@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 {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 {1431, title = {Assessment of cerebrovascular disease in the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {3}, year = {1993}, month = {1993 Sep}, pages = {504-7}, abstract = {

The Cardiovascular Health Study (CHS) is a longitudinal population-based study of coronary heart disease and stroke in men and women 65 years and older. The initial CHS cohort consisted of 5201 men and women recruited from a random sample of the Health Care Financing Administration (HCFA) Medicare eligibility lists in four communities in the United States. Extensive historical, physical, and laboratory evaluations were performed at the baseline examination in 1989 to 1990 to identify risk factors and subclinical disease. Periodic contacts are carried out to ascertain and verify incident cardiac and stroke events and their sequelae. Since only a short time has passed since entry of all the patients into the study, data are not available on time trends in the mortality rate of stroke, but we expect to contribute in this area in the years ahead. This article then is a description of the CHS, of methods of assessing stroke in the CHS cohort, and of prevalence of stroke and transient ischemic attacks at the initial examination.

}, keywords = {Aged, Aged, 80 and over, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Female, Humans, Ischemic Attack, Transient, Longitudinal Studies, Male, Prevalence}, issn = {1047-2797}, author = {Price, T R and Psaty, B and O{\textquoteright}Leary, D and Burke, G and Gardin, J} } @article {1445, title = {Epidemiology of low cholesterol levels in older adults. The Cardiovascular Health Study.}, journal = {Circulation}, volume = {87}, year = {1993}, month = {1993 Mar}, pages = {728-37}, abstract = {

BACKGROUND: Low cholesterol levels have been associated with increased mortality from stroke, cancer, and other noncardiovascular diseases, but the reasons for this association remain unclear. One explanation is that persons with low cholesterol levels have early or occult disease that eventually leads to their deaths.

METHODS AND RESULTS: This possibility was explored in 2,091 men and 2,714 women 65-100 years old in the Cardiovascular Health Study, a multicenter observational study of risk factors for heart disease and stroke in older adults. Cholesterol levels < or = 160 mg/dL were present in 11.6\% of men and 3.7\% of women and increased in prevalence with age. After adjustment for age, total cholesterol levels in this range were associated with a twofold increased prevalence of treated diabetes in men and women and with a twofold increased prevalence of cancer diagnosed in the preceding 5 years in women only. Low cholesterol was also associated with lower levels of hemoglobin, albumin, and factor VII, suggesting a link with hepatic synthetic function. On multivariate analysis, factors most strongly associated with low cholesterol levels in men and women were decreased factor VII levels, decreased albumin, and diabetes.

CONCLUSIONS: Cross-sectional associations with low cholesterol levels differ by sex and suggest poorer health by some measures. The observed relations with treated diabetes and impaired hepatic synthetic function should be examined for risk of mortality in longitudinal data from this and other observational studies.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cardiovascular Physiological Phenomena, Cholesterol, Female, Health Status, Humans, Longitudinal Studies, Male, Prevalence, Probability, Regression Analysis, Risk Factors}, issn = {0009-7322}, author = {Manolio, T A and Ettinger, W H and Tracy, R P and Kuller, L H and Borhani, N O and Lynch, J C and Fried, L P} } @article {1446, title = {Prevalence of cardiovascular diseases among older adults. The Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {137}, year = {1993}, month = {1993 Feb 01}, pages = {311-7}, abstract = {

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Bias, California, Cardiovascular Diseases, Electrocardiography, Female, Health Surveys, Humans, Longitudinal Studies, Male, Maryland, Mass Screening, North Carolina, Pennsylvania, Population Surveillance, Prevalence, Reproducibility of Results}, issn = {0002-9262}, author = {Mittelmark, M B and Psaty, B M and Rautaharju, P M and Fried, L P and Borhani, N O and Tracy, R P and Gardin, J M and O{\textquoteright}Leary, D H} } @article {1430, title = {Cardiac arrhythmias on 24-h ambulatory electrocardiography in older women and men: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {23}, year = {1994}, month = {1994 Mar 15}, pages = {916-25}, abstract = {

OBJECTIVES: This study describes the prevalence and correlates of cardiac arrhythmias in older persons.

BACKGROUND: Cardiac arrhythmias are frequent in selected samples of elderly persons, but their prevalence and association with cardiovascular disease and its risk factors have not been examined in a large population-based sample.

METHODS: In 1,372 participants in the Cardiovascular Health Study, a population-based study of cardiovascular disease risk factors, 24-h ambulatory electrocardiography was performed.

RESULTS: Serious arrhythmias, such as sustained ventricular tachycardia and complete atrioventricular block, were uncommon, but brief episodes of ventricular tachycardia (> or = 3 consecutive ventricular depolarizations) were detected in 4.3\% of women and 10.3\% of men. Ventricular arrhythmias as a group (excluding ectopic beats < 15/h) were more common in men than in women but were not significantly associated with age. The same patterns were true for bradycardia/conduction blocks. Supraventricular arrhythmias as a group (excluding ectopic beats < 15/h), in contrast, did not differ by gender but were strongly associated with increased age. Multivariate analyses showed associations with arrhythmias to differ by gender, with only one association (increased age and supraventricular arrhythmias) present in both women and men. Ventricular arrhythmias, particularly in men, were associated with a higher prevalence of cardiovascular disease and its risk factors and with subclinical disease, as measured by increased left ventricular mass and impaired left ventricular function.

CONCLUSIONS: Arrhythmias are common in the elderly, and their association with cardiovascular disease differs by gender. Although risk related to arrhythmias can only be determined by prospective study, such studies should have adequate power to examine potential gender differences in associations.

}, keywords = {Aged, Aged, 80 and over, Arrhythmias, Cardiac, Cardiovascular Diseases, Circadian Rhythm, Electrocardiography, Ambulatory, Female, Humans, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Sex Factors}, issn = {0735-1097}, author = {Manolio, T A and Furberg, C D and Rautaharju, P M and Siscovick, D and Newman, A B and Borhani, N O and Gardin, J M and Tabatznik, B} } @article {1433, title = {Correlates of QT prolongation in older adults (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.}, journal = {Am J Cardiol}, volume = {73}, year = {1994}, month = {1994 May 15}, pages = {999-1002}, keywords = {Aged, Aged, 80 and over, Female, Humans, Logistic Models, Long QT Syndrome, Longitudinal Studies, Male, Sex Factors}, issn = {0002-9149}, author = {Rautaharju, P M and Manolio, T A and Psaty, B M and Borhani, N O and Furberg, C D} } @article {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 {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 {1415, title = {Subclinical disease as an independent risk factor for cardiovascular disease.}, journal = {Circulation}, volume = {92}, year = {1995}, month = {1995 Aug 15}, pages = {720-6}, abstract = {

BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study.

METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes.

CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Female, Humans, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Odds Ratio, Reference Values, Risk Factors}, issn = {0009-7322}, author = {Kuller, L H and Shemanski, L and Psaty, B M and Borhani, N O and Gardin, J and Haan, M N and O{\textquoteright}Leary, D H and Savage, P J and Tell, G S and Tracy, R} } @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 {1463, title = {Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {27}, year = {1996}, month = {1996 Sep}, pages = {1479-86}, abstract = {

BACKGROUND AND PURPOSE: Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease.

METHODS: Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study.

RESULTS: During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft. frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P < .001). Aspirin users had a 52\% higher risk of stroke (relative risk, 1.52; 95\% confidence interval, 1.1 to 2.0; P < .007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84\% higher risk (relative risk, 1.84; 95\% confidence interval, 1.2 to 2.8).

CONCLUSIONS: Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.

}, keywords = {Age Factors, Aged, Cardiovascular Physiological Phenomena, Cerebrovascular Disorders, Cohort Studies, Female, Health Status, Humans, Incidence, Longitudinal Studies, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, Time Factors}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and O{\textquoteright}Leary, D H and Price, T R} } @article {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 {1487, title = {Carrying the burden of cardiovascular risk in old age: associations of weight and weight change with prevalent cardiovascular disease, risk factors, and health status in the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {66}, year = {1997}, month = {1997 Oct}, pages = {837-44}, abstract = {

Measured weight in old age, reported weight at age 50 y, and weight change from age 50 y to old age were studied in association with prevalent cardiovascular disease (CVD), CVD risk factors, and health status in a population of 4954 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). Heavier weight (i.e., generally weight in the fourth quartile for the cohort) at age 50 y was more closely associated with prevalent CVD than was current weight, with these associations stronger in women than in men. Heavier current weight and heavier weight at age 50 y were associated with cardiovascular risk factors, including higher blood pressure, lower high-density-lipoprotein cholesterol, and higher fasting insulin. Heavier weight at both time points was related to mobility problems in both men and women and to lower current physical activity levels; among women, strong associations were also seen with lower education and current income. Remaining within 10\% of reported weight at age 50 y was associated with better health status as measured by reported health, mobility difficulty, number of medications, and prevalent CVD in men. Paradoxically, most cardiovascular risk factors were lowest for weight losers despite an association of weight loss with poorer health. In this cohort of persons aged > or = 65 y, heavier weight was associated with CVD and CVD risk factors, suggesting that prevention of overweight may prove beneficial in improving cardiovascular risk in older persons. Weight stability from age 50 y to old age was associated with better health status than was weight gain or loss.

}, keywords = {Aged, Blood Pressure, Body Constitution, Body Weight, Cardiovascular Diseases, Cholesterol, LDL, Female, Health Status, Humans, Insulin, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prevalence, Risk Factors, Sex Characteristics}, issn = {0002-9165}, doi = {10.1093/ajcn/66.4.837}, author = {Harris, T B and Savage, P J and Tell, G S and Haan, M and Kumanyika, S and Lynch, J C} } @article {1470, title = {Clinically serious abnormalities found incidentally at MR imaging of the brain: data from the Cardiovascular Health Study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {41-6}, abstract = {

PURPOSE: To determine the prevalence of clinically serious findings unrelated to stroke on cranial magnetic resonance (MR) images in a population of community-dwelling elderly people.

MATERIALS AND METHODS: Neuroradiologists reviewed MR images of 3,672 people aged 65 years and older who were enrolled in a longitudinal, population-based study of cardiovascular and cerebrovascular disease. The neuroradiologists alerted MR imaging field centers about potentially serious abnormalities. Clinical information was obtained from clinical examinations performed before MR imaging, hospital discharge summaries, and the field centers at which MR imaging was performed.

RESULTS: On 3,672 image sets, 64 (1.74\%) clinically serious abnormalities were found. Among the presumptive diagnoses were 19 meningiomas (0.52\%), six pituitary adenomas (0.16\%), five cavernous malformations (0.14\%), eight vascular stenoses (0.22\%), four aneurysms (0.11\%), two intraventricular masses (0.05\%), two subdural fluid collections (0.05\%), and two other tumors (0.05\%). Only nine participants with these abnormalities required surgery. All but one of the meningiomas were in women, and the prevalence of the tumor decreased with increasing age.

CONCLUSION: Physicians should be alert to the possible presence of clinically serious conditions in otherwise asymptomatic elderly individuals.

}, keywords = {Aged, Aged, 80 and over, Brain, Brain Diseases, Cardiovascular Diseases, Cohort Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988190}, author = {Yue, N C and Longstreth, W T and Elster, A D and Jungreis, C A and O{\textquoteright}Leary, D H and Poirier, V C} } @article {1482, title = {Exercise intensity and subclinical cardiovascular disease in the elderly. The Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {145}, year = {1997}, month = {1997 Jun 01}, pages = {977-86}, abstract = {

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

}, keywords = {Aged, Cardiovascular Diseases, Cross-Sectional Studies, Energy Metabolism, Exercise, Female, Fibrinogen, Humans, Insulin, Life Style, Longitudinal Studies, Male, Prevalence, Risk Factors}, issn = {0002-9262}, author = {Siscovick, D S and Fried, L and Mittelmark, M and Rutan, G and Bild, D and O{\textquoteright}Leary, D H} } @article {1471, title = {Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {47-54}, abstract = {

PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images.

MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images.

RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36\%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9\% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1\% (86 of 389) in the 65-69-year age group to 42.9\% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5\%]) than in women (631 of 2,131 [29.6\%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2\% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7\% (218 of 1,856) and 10.1\% (187 of 1,856) of lesions, respectively.

CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cerebral Infarction, Cohort Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prevalence}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988191}, author = {Bryan, R N and Wells, S W and Miller, T J and Elster, A D and Jungreis, C A and Poirier, V C and Lind, B K and Manolio, T A} } @article {1499, title = {The Sleep Heart Health Study: design, rationale, and methods.}, journal = {Sleep}, volume = {20}, year = {1997}, month = {1997 Dec}, pages = {1077-85}, abstract = {

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

}, keywords = {Adult, Aged, Aged, 80 and over, Arteriosclerosis, Cohort Studies, Coronary Disease, Female, Humans, Hypertension, Longitudinal Studies, Male, Middle Aged, Polysomnography, Positive-Pressure Respiration, Prospective Studies, Research Design, Sleep Apnea Syndromes}, issn = {0161-8105}, author = {Quan, S F and Howard, B V and Iber, C and Kiley, J P and Nieto, F J and O{\textquoteright}Connor, G T and Rapoport, D M and Redline, S and Robbins, J and Samet, J M and Wahl, P W} } @article {1469, title = {Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {33-9}, abstract = {

PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex.

MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex.

RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race.

CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

}, keywords = {Aged, Aged, 80 and over, Aging, Brain, Cardiovascular Diseases, Cerebral Ventricles, Cohort Studies, Continental Population Groups, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Reproducibility of Results, Sex Factors}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988189}, author = {Yue, N C and Arnold, A M and Longstreth, W T and Elster, A D and Jungreis, C A and O{\textquoteright}Leary, D H and Poirier, V C and Bryan, R N} } @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 {1514, title = {Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {55}, year = {1998}, month = {1998 Sep}, pages = {1217-25}, abstract = {

OBJECTIVE: To identify risk factors for and functional consequences of lacunar infarct in elderly people.

METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings.

RESULTS: Of the 3660 subjects who underwent MRI, 2529 (69\%) were free of infarcts of any kind and 841 (23\%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66\%) and silent (89\%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50\% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts.

CONCLUSIONS: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.

}, keywords = {Aged, Cerebral Infarction, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Multivariate Analysis, Risk Factors}, issn = {0003-9942}, author = {Longstreth, W T and Bernick, C and Manolio, T A and Bryan, N and Jungreis, C A and Price, T R} } @article {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 {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 {619, title = {Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.}, journal = {Psychol Aging}, volume = {15}, year = {2000}, month = {2000 Jun}, pages = {259-71}, abstract = {

Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.

}, keywords = {Aged, Anxiety, Caregivers, Depression, Disabled Persons, Female, Health Behavior, Health Status, Humans, Longitudinal Studies, Male, Mental Health, Risk-Taking, Spouses}, issn = {0882-7974}, doi = {10.1037//0882-7974.15.2.259}, author = {Beach, S R and Schulz, R and Yee, J L and Jackson, S} } @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 {630, title = {Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.}, journal = {Ann Intern Med}, volume = {134}, year = {2001}, month = {2001 Feb 06}, pages = {182-90}, abstract = {

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

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

DESIGN: Longitudinal cohort study.

SETTING: Four communities in the United States.

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal, Aortic Rupture, Cardiovascular Diseases, Disease Progression, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Proportional Hazards Models, Risk Factors, Ultrasonography, United States}, issn = {0003-4819}, doi = {10.7326/0003-4819-134-3-200102060-00008}, author = {Newman, A B and Arnold, A M and Burke, G L and O{\textquoteright}Leary, D H and Manolio, T A} } @article {644, title = {Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {58}, year = {2001}, month = {2001 Apr}, pages = {635-40}, abstract = {

OBJECTIVE: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis.

SUBJECTS AND METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations.

RESULTS: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected.

CONCLUSIONS: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebrovascular Disorders, Cluster Analysis, Cohort Studies, Discriminant Analysis, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors}, issn = {0003-9942}, doi = {10.1001/archneur.58.4.635}, author = {Longstreth, W T and Diehr, P and Manolio, T A and Beauchamp, N J and Jungreis, C A and Lefkowitz, D} } @article {670, title = {Estrogen replacement and brachial artery flow-mediated vasodilation in older women.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {21}, year = {2001}, month = {2001 Dec}, pages = {1955-61}, abstract = {

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9\%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Brachial Artery, Cardiovascular Diseases, Drug Therapy, Combination, Estrogen Replacement Therapy, Estrogens, Female, Humans, Longitudinal Studies, Progestins, Risk Factors, Ultrasonography, Vasodilation}, issn = {1524-4636}, doi = {10.1161/hq1201.100241}, author = {Herrington, D M and Espeland, M A and Crouse, J R and Robertson, J and Riley, W A and McBurnie, M A and Burke, G L} } @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 {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 {631, title = {Hormone replacement therapy is associated with higher FEV1 in elderly women.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Feb}, pages = {423-8}, abstract = {

Estrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65\%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95\% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95\% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Estrogen Replacement Therapy, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Spirometry, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.2.2003040}, author = {Carlson, C L and Cushman, M and Enright, P L and Cauley, J A and Newman, A B} } @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 {634, title = {Patterns of self-rated health in older adults before and after sentinel health events.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Jan}, pages = {36-44}, abstract = {

OBJECTIVES: To describe and compare patterns of change in self-rated health for older adults before death and before and after stroke, myocardial infarction, congestive heart failure, cardiac procedure, hospital admission for cancer, and hip fracture.

DESIGN: "Event cohort," measuring time in months before and after the event.

SETTING: Four U.S. communities.

PARTICIPANTS: 5888 participants in the Cardiovascular Health Study (CHS), sampled from Medicare rolls and followed up to 8 years. Mean age at baseline was 73.

MEASUREMENTS: Self-rated health, including a category for death, assessed at 6-month intervals, and ascertainment of events.

METHODS: We examined the percentage that was healthy each month in the 5 years before death and in the 2 years before and after the other events, and compared the patterns to a "no event" group and to one another, using graphs and linear regression.

RESULTS: For people who died, health status declined slowly until about 9 months before death, when it dropped steeply. Comparing persons equally far from death, health was unrelated to age, but men and whites were healthier than women and blacks. Health for other events declined before the event, dropped steeply at the event, showed some recovery, and then declined further after the event. About 65\% to 80\% of the subjects were healthy 2 years before their event, but only 35\% to 65\% were healthy two years afterwards. Patterns were similar although less extreme for the "no event" group.

CONCLUSION: Visualizing trajectories of health helps us understand how serious health events changes health. Conclusions about change must be drawn with care because of a variety of possible biases. We have described the trajectories in detail. Work is now needed to explain, predict, and possibly prevent such changes in health.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Death, Female, Follow-Up Studies, Health Status, Health Status Indicators, Hip Fractures, Hospitalization, Humans, Linear Models, Longitudinal Studies, Male, Random Allocation, Time Factors}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49007.x}, author = {Diehr, P and Williamson, J and Patrick, D L and Bild, D E and Burke, G L} } @article {637, title = {Predictors of loss of lung function in the elderly: the Cardiovascular Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Jan}, pages = {61-8}, abstract = {

Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6\% female, mean age 73 yr, 87.5\% white and 12.5\% African-American) with eligible FEV1 measures representing 89\% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Lung, Lung Volume Measurements, Male}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.1.9906089}, author = {Griffith, K A and Sherrill, D L and Siegel, E M and Manolio, T A and Bonekat, H W and Enright, P L} } @article {661, title = {The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.}, journal = {Diabetes}, volume = {50}, year = {2001}, month = {2001 Oct}, pages = {2384-9}, abstract = {

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5\%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95\% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.

}, keywords = {Aged, Biomarkers, Blood Glucose, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Humans, Hypoglycemia, Inflammation, Longitudinal Studies, Male, Reference Values, Risk Factors}, issn = {0012-1797}, doi = {10.2337/diabetes.50.10.2384}, author = {Barzilay, J I and Abraham, L and Heckbert, S R and Cushman, M and Kuller, L H and Resnick, H E and Tracy, R P} } @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 {658, title = {Transforming self-rated health and the SF-36 scales to include death and improve interpretability.}, journal = {Med Care}, volume = {39}, year = {2001}, month = {2001 Jul}, pages = {670-80}, abstract = {

BACKGROUND: Most measures of health-related quality of life are undefined for people who die. Longitudinal analyses are often limited to a healthier cohort (survivors) that cannot be identified prospectively, and that may have had little change in health.

OBJECTIVE: To develop and evaluate methods to transform a single self-rated health item (excellent to poor; EVGGFP) and the physical component score of the SF-36 (PCS) to new variables that include a defensible value for death.

METHODS: Using longitudinal data from two large studies of older adults, health variables were transformed to the probability of being healthy in the future, conditional on the current observed value; death then has the value of 0. For EVGGFP, the new transformations were compared with some that were published earlier, based on different data. For the PCS, how well three different transformations, based on different definitions of being healthy, discriminated among groups of patients, and detected change in time were assessed.

RESULTS: The new transformation for EVGGFP was similar to that published previously. Coding the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended. The three transformations of the PCS detected group differences and change at least as well as the standard PCS.

CONCLUSION: These easily interpretable transformed variables permit keeping persons who die in the analyses. Using the transformed variables for longitudinal analyses of health when deaths occur, either for secondary or primary analysis, is recommended. This approach can be applied to other measures of health.

}, keywords = {Aged, Data Interpretation, Statistical, Death, Decision Making, Female, Health Status, Humans, Logistic Models, Longitudinal Studies, Male, Models, Statistical, Quality of Life, ROC Curve, Surveys and Questionnaires}, issn = {0025-7079}, doi = {10.1097/00005650-200107000-00004}, author = {Diehr, P and Patrick, D L and Spertus, J and Kiefe, C I and McDonell, M and Fihn, S D} } @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 {680, title = {The aging and dying processes and the health of older adults.}, journal = {J Clin Epidemiol}, volume = {55}, year = {2002}, month = {2002 Mar}, pages = {269-78}, abstract = {

It is difficult to distinguish changes in health due to aging from those related to dying, because the two processes are highly related. Some potentially treatable conditions may mistakenly be dismissed as due to old age. The goal of this article was to examine the relationships of aging and of dying to changes in 10 health-related variables: self-rated health, depression, ADLs, IADLs, minimental state examination, body mass index, blocks walked per week, bed days, hospitalization, and walking speed (all coded so that higher values were better). We used longitudinal data from the Cardiovascular Health Study to estimate the changes in the variables associated with 5 years of aging and also in the 5 years before death, controlling for years from death and for age, respectively. All 10 health variables declined as death approached, and most of them also declined with age. The "effect" of the dying process was usually significantly larger than the effect of aging. Large declines in these health measures are probably not due to aging, and should be taken seriously by patients and their providers.

}, keywords = {Aged, Aging, Death, Female, Health Status Indicators, Humans, Linear Models, Longitudinal Studies, Male, Muscular Atrophy}, issn = {0895-4356}, doi = {10.1016/s0895-4356(01)00462-0}, author = {Diehr, Paula and Williamson, Jeff and Burke, Gregory L and Psaty, Bruce M} } @article {712, title = {Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study.}, journal = {Br J Haematol}, volume = {119}, year = {2002}, month = {2002 Dec}, pages = {1005-10}, abstract = {

Anticardiolipin antibodies, one of the family of {\textquoteright}antiphospholipid{\textquoteright} antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95\% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.

}, keywords = {Aged, Aged, 80 and over, Antibodies, Anticardiolipin, Case-Control Studies, Female, Humans, Immunoglobulin G, Immunoglobulin M, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prospective Studies, Reference Values, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0007-1048}, doi = {10.1046/j.1365-2141.2002.03949.x}, author = {Runchey, Shauna S and Folsom, Aaron R and Tsai, Michael Y and Cushman, Mary and McGovern, Paul D} } @article {716, title = {Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE).}, journal = {Am J Med}, volume = {113}, year = {2002}, month = {2002 Dec 01}, pages = {636-42}, abstract = {

PURPOSE: We sought to assess prospectively whether higher levels of blood coagulation factors and inflammation markers are risk factors for venous thromboembolism.

SUBJECTS AND METHODS: In two pooled population-based cohort studies, we measured levels of factor VII, factor VIII, von Willebrand factor, fibrinogen, and C-reactive protein, and white blood cell count, in samples obtained from 19,237 adults with no baseline history of venous thromboembolism, cancer, or warfarin use. The endpoint was validated venous thromboembolism during follow-up (median, 7.8 years).

RESULTS: A total of 159 venous thromboembolism events occurred. Factor VIII and von Willebrand factor were linearly associated with increased risk of venous thromboembolism (P for trend <0.0001). As compared with those in the lowest quartile, the multivariate-adjusted hazard ratio (HR) of venous thromboembolism was 2.6 (95\% confidence interval [CI]: 1.6 to 4.3) for factor VIII levels in the highest quartile and 3.8 (95\% CI: 2.0 to 7.2) for the highest fifth percentile. For von Willebrand factor, the hazard ratios in middle-aged subjects were 4.6 (95\% CI: 2.2 to 9.2) for the highest quartile and 7.6 (95\% CI: 3.1 to 18) for the highest fifth percentile. Factor VII levels above the 95th percentile, as compared with the lowest quartile, also conveyed a higher risk of venous thromboembolism (HR = 2.4; 95\% CI: 1.2 to 4.8). In contrast, there was no association of venous thromboembolism with fibrinogen or C-reactive protein levels, or white cell count.

CONCLUSIONS: In this prospective study, elevated factor VIII and von Willebrand factor levels were common, independent, and dose-dependent risk factors for venous thromboembolism, and an elevated factor VII level was a possible risk factor. Venous thromboembolism, unlike arterial disease, was not related to inflammatory markers.

}, keywords = {Aged, Biomarkers, Blood Coagulation Factors, C-Reactive Protein, Cohort Studies, Confidence Intervals, Factor VII, Female, Fibrinogen, Humans, Inflammation Mediators, Longitudinal Studies, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Risk Assessment, Risk Factors, Sensitivity and Specificity, Thromboembolism, Venous Thrombosis, von Willebrand Factor}, issn = {0002-9343}, doi = {10.1016/s0002-9343(02)01345-1}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Tracy, Russell P and Aleksic, Nena and Folsom, Aaron R} } @article {677, title = {Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {15}, year = {2002}, month = {2002 Jan}, pages = {16-23}, abstract = {

BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals.

METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4\% women, 25.3\% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998.

RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993.

CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.

}, keywords = {Aged, Aged, 80 and over, Aging, Aorta, Female, Heart Rate, Humans, Hypertension, Insulin Resistance, Longitudinal Studies, Male, Pulsatile Flow, Risk Factors, Sex Distribution}, issn = {0895-7061}, doi = {10.1016/s0895-7061(01)02228-2}, author = {Mackey, Rachel H and Sutton-Tyrrell, Kim and Vaitkevicius, Peter V and Sakkinen, Pamela A and Lyles, Mary F and Spurgeon, Harold A and Lakatta, Edward G and Kuller, Lewis H} } @article {709, title = {Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Nov 11}, pages = {2333-41}, abstract = {

BACKGROUND: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness.

OBJECTIVE: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus.

METHODS: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson chi2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures.

RESULTS: Of 4735 Cardiovascular Health Study participants, 299 (6.3\%) were identified as frail, 2147 (45.3\%) as intermediate, and 2289 (48.3\%) as not frail. Frail vs nonfrail participants had increased mean +/- SD levels of C-reactive protein (5.5 +/- 9.8 vs 2.7 +/- 4.0 mg/L), factor VIII (13 790 +/- 4480 vs 11 860 +/- 3460 mg/dL), and, in a smaller subset, D dimer (647 +/- 1033 vs 224 +/- 258 ng/mL) (P< or =.001 for all, chi2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race.

CONCLUSIONS: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.

}, keywords = {Aged, Aged, 80 and over, Blood Coagulation Disorders, Cardiovascular Diseases, Cohort Studies, Diabetes Complications, Diabetes Mellitus, Female, Frail Elderly, Geriatric Assessment, Humans, Inflammation, Longitudinal Studies, Male}, issn = {0003-9926}, doi = {10.1001/archinte.162.20.2333}, author = {Walston, Jeremy and McBurnie, Mary Ann and Newman, Anne and Tracy, Russell P and Kop, Willem J and Hirsch, Calvin H and Gottdiener, John and Fried, Linda P} } @article {703, title = {Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Oct}, pages = {2376-82}, abstract = {

BACKGROUND AND PURPOSE: MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts.

METHODS: The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged > or =65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI.

RESULTS: On follow-up MRI, 254 participants (17.7\%) had 1 or more infarcts. Most were single (75.6\%), subcortical (79.9\%), and small (3 to 20 mm in 87.0\%). Only 11.4\% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index.

CONCLUSIONS: Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.

}, keywords = {Aged, Brain Infarction, California, Cohort Studies, Creatinine, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Maryland, Multivariate Analysis, Neuropsychological Tests, North Carolina, Odds Ratio, Pennsylvania, Predictive Value of Tests, Risk Factors}, issn = {1524-4628}, doi = {10.1161/01.str.0000032241.58727.49}, author = {Longstreth, W T and Dulberg, Corinne and Manolio, Teri A and Lewis, Michael R and Beauchamp, Norman J and O{\textquoteright}Leary, Daniel and Carr, Jeff and Furberg, Curt D} } @article {705, title = {Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.}, journal = {Ann Intern Med}, volume = {137}, year = {2002}, month = {2002 Oct 15}, pages = {631-9}, abstract = {

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.

OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.

DESIGN: Population-based longitudinal study of coronary heart disease and stroke.

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

PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community.

MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality.

RESULTS: Of 5532 participants, 269 (4.9\%) had congestive heart failure. Among these, left ventricular function was normal in 63\%, borderline decreased in 15\%, and overtly impaired in 22\%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category.

CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

}, keywords = {Aged, Cause of Death, Echocardiography, Female, Heart Failure, Humans, Longitudinal Studies, Male, Myocardial Infarction, Prevalence, Prognosis, Risk Factors, Stroke, Ventricular Dysfunction, Right, Ventricular Function, Left}, issn = {1539-3704}, doi = {10.7326/0003-4819-137-8-200210150-00006}, author = {Gottdiener, John S and McClelland, Robyn L and Marshall, Robert and Shemanski, Lynn and Furberg, Curt D and Kitzman, Dalane W and Cushman, Mary and Polak, Joseph and Gardin, Julius M and Gersh, Bernard J and Aurigemma, Gerard P and Manolio, Teri A} } @article {702, title = {Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.}, journal = {JAMA}, volume = {288}, year = {2002}, month = {2002 Sep 25}, pages = {1475-83}, abstract = {

CONTEXT: Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI.

OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study.

DESIGN: Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study.

SETTING AND PARTICIPANTS: A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia.

MAIN OUTCOME MEASURE: Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms.

RESULTS: Of the 682 individuals with dementia or MCI, 43\% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29\% rated as clinically significant) with depression (20\%), apathy (15\%), and irritability (15\%) being most common. Among the dementia participants, 75\% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62\% were clinically significant); 55\% (n = 199) reported 2 or more and 44\% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36\%), depression (32\%), and agitation/aggression (30\%). Eighty percent of dementia participants (n = 233) and 50\% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4\% vs 1\%; P =.02).

CONCLUSIONS: Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.

}, keywords = {Aged, Aggression, Anxiety, Behavioral Symptoms, Cognition Disorders, Comorbidity, Cross-Sectional Studies, Delusions, Dementia, Depression, Feeding and Eating Disorders, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Prevalence, Sleep Wake Disorders}, issn = {0098-7484}, doi = {10.1001/jama.288.12.1475}, author = {Lyketsos, Constantine G and Lopez, Oscar and Jones, Beverly and Fitzpatrick, Annette L and Breitner, John and DeKosky, Steven} } @article {700, title = {Prevalence of renovascular disease in the elderly: a population-based study.}, journal = {J Vasc Surg}, volume = {36}, year = {2002}, month = {2002 Sep}, pages = {443-51}, abstract = {

PURPOSE: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as > or = 60\% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS).

METHODS: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with chi(2) and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis.

RESULTS: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96\%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 +/- 4.9 years and consisted of 63\% women and 37\% men. Participant race was 76\% white and 23\% African American. The overall prevalence rate of RVD was 6.8\%. Among the 57 patients with RVD, 50 (88\%) had unilateral disease and seven (12\%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1 +/- 4.9 years (P =.018). RVD was present in 5.5\% of women and 9.1\% of men (P =.053). RVD was present in 6.9\% of white participants and 6.7\% of African American participants (P =.933). Multivariate analysis revealed increasing participant age (P =.028; odds ratio, 1.34; 95\% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63; 95\% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio, 1.44; 95\% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD.

CONCLUSION: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8\% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cohort Studies, Ethnic Groups, Female, Humans, Longitudinal Studies, Male, Prevalence, Prospective Studies, Renal Artery, Renal Artery Obstruction, Risk Factors, Sex Factors, Ultrasonography, Doppler, Duplex}, issn = {0741-5214}, doi = {10.1067/mva.2002.127351}, author = {Hansen, Kimberley J and Edwards, Matthew S and Craven, Timothy E and Cherr, Gregory S and Jackson, Sharon A and Appel, Richard G and Burke, Gregory L and Dean, Richard H} } @article {684, title = {A prospective study of venous thromboembolism in relation to factor V Leiden and related factors.}, journal = {Blood}, volume = {99}, year = {2002}, month = {2002 Apr 15}, pages = {2720-5}, abstract = {

The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95\% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95\% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95\% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR = 1.05; 95\% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95\% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95\% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden.

}, keywords = {Activated Protein C Resistance, Aged, Cohort Studies, Continental Population Groups, Factor V, Genotype, Haplotypes, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0006-4971}, doi = {10.1182/blood.v99.8.2720}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Aleksic, Nena and Heckbert, Susan R and Boland, Lori L and Tsai, Albert W and Yanez, N David and Rosamond, Wayne D} } @article {693, title = {Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Jun 01}, pages = {1018-22}, abstract = {

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95\% CI 1.24 to 9.11) in the 1.1\% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for approximately 2.5\% of venous thromboembolic events in the ARIC population.

}, keywords = {Adult, Aged, Aged, 80 and over, Antithrombins, Arteriosclerosis, Cohort Studies, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Population Surveillance, Prospective Studies, Protein C, Protein C Deficiency, Pulmonary Embolism, Thromboembolism, Venous Thrombosis}, issn = {1524-4636}, doi = {10.1161/01.atv.0000017470.08363.ab}, author = {Folsom, Aaron R and Aleksic, Nena and Wang, Lu and Cushman, Mary and Wu, Kenneth K and White, Richard H} } @article {674, title = {The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study.}, journal = {Br J Ophthalmol}, volume = {86}, year = {2002}, month = {2002 Jan}, pages = {84-90}, abstract = {

AIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes.

METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system.

RESULTS: Retinopathy was present in 20\% of the diabetic cohort, with the lowest prevalence (16\%), in those 80 years of age or older. Retinopathy was detected in 20.3\% of the 296 people with diabetes; 2.7\% of the 296 had signs of proliferative retinopathy and 2.1\% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4\%) than white (16.0\%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95\% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95\% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95\% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95\% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95\% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95\% CI 1.53, 14.86).

CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.

}, keywords = {Age of Onset, Aged, Aged, 80 and over, Arteriosclerosis, Black People, Blood Pressure, Cohort Studies, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Humans, Longitudinal Studies, Male, Odds Ratio, Prospective Studies, Regression Analysis, Risk Factors, Time Factors, White People}, issn = {0007-1161}, doi = {10.1136/bjo.86.1.84}, author = {Klein, Ronald and Marino, Emily K and Kuller, Lewis H and Polak, Joseph F and Tracy, Russell P and Gottdiener, John S and Burke, Gregory L and Hubbard, Larry D and Boineau, Robin} } @article {753, title = {Alcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {23}, year = {2003}, month = {2003 Dec}, pages = {2252-9}, abstract = {

OBJECTIVE: The association of alcohol use with atherosclerosis is inconsistent in previous studies.

METHODS AND RESULTS: For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07+/-0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07+/-0.05-mm higher IMT than abstainers (P quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24+/-0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22\%.

CONCLUSIONS: Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.

}, keywords = {Aged, Alcohol Drinking, Cardiovascular Diseases, Carotid Artery Diseases, Cross-Sectional Studies, Female, Health Surveys, Humans, Longitudinal Studies, Male, Prospective Studies}, issn = {1524-4636}, doi = {10.1161/01.ATV.0000101183.58453.39}, author = {Mukamal, Kenneth J and Kronmal, Richard A and Mittleman, Murray A and O{\textquoteright}Leary, Daniel H and Polak, Joseph F and Cushman, Mary and Siscovick, David S} } @article {741, title = {C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Jul 15}, pages = {166-70}, abstract = {

BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT.

METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95\% CI 0.92 to 1.53), 1.05 (95\% CI 0.81 to 1.37), and 1.60 (95\% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT.

CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.

}, keywords = {Aged, Brain Ischemia, C-Reactive Protein, California, Carotid Arteries, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Maryland, North Carolina, Odds Ratio, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000079160.07364.6A}, author = {Cao, Jie J and Thach, Chau and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis H and Chaves, Paulo H M and Polak, Joseph F and Sutton-Tyrrell, Kim and Herrington, David M and Price, Thomas R and Cushman, Mary} } @article {718, title = {Early age-related maculopathy in the cardiovascular health study.}, journal = {Ophthalmology}, volume = {110}, year = {2003}, month = {2003 Jan}, pages = {25-33}, abstract = {

OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes.

DESIGN: Population-based cohort study.

PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998.

METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System.

MAIN OUTCOME MEASURES: Early ARM.

RESULTS: Early ARM was present in 15.5\% and late ARM in 1.3\% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1\%) compared with whites (18.2\%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95\% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95\% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM.

CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Arteriosclerosis, Blood Pressure, C-Reactive Protein, California, Cohort Studies, Diet, European Continental Ancestry Group, Female, Humans, Hypertension, Leukocyte Count, Longitudinal Studies, Macular Degeneration, Male, Mid-Atlantic Region, North Carolina, Prevalence, Prospective Studies, Risk Factors, Serum Albumin}, issn = {0161-6420}, doi = {10.1016/s0161-6420(02)01565-8}, author = {Klein, Ronald and Klein, Barbara E K and Marino, Emily K and Kuller, Lewis H and Furberg, Curt and Burke, Gregory L and Hubbard, Larry D} } @article {723, title = {Evaluation of dementia in the cardiovascular health cognition study.}, journal = {Neuroepidemiology}, volume = {22}, year = {2003}, month = {2003 Jan-Feb}, pages = {1-12}, abstract = {

OBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS).

METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists.

RESULTS: There were 480 cases of (13.3\%) incident dementia in the total sample, 227 (6.3\%) prevalent dementia, 577 (16.0\%) MCI, and 2,318 (64.4\%) normal. The adjudication committee classified 69\% of the incident dementia as Alzheimer{\textquoteright}s disease (AD), 11\% as vascular dementia (VaD), 16\% as both, and 4\% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5\% for white men, 14.5\% for white women, 22.2\% for black men and 23.4\% for black women.

CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Cross-Sectional Studies, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prevalence, Risk Factors, Sex Distribution}, issn = {0251-5350}, doi = {10.1159/000067110}, author = {Lopez, Oscar L and Kuller, Lewis H and Fitzpatrick, Annette and Ives, Diane and Becker, James T and Beauchamp, Norman} } @article {706, title = {Fibrin fragment D-dimer and the risk of future venous thrombosis.}, journal = {Blood}, volume = {101}, year = {2003}, month = {2003 Feb 15}, pages = {1243-8}, abstract = {

Plasma D-dimer concentration rises more than 100-fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in 2 prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21 690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (P for trend <.0001). Following added adjustment for sex, race, body mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIII coagulant activity (factor VIII:c), these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (P for trend <.0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio, 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow-up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis.

}, keywords = {Aged, Body Mass Index, Cohort Studies, Continental Population Groups, Factor V, Factor VIII, Female, Fibrin Fibrinogen Degradation Products, Humans, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prospective Studies, Prothrombin, Risk Factors, Venous Thrombosis}, issn = {0006-4971}, doi = {10.1182/blood-2002-05-1416}, author = {Cushman, Mary and Folsom, Aaron R and Wang, Lu and Aleksic, Nena and Rosamond, Wayne D and Tracy, Russell P and Heckbert, Susan R} } @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 {758, title = {Inflammation as a risk factor for atrial fibrillation.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Dec 16}, pages = {3006-10}, abstract = {

BACKGROUND: The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort.

METHODS AND RESULTS: CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9+/-1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5\%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4\% versus 3.7\%, adjusted OR 1.8, 95\% CI 1.2 to 2.5; P=0.002). Of 5491 subjects without AF at baseline, 897 (16\%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95\% CI 1.08 to 1.58; P=0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95\% CI 1.11 to 1.40; P<0.001).

CONCLUSIONS: CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.

}, keywords = {Aged, Atrial Fibrillation, C-Reactive Protein, Cross-Sectional Studies, Female, Humans, Inflammation, Longitudinal Studies, Male, Risk Factors}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000103131.70301.4F}, author = {Aviles, Ronnier J and Martin, David O and Apperson-Hansen, Carolyn and Houghtaling, Penny L and Rautaharju, Pentti and Kronmal, Richard A and Tracy, Russell P and Van Wagoner, David R and Psaty, Bruce M and Lauer, Michael S and Chung, Mina K} } @article {751, title = {Perceptions and implications of received spousal care: evidence from the Caregiver Health Effects Study.}, journal = {Psychol Aging}, volume = {18}, year = {2003}, month = {2003 Sep}, pages = {593-601}, abstract = {

The experiences of older care recipients have received far less theoretical and empirical attention than those of their family caregivers. In this study of 91 care recipients, the authors assessed perceptions of the amount, timing, and manner of spousal assistance; the amount of strain experienced from receiving care; and psychological well-being. Although female care recipients were more likely to report dissatisfaction with the manner in which assistance was provided, there were few gender differences in perceptions of care overall. In a stringent test of the hypothesis that perceived quality of spousal care affects recipient well-being, the authors found that poorer quality of care was related to increased depressive symptoms and a decreased sense of mastery 1 year later. These longitudinal effects were independent of the recipient{\textquoteright}s physical disability, marital quality, and care-receiving strain as well as the caregiver{\textquoteright}s well-being. These findings argue for a comprehensive assessment of the care-receiving experience that includes both care-recipient and caregiver perspectives.

}, keywords = {Aged, Caregivers, Chronic Disease, Disabled Persons, Family Health, Female, Health Status, Humans, Longitudinal Studies, Male, Mental Health, Quality of Health Care, Research Design, Spouses}, issn = {0882-7974}, doi = {10.1037/0882-7974.18.3.593}, author = {Martire, Lynn M and Schulz, Richard and Wrosch, Carsten and Newsom, Jason T} } @article {755, title = {Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.}, journal = {Arch Neurol}, volume = {60}, year = {2003}, month = {2003 Oct}, pages = {1385-9}, abstract = {

OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study.

DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort.

SETTING: Multicenter population study.

PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI.

MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type.

RESULTS: The overall prevalence of MCI was 19\% (465 of 2470 participants); prevalence increased with age from 19\% in participants younger than 75 years to 29\% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22\% (130 of 599 participants); prevalence of the MCI amnesic-type was 6\% and of the MCI multiple cognitive deficits-type was 16\%.

CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory Disorders, Neuropsychological Tests, Pennsylvania, Population, Psychiatric Status Rating Scales}, issn = {0003-9942}, doi = {10.1001/archneur.60.10.1385}, author = {Lopez, Oscar L and Jagust, William J and DeKosky, Steven T and Becker, James T and Fitzpatrick, Annette and Dulberg, Corinne and Breitner, John and Lyketsos, Constantine and Jones, Beverly and Kawas, Claudia and Carlson, Michelle and Kuller, Lewis H} } @article {756, title = {Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.}, journal = {Arch Neurol}, volume = {60}, year = {2003}, month = {2003 Oct}, pages = {1394-9}, abstract = {

OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study.

DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type.

SETTING: Multicenter population study.

PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort.

MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease.

RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores.

CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.

}, keywords = {Aged, Apolipoprotein E4, Apolipoproteins E, Brain, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Depressive Disorder, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mood Disorders, Pennsylvania, Population, Risk Factors}, issn = {0003-9942}, doi = {10.1001/archneur.60.10.1394}, author = {Lopez, Oscar L and Jagust, William J and Dulberg, Corinne and Becker, James T and DeKosky, Steven T and Fitzpatrick, Annette and Breitner, John and Lyketsos, Constantine and Jones, Beverly and Kawas, Claudia and Carlson, Michelle and Kuller, Lewis H} } @article {726, title = {Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Am J Hematol}, volume = {72}, year = {2003}, month = {2003 Mar}, pages = {192-200}, abstract = {

We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95\% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95\% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95\% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.

}, keywords = {Aged, Aging, Animals, Case-Control Studies, Cohort Studies, Factor V, Female, Genotype, Homocysteine, Humans, Longitudinal Studies, Male, Methylenetetrahydrofolate Reductase (NADPH2), Middle Aged, Odds Ratio, Oxidoreductases Acting on CH-NH Group Donors, Polymorphism, Genetic, Prospective Studies, Risk Factors, Venous Thrombosis}, issn = {0361-8609}, doi = {10.1002/ajh.10287}, author = {Tsai, Albert W and Cushman, Mary and Tsai, Michael Y and Heckbert, Susan R and Rosamond, Wayne D and Aleksic, Nena and Yanez, N David and Psaty, Bruce M and Folsom, Aaron R} } @article {757, title = {"Successful aging": effect of subclinical cardiovascular disease.}, journal = {Arch Intern Med}, volume = {163}, year = {2003}, month = {2003 Oct 27}, pages = {2315-22}, abstract = {

BACKGROUND: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined.

METHODS: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning.

RESULTS: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95\% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95\% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself.

CONCLUSIONS: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.

}, keywords = {Aged, Aged, 80 and over, Aging, C-Reactive Protein, Cardiovascular Diseases, Female, Health Status, Humans, Longitudinal Studies, Male, Quality of Life, Regression Analysis, Risk Factors}, issn = {0003-9926}, doi = {10.1001/archinte.163.19.2315}, author = {Newman, Anne B and Arnold, Alice M and Naydeck, Barbara L and Fried, Linda P and Burke, Gregory L and Enright, Paul and Gottdiener, John and Hirsch, Calvin and O{\textquoteright}Leary, Daniel and Tracy, Russell} } @article {786, title = {Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {173}, year = {2004}, month = {2004 Mar}, pages = {79-87}, abstract = {

OBJECTIVE: We sought to determine the relation of alcohol intake and systemic inflammation in a population-based sample of older adults.

METHODS AND RESULTS: As part of the Cardiovascular Health Study (CHS), 5865 adults aged 65 years and older reported their intake of beer, wine, and liquor. We determined white blood cell count (WBC), factor VIII coagulant activity (factor VIIIc), and levels of C-reactive protein (CRP), fibrinogen, and albumin as markers of systemic inflammation. Among participants without confirmed cardiovascular disease, alcohol consumption was inversely associated with WBC, factor VIIIc, and fibrinogen level, and positively associated with albumin concentration in multivariate analyses. We found no consistent modification of these results by sex, obesity, or beverage type. The relation of alcohol use and CRP levels was significantly modified by apoE genotype (P interaction 0.03), with a positive association among participants with an apoE4 allele (P = 0.05), but a trend toward an inverse association among those without an apoE4 allele (P = 0.15).

CONCLUSIONS: Alcohol intake is associated with lower levels of inflammatory markers in older adults free of cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Alcohol Drinking, Apolipoproteins E, C-Reactive Protein, Coronary Artery Disease, Female, Fibrinogen, Geriatric Assessment, Humans, Inflammation Mediators, Leukocyte Count, Logistic Models, Longitudinal Studies, Male, Probability, Prospective Studies, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2003.10.011}, author = {Mukamal, Kenneth J and Cushman, Mary and Mittleman, Murray A and Tracy, Russell P and Siscovick, David S} } @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 {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 {790, title = {Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {43}, year = {2004}, month = {2004 Jun 16}, pages = {2207-15}, abstract = {

OBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF).

BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF.

METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55\%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF.

RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8\% in quartile 1, 4.4\% in quartile 2, 7.5\% in quartile 3, and 14.1\% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF.

CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.

}, keywords = {Aged, Body Surface Area, Coronary Artery Disease, Diastole, Echocardiography, Electrocardiography, Female, Follow-Up Studies, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Longitudinal Studies, Male, Multivariate Analysis, Prospective Studies, Risk Factors, Sensitivity and Specificity, Statistics as Topic, Stroke Volume, Ventricular Dysfunction, Left}, issn = {0735-1097}, doi = {10.1016/j.jacc.2003.11.064}, author = {Drazner, Mark H and Rame, J Eduardo and Marino, Emily K and Gottdiener, John S and Kitzman, Dalane W and Gardin, Julius M and Manolio, Teri A and Dries, Daniel L and Siscovick, David S} } @article {813, title = {Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals.}, journal = {J Am Soc Nephrol}, volume = {15}, year = {2004}, month = {2004 Dec}, pages = {3184-91}, abstract = {

Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7\%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Creatinine, Factor VII, Female, Fibrinogen, Follow-Up Studies, Glomerular Filtration Rate, Hemoglobins, Humans, Leukocyte Count, Linear Models, Longitudinal Studies, Male, Predictive Value of Tests, Prospective Studies, Renal Insufficiency, Serum Albumin, Thrombosis}, issn = {1046-6673}, doi = {10.1097/01.ASN.0000146422.45434.35}, author = {Fried, Linda and Solomon, Cam and Shlipak, Michael and Seliger, Stephen and Stehman-Breen, Catherine and Bleyer, Anthony J and Chaves, Paolo and Furberg, Curt and Kuller, Lewis and Newman, Anne} } @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 {778, title = {Subclinical cardiovascular disease in older adults: insights from the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 May-Jun}, pages = {137-51}, abstract = {

Knowledge about the epidemiology of subclinical cardiovascular disease (SCVD) in older adults may hold the key for improved opportunities for primary prevention of cardiovascular disease (CVD), a top clinical and public health priority. This review reports findings on the prevalence of SCVD and the ability of SCVD measures to predict incident and adverse outcomes from one of the largest (N=5888) and most comprehensive prospective observational studies on SCVD in older adults, the Cardiovascular Health Study. According to a composite index that combined SCVD measures from different vascular beds, the overall prevalence of SCVD was 37\%, making it as common as clinically overt CVD in older adults. SCVD measures strongly predicted incident CVD, stroke, mortality, frailty, and physical and cognitive decline, even after adjustment for traditional CVD risk factors. Ongoing research will address the potential use of SCVD for clinical decision making in older adults.

}, keywords = {Aged, Cardiovascular Diseases, Coronary Artery Disease, Heart Failure, Humans, Longitudinal Studies, Prevalence, Risk Assessment, Risk Factors}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02120.x}, author = {Chaves, Paulo H M and Kuller, Lewis H and O{\textquoteright}Leary, Daniel H and Manolio, Teri A and Newman, Anne B} } @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 {831, title = {Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors.}, journal = {JAMA}, volume = {293}, year = {2005}, month = {2005 Apr 13}, pages = {1737-45}, abstract = {

CONTEXT: Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown.

OBJECTIVE: To compare traditional and novel risk factors as predictors of cardiovascular mortality.

DESIGN, SETTING, AND PATIENTS: A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years.

MAIN OUTCOME MEASURES: Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2.

RESULTS: Among the participants, 1249 (22\%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P = .05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95\% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95\% confidence interval, 0.71-0.78; P for difference = .15).

CONCLUSIONS: Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.

}, keywords = {Aged, Cardiovascular Diseases, Chronic Disease, Humans, Kidney Diseases, Longitudinal Studies, Risk Factors}, issn = {1538-3598}, doi = {10.1001/jama.293.14.1737}, author = {Shlipak, Michael G and Fried, Linda F and Cushman, Mary and Manolio, Teri A and Peterson, Do and Stehman-Breen, Catherine and Bleyer, Anthony and Newman, Anne and Siscovick, David and Psaty, Bruce} } @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 {852, title = {Dementia and Alzheimer{\textquoteright}s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Jul}, pages = {1101-7}, abstract = {

OBJECTIVES: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer{\textquoteright}s disease (AD).

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded.

MEASUREMENTS: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders.

RESULTS: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95\% confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95\% CI=1.4-4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease.

CONCLUSION: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Peripheral Vascular Diseases, Risk Factors}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53360.x}, author = {Newman, Anne B and Fitzpatrick, Annette L and Lopez, Oscar and Jackson, Sharon and Lyketsos, Constantine and Jagust, William and Ives, Diane and DeKosky, Steven T and Kuller, Lewis H} } @article {812, title = {Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Jan}, pages = {56-61}, abstract = {

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.

METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.

RESULTS: Worsening was evident in 538 participants (28\%), mostly (85\%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.

CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Stroke}, issn = {1524-4628}, doi = {10.1161/01.STR.0000149625.99732.69}, author = {Longstreth, W T and Arnold, Alice M and Beauchamp, Norman J and Manolio, Teri A and Lefkowitz, David and Jungreis, Charles and Hirsch, Calvin H and O{\textquoteright}Leary, Daniel H and Furberg, Curt D} } @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 {861, title = {Methods for incorporating death into health-related variables in longitudinal studies.}, journal = {J Clin Epidemiol}, volume = {58}, year = {2005}, month = {2005 Nov}, pages = {1115-24}, abstract = {

BACKGROUND AND OBJECTIVES: Longitudinal studies of health over time may be misleading if some people die. Self-rated health (excellent to poor) and the SF-36 profile scores have been transformed to incorporate death. We applied the same approaches to incorporate death into activities of daily living difficulties (ADLs), IADLs, mini-mental state examination, depressive symptoms, blocks walked per week, bed days, the timed walk, body mass index and blood pressure.

STUDY DESIGN AND SETTING: The Cardiovascular Health Study of 5,888 older adults, was followed up to 9 years. Mean age was 73 at baseline, and 658 had an incident stroke during follow-up.

METHODS: We recoded each variable as the probability of being healthy 1 year in the future (PHF), conditional on the current value of the variable. This was done for 11 health variables, using three definitions of healthy, and two estimation models. Deaths were set to zero, and mean PHF was plotted in the 3 years before and after an incident stroke.

RESULTS: Analyses without the deaths were too optimistic. The effect of stroke was greatest on hospitalization, self-rated health, and IADLs. Alternative transformation approaches had slightly different results.

CONCLUSION: These methods provide an additional approach for handling death in longitudinal studies.

}, keywords = {Activities of Daily Living, Death, Health Status Indicators, Humans, Longitudinal Studies, Proportional Hazards Models}, issn = {0895-4356}, doi = {10.1016/j.jclinepi.2005.05.002}, author = {Diehr, Paula and Johnson, Laura Lee and Patrick, Donald L and Psaty, Bruce} } @article {869, title = {Statins and cognitive function in the elderly: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1388-94}, abstract = {

OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults.

METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy.

RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups.

CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

}, keywords = {Aged, Aged, 80 and over, Aging, Anticholesteremic Agents, Atrophy, Brain, Cholesterol, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Longitudinal Studies, Male, Memory Disorders, Nootropic Agents, Treatment Outcome}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000182897.18229.ec}, author = {Bernick, C and Katz, R and Smith, N L and Rapp, S and Bhadelia, R and Carlson, M and Kuller, L} } @article {927, title = {African ancestry, socioeconomic status, and kidney function in elderly African Americans: a genetic admixture analysis.}, journal = {J Am Soc Nephrol}, volume = {17}, year = {2006}, month = {2006 Dec}, pages = {3491-6}, abstract = {

Kidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged >65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine > or =0.05 mg/dl per yr (odds ratio [OR] 0.94; 95\% confidence interval [CI] 0.83 to 1.06) or with change in eGFR > or =3 ml/min per 1.73 m(2) per yr (OR 1.02; 95\% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95\% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95\% CI 2.54 to 4.06). Among self-identified African Americans, low income (< US dollars 8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C >1.29 g/dl (adjusted OR 2.7; 95\% CI 1.0 to 7.5) or by eGFR <60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95\% CI 1.1 to 9.4) compared with those with incomes >US dollars 35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors.

}, keywords = {African Americans, Aged, Creatinine, Cross-Sectional Studies, Cystatin C, Cystatins, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Linear Models, Longitudinal Studies, Male, Social Class}, issn = {1046-6673}, doi = {10.1681/ASN.2006050493}, author = {Peralta, Carmen A and Ziv, Elad and Katz, Ronit and Reiner, Alex and Burchard, Esteban Gonz{\'a}lez and Fried, Linda and Kwok, Pui-Yan and Psaty, Bruce and Shlipak, Michael} } @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 {912, title = {Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.}, journal = {Ann Intern Med}, volume = {145}, year = {2006}, month = {2006 Aug 15}, pages = {237-46}, abstract = {

BACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).

OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.

DESIGN: Cohort study.

SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.

PARTICIPANTS: 4663 elderly persons.

MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).

RESULTS: At baseline, 78\% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95\% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.

LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.

CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Creatinine, Cystatin C, Cystatins, Glomerular Filtration Rate, Humans, Kidney, Longitudinal Studies, Prognosis, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors}, issn = {1539-3704}, doi = {10.7326/0003-4819-145-4-200608150-00003}, author = {Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Stehman-Breen, Catherine and Seliger, Stephen L and Kestenbaum, Brian and Psaty, Bruce and Tracy, Russell P and Siscovick, David S} } @article {891, title = {Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study.}, journal = {Arch Gen Psychiatry}, volume = {63}, year = {2006}, month = {2006 Mar}, pages = {273-9}, abstract = {

CONTEXT: Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons.

OBJECTIVES: To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease.

DESIGN: Prospective, population-based, longitudinal study.

SETTING: Random sample of adults 65 years or older recruited from 4 US communities.

PARTICIPANTS: Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria.

MAIN OUTCOME MEASURE: Diagnosis of MCI.

RESULTS: Depressive symptoms at baseline were associated with increased risk of MCI (10.0\%, 13.3\%, and 19.7\% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics.

CONCLUSION: Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.

}, keywords = {Aged, Cerebrovascular Disorders, Cognition Disorders, Comorbidity, Dementia, Dementia, Vascular, Depressive Disorder, Female, Follow-Up Studies, Geriatric Assessment, Humans, Longitudinal Studies, Male, Prospective Studies, Psychiatric Status Rating Scales, Risk Factors, Sampling Studies, Vascular Diseases}, issn = {0003-990X}, doi = {10.1001/archpsyc.63.3.273}, author = {Barnes, Deborah E and Alexopoulos, George S and Lopez, Oscar L and Williamson, Jeff D and Yaffe, Kristine} } @article {911, title = {Education and the cognitive decline associated with MRI-defined brain infarct.}, journal = {Neurology}, volume = {67}, year = {2006}, month = {2006 Aug 08}, pages = {435-40}, abstract = {

OBJECTIVE: To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct.

METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI.

RESULTS: In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95\% CI 4.4- to 8.2-point decline vs 1.7, 95\% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct.

CONCLUSIONS: Education seems to modify an individual{\textquoteright}s decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.

}, keywords = {Cerebral Infarction, Cognition Disorders, Cross-Sectional Studies, Educational Status, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Neuropsychological Tests}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000228246.89109.98}, author = {Elkins, J S and Longstreth, W T and Manolio, T A and Newman, A B and Bhadelia, R A and Johnston, S C} } @article {908, title = {Kidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {61}, year = {2006}, month = {2006 Jul}, pages = {743-8}, abstract = {

BACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old.

METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (\%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women.

RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66\%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94\%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women.

CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.

}, keywords = {Absorptiometry, Photon, Aged, Bone Density, Creatinine, Cystatin C, Cystatins, Female, Hip, Humans, Kidney Diseases, Kidney Function Tests, Linear Models, Longitudinal Studies, Male, Osteoporosis, Predictive Value of Tests}, issn = {1079-5006}, doi = {10.1093/gerona/61.7.743}, author = {Fried, Linda F and Shlipak, Michael G and Stehman-Breen, Catherine and Mittalhenkle, Anuja and Seliger, Stephen and Sarnak, Mark and Robbins, John and Siscovick, David and Harris, Tamara B and Newman, Anne B and Cauley, Jane A} } @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 {884, title = {Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study.}, journal = {Circulation}, volume = {113}, year = {2006}, month = {2006 Jan 24}, pages = {388-93}, abstract = {

BACKGROUND: A low ankle-arm index (AAI) is a strong predictor of mortality and cardiovascular events. A high AAI also appears to be associated with higher mortality risk in select populations. However, mortality and cardiovascular risk across the AAI spectrum have not been described in a more broadly defined population.

METHODS AND RESULTS: We examined total and cardiovascular mortality and cardiovascular events across the AAI spectrum among 5748 participants in the Cardiovascular Health Study (CHS). The mean age of the sample population was 73+/-6 years, and the sample included 3289 women (57\%) and 883 blacks (15\%). The median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6 (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of which were cardiovascular) and 1491 cardiovascular events during follow-up. After adjustment for potential confounders, AAI measurements < or =0.60 (hazard ratio [HR] 1.82, 95\% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95\% CI 1.61 to 2.69), 0.71 to 0.8 (HR 1.80, 95\% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95\% CI 1.43 to 2.11), 0.91 to 1.0 (HR 1.40, 95\% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95\% CI 1.07 to 2.31) were associated with higher mortality risk from all causes compared with the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular mortality. For cardiovascular events, risk was higher at all AAI levels <1 but not for AAI levels >1.4 (HR 1.00, 95\% CI 0.57 to 1.74). The association of a high AAI with mortality was stronger in men than in women and in younger than in older cohort members.

CONCLUSIONS: In a cohort of community-dwelling elders, mortality risk was higher than the referent category of 1.11 to 1.2 among participants with AAI values above the traditional cutpoint of 0.9 (ie, 0.91 to 1.0 and >1.4), and the specific association of AAI with mortality varied by age and gender.

}, keywords = {Aged, Ankle, Arm, Blood Pressure, Body Mass Index, Cholesterol, LDL, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Peripheral Vascular Diseases, Risk Factors, Smoking}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.105.570903}, author = {O{\textquoteright}Hare, Ann M and Katz, Ronit and Shlipak, Michael G and Cushman, Mary and Newman, Anne B} } @article {956, title = {ABO blood group, other risk factors and incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {J Thromb Haemost}, volume = {5}, year = {2007}, month = {2007 Jul}, pages = {1455-61}, abstract = {

BACKGROUND: Numerous case-control studies have reported higher prevalence of non-O blood type among venous thromboembolism (VTE) patients than controls, but potential mechanisms or effect modifiers for the association are not fully established.

PATIENTS/METHODS: Using a nested case-control design combining the Atherosclerosis Risk in Communities and the Cardiovascular Health Study cohort, ABO blood type and other VTE risk factors were measured on pre-event blood samples of 492 participants who subsequently developed VTE and 1008 participants who remained free of VTE.

RESULTS: A total of 64.4\% of cases and 52.5\% of controls had non-O blood type. Among controls, mean values of factor VIIIc (FVIIIc) and von Willebrand factor among the non-O blood type group were higher than among the O group. Compared with O blood type, the age-adjusted odds ratio (OR) of VTE for non-O blood type was 1.64 (95\% CI, 1.32-2.05) and was similar for the two parent studies and race groups. Further adjustment for sex, race, body mass index, diabetes mellitus and FVIIIc reduced the OR: 1.31 (95\% CI, 1.02-1.68). Factor V Leiden (FV Leiden) appeared to modify the non-O blood type association with VTE in a supra-additive fashion, with an age-, sex- and race-adjusted OR of 6.77 (95\% CI, 3.65-12.6) for having both risk factors.

CONCLUSIONS: Non-O blood type was independently associated with risk of VTE, and added to the risk associated with FV Leiden.

}, keywords = {ABO Blood-Group System, Aged, Case-Control Studies, Diabetes Complications, Factor V, Factor VIII, Female, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, Thromboembolism, Venous Thrombosis, von Willebrand Factor}, issn = {1538-7933}, doi = {10.1111/j.1538-7836.2007.02579.x}, author = {Ohira, T and Cushman, M and Tsai, M Y and Zhang, Y and Heckbert, S R and Zakai, N A and Rosamond, W D and Folsom, A R} } @article {909, title = {Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study.}, journal = {Neurobiol Aging}, volume = {28}, year = {2007}, month = {2007 Sep}, pages = {1316-21}, abstract = {

Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.

}, keywords = {Aged, Analysis of Variance, Cardiovascular Diseases, Cerebral Ventricles, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Reference Values, Retrospective Studies, Sex Factors, Time Factors}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2006.06.016}, author = {Carmichael, Owen T and Kuller, L H and Lopez, O L and Thompson, P M and Dutton, R A and Lu, A and Lee, S E and Lee, J Y and Aizenstein, H J and Meltzer, C C and Liu, Y and Toga, A W and Becker, J T} } @article {939, title = {Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.}, journal = {Am Heart J}, volume = {153}, year = {2007}, month = {2007 Feb}, pages = {260-6}, abstract = {

BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations.

RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95\% CI, 1.02-1.54) among former drinkers, 1.09 (95\% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95\% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95\% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95\% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95\% CI, 1.06-1.52) among former drinkers, 0.94 (95\% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95\% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95\% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95\% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12).

CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.

}, keywords = {Aged, Alcohol Drinking, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Prognosis, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2006.10.039}, author = {Mukamal, Kenneth J and Psaty, Bruce M and Rautaharju, Pentti M and Furberg, Curt D and Kuller, Lewis H and Mittleman, Murray A and Gottdiener, John S and Siscovick, David S} } @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 {933, title = {Association of kidney function with incident hip fracture in older adults.}, journal = {J Am Soc Nephrol}, volume = {18}, year = {2007}, month = {2007 Jan}, pages = {282-6}, abstract = {

Kidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95\% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95\% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95\% CI 1.01, 1.33) but not in men (HR 1.14; 95\% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk.

}, keywords = {Aged, Aged, 80 and over, Cystatin C, Cystatins, Female, Hip Fractures, Humans, Kidney, Kidney Failure, Chronic, Longitudinal Studies, Male, Osteoporosis, Prospective Studies, Risk Factors, Sex Factors}, issn = {1046-6673}, doi = {10.1681/ASN.2006050546}, author = {Fried, Linda F and Biggs, Mary Louise and Shlipak, Michael G and Seliger, Stephen and Kestenbaum, Bryan and Stehman-Breen, Catherine and Sarnak, Mark and Siscovick, David and Harris, Tamara and Cauley, Jane and Newman, Anne B and Robbins, John} } @article {937, title = {Association of physical activity with sleep-disordered breathing.}, journal = {Sleep Breath}, volume = {11}, year = {2007}, month = {2007 Sep}, pages = {149-57}, abstract = {

This study was performed to determine whether there is a protective association between participation in vigorous or vigorous/moderately vigorous physical activity and the prevalence of sleep-disordered breathing (SDB). Polysomnographic and questionnaire data from the baseline examination of 4,275 participants in the Sleep Heart Health Study (SHHS) were analyzed in relation to information on amount of physical activity and other potentially relevant factors collected from five SHHS parent cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, Strong Heart Study, and Tucson Epidemiologic Study of Airways Obstructive Diseases). Logistic regression models were fitted to determine if amount and strenuousness of physical activity was associated with the presence of SDB. At least 3 h per week of vigorous physical activity reduced the odds of SDB, defined as a respiratory disturbance index (RDI) of at least 15 apneas/hypopneas per hour (Adjusted OR, 0.68; 95\%CI, 0.51-0.91). A qualitatively similar but slightly weaker association was observed when SDB was defined as a RDI > or = 10 per hour (Adjusted OR, 0.81; 95\%CI, 0.64-1.02). These findings remained after adjustment for sleepiness and restricting analyses to participants with good health. Three or more hours of moderately vigorous or vigorous physical activity also appeared to confer some protection against SDB, but these associations were weaker. Gender- and obesity-stratified analyses suggested that the protective association between physical activity and SDB occurred primarily in men and those who were obese. A program of regular vigorous physical activity of at least 3 h per week may be a useful adjunctive treatment modality for SDB, but this association needs confirmation with a prospective clinical trial.

}, keywords = {Adult, Cardiac Rehabilitation, Cardiovascular Diseases, Cohort Studies, Exercise, Female, Humans, Longitudinal Studies, Male, Middle Aged, Obesity, Polysomnography, Pulmonary Disease, Chronic Obstructive, Pulmonary Ventilation, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Sleep Stages, Weight Loss}, issn = {1520-9512}, doi = {10.1007/s11325-006-0095-5}, author = {Quan, Stuart F and O{\textquoteright}Connor, George T and Quan, Jason S and Redline, Susan and Resnick, Helaine E and Shahar, Eyal and Siscovick, David and Sherrill, Duane L} } @article {921, title = {Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {165}, year = {2007}, month = {2007 Jan 01}, pages = {78-84}, abstract = {

Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio--the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95\% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95\% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95\% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95\% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95\% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Arteriosclerosis, Cerebral Infarction, Female, Humans, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Microcirculation, Photography, Retina, Retinal Diseases, Retinal Vessels, Risk Assessment, Risk Factors}, issn = {0002-9262}, doi = {10.1093/aje/kwj350}, author = {Longstreth, Wt and Larsen, Emily K Marino and Klein, Ronald and Wong, Tien Yin and Sharrett, A Richey and Lefkowitz, David and Manolio, Teri A} } @article {945, title = {Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia.}, journal = {Alzheimer Dis Assoc Disord}, volume = {21}, year = {2007}, month = {2007 Jan-Mar}, pages = {14-24}, abstract = {

Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.

}, keywords = {Aged, Aged, 80 and over, Case-Control Studies, Cerebral Ventricles, Cognition Disorders, Dementia, Disease Progression, Female, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Severity of Illness Index, Time Factors}, issn = {0893-0341}, doi = {10.1097/WAD.0b013e318032d2b1}, author = {Carmichael, Owen T and Kuller, Lewis H and Lopez, Oscar L and Thompson, Paul M and Dutton, Rebecca A and Lu, Allen and Lee, Sharon E and Lee, Jessica Y and Aizenstein, Howard J and Meltzer, Carolyn C and Liu, Yanxi and Toga, Arthur W and Becker, James T} } @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 {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 {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 {982, title = {IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study.}, journal = {Hum Genet}, volume = {122}, year = {2007}, month = {2007 Dec}, pages = {485-94}, abstract = {

Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95\% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95\% CI 1.05-1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.

}, keywords = {African Americans, Aged, Alleles, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Humans, Interleukin-6, Introns, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic}, issn = {1432-1203}, doi = {10.1007/s00439-007-0428-x}, author = {Walston, Jeremy D and Fallin, M Daniele and Cushman, Mary and Lange, Leslie and Psaty, Bruce and Jenny, Nancy and Browner, Warren and Tracy, Russell and Durda, Peter and Reiner, Alex} } @article {961, title = {Longitudinal association between depressive symptoms and incident type 2 diabetes mellitus in older adults: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {167}, year = {2007}, month = {2007 Apr 23}, pages = {802-7}, abstract = {

BACKGROUND: Prospective studies indicate that a single self-report of high depressive symptoms is associated with an increased risk of developing type 2 diabetes mellitus.

METHODS: We tested whether a single report of high depressive symptoms, an increase in depressive symptoms, or persistently high depressive symptoms over time were associated with the development of diabetes in adults 65 years and older. Participants from the Cardiovascular Health Study completed the 10-item Center for Epidemiological Studies-Depression Scale (CES-D) annually from 1989 to 1999. A single report of high depressive symptoms (CES-D score, >/=8), an increase in symptoms during follow-up (>/=5 from baseline), and persistently high symptoms (2 consecutive scores >/=8) were each studied in relation to incident diabetes, defined by initiation of diabetes control medications among participants who were free from diabetes at baseline (n = 4681).

RESULTS: The mean CES-D score at baseline was 4.5 (SD, 4.5). The incidence rate of diabetes was 4.4 per 1000 person-years. Following adjustment for baseline demographic characteristics and measures of physical activity, smoking, alcohol intake, body mass index, and C-reactive protein during follow-up, each measure of depressive symptoms was significantly associated with incident diabetes (high baseline CES-D score: hazard ratio, 1.6 [95\% confidence interval, 1.1-2.3]; CES-D score increase: hazard ratio, 1.5 [95\% confidence interval, 1.1-2.2]; and persistently high symptoms: hazard ratio, 1.5 [95\% confidence interval, 1.1-2.3]).

CONCLUSION: Older adults who reported higher depressive symptoms were more likely to develop diabetes than their counterparts; this association was not fully explained by risk factors for diabetes.

}, keywords = {Aged, Body Mass Index, C-Reactive Protein, Depression, Diabetes Mellitus, Type 2, Drinking, Female, Humans, Longitudinal Studies, Male, Smoking}, issn = {0003-9926}, doi = {10.1001/archinte.167.8.802}, author = {Carnethon, Mercedes R and Biggs, Mary L and Barzilay, Joshua I and Smith, Nicholas L and Vaccarino, Viola and Bertoni, Alain G and Arnold, Alice and Siscovick, David} } @article {965, title = {Retinal microvascular signs, cognitive function, and dementia in older persons: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {38}, year = {2007}, month = {2007 Jul}, pages = {2041-7}, abstract = {

BACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals.

METHODS: In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded.

RESULTS: After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95\% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95\% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension.

CONCLUSIONS: In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition, Cross-Sectional Studies, Dementia, Female, Humans, Longitudinal Studies, Male, Microcirculation, Neuropsychological Tests, Retinal Vessels, Risk Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.483586}, author = {Baker, Michelle L and Marino Larsen, Emily K and Kuller, Lewis H and Klein, Ronald and Klein, Barbara E K and Siscovick, David S and Bernick, Charles and Manolio, Teri A and Wong, Tien Yin} } @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 {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 {907, title = {White matter grade and ventricular volume on brain MRI as markers of longevity in the cardiovascular health study.}, journal = {Neurobiol Aging}, volume = {28}, year = {2007}, month = {2007 Sep}, pages = {1307-15}, abstract = {

High white matter grade (WMG) on magnetic resonance imaging (MRI) is a risk factor for dementia, stroke and disability. Higher ventricular size is a marker of brain "atrophy." In the Cardiovascular Health Study (CHS) (n=3245) mean age 75 years, 50\% black and 40\% men, we evaluated WM and ventricular grade (VG), total, cardiovascular and noncardiovascular mortality and longevity before and after adjusting for numerous determinants of longevity over an approximate 10-12 years of follow-up. A low WMG and VG was a marker for low total, cardiovascular and noncardiovascular mortality and for increased longevity over 10+ years of follow-up. We estimated that a 75-year-old with WMG below median would have about a 5-6 years greater longevity and for VG about 3 years, than above the median even after adjustment for numerous risk factors. Low WMG and VG on MRI is a powerful determinant of long-term survival among older individuals.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Biomarkers, Brain, Cardiovascular Diseases, Cerebral Ventricles, European Continental Ancestry Group, Female, Geriatric Assessment, Health Status, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Retrospective Studies, Risk Factors, Sex Factors}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2006.06.010}, author = {Kuller, Lewis H and Arnold, Alice M and Longstreth, W T and Manolio, Teri A and O{\textquoteright}Leary, Daniel H and Burke, Gregory L and Fried, Linda P and Newman, Anne B} } @article {1038, title = {Adiponectin and risk of coronary heart disease in older men and women.}, journal = {J Clin Endocrinol Metab}, volume = {93}, year = {2008}, month = {2008 Sep}, pages = {3357-64}, abstract = {

CONTEXT: Despite established insulin-sensitizing and antiatherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain.

OBJECTIVE: Our objective was to investigate the relationship between adiponectin and CHD in older adults.

DESIGN, SETTING, AND PARTICIPANTS: This was a case-control study (n = 1386) nested within the population-based Cardiovascular Health Study from 1992--2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease, and center.

MAIN OUTCOME MEASURES: Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, nonfatal myocardial infarction (MI), or CHD death. A more restrictive CHD endpoint was limited to nonfatal MI and CHD death.

RESULTS: Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist to hip ratio, hypertension, smoking, alcohol, low-density lipoprotein cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end [odds ratio = 1.37 (quintile 5 vs. 1-4), 95\% confidence interval 1.02-1.84]. This association was stronger when the outcome was limited to nonfatal MI and fatal CHD (odds ratio = 1.69, 95\% confidence interval 1.23-2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators.

CONCLUSIONS: This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.

}, keywords = {Adiponectin, Age Factors, Aged, Aged, 80 and over, Body Weight, Case-Control Studies, Cohort Studies, Coronary Disease, Female, Humans, Longitudinal Studies, Male, Odds Ratio, Risk Factors}, issn = {0021-972X}, doi = {10.1210/jc.2008-0640}, author = {Kizer, Jorge R and Barzilay, Joshua I and Kuller, Lewis H and Gottdiener, John S} } @article {981, title = {Age-specific prevalence and years of healthy life in a system with three health states.}, journal = {Stat Med}, volume = {27}, year = {2008}, month = {2008 Apr 30}, pages = {1371-86}, abstract = {

Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an {\textquoteright}equilibrium{\textquoteright} value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to the one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate when a valid survival table was known from other sources, or when the available data set was sufficient to estimate survival accurately. Performance was better with fewer waves of data. If validated in other situations, these estimates of prevalence and years of healthy life (YHL) and their standard errors may be useful when the goal is to compare YHL for different populations.

}, keywords = {Age Factors, Biometry, Health Status, Humans, Life Tables, Longitudinal Studies, Middle Aged, Models, Statistical, Probability, Quality-Adjusted Life Years}, issn = {0277-6715}, doi = {10.1002/sim.3056}, author = {Diehr, Paula and Yanez, David and Derleth, Ann and Newman, Anne B} } @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 {1001, title = {Chronic kidney disease increases risk for venous thromboembolism.}, journal = {J Am Soc Nephrol}, volume = {19}, year = {2008}, month = {2008 Jan}, pages = {135-40}, abstract = {

Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95\% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95\% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95\% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Diabetic Nephropathies, Factor VIII, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Failure, Chronic, Longitudinal Studies, Male, Middle Aged, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {1533-3450}, doi = {10.1681/ASN.2007030308}, author = {Wattanakit, Keattiyoat and Cushman, Mary and Stehman-Breen, Catherine and Heckbert, Susan R and Folsom, Aaron R} } @article {1012, title = {Cystatin C concentration as a predictor of systolic and diastolic heart failure.}, journal = {J Card Fail}, volume = {14}, year = {2008}, month = {2008 Feb}, pages = {19-26}, abstract = {

BACKGROUND: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study.

METHODS AND RESULTS: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF > or = 50\%) or SHF (EF < 50\%). We compared the association of cystatin C with the risk for DHF and SHF, after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHF. After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95\% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]).

CONCLUSIONS: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Confidence Intervals, Cystatin C, Cystatins, Echocardiography, Female, Heart Failure, Diastolic, Heart Failure, Systolic, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Probability, Proportional Hazards Models, Risk Assessment, Sensitivity and Specificity, Stroke Volume, Survival Analysis}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2007.09.002}, author = {Moran, Andrew and Katz, Ronit and Smith, Nicolas L and Fried, Linda F and Sarnak, Mark J and Seliger, Stephen L and Psaty, Bruce and Siscovick, David S and Gottdiener, John S and Shlipak, Michael G} } @article {1052, title = {Diabetes mellitus and gait dysfunction: possible explanatory factors.}, journal = {Phys Ther}, volume = {88}, year = {2008}, month = {2008 Nov}, pages = {1365-74}, abstract = {

BACKGROUND AND OBJECTIVE: Gait characteristics differ in individuals with diabetes compared with those without diabetes. Limited information regarding potential explanatory factors for this association exists. This study examined the association between diabetes and gait characteristics in older adults and explored potential explanatory factors.

DESIGN: A cross-sectional, observational study design was used.

METHODS: At the 1998-1999 clinic visit, 558 ambulatory older adults (mean age=79 years) from the Pittsburgh site of the Cardiovascular Health Study had an assessment of their gait characteristics, diabetes, health status, cognition, mood, lower-extremity circulation and sensation, vision, lower-extremity strength (force-producing capacity), physical activity, and body mass index (BMI). A series of linear regression models were developed to examine the association between diabetes and gait characteristics and to examine potential explanatory factors for the associations.

RESULTS: Diabetes was related to gait speed (beta=-.06 m/s); however, the association was partially explained by health status variables, cognition, mood, lower-extremity circulation and sensation, visual impairment, lower-extremity strength, physical activity, and BMI. Health status and lower-extremity strength each explained the greatest proportion of the association (beta reduced 66\% by each). Diabetes was related to step width (beta=.02 m), and the association could not be explained by the examined factors.

CONCLUSIONS: Diabetes was associated with gait alterations in older adults. Slowed gait speed appears to be secondary to the peripheral effect of the disease on other body systems. The effect of diabetes on step width was not explained in the analyses and may be related to peripheral motor nerve function or central influences of the disease, which could not be assessed in this study.

}, keywords = {Aged, Body Mass Index, Cognition, Cross-Sectional Studies, Diabetes Mellitus, Female, Gait, Geriatric Assessment, Health Status, Humans, Linear Models, Longitudinal Studies, Male, Multicenter Studies as Topic, Muscle Strength}, issn = {1538-6724}, doi = {10.2522/ptj.20080016}, author = {Brach, Jennifer S and Talkowski, Jaime B and Strotmeyer, Elsa S and Newman, Anne B} } @article {1009, title = {Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study.}, journal = {Arch Neurol}, volume = {65}, year = {2008}, month = {2008 Jan}, pages = {89-93}, abstract = {

BACKGROUND: Diabetes and the apolipoprotein E epsilon4 allele (APOE epsilon4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE epsilon4 may modify the risk for AD in individuals with diabetes.

OBJECTIVE: To examine the joint effect of type 2 diabetes and APOE epsilon4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD.

DESIGN: The Cardiovascular Health Study (CHS) Cognition Study (1992-2000) is a prospective study designed to identify all existing and new cases of dementia among study participants. Diagnoses were made according to international criteria for dementia and subtypes. There were 2547 dementia-free participants in the CHS Cognition Study cohort with complete information on APOE epsilon4 and type 2 diabetes status; among these, 411 new cases of dementia developed. Risk of dementia was estimated with a Cox proportional hazard model adjusted for age and other demographic and cardiovascular risk factors.

RESULTS: Compared with those who had neither type 2 diabetes nor APOE epsilon4, those with both factors had a significantly higher risk of AD (hazard ratio, 4.58; 95\% confidence interval, 2.18-9.65) and mixed AD (hazard ratio, 3.89; 95\% confidence interval, 1.46-10.40).

CONCLUSION: These data suggest that having both diabetes and APOE epsilon4 increases the risk of dementia, especially for AD and mixed AD.

}, keywords = {African Americans, Age Factors, Aged, Alzheimer Disease, Apolipoprotein E4, Cognition, Cohort Studies, Confidence Intervals, Dementia, Vascular, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Genotype, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors}, issn = {0003-9942}, doi = {10.1001/archneurol.2007.29}, author = {Irie, Fumiko and Fitzpatrick, Annette L and Lopez, Oscar L and Kuller, Lewis H and Peila, Rita and Newman, Anne B and Launer, Lenore J} } @article {1050, title = {Evaluation of a method for fitting a semi-Markov process model in the presence of left-censored spells using the Cardiovascular Health Study.}, journal = {Stat Med}, volume = {27}, year = {2008}, month = {2008 Nov 20}, pages = {5509-24}, abstract = {

We used a longitudinal data set covering 13 years from the Cardiovascular Health Study to evaluate the properties of a recently developed approach to deal with left censoring that fits a semi-Markov process (SMP) model by using an analog to the stochastic EM algorithm--the SMP-EM approach. It appears that the SMP-EM approach gives estimates of duration-dependent probabilities of health changes similar to those obtained by using SMP models that have the advantage of actual duration data. SMP-EM estimates of duration-dependent transition probabilities also appear more accurate and less variable than multi-state life table estimates.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Cardiovascular Diseases, Cardiovascular System, Data Interpretation, Statistical, Disease Progression, Female, Humans, Longitudinal Studies, Male, Markov Chains, Models, Statistical, Stochastic Processes, Time Factors}, issn = {0277-6715}, doi = {10.1002/sim.3382}, author = {Cai, Liming and Schenker, Nathaniel and Lubitz, James and Diehr, Paula and Arnold, Alice and Fried, Linda P} } @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 {1048, title = {Inflammatory markers and longitudinal lung function decline in the elderly.}, journal = {Am J Epidemiol}, volume = {168}, year = {2008}, month = {2008 Sep 15}, pages = {602-10}, abstract = {

Longitudinal studies examining associations of the inflammatory markers fibrinogen and C-reactive protein (CRP) with lung function decline are sparse. The authors examined whether elevated fibrinogen and CRP levels were associated with greater longitudinal lung function decline in the elderly. The Cardiovascular Health Study measured fibrinogen and CRP in 5,790 Whites and African Americans from four US communities aged 65 years or older in 1989-1990 or 1992-1993. Spirometry was performed in 1989-1990 and 4, 7, and 16 years later. Fibrinogen and CRP were inversely associated with lung function at baseline after adjustment for multiple potential confounders. In mixed models, the rate of decline in forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) ratio with increasing age was faster among those with higher baseline fibrinogen (-0.032\%/year per standard deviation higher fibrinogen (95\% confidence interval: -0.057, -0.0074)) but not among those with higher CRP (-0.0037\%/year per standard deviation higher CRP (95\% confidence interval: -0.013, 0.0056)). Longitudinal analyses for FEV(1) and FVC yielded results in the direction opposite of that hypothesized, possibly because of the high mortality rate and strong inverse association of FEV(1) and FVC but not FEV(1)/FVC with mortality. An alternative approach to missing data yielded similar results. In conclusion, higher levels of fibrinogen, but not CRP, independently predicted greater FEV(1)/FVC decline in the elderly.

}, keywords = {Aged, C-Reactive Protein, Cross-Sectional Studies, Female, Fibrinogen, Forced Expiratory Volume, Geriatric Assessment, Humans, Logistic Models, Longitudinal Studies, Lung Volume Measurements, Male, Multicenter Studies as Topic, Pulmonary Disease, Chronic Obstructive, Spirometry}, issn = {1476-6256}, doi = {10.1093/aje/kwn174}, author = {Jiang, Rui and Burke, Gregory L and Enright, Paul L and Newman, Anne B and Margolis, Helene G and Cushman, Mary and Tracy, Russell P and Wang, Yuanjia and Kronmal, Richard A and Barr, R Graham} } @article {1025, title = {Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 May 06}, pages = {1664-71}, abstract = {

OBJECTIVES: To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study.

METHODS: We determined the plasma A beta 1-40 and A beta 1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 +/- 3.6 years. We examined the association between A beta levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts.

RESULTS: In an unadjusted prospective model in normal subjects, both A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD.

CONCLUSIONS: Plasma A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of A beta do not seem to be useful biomarkers for AD.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Cerebrovascular Disorders, Comorbidity, Cross-Sectional Studies, Cystatin C, Cystatins, Female, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Models, Statistical, Neuropsychological Tests, Peptide Fragments, Predictive Value of Tests, Prospective Studies, Reference Values, Risk Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000306696.82017.66}, author = {Lopez, O L and Kuller, L H and Mehta, P D and Becker, J T and Gach, H M and Sweet, R A and Chang, Y F and Tracy, R and DeKosky, S T} } @article {970, title = {Stance time and step width variability have unique contributing impairments in older persons.}, journal = {Gait Posture}, volume = {27}, year = {2008}, month = {2008 Apr}, pages = {431-9}, abstract = {

Gait variability may have multiple causes. We hypothesized that central nervous system (CNS) impairments would affect motor control and be manifested as increased stance time and step length variability, while sensory impairments would affect balance and be manifested as increased step width variability. Older adults (mean+/-standard deviation (S.D.) age=79.4+/-4.1, n=558) from the Pittsburgh site of the Cardiovascular Health Study participated. The S.D. across steps was the indicator of gait variability, determined for three gait measures, step length, stance time and step width, using a computerized walkway. Impairment measures included CNS function (modified mini-mental state examination, Trails A and B, Digit Symbol Substitution, finger tapping), sensory function (lower extremity (LE) vibration, vision), strength (grip strength, repeated chair stands), mood, and LE pain. Linear regression models were fit for the three gait variability characteristics using impairment measures as independent variables, adjusted for age, race, gender, and height. Analyses were repeated stratified by gait speed. All measures of CNS impairment were directly related to stance time variability (p<0.01), with increased CNS impairment associated with increased stance time variability. CNS impairments were not related to step length or width variability. Both sensory impairments were inversely related to step width (p<0.01) but not step length or stance time variability. CNS impairments affected stance time variability especially in slow walkers while sensory impairments affected step width variability in fast walkers. Specific patterns of gait variability may imply different underlying causes. Types of gait variability should be specified. Interventions may be targeted at specific types of gait variability.

}, keywords = {Aged, Aged, 80 and over, Biomechanical Phenomena, Female, Gait Disorders, Neurologic, Humans, Linear Models, Longitudinal Studies, Male, Neuropsychological Tests, Postural Balance, Range of Motion, Articular, Risk Factors, Signal Processing, Computer-Assisted}, issn = {0966-6362}, doi = {10.1016/j.gaitpost.2007.05.016}, author = {Brach, Jennifer S and Studenski, Stephanie and Perera, Subashan and VanSwearingen, Jessie M and Newman, Anne B} } @article {1063, title = {Agreement between nosologist and cardiovascular health study review of deaths: implications of coding differences.}, journal = {J Am Geriatr Soc}, volume = {57}, year = {2009}, month = {2009 Jan}, pages = {133-9}, abstract = {

OBJECTIVES: To compare nosologist coding of underlying cause of death according to the death certificate with adjudicated cause of death for subjects aged 65 and older in the Cardiovascular Health Study (CHS).

DESIGN: Observational.

SETTING: Four communities: Forsyth County, North Carolina (Wake Forest University); Sacramento County, California (University of California at Davis); Washington County, Maryland (Johns Hopkins University); and Pittsburgh, Pennsylvania (University of Pittsburgh).

PARTICIPANTS: Men and women aged 65 and older participating in CHS, a longitudinal study of coronary heart disease and stroke, who died through June 2004.

MEASUREMENTS: The CHS centrally adjudicated underlying cause of death for 3,194 fatal events from June 1989 to June 2004 using medical records, death certificates, proxy interviews, and autopsies, and results were compared with underlying cause of death assigned by a trained nosologist based on death certificate only.

RESULTS: Comparison of 3,194 CHS versus nosologist underlying cause of death revealed moderate agreement except for cancer (kappa=0.91, 95\% confidence interval (CI)=0.89-0.93). kappas varied according to category (coronary heart disease, kappa=0.61, 95\% CI=0.58-0.64; stroke, kappa=0.59, 95\% CI=0.54-0.64; chronic obstructive pulmonary disease, kappa=0.58, 95\% CI=0.51-0.65; dementia, kappa=0.40, 95\% CI=0.34-0.45; and pneumonia, kappa=0.35, 95\% CI=0.29-0.42). Differences between CHS and nosologist coding of dementia were found especially in older ages in the sex and race categories. CHS attributed 340 (10.6\%) deaths due to dementia, whereas nosologist coding attributed only 113 (3.5\%) to dementia as the underlying cause.

CONCLUSION: Studies that use only death certificates to determine cause of death may result in misclassification and potential bias. Changing trends in cause-specific mortality in older individuals may be a function of classification process rather than incidence and case fatality.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Coronary Disease, Death Certificates, Female, Forms and Records Control, Humans, Longitudinal Studies, Male, Stroke}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.02056.x}, author = {Ives, Diane G and Samuel, Paulraj and Psaty, Bruce M and Kuller, Lewis H} } @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 {1115, title = {Coagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology.}, journal = {Blood}, volume = {114}, year = {2009}, month = {2009 Oct 01}, pages = {2878-83}, abstract = {

Higher levels of procoagulant factors and factor XII deficiency may be risk factors for first venous thromboembolism (VTE). We studied associations of coagulation factors IX through XIII with risk of future VTE in 2 general population samples. Using a nested case-control study combining the 21 860 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study, we determined antigenic levels of these coagulation factors in primarily pre-event blood samples from 462 participants who subsequently developed VTE and 1047 participants who remained free of VTE. Only elevated levels of factors IX and XI were associated with increased risk of VTE after adjustment for age, sex, race, and study. For factor IX, the odds ratio (OR) was 1.4 (95\% confidence interval [CI], 1.0-2.0) comparing the top to bottom quintile. The OR for factor XI was higher: 2.0 (95\% CI, 1.4-2.9). With further adjustment for body mass index and diabetes, only elevated factor XI remained associated with VTE risk: OR 1.8 (95\% CI, 1.3-2.7). Associations were similar by study and whether the thrombosis was idiopathic or secondary. Factor XII deficiency was not related to VTE risk. Among these procoagulant factors, only elevated factor XI was a risk factor for VTE.

}, keywords = {Aged, Aged, 80 and over, Case-Control Studies, Factor IX, Factor X, Factor XI, Factor XII, Factor XIII, Female, Humans, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Venous Thromboembolism}, issn = {1528-0020}, doi = {10.1182/blood-2009-05-219915}, author = {Cushman, Mary and O{\textquoteright}Meara, Ellen S and Folsom, Aaron R and Heckbert, Susan R} } @article {1118, title = {Depressed mood is not a risk factor for incident dementia in a community-based cohort.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Aug}, pages = {653-63}, abstract = {

OBJECTIVES: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals.

DESIGN: Longitudinal and observational.

SETTING: Community-based cohort study.

PARTICIPANTS: A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years).

MEASUREMENTS: The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams.

RESULTS: The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood.

CONCLUSION: Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Dementia, Depression, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Prospective Studies, Psychiatric Status Rating Scales, Residence Characteristics, Risk Factors}, issn = {1545-7214}, author = {Becker, James T and Chang, Yue-Fang and Lopez, Oscar L and Dew, Mary Amanda and Sweet, Robert A and Barnes, Deborah and Yaffe, Kristine and Young, Jeffrey and Kuller, Lewis and Reynolds, Charles F} } @article {1070, title = {Hypertension genes and retinal vascular calibre: the Cardiovascular Health Study.}, journal = {J Hum Hypertens}, volume = {23}, year = {2009}, month = {2009 Sep}, pages = {578-84}, abstract = {

We examined the associations of single nucleotide polymorphisms (SNPs) in three candidate hypertension genes, alpha-adducin (ADD1/G460W), beta2-adrenergic receptor (ADRB2/Arg16Gly and Gln27Glu) and G-protein beta3 subunit (GNB3/C825T), with retinal arteriolar calibre (an intermediate marker of chronic hypertension) and venular calibre. Data in 1842 participants (1554 whites and 288 African Americans) aged 69-96 years from the Cardiovascular Health Study with genotype and retinal vascular calibre data were included. A computer-assisted method was used to measure retinal vascular calibre. We analysed four SNPs and multilocus interaction for three genes. All SNPs were in Hardy-Weinberg equilibrium in whites and African Americans. The study had sufficient power to detect 0.5\% of the total variance of retinal vascular calibre contributed by each SNP in the total population, except for the GNB3 gene variant. No significant associations between these SNPs in the genes studied and mean retinal arteriolar and venular calibre were found in single-gene or multilocus analysis (for example, age-, gender-, race-adjusted mean retinal arteriolar calibre was similar between participants who were ADD1/460W homozygotes and ADD1/G allele carriers, 166.2 vs 167.7 microm). In conclusion, this study found no evidence of an association of SNPs in candidate hypertension genes studied here with retinal vascular calibre.

}, keywords = {African Americans, Aged, Aged, 80 and over, Arterioles, Calmodulin-Binding Proteins, European Continental Ancestry Group, Heterotrimeric GTP-Binding Proteins, Humans, Hypertension, Longitudinal Studies, Polymorphism, Single Nucleotide, Receptors, Adrenergic, beta-2, Retinal Vessels}, issn = {1476-5527}, doi = {10.1038/jhh.2008.168}, author = {Sun, C and Wang, J J and Islam, F M and Heckbert, S R and Klein, R and Siscovick, D S and Klein, B E K and Wong, T Y} } @article {1125, title = {Longitudinal evaluation of sleep-disordered breathing and sleep symptoms with change in quality of life: the Sleep Heart Health Study (SHHS).}, journal = {Sleep}, volume = {32}, year = {2009}, month = {2009 Aug}, pages = {1049-57}, abstract = {

STUDY OBJECTIVES: Findings from population studies evaluating the progression and incidence of sleep disordered breathing have shown evidence of a longitudinal increase in the severity of sleep disordered breathing. The present study evaluates the association among changes in sleep disordered breathing, sleep symptoms, and quality of life over time.

DESIGN: Prospective cohort study. Data were from the Sleep Heart Health Study.

SETTING: Multicenter study.

PARTICIPANTS: Three thousand seventy-eight subjects aged 40 years and older from the baseline and follow-up examination cycles were included.

MEASUREMENTS: The primary outcomes were changes in the Physical Component Summary and Mental Component Summary scales obtained from the Medical Outcomes Study Short-Form Health Survey. The primary exposure was change in the respiratory disturbance index obtained from unattended overnight polysomnograms performed approximately 5 years apart. Other covariates included measures of excessive daytime sleepiness and difficulty initiating and maintaining sleep.

RESULTS: Mean respiratory disturbance index increased from 8.1 +/- 11 SD at baseline to 10.9 +/- 14 (P < 0.0001) at follow-up. The mean Physical Component Summary and Mental Component Summary scores were 48.5 and 54.1 at baseline and 46.3 and 54.8 at follow-up. No associations between change in respiratory disturbance index and changes in Physical Component Summary or Mental Component Summary scores were seen. However, worsening of difficulty initiating and maintaining sleep and excessive daytime sleepiness were significantly associated with lower quality of life.

CONCLUSIONS: A slight increase in severity of sleep disordered breathing was seen over 5 years; this was not associated with worsening of quality of life. However, subjective symptoms of quality of sleep and daytime sleepiness were associated with declining quality of life.

}, keywords = {Aged, Attitude to Health, Cohort Studies, Comorbidity, Disease Progression, Disorders of Excessive Somnolence, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polysomnography, Quality of Life, Sleep Apnea, Obstructive, Sleep Initiation and Maintenance Disorders}, issn = {0161-8105}, author = {Silva, Graciela E and An, Ming-Wen and Goodwin, James L and Shahar, Eyal and Redline, Susan and Resnick, Helaine and Baldwin, Carol M and Quan, Stuart F} } @article {1073, title = {Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 May}, pages = {746-51}, abstract = {

SUMMARY BACKGROUND: In a recent case-control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among controls. We tested the hypothesis that the incidence of non-cancer-related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE.

METHODS: A total of 20 374 middle-aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Investigation of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined using ATP III guidelines, including >or=3 of the following components: abdominal obesity, elevated blood pressure, low HDL-cholesterol, high triglycerides and high glucose. Because sex modified the relation between MetSyn and VTE (p(interaction) = 0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non-cancer-related VTE, adjusting for potential confounders.

RESULTS: Incident VTE (n = 358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR) = 1.84, 95\% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95\% CI = 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95\% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95\% CI = 1.24, 2.34, in women), with no additional contribution by the other MetSyn components.

CONCLUSION: Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.

}, keywords = {Blood Coagulation Factors, Blood Glucose, Blood Pressure, Body Mass Index, Cohort Studies, Female, Fibrinogen, Humans, Lipids, Longitudinal Studies, Male, Metabolic Syndrome, Proportional Hazards Models, Risk Factors, Venous Thromboembolism}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2009.03295.x}, author = {Steffen, L M and Cushman, M and Peacock, J M and Heckbert, S R and Jacobs, D R and Rosamond, W D and Folsom, A R} } @article {1085, title = {Midlife and late-life obesity and the risk of dementia: cardiovascular health study.}, journal = {Arch Neurol}, volume = {66}, year = {2009}, month = {2009 Mar}, pages = {336-42}, abstract = {

BACKGROUND: While high adiposity in middle age appears to be related to greater dementia risk, studies exploring this association in the elderly are conflicting.

OBJECTIVE: To evaluate associations between midlife and late-life obesity and risk of dementia.

DESIGN: Prospective study with mean follow-up of 5.4 years (1992-1994 through 1999).

SETTING: Community-dwelling sample in 4 US sites recruited from Medicare eligibility files.

PARTICIPANTS: A total of 2798 adults without dementia (mean age, 74.7 years; 59.1\% women) participating in the Cardiovascular Health Study who underwent magnetic resonance imaging were measured for height and weight at baseline at age 65 years or older (late life), and self-reported weight at age 50 years (midlife). Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was calculated at both times.

MAIN OUTCOME MEASURES: Dementia, Alzheimer disease, and vascular dementia classified by a multidisciplinary committee using standardized criteria.

RESULTS: Classification resulted in 480 persons with incident dementia, 245 with Alzheimer disease (no vascular dementia), and 213 with vascular dementia (with or without Alzheimer disease). In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95\% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI.

CONCLUSION: These results help explain the "obesity paradox" as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability.

}, keywords = {Aged, Aged, 80 and over, Aging, Alzheimer Disease, Anthropometry, Body Mass Index, Dementia, Vascular, Evaluation Studies as Topic, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Prospective Studies, Risk, Survival Analysis}, issn = {1538-3687}, doi = {10.1001/archneurol.2008.582}, author = {Fitzpatrick, Annette L and Kuller, Lewis H and Lopez, Oscar L and Diehr, Paula and O{\textquoteright}Meara, Ellen S and Longstreth, W T and Luchsinger, Jos{\'e} A} } @article {1138, title = {N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {120}, year = {2009}, month = {2009 Nov 03}, pages = {1768-74}, abstract = {

BACKGROUND: Atrial fibrillation (AF), the most common cardiac rhythm abnormality, is associated with significant morbidity, mortality, and healthcare expenditures. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure, AF, and mortality.

METHODS AND RESULTS: The relation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and AF was studied in 5445 Cardiovascular Health Study participants with the use of relative risk regression for predicting prevalent AF and Cox proportional hazards for predicting incident AF. NT-proBNP levels were strongly associated with prevalent AF, with an unadjusted prevalence ratio of 128 for the highest quintile (95\% confidence interval, 17.9 to 913.3; P<0.001) and adjusted prevalence ratio of 147 for the highest quintile (95\% confidence interval, 20.4 to 1064.3; P<0.001) compared with the lowest. After a median follow-up of 10 years (maximum of 16 years), there were 1126 cases of incident AF (a rate of 2.2 per 100 person-years). NT-proBNP was highly predictive of incident AF, with an unadjusted hazard ratio of 5.2 (95\% confidence interval, 4.3 to 6.4; P<0.001) for the development of AF for the highest quintile compared with the lowest; for the same contrast, NT-proBNP remained the strongest predictor of incident AF after adjustment for an extensive number of covariates, including age, sex, medication use, blood pressure, echocardiographic parameters, diabetes mellitus, and heart failure, with an adjusted hazard ratio of 4.0 (95\% confidence interval, 3.2 to 5.0; P<0.001).

CONCLUSIONS: In a community-based population of older adults, NT-proBNP was a remarkable predictor of incident AF, independent of any other previously described risk factor.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Female, Humans, Immunoassay, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Prevalence, Proportional Hazards Models, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.109.873265}, author = {Patton, Kristen K and Ellinor, Patrick T and Heckbert, Susan R and Christenson, Robert H and DeFilippi, Christopher and Gottdiener, John S and Kronmal, Richard A} } @article {1131, title = {Obesity and change in estimated GFR among older adults.}, journal = {Am J Kidney Dis}, volume = {54}, year = {2009}, month = {2009 Dec}, pages = {1043-51}, abstract = {

BACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.

PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.

OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.

MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.

RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16\%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95\% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95\% CI, 1.16-1.36) per 12 cm, and 1.14 (95\% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.

LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.

CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.

}, keywords = {Aged, Aging, Body Composition, Body Mass Index, Chronic Disease, Cohort Studies, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Longitudinal Studies, Male, Obesity, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2009.07.018}, author = {de Boer, Ian H and Katz, Ronit and Fried, Linda F and Ix, Joachim H and Luchsinger, Jose and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S and Kestenbaum, Bryan} } @article {1148, title = {Physical activity and rapid decline in kidney function among older adults.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Dec 14}, pages = {2116-23}, abstract = {

BACKGROUND: Habitual physical activity (PA) has both physiologic and metabolic effects that may moderate the risk of kidney function decline. We tested the hypothesis that higher levels of PA are associated with a lower risk of kidney function decline using longitudinal data from a large cohort of older adults.

METHODS: We studied 4011 ambulatory participants aged 65 or older from the Cardiovascular Health Study (CHS) who completed at least 2 measurements of kidney function over 7 years. We calculated a PA score (range, 2-8) by summing kilocalories expended per week (ordinal score of 1-5 from quintiles of kilocalories per week) and walking pace (ordinal score for categories of <2, 2-3, and >3 mph). Rapid decline in kidney function decline (RDKF) was defined by loss of more than 3.0 mL/min/1.73 m(2) per year in glomerular filtration rate, which we estimated by using longitudinal measurements of cystatin C levels.

RESULTS: A total of 958 participants had RDKF (23.9\%; 4.1 events per 100 person-years). The estimated risk of RDKF was 16\% in the highest PA group (score of 8) and 30\% in the lowest PA group (score of 2). After multivariate adjustment, we found that the 2 highest PA groups (scores of 7-8) were associated with a 28\% lower risk of RDKF (95\% confidence interval, 21\%-41\% lower risk) than the 2 lowest PA groups (score of 2-3). Greater kilocalories of leisure-time PA and walking pace were also each associated with a lower incidence of RDKF.

CONCLUSION: Higher levels of PA are associated with a lower risk of RDKF among older adults.

}, keywords = {Aged, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Motor Activity, Renal Insufficiency, Time Factors}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.438}, author = {Robinson-Cohen, Cassianne and Katz, Ronit and Mozaffarian, Dariush and Dalrymple, Lorien S and de Boer, Ian and Sarnak, Mark and Shlipak, Mike and Siscovick, David and Kestenbaum, Bryan} } @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 {1102, title = {Spousal suffering and partner{\textquoteright}s depression and cardiovascular disease: the Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Mar}, pages = {246-54}, abstract = {

OBJECTIVES: To assess the effects of suffering in a spouse on prevalent and incident psychiatric (depression) and physical morbidity (cardiovascular disease [CVD]) in their partner, controlling for known risk factors for depression and CVD.

DESIGN: Descriptive longitudinal study.

PARTICIPANTS: A total of 1,330 older married couples enrolled in the Cardiovascular Health Study, a large epidemiologic study of the elderly.

MEASUREMENTS: Predictor variables were physical, psychological, and existential/spiritual indicators of suffering. Primary outcomes were prevalent and incident depression and CVD.

RESULTS: Controlling for known risk factors for depression, the authors found a dose-response relationship between suffering in a spouse and concurrent depression in their partner as well as a relationship between suffering and the partner{\textquoteright}s future risk for depression. With respect to CVD, and controlling for subclinical CVD at baseline, husbands whose wives reported high levels of suffering also had higher rates of prevalent CVD, but there were no significant associations between wives suffering and husbands incident CVD. There were no associations between husbands{\textquoteright} suffering and wives{\textquoteright} prevalent or incident CVD.

CONCLUSION: Exposure to spousal suffering is an independent and unique source of distress in married couples that contributes to psychiatric and physical morbidity. More attention should be paid to the interpersonal effects of suffering in married couples and to its role in contributing to morbidity.

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Caregivers, Depression, Female, Follow-Up Studies, Humans, Incidence, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Socioeconomic Factors, Spouses, Stress, Psychological, Surveys and Questionnaires}, issn = {1545-7214}, doi = {10.1097/JGP.0b013e318198775b}, author = {Schulz, Richard and Beach, Scott R and Hebert, Randy S and Martire, Lynn M and Monin, Joan K and Tompkins, Connie A and Albert, Steven M} } @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 {1096, title = {Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure.}, journal = {Am J Cardiol}, volume = {103}, year = {2009}, month = {2009 May 01}, pages = {1269-74}, abstract = {

Increased systemic myeloperoxidase (MPO) has been associated with both the presence and severity of heart failure (HF). This study tested the hypothesis that increased systemic MPO in apparently healthy elderly subjects may predict increased risk of developing HF. Systemic MPO was measured in all available samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS). After excluding subjects without available blood samples or with a history of prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were included. A total of 569 subjects developed incident HF during 7.2 +/- 2.3 years of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher risk of developing incident HF after adjusting for MI, age, gender, systolic blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus, and any subclinical cardiovascular disease (hazard ratio 1.34, 95\% confidence interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after censoring subjects with incident MI before incident HF, even when adjusted for C-reactive protein and cystatin C (hazard ratio 1.46, 95\% confidence interval 1.08 to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation between increased MPO and HF risk was stronger in subjects without traditional cardiovascular risk factors (}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Disease Progression, Female, Geriatric Assessment, Heart Failure, Humans, Longitudinal Studies, Male, Peroxidase, Predictive Value of Tests, Probability, Prognosis, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Sex Factors}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2009.01.026}, author = {Tang, W H Wilson and Katz, Ronit and Brennan, Marie-Luise and Aviles, Ronnier J and Tracy, Russell P and Psaty, Bruce M and Hazen, Stanley L} } @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 {1228, title = {Albuminuria and the risk of incident stroke and stroke types in older adults.}, journal = {Neurology}, volume = {75}, year = {2010}, month = {2010 Oct 12}, pages = {1343-50}, abstract = {

BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate.

METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006.

RESULTS: A total of 390 participants had an incident stroke: 81\% ischemic, 12\% hemorrhagic, and 7\% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95\% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95\% CI 0.91-1.84) and for cystatin C was 1.22 (95\% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories.

CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Community Health Services, Confidence Intervals, Female, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Longitudinal Studies, Male, Proportional Hazards Models, Retrospective Studies, Risk Factors, Stroke}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181f73638}, author = {Aguilar, M I and O{\textquoteright}Meara, E S and Seliger, S and Longstreth, W T and Hart, R G and Pergola, P E and Shlipak, M G and Katz, R and Sarnak, M J and Rifkin, D E} } @article {1190, title = {Association between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.}, journal = {Nephron Clin Pract}, volume = {115}, year = {2010}, month = {2010}, pages = {c114-21}, abstract = {

BACKGROUND: In cross-sectional analyses, C-reactive protein (CRP) levels are inversely related to levels of kidney function. The relationship between kidney function and subsequent changes in CRP is unknown.

METHODS: We studied 4,364 individuals from the Cardiovascular Health Study, a longitudinal cohort of community-dwelling older adults. Baseline eGFRcys was estimated using cystatin C. CRP was measured at baseline and after 3 and 7 years of follow-up; slopes of change in CRP were calculated.

RESULTS: The mean (SD) age of the cohort was 72 (5.2) years; mean (SD) eGFRcys was 78.9 (18.4) ml/min/1.73 m(2). The median (interquartile range IQR) baseline CRP was 2.39 (1.22, 4.33) mg/l; the median (IQR) yearly change in CRP was -0.0051 (-0.020 to 0.27) mg/l/year. After adjustment for demographic characteristics and the initial level of CRP, each standard deviation lower baseline eGFR was associated with a small and non-significant yearly increase in CRP (0.032 mg/l/year; 95\% CI: -0.005 to 0.070, p = 0.094).

CONCLUSIONS: We did not find a relationship between eGFR and subsequent changes in CRP. The association between kidney function and CRP in cross-sectional analyses may reflect unmeasured confounding by atherosclerosis; alternatively, the burden of comorbidity and interval mortality in this population may have masked a stronger longitudinal association between kidney function and change in CRP. Further study in younger populations may clarify whether impaired kidney function leads to change in inflammation over time.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Residence Characteristics}, issn = {1660-2110}, doi = {10.1159/000312874}, author = {Rifkin, Dena E and Katz, Ronit and Fried, Linda F and Kestenbaum, Bryan and Jenny, Nancy Swords and Newman, Anne B and Siscovick, David S and Shlipak, Michael G and Sarnak, Mark J} } @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 {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 {1201, title = {Health benefits of increased walking for sedentary, generally healthy older adults: using longitudinal data to approximate an intervention trial.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Sep}, pages = {982-9}, abstract = {

BACKGROUND: Older adults are often advised to walk more, but randomized trials have not conclusively established the benefits of walking in this age group. Typical analyses based on observational data may have biased results. Here, we propose a "limited-bias," more interpretable estimate of the health benefits to sedentary healthy older adults of walking more, using longitudinal data from the Cardiovascular Health Study.

METHODS: The number of city blocks walked per week, collected annually, was classified as sedentary (<7 blocks per week), somewhat active, or active (>or=28). Analysis was restricted to persons sedentary and healthy in the first 2 years. In Year 3, some became more active (the treatment groups). Self-rated health at Year 5 (follow-up) was regressed on walking at Year 3, with additional covariates from Year 2, when all were sedentary.

RESULTS: At follow-up, 83.5\% of those active at baseline had excellent, very good, or good self-rated health, as compared with 63.9\% of the sedentary, an apparent benefit of 19.6 percentage points. After covariate adjustment, the limited-bias estimate of the benefit was 11.2 percentage points (95\% confidence interval 3.7-18.6). Ten different outcome measures showed a benefit, ranging from 5 to 11 percentage points. Estimates from other study designs were smaller, less interpretable, and potentially more biased.

CONCLUSIONS: In longitudinal studies where walking and health are ascertained at every wave, limited-bias estimates can provide better estimates of the benefits of walking. A surprisingly small increase in walking was associated with meaningful health benefits.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Data Interpretation, Statistical, Female, Health Status, Health Surveys, Humans, Longitudinal Studies, Male, Regression Analysis, Sedentary Lifestyle, Walking}, issn = {1758-535X}, doi = {10.1093/gerona/glq070}, author = {Diehr, Paula and Hirsch, Calvin} } @article {1127, title = {Inflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Jan}, pages = {119-24}, abstract = {

BACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline.

METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin.

RESULTS: During the study, 1059 subjects (26\%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95\% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95\% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen.

CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-6, Kidney, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Serum Albumin}, issn = {1460-2385}, doi = {10.1093/ndt/gfp429}, author = {Keller, Christopher and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Kestenbaum, Bryan and Cushman, Mary and Shlipak, Michael G} } @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 {1208, title = {Obesity is linked with lower brain volume in 700 AD and MCI patients.}, journal = {Neurobiol Aging}, volume = {31}, year = {2010}, month = {2010 Aug}, pages = {1326-39}, abstract = {

Obesity is associated with lower brain volumes in cognitively normal elderly subjects, but no study has yet investigated the effects of obesity on brain structure in patients with mild cognitive impairment (MCI) or Alzheimer{\textquoteright}s disease (AD). To determine if higher body mass index (BMI) is associated with brain volume deficits in cognitively impaired elderly subjects, we analyzed brain magnetic resonance imaging (MRI) scans of 700 MCI or AD patients from 2 different cohorts: the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) and the Cardiovascular Health Study-Cognition Study (CHS-CS). Tensor-based morphometry (TBM) was used to create 3-dimensional maps of regional tissue excess or deficits in subjects with MCI (ADNI, n = 399; CHS-CS, n = 77) and AD (ADNI, n = 188; CHS, n = 36). In both AD and MCI groups, higher body mass index was associated with brain volume deficits in frontal, temporal, parietal, and occipital lobes; the atrophic pattern was consistent in both ADNI and CHS populations. Cardiovascular risk factors, especially obesity, should be considered as influencing brain structure in those already afflicted by cognitive impairment and dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Body Mass Index, Brain, Cognition Disorders, Cohort Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Obesity, Organ Size, Prospective Studies, Risk Factors}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2010.04.006}, author = {Ho, April J and Raji, Cyrus A and Becker, James T and Lopez, Oscar L and Kuller, Lewis H and Hua, Xue and Lee, Suh and Hibar, Derrek and Dinov, Ivo D and Stein, Jason L and Jack, Clifford R and Weiner, Michael W and Toga, Arthur W and Thompson, Paul M} } @article {1181, title = {Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.}, journal = {Am J Respir Crit Care Med}, volume = {182}, year = {2010}, month = {2010 Jul 15}, pages = {269-77}, abstract = {

RATIONALE: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.

OBJECTIVES: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.

METHODS: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke.

MEASUREMENTS AND MAIN RESULTS: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95\% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6\% (95\% confidence interval, 2-10\%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.

CONCLUSIONS: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

}, keywords = {Aged, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polysomnography, Proportional Hazards Models, Prospective Studies, Severity of Illness Index, Sex Factors, Sleep Apnea, Obstructive, Stroke}, issn = {1535-4970}, doi = {10.1164/rccm.200911-1746OC}, author = {Redline, Susan and Yenokyan, Gayane and Gottlieb, Daniel J and Shahar, Eyal and O{\textquoteright}Connor, George T and Resnick, Helaine E and Diener-West, Marie and Sanders, Mark H and Wolf, Philip A and Geraghty, Estella M and Ali, Tauqeer and Lebowitz, Michael and Punjabi, Naresh M} } @article {1239, title = {Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {75}, year = {2010}, month = {2010 Oct 19}, pages = {1415-22}, abstract = {

OBJECTIVES: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation.

METHODS: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline.

RESULTS: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold.

CONCLUSION: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.

}, keywords = {Aged, Aged, 80 and over, Brain, Brain Mapping, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Motor Activity, Neuropsychological Tests, Odds Ratio, Predictive Value of Tests, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181f88359}, author = {Erickson, K I and Raji, C A and Lopez, O L and Becker, J T and Rosano, C and Newman, A B and Gach, H M and Thompson, P M and Ho, A J and Kuller, L H} } @article {1180, title = {Prevalence, incidence, and persistence of major depressive symptoms in the Cardiovascular Health Study.}, journal = {Aging Ment Health}, volume = {14}, year = {2010}, month = {2010 Mar}, pages = {168-76}, abstract = {

PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults.

DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated.

RESULTS: The prevalence of a major depressive state was higher in women, and increased with advancing age. The probability of becoming depressed increased with advancing age among the healthy but not the sick. Women showed a greater probability than men of becoming depressed, regardless of health status. Major depressive symptoms persisted over one-year intervals in about 60\% of the healthy and 75\% of the sick, with little difference between men and women.

IMPLICATIONS: Clinically significant depressive symptoms occur commonly in older adults, especially women, increase with advancing age, are associated with poor self-rated health, and are largely intransigent. In order to limit the deleterious consequences of depression among older adults, increased attention to prevention, screening, and treatment is warranted. A self-rated health item could be used in clinical settings to refine the prognosis of late-life depression.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cohort Studies, Depression, Depressive Disorder, Major, Female, Geriatric Assessment, Health Status, Humans, Incidence, Longitudinal Studies, Male, Personality Assessment, Prevalence, Psychiatric Status Rating Scales, Quality of Life, Sex Factors, Surveys and Questionnaires}, issn = {1364-6915}, doi = {10.1080/13607860903046537}, author = {Thielke, Stephen M and Diehr, Paula and Unutzer, Jurgen} } @article {1215, title = {Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study.}, journal = {Circulation}, volume = {122}, year = {2010}, month = {2010 Jul 27}, pages = {352-60}, abstract = {

BACKGROUND: Clinic-based observational studies in men have reported that obstructive sleep apnea is associated with an increased incidence of coronary heart disease. The objective of this study was to assess the relation of obstructive sleep apnea to incident coronary heart disease and heart failure in a general community sample of adult men and women.

METHODS AND RESULTS: A total of 1927 men and 2495 women > or =40 years of age and free of coronary heart disease and heart failure at the time of baseline polysomnography were followed up for a median of 8.7 years in this prospective longitudinal epidemiological study. After adjustment for multiple risk factors, obstructive sleep apnea was a significant predictor of incident coronary heart disease (myocardial infarction, revascularization procedure, or coronary heart disease death) only in men < or =70 years of age (adjusted hazard ratio 1.10 [95\% confidence interval 1.00 to 1.21] per 10-unit increase in apnea-hypopnea index [AHI]) but not in older men or in women of any age. Among men 40 to 70 years old, those with AHI > or =30 were 68\% more likely to develop coronary heart disease than those with AHI <5. Obstructive sleep apnea predicted incident heart failure in men but not in women (adjusted hazard ratio 1.13 [95\% confidence interval 1.02 to 1.26] per 10-unit increase in AHI). Men with AHI > or =30 were 58\% more likely to develop heart failure than those with AHI <5.

CONCLUSIONS: Obstructive sleep apnea is associated with an increased risk of incident heart failure in community-dwelling middle-aged and older men; its association with incident coronary heart disease in this sample is equivocal.

}, keywords = {Adult, Aged, Coronary Disease, Female, Heart Failure, Humans, Longitudinal Studies, Male, Middle Aged, Polysomnography, Proportional Hazards Models, Prospective Studies, Sleep Apnea, Obstructive, Survival Analysis}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.109.901801}, author = {Gottlieb, Daniel J and Yenokyan, Gayane and Newman, Anne B and O{\textquoteright}Connor, George T and Punjabi, Naresh M and Quan, Stuart F and Redline, Susan and Resnick, Helaine E and Tong, Elisa K and Diener-West, Marie and Shahar, Eyal} } @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 {1348, title = {Antihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis.}, journal = {Int J Biostat}, volume = {7}, year = {2011}, month = {2011}, pages = {Article 34}, abstract = {

BACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.

METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.

RESULTS: The mean annual decline in eGFR was 2.41 {\textpm} 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.

CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.

}, keywords = {Aged, Antihypertensive Agents, Cystatin C, Data Interpretation, Statistical, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney, Longitudinal Studies, Male, Models, Statistical}, issn = {1557-4679}, doi = {10.2202/1557-4679.1320}, author = {Odden, Michelle C and Tager, Ira B and van der Laan, Mark J and Delaney, Joseph A C and Peralta, Carmen A and Katz, Ronit and Sarnak, Mark J and Psaty, Bruce M and Shlipak, Michael G} } @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 {1230, title = {Chronic kidney disease and the risk of end-stage renal disease versus death.}, journal = {J Gen Intern Med}, volume = {26}, year = {2011}, month = {2011 Apr}, pages = {379-85}, abstract = {

BACKGROUND: Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown.

OBJECTIVE: To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants.

DESIGN: The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older.

PARTICIPANTS: 1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2) were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003.

MAIN MEASURES: The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol.

KEY RESULTS: During 9.7 years of follow-up, 5\% of the cohort progressed to ESRD, and 61\% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD.

CONCLUSIONS: Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic, Longitudinal Studies, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Treatment Outcome}, issn = {1525-1497}, doi = {10.1007/s11606-010-1511-x}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and Shlipak, Michael G and Sarnak, Mark J and Stehman-Breen, Catherine and Seliger, Stephen and Siscovick, David and Newman, Anne B and Fried, Linda} } @article {1315, title = {Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study.}, journal = {J Alzheimers Dis}, volume = {27}, year = {2011}, month = {2011}, pages = {553-66}, abstract = {

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Coffee, Cognition Disorders, Cohort Studies, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Prospective Studies, Sex Characteristics, Tea}, issn = {1875-8908}, doi = {10.3233/JAD-2011-110431}, author = {Arab, Lenore and Biggs, Mary L and O{\textquoteright}Meara, Ellen S and Longstreth, W T and Crane, Paul K and Fitzpatrick, Annette L} } @article {1276, title = {High blood pressure accelerates gait slowing in well-functioning older adults over 18-years of follow-up.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Mar}, pages = {390-7}, abstract = {

OBJECTIVES: To examine whether the association between hypertension and decline in gait speed is significant in well-functioning older adults and whether other health-related factors, such as brain, kidney, and heart function, can explain it.

DESIGN: Longitudinal cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Of 2,733 potential participants with a brain magnetic resonance imaging (MRI) scan, measures of mobility and systolic blood pressure (BP), no self-reported disability in 1992 to 1994 (baseline), and with at least 1 follow-up gait speed measurement through 1997 to 1999, 643 (aged 73.6, 57\% female, 15\% black) who had received a second MRI in 1997 to 1999 and an additional gait speed measure in 2005 to 2006 were included.

MEASUREMENTS: Mixed models with random slopes and intercepts were adjusted for age, race, and sex. Main explanatory factors included white matter hyperintensity progression, baseline cystatin-C, and left cardiac ventricular mass. Incidence of stroke and dementia, BP trajectories, and intake of antihypertensive medications during follow-up were tested as other potential explanatory factors.

RESULTS: Higher systolic BP was associated with faster rate of gait speed decline in this selected group of 643 participants, and results were similar in the parent cohort (N = 2,733). Participants with high BP (n = 293) had a significantly faster rate of gait speed decline than those with baseline BP less than 140/90 mmHg and no history of hypertension (n = 350). Rates were similar for those with history of hypertension who were uncontrolled (n = 110) or controlled (n = 87) at baseline and for those who were newly diagnosed (n = 96) at baseline. Adjustment for explanatory factors or for other covariates (education, prevalent cardiovascular disease, physical activity, vision, mood, cognition, muscle strength, body mass index, osteoporosis) did not change the results.

CONCLUSION: High BP accelerates gait slowing in well-functioning older adults over a long period of time, even for those who control their BP or develop hypertension later in life. Health-related measurements did not explain these associations. Future studies to investigate the mechanisms linking hypertension to slowing gait in older adults are warranted.

}, keywords = {Aged, Antihypertensive Agents, Comorbidity, Female, Follow-Up Studies, Gait, Geriatric Assessment, Humans, Hypertension, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Statistics, Nonparametric}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03282.x}, author = {Rosano, Caterina and Longstreth, William T and Boudreau, Robert and Taylor, Christopher A and Du, Yan and Kuller, Lewis H and Newman, Anne B} } @article {1269, title = {Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {123}, year = {2011}, month = {2011 Mar 01}, pages = {858-65}, abstract = {

BACKGROUND: Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.

METHODS AND RESULTS: -Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58\% women, 17\% blacks, 68\% hypertension, 3600 had brain magnetic resonance imaging in 1992-1993, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11\%) subjects had concurrent impairments and 3086 (66\%) were intact on all 3 measures. Between 1992 and 1999, 651 (21\%) became impaired in all 3 domains. Hypertensive individuals were more likely to be impaired at baseline (odds ratio 1.23, 95\% confidence interval 1.04 to 1.42, P=0.01) and become impaired during the follow-up (hazard ratio=1.3, 95\% confidence interval 1.02 to 1.66, P=0.037). A greater degree of white matter hyperintensities was associated with impairments in the 3 domains (P=0.007) and mediated the association with hypertension (P=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21\% hazard ratio change). Impairments in the 3 domains increased subsequent disability with hypertension (P<0.0001). Hypertension mortality also was increased in those impaired (compared with unimpaired hypertensive individuals: HR=1.10, 95\% confidence interval 1.04 to 1.17, P=0.004).

CONCLUSIONS: Hypertension increases the risk of concurrent impairments in mobility, cognition, and mood, which increases disability and mortality. This association is mediated in part by microvascular brain injury.

}, keywords = {Aged, Aged, 80 and over, Brain, Cognition Disorders, Female, Humans, Hypertension, Kaplan-Meier Estimate, Longitudinal Studies, Magnetic Resonance Imaging, Male, Microcirculation, Mobility Limitation, Mood Disorders, Nerve Fibers, Myelinated, Retrospective Studies, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.978114}, author = {Hajjar, Ihab and Quach, Lien and Yang, Frances and Chaves, Paulo H M and Newman, Anne B and Mukamal, Kenneth and Longstreth, Will and Inzitari, Marco and Lipsitz, Lewis A} } @article {1265, title = {Leukocyte telomere length and mortality in the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Apr}, pages = {421-9}, abstract = {

BACKGROUND: Leukocyte telomere length (LTL) is related to diseases of aging, but studies of mortality have been inconsistent.

METHODS: We evaluated LTL in relation to total mortality and specific cause of death in 1,136 participants of the Cardiovascular Health Study who provided blood samples in 1992-1993 and survived through 1997-1998. LTL was measured by Southern blots of the terminal restriction fragments. Cause of death was classified by a committee of physicians reviewing death certificates, medical records, and informant interviews.

RESULTS: A total of 468 (41.2\%) deaths occurred over 6.1 years of follow-up in participants with mean age of 73.9 years (SD 4.7), 65.4\% female, and 14.8\% African American. Although increased age and male gender were associated with shorter LTLs, African Americans had significantly longer LTLs independent of age and sex (p < .001). Adjusted for age, sex, and race, persons with the shortest quartile of LTL were 60\% more likely to die during follow-up than those within the longest quartile (hazard ratio: 1.61, 95\% confidence interval: 1.22-2.12, p = .001). The association remained after adjustment for cardiovascular disease risk factors. Evaluations of cause of death found LTL to be related to deaths due to an infectious disease etiology (hazard ratio: 2.80, 95\% confidence interval: 1.32-5.94, p = .007), whereas a borderline association was found for cardiac deaths (hazard ratio: 1.82, 95\% confidence interval: 0.95-3.49, p = .07) in adjusted models. Risk estimates for deaths due to cancer, dementia, and ischemic stroke were not significant.

CONCLUSION: These data weakly corroborate prior findings of associations between LTL and mortality in the elderly.

}, keywords = {Aged, Aged, 80 and over, Aging, Body Mass Index, Cardiovascular Diseases, Cause of Death, Comorbidity, Coronary Disease, Diabetes Mellitus, Female, Humans, Hypertension, Leukocytes, Longitudinal Studies, Male, Prospective Studies, Smoking, Stroke, Telomere}, issn = {1758-535X}, doi = {10.1093/gerona/glq224}, author = {Fitzpatrick, Annette L and Kronmal, Richard A and Kimura, Masayuki and Gardner, Jeffrey P and Psaty, Bruce M and Jenny, Nancy S and Tracy, Russell P and Hardikar, Sheetal and Aviv, Abraham} } @article {1277, title = {Longitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Apr}, pages = {834-44}, abstract = {

BACKGROUND AND OBJECTIVES: Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (>=8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.

RESULTS: Depressed participants (21.2\%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.

CONCLUSIONS: Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

}, keywords = {Acute Kidney Injury, Aged, Chronic Disease, Cohort Studies, Comorbidity, Depression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Longitudinal Studies, Male}, issn = {1555-905X}, doi = {10.2215/CJN.03840510}, author = {Kop, Willem J and Seliger, Stephen L and Fink, Jeffrey C and Katz, Ronit and Odden, Michelle C and Fried, Linda F and Rifkin, Dena E and Sarnak, Mark J and Gottdiener, John S} } @article {1332, title = {Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Dec}, pages = {3363-8}, abstract = {

BACKGROUND AND PURPOSE: Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations.

METHODS: We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages>=65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors.

RESULTS: Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95\% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke.

CONCLUSIONS: Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

}, keywords = {Aged, Aged, 80 and over, Brain Ischemia, Female, Health Status Disparities, Humans, Incidence, Longitudinal Studies, Male, Poverty, Residence Characteristics, Risk, Risk Factors, Social Class, Social Environment, Socioeconomic Factors, Stroke, Urban Population}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.622134}, author = {Brown, Arleen F and Liang, Li-Jung and Vassar, Stefanie D and Stein-Merkin, Sharon and Longstreth, W T and Ovbiagele, Bruce and Yan, Tingjian and Escarce, Jos{\'e} J} } @article {1310, title = {Progression of magnetic resonance imaging-defined brain vascular disease predicts vascular events in elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Oct}, pages = {2970-2}, abstract = {

BACKGROUND AND PURPOSE: To determine whether progression of MRI-defined vascular disease predicts subsequent vascular events in the elderly.

METHODS: The Cardiovascular Health Study, a longitudinal cohort study of vascular disease in the elderly, allows us to address this question because its participants had 2 MRI scans≈5 years apart and have been followed for ≈9 years since the follow-up scan for incident vascular events.

RESULTS: Both MRI-defined incident infarcts and worsened white matter grade were significantly associated with heart failure, stroke, and death, but not transient ischemic attacks, angina, or myocardial infarction. Strongest associations occurred when both incident infarcts and worsened white matter grade were present for heart failure (hazard ratio, 1.79; 95\% confidence interval, 1.18-2.73), stroke (hazard ratio, 2.58; 95\% confidence interval, 1.53-4.36), death (hazard ratio, 1.69; 95\% confidence interval, 1.28-2.24), and cardiovascular death (hazard ratio, 1.97; 95\% confidence interval, 1.24-3.14).

CONCLUSIONS: Progression of MRI-defined vascular disease identifies elderly people at increased risk for subsequent heart failure, stroke, and death. Whether aggressive risk factor management would reduce risk is unknown.

}, keywords = {Aged, Brain, Disease Progression, Female, Follow-Up Studies, Heart Failure, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Predictive Value of Tests, Prognosis, Stroke}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.622977}, author = {Longstreth, W T and Arnold, Alice M and Kuller, Lewis H and Bernick, Charles and Lefkowitz, David S and Beauchamp, Norman J and Manolio, Teri A} } @article {1317, title = {Risk factors for onset of disability among older persons newly diagnosed with heart failure: the Cardiovascular Health Study.}, journal = {J Card Fail}, volume = {17}, year = {2011}, month = {2011 Sep}, pages = {764-70}, abstract = {

BACKGROUND: As the heart failure population continues to age, disability is becoming an increasingly important issue. Our objective was to identify risk factors for the onset of disability in activities of daily living among older persons with heart failure.

METHODS: The study population included participants with newly diagnosed heart failure from the Cardiovascular Health Study, a longitudinal study of community-living, older persons. Data were collected through annual examinations. Cox regression modeling was used to examine associations between time-dependent predictors and onset of disability.

RESULTS: Of 461 participants newly diagnosed with heart failure (mean age 78.7 [SD 5.89]), 23\% subsequently developed disability. The first year after heart failure diagnosis was the period of greatest risk for onset of disability (chi-square P value <.001). Factors that were independently associated with disability included: impaired gait speed (HR 2.29, 95\% CI 1.34-3.90); impaired cognition (HR 1.87, 95\% CI 1.14-3.05); and depressive symptoms (HR 1.72, 95\% CI 1.04-2.83).

CONCLUSIONS: Onset of disability is a common occurrence among older persons newly diagnosed with heart failure. Risk factors for onset of disability in this population are potentially modifiable, and should be routinely assessed in an effort to reduce disability in this growing population.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Disability Evaluation, Disabled Persons, Female, Health Status, Heart Failure, Humans, Longitudinal Studies, Male, Risk Factors}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2011.04.015}, author = {Chaudhry, Sarwat I and McAvay, Gail and Ning, Yuming and Allore, Heather G and Newman, Anne B and Gill, Thomas M} } @article {1227, title = {Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study.}, journal = {Am J Geriatr Psychiatry}, volume = {19}, year = {2011}, month = {2011 Feb}, pages = {160-8}, abstract = {

OBJECTIVE: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI).

DESIGN: : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data.

SETTING: Community.

PARTICIPANTS: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping.

MEASUREMENTS: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status.

RESULTS: : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis.

CONCLUSIONS: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.

}, keywords = {Aged, Alzheimer Disease, Chi-Square Distribution, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotic Disorders, Time Factors}, issn = {1545-7214}, doi = {10.1097/JGP.0b013e3181e446c8}, author = {Emanuel, James E and Lopez, Oscar L and Houck, Patricia R and Becker, James T and Weamer, Elise A and Demichele-Sweet, Mary Ann A and Kuller, Lewis and Sweet, Robert A} } @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 {1389, title = {Cardiac microinjury measured by troponin T predicts collagen metabolism in adults aged >=65 years with heart failure.}, journal = {Circ Heart Fail}, volume = {5}, year = {2012}, month = {2012 Jul 01}, pages = {406-13}, abstract = {

BACKGROUND: Repeated myocardial microinjuries lead to collagen deposition and fibrosis, thereby increasing the risk of clinical heart failure. Little is known about the longitudinal association between increases in myocardial injury and the biology of collagen synthesis and deposition.

METHODS AND RESULTS: Repeated measures of highly sensitive cardiac troponin T (cTnT) were obtained in participants of the Cardiovascular Health Study (N=353; mean age, 74{\textpm}6 years; 52\% women) at baseline and at 3 years follow-up. Biomarkers of collagen metabolism were obtained at follow-up and included carboxyterminal propeptide of procollagen type I, carboxyterminal telopeptide of type I collagen, and aminoterminal propeptide of procollagen III. Multivariable linear regression analyses were used to examine the association between baseline cTnT and changes in cTnT with collagen metabolism markers at follow-up adjusting for demographics, heart failure status, and cardiovascular risk factors. Results indicated that cTnT increases over 3-years were significantly associated with higher levels of carboxyterminal telopeptide of type I collagen (β=0.22, P<0.001) and aminoterminal propeptide of procollagen III (β=0.12, P=0.035) at follow-up when adjusting for demographic, clinical, and biochemical covariates including baseline cTnT. These associations were stronger in patients with heart failure than in control subjects. Conclusions- Increases in myocardial microinjury measured by changes in cTnT adversely affect markers of collagen metabolism. These findings are important to the biology of myocardial fibrosis and tissue repair. Serial evaluation of cTnT combined with collagen metabolism markers may further elucidate the pathophysiology of heart failure.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Case-Control Studies, Chi-Square Distribution, Collagen, Collagen Type I, Female, Fibrosis, Heart Failure, Humans, Linear Models, Longitudinal Studies, Male, Multivariate Analysis, Myocardium, Peptide Fragments, Peptides, Predictive Value of Tests, Procollagen, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Troponin T, Up-Regulation}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.111.965327}, author = {Kop, Willem J and Gottdiener, John S and deFilippi, Christopher R and Barasch, Eddy and Seliger, Stephen L and Jenny, Nancy S and Christenson, Robert H} } @article {1391, title = {Cardiovascular physiology in premotor Parkinson{\textquoteright}s disease: a neuroepidemiologic study.}, journal = {Mov Disord}, volume = {27}, year = {2012}, month = {2012 Jul}, pages = {988-95}, abstract = {

Changes in cardiovascular physiology in Parkinson{\textquoteright}s disease (PD) are common and may occur prior to diagnostic parkinsonian motor signs. We investigated associations of electrocardiographic (ECG) abnormalities, orthostasis, heart rate variability, and carotid stenosis with the risk of PD diagnosis in the Cardiovascular Health Study, a community-based cohort of older adults. ECG abnormality, orthostasis (symptomatic or asymptomatic), heart rate variability (24-hour Holter monitoring), and any carotid stenosis (>=1\%) by ultrasound were modeled as primary predictors of incident PD diagnosis using multivariable logistic regression. Incident PD cases were identified by at least 1 of the following: self-report, antiparkinsonian medication use, and ICD-9. If unadjusted models were significant, they were adjusted or stratified by age, sex, and smoking status, and those in which predictors were still significant (P <= .05) were also adjusted for race, diabetes, total cholesterol, low-density lipoprotein, blood pressure, body mass index, physical activity, education level, stroke, and C-reactive protein. Of 5888 participants, 154 incident PD cases were identified over 14 years of follow-up. After adjusting models with all covariates, those with any ECG abnormality (odds ratio [OR], 1.45; 95\% CI, 1.02-2.07; P = .04) or any carotid stenosis (OR, 2.40; 95\% CI, 1.40-4.09; P = .001) at baseline had a higher risk of incident PD diagnosis. Orthostasis and heart rate variability were not significant predictors. This exploratory study suggests that carotid stenosis and ECG abnormalities occur prior to motor signs in PD, thus serving as potential premotor features or risk factors for PD diagnosis. Replication is needed in a population with more thorough ascertainment of PD onset.

}, keywords = {Aged, Antiparkinson Agents, Cardiovascular Physiological Phenomena, Carotid Stenosis, Cohort Studies, Data Interpretation, Statistical, Dizziness, Electrocardiography, Female, Heart Rate, Hospitalization, Humans, Longitudinal Studies, Male, Movement Disorders, Neurologic Examination, Parkinson Disease, Risk, Ultrasonography}, issn = {1531-8257}, doi = {10.1002/mds.24979}, author = {Jain, Samay and Ton, Thanh G and Perera, Subashan and Zheng, Yan and Stein, Phyllis K and Thacker, Evan and Strotmeyer, Elsa S and Newman, Anne B and Longstreth, Will T} } @article {1374, title = {Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 Jun}, pages = {1970-6}, abstract = {

BACKGROUND: The association between changes in IGF-I and IGF binding protein (IGFBP) levels and mortality in older adults is unknown.

STUDY DESIGN: Participants were 997 persons 77 to 100 yr old enrolled in the Cardiovascular Health Study All Stars Study. Plasma levels of IGF-I, IGFBP-1, and IGFBP-3 were assessed at two study examinations (1996-1997 and 2005-2006). Mortality was assessed between 2006 and 2010.

RESULTS: Cumulative mortality (CM) was similar among individuals who had at least 10\% decreases over time in IGF-I levels (CM = 29.6\%), individuals who had at least 10\% increases over time in IGF-I levels (CM = 24.7\%), and individuals who had IGF-I levels remaining within {\textpm}10\% over time (CM = 23.5\%). Adjusted for age, sex, race, diabetes, body mass index, creatinine, albumin, and C-reactive protein, decreasing IGF-I level had no significant association with overall cancer mortality or noncancer mortality. Levels of IGFBP-1 increased markedly over time by 38\% (median). Individuals with the largest increases in IGFBP-1 level over time had significantly increased risk of mortality. The adjusted hazard ratio per sd of IGFBP-1 change was 1.40 for overall cancer mortality (95\% confidence interval = 1.10, 1.77; P = 0.01) and 1.14 for noncancer mortality (95\% confidence interval = 1.02, 1.27; P = 0.02). Changes in IGFBP-3 levels were not significantly associated with mortality.

CONCLUSION: Among older adults, decreasing IGF-I level over time does not predict subsequent all-cause mortality, whereas increasing IGFBP-1 predicts increased risk of mortality.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Cardiovascular Diseases, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Longitudinal Studies, Male, Mortality, Predictive Value of Tests, Risk Factors}, issn = {1945-7197}, doi = {10.1210/jc.2011-2967}, author = {Kaplan, Robert C and B{\r u}zkov{\'a}, Petra and Cappola, Anne R and Strickler, Howard D and McGinn, Aileen P and Mercer, Laina D and Arnold, Alice M and Pollak, Michael N and Newman, Anne B} } @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 {6085, title = {Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project.}, journal = {Circulation}, volume = {125}, year = {2012}, month = {2012 Jan 03}, pages = {37-44}, abstract = {

BACKGROUND: Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke.

METHODS AND RESULTS: Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5\% (95\% confidence interval, 51.3-53.7) for men and 39.9\% (95\% confidence interval, 38.7-41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22\% to 41\%, compared with individuals who had or developed hypertension by 55 years of age, 42\% to 69\%, suggesting a dose-response effect for the length of time at high BP levels.

CONCLUSIONS: Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Humans, Hypertension, Life Tables, Longitudinal Studies, Male, Middle Aged, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.002774}, author = {Allen, Norrina and Berry, Jarett D and Ning, Hongyan and Van Horn, Linda and Dyer, Alan and Lloyd-Jones, Donald M} } @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 {1404, title = {Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 Nov}, pages = {3944-50}, abstract = {

CONTEXT: Data on thyroid function in the oldest old are sparse, and existing studies show conflicting evidence on the relationship between thyroid function and mortality in this age group.

OBJECTIVE: We describe longitudinal changes in thyroid function in a cohort of elderly individuals and determine the relationship between thyroid function and mortality.

DESIGN, SETTING, AND PARTICIPANTS: Eight hundred forty-three participants in the Cardiovascular Health Study All Stars Study who were not taking thyroid medications and had thyroid function testing in 2005-2006 (mean age 85 yr).

MAIN OUTCOME MEASURE: Thyroid-stimulating hormone (TSH), free T(4) (FT4), total T(3), and thyroid peroxidase antibody status were measured in 1992-1993 and 2005-2006. Deaths were ascertained through February 2011.

RESULTS: There was a statistically significant 13\% increase in TSH, 1.7\% increase in FT4, and 13\% decrease in total T(3) over the 13-yr period. Two hundred eighty-seven deaths occurred over a median follow-up of 5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio (HR) 0.97, 95\% confidence interval (CI) 0.66-1.43], TSH level (HR per milliunits per liter 0.94, 95\% CI 0.88-1.01), or persistent thyroid peroxidase antibody positivity (HR 1.09, 95\% CI 0.62-1.92), and death. However, FT4 was positively associated with death (HR per nanograms per deciliter 2.57, 95\% CI 1.32-5.02).

CONCLUSIONS: TSH increased over time in these older individuals. This elevation was not associated with increased or decreased mortality, although higher FT4 levels were associated with death. These findings raise concern for treatment of mild elevations of TSH in advanced age. Further studies are needed to determine the potential benefit of treating age-related changes in thyroid function.

}, keywords = {Aged, 80 and over, Female, Humans, Longitudinal Studies, Male, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine}, issn = {1945-7197}, doi = {10.1210/jc.2012-2481}, author = {Waring, Avantika C and Arnold, Alice M and Newman, Anne B and B{\r u}zkov{\'a}, Petra and Hirsch, Calvin and Cappola, Anne R} } @article {1366, title = {Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {67}, year = {2012}, month = {2012 Sep}, pages = {970-6}, abstract = {

BACKGROUND: Associations of inflammation with age-related pathologies are documented; however, it is not understood how changes in inflammation over time impact healthy aging.

METHODS: We examined associations of long-term change in C-reactive protein (CRP) and interleukin-6 (IL-6) with concurrent onset of physical and cognitive impairment, subsequent cardiovascular disease (CVD), and mortality in 1,051 participants in the Cardiovascular Health Study All Stars Study. Biomarkers were measured in 1996-1997 and 2005-2006.

RESULTS: In 2005-2006, median age was 84.9 years, 63\% were women and 17\% non-white; 21\% had at least a doubling in CRP over time and 23\% had at least a doubling in IL-6. Adjusting for demographics, CVD risk factors, and 1996-1997 CRP level, each doubling in CRP change over 9 years was associated with higher risk of physical or cognitive impairment (odds ratio 1.29; 95\% confidence interval 1.15, 1.45). Results were similar for IL-6 (1.45; 1.20, 1.76). A doubling in IL-6 change over time, but not CRP, was associated with incident CVD events; hazard ratio (95\% confidence interval) 1.34 (1.03, 1.75). Doubling in change in each biomarker was individually associated with mortality (CRP: 1.12 [1.03, 1.22]; IL-6 1.39 [1.16, 1.65]). In models containing both change and 2005-2006 level, only level was associated with CVD events and mortality.

CONCLUSIONS: Although increases in inflammation markers over 9 years were associated with higher concurrent risk of functional impairment and subsequent CVD events and mortality, final levels of each biomarker appeared to be more important in determining risk of subsequent events than change over time.

}, keywords = {Aged, Aged, 80 and over, Aging, C-Reactive Protein, Cardiovascular Diseases, Cognition, Cohort Studies, Cross-Sectional Studies, Female, Humans, Inflammation, Inflammation Mediators, Interleukin-6, Longitudinal Studies, Male, Risk Factors, Vermont}, issn = {1758-535X}, doi = {10.1093/gerona/glr261}, author = {Jenny, Nancy S and French, Benjamin and Arnold, Alice M and Strotmeyer, Elsa S and Cushman, Mary and Chaves, Paulo H M and Ding, Jingzhong and Fried, Linda P and Kritchevsky, Stephen B and Rifkin, Dena E and Sarnak, Mark J and Newman, Anne B} } @article {1373, title = {The natural history of subclinical hypothyroidism in the elderly: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 Jun}, pages = {1962-9}, abstract = {

CONTEXT: Studies of long-term outcomes of subclinical hypothyroidism have assessed only baseline thyroid function, despite natural transitions to euthyroidism and overt hypothyroidism over time.

OBJECTIVE: We provide estimates of persistence, resolution, and progression of subclinical hypothyroidism over 4 yr, stratified by baseline TSH, anti-thyroid peroxidase antibody (TPOAb) status, age, and sex.

DESIGN, SETTING, AND PARTICIPANTS: Participants were 3996 U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study. Subclinical hypothyroidism was detected at baseline in 459 individuals not taking thyroid medication.

MAIN OUTCOME MEASURE: Thyroid function was evaluated at 2 and 4 yr and initiation of thyroid medication annually. Results were stratified by baseline TSH, TPOAb status, age, and sex.

RESULTS: Persistence of subclinical hypothyroidism was 56\% at 2 and 4 yr. At 2 yr, resolution was more common with a TSH of 4.5-6.9 mU/liter (46 vs. 10\% with TSH 7-9.9 mU/liter and 7\% with TSH >=10 mU/liter; P < 0.001) and with TPOAb negativity (48 vs. 15\% for positive; P < 0.001). Higher TSH and TPOAb positivity were independently associated with lower likelihood of reversion to euthyroidism (P < 0.05). TSH of 10 mU/liter or higher was independently associated with progression to overt hypothyroidism (P < 0.05). Transitions between euthyroidism and subclinical hypothyroidism were common between 2 and 4 yr. Age and sex did not affect transitions.

CONCLUSIONS: Subclinical hypothyroidism persists for 4 yr in just over half of older individuals, with high rates of reversion to euthyroidism in individuals with lower TSH concentrations and TPOAb negativity. Future studies should examine the impact of transitions in thyroid status on clinical outcomes.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Autoantibodies, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Humans, Hypothyroidism, Iodide Peroxidase, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Seroepidemiologic Studies, Severity of Illness Index, Sex Distribution, Thyrotropin}, issn = {1945-7197}, doi = {10.1210/jc.2011-3047}, author = {Somwaru, Lily L and Rariy, Chevon M and Arnold, Alice M and Cappola, Anne R} } @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 {1390, title = {Racial differences in risks for first cardiovascular events and noncardiovascular death: the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, and the Multi-Ethnic Study of Atherosclerosis.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Jul 03}, pages = {50-9}, abstract = {

BACKGROUND: No studies have compared first cardiovascular disease (CVD) events and non-CVD death between races in a competing risks framework, which examines risks for numerous events simultaneously.

METHODS AND RESULTS: We used competing Cox models to estimate hazards for first CVD events and non-CVD death within and between races in 3 multicenter, National Heart, Lung, and Blood Institute-sponsored cohorts. Of 14 569 Atherosclerosis Risk in Communities (ARIC) study participants aged 45 to 64 years with mean follow-up of 10.5 years, 11.6\% had CVD and 5.0\% had non-CVD death as first events; among 4237 Cardiovascular Health Study (CHS) study participants aged 65 to 84 years and followed for 8.5 years, these figures were 43.2\% and 15.7\%, respectively. Middle-aged blacks were significantly more likely than whites to experience any CVD as a first event; this disparity disappeared by older adulthood and after adjustment for CVD risk factors. The pattern of results was similar for Multi-Ethnic Study of Atherosclerosis (MESA) participants. Traditional Cox and competing risks models yielded different results for coronary heart disease risk. Black men appeared somewhat more likely than white men to experience coronary heart disease with use of a standard Cox model (hazard ratio 1.06; 95\% CI 0.90, 1.26), whereas they appeared less likely than white men to have a first coronary heart disease event with use of a competing risks model (hazard ratio, 0.77; 95\% CI, 0.60, 1.00).

CONCLUSIONS: CVD affects blacks at an earlier age than whites; this may be attributable in part to elevated CVD risk factor levels among blacks. Racial disparities in first CVD incidence disappear by older adulthood. Competing risks analyses may yield somewhat different results than traditional Cox models and provide a complementary approach to examining risks for first CVD events.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Atherosclerosis, Cardiovascular Diseases, Cohort Studies, Continental Population Groups, Ethnic Groups, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Residence Characteristics, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.111.057232}, author = {Feinstein, Matthew and Ning, Hongyan and Kang, Joseph and Bertoni, Alain and Carnethon, Mercedes and Lloyd-Jones, Donald M} } @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 {1333, title = {White matter lesions and brain gray matter volume in cognitively normal elders.}, journal = {Neurobiol Aging}, volume = {33}, year = {2012}, month = {2012 Apr}, pages = {834.e7-16}, abstract = {

Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals, and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software. WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age-related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores. Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.

}, keywords = {Aged, Aged, 80 and over, Aging, Apolipoprotein E4, Brain, Cognition Disorders, Female, Humans, Imaging, Three-Dimensional, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory Disorders, Mental Status Schedule, Neuropsychological Tests, Regression Analysis, Retrospective Studies}, issn = {1558-1497}, doi = {10.1016/j.neurobiolaging.2011.08.010}, author = {Raji, Cyrus A and Lopez, Oscar L and Kuller, Lewis H and Carmichael, Owen T and Longstreth, William T and Gach, H Michael and Boardman, John and Bernick, Charles B and Thompson, Paul M and Becker, James T} } @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 {6002, title = {Atrial fibrillation and cognitive decline: a longitudinal cohort study.}, journal = {Neurology}, volume = {81}, year = {2013}, month = {2013 Jul 09}, pages = {119-25}, abstract = {

OBJECTIVE: We sought to determine whether in the absence of clinical stroke, people with atrial fibrillation experience faster cognitive decline than people without atrial fibrillation.

METHODS: We conducted a longitudinal analysis in the Cardiovascular Health Study, a community-based study of 5,888 men and women aged 65 years and older, enrolled in 1989/1990 or 1992/1993. Participants did not have atrial fibrillation or a history of stroke at baseline. Participants were censored when they experienced incident clinical stroke. Incident atrial fibrillation was identified by hospital discharge diagnosis codes and annual study ECGs. The main outcome was rate of decline in mean scores on the 100-point Modified Mini-Mental State Examination (3MSE), administered annually up to 9 times.

RESULTS: Analyses included 5,150 participants, of whom 552 (10.7\%) developed incident atrial fibrillation during a mean of 7 years of follow-up. Mean 3MSE scores declined faster after incident atrial fibrillation compared with no prior atrial fibrillation. For example, the predicted 5-year decline in mean 3MSE score from age 80 to age 85 was -6.4 points (95\% confidence interval [CI]: -7.0, -5.9) for participants without a history of atrial fibrillation, but was -10.3 points (95\% CI: -11.8, -8.9) for participants experiencing incident atrial fibrillation at age 80, a 5-year difference of -3.9 points (95\% CI: -5.3, -2.5).

CONCLUSIONS: In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Luria-Nebraska Neuropsychological Battery, Male, Predictive Value of Tests}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31829a33d1}, author = {Thacker, Evan L and McKnight, Barbara and Psaty, Bruce M and Longstreth, W T and Sitlani, Colleen M and Dublin, Sascha and Arnold, Alice M and Fitzpatrick, Annette L and Gottesman, Rebecca F and Heckbert, Susan R} } @article {6285, title = {Bidirectional relationship between cognitive function and pneumonia.}, journal = {Am J Respir Crit Care Med}, volume = {188}, year = {2013}, month = {2013 Sep 01}, pages = {586-92}, abstract = {

RATIONALE: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems.

OBJECTIVES: To determine bidirectional relationships between cognition and pneumonia.

METHODS: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate.

MEASUREMENTS AND MAIN RESULTS: Of the 5,888 participants, 639 (10.9\%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1\%, 22.8\%, and 10.0\% vs. 76.0\%, 19.3\%, and 4.6\% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95\% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections.

CONCLUSIONS: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence.

}, keywords = {Aged, Cognition Disorders, Dementia, Female, Hospitalization, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Pneumonia, Proportional Hazards Models, Risk Factors}, issn = {1535-4970}, doi = {10.1164/rccm.201212-2154OC}, author = {Shah, Faraaz Ali and Pike, Francis and Alvarez, Karina and Angus, Derek and Newman, Anne B and Lopez, Oscar and Tate, Judith and Kapur, Vishesh and Wilsdon, Anthony and Krishnan, Jerry A and Hansel, Nadia and Au, David and Avdalovic, Mark and Fan, Vincent S and Barr, R Graham and Yende, Sachin} } @article {5999, title = {Blood pressure components and decline in kidney function in community-living older adults: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Aug}, pages = {1037-44}, abstract = {

BACKGROUND: Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown.

METHODS: We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline >= 3ml/min/year.

RESULTS: Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95\% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14\% increased hazard of rapid decline (95\% confidence interval, 10\% to 17\%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline.

CONCLUSIONS: Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults.

}, keywords = {Aged, Blood Pressure, Cohort Studies, Cystatin C, Diastole, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Logistic Models, Longitudinal Studies, Male, Pulse, Renal Insufficiency, Chronic, Systole}, issn = {1941-7225}, doi = {10.1093/ajh/hpt067}, author = {Rifkin, Dena E and Katz, Ronit and Chonchol, Michel and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Siscovick, David S and Peralta, Carmen A} } @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 {6071, title = {Cardiomyocyte injury assessed by a highly sensitive troponin assay and sudden cardiac death in the community: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {62}, year = {2013}, month = {2013 Dec 03}, pages = {2112-20}, abstract = {

OBJECTIVES: This study sought to determine the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD).

BACKGROUND: The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated.

METHODS: Levels of cardiac troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3,089 subjects. All deaths, including SCD, were adjudicated by a central events committee.

RESULTS: Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard ratio [HR] for +1 log(hsTnT): 2.04, 95\% confidence interval [CI]: 1.78 to 2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR: 1.30, 95\% CI: 1.05 to 1.62), as well as for incident heart failure and myocardial infarction (HR: 1.26, 95\% CI: 1.01 to 1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT >=12.10 vs. 5.01 to 12.09 vs. <= 5.00 pg/ml, respectively; p trend = 0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95\% CI: 1.01 to 1.06).

CONCLUSIONS: The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.

}, keywords = {Aged, Ambulatory Care, Biomarkers, Death, Sudden, Cardiac, Female, Heart Arrest, Humans, Longitudinal Studies, Male, Middle Aged, Myocardium, Myocytes, Cardiac, Proportional Hazards Models, Risk Assessment, Troponin T}, issn = {1558-3597}, doi = {10.1016/j.jacc.2013.07.049}, author = {Hussein, Ayman A and Gottdiener, John S and Bartz, Traci M and Sotoodehnia, Nona and DeFilippi, Christopher and Dickfeld, Timm and Deo, Rajat and Siscovick, David and Stein, Phyllis K and Lloyd-Jones, Donald} } @article {6062, title = {Circulating 25-hydroxyvitamin D is associated with insulin resistance cross-sectionally but not longitudinally in older adults: The Cardiovascular Health Study.}, journal = {Metabolism}, volume = {62}, year = {2013}, month = {2013 Dec}, pages = {1788-94}, abstract = {

BACKGROUND: Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear.

OBJECTIVE: To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults.

METHODS AND RESULTS: Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992-1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996-1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95\% CI (-0.17, -0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis.

CONCLUSIONS: Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors.

}, keywords = {Adiposity, Aged, Anthropometry, Cardiovascular Diseases, Cross-Sectional Studies, Exercise, Female, Humans, Hydroxycholecalciferols, Inflammation, Insulin, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Obesity, Risk Factors, Surveys and Questionnaires}, issn = {1532-8600}, doi = {10.1016/j.metabol.2013.07.008}, author = {Danziger, John and Biggs, Mary L and Niemi, Matt and Ix, Joachim H and Kizer, Jorge R and Djouss{\'e}, Luc and de Boer, Ian H and Siscovick, David S and Kestenbaum, Bryan and Mukamal, Kenneth J} } @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 {5997, title = {Effects of respiratory and non-respiratory factors on disability among older adults with airway obstruction: the Cardiovascular Health Study.}, journal = {COPD}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {588-96}, abstract = {

BACKGROUND: High rates of disability associated with chronic airway obstruction may be caused by impaired pulmonary function, pulmonary symptoms, other chronic diseases, or systemic inflammation.

METHODS: We analyzed data from the Cardiovascular Health Study, a longitudinal cohort of 5888 older adults. Categories of lung function (normal; restricted; borderline, mild-moderate, and severe obstruction) were delineated by baseline spirometry (without bronchodilator). Disability-free years were calculated as total years alive and without self-report of difficulty performing \&γτ;1 Instrumental Activities of Daily Living over 6 years of follow-up. Using linear regression, we compared disability-free years by lung disease category, adjusting for demographic factors, body mass index, smoking, cognition, and other chronic co-morbidities. Among participants with airflow obstruction, we examined the association of respiratory factors (FEV1 and dyspnea) and non-respiratory factors (ischemic heart disease, congestive heart failure, diabetes, muscle weakness, osteoporosis, depression and cognitive impairment) on disability-free years.

RESULTS: The average disability free years were 4.0 out of a possible 6 years. Severe obstruction was associated with 1 fewer disability-free year compared to normal spirometry in the adjusted model. For the 1,048 participants with airway obstruction, both respiratory factors (FEV1 and dyspnea) and non-respiratory factors (heart disease, coronary artery disease, diabetes, depression, osteoporosis, cognitive function, and weakness) were associated with decreased disability-free years.

CONCLUSIONS: Severe obstruction is associated with greater disability compared to patients with normal spirometery. Both respiratory and non-respiratory factors contribute to disability in older adults with abnormal spirometry.

}, keywords = {Activities of Daily Living, Aged, Cognition Disorders, Cohort Studies, Comorbidity, Depression, Diabetes Mellitus, Disease Progression, Dyspnea, Female, Heart Failure, Humans, Linear Models, Longitudinal Studies, Male, Muscle Weakness, Myocardial Ischemia, Osteoporosis, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Spirometry}, issn = {1541-2563}, doi = {10.3109/15412555.2013.781148}, author = {Locke, Emily and Thielke, Stephen and Diehr, Paula and Wilsdon, Anthony G and Barr, R Graham and Hansel, Nadia and Kapur, Vishesh K and Krishnan, Jerry and Enright, Paul and Heckbert, Susan R and Kronmal, Richard A and Fan, Vincent S} } @article {1552, title = {Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the cardiovascular health study.}, journal = {Diabetes Care}, volume = {36}, year = {2013}, month = {2013 May}, pages = {1222-8}, abstract = {

OBJECTIVE: Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes.

RESEARCH DESIGN AND METHODS: This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.

RESULTS: Mean age was 75 years, and 61\% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95\% CI, 0.88-0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93-1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85-0.97) and 0.87 (0.79-0.95), respectively].

CONCLUSIONS: The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Fetuins, Humans, Incidence, Longitudinal Studies, Male, Risk Factors}, issn = {1935-5548}, doi = {10.2337/dc12-1591}, author = {Jensen, Majken K and Bartz, Traci M and Mukamal, Kenneth J and Djouss{\'e}, Luc and Kizer, Jorge R and Tracy, Russell P and Zieman, Susan J and Rimm, Eric B and Siscovick, David S and Shlipak, Michael and Ix, Joachim H} } @article {5996, title = {Fibroblast growth factor 23, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {98}, year = {2013}, month = {2013 Aug}, pages = {3323-31}, abstract = {

CONTEXT: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that also inhibits calcitriol synthesis.

OBJECTIVE: Our objective was to evaluate the relationships of plasma FGF23 concentrations with bone mineral density (BMD) and hip fracture in community-dwelling older adults.

DESIGN AND SETTING: Linear regression and Cox proportional hazard models were used to examine the associations of plasma FGF23 concentrations with BMD and incident hip fracture, respectively. Analyses were also stratified by chronic kidney disease.

PARTICIPANTS: Participants included 2008 women and 1329 men >=65 years from the 1996 to 1997 Cardiovascular Health Study visit.

MAIN OUTCOME MEASURES: Dual x-ray absorptiometry measured total hip (TH) and lumbar spine (LS) BMD in 1291 participants. Hip fracture incidence was assessed prospectively through June 30, 2008 by hospitalization records in all participants.

RESULTS: Women had higher plasma FGF23 concentrations than men (75 [56-107] vs 66 [interquartile range = 52-92] relative units/mL; P < .001). After adjustment, higher FGF23 concentrations were associated with greater total hip and lumbar spine BMD in men only (β per doubling of FGF23 = 0.02, with 95\% confidence interval [CI] = 0.001-0.04 g/cm(2), and 0.03 with 95\% CI = 0.01-0.06 g/cm(2)). During 9.6 {\textpm} 5.1-11.0 years of follow-up, 328 hip fractures occurred. Higher FGF23 concentrations were not associated with hip fracture risk in women or men (adjusted hazard ratio = 0.95, with 95\% CI = 0.78-1.15, and 1.09 with 95\% CI = 0.82-1.46 per doubling of FGF23). Results did not differ by chronic kidney disease status (P > .4 for interactions).

CONCLUSIONS: In this large prospective cohort of community-dwelling older adults, higher FGF23 concentrations were weakly associated with greater lumbar spine and total hip BMD but not with hip fracture risk.

}, keywords = {Aged, Aged, 80 and over, Bone Density, Female, Fibroblast Growth Factors, Hip Fractures, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk, Spinal Fractures}, issn = {1945-7197}, doi = {10.1210/jc.2013-1152}, author = {Jovanovich, Anna and B{\r u}zkov{\'a}, Petra and Chonchol, Michel and Robbins, John and Fink, Howard A and de Boer, Ian H and Kestenbaum, Bryan and Katz, Ronit and Carbone, Laura and Lee, Jennifer and Laughlin, Gail A and Mukamal, Kenneth J and Fried, Linda F and Shlipak, Michael G and Ix, Joachim H} } @article {7379, title = {Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults.}, journal = {Atherosclerosis}, volume = {231}, year = {2013}, month = {2013 Nov}, pages = {114-9}, abstract = {

OBJECTIVES: In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain.

METHODS: C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals >=65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH.

RESULTS: Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95\% CI 4.35-9.01] g per doubling of FGF23). 32\% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95\% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95\% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95\% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95\% CI 0.97-1.48]).

CONCLUSION: In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.

}, keywords = {Aged, Female, Fibroblast Growth Factors, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Longitudinal Studies, Male, Renal Insufficiency, Chronic, Risk Factors, Ultrasonography}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.09.002}, author = {Jovanovich, Anna and Ix, Joachim H and Gottdiener, John and McFann, Kim and Katz, Ronit and Kestenbaum, Bryan and de Boer, Ian H and Sarnak, Mark and Shlipak, Michael G and Mukamal, Kenneth J and Siscovick, David and Chonchol, Michel} } @article {5848, title = {Long-chain monounsaturated Fatty acids and incidence of congestive heart failure in 2 prospective cohorts.}, journal = {Circulation}, volume = {127}, year = {2013}, month = {2013 Apr 09}, pages = {1512-21, 1521e1-18}, chapter = {1512}, abstract = {

BACKGROUND: Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown.

METHODS AND RESULTS: We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2{\textpm}5.2 years) in the Cardiovascular Health Study (CHS; 1992-2006) and 3577 middle-aged adults (mean age, 54.1{\textpm}5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987-2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95\% confidence interval, 1.02-1.76) and 1.57 (95\% confidence interval, 1.11-2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95\% confidence interval, 1.23-2.50) and 1.92 (95\% confidence interval, 1.22-3.03) for 24:1, respectively (P for trend <=0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard.

CONCLUSIONS: Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.

}, keywords = {Aged, Aged, 80 and over, Cross-Sectional Studies, Dietary Fats, Fatty Acids, Monounsaturated, Feeding Behavior, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Nutrition Surveys, Prospective Studies, Risk Factors, Stroke}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.001197}, author = {Imamura, Fumiaki and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Steffen, Lyn M and Folsom, Aaron R and Siscovick, David S and Mozaffarian, Dariush} } @article {1551, title = {Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {98}, year = {2013}, month = {2013 Feb}, pages = {533-40}, abstract = {

CONTEXT: Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies.

OBJECTIVE: We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism.

DESIGN, SETTING, AND PARTICIPANTS: The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations.

MAIN OUTCOME MEASURE: We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5-6.9, 7.0-9.9, and 10.0-19.9 mU/liter).

RESULTS: There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95\% confidence interval (CI), 0.93-1.36], HF (HR, 1.05; 95\% CI, 0.97-1.27), or CV death (HR, 1.07; 95\% CI, 0.87-1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death.

CONCLUSIONS: Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism.

}, keywords = {Aged, Aged, 80 and over, Coronary Disease, Female, Heart Failure, Humans, Hypothyroidism, Incidence, Longitudinal Studies, Male, Risk, Thyroid Function Tests}, issn = {1945-7197}, doi = {10.1210/jc.2012-2180}, author = {Hyland, Kristen A and Arnold, Alice M and Lee, Jennifer S and Cappola, Anne R} } @article {6074, title = {Resequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham heart study.}, journal = {Circulation}, volume = {127}, year = {2013}, month = {2013 Feb 19}, pages = {799-810}, abstract = {

BACKGROUND: 9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS).

METHODS AND RESULTS: We sequenced 281 individuals (94 with myocardial infarction, 94 with high coronary artery calcium levels, and 93 control subjects free of elevated coronary artery calcium or myocardial infarction), followed by genotyping and association in >7000 additional FHS individuals. We assessed genetic associations with clinical and subclinical cardiovascular disease, risk factor phenotypes, and gene expression levels of the protein-coding genes CDKN2A and CDKN2B and the noncoding gene ANRIL in freshly harvested leukocytes and platelets. Within this large sample, we found strong associations of 9p21.3 variants with increased risk for myocardial infarction, higher coronary artery calcium levels, and larger abdominal aorta diameters and no evidence for association with traditional cardiovascular disease risk factors. No common protein-coding variation, variants in splice donor or acceptor sites, or copy number variation events were observed. By contrast, strong associations were observed between genetic variants and gene expression, particularly for a short isoform of ANRIL and for CDKN2B.

CONCLUSIONS: Our thorough genomic characterization of 9p21.3 suggests common variants likely account for observed disease associations and provides further support for the hypothesis that complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease.

}, keywords = {Calcinosis, Chromosomes, Human, Pair 9, Coronary Artery Disease, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genotype, Humans, Longitudinal Studies, Male, Massachusetts, Middle Aged, Myocardial Infarction, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, RNA, Long Noncoding, Sequence Analysis, DNA}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.111559}, author = {Johnson, Andrew D and Hwang, Shih-Jen and Voorman, Arend and Morrison, Alanna and Peloso, Gina M and Hsu, Yi-Hsiang and Thanassoulis, George and Newton-Cheh, Christopher and Rogers, Ian S and Hoffmann, Udo and Freedman, Jane E and Fox, Caroline S and Psaty, Bruce M and Boerwinkle, Eric and Cupples, L Adrienne and O{\textquoteright}Donnell, Christopher J} } @article {5853, title = {Results differ by applying distinctive multiple imputation approaches on the longitudinal cardiovascular health study data.}, journal = {Exp Aging Res}, volume = {39}, year = {2013}, month = {2013}, pages = {27-43}, abstract = {

UNLABELLED: BACKGROUND/STUDY CONTEXT: The objective of this study was to examine sequential and simultaneous approaches to multiple imputation of missing data in a longitudinal data set where losses due to death were common.

METHODS: Comparison of results from analyses and simulations of time to incident difficulty of activities of daily living (ADL) in the Cardiovascular Health Study when missing data were imputed simultaneously or sequentially.

RESULTS: Results differed with imputation methods. The largest proportional differences in 12 risk factor parameter estimates were heart failure by 106\%, social support by 33\%, and arthritis by 27\%.

CONCLUSION: Decedents{\textquoteright} final characteristics were influential on future imputations of those with missing values.

}, keywords = {Activities of Daily Living, Aged, Arthritis, Cardiac Rehabilitation, Cardiovascular Diseases, Data Interpretation, Statistical, Female, Humans, Longitudinal Studies, Male, Outcome Assessment (Health Care), Regression Analysis, Social Support}, issn = {1096-4657}, doi = {10.1080/0361073X.2013.741968}, author = {Ning, Yuming and McAvay, Gail and Chaudhry, Sarwat I and Arnold, Alice M and Allore, Heather G} } @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 {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 {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 {6563, title = {Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations.}, journal = {Am J Hum Genet}, volume = {95}, year = {2014}, month = {2014 Jul 03}, pages = {49-65}, abstract = {

Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 {\texttimes} 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGFBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p < 0.05). We estimated a 20\% gain in statistical power with long-term average (LTA) as compared to single-visit BP association studies. Using LTA analysis, we identified genetic loci influencing BP. LTA might be one way of increasing the power of genetic associations for continuous traits in extant samples for other phenotypes that are measured serially over time.

}, keywords = {Blood Pressure, Genome-Wide Association Study, Humans, Longitudinal Studies, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2014.06.002}, author = {Ganesh, Santhi K and Chasman, Daniel I and Larson, Martin G and Guo, Xiuqing and Verwoert, Germain and Bis, Joshua C and Gu, Xiangjun and Smith, Albert V and Yang, Min-Lee and Zhang, Yan and Ehret, Georg and Rose, Lynda M and Hwang, Shih-Jen and Papanicolau, George J and Sijbrands, Eric J and Rice, Kenneth and Eiriksdottir, Gudny and Pihur, Vasyl and Ridker, Paul M and Vasan, Ramachandran S and Newton-Cheh, Christopher and Raffel, Leslie J and Amin, Najaf and Rotter, Jerome I and Liu, Kiang and Launer, Lenore J and Xu, Ming and Caulfield, Mark and Morrison, Alanna C and Johnson, Andrew D and Vaidya, Dhananjay and Dehghan, Abbas and Li, Guo and Bouchard, Claude and Harris, Tamara B and Zhang, He and Boerwinkle, Eric and Siscovick, David S and Gao, Wei and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Hofman, Albert and Willer, Cristen J and Franco, Oscar H and Huo, Yong and Witteman, Jacqueline C M and Munroe, Patricia B and Gudnason, Vilmundur and Palmas, Walter and van Duijn, Cornelia and Fornage, Myriam and Levy, Daniel and Psaty, Bruce M and Chakravarti, Aravinda} } @article {6308, title = {Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.}, journal = {Clin J Am Soc Nephrol}, volume = {9}, year = {2014}, month = {2014 Feb}, pages = {239-46}, abstract = {

BACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.

RESULTS: The mean participant age was 78 years; 60\% of participants were women and 16\% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (>=100 RU/ml) and UACR (>=20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95\% confidence interval [95\% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95\% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95\% CI, 1.21 to 3.82).

CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.

}, keywords = {Acute Kidney Injury, Age Factors, Aged, Aged, 80 and over, Albuminuria, Biomarkers, Creatinine, Cystatin C, Female, Fibroblast Growth Factors, Glomerular Filtration Rate, Hospitalization, Humans, Independent Living, Kidney, Longitudinal Studies, Male, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors}, issn = {1555-905X}, doi = {10.2215/CJN.05830513}, author = {Brown, Jeremiah R and Katz, Ronit and Ix, Joachim H and de Boer, Ian H and Siscovick, David S and Grams, Morgan E and Shlipak, Michael and Sarnak, Mark J} } @article {6595, title = {Genetic variants related to height and risk of atrial fibrillation: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {180}, year = {2014}, month = {2014 Jul 15}, pages = {215-22}, abstract = {

Increased height is a known independent risk factor for atrial fibrillation (AF). However, whether genetic determinants of height influence risk is uncertain. In this candidate gene study, we examined the association of 209 height-associated single-nucleotide polymorphisms (SNPs) with incident AF in 3,309 persons of European descent from the Cardiovascular Health Study, a prospective cohort study of older adults (aged >= 65 years) enrolled in 1989-1990. After a median follow-up period of 13.2 years, 879 participants developed incident AF. The height-associated SNPs together explained approximately 10\% of the variation in height (P = 6.0 {\texttimes} 10(-8)). Using an unweighted genetic height score, we found a nonsignificant association with risk of AF (per allele, hazard ratio = 1.01, 95\% confidence interval: 1.00, 1.02; P = 0.06). In weighted analyses, we found that genetically predicted height was strongly associated with AF risk (per 10 cm, hazard ratio = 1.30, 95\% confidence interval: 1.03, 1.64; P = 0.03). Importantly, for all models, the inclusion of actual height completely attenuated the genetic height effect. Finally, we identified 1 nonsynonymous SNP (rs1046934) that was independently associated with AF and may warrant future study. In conclusion, we found that genetic determinants of height appear to increase the risk of AF, primarily via height itself. This approach of examining SNPs associated with an intermediate phenotype should be considered as a method for identifying novel genetic targets.

}, keywords = {African Americans, Aged, Atrial Fibrillation, Body Height, Endonucleases, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Humans, Longitudinal Studies, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors}, issn = {1476-6256}, doi = {10.1093/aje/kwu126}, author = {Rosenberg, Michael A and Kaplan, Robert C and Siscovick, David S and Psaty, Bruce M and Heckbert, Susan R and Newton-Cheh, Christopher and Mukamal, Kenneth J} } @article {6210, title = {The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults.}, journal = {J Diabetes Complications}, volume = {28}, year = {2014}, month = {2014 May-Jun}, pages = {316-22}, abstract = {

AIMS: It is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.

METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged >=65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.

RESULTS: Over a median follow-up of 12.5years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95\% CI, 1.70-3.40]) than black men (1.39 [0.83-2.34]); this finding did not reach statistical significance (P for interaction=0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs. (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P=0.07).

CONCLUSIONS: Overall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Coronary Disease, Diabetes Complications, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Prospective Studies, Regression Analysis, Retrospective Studies, Risk Factors, Sex Factors, Survival Rate}, issn = {1873-460X}, doi = {10.1016/j.jdiacomp.2013.12.004}, author = {Vimalananda, Varsha G and Biggs, Mary L and Rosenzweig, James L and Carnethon, Mercedes R and Meigs, James B and Thacker, Evan L and Siscovick, David S and Mukamal, Kenneth J} } @article {6604, title = {Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e100776}, abstract = {

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.

METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.

RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 {\texttimes} 10(-7)). In addition, meta-analysis using the five cohorts with >=3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 {\texttimes} 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.

CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

}, keywords = {Adult, Chromosomes, Human, Pair 11, Female, Gene Expression Regulation, Genetic Loci, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Respiration}, issn = {1932-6203}, doi = {10.1371/journal.pone.0100776}, author = {Tang, Wenbo and Kowgier, Matthew and Loth, Daan W and Soler Artigas, Maria and Joubert, Bonnie R and Hodge, Emily and Gharib, Sina A and Smith, Albert V and Ruczinski, Ingo and Gudnason, Vilmundur and Mathias, Rasika A and Harris, Tamara B and Hansel, Nadia N and Launer, Lenore J and Barnes, Kathleen C and Hansen, Joyanna G and Albrecht, Eva and Aldrich, Melinda C and Allerhand, Michael and Barr, R Graham and Brusselle, Guy G and Couper, David J and Curjuric, Ivan and Davies, Gail and Deary, Ian J and Dupuis, Jos{\'e}e and Fall, Tove and Foy, Millennia and Franceschini, Nora and Gao, Wei and Gl{\"a}ser, Sven and Gu, Xiangjun and Hancock, Dana B and Heinrich, Joachim and Hofman, Albert and Imboden, Medea and Ingelsson, Erik and James, Alan and Karrasch, Stefan and Koch, Beate and Kritchevsky, Stephen B and Kumar, Ashish and Lahousse, Lies and Li, Guo and Lind, Lars and Lindgren, Cecilia and Liu, Yongmei and Lohman, Kurt and Lumley, Thomas and McArdle, Wendy L and Meibohm, Bernd and Morris, Andrew P and Morrison, Alanna C and Musk, Bill and North, Kari E and Palmer, Lyle J and Probst-Hensch, Nicole M and Psaty, Bruce M and Rivadeneira, Fernando and Rotter, Jerome I and Schulz, Holger and Smith, Lewis J and Sood, Akshay and Starr, John M and Strachan, David P and Teumer, Alexander and Uitterlinden, Andr{\'e} G and V{\"o}lzke, Henry and Voorman, Arend and Wain, Louise V and Wells, Martin T and Wilk, Jemma B and Williams, O Dale and Heckbert, Susan R and Stricker, Bruno H and London, Stephanie J and Fornage, Myriam and Tobin, Martin D and O{\textquoteright}Connor, George T and Hall, Ian P and Cassano, Patricia A} } @article {6148, title = {Metabolic syndrome and risk of incident peripheral artery disease: the cardiovascular health study.}, journal = {Hypertension}, volume = {63}, year = {2014}, month = {2014 Feb}, pages = {413-9}, abstract = {

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged >=65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95\% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95\% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16\% to 20\% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95\% CI, 1.07-1.72 and risk ratio, 1.43; 95\% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95\% CI, 1.17-2.08 and hazard ratio, 1.55; 95\% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension.

}, keywords = {Aged, Ankle Brachial Index, C-Reactive Protein, Female, Fibrinogen, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Metabolic Syndrome, Peripheral Arterial Disease, Prevalence, Risk Factors, Vasculitis}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.113.01925}, author = {Garg, Parveen K and Biggs, Mary L and Carnethon, Mercedes and Ix, Joachim H and Criqui, Michael H and Britton, Kathryn A and Djouss{\'e}, Luc and Sutton-Tyrrell, Kim and Newman, Anne B and Cushman, Mary and Mukamal, Kenneth J} } @article {6361, title = {Physical activity and heart rate variability in older adults: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {129}, year = {2014}, month = {2014 May 27}, pages = {2100-10}, abstract = {

BACKGROUND: Cardiac mortality and electrophysiological dysfunction both increase with age. Heart rate variability (HRV) provides indices of autonomic function and electrophysiology that are associated with cardiac risk. How habitual physical activity among older adults prospectively relates to HRV, including nonlinear indices of erratic sinus patterns, is not established. We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospectively associated with more favorable time-domain, frequency-domain, and nonlinear HRV measures in older adults.

METHODS AND RESULTS: We evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study. After multivariable adjustment, greater total leisure-time activity, walking distance, and walking pace were each prospectively associated with specific, more favorable HRV indices, including higher 24-hour standard deviation of all normal-to-normal intervals (Ptrend=0.009, 0.02, 0.06, respectively) and ultralow-frequency power (Ptrend=0.02, 0.008, 0.16, respectively). Greater walking pace was also associated with a higher short-term fractal scaling exponent (Ptrend=0.003) and lower Poincar{\'e} ratio (Ptrend=0.02), markers of less erratic sinus patterns.

CONCLUSIONS: Greater total leisure-time activity, and walking alone, as well, were prospectively associated with more favorable and specific indices of autonomic function in older adults, including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing. Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life.

}, keywords = {Aged, Cardiovascular Diseases, Cross-Sectional Studies, Electrocardiography, Ambulatory, Female, Follow-Up Studies, Health Status, Heart Rate, Humans, Leisure Activities, Longitudinal Studies, Male, Motor Activity, Prospective Studies, Walking}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.005361}, author = {Soares-Miranda, Luisa and Sattelmair, Jacob and Chaves, Paulo and Duncan, Glen E and Siscovick, David S and Stein, Phyllis K and Mozaffarian, Dariush} } @article {6365, title = {Physical activity, inflammation, and volume of the aging brain.}, journal = {Neuroscience}, volume = {273}, year = {2014}, month = {2014 Jul 25}, pages = {199-209}, abstract = {

Physical activity influences inflammation, and both affect brain structure and Alzheimer{\textquoteright}s disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor α (TNFα) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3{\textpm}4.8 years) and 39 patients with AD (81.9{\textpm}5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNFα measures, and year-9 volumetric brain MRI scans. We examined how prior physical activity intensity and TNFα related to subsequent total and regional brain volumes. Physical activity intensity was measured using the modified Minnesota Leisure Time Physical Activities questionnaire at year 1 of the study, when all subjects included here were cognitively intact. Stability of measures was established for exercise intensity over 9 years and TNFα over 3 years in a subset of subjects who had these measurements at multiple time points. When considered together, more intense physical activity intensity and lower serum TNFα were both associated with greater total brain volume on follow-up MRI scans. TNFα, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNFα may independently influence brain structure in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Brain, Female, Humans, Inflammation, Longitudinal Studies, Magnetic Resonance Imaging, Male, Motor Activity, Neuroimmunomodulation, Neuropsychological Tests, Organ Size, Parietal Lobe, Surveys and Questionnaires, Tumor Necrosis Factor-alpha}, issn = {1873-7544}, doi = {10.1016/j.neuroscience.2014.05.005}, author = {Braskie, M N and Boyle, C P and Rajagopalan, P and Gutman, B A and Toga, A W and Raji, C A and Tracy, R P and Kuller, L H and Becker, J T and Lopez, O L and Thompson, P M} } @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 {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 {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 {6398, title = {Systolic and diastolic blood pressure, incident cardiovascular events, and death in elderly persons: the role of functional limitation in the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {64}, year = {2014}, month = {2014 Sep}, pages = {472-80}, abstract = {

Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78{\textpm}5 and 21\% reported limitation in >=1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95\% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <=65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <=65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.

}, keywords = {Activities of Daily Living, African Continental Ancestry Group, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Diastole, European Continental Ancestry Group, Female, Follow-Up Studies, Gait, Heart Rate, Humans, Incidence, Longitudinal Studies, Male, Risk Factors, Survival Rate, Systole}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.114.03831}, author = {Peralta, Carmen A and Katz, Ronit and Newman, Anne B and Psaty, Bruce M and Odden, Michelle C} } @article {6277, title = {Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.}, journal = {Clin Endocrinol (Oxf)}, volume = {81}, year = {2014}, month = {2014 Nov}, pages = {746-53}, abstract = {

OBJECTIVE: Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men.

DESIGN: Cohort study.

PARTICIPANTS: Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010.

MEASUREMENTS: Adjudicated ischaemic stroke.

RESULTS: Among 1032 men (mean age 76, range 66-97), followed for a median of 10~years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P~=~0{\textperiodcentered}006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75~ng/dl, with greater risk of stroke at DHT levels above 75~ng/dl or below 50~ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0{\textperiodcentered}77 (95\% CI, 0{\textperiodcentered}61, 0{\textperiodcentered}98) per standard deviation in analyses adjusted for stroke risk factors.

CONCLUSIONS: Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.

}, keywords = {Aged, Aged, 80 and over, Brain Ischemia, Cardiovascular Physiological Phenomena, Dihydrotestosterone, Health, Humans, Incidence, Longitudinal Studies, Male, Stroke, Testosterone}, issn = {1365-2265}, doi = {10.1111/cen.12452}, author = {Shores, Molly M and Arnold, Alice M and Biggs, Mary L and Longstreth, W T and Smith, Nicholas L and Kizer, Jorge R and Cappola, Anne R and Hirsch, Calvin H and Marck, Brett T and Matsumoto, Alvin M} } @article {6278, title = {Testosterone, dihydrotestosterone, and incident cardiovascular disease and mortality in the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {99}, year = {2014}, month = {2014 Jun}, pages = {2061-8}, abstract = {

CONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this.

OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality.

DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection.

MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality.

RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both).

CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Dihydrotestosterone, Humans, Incidence, Longitudinal Studies, Male, Mortality, Residence Characteristics, Risk Factors, Testosterone}, issn = {1945-7197}, doi = {10.1210/jc.2013-3576}, author = {Shores, Molly M and Biggs, Mary L and Arnold, Alice M and Smith, Nicholas L and Longstreth, W T and Kizer, Jorge R and Hirsch, Calvin H and Cappola, Anne R and Matsumoto, Alvin M} } @article {6235, title = {Troponin T, NT-proBNP, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Vasc Med}, volume = {19}, year = {2014}, month = {2014 Feb}, pages = {33-41}, abstract = {

Increased levels of plasma troponins and natriuretic peptides are markers of cardiac dysfunction associated with increased risk of cardiovascular disease. Little information exists on cardiac dysfunction and occurrence of venous thromboembolism (VTE). In two prospective epidemiological cohorts, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with VTE occurrence. The Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS) measured plasma TnT and NT-proBNP in 13,719 men or women with no history of venous thrombosis, coronary heart disease, or heart failure and followed them for approximately 10 years for VTE occurrence (n = 348 VTEs). In both ARIC and CHS, TnT was associated positively with incidence of total VTE and provoked VTE, but not with unprovoked VTE: age, race, and sex-adjusted hazard ratios for total VTE in the pooled analysis were 1.00, 0.85, 1.36, 1.51, and 1.98 (p-trend <0.0001) across five categories of TnT. In contrast, the association of NT-proBNP with VTE was positive in ARIC (hazard ratios approximately 2.5-fold for the highest versus lowest NT-proBNP quintiles), but non-existent in CHS.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Prospective Studies, Risk Factors, Troponin T, Venous Thromboembolism}, issn = {1477-0377}, doi = {10.1177/1358863X14520869}, author = {Folsom, Aaron R and Lutsey, Pamela L and Nambi, Vijay and deFilippi, Christopher R and Heckbert, Susan R and Cushman, Mary and Ballantyne, Christie M} } @article {6564, title = {What do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.}, journal = {J Am Soc Echocardiogr}, volume = {27}, year = {2014}, month = {2014 Sep}, pages = {998-1005.e2}, abstract = {

BACKGROUND: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults.

METHODS: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell{\textquoteright}s c-statistic were calculated.

RESULTS: In 4,384 Cardiovascular Health Study participants (61\% women, 14\% black; mean baseline age, 72~{\textpm}~5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI~= 0.062, P~=~.015, and NRI~= 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT~did not result in a significant NRI for either outcome, it was significant among those without incident disease.

CONCLUSIONS: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events.

}, keywords = {Aged, Cardiovascular Diseases, Carotid Intima-Media Thickness, Carotid Stenosis, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Male, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Stroke, Survival Rate}, issn = {1097-6795}, doi = {10.1016/j.echo.2014.06.013}, author = {Gardin, Julius M and Bartz, Traci M and Polak, Joseph F and O{\textquoteright}Leary, Daniel H and Wong, Nathan D} } @article {6851, title = {Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.}, journal = {Respir Res}, volume = {16}, year = {2015}, month = {2015}, pages = {81}, abstract = {

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09).

CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

}, keywords = {Adult, Aged, Cohort Studies, Cross-Sectional Studies, DNA-Binding Proteins, Female, Genetic Variation, Humans, Longitudinal Studies, Male, Massachusetts, Metabolic Networks and Pathways, Middle Aged, Nuclear Proteins, Polymorphism, Single Nucleotide, Vitamin D}, issn = {1465-993X}, doi = {10.1186/s12931-015-0238-y}, author = {Hansen, J G and Gao, W and Dupuis, J and O{\textquoteright}Connor, G T and Tang, W and Kowgier, M and Sood, A and Gharib, S A and Palmer, L J and Fornage, M and Heckbert, S R and Psaty, B M and Booth, S L and Cassano, Patricia A} } @article {6768, title = {Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {542-50}, abstract = {

OBJECTIVES: The purpose of this study was to determine the prevalence of clinically relevant comorbidities and measures of physical and cognitive impairment in elderly persons with incident heart failure (HF).

BACKGROUND: Comorbidities and functional and cognitive impairments are common in the elderly and often associated with greater mortality risk.

METHODS: We examined the prevalence of 9 comorbidities and 4 measures of functional and cognitive impairments in 558 participants from the Cardiovascular Health Study who developed incident HF between 1990 and 2002. Participants were followed prospectively until mid-2008 to determine their mortality risk.

RESULTS: Mean age of participants was 79.2 {\textpm} 6.3 years with 52\% being men. Sixty percent of participants had >=3 comorbidities, and only 2.5\% had none. Twenty-two percent and 44\% of participants had >=1 activity of daily living (ADL) and >=1 instrumental activity of daily living (IADL) impaired respectively. Seventeen percent of participants had cognitive impairment (modified mini-mental state exam score <80, scores range between 0 and 100). During follow up, 504 participants died, with 1-, 5-, and 10-year mortality rates of 19\%, 56\%, and 83\%, respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality risk: diabetes mellitus (hazard ratio [HR]: 1.64; 95\% confidence interval [CI]: 1.33 to 2.03), chronic kidney disease (HR: 1.32; 95\% CI: 1.07 to 1.62 for moderate disease; HR: 3.00; 95\% CI: 1.82 to 4.95 for severe), cerebrovascular disease (HR: 1.53; 95\% CI: 1.22 to 1.92), depression (HR: 1.44; 95\% CI: 1.09 to 1.90), functional impairment (HR: 1.30; 95\% CI: 1.04 to 1.63 for 1 IADL impaired; HR: 1.49; 95\% CI: 1.07 to 2.04 for >=2 IADL impaired), and cognitive impairment (HR: 1.33; 95\% CI: 1.02 to 1.73). Other comorbidities (hypertension, coronary heart disease, peripheral arterial disease, atrial fibrillation, and obstructive airway disease) and measures of functional impairments (ADLs and 15-ft walk time) were not associated with mortality.

CONCLUSIONS: Elderly patients with incident HF have a high burden of comorbidities and functional and cognitive impairments. Some of these conditions are associated with greater mortality risk.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Cohort Studies, Comorbidity, Coronary Disease, Female, Heart Failure, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Peripheral Arterial Disease, Physical Fitness, Prevalence, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.03.004}, author = {Murad, Khalil and Goff, David C and Morgan, Timothy M and Burke, Gregory L and Bartz, Traci M and Kizer, Jorge R and Chaudhry, Sarwat I and Gottdiener, John S and Kitzman, Dalane W} } @article {6853, title = {Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies.}, journal = {Atherosclerosis}, volume = {243}, year = {2015}, month = {2015 Nov}, pages = {44-52}, abstract = {

BACKGROUND AND AIMS: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification).

METHODS: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993.

RESULTS: Among Caucasians, both rs2248690 and rs4917 were associated with 12\% lower fetuin-A concentrations per minor allele (P~<~0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95\% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95\% CI: 0.70-1.00) for rs2248690 and 0.97 (95\% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048).

CONCLUSION: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk.

}, keywords = {Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Carotid Intima-Media Thickness, Coronary Vessels, Female, Genetic Variation, Genotype, Heart Diseases, Humans, Insulin Resistance, Longitudinal Studies, Male, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Vascular Calcification}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2015.08.031}, author = {Laugsand, Lars E and Ix, Joachim H and Bartz, Traci M and Djouss{\'e}, Luc and Kizer, Jorge R and Tracy, Russell P and Dehghan, Abbas and Rexrode, Kathryn and Lopez, Oscar L and Rimm, Eric B and Siscovick, David S and O{\textquoteright}Donnell, Christopher J and Newman, Anne and Mukamal, Kenneth J and Jensen, Majken K} } @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 {6696, title = {Husbands{\textquoteright} and Wives{\textquoteright} Physical Activity and Depressive Symptoms: Longitudinal Findings from the Cardiovascular Health Study.}, journal = {Ann Behav Med}, volume = {49}, year = {2015}, month = {2015 Oct}, pages = {704-14}, abstract = {

BACKGROUND: When examining older adults{\textquoteright} health behaviors and psychological health, it is important to consider the social context.

PURPOSE: The purpose of this study was to examine in older adult marriages whether each spouse{\textquoteright}s physical activity predicted changes in their own (actor effects) and their partner{\textquoteright}s (partner effects) depressive symptoms. Gender differences were also examined.

METHOD: Each spouse within 1260 married couples (at baseline) in the Cardiovascular Health Study completed self-report measures at wave 1 (1989-1990), wave 3 (1992-1993), and wave 7 (1996-1997). Dyadic path analyses were performed.

RESULTS: Husbands{\textquoteright} physical activity significantly predicted own decreased depressive symptoms (actor effect). For both spouses, own physical activity did not significantly predict the spouse{\textquoteright}s depressive symptoms (partner effects). However, husbands{\textquoteright} physical activity and depressive symptoms predicted wives{\textquoteright} physical activity and depressive symptoms (partner effects), respectively. Depressive symptoms did not predict physical activity.

CONCLUSION: Findings suggest that husbands{\textquoteright} physical activity is particularly influential for older married couples{\textquoteright} psychological health.

}, keywords = {Aged, Cardiovascular System, Depression, Female, Health Surveys, Humans, Longitudinal Studies, Male, Motor Activity, Sex Characteristics, Spouses}, issn = {1532-4796}, doi = {10.1007/s12160-015-9705-4}, author = {Monin, Joan K and Levy, Becca and Chen, Baibing and Fried, Terri and Stahl, Sarah T and Schulz, Richard and Doyle, Margaret and Kershaw, Trace} } @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 {6878, title = {Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis.}, journal = {Clin Chem}, volume = {61}, year = {2015}, month = {2015 Dec}, pages = {1524-31}, abstract = {

BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB.

METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined.

RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95\% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95\% CI, 1.06-1.57).

CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).

}, keywords = {Aged, Atherosclerosis, Biomarkers, Cross-Sectional Studies, Female, Heart Failure, Humans, Independent Living, Limit of Detection, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction, Prognosis, Risk Assessment, Risk Factors, Sex Factors, Troponin T}, issn = {1530-8561}, doi = {10.1373/clinchem.2015.244160}, author = {Parikh, Ravi H and Seliger, Stephen L and de Lemos, James and Nambi, Vijay and Christenson, Robert and Ayers, Colby and Sun, Wensheng and Gottdiener, John S and Kuller, Lewis H and Ballantyne, Christie and deFilippi, Christopher R} } @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 {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 {6990, title = {Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Feb}, pages = {270-6}, abstract = {

OBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality.

DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 {\textpm} 4.7, 40\% male, 83\% white).

MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality.

RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 {\textpm} 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52\% were prefrail, and 13\% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38\% (95\% confidence interval (CI) = 17-62\%) higher odds of frailty than of nonfrailty and 16\% (95\% CI = 3-30\%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95\% CI = 1.10-1.23) and frailty (HR = 1.82, 95\% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.

CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.

}, keywords = {Aged, Anthropometry, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors, Frail Elderly, Glomerular Filtration Rate, Humans, Independent Living, Longitudinal Studies, Male, Phenotype, Risk Factors, Surveys and Questionnaires}, issn = {1532-5415}, doi = {10.1111/jgs.13951}, author = {Beben, Tomasz and Ix, Joachim H and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Hoofnagle, Andrew N and Chonchol, Michel and Kestenbaum, Bryan R and de Boer, Ian H and Rifkin, Dena E} } @article {8095, title = {Galectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS).}, journal = {Am J Kidney Dis}, volume = {67}, year = {2016}, month = {2016 06}, pages = {994-6}, keywords = {Aged, Cohort Studies, Creatinine, Cystatin C, Female, Galectin 3, Glomerular Filtration Rate, Humans, Interleukin-1 Receptor-Like 1 Protein, Logistic Models, Longitudinal Studies, Male, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.12.022}, author = {Bansal, Nisha and Katz, Ronit and Seliger, Stephen and DeFilippi, Christopher and Sarnak, Mark J and Delaney, Joseph A and Christenson, Robert and de Boer, Ian H and Kestenbaum, Bryan and Robinson-Cohen, Cassianne and Ix, Joachim H and Shlipak, Michael G} } @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 {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 {7547, title = {The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.}, journal = {J Clin Endocrinol Metab}, volume = {102}, year = {2017}, month = {2017 Dec 01}, pages = {4541-4547}, abstract = {

Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.

Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.

Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged >=65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.

Setting: General community.

Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.

Interventions: Not applicable.

Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) >=126 mg/dL, non-FPG >=200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare \& Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.

Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95\% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.

Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Longitudinal Studies, Male, New England, Prospective Studies, Risk}, issn = {1945-7197}, doi = {10.1210/jc.2017-01273}, author = {Aneke-Nash, Chino S and Xue, XiaoNan and Qi, Qibin and Biggs, Mary L and Cappola, Anne and Kuller, Lewis and Pollak, Michael and Psaty, Bruce M and Siscovick, David and Mukamal, Kenneth and Strickler, Howard D and Kaplan, Robert C} } @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 {8572, title = {Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study.}, journal = {Am J Hypertens}, volume = {30}, year = {2017}, month = {2017 Feb}, pages = {151-158}, abstract = {

BACKGROUND: Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.

METHODS: We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.

RESULTS: Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95\% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95\% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (>=10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95\% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95\% CI = 1.05-1.61); considerable increases of SBP (>=20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95\% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95\% CI = 1.08-1.74).

CONCLUSIONS: Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.

}, keywords = {Aged, Aging, Blood Pressure, Blood Pressure Determination, Body Composition, California, Cohort Studies, Female, Health Status, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Office Visits, Prognosis, Retrospective Studies, Risk Factors, Stroke, Survival Rate}, issn = {1941-7225}, doi = {10.1093/ajh/hpw106}, author = {Wu, Chenkai and Shlipak, Michael G and Stawski, Robert S and Peralta, Carmen A and Psaty, Bruce M and Harris, Tamara B and Satterfield, Suzanne and Shiroma, Eric J and Newman, Anne B and Odden, Michelle C} } @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 {8632, title = {Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study.}, journal = {PLoS One}, volume = {15}, year = {2020}, month = {2020}, pages = {e0242062}, abstract = {

OBJECTIVE: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time.

METHODS: Data from the population-based Cardiovascular Health Study (n = 5,888, aged >=65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function.

RESULTS: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95\% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95\% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95\%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95\%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95\% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95\% CI -0.97 to 0.53, N = 2,306) after confounding adjustment.

INTERPRETATION: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses.

}, keywords = {Aged, Blood Coagulation, Cognition, Cross-Sectional Studies, Factor VIII, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status and Dementia Tests, Up-Regulation, White Matter}, issn = {1932-6203}, doi = {10.1371/journal.pone.0242062}, author = {Rohmann, Jessica L and Longstreth, W T and Cushman, Mary and Fitzpatrick, Annette L and Heckbert, Susan R and Rice, Kenneth and Rosendaal, Frits R and Sitlani, Colleen M and Psaty, Bruce M and Siegerink, Bob} } @article {8626, title = {Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.}, journal = {JAMA Netw Open}, volume = {3}, year = {2020}, month = {2020 10 01}, pages = {e2023242}, abstract = {

Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.

Objective: To assess performance of the PCE across clinical BMI categories.

Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020.

Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (>=35).

Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D{\textquoteright}Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE.

Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7\%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0\%) were in the underweight category, 9937 individuals (26.6\%) were in the normal weight category, 13 601 individuals (36.4\%) were in the overweight category, 7783 individuals (20.9\%) were in the mild obesity category, and 5630 individuals (15.1\%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1\% (2.5\%-15.4\%), and 3709 individuals (9.9\%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95\% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95\% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk >=20\%. The PCE C statistic overall was 0.760 (95\% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95\% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95\% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95\% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95\% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95\% CI, 0.753-0.767) with or without added metrics.

Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

}, keywords = {Adult, Aged, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Correlation of Data, Female, Humans, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2020.23242}, author = {Khera, Rohan and Pandey, Ambarish and Ayers, Colby R and Carnethon, Mercedes R and Greenland, Philip and Ndumele, Chiadi E and Nambi, Vijay and Seliger, Stephen L and Chaves, Paulo H M and Safford, Monika M and Cushman, Mary and Xanthakis, Vanessa and Vasan, Ramachandran S and Mentz, Robert J and Correa, Adolfo and Lloyd-Jones, Donald M and Berry, Jarett D and de Lemos, James A and Neeland, Ian J} } @article {9245, title = {Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {11}, year = {2022}, month = {2022 Nov}, pages = {e024374}, abstract = {

Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome-wide association study to identify sCD163-associated variants. Methods and Results We measured plasma sCD163 in 5214 adults (aged >=65 years, 58.7\% women, 16.2\% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow-up was 26 years. Genome-wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all-cause mortality (hazard ratio [HR], 1.08 [95\% CI, 1.04-1.12] per SD increase), cardiovascular disease mortality (HR, 1.15 [95\% CI, 1.09-1.21]), incident coronary heart disease (HR, 1.10 [95\% CI, 1.04-1.16]), and incident heart failure (HR, 1.18 [95\% CI, 1.12-1.25]). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome-wide association studies identified 38 variants on chromosome 2 near (top result rs62165726, =3.3{\texttimes}10),19 variants near chromosome 17 gene (rs55714927, =1.5{\texttimes}10), and 18 variants near chromosome 11 gene . These regions replicated in the European ancestry ADDITION-PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo-Danish-Dutch~study~of~Intensive~Treatment~Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781 =7.1{\texttimes}10) in the region, and 3 variants (rs115391969 =4.3{\texttimes}10) near the chromosome 16 gene Conclusions Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.

}, keywords = {Aged, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Asialoglycoprotein Receptor, Biomarkers, Cardiovascular Diseases, Female, Genome-Wide Association Study, Heart Failure, Humans, Longitudinal Studies, Male}, issn = {2047-9980}, doi = {10.1161/JAHA.121.024374}, author = {Durda, Peter and Raffield, Laura M and Lange, Ethan M and Olson, Nels C and Jenny, Nancy Swords and Cushman, Mary and Deichgraeber, Pia and Grarup, Niels and Jonsson, Anna and Hansen, Torben and Mychaleckyj, Josyf C and Psaty, Bruce M and Reiner, Alex P and Tracy, Russell P and Lange, Leslie A} } @article {9234, title = {Epilepsy, Vascular Risk Factors, and Cognitive Decline in Older Adults: The Cardiovascular Health Study.}, journal = {Neurology}, volume = {99}, year = {2022}, month = {2022 Nov 22}, pages = {e2346-e2358}, abstract = {

BACKGROUND AND OBJECTIVES: Recent studies have shown that global cognitive ability tends to decline faster over time in older adults (>=65 years) with epilepsy compared with older adults without epilepsy. Scarce data exist about the role of vascular risk factors (VRFs) on cognitive course in epilepsy. We assessed whether the associations of individual VRFs with cognitive trajectory differed depending on the presence of prevalent epilepsy.

METHODS: The Cardiovascular Health Study is a population-based longitudinal cohort study of 5,888 US adults aged >=65 years. Cognitive function was assessed annually with modified Mini-Mental State Examination (3MS; global cognitive ability) and Digit Symbol Substitution Test (DSST; information processing speed). We used linear mixed models to estimate the individual and joint associations of epilepsy and VRFs with cognitive decline by modeling epilepsy {\texttimes} VRF interactions one by one, each adjusted for all other VRFs considered, including demographics, health behaviors, clinical characteristics, and comorbid diagnoses. From these models, we estimated excess mean cognitive decline due to interaction of epilepsy with each VRF.

RESULTS: We observed excess mean decline in global cognitive ability (3MS) due to interactions of epilepsy with hypertension (6.6 points greater mean 8-year decline than expected if no interaction; 95\% CI 1.3-12.0) and with abstaining from alcohol (5.8 points greater than expected; 95\% CI 0.3-11.3). We also observed excess mean decline in information processing speed (DSST) due to interactions of epilepsy with prior stroke (18.1 points greater mean 9-year decline than expected; 95\% CI 7.6-28.5), with abstaining from alcohol (6.1 points greater than expected; 95\% CI 2.5-9.8), and with higher triglyceride levels (2.4 points greater than expected per SD; 95\% CI 0.4-4.3).

DISCUSSION: Associations of some VRFs with cognitive decline in older adults are stronger in the presence of epilepsy, suggesting a need for greater attention to vascular protection for preserving brain health in older adults with epilepsy.

}, keywords = {Aged, Cognition, Cognitive Dysfunction, Epilepsy, Humans, Longitudinal Studies, Neuropsychological Tests, Risk Factors}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000201187}, author = {Choi, Hyunmi and Elkind, Mitchell S V and Longstreth, W T and Boehme, Amelia K and Hafen, Rebekah and Hoyt, Emma J and Thacker, Evan L} } @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} }