-2.1), 1.7 (1.5-1.9), and 2.4 (1.7-3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when IPF was added to the adjusted model with LVSD or LVSD to IPF.

CONCLUSIONS: While risk of cardiovascular outcomes was the highest among elderly with both LVSD and IPF, risk was comparable between subjects with IPF alone and those with LVSD alone. This observation, combined with improved risk classification by adding IPF to LVSD or LVSD to IPF, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Heart Diseases, Heart Failure, Hospitalization, Humans, Kaplan-Meier Estimate, Lung Diseases, Male, Mortality, Prospective Studies, Respiratory Function Tests, Risk Assessment, Risk Factors, Stroke Volume, United States, Ventricular Dysfunction, Left}, issn = {2047-9980}, doi = {10.1161/JAHA.115.002308}, author = {Waheed, Salman and Chaves, Paulo H M and Gardin, Julius M and Cao, Jie Jane} } @article {6810, title = {Coagulation factor~XII genetic variation, ex~vivo thrombin generation, and stroke risk in the elderly: results from the Cardiovascular Health Study.}, journal = {J Thromb Haemost}, volume = {13}, year = {2015}, month = {2015 Oct}, pages = {1867-77}, abstract = {

BACKGROUND: The relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts.

OBJECTIVES: To evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex~vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke.

PATIENTS/METHODS: We measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n~=~5411), both with and without inhibitory anti-factor~XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~~50~000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2~years.

RESULTS: The minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (β~=~-~34.2~{\textpm}~3.5~nm; P~=~3.3~{\texttimes}~10(-22) ; minor allele frequency [MAF]~=~0.23) and African-Americans (β~=~-~31.1~{\textpm}~7.9~nm; P~=~9.0~{\texttimes} 10(-5) ; MAF~=~0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (β~=~16.3~nm; P~=~4.3~{\texttimes}~10(-9) ; MAF~=~0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95\% confidence interval CI~1.01-1.17; P~=~0.03) for pTG, 1.06 (95\% CI~0.98-1.15; P~=~0.17) for pTG/FXIa(-) , and 1.11 (95\% CI~1.02-1.21; P~=~0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n~=~834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (β~=~-~0.02; standard error~=~0.08; P~=~0.81).

CONCLUSIONS: These results support the importance of contact activation pathway-dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex~vivo and in~vivo.

}, keywords = {African Americans, Age Factors, Aged, Blood Coagulation, Brain Ischemia, European Continental Ancestry Group, Factor XII, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Incidence, Male, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Thrombin, Time Factors, United States}, issn = {1538-7836}, doi = {10.1111/jth.13111}, author = {Olson, N C and Butenas, S and Lange, L A and Lange, E M and Cushman, M and Jenny, N S and Walston, J and Souto, J C and Soria, J M and Chauhan, G and Debette, S and Longstreth, W T and Seshadri, S and Reiner, A P and Tracy, R P} } @article {6769, title = {Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {520-8}, abstract = {

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults.

BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults >=65 years of age, which is the most rapidly growing segment of the U.S.

METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity.

RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26\% and 22\% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95\% confidence interval [CI]: 0.63 to 0.86; leisure activity >=845 kcal/week vs. <845 kcal/week; HR: 0.78; 95\% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with >=4 healthy lifestyle factors had a 45\% (HR: 0.55; 95\% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed.

CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.

}, keywords = {Aged, Alcohol Drinking, Cohort Studies, Diet, Female, Heart Failure, Humans, Incidence, Male, Motor Activity, Obesity, Proportional Hazards Models, Prospective Studies, Risk Factors, Sedentary Lifestyle, Smoking, United States}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.02.009}, author = {Del Gobbo, Liana C and Kalantarian, Shadi and Imamura, Fumiaki and Lemaitre, Rozenn and Siscovick, David S and Psaty, Bruce M and Mozaffarian, Dariush} } @article {6691, title = {Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.}, journal = {Nature}, volume = {518}, year = {2015}, month = {2015 Feb 5}, pages = {102-6}, abstract = {

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (<=50 years in males and <=60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2\% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190~mg~dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

}, keywords = {Age Factors, Age of Onset, Alleles, Apolipoproteins A, Case-Control Studies, Cholesterol, LDL, Coronary Artery Disease, Exome, Female, Genetic Predisposition to Disease, Genetics, Population, Heterozygote, Humans, Male, Middle Aged, Mutation, Myocardial Infarction, National Heart, Lung, and Blood Institute (U.S.), Receptors, LDL, Triglycerides, United States}, issn = {1476-4687}, doi = {10.1038/nature13917}, author = {Do, Ron and Stitziel, Nathan O and Won, Hong-Hee and J{\o}rgensen, Anders Berg and Duga, Stefano and Angelica Merlini, Pier and Kiezun, Adam and Farrall, Martin and Goel, Anuj and Zuk, Or and Guella, Illaria and Asselta, Rosanna and Lange, Leslie A and Peloso, Gina M and Auer, Paul L and Girelli, Domenico and Martinelli, Nicola and Farlow, Deborah N and DePristo, Mark A and Roberts, Robert and Stewart, Alexander F R and Saleheen, Danish and Danesh, John and Epstein, Stephen E and Sivapalaratnam, Suthesh and Hovingh, G Kees and Kastelein, John J and Samani, Nilesh J and Schunkert, Heribert and Erdmann, Jeanette and Shah, Svati H and Kraus, William E and Davies, Robert and Nikpay, Majid and Johansen, Christopher T and Wang, Jian and Hegele, Robert A and Hechter, Eliana and M{\"a}rz, Winfried and Kleber, Marcus E and Huang, Jie and Johnson, Andrew D and Li, Mingyao and Burke, Greg L and Gross, Myron and Liu, Yongmei and Assimes, Themistocles L and Heiss, Gerardo and Lange, Ethan M and Folsom, Aaron R and Taylor, Herman A and Olivieri, Oliviero and Hamsten, Anders and Clarke, Robert and Reilly, Dermot F and Yin, Wu and Rivas, Manuel A and Donnelly, Peter and Rossouw, Jacques E and Psaty, Bruce M and Herrington, David M and Wilson, James G and Rich, Stephen S and Bamshad, Michael J and Tracy, Russell P and Cupples, L Adrienne and Rader, Daniel J and Reilly, Muredach P and Spertus, John A and Cresci, Sharon and Hartiala, Jaana and Tang, W H Wilson and Hazen, Stanley L and Allayee, Hooman and Reiner, Alex P and Carlson, Christopher S and Kooperberg, Charles and Jackson, Rebecca D and Boerwinkle, Eric and Lander, Eric S and Schwartz, Stephen M and Siscovick, David S and McPherson, Ruth and Tybjaerg-Hansen, Anne and Abecasis, Goncalo R and Watkins, Hugh and Nickerson, Deborah A and Ardissino, Diego and Sunyaev, Shamil R and O{\textquoteright}Donnell, Christopher J and Altshuler, David and Gabriel, Stacey and Kathiresan, Sekar} } @article {6662, title = {Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Jul}, pages = {40-6}, abstract = {

BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 3,244 participants 65 years or older in the community-based Cardiovascular Health Study.

PREDICTOR: Plasma FGF-23 concentrations.

OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.

MEASUREMENTS: We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.

RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95\% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95\% CI, 0.85-1.35). In stratified analysis by CKD status (36.5\% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95\% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95\% CI, 0.89-1.62).

LIMITATIONS: Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.

CONCLUSIONS: In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Death, Sudden, Cardiac, Electrocardiography, Female, Fibroblast Growth Factors, Follow-Up Studies, Heart Arrest, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Sympathetic Nervous System, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2014.10.025}, author = {Deo, Rajat and Katz, Ronit and de Boer, Ian H and Sotoodehnia, Nona and Kestenbaum, Bryan and Mukamal, Kenneth J and Chonchol, Michel and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G and Ix, Joachim H} } @article {6665, title = {Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {239}, year = {2015}, month = {2015 Apr}, pages = {539-46}, abstract = {

OBJECTIVE: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.

METHODS: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998.

RESULTS: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR]~=~1.36 per doubling of TGF-β, 95\% confidence interval [CI]~=~1.04, 1.78) and retinal venular diameter (1.63~μm per doubling of TGF-β, CI~=~0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102~mm per doubling of PIIINP, CI~=~0.029, 0.174) and impaired brachial artery reactivity (-0.20\% change per doubling of PIIINP, CI~=~-0.39,~-0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy.

CONCLUSIONS: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Brachial Artery, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Fibrosis, Humans, Incidence, Male, Peptide Fragments, Peripheral Arterial Disease, Predictive Value of Tests, Procollagen, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Transforming Growth Factor beta, United States, Vasodilation}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2015.02.020}, author = {Agarwal, Isha and Arnold, Alice and Glazer, Nicole L and Barasch, Eddy and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Gottdiener, John S and Ix, Joachim H and Jensen, Richard A and Kizer, Jorge R and Rimm, Eric B and Siscovick, David S and Tracy, Russell P and Wong, Tien Y and Mukamal, Kenneth J} } @article {6602, title = {Generalized estimating equations for genome-wide association studies using longitudinal phenotype data.}, journal = {Stat Med}, volume = {34}, year = {2015}, month = {2015 Jan 15}, pages = {118-30}, abstract = {

Many longitudinal cohort studies have both genome-wide measures of genetic variation and repeated measures of phenotypes and environmental exposures. Genome-wide association study analyses have typically used only cross-sectional data to evaluate quantitative phenotypes and binary traits. Incorporation of repeated measures may increase power to detect associations, but also requires specialized analysis methods. Here, we discuss one such method-generalized estimating equations (GEE)-in the contexts of analysis of main effects of rare genetic variants and analysis of gene-environment interactions. We illustrate the potential for increased power using GEE analyses instead of cross-sectional analyses. We also address challenges that arise, such as the need for small-sample corrections when the minor allele frequency of a genetic variant and/or the prevalence of an environmental exposure is low. To illustrate methods for detection of gene-drug interactions on a genome-wide scale, using repeated measures data, we conduct single-study analyses and meta-analyses across studies in three large cohort studies participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium-the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Rotterdam Study.

}, keywords = {Aged, Aging, Cardiovascular Diseases, Cohort Studies, Computer Simulation, Cross-Sectional Studies, Epidemiologic Research Design, Gene-Environment Interaction, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Longitudinal Studies, Meta-Analysis as Topic, Models, Genetic, Pharmacogenetics, Risk Assessment, United States}, issn = {1097-0258}, doi = {10.1002/sim.6323}, author = {Sitlani, Colleen M and Rice, Kenneth M and Lumley, Thomas and McKnight, Barbara and Cupples, L Adrienne and Avery, Christy L and Noordam, Raymond and Stricker, Bruno H C and Whitsel, Eric A and Psaty, Bruce M} } @article {6801, title = {Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults.}, journal = {Heart}, volume = {101}, year = {2015}, month = {2015 Sep}, pages = {1368-74}, abstract = {

BACKGROUND: Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.

METHODS: We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74{\textpm}5 years).

RESULTS: During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95\% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates.

CONCLUSIONS: The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.

}, keywords = {Adiponectin, Age Factors, Aged, Aged, 80 and over, Aging, Atrial Fibrillation, Biomarkers, Female, Humans, Incidence, Linear Models, Male, Multivariate Analysis, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1468-201X}, doi = {10.1136/heartjnl-2014-307015}, author = {Macheret, Fima and Bartz, Traci M and Djouss{\'e}, Luc and Ix, Joachim H and Mukamal, Kenneth J and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Heckbert, Susan R and Psaty, Bruce M and Kizer, Jorge R} } @article {6772, title = {Impact of gait speed and instrumental activities of daily living on all-cause mortality in adults >=65~years with heart failure.}, journal = {Am J Cardiol}, volume = {115}, year = {2015}, month = {2015 Mar 15}, pages = {797-801}, abstract = {

Mobility and function are important predictors of survival. However, their combined impact on mortality in adults >=65 years with heart failure (HF) is not well understood. This study examined the role of gait speed and instrumental activities of daily living (IADL) in all-cause mortality in a cohort of 1,119 community-dwelling Cardiovascular Health Study participants >=65 years with incident HF. Data on HF and mortality were collected through annual examinations or contact during the 10-year follow-up period. Slower gait speed (<0.8 m/s vs >=0.8 m/s) and IADL impairment (>=1 vs 0 areas of dependence) were determined from baseline and follow-up assessments. A total of 740 (66\%) of the 1,119 participants died during the follow-up period. Multivariate Cox proportional hazards models showed that impairments in either gait speed (hazard ratio 1.37, 95\% confidence interval 1.10 to 1.70; p = 0.004) or IADL (hazard ratio 1.56, 95\% confidence interval 1.29-1.89; p <0.001), measured within 1 year before the diagnosis of incident HF, were independently associated with mortality, adjusting for sociodemographic and clinical characteristics. The combined presence of slower gait speed and IADL impairment was associated with a greater risk of mortality and suggested an additive relation between gait speed and IADL. In conclusion, gait speed and IADL are important risk factors for mortality in adults >=65 years with HF, but the combined impairments of both gait speed and IADL can have an especially important impact on mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Early Diagnosis, Female, Follow-Up Studies, Gait, Geriatric Assessment, Heart Failure, Humans, Male, Odds Ratio, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sensitivity and Specificity, Survival Analysis, United States, Walking}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2014.12.044}, author = {Lo, Alexander X and Donnelly, John P and McGwin, Gerald and Bittner, Vera and Ahmed, Ali and Brown, Cynthia J} } @article {6821, title = {Lower Extremity Proximal Muscle Function and Dyspnea in Older Persons.}, journal = {J Am Geriatr Soc}, volume = {63}, year = {2015}, month = {2015 Aug}, pages = {1628-33}, abstract = {

OBJECTIVES: To evaluate the association between performance on a single chair stand and moderate to severe exertional dyspnea.

DESIGN: Cross-sectional.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Community-dwelling individuals aged 65 and older (N = 4,413; mean age 72.6; female, n = 2,518 (57.1\%); nonwhite, n = 199 (4.5\%); obese, n = 788 (17.9\%); history of smoking, n = 2,410 (54.6\%)).

MEASUREMENTS: Performance on single chair stand (poor (unable to rise without arm use) vs normal (able to rise without arm use)), moderate to severe exertional dyspnea (American Thoracic Society grade >=2), age, sex, ethnicity, obesity, smoking, frailty status (Fried-defined nonfrail, prefrail, frail), high cardiopulmonary risk (composite of cardiopulmonary diseases and diabetes mellitus), spirometric impairment, arthritis, depression, stroke, and kidney disease.

RESULTS: Poor performance on the single chair stand was established in 369 (8.4\%) and moderate to severe exertional dyspnea in 773 (17.5\%). Prefrail status was established in 2,210 (50.1\%), frail status in 360 (8.2\%), arthritis in 2,241 (51.4\%), high cardiopulmonary risk in 2,469 (55.9\%), spirometric impairment in 1,076 (24.4\%), kidney disease in 111 (2.5\%), depression in 107 (2.4\%), and stroke in 93 (2.1\%). In multivariable regression models, poor performance on the single chair stand was associated with moderate to severe exertional dyspnea (unadjusted odds ratio (OR) = 3.48, 95\% confidence interval (CI) = 2.78-4.36; adjusted OR = 1.85, 95\% CI = 1.41-2.41).

CONCLUSION: Poor performance on a single chair stand was associated with an adjusted 85\% greater likelihood of moderate to severe exertional dyspnea than normal performance. These results suggest that reduced proximal muscle function of the lower extremities is associated with moderate to severe exertional dyspnea, even after adjusting for multiple confounders.

}, keywords = {Aged, Aged, 80 and over, Cross-Sectional Studies, Dyspnea, Female, Frail Elderly, Geriatric Assessment, Humans, Lower Extremity, Male, Motor Activity, Muscle Contraction, Prevalence, Retrospective Studies, Spirometry, United States}, issn = {1532-5415}, doi = {10.1111/jgs.13529}, author = {Vaz Fragoso, Carlos A and Araujo, Katy and Leo-Summers, Linda and Van Ness, Peter H} } @article {6826, title = {LV Mass as a Predictor of CVD Events in~Older Adults With and Without Metabolic Syndrome and Diabetes.}, journal = {JACC Cardiovasc Imaging}, volume = {8}, year = {2015}, month = {2015 Sep}, pages = {1007-15}, abstract = {

OBJECTIVES: The purpose of this study was to examine the prognostic significance of left ventricular (LV) mass for cardiovascular disease (CVD) events in older adults with and without metabolic syndrome (MetS) and diabetes mellitus (DM).

BACKGROUND: MetS and DM are associated with increased CVD risk, but it is unclear in these groups whether subclinical CVD as shown by increased LV mass improves risk prediction compared to standard risk factors in older individuals.

METHODS: We studied 3,724 adults (mean 72.4 {\textpm} 5.4 years of age, 61.0\% female, 4.4\% African-American) from the Cardiovascular Health Study who had MetS but not DM or had DM alone or had neither condition. Cox regression was used to examine the association of LV mass, (alone and indexed by height and body surface area [BSA]) as determined by echocardiography, with CVD events, including coronary heart disease (CHD), stroke, heart failure (HF), and CVD death, as well as total mortality. We also assessed the added prediction, discriminative value, and net reclassification improvement (NRI) for clinical utility of LV mass compared to standard risk factors.

RESULTS: Over a mean follow-up of 14.2 {\textpm} 6.3 years, 2,180 subjects experienced CVD events, including 986 CVD deaths. After adjustment for age, sex and standard risk factors, LV mass was positively associated with CVD events in those with MetS (hazard ratio [HR]: 1.4, p~< 0.001) and without MetS (HR: 1.4, p~< 0.001), but not DM (HR: 1.0, p~= 0.62), with similar findings for LV mass indexed for height or BSA. Adding LV mass to standard risk factors moderately improved the prediction accuracy in the overall sample and MetS group from changes in C-statistics (p~< 0.05). Categorical-free net reclassification improvement increased significantly by 17\% to 19\% in those with MetS. Findings were comparable for CHD, CVD mortality, and total mortality.

CONCLUSIONS: LV mass is associated with increased CVD risk and provides modest added prediction and clinical utility compared to standard risk factors in older persons with and without MetS but not with DM.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Comorbidity, Diabetes Mellitus, Female, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Logistic Models, Male, Metabolic Syndrome X, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1876-7591}, doi = {10.1016/j.jcmg.2015.04.019}, author = {Hoang, Khiet and Zhao, Yanglu and Gardin, Julius M and Carnethon, Mercedes and Mukamal, Ken and Yanez, David and Wong, Nathan D} } @article {6661, title = {NT-proBNP and troponin T and risk of rapid kidney function decline and incident CKD in elderly adults.}, journal = {Clin J Am Soc Nephrol}, volume = {10}, year = {2015}, month = {2015 Feb 6}, pages = {205-14}, abstract = {

BACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR>=30\%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67\% higher risk of rapid decline and 38\% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95\% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95\% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80\% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95\% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95\% confidence interval, 0.92 to 1.50).

CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.

}, keywords = {Age Factors, Aged, Aging, Biomarkers, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney, Linear Models, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Time Factors, Troponin T, United States, Up-Regulation}, issn = {1555-905X}, doi = {10.2215/CJN.04910514}, author = {Bansal, Nisha and Katz, Ronit and Dalrymple, Lorien and de Boer, Ian and DeFilippi, Christopher and Kestenbaum, Bryan and Park, Meyeon and Sarnak, Mark and Seliger, Stephen and Shlipak, Michael} } @article {6400, title = {Potassium and glucose measures in older adults: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {70}, year = {2015}, month = {2015 Feb}, pages = {255-61}, abstract = {

BACKGROUND: We sought to determine the impacts of serum and dietary potassium measures on glucose metabolism and diabetes risk in older adults.

METHODS: Among participants of the Cardiovascular Health Study, a community-based cohort of older American adults, we examined a) cross-sectional associations between potassium and measures of insulin sensitivity and secretion estimated from oral glucose tolerance tests and b) longitudinal associations of serum and dietary potassium with diabetes risk.

RESULTS: Among 4,754 participants aged >=65 years at baseline, there were 445 cases of incident diabetes during a median follow-up of 12 years. In multivariate models, baseline serum and dietary potassium were both associated with lower insulin sensitivity and greater insulin secretion. Compared with those with a serum potassium >=4.5 mEq/L, participants with a serum potassium <4.0mEq/L had an adjusted mean difference in Matsuda insulin sensitivity index of -0.18 (-0.39, 0.02). Compared with those in the highest quartile, participants in the lowest quartile of dietary potassium intake had a corresponding adjusted mean difference in Matsuda insulin sensitivity index of -0.61 (-0.94, -0.29). In multivariate models, neither serum nor dietary potassium intake was associated with long-term diabetes risk.

CONCLUSIONS: Although we did not identify serum and dietary potassium as risk factors for incident diabetes in older adults, results from cross-sectional analyses suggest that both may be associated with increased insulin resistance. This relationship with insulin resistance needs to be confirmed, and its importance on diabetes risk, cardiovascular risk, and conditions specific to older adults should be determined as well.

}, keywords = {Aged, Blood Glucose, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Female, Humans, Insulin, Insulin Resistance, Longitudinal Studies, Male, Multivariate Analysis, Potassium, Potassium, Dietary, Risk Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glu071}, author = {Chatterjee, Ranee and Biggs, Mary L and de Boer, Ian H and Brancati, Frederick L and Svetkey, Laura P and Barzilay, Joshua and Djouss{\'e}, Luc and Ix, Joachim H and Kizer, Jorge R and Siscovick, David S and Mozaffarian, Dariush and Edelman, David and Mukamal, Kenneth J} } @article {6616, title = {Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 Jan}, pages = {153-63}, abstract = {

BACKGROUND: Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.

OBJECTIVES: We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs.

DESIGN: In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.

RESULTS: At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95\% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95\% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95\% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.

CONCLUSIONS: In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.

}, keywords = {Aged, Biomarkers, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Incidence, Lipogenesis, Liver, Male, Palmitic Acid, Phospholipids, Prevalence, Proportional Hazards Models, Risk Factors, Stearic Acids, United States, Up-Regulation}, issn = {1938-3207}, doi = {10.3945/ajcn.114.092601}, author = {Ma, Wenjie and Wu, Jason H Y and Wang, Qianyi and Lemaitre, Rozenn N and Mukamal, Kenneth J and Djouss{\'e}, Luc and King, Irena B and Song, Xiaoling and Biggs, Mary L and Delaney, Joseph A and Kizer, Jorge R and Siscovick, David S and Mozaffarian, Dariush} } @article {6930, title = {Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Am J Hematol}, volume = {90}, year = {2015}, month = {2015 Nov}, pages = {1047-51}, abstract = {

Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95\% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95\% CI 1.03, 1.95) in whites and 1.72 (95\% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans.

}, keywords = {African Americans, Aged, Alleles, European Continental Ancestry Group, Factor XI, Female, Gene Expression, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Factors, United States, Venous Thromboembolism}, issn = {1096-8652}, doi = {10.1002/ajh.24168}, author = {Folsom, Aaron R and Tang, Weihong and Roetker, Nicholas S and Heckbert, Susan R and Cushman, Mary and Pankow, James S} } @article {6849, title = {Rare and Coding Region Genetic Variants Associated With Risk of Ischemic Stroke: The NHLBI Exome Sequence Project.}, journal = {JAMA Neurol}, volume = {72}, year = {2015}, month = {2015 Jul}, pages = {781-8}, abstract = {

IMPORTANCE: Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk.

OBJECTIVE: To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome.

DESIGN, SETTING, AND PARTICIPANTS: The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP{\textquoteright}s exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013.

MAIN OUTCOMES AND MEASURES: Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis).

RESULTS: We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 {\texttimes} 10(-8)) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 {\texttimes} 10(-7)) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).

CONCLUSIONS AND RELEVANCE: Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.

}, keywords = {Aged, Brain Ischemia, Exome, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Muscle Proteins, National Heart, Lung, and Blood Institute (U.S.), Nuclear Proteins, Open Reading Frames, Palmitoyl-CoA Hydrolase, Stroke, United States}, issn = {2168-6157}, doi = {10.1001/jamaneurol.2015.0582}, author = {Auer, Paul L and Nalls, Mike and Meschia, James F and Worrall, Bradford B and Longstreth, W T and Seshadri, Sudha and Kooperberg, Charles and Burger, Kathleen M and Carlson, Christopher S and Carty, Cara L and Chen, Wei-Min and Cupples, L Adrienne and DeStefano, Anita L and Fornage, Myriam and Hardy, John and Hsu, Li and Jackson, Rebecca D and Jarvik, Gail P and Kim, Daniel S and Lakshminarayan, Kamakshi and Lange, Leslie A and Manichaikul, Ani and Quinlan, Aaron R and Singleton, Andrew B and Thornton, Timothy A and Nickerson, Deborah A and Peters, Ulrike and Rich, Stephen S} } @article {6702, title = {Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.}, journal = {Heart Rhythm}, volume = {12}, year = {2015}, month = {2015 May}, pages = {879-85}, abstract = {

BACKGROUND: Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset.

OBJECTIVE: The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF).

METHODS: In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses.

RESULTS: Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0\%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95\% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95\% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF.

CONCLUSION: The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Electrocardiography, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Outpatients, Risk Assessment, Risk Factors, Statistics as Topic, Troponin T, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2015.01.020}, author = {Hussein, Ayman A and Bartz, Traci M and Gottdiener, John S and Sotoodehnia, Nona and Heckbert, Susan R and Lloyd-Jones, Donald and Kizer, Jorge R and Christenson, Robert and Wazni, Oussama and DeFilippi, Christopher} } @article {6624, title = {Serum urate levels and the risk of hip fractures: data from the Cardiovascular Health Study.}, journal = {Metabolism}, volume = {64}, year = {2015}, month = {2015 Mar}, pages = {438-46}, abstract = {

PURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults.

METHODS: 1963 men and 2729 women >=65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori.

RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and >=6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95\% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women.

CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Health Surveys, Hip Fractures, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Risk, Sex Factors, United States, Uric Acid}, issn = {1532-8600}, doi = {10.1016/j.metabol.2014.11.006}, author = {Mehta, Tapan and B{\r u}zkov{\'a}, Petra and Sarnak, Mark J and Chonchol, Michel and Cauley, Jane A and Wallace, Erin and Fink, Howard A and Robbins, John and Jalal, Diana} } @article {6854, title = {Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.}, journal = {Diabetes Care}, volume = {38}, year = {2015}, month = {2015 Nov}, pages = {2050-8}, abstract = {

OBJECTIVE: We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.

RESEARCH DESIGN AND METHODS: Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants >=65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.

RESULTS: Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95\% CI 1.19-2.86]), snoring (HR 1.27 [95\% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95\% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.

CONCLUSIONS: Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

}, keywords = {Adult, Aged, Blood Glucose, Cardiovascular System, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Fasting, Female, Glucose Tolerance Test, Humans, Incidence, Insulin, Insulin Resistance, Male, Middle Aged, Sleep Apnea Syndromes, Sleep Initiation and Maintenance Disorders, Snoring, United States}, issn = {1935-5548}, doi = {10.2337/dc15-0137}, author = {Strand, Linn Beate and Carnethon, Mercedes and Biggs, Mary Lou and Djouss{\'e}, Luc and Kaplan, Robert C and Siscovick, David S and Robbins, John A and Redline, Susan and Patel, Sanjay R and Janszky, Imre and Mukamal, Kenneth J} } @article {6931, title = {APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {398-403}, abstract = {

OBJECTIVE: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.

APPROACH AND RESULTS: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged >=65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95\% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95\% CI, 12.5-14.3) among other African Americans and 13.3 years (95\% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95\% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95\% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.

CONCLUSIONS: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.

}, keywords = {African Americans, Age Factors, Aged, Albuminuria, Apolipoproteins, Atherosclerosis, Cardiovascular Diseases, Cause of Death, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Health Status Disparities, Heterozygote, Homozygote, Humans, Incidence, Kaplan-Meier Estimate, Kidney Diseases, Lipoproteins, HDL, Male, Myocardial Infarction, Phenotype, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.305970}, author = {Mukamal, Kenneth J and Tremaglio, Joseph and Friedman, David J and Ix, Joachim H and Kuller, Lewis H and Tracy, Russell P and Pollak, Martin R} } @article {7161, title = {Gait Speed Predicts Incident Disability: A Pooled Analysis.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Jan}, pages = {63-71}, abstract = {

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking {\textonequarter} - {\textonehalf} mile or climbing 10 steps within 3 years.

RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10\% to 1\% in men, and from 15\% to 1\% in women, while mobility difficulty trended from 47\% to 4\% in men and 40\% to 6\% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.

CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Gait, Geriatric Assessment, Humans, Independent Living, Male, Mobility Limitation, Predictive Value of Tests, Prognosis, Psychomotor Performance, Risk Assessment, Risk Factors, ROC Curve, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv126}, author = {Perera, Subashan and Patel, Kushang V and Rosano, Caterina and Rubin, Susan M and Satterfield, Suzanne and Harris, Tamara and Ensrud, Kristine and Orwoll, Eric and Lee, Christine G and Chandler, Julie M and Newman, Anne B and Cauley, Jane A and Guralnik, Jack M and Ferrucci, Luigi and Studenski, Stephanie A} } @article {7002, title = {Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Apr}, pages = {838-43}, abstract = {

OBJECTIVES: To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability.

DESIGN: Prospective cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded.

MEASUREMENTS: Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models.

RESULTS: Over an average of 7.0 years of follow-up, 660 individuals (16.3\%) developed incident AF, and 3,112 (77\%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95\% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95\% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure.

CONCLUSION: These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Atrial Fibrillation, Disability Evaluation, Electrocardiography, Female, Geriatric Assessment, Humans, Incidence, Longevity, Longitudinal Studies, Male, Medicare, Prevalence, Prospective Studies, Survival Rate, United States}, issn = {1532-5415}, doi = {10.1111/jgs.14037}, author = {Wallace, Erin R and Siscovick, David S and Sitlani, Colleen M and Dublin, Sascha and Mitchell, Pamela H and Odden, Michelle C and Hirsch, Calvin H and Thielke, Stephen and Heckbert, Susan R} } @article {6906, title = {Lifetime Risk of Venous Thromboembolism in Two Cohort Studies.}, journal = {Am J Med}, volume = {129}, year = {2016}, month = {2016 Mar}, pages = {339.e19-26}, abstract = {

BACKGROUND: Greater public awareness of venous thromboembolism may be an important next step for optimizing venous thromboembolism prevention and treatment. "Lifetime risk" is an easily interpretable way of presenting risk information. Therefore, we sought to calculate the lifetime risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism) using data from 2 large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study.

METHODS: We followed participants aged 45-64 years in ARIC (n = 14,185) and >=65 in CHS (n = 5414) at baseline visits (1987-1989 in ARIC, 1989-1990 and 1992-1993 in CHS) for incident venous thromboembolism (n = 728 in ARIC through 2011 and n = 172 in CHS through 2001). We estimated lifetime risks and 95\% confidence intervals of incident venous thromboembolism using a modified Kaplan-Meier method, accounting for the competing risk of death from other causes.

RESULTS: At age 45 years, the remaining lifetime risk of venous thromboembolism in ARIC was 8.1\% (95\% confidence interval, 7.1-8.7). High-risk groups were African Americans (11.5\% lifetime risk), those with obesity (10.9\%), heterozygous for the factor V Leiden (17.1\%), or with sickle cell trait or disease (18.2\%). Lifetime risk estimates differed by cohort; these differences were explained by differences in time period of venous thromboembolism ascertainment.

CONCLUSIONS: At least 1 in 12 middle-aged adults will develop venous thromboembolism in their remaining lifetime. This estimate of lifetime risk may be useful to promote awareness of venous thromboembolism and guide decisions at both clinical and policy levels.

}, keywords = {African Continental Ancestry Group, Aged, Anemia, Sickle Cell, Cohort Studies, Factor V, Follow-Up Studies, Heterozygote, Humans, Kaplan-Meier Estimate, Middle Aged, Obesity, Risk, Sickle Cell Trait, United States, Venous Thromboembolism}, issn = {1555-7162}, doi = {10.1016/j.amjmed.2015.10.014}, author = {Bell, Elizabeth J and Lutsey, Pamela L and Basu, Saonli and Cushman, Mary and Heckbert, Susan R and Lloyd-Jones, Donald M and Folsom, Aaron R} } @article {6996, title = {Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Apr}, pages = {750-6}, abstract = {

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged >=65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95\% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95\% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95\% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95\% confidence interval 1.09, 1.50).

CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.306647}, author = {Garg, Parveen K and Arnold, Alice M and Hinckley Stukovsky, Karen D and Koro, Carol and Jenny, Nancy S and Mukamal, Kenneth J and Criqui, Michael H and Furberg, Curt D and Newman, Anne B and Cushman, Mary} } @article {6933, title = {Physical Activity and Risk of Coronary Heart Disease and Stroke in Older Adults: The Cardiovascular Health Study.}, journal = {Circulation}, volume = {133}, year = {2016}, month = {2016 Jan 12}, pages = {147-55}, abstract = {

BACKGROUND: Although guidelines suggest that older adults engage in regular physical activity (PA) to reduce cardiovascular disease (CVD), surprisingly few studies have evaluated this relationship, especially in those >75 years. In addition, with advancing age the ability to perform some types of PA might decrease, making light-moderate exercise such as walking especially important to meet recommendations.

METHODS AND RESULTS: Prospective cohort analysis among 4207 US men and women of a mean age of 73 years (standard deviation=6) who were free of CVD at baseline in the Cardiovascular Health Study were followed from 1989 to 1999. PA was assessed and cumulatively updated over time to minimize misclassification and assess the long-term effects of habitual activity. Walking (pace, blocks, combined walking score) was updated annually from baseline through 1999. Leisure-time activity and exercise intensity were updated at baseline, 1992, and 1996. Incident CVD (fatal or nonfatal myocardial infarction, coronary death, or stroke) was adjudicated using medical records. During 41,995 person-years of follow-up, 1182 CVD events occurred. After multivariable adjustment, greater PA was inversely associated with coronary heart disease, stroke (especially ischemic stroke), and total CVD, even in those >=75 years. Walking pace, distance, and overall walking score, leisure-time activity, and exercise intensity were each associated with lower risk. For example, in comparison with a walking pace <2 mph, those that habitually walked at a pace >3 mph had a lower risk of coronary heart disease (0.50; confidence interval, 0.38-0.67), stroke (0.47; confidence interval, 033-0.66), and CVD (0.50; confidence interval, 0.40-0.62).

CONCLUSIONS: These data provide empirical evidence supporting PA recommendations, in particular, walking, to reduce the incidence of CVD among older adults.

}, keywords = {Aged, Aged, 80 and over, Coronary Disease, Female, Follow-Up Studies, Health Status, Humans, Leisure Activities, Male, Motor Activity, Proportional Hazards Models, Prospective Studies, Sampling Studies, Stroke, United States, Walking}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.115.018323}, author = {Soares-Miranda, Luisa and Siscovick, David S and Psaty, Bruce M and Longstreth, W T and Mozaffarian, Dariush} } @article {6850, title = {Relations of Postload and Fasting Glucose With Incident Cardiovascular Disease and Mortality Late in Life: The Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Mar}, pages = {370-7}, abstract = {

BACKGROUND: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse.

METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic.

RESULTS: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models.

CONCLUSION: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life.

}, keywords = {Aged, Aging, Blood Glucose, Cardiovascular Diseases, Fasting, Female, Follow-Up Studies, Glucose, Glucose Tolerance Test, Health Surveys, Humans, Incidence, Male, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv106}, author = {Brutsaert, Erika F and Shitole, Sanyog and Biggs, Mary Lou and Mukamal, Kenneth J and deBoer, Ian H and Thacker, Evan L and Barzilay, Joshua I and Djouss{\'e}, Luc and Ix, Joachim H and Smith, Nicholas L and Kaplan, Robert C and Siscovick, David S and Psaty, Bruce M and Kizer, Jorge R} } @article {7127, title = {Spousal Associations Between Frailty and Depressive Symptoms: Longitudinal Findings from the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Apr}, pages = {824-30}, abstract = {

OBJECTIVES: To determine whether older adult spouses{\textquoteright} frailty states and depressive symptoms are interrelated over time.

DESIGN: Longitudinal, dyadic path analysis using the Actor-Partner Interdependence Model.

SETTING: Data were from baseline (1989-90), Wave 3 (1992-93), and Wave 7 (1996-97), all waves in which frailty and depressive symptoms were measured, of the Cardiovascular Health Study (CHS), a multisite, longitudinal, observational study of risk factors for cardiovascular disease in adults aged 65 and older.

PARTICIPANTS: Spouses in 1,260 community-dwelling married couples.

MEASUREMENTS: Frailty was measured using the CHS criteria, categorized as nonfrail, prefrail, or frail. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale.

RESULTS: Within individuals (actor effects), greater frailty predicted greater subsequent depressive symptoms, and greater depressive symptoms predicted greater subsequent frailty. Between spouses (partner effects), an individual{\textquoteright}s greater frailty predicted the spouse{\textquoteright}s greater frailty, and an individual{\textquoteright}s greater depressive symptoms predicted the spouse{\textquoteright}s greater depressive symptoms.

CONCLUSION: Frailty and depressive symptoms are interrelated in older adult spouses. For older couples, interventions to prevent or treat frailty and depression that focus on couples may be more effective than those that focus on individuals.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Depression, Female, Frail Elderly, Humans, Longitudinal Studies, Male, Risk Factors, Spouses, United States}, issn = {1532-5415}, doi = {10.1111/jgs.14023}, author = {Monin, Joan and Doyle, Margaret and Levy, Becca and Schulz, Richard and Fried, Terri and Kershaw, Trace} } @article {6932, title = {Study of Cardiovascular Health Outcomes in the Era of Claims Data: The Cardiovascular Health Study.}, journal = {Circulation}, volume = {133}, year = {2016}, month = {2016 Jan 12}, pages = {156-64}, abstract = {

BACKGROUND: Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes.

METHODS AND RESULTS: Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure were defined in 3 ways: the CHS adjudicated event (CHS[adj]), selected International Classification of Diseases, Ninth Edition diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare \& Medicaid Services (CMS[1st]), and the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values but low sensitivities. For instance, the positive predictive value of International Classification of Diseases, Ninth Edition code 410.x1 for a new acute MI in the first position was 90.6\%, but this code identified only 53.8\% of incident MIs. The observed event rates for CMS[1st] were low. For MI, the incidence was 14.9 events per 1000 person-years for CHS[adj] MI, 8.6 for CMS[1st] MI, and 12.2 for CMS[any] MI. In general, cardiovascular disease risk factor associations were similar across the 3 methods of defining events. Indeed, traditional cardiovascular disease risk factors were also associated with all first hospitalizations not resulting from an MI.

CONCLUSIONS: The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite end point that includes the outcome of interest and selected (misclassified) nonevent hospitalizations.

}, keywords = {Blood Glucose, Cardiovascular Diseases, Female, Follow-Up Studies, Health Surveys, Hospitalization, Hospitals, Veterans, Humans, Insurance Claim Review, International Classification of Diseases, Lipids, Male, Managed Care Programs, Medicare, Risk Factors, Sampling Studies, Treatment Outcome, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.115.018610}, author = {Psaty, Bruce M and Delaney, Joseph A and Arnold, Alice M and Curtis, Lesley H and Fitzpatrick, Annette L and Heckbert, Susan R and McKnight, Barbara and Ives, Diane and Gottdiener, John S and Kuller, Lewis H and Longstreth, W T} } @article {7466, title = {Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {37}, year = {2017}, month = {2017 Aug}, pages = {1579-1586}, abstract = {

OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings.

APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15\% and worsening white matter grade in 27\%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95\% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95\% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses.

CONCLUSIONS: Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ.

}, keywords = {Age Factors, Aged, Antihypertensive Agents, Blood Pressure, Cerebral Infarction, Disease Progression, Female, Heart Rate, Humans, Hypertension, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prospective Studies, Pulsatile Flow, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.117.309298}, author = {Leung, Lester Y and Bartz, Traci M and Rice, Kenneth and Floyd, James and Psaty, Bruce and Gutierrez, Jose and Longstreth, W T and Mukamal, Kenneth J} } @article {7563, title = {Concordance With Prevention Guidelines and Subsequent Cancer, Cardiovascular Disease, and Mortality: A Longitudinal Study of Older Adults.}, journal = {Am J Epidemiol}, volume = {186}, year = {2017}, month = {2017 Nov 15}, pages = {1168-1179}, abstract = {

Reports on the associations between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with guidelines from the American Cancer Society and American Heart Association for disease prevention in relation to cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n = 3,491), were free of CVD and cancer. Total and cause-specific mortality, as well as incidence of cancer and CVD, were lower with higher guideline concordance. Independent of body mass index, blood pressure, total cholesterol, and fasting plasma glucose, better health behaviors (diet, physical activity, and alcohol consumption) were associated with lower mortality (2-sided P < 0.0001). Among individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers, those with poor concordance with health behavior recommendations had higher mortality compared with those who had the highest concordance with these behavioral recommendations (adjusted mortality hazard ratio = 1.82, 95\% confidence interval: 1.25, 2.67). Older adults who are concordant with recommendations for cancer and CVD prevention have reduced rates of chronic disease and mortality. Interventions to achieve and maintain healthy lifestyle behaviors may offer benefits both in the presence and absence of adverse traditional clinical risk factors.

}, keywords = {Aged, Aged, 80 and over, American Cancer Society, American Heart Association, Body Mass Index, Cardiovascular Diseases, Cause of Death, Diet, Exercise, Female, Guideline Adherence, Healthy Lifestyle, Humans, Incidence, Longitudinal Studies, Male, Neoplasms, Practice Guidelines as Topic, Prospective Studies, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwx150}, author = {Greenlee, Heather and Strizich, Garrett and Lovasi, Gina S and Kaplan, Robert C and Biggs, Mary L and Li, Christopher I and Richardson, John and Burke, Gregory L and Fitzpatrick, Annette L and Fretts, Amanda M and Psaty, Bruce M and Fried, Linda P} } @article {7578, title = {Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0186456}, abstract = {

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences.

OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption.

DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts.

RESULTS: Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95\% statistical power to detect a genetic variant associated with effect size of 0.05\% for fish and 0.08\% for EPA+DHA.

CONCLUSIONS: These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

}, keywords = {Adult, Aged, Cohort Studies, Docosahexaenoic Acids, Eicosapentaenoic Acid, Europe, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Seafood, United States}, issn = {1932-6203}, doi = {10.1371/journal.pone.0186456}, author = {Mozaffarian, Dariush and Dashti, Hassan S and Wojczynski, Mary K and Chu, Audrey Y and Nettleton, Jennifer A and M{\"a}nnist{\"o}, Satu and Kristiansson, Kati and Reedik, M{\"a}gi and Lahti, Jari and Houston, Denise K and Cornelis, Marilyn C and van Rooij, Frank J A and Dimitriou, Maria and Kanoni, Stavroula and Mikkil{\"a}, Vera and Steffen, Lyn M and de Oliveira Otto, Marcia C and Qi, Lu and Psaty, Bruce and Djouss{\'e}, Luc and Rotter, Jerome I and Harald, Kennet and Perola, Markus and Rissanen, Harri and Jula, Antti and Krista, Fischer and Mihailov, Evelin and Feitosa, Mary F and Ngwa, Julius S and Xue, Luting and Jacques, Paul F and Per{\"a}l{\"a}, Mia-Maria and Palotie, Aarno and Liu, Yongmei and Nalls, Nike A and Ferrucci, Luigi and Hernandez, Dena and Manichaikul, Ani and Tsai, Michael Y and Kiefte-de Jong, Jessica C and Hofman, Albert and Uitterlinden, Andr{\'e} G and Rallidis, Loukianos and Ridker, Paul M and Rose, Lynda M and Buring, Julie E and Lehtim{\"a}ki, Terho and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Lemaitre, Rozenn and Salomaa, Veikko and Knekt, Paul and Metspalu, Andres and Borecki, Ingrid B and Cupples, L Adrienne and Eriksson, Johan G and Kritchevsky, Stephen B and Bandinelli, Stefania and Siscovick, David and Franco, Oscar H and Deloukas, Panos and Dedoussis, George and Chasman, Daniel I and Raitakari, Olli and Tanaka, Toshiko} } @article {7490, title = {Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.}, journal = {Stroke}, volume = {48}, year = {2017}, month = {2017 Oct}, pages = {2678-2685}, abstract = {

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.

METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses{\textquoteright} Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.

RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95\% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95\% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95\% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95\% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95\% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results.

CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

}, keywords = {Adult, Aged, Aged, 80 and over, Biomarkers, Brain Ischemia, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Fatty Acids, Omega-3, Female, Follow-Up Studies, Humans, Incidence, Intracranial Arteriosclerosis, Intracranial Embolism, Intracranial Thrombosis, Male, Middle Aged, Prospective Studies, Random Allocation, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.117.018235}, author = {Saber, Hamidreza and Yakoob, Mohammad Yawar and Shi, Peilin and Longstreth, W T and Lemaitre, Rozenn N and Siscovick, David and Rexrode, Kathryn M and Willett, Walter C and Mozaffarian, Dariush} } @article {8555, title = {Phenotype-Specific Association of Single-Nucleotide Polymorphisms with Heart Failure and Preserved Ejection Fraction: a Genome-Wide Association Analysis of the Cardiovascular Health Study.}, journal = {J Cardiovasc Transl Res}, volume = {10}, year = {2017}, month = {2017 Jun}, pages = {285-294}, abstract = {

Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP- and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes. Among 3804 patients, 7 clinical factors and 9 SNPs were significantly associated with HFpEF; the most notable of which was rs6996224, a SNP associated with transforming growth factor-beta receptor 3. Most SNPs were associated with HFpEF only in the absence of a clinical predictor. Significant SNPs represented genes involved in myocyte proliferation, transforming growth factor-beta/erbB signaling, and extracellular matrix formation. These findings suggest that genetic factors may be more important in some phenotypes than others.

}, keywords = {Aged, Computational Biology, Databases, Genetic, European Continental Ancestry Group, Female, Gene Expression Profiling, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Failure, Humans, Male, Oligonucleotide Array Sequence Analysis, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prognosis, Proteoglycans, Receptors, Transforming Growth Factor beta, Risk Assessment, Risk Factors, Stroke Volume, United States}, issn = {1937-5395}, doi = {10.1007/s12265-017-9729-1}, author = {Kao, David P and Stevens, Laura M and Hinterberg, Michael A and G{\"o}rg, Carsten} } @article {8041, title = {Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.}, journal = {PLoS Med}, volume = {15}, year = {2018}, month = {2018 10}, pages = {e1002670}, abstract = {

BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).

METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95\% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.

CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

}, keywords = {Aged, Australia, Biomarkers, Dairy Products, Diabetes Mellitus, Type 2, Dietary Fats, Europe, Fatty Acids, Fatty Acids, Monounsaturated, Female, Humans, Incidence, Male, Middle Aged, Prospective Studies, Sex Factors, Taiwan, United States}, issn = {1549-1676}, doi = {10.1371/journal.pmed.1002670}, author = {Imamura, Fumiaki and Fretts, Amanda and Marklund, Matti and Ardisson Korat, Andres V and Yang, Wei-Sin and Lankinen, Maria and Qureshi, Waqas and Helmer, Catherine and Chen, Tzu-An and Wong, Kerry and Bassett, Julie K and Murphy, Rachel and Tintle, Nathan and Yu, Chaoyu Ian and Brouwer, Ingeborg A and Chien, Kuo-Liong and Frazier-Wood, Alexis C and Del Gobbo, Liana C and Djouss{\'e}, Luc and Geleijnse, Johanna M and Giles, Graham G and de Goede, Janette and Gudnason, Vilmundur and Harris, William S and Hodge, Allison and Hu, Frank and Koulman, Albert and Laakso, Markku and Lind, Lars and Lin, Hung-Ju and McKnight, Barbara and Rajaobelina, Kalina and Riserus, Ulf and Robinson, Jennifer G and Samieri, Cecilia and Siscovick, David S and Soedamah-Muthu, Sabita S and Sotoodehnia, Nona and Sun, Qi and Tsai, Michael Y and Uusitupa, Matti and Wagenknecht, Lynne E and Wareham, Nick J and Wu, Jason HY and Micha, Renata and Forouhi, Nita G and Lemaitre, Rozenn N and Mozaffarian, Dariush} } @article {8539, title = {Metabolic Clusters and Outcomes in Older Adults: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {66}, year = {2018}, month = {2018 02}, pages = {289-296}, abstract = {

BACKGROUND/OBJECTIVES: Few studies have the requisite phenotypic information to define metabolic patterns that may inform our understanding of the pathophysiology and consequences of diabetes in older adults. We sought to characterize clusters of older adults on the basis of shared metabolic features.

DESIGN: Population-based prospective cohort study.

SETTING: Four U.S. Cardiovascular Health Study field centers.

PARTICIPANTS: Individuals aged 65 and older taking no glucose-lowering agents (N~=~2,231).

MEASUREMENTS: K-means cluster analysis of 11 metabolic parameters (fasting and postload serum glucose and plasma insulin, fasting C-peptide, body mass index, C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), albuminuria, carboxymethyl lysine (an advanced glycation end-product), procollagen III N-terminal propeptide (a fibrotic marker)) and their associations with incident cardiovascular disease, diabetes, disability, and mortality over 8 to 14.5~years of follow-up and with measures of subclinical cardiovascular disease.

RESULTS: A 6-cluster solution provided robust differentiation into distinct, identifiable clusters. Cluster A (n~=~739) had the lowest glucose and insulin and highest eGFR and the lowest rates of all outcomes. Cluster B (n~=~419) had high glucose and insulin and intermediate rates of most outcomes. Cluster C (n~=~118) had the highest insulin. Cluster D (n~=~129) had the highest glucose with much lower insulin. Cluster E (n~=~314) had the lowest eGFR and highest albuminuria. Cluster F (n~=~512) had the highest CRP. Rates of CVD, mortality, and subclinical atherosclerosis were highest in clusters C, D, and E and were similar to rates in participants with treated diabetes. Incidence of disability was highest in Cluster C.

CONCLUSION: Clustering according to metabolic parameters identifies distinct phenotypes that are strongly associated with clinical and functional outcomes, even at advanced age.

}, keywords = {Aged, Aged, 80 and over, Blood Glucose, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Incidence, Insulin, Longitudinal Studies, Male, Prospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/jgs.15205}, author = {Mukamal, Kenneth J and Siscovick, David S and de Boer, Ian H and Ix, Joachim H and Kizer, Jorge R and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Tracy, Russell P and Boyko, Edward J and Kahn, Steven E and Arnold, Alice M} } @article {8507, title = {Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.}, journal = {Circulation}, volume = {140}, year = {2019}, month = {2019 08 20}, pages = {645-657}, abstract = {

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

RESULTS: Among 11 461 individuals (mean age 64 years, 67\% women, 35\% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.

CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

}, keywords = {Adult, Aged, Cohort Studies, Coronary Disease, CpG Islands, DNA Methylation, Europe, Female, Genome-Wide Association Study, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Population Groups, Prognosis, Prospective Studies, Risk, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.118.039357}, author = {Agha, Golareh and Mendelson, Michael M and Ward-Caviness, Cavin K and Joehanes, Roby and Huan, Tianxiao and Gondalia, Rahul and Salfati, Elias and Brody, Jennifer A and Fiorito, Giovanni and Bressler, Jan and Chen, Brian H and Ligthart, Symen and Guarrera, Simonetta and Colicino, Elena and Just, Allan C and Wahl, Simone and Gieger, Christian and Vandiver, Amy R and Tanaka, Toshiko and Hernandez, Dena G and Pilling, Luke C and Singleton, Andrew B and Sacerdote, Carlotta and Krogh, Vittorio and Panico, Salvatore and Tumino, Rosario and Li, Yun and Zhang, Guosheng and Stewart, James D and Floyd, James S and Wiggins, Kerri L and Rotter, Jerome I and Multhaup, Michael and Bakulski, Kelly and Horvath, Steven and Tsao, Philip S and Absher, Devin M and Vokonas, Pantel and Hirschhorn, Joel and Fallin, M Daniele and Liu, Chunyu and Bandinelli, Stefania and Boerwinkle, Eric and Dehghan, Abbas and Schwartz, Joel D and Psaty, Bruce M and Feinberg, Andrew P and Hou, Lifang and Ferrucci, Luigi and Sotoodehnia, Nona and Matullo, Giuseppe and Peters, Annette and Fornage, Myriam and Assimes, Themistocles L and Whitsel, Eric A and Levy, Daniel and Baccarelli, Andrea A} } @article {9372, title = {Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.}, journal = {Am J Hypertens}, volume = {32}, year = {2019}, month = {2019 Nov 15}, pages = {1146-1153}, abstract = {

BACKGROUND: Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.

METHODS: We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP >= 140 mm Hg and/or diastolic BP >= 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL.

RESULTS: The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 {\texttimes} 10-8) and in the race-combined analysis (P = 1.5 {\texttimes} 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95\% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls.

CONCLUSION: This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.

}, keywords = {Aged, Antihypertensive Agents, Black or African American, Blood Pressure, Case-Control Studies, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, DNA-Binding Proteins, Drug Resistance, Dystrophin-Associated Proteins, Europe, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Myosin Heavy Chains, Myosin Type V, Neuropeptides, Pharmacogenetics, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Transcription Factors, United States, White People}, issn = {1941-7225}, doi = {10.1093/ajh/hpz150}, author = {Irvin, Marguerite R and Sitlani, Colleen M and Floyd, James S and Psaty, Bruce M and Bis, Joshua C and Wiggins, Kerri L and Whitsel, Eric A and St{\"u}rmer, Til and Stewart, James and Raffield, Laura and Sun, Fangui and Liu, Ching-Ti and Xu, Hanfei and Cupples, Adrienne L and Tanner, Rikki M and Rossing, Peter and Smith, Albert and Zilh{\~a}o, Nuno R and Launer, Lenore J and Noordam, Raymond and Rotter, Jerome I and Yao, Jie and Li, Xiaohui and Guo, Xiuqing and Limdi, Nita and Sundaresan, Aishwarya and Lange, Leslie and Correa, Adolfo and Stott, David J and Ford, Ian and Jukema, J Wouter and Gudnason, Vilmundur and Mook-Kanamori, Dennis O and Trompet, Stella and Palmas, Walter and Warren, Helen R and Hellwege, Jacklyn N and Giri, Ayush and O{\textquoteright}donnell, Christopher and Hung, Adriana M and Edwards, Todd L and Ahluwalia, Tarunveer S and Arnett, Donna K and Avery, Christy L} } @article {8402, title = {Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.}, journal = {Lancet Respir Med}, volume = {8}, year = {2020}, month = {2020 01}, pages = {34-44}, abstract = {

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.

METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (>=17 years), two recruited middle-aged and older adults (>=45 years), and two recruited only elderly adults (>=65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.

FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31{\textperiodcentered}01 mL per year (95\% CI 30{\textperiodcentered}66-31{\textperiodcentered}37) in sustained never-smokers, 34{\textperiodcentered}97 mL per year (34{\textperiodcentered}36-35{\textperiodcentered}57) in former smokers, and 39{\textperiodcentered}92 mL per year (38{\textperiodcentered}92-40{\textperiodcentered}92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1{\textperiodcentered}82 mL per year (95\% CI 1{\textperiodcentered}24-2{\textperiodcentered}40) compared to never-smokers, which was approximately 20\% of the effect estimate for current smokers (9{\textperiodcentered}21 mL per year; 95\% CI 8{\textperiodcentered}35-10{\textperiodcentered}08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7{\textperiodcentered}65 mL per year; 95\% CI 6{\textperiodcentered}21-9{\textperiodcentered}09) was 68\% of that in current smokers consuming 30 or more cigarettes per day (11{\textperiodcentered}24 mL per year; 9{\textperiodcentered}86-12{\textperiodcentered}62), and around five times greater than in former smokers (1{\textperiodcentered}57 mL per year; 1{\textperiodcentered}00-2{\textperiodcentered}14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.

INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.

FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

}, keywords = {Adult, Aged, Case-Control Studies, Ex-Smokers, Female, Follow-Up Studies, Humans, Lung, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Non-Smokers, Respiratory Physiological Phenomena, Smokers, Smoking, Spirometry, United States, Young Adult}, issn = {2213-2619}, doi = {10.1016/S2213-2600(19)30276-0}, author = {Oelsner, Elizabeth C and Balte, Pallavi P and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Folsom, Aaron R and Freedman, Neal D and Jacobs, David R and Kalhan, Ravi and Mathew, Amanda R and Kronmal, Richard A and Loehr, Laura R and London, Stephanie J and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Lewis J and White, Wendy B and Yende, Sachin} } @article {8499, title = {Pre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.}, journal = {Diab Vasc Dis Res}, volume = {17}, year = {2020}, month = {2020 Jan-Feb}, pages = {1479164119888476}, abstract = {

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 {\textpm} 6.9 years of follow-up. Overall, 39.1\% of participants had pre-diabetes mellitus, 14.0\% had diabetes mellitus and 532 (11.8\%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all < 0.05 to < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

}, keywords = {Age Factors, Aged, Angina Pectoris, Diabetes Mellitus, Female, Humans, Incidence, Male, Prediabetic State, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1752-8984}, doi = {10.1177/1479164119888476}, author = {Mathenge, Njambi and Fan, Wenjun and Wong, Nathan D and Hirsch, Calvin and Delaney, Chris Joseph and Amsterdam, Ezra A and Koch, Bruce and Calara, Rico and Gardin, Julius M} } @article {9114, title = {Association Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.}, journal = {JAMA}, volume = {326}, year = {2021}, month = {2021 12 14}, pages = {2287-2298}, abstract = {

Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood.

Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults.

Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65 251 participants aged 18 to 102 years of whom 53 701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018).

Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1 less than 80\% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1 greater than or equal to 80\% predicted.

Main Outcomes and Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities.

Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4\% women, 48.5\% never-smokers), 4582 (8.5\%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3\% vs 31.4\%; prevalence ratio [PR], 1.68 [95\% CI, 1.55-1.82]), underweight (prevalence, 1.4\% vs 1.0\%; PR, 2.20 [95\% CI, 1.72-2.82]), female sex (prevalence, 60.3\% vs 59.0\%; PR, 1.07 [95\% CI, 1.01-1.13]), and current smoking (prevalence, 25.2\% vs 17.5\%; PR, 1.33 [95\% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95\% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95\% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95\% CI, 0.7-1.6]; adjusted HR, 1.95 [95\% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95\% CI, 2.1-3.4]; adjusted HR, 1.55 [95\% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95\% CI, 4.9-7.5]; adjusted HR, 1.90 [95\% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95\% CI, 3.7-5.8]; adjusted HR, 1.30 [95\% CI, 1.18-1.42]).

Conclusions and Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal.

}, keywords = {Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Forced Expiratory Volume, Humans, Lung, Lung Diseases, Male, Middle Aged, Prevalence, Retrospective Studies, Spirometry, United States, Vital Capacity}, issn = {1538-3598}, doi = {10.1001/jama.2021.20939}, author = {Wan, Emily S and Balte, Pallavi and Schwartz, Joseph E and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Daviglus, Martha L and Dransfield, Mark T and Gharib, Sina A and Jacobs, David R and Kalhan, Ravi and London, Stephanie J and Navas-Acien, Ana and O{\textquoteright}Connor, George T and Sanders, Jason L and Smith, Benjamin M and White, Wendy and Yende, Sachin and Oelsner, Elizabeth C} } @article {9000, title = {Associations of Body Mass Index and Waist Circumference in Young Adulthood with Later Life Incident Diabetes.}, journal = {J Clin Endocrinol Metab}, volume = {106}, year = {2021}, month = {2021 11 19}, pages = {e5011-e5020}, abstract = {

CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied.

OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (>=40 years).

DESIGN: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis.

SETTING: Population-based cohort studies.

PARTICIPANTS: 30 780 participants (56.1\% female, 69.8\% non-Hispanic white) without a diagnosis of diabetes by age 40.

INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life.

MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose >=126 mg/dL, nonfasting glucose >=200 mg/dL, or use of diabetes medications.

RESULTS: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI >= 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49\% and 44\% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations.

CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator.

}, keywords = {Adolescent, Adult, Biomarkers, Body Mass Index, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Male, Obesity, Overweight, Prognosis, Prospective Studies, Risk Factors, United States, Waist Circumference, Young Adult}, issn = {1945-7197}, doi = {10.1210/clinem/dgab551}, author = {Nair, Nandini and Vittinghoff, Eric and Pletcher, Mark J and Oelsner, Elizabeth C and Allen, Norrina B and Ndumele, Chiadi E and West, Nancy A and Strotmeyer, Elsa S and Mukamal, Kenneth J and Siscovick, David S and Biggs, Mary L and Laferr{\`e}re, Blandine and Moran, Andrew E and Zhang, Yiyi} } @article {8921, title = {Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts.}, journal = {Clin Nutr}, volume = {40}, year = {2021}, month = {2021 05}, pages = {2475-2482}, abstract = {

BACKGROUND AND AIMS: Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults.

DESIGN: We used prospective cohort design to complete time-to-event analyses.

METHODS: We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n~=~103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks.

RESULTS: Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of >=2 eggs per week was associated with elevated risk [27\% elevated risk of T2D comparing 7+ eggs/week with none (95\% CI: 16\%-37\%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30\% higher risk of CHD (95\% CI: 3\%-56\%) restricted to older adults consuming 5-6 eggs/week.

CONCLUSIONS: Our data showed an elevated risk of T2D with egg consumption of >=2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation.

}, keywords = {Adult, Aged, Cohort Studies, Coronary Disease, Diabetes Mellitus, Type 2, Diet, Eggs, Humans, Middle Aged, Prospective Studies, Risk Factors, United States}, issn = {1532-1983}, doi = {10.1016/j.clnu.2021.03.003}, author = {Djouss{\'e}, Luc and Zhou, Guohai and McClelland, Robyn L and Ma, Nanxun and Zhou, Xia and Kabagambe, Edmond K and Talegawkar, Sameera A and Judd, Suzanne E and Biggs, Mary L and Fitzpatrick, Annette L and Clark, Cheryl R and Gagnon, David R and Steffen, Lyn M and Gaziano, J Michael and Lee, I-Min and Buring, Julie E and Manson, JoAnn E} } @article {8709, title = {Sex Differences in Cognitive Decline Among US Adults.}, journal = {JAMA Netw Open}, volume = {4}, year = {2021}, month = {2021 02 01}, pages = {e210169}, abstract = {

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women.

Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.

Design, Setting, and Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.

Exposure: Sex.

Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.

Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7\%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9\%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4\%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95\% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95\% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95\% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95\% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95\% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95\% CI, -0.023 to 0.014; P = .61).

Conclusions and Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.

}, keywords = {Aged, Cognitive Dysfunction, Cognitive Reserve, Cohort Studies, Executive Function, Humans, Memory, Middle Aged, Risk, Sex Factors, Time Factors, United States}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2021.0169}, author = {Levine, Deborah A and Gross, Alden L and Brice{\~n}o, Emily M and Tilton, Nicholas and Giordani, Bruno J and Sussman, Jeremy B and Hayward, Rodney A and Burke, James F and Hingtgen, Stephanie and Elkind, Mitchell S V and Manly, Jennifer J and Gottesman, Rebecca F and Gaskin, Darrell J and Sidney, Stephen and Sacco, Ralph L and Tom, Sarah E and Wright, Clinton B and Yaffe, Kristine and Galecki, Andrzej T} } @article {8779, title = {Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.}, journal = {Am J Hum Genet}, volume = {108}, year = {2021}, month = {2021 05 06}, pages = {874-893}, abstract = {

Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3~bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.

}, keywords = {Adult, Aged, Chromosomes, Human, Pair 16, Datasets as Topic, Erythrocytes, Female, Gene Editing, Genetic Variation, Genome-Wide Association Study, HEK293 Cells, Humans, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Quality Control, Reproducibility of Results, United States}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2021.04.003}, author = {Hu, Yao and Stilp, Adrienne M and McHugh, Caitlin P and Rao, Shuquan and Jain, Deepti and Zheng, Xiuwen and Lane, John and M{\'e}ric de Bellefon, S{\'e}bastian and Raffield, Laura M and Chen, Ming-Huei and Yanek, Lisa R and Wheeler, Marsha and Yao, Yao and Ren, Chunyan and Broome, Jai and Moon, Jee-Young and de Vries, Paul S and Hobbs, Brian D and Sun, Quan and Surendran, Praveen and Brody, Jennifer A and Blackwell, Thomas W and Choquet, Helene and Ryan, Kathleen and Duggirala, Ravindranath and Heard-Costa, Nancy and Wang, Zhe and Chami, Nathalie and Preuss, Michael H and Min, Nancy and Ekunwe, Lynette and Lange, Leslie A and Cushman, Mary and Faraday, Nauder and Curran, Joanne E and Almasy, Laura and Kundu, Kousik and Smith, Albert V and Gabriel, Stacey and Rotter, Jerome I and Fornage, Myriam and Lloyd-Jones, Donald M and Vasan, Ramachandran S and Smith, Nicholas L and North, Kari E and Boerwinkle, Eric and Becker, Lewis C and Lewis, Joshua P and Abecasis, Goncalo R and Hou, Lifang and O{\textquoteright}Connell, Jeffrey R and Morrison, Alanna C and Beaty, Terri H and Kaplan, Robert and Correa, Adolfo and Blangero, John and Jorgenson, Eric and Psaty, Bruce M and Kooperberg, Charles and Walton, Russell T and Kleinstiver, Benjamin P and Tang, Hua and Loos, Ruth J F and Soranzo, Nicole and Butterworth, Adam S and Nickerson, Debbie and Rich, Stephen S and Mitchell, Braxton D and Johnson, Andrew D and Auer, Paul L and Li, Yun and Mathias, Rasika A and Lettre, Guillaume and Pankratz, Nathan and Laurie, Cathy C and Laurie, Cecelia A and Bauer, Daniel E and Conomos, Matthew P and Reiner, Alexander P} } @article {8914, title = {Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program.}, journal = {Am J Hum Genet}, volume = {108}, year = {2021}, month = {2021 10 07}, pages = {1836-1851}, abstract = {

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.

}, keywords = {Asthma, Biomarkers, Dermatitis, Atopic, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Leukocytes, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Polymorphism, Single Nucleotide, Prognosis, Proteome, Pulmonary Disease, Chronic Obstructive, Quantitative Trait Loci, United Kingdom, United States, Whole Genome Sequencing}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2021.08.007}, author = {Mikhaylova, Anna V and McHugh, Caitlin P and Polfus, Linda M and Raffield, Laura M and Boorgula, Meher Preethi and Blackwell, Thomas W and Brody, Jennifer A and Broome, Jai and Chami, Nathalie and Chen, Ming-Huei and Conomos, Matthew P and Cox, Corey and Curran, Joanne E and Daya, Michelle and Ekunwe, Lynette and Glahn, David C and Heard-Costa, Nancy and Highland, Heather M and Hobbs, Brian D and Ilboudo, Yann and Jain, Deepti and Lange, Leslie A and Miller-Fleming, Tyne W and Min, Nancy and Moon, Jee-Young and Preuss, Michael H and Rosen, Jonathon and Ryan, Kathleen and Smith, Albert V and Sun, Quan and Surendran, Praveen and de Vries, Paul S and Walter, Klaudia and Wang, Zhe and Wheeler, Marsha and Yanek, Lisa R and Zhong, Xue and Abecasis, Goncalo R and Almasy, Laura and Barnes, Kathleen C and Beaty, Terri H and Becker, Lewis C and Blangero, John and Boerwinkle, Eric and Butterworth, Adam S and Chavan, Sameer and Cho, Michael H and Choquet, Helene and Correa, Adolfo and Cox, Nancy and DeMeo, Dawn L and Faraday, Nauder and Fornage, Myriam and Gerszten, Robert E and Hou, Lifang and Johnson, Andrew D and Jorgenson, Eric and Kaplan, Robert and Kooperberg, Charles and Kundu, Kousik and Laurie, Cecelia A and Lettre, Guillaume and Lewis, Joshua P and Li, Bingshan and Li, Yun and Lloyd-Jones, Donald M and Loos, Ruth J F and Manichaikul, Ani and Meyers, Deborah A and Mitchell, Braxton D and Morrison, Alanna C and Ngo, Debby and Nickerson, Deborah A and Nongmaithem, Suraj and North, Kari E and O{\textquoteright}Connell, Jeffrey R and Ortega, Victor E and Pankratz, Nathan and Perry, James A and Psaty, Bruce M and Rich, Stephen S and Soranzo, Nicole and Rotter, Jerome I and Silverman, Edwin K and Smith, Nicholas L and Tang, Hua and Tracy, Russell P and Thornton, Timothy A and Vasan, Ramachandran S and Zein, Joe and Mathias, Rasika A and Reiner, Alexander P and Auer, Paul L} } @article {8976, title = {Diabetes Status Modifies the Association Between Different Measures of Obesity and Heart Failure Risk Among Older Adults: A Pooled Analysis of Community-Based NHLBI Cohorts.}, journal = {Circulation}, volume = {145}, year = {2022}, month = {2022 01 25}, pages = {268-278}, abstract = {

BACKGROUND: Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established.

METHODS: Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI>=30 kg/m), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes.

RESULTS: The study included 10 387 participants (52.9\% ARIC; 25.1\% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (=0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3\%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95\% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI ( interaction=0.04) and WC ( interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95\% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8\%, 29.9\%, and 13.7\%, respectively) versus those without diabetes (<=1\% for each).

CONCLUSIONS: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.

}, keywords = {Aged, Cohort Studies, Diabetes Mellitus, Female, Heart Failure, Humans, Male, National Heart, Lung, and Blood Institute (U.S.), Obesity, Risk Factors, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.121.055830}, author = {Patel, Kershaw V and Segar, Matthew W and Lavie, Carl J and Kondamudi, Nitin and Neeland, Ian J and Almandoz, Jaime P and Martin, Corby K and Carbone, Salvatore and Butler, Javed and Powell-Wiley, Tiffany M and Pandey, Ambarish} } @article {9095, title = {Longitudinal Changes in Hearing and Visual Impairments and Risk of Dementia in Older Adults in the United States.}, journal = {JAMA Netw Open}, volume = {5}, year = {2022}, month = {2022 05 02}, pages = {e2210734}, abstract = {

Importance: Hearing and vision problems are individually associated with increased dementia risk, but the impact of having concurrent hearing and vision deficits, ie, dual sensory impairment (DSI), on risk of dementia, including its major subtypes Alzheimer disease (AD) and vascular dementia (VaD), is not well known.

Objective: To evaluate whether DSI is associated with incident dementia in older adults.

Design, Setting, and Participants: This prospective cohort study from the Cardiovascular Health Study (CHS) was conducted between 1992 and 1999, with as many as 8 years of follow-up. The multicenter, population-based sample was recruited from Medicare eligibility files in 4 US communities with academic medical centers. Of 5888 participants aged 65 years and older in CHS, 3602 underwent cranial magnetic resonance imaging and completed the modified Mini-Mental State Examination in 1992 to 1994 as part of the CHS Cognition Study. A total of 227 participants were excluded due to prevalent dementia, leaving a total of 3375 participants without dementia at study baseline. The study hypothesis was that DSI would be associated with increased risk of dementia compared with no sensory impairment. The association between the duration of DSI with risk of dementia was also evaluated. Data analysis was conducted from November 2019 to February 2020.

Exposures: Hearing and vision impairments were collected via self-report at baseline and as many as 5 follow-up visits.

Main Outcomes and Measures: All-cause dementia, AD, and VaD, classified by a multidisciplinary committee using standardized criteria.

Results: A total of 2927 participants with information on hearing and vision at all available study visits were included in the analysis (mean [SD] age, 74.6 [4.8] years; 1704 [58.2\%] women; 455 [15.5\%] African American or Black; 2472 [85.5\%] White). Compared with no sensory impairment, DSI was associated with increased risk of all-cause dementia (hazard ratio [HR], 2.60; 95\% CI, 1.66-2.06; P < .001), AD (HR, 3.67; 95\% CI, 2.04-6.60; P < .001) but not VaD (HR, 2.03; 95\% CI, 1.00-4.09; P = .05).

Conclusions and Relevance: In this cohort study, DSI was associated with increased risk of dementia, particularly AD. Evaluation of hearing and vision in older adults may help to identify those at high risk of developing dementia.

}, keywords = {Aged, Alzheimer Disease, Cohort Studies, Female, Hearing, Hearing Loss, Humans, Male, Medicare, Prospective Studies, United States, Vision Disorders}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2022.10734}, author = {Hwang, Phillip H and Longstreth, W T and Thielke, Stephen M and Francis, Courtney E and Carone, Marco and Kuller, Lewis H and Fitzpatrick, Annette L} } @article {9160, title = {Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.}, journal = {Eur Heart J}, volume = {43}, year = {2022}, month = {2022 06 14}, pages = {2196-2208}, abstract = {

AIMS: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF).

METHODS AND RESULTS: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC >=0.70, FVC <80\%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50\%) or preserved EF (HFpEF; EF >=50\%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95\% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95\% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking.

CONCLUSION: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

}, keywords = {Adult, Heart Failure, Hospitalization, Humans, Lung, National Heart, Lung, and Blood Institute (U.S.), Prognosis, Risk Factors, Stroke Volume, United States}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehac205}, author = {Eckhardt, Christina M and Balte, Pallavi P and Barr, Robert Graham and Bertoni, Alain G and Bhatt, Surya P and Cuttica, Michael and Cassano, Patricia A and Chaves, Paolo and Couper, David and Jacobs, David R and Kalhan, Ravi and Kronmal, Richard and Lange, Leslie and Loehr, Laura and London, Stephanie J and O{\textquoteright}Connor, George T and Rosamond, Wayne and Sanders, Jason and Schwartz, Joseph E and Shah, Amil and Shah, Sanjiv J and Smith, Lewis and White, Wendy and Yende, Sachin and Oelsner, Elizabeth C} } @article {9158, title = {Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program.}, journal = {Commun Biol}, volume = {5}, year = {2022}, month = {2022 07 28}, pages = {756}, abstract = {

The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI{\textquoteright}s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.

}, keywords = {Diabetes Mellitus, Type 2, Fasting, Glucose, Humans, Insulin, National Heart, Lung, and Blood Institute (U.S.), Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Precision Medicine, Receptors, Immunologic, United States}, issn = {2399-3642}, doi = {10.1038/s42003-022-03702-4}, author = {DiCorpo, Daniel and Gaynor, Sheila M and Russell, Emily M and Westerman, Kenneth E and Raffield, Laura M and Majarian, Timothy D and Wu, Peitao and Sarnowski, Chloe and Highland, Heather M and Jackson, Anne and Hasbani, Natalie R and de Vries, Paul S and Brody, Jennifer A and Hidalgo, Bertha and Guo, Xiuqing and Perry, James A and O{\textquoteright}Connell, Jeffrey R and Lent, Samantha and Montasser, May E and Cade, Brian E and Jain, Deepti and Wang, Heming and D{\textquoteright}Oliveira Albanus, Ricardo and Varshney, Arushi and Yanek, Lisa R and Lange, Leslie and Palmer, Nicholette D and Almeida, Marcio and Peralta, Juan M and Aslibekyan, Stella and Baldridge, Abigail S and Bertoni, Alain G and Bielak, Lawrence F and Chen, Chung-Shiuan and Chen, Yii-Der Ida and Choi, Won Jung and Goodarzi, Mark O and Floyd, James S and Irvin, Marguerite R and Kalyani, Rita R and Kelly, Tanika N and Lee, Seonwook and Liu, Ching-Ti and Loesch, Douglas and Manson, JoAnn E and Minster, Ryan L and Naseri, Take and Pankow, James S and Rasmussen-Torvik, Laura J and Reiner, Alexander P and Reupena, Muagututi{\textquoteright}a Sefuiva and Selvin, Elizabeth and Smith, Jennifer A and Weeks, Daniel E and Xu, Huichun and Yao, Jie and Zhao, Wei and Parker, Stephen and Alonso, Alvaro and Arnett, Donna K and Blangero, John and Boerwinkle, Eric and Correa, Adolfo and Cupples, L Adrienne and Curran, Joanne E and Duggirala, Ravindranath and He, Jiang and Heckbert, Susan R and Kardia, Sharon L R and Kim, Ryan W and Kooperberg, Charles and Liu, Simin and Mathias, Rasika A and McGarvey, Stephen T and Mitchell, Braxton D and Morrison, Alanna C and Peyser, Patricia A and Psaty, Bruce M and Redline, Susan and Shuldiner, Alan R and Taylor, Kent D and Vasan, Ramachandran S and Viaud-Martinez, Karine A and Florez, Jose C and Wilson, James G and Sladek, Robert and Rich, Stephen S and Rotter, Jerome I and Lin, Xihong and Dupuis, Jos{\'e}e and Meigs, James B and Wessel, Jennifer and Manning, Alisa K} } @article {9291, title = {Association of Obesity With Cognitive Decline in Black and White Americans.}, journal = {Neurology}, volume = {100}, year = {2023}, month = {2023 Jan 10}, pages = {e220-e231}, abstract = {

BACKGROUND AND OBJECTIVES: There are disparities in the prevalence of obesity by race, and the relationship between obesity and cognitive decline is unclear. The objective of this study was to determine whether obesity is independently associated with cognitive decline and whether the association between obesity and cognitive decline differs in Black and White adults. We hypothesized that obesity is associated with greater cognitive decline compared with normal weight and that the effect of obesity on cognitive decline is more pronounced in Black adults compared with their White counterparts.

METHODS: We pooled data from 28,867 participants free of stroke and dementia (mean, SD: age 61 [10.7] years at the first cognitive assessment, 55\% female, 24\% Black, and 29\% obese) from 6 cohorts. The primary outcome was the annual change in global cognition. We performed linear mixed-effects models with and without time-varying cumulative mean systolic blood pressure (SBP) and fasting plasma glucose (FPG). Global cognition was set to a t-score metric (mean 50, SD 10) at a participant{\textquoteright}s first cognitive assessment; a 1-point difference represents a 0.1 SD difference in global cognition across the 6 cohorts. The median follow-up was 6.5 years (25th percentile, 75th percentile: 5.03, 20.15).

RESULTS: Obese participants had lower baseline global cognition than normal-weight participants (difference in intercepts, -0.36 [95\% CI, -0.46 to -0.17]; < 0.001). This difference in baseline global cognition was attenuated but was borderline significant after accounting for SBP and FPG (adjusted differences in intercepts, -0.19 [95\% CI, -0.39 to 0.002]; = 0.05). There was no difference in the rate of decline in global cognition between obese and normal-weight participants (difference in slope, 0.009 points/year [95\% CI, -0.009 to 0.03]; = 0.32). After accounting for SBP and FPG, obese participants had a slower decline in global cognition (adjusted difference in slope, 0.03 points/year slower [95\% CI, 0.01 to 0.05]; < 0.001). There was no evidence that race modified the association between body mass index and global cognitive decline ( = 0.34).

DISCUSSION: These results suggest that obesity is associated with lower initial cognitive scores and may potentially attenuate declines in cognition after accounting for BP and FPG.

}, keywords = {Aged, Black or African American, Cognition, Cognitive Dysfunction, Female, Humans, Male, Middle Aged, Obesity, Risk Factors, United States, White}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000201367}, author = {Quaye, Emmanuel and Galecki, Andrzej T and Tilton, Nicholas and Whitney, Rachael and Brice{\~n}o, Emily M and Elkind, Mitchell S V and Fitzpatrick, Annette L and Gottesman, Rebecca F and Griswold, Michael and Gross, Alden L and Heckbert, Susan R and Hughes, Timothy M and Longstreth, W T and Sacco, Ralph L and Sidney, Stephen and Windham, B Gwen and Yaffe, Kristine and Levine, Deborah A} } @article {9382, title = {Effect of 2022 ACC/AHA/HFSA Criteria on Stages of Heart~Failure in a Pooled Community Cohort.}, journal = {J Am Coll Cardiol}, volume = {81}, year = {2023}, month = {2023 Jun 13}, pages = {2231-2242}, abstract = {

BACKGROUND: The 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart~Failure Society of America (HFSA) clinical practice guideline proposed an updated definition for heart failure (HF) stages.

OBJECTIVES: This study aimed to compare prevalence and prognosis of HF stages according to classification/definition originally described in 2013 and 2022 ACC/AHA/HFSA definitions.

METHODS: Study participants from 3 longitudinal cohorts (the MESA [Multi-Ethnic Study of Atherosclerosis], CHS [Cardiovascular Health Study], and the FHS [Framingham Heart Study]), were categorized into 4 HF stages according to the 2013 and 2022 criteria. Cox proportional hazards regression was used to assess predictors of progression to symptomatic HF and adverse clinical outcomes associated with each HF stage.

RESULTS: Among 11,618 study participants, according to the 2022 staging, 1,943 (16.7\%) were healthy, 4,348 (37.4\%) were in stage A (at risk), 5,019 (43.2\%) were in stage B (pre-HF), and 308 (2.7\%) were in stage C/D (symptomatic HF). Compared to the classification/definition originally described in 2013, the 2022 ACC/AHA/HFSA approach resulted in a higher proportion of individuals with stage B HF (increase from 15.9\% to 43.2\%); this shift disproportionately involved women as well as Hispanic and Black individuals. Despite the 2022 criteria designating a greater proportion of individuals as stage B, the relative risk of progression to symptomatic HF remained similar (HR: 10.61; 95\%~CI: 9.00-12.51; P~< 0.001).

CONCLUSIONS: New standards for HF staging resulted in a substantial shift of community-based individuals from stage A to stage B. Those with stage B HF in the new system were at high risk for progression to symptomatic HF.

}, keywords = {American Heart Association, Atherosclerosis, Cardiology, Female, Heart Failure, Humans, Longitudinal Studies, Prognosis, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2023.04.007}, author = {Mohebi, Reza and Wang, Dongyu and Lau, Emily S and Parekh, Juhi K and Allen, Norrina and Psaty, Bruce M and Benjamin, Emelia J and Levy, Daniel and Wang, Thomas J and Shah, Sanjiv J and Gottdiener, John S and Januzzi, James L and Ho, Jennifer E} } @article {9451, title = {Plasma Trimethylamine--Oxide and Incident Ischemic Stroke: The Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis.}, journal = {J Am Heart Assoc}, volume = {12}, year = {2023}, month = {2023 Aug 15}, pages = {e8711}, abstract = {

Background The association of circulating trimethylamine--oxide (TMAO) with stroke has received limited attention. To address this gap, we examined the associations of serial measures of plasma TMAO with incident ischemic stroke. Methods and Results We used a prospective cohort design with data pooled from 2 cohorts. The settings were the CHS (Cardiovascular Health Study), a cohort of older adults, and the MESA (Multi-Ethnic Study of Atherosclerosis), both in the United States. We measured plasma concentrations of TMAO at baseline and again during the follow-up using high-performance liquid chromatography and mass spectrometry. We assessed the association of plasma TMAO with incident ischemic stroke using proportional hazards regression adjusted for risk factors. The combined cohorts included 11 785 participants without a history of stroke, on average 73 (CHS) and 62 (MESA) years old at baseline, including 60\% (CHS) and 53\% (MESA) women. We identified 1031 total incident ischemic strokes during a median 15-year follow-up in the combined cohorts. In multivariable analyses, TMAO was significantly associated with incident ischemic stroke risk (hazard ratios comparing a doubling of TMAO: 1.11 [1.03-1.18], =0.004). The association was linear over the range of TMAO concentrations and appeared restricted to those without diagnosed coronary heart disease. An association with hemorrhagic stroke was not found. Conclusions Plasma TMAO levels are associated with incident ischemic stroke in a diverse population. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005133.

}, keywords = {Aged, Atherosclerosis, Female, Humans, Ischemic Stroke, Methylamines, Oxides, Prospective Studies, Risk Factors, Stroke, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.122.029230}, author = {Lemaitre, Rozenn N and Jensen, Paul N and Wang, Zeneng and Fretts, Amanda M and Sitlani, Colleen M and Nemet, Ina and Sotoodehnia, Nona and de Oliveira Otto, Marcia C and Zhu, Weifei and Budoff, Matt and Longstreth, W T and Psaty, Bruce M and Siscovick, David S and Hazen, Stanley L and Mozaffarian, Dariush} }