@article {1429, title = {Temporal patterns of antihypertensive medication use among elderly patients. The Cardiovascular Health Study.}, journal = {JAMA}, volume = {270}, year = {1993}, month = {1993 Oct 20}, pages = {1837-41}, abstract = {

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

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

INTERVENTIONS: None.

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

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

}, keywords = {Adrenergic beta-Antagonists, Aged, Analysis of Variance, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Calcium Channel Blockers, Cohort Studies, Diuretics, Drug Utilization, Female, Follow-Up Studies, Humans, Hypertension, Linear Models, Logistic Models, Male, Medicare, Practice Patterns, Physicians{\textquoteright}, Recurrence, United States, Vasodilator Agents}, issn = {0098-7484}, author = {Psaty, B M and Savage, P J and Tell, G S and Polak, J F and Hirsch, C H and Gardin, J M and McDonald, R H} } @article {1438, title = {Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {25}, year = {1994}, month = {1994 Feb}, pages = {318-27}, abstract = {

BACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease.

METHODS: Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors.

RESULTS: Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound.

CONCLUSIONS: Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Cerebral Ventricles, Cerebrovascular Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Regression Analysis, Risk Factors, Sex Factors}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and Poirier, V and O{\textquoteright}Leary, D H and Gardin, J M and Fried, L P and Steinberg, E P and Bryan, R N} } @article {1423, title = {Evidence for inflammation as a cause of hypocholesterolemia in older people.}, journal = {J Am Geriatr Soc}, volume = {43}, year = {1995}, month = {1995 Mar}, pages = {264-6}, keywords = {Age Factors, Aged, Analysis of Variance, C-Reactive Protein, Case-Control Studies, Cholesterol, Female, Fibrinogen, Humans, Hypolipoproteinemias, Inflammation, Interleukin-1, Interleukin-6, Male}, issn = {0002-8614}, author = {Ettinger, W H and Harris, T and Verdery, R B and Tracy, R and Kouba, E} } @article {1413, title = {Hematological and biochemical laboratory values in older Cardiovascular Health Study participants.}, journal = {J Am Geriatr Soc}, volume = {43}, year = {1995}, month = {1995 Aug}, pages = {855-9}, abstract = {

OBJECTIVE: To define reference hematologic and biochemical lab values in older individuals.

DESIGN: Randomly selected, age- and gender-stratified participants.

SETTING: Visits by participants to four research clinics.

PATIENTS: A total of 5201 participants in the Cardiovascular Health Study, an observational study of older Medicare-eligible individuals living at home.

MEASUREMENT: Information about health status, previous illness, and medication use was obtained from participants and/or their MDs. This information was used to define a healthy subset of the population. Blood samples were obtained for Cholesterol, HDL and LDL cholesterol, fasting and 2-hour postload glucose and insulin, fibrinogen, factors VII and VIII, potassium, creatinine, albumin, uric acid, white blood count, hematocrit, hemoglobin, and platelet count.

RESULTS: Significant differences were found for age group and/or gender for all mean values. Many tests were significantly different from the generally accepted reference ranges used in clinical laboratories.

CONCLUSIONS: In some situations accepted laboratory norms for the general population can not be extrapolated to older adults. There are implications for both research and clinical practice.

}, keywords = {Age Factors, Aged, Analysis of Variance, California, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Humans, Male, Maryland, Middle Aged, North Carolina, Pennsylvania, Reference Values, Risk Factors, Sex Characteristics}, issn = {0002-8614}, author = {Robbins, J and Wahl, P and Savage, P and Enright, P and Powe, N and Lyles, M} } @article {1457, title = {Association of fibrinogen and coagulation factors VII and VIII with cardiovascular risk factors in the elderly: the Cardiovascular Health Study. Cardiovascular Health Study Investigators.}, journal = {Am J Epidemiol}, volume = {143}, year = {1996}, month = {1996 Apr 01}, pages = {665-76}, abstract = {

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

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Cohort Studies, Factor VII, Factor VIII, Female, Fibrinogen, Humans, Linear Models, Logistic Models, Male, Prevalence, Risk Factors, Sex Distribution, United States}, issn = {0002-9262}, author = {Cushman, M and Yanez, D and Psaty, B M and Fried, L P and Heiss, G and Lee, M and Polak, J F and Savage, P J and Tracy, R P} } @article {1477, title = {Preventive health behaviors among spousal caregivers.}, journal = {Prev Med}, volume = {26}, year = {1997}, month = {1997 Mar-Apr}, pages = {162-9}, abstract = {

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

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

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

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Caregivers, Case-Control Studies, Chi-Square Distribution, Confidence Intervals, Exercise, Female, Health Behavior, Health Status, Health Surveys, Humans, Internal-External Control, Life Style, Logistic Models, Male, Odds Ratio, Preventive Health Services, Self Care, Social Support, Spouses, United States}, issn = {0091-7435}, doi = {10.1006/pmed.1996.0129}, author = {Burton, L C and Newsom, J T and Schulz, R and Hirsch, C H and German, P S} } @article {1570, title = {Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.}, journal = {Thromb Haemost}, volume = {80}, year = {1998}, month = {1998 Jul}, pages = {134-9}, abstract = {

The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Anticoagulants, Antithrombin III, Biomarkers, Cross-Sectional Studies, Disease Susceptibility, Female, Humans, Lipoproteins, Male, Prevalence, Protein C, Protein S, Reference Values, Risk Factors, Thrombosis}, issn = {0340-6245}, author = {Sakkinen, P A and Cushman, M and Psaty, B M and Kuller, L H and Bajaj, S P and Sabharwal, A K and Boineau, R and Macy, E and Tracy, R P} } @article {1510, title = {Left ventricular diastolic filling in the elderly: the cardiovascular health study.}, journal = {Am J Cardiol}, volume = {82}, year = {1998}, month = {1998 Aug 01}, pages = {345-51}, abstract = {

Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Blood Flow Velocity, Cardiovascular Diseases, Cohort Studies, Diastole, Echocardiography, Doppler, Electrocardiography, Female, Health Status, Heart Ventricles, Humans, Male, Ventricular Function, Left}, issn = {0002-9149}, author = {Gardin, J M and Arnold, A M and Bild, D E and Smith, V E and Lima, J A and Klopfenstein, H S and Kitzman, D W} } @article {1522, title = {Analytical and biologic variability in measures of hemostasis, fibrinolysis, and inflammation: assessment and implications for epidemiology.}, journal = {Am J Epidemiol}, volume = {149}, year = {1999}, month = {1999 Feb 01}, pages = {261-7}, abstract = {

An increasing number of cardiovascular epidemiologic studies are measuring non-traditional risk markers of disease, most of which do not have established biovariability characteristics. When biovariability data have been reported, they usually represent a short time period, and, in any case, there is little consensus on how the information should be used. The authors performed a long-term (6-month) repeated measures study on 26 healthy individuals, and, using a nested analysis of variance (ANOVA) approach, report on the analytical (CVA), intraindividual (CVI), and between individual (CVG) variability of 12 procoagulant, fibrinolysis, and inflammation assays, including total cholesterol for comparison. The results suggest acceptable analytical variability (CVA < or = 1/2 CVI) for all assays. However, there was a large range of intraindividual variation as a proportion of total variance (2-78\%), and adjusting for intraindividual and between individual variation in bivariate correlations increased the observed correlation by more than 30 percent for three of these assays. Overall, the assays showed a significant increase in intraindividual variation over 6 months (p < 0.05). While these findings suggest that most of these assays have biovariability characteristics similar to cholesterol, there is variation among assays. Some assays may be better suited to epidemiologic studies, and knowledge of an assay{\textquoteright}s biovariability data may be useful in interpreting simple statistics, and in designing multivariate models.

}, keywords = {Adult, Aged, Analysis of Variance, Cardiovascular Diseases, Cholesterol, Epidemiology, Female, Fibrinolysis, Hemostasis, Humans, Inflammation, Male, Middle Aged, Models, Statistical, Multivariate Analysis, Risk Factors}, issn = {0002-9262}, author = {Sakkinen, P A and Macy, E M and Callas, P W and Cornell, E S and Hayes, T E and Kuller, L H and Tracy, R P} } @article {612, title = {Coronary artery calcification in older adults with minimal clinical or subclinical cardiovascular disease.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 Mar}, pages = {256-63}, abstract = {

BACKGROUND: Coronary artery calcification (CAC) reflects the extent of coronary artery atherosclerosis. The extent of coronary artery calcification is not well described in older adults.

OBJECTIVE: To determine the extent of CAC in older adults participating in a large population study of cardiovascular disease (CVD), especially those characterized as having minimal clinical or subclinical cardiovascular disease.

DESIGN: An observational epidemiologic study.

POPULATION: Participants in the Cardiovascular Health Study Cohort, mean age 78 years, who had electron beam computed tomography (EBT) scan of the heart (n = 133); included were 106 persons with no prior evidence of clinical or subclinical CVD.

MEASUREMENTS: Total CAC score was measured using cardiac EBT. Cardiovascular disease and risk factors, as well as carotid ultrasound, electrocardiogram, echocardiogram, and ankle-arm index, had been measured previously to define subclinical disease. Previous cerebral magnetic resonance imaging was also evaluated.

RESULTS: Overall, the CAC scores were higher in those with clinical cardiovascular disease or evidence of subclinical cardiovascular disease than in those with no evidence of disease. For the 106 participants without evidence of clinical or subclinical disease, the median score was 176, compared with 367 in those with subclinical disease and 923 in those with clinical CVD. Seventeen persons had scores of zero. There was little difference in risk factors across quartiles of CAC in the subgroup of 106 with prior characterization of minimal CVD despite the broad range of CAC scores. There was a higher proportion of those with white matter grade > or = 2 by magnetic resonance imaging among those with higher CAC scores (P = .025). Infarct-like lesions prevalence ranged from 12.5\% in the lowest group to 47.1\% in the highest CAC group (P = .019).

CONCLUSIONS: Older adults with evidence of clinical or subclinical CVD have higher total CAC scores. Though the extent of coronary artery calcification was lower in those with minimal evidence of CVD, the range was broad and not explained by CVD risk factors.

}, keywords = {Aged, Aging, Analysis of Variance, Calcinosis, Cardiovascular Diseases, Chi-Square Distribution, Coronary Artery Disease, Coronary Disease, Female, Humans, Male, Risk Factors, Statistics, Nonparametric, Tomography, X-Ray Computed}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb02643.x}, author = {Newman, A B and Naydeck, B and Sutton-Tyrrell, K and Edmundowicz, D and Gottdiener, J and Kuller, L H} } @article {628, title = {Association between physical activity and markers of inflammation in a healthy elderly population.}, journal = {Am J Epidemiol}, volume = {153}, year = {2001}, month = {2001 Feb 01}, pages = {242-50}, abstract = {

Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19\%, 6\%, 4\%, and 3\% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.

}, keywords = {Aged, Analysis of Variance, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Factor VIII, Female, Fibrinogen, Humans, Inflammation, Leukocyte Count, Male, Physical Exertion, Sex Factors, Smoking}, issn = {0002-9262}, doi = {10.1093/aje/153.3.242}, author = {Geffken, D F and Cushman, M and Burke, G L and Polak, J F and Sakkinen, P A and Tracy, R P} } @article {656, title = {The association of bone mineral density and depression in an older population.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Jun}, pages = {732-6}, abstract = {

OBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population.

DESIGN: Population-based, cross-sectional study.

SETTING: Study subjects were participants in the Cardiovascular Health Study (CHS), a longitudinal, long-term, follow-up study, at the University of California Davis (Sacramento, California) and the University of Pittsburgh (Pittsburgh, Pennsylvania) clinical centers.

PARTICIPANTS: A random sample of 1,566 Medicare enrollees age 65 and older enrolled in the CHS.

MEASUREMENTS: Total hip BMD, measured using dual energy x-ray absorptiometry (DEXA), after adjustment for multiple covariates, was compared with depression evaluated with the Center for Epidemiological Studies 10-item Depression Scale (CES-Dm). Risk factors for osteoporosis were compared in depressed and nondepressed participants. Potential correlates were entered into a regression model. Depression scores were compared in normal, osteopenic, and osteoporotic individuals.

RESULTS: Sixteen percent of participants were clinically depressed; 9\% had BMDs in the osteoporotic range. Mean BMD was 40 mg/cm2 lower in those with clinical depression. High CES-Dm scores were associated with lower BMD (P < .001) when adjusted for body mass index (BMI), age, kilocalories of activity, estrogen use, gender, race, smoking and drinking. When stratified by race, this remained true for all Caucasians (P < .01), all African Americans (P < .05), and when stratified by race and gender the association remained only for all Caucasian women (P < .001). In women and Caucasian men there was an increase in depression scores among individuals with osteoporotic-range BMDs.

CONCLUSIONS: A significant association was found between BMD and depressive symptoms after adjustment for osteoporosis risk factors. In Caucasians, depressive symptoms were associated with both osteoporotic and osteopenic levels of BMD. Causality cannot be ascribed, with only one measurement of BMD. We postulate that there may be an unmeasured third factor, such as an endogenous steroid, that is responsible for both low BMD and depression.

}, keywords = {Absorptiometry, Photon, Aged, Analysis of Variance, Black People, Body Mass Index, Bone Density, Bone Diseases, Metabolic, California, Cross-Sectional Studies, Depression, Energy Metabolism, Exercise, Female, Follow-Up Studies, Fractures, Bone, Humans, Linear Models, Male, Osteoporosis, Pennsylvania, Population Surveillance, Psychiatric Status Rating Scales, Radionuclide Imaging, Risk Factors, Sex Distribution, Single-Blind Method, White People}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49149.x}, author = {Robbins, J and Hirsch, C and Whitmer, R and Cauley, J and Harris, T} } @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 {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 {648, title = {M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {87}, year = {2001}, month = {2001 May 01}, pages = {1051-7}, abstract = {

Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86\% vs 97\%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Coronary Disease, Echocardiography, Doppler, Female, Heart Failure, Humans, Incidence, Male, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke}, issn = {0002-9149}, doi = {10.1016/s0002-9149(01)01460-6}, author = {Gardin, J M and McClelland, R and Kitzman, D and Lima, J A and Bommer, W and Klopfenstein, H S and Wong, N D and Smith, V E and Gottdiener, J} } @article {654, title = {Relation of sleep-disordered breathing to cardiovascular disease risk factors: the Sleep Heart Health Study.}, journal = {Am J Epidemiol}, volume = {154}, year = {2001}, month = {2001 Jul 01}, pages = {50-9}, abstract = {

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

}, keywords = {Adult, Aged, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Polysomnography, Risk Factors, Sleep Apnea Syndromes, United States}, issn = {0002-9262}, doi = {10.1093/aje/154.1.50}, author = {Newman, A B and Nieto, F J and Guidry, U and Lind, B K and Redline, S and Pickering, T G and Quan, S F} } @article {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 {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 {717, title = {Multiple imputation of baseline data in the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {157}, year = {2003}, month = {2003 Jan 01}, pages = {74-84}, abstract = {

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

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Cause of Death, Cohort Studies, Data Collection, Data Interpretation, Statistical, Epidemiologic Studies, Female, Humans, Linear Models, Male, Mathematical Computing, Models, Statistical, Predictive Value of Tests, Proportional Hazards Models, Risk Factors, Software, Survival Analysis, United States, Ventricular Remodeling}, issn = {0002-9262}, doi = {10.1093/aje/kwf156}, author = {Arnold, Alice M and Kronmal, Richard A} } @article {819, title = {Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {207-13}, abstract = {

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

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

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

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

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cohort Studies, Comorbidity, Coronary Disease, Female, Geriatric Assessment, Heart Function Tests, Humans, Hypertension, Renovascular, Incidence, Kidney Function Tests, Male, Multivariate Analysis, Probability, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate, Ultrasonography, Doppler, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.207}, author = {Edwards, Matthew S and Craven, Timothy E and Burke, Gregory L and Dean, Richard H and Hansen, Kimberley J} } @article {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 {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 {1049, title = {Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Sep}, pages = {1618-25}, abstract = {

OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.

DESIGN: Observational cohort study.

SETTING: Community.

PARTICIPANTS: Three thousand one hundred fifty-six (43\% men, 29\% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher.

MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years.

RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively).

CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Brain Diseases, Cause of Death, Cohort Studies, Disability Evaluation, Discrimination Learning, Female, Gait, Humans, Male, Memory, Short-Term, Mobility Limitation, Neuropsychological Tests, Pattern Recognition, Visual, Psychometrics, Psychomotor Performance, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01856.x}, author = {Rosano, Caterina and Newman, Anne B and Katz, Ronit and Hirsch, Calvin H and Kuller, Lewis H} } @article {1060, title = {Coronary artery calcium and physical function in older adults: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {63}, year = {2008}, month = {2008 Oct}, pages = {1112-8}, abstract = {

BACKGROUND: In older adults without clinical cardiovascular disease, coronary artery calcium (CAC) is associated with other subclinical vascular diseases, which, in turn, predict physical dysfunction. However, the association between CAC and physical function is unstudied.

METHODS: In 387 older community-dwellers from the Cardiovascular Health Study without clinical cardiovascular diseases (mean age +/- standard deviation = 78.7 +/- 3.7, 35\% men, 22\% African Americans), CAC was measured using electron beam tomography, and physical performance was assessed by usual pace gait speed, chair stand, and tandem stand. Differences in physical performance across CAC quartiles were investigated in the whole cohort and by gender. Associations with gait speed (m/s) were assessed in multivariable models using both the continuous form of CAC score (log(CAC)) and quartiles of CAC, adjusting for demographics and comorbidities.

RESULTS: No differences in physical performance were observed across CAC quartiles in the whole group. In gender-stratified analyses, a significant association was shown among women, who had progressively lower gait speed across CAC quartiles: Those with CAC > 220 walked more than 0.1 m/s slower than those with CAC < 35 (age-adjusted ptrend =.017). After multivariable adjustment, the association remained statistically significant for women in both linear (log(CAC) and gait speed, p =.025) and logistic models: Each of the top three CAC quartiles (35-220, 221-659, and > or = 660) had a more than twofold odds of walking slower than 1 m/s, compared to the lowest CAC quartile (< 35; p =.021).

CONCLUSIONS: In this sample of older community-dwellers without overt cardiovascular disease, CAC was inversely related to gait speed in women, but not in men.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Calcinosis, Coronary Artery Disease, Female, Geriatric Assessment, Humans, Male, Regression Analysis, Risk Factors, Tomography, X-Ray Computed, Walking}, issn = {1079-5006}, doi = {10.1093/gerona/63.10.1112}, author = {Inzitari, Marco and Naydeck, Barbara L and Newman, Anne B} } @article {1120, title = {Brain structure and obesity.}, journal = {Hum Brain Mapp}, volume = {31}, year = {2010}, month = {2010 Mar}, pages = {353-64}, abstract = {

Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5\%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5-25). Overweight subjects (BMI: 25-30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects.

}, keywords = {Age Factors, Aged, Analysis of Variance, Body Mass Index, Brain, Continental Population Groups, Diabetes Mellitus, Type 2, Fasting, Female, Humans, Insulin, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Nerve Fibers, Unmyelinated, Obesity, Organ Size, Regression Analysis, Sex Factors}, issn = {1097-0193}, doi = {10.1002/hbm.20870}, author = {Raji, Cyrus A and Ho, April J and Parikshak, Neelroop N and Becker, James T and Lopez, Oscar L and Kuller, Lewis H and Hua, Xue and Leow, Alex D and Toga, Arthur W and Thompson, Paul M} } @article {1214, title = {Change in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Nov}, pages = {1208-14}, abstract = {

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

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

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

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

}, keywords = {Adiponectin, Age Factors, Aged, Aging, Analysis of Variance, Cardiovascular Diseases, Cause of Death, Chi-Square Distribution, Cohort Studies, Cross-Sectional Studies, Female, Health Status, Humans, Linear Models, Male, Physical Fitness, Proportional Hazards Models, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glq122}, author = {Kizer, Jorge R and Arnold, Alice M and Strotmeyer, Elsa S and Ives, Diane G and Cushman, Mary and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Hirsch, Calvin H and Newman, Anne B} } @article {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 {1286, title = {Chronic kidney disease in octogenarians.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Jun}, pages = {1410-7}, abstract = {

BACKGROUND AND OBJECTIVES: There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.

RESULTS: Mean age was 86 years, 64\% were women, 86\% were Caucasians, 14\% had diabetes, and 39\% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51\%, 46\%, and 33\% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95\% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95\% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95\% CI, 1.55, 2.83).

CONCLUSIONS: Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.

}, keywords = {Age Factors, Aged, 80 and over, Analysis of Variance, Biomarkers, Cardiovascular Diseases, Chi-Square Distribution, Chronic Disease, Creatinine, Cross-Sectional Studies, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Logistic Models, Male, Models, Biological, Prevalence, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.08801010}, author = {Shastri, Shani and Tighiouart, Hocine and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1225, title = {The effects of physical activity, education, and body mass index on the aging brain.}, journal = {Hum Brain Mapp}, volume = {32}, year = {2011}, month = {2011 Sep}, pages = {1371-82}, abstract = {

Normal human aging is accompanied by progressive brain tissue loss and cognitive decline; however, several factors are thought to influence brain aging. We applied tensor-based morphometry to high-resolution brain MRI scans to determine whether educational level or physical activity was associated with brain tissue volumes in the elderly, particularly in regions susceptible to age-related atrophy. We mapped the 3D profile of brain volume differences in 226 healthy elderly subjects (130F/96M; 77.9 {\textpm} 3.6 SD years) from the Cardiovascular Health Study-Cognition Study. Statistical maps revealed the 3D profile of brain regions whose volumes were associated with educational level and physical activity (based on leisure-time energy expenditure). After controlling for age, sex, and physical activity, higher educational levels were associated with ~2-3\% greater tissue volumes, on average, in the temporal lobe gray matter. After controlling for age, sex, and education, greater physical activity was associated with ~2-2.5\% greater average tissue volumes in the white matter of the corona radiata extending into the parietal-occipital junction. Body mass index (BMI) was highly correlated with both education and physical activity, so we examined BMI as a contributing factor by including physical activity, education, and BMI in the same model; only BMI effects remained significant. This is one of the largest MRI studies of factors influencing structural brain aging, and BMI may be a key factor explaining the observed relationship between education, physical activity, and brain structure. Independent contributions to brain structure could not be teased apart as all these factors were highly correlated with one another.

}, keywords = {Aged, Aged, 80 and over, Aging, Analysis of Variance, Body Mass Index, Brain, Brain Mapping, Educational Status, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Motor Activity, Neuropsychological Tests, Statistics as Topic}, issn = {1097-0193}, doi = {10.1002/hbm.21113}, author = {Ho, April J and Raji, Cyrus A and Becker, James T and Lopez, Oscar L and Kuller, Lewis H and Hua, Xue and Dinov, Ivo D and Stein, Jason L and Rosano, Caterina and Toga, Arthur W and Thompson, Paul M} } @article {1395, title = {Kidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {60}, year = {2012}, month = {2012 Jul}, pages = {1201-7}, abstract = {

OBJECTIVES: To examine the association between kidney function and all-cause mortality in octogenarians.

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: Community.

PARTICIPANTS: Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.

MEASUREMENTS: Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.

RESULTS: Mean age of the participants was 85, 64\% were female, 66\% had hypertension, 14\% had diabetes mellitus, and 39\% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (>= 75 mL/min per 1.73 m(2) ) and lowest (<= 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95\% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95\% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95\% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).

CONCLUSION: Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

}, keywords = {Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Creatinine, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Diseases, Male, Prevalence, Proportional Hazards Models, Retrospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2012.04046.x}, author = {Shastri, Shani and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Odden, Michelle C and Peralta, Carmen A and Chonchol, Michel and Siscovick, David and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {6075, title = {Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.}, journal = {Nat Genet}, volume = {45}, year = {2013}, month = {2013 Feb}, pages = {145-54}, abstract = {

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

}, keywords = {Analysis of Variance, European Continental Ancestry Group, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Glucose, Gout, Humans, Inhibins, Polymorphism, Single Nucleotide, Signal Transduction, Uric Acid}, issn = {1546-1718}, doi = {10.1038/ng.2500}, author = {K{\"o}ttgen, Anna and Albrecht, Eva and Teumer, Alexander and Vitart, Veronique and Krumsiek, Jan and Hundertmark, Claudia and Pistis, Giorgio and Ruggiero, Daniela and O{\textquoteright}Seaghdha, Conall M and Haller, Toomas and Yang, Qiong and Tanaka, Toshiko and Johnson, Andrew D and Kutalik, Zolt{\'a}n and Smith, Albert V and Shi, Julia and Struchalin, Maksim and Middelberg, Rita P S and Brown, Morris J and Gaffo, Angelo L and Pirastu, Nicola and Li, Guo and Hayward, Caroline and Zemunik, Tatijana and Huffman, Jennifer and Yengo, Loic and Zhao, Jing Hua and Demirkan, Ayse and Feitosa, Mary F and Liu, Xuan and Malerba, Giovanni and Lopez, Lorna M and van der Harst, Pim and Li, Xinzhong and Kleber, Marcus E and Hicks, Andrew A and Nolte, Ilja M and Johansson, Asa and Murgia, Federico and Wild, Sarah H and Bakker, Stephan J L and Peden, John F and Dehghan, Abbas and Steri, Maristella and Tenesa, Albert and Lagou, Vasiliki and Salo, Perttu and Mangino, Massimo and Rose, Lynda M and Lehtim{\"a}ki, Terho and Woodward, Owen M and Okada, Yukinori and Tin, Adrienne and M{\"u}ller, Christian and Oldmeadow, Christopher and Putku, Margus and Czamara, Darina and Kraft, Peter and Frogheri, Laura and Thun, Gian Andri and Grotevendt, Anne and Gislason, Gauti Kjartan and Harris, Tamara B and Launer, Lenore J and McArdle, Patrick and Shuldiner, Alan R and Boerwinkle, Eric and Coresh, Josef and Schmidt, Helena and Schallert, Michael and Martin, Nicholas G and Montgomery, Grant W and Kubo, Michiaki and Nakamura, Yusuke and Tanaka, Toshihiro and Munroe, Patricia B and Samani, Nilesh J and Jacobs, David R and Liu, Kiang and D{\textquoteright}Adamo, Pio and Ulivi, Sheila and Rotter, Jerome I and Psaty, Bruce M and Vollenweider, Peter and Waeber, G{\'e}rard and Campbell, Susan and Devuyst, Olivier and Navarro, Pau and Kolcic, Ivana and Hastie, Nicholas and Balkau, Beverley and Froguel, Philippe and Esko, T{\~o}nu and Salumets, Andres and Khaw, Kay Tee and Langenberg, Claudia and Wareham, Nicholas J and Isaacs, Aaron and Kraja, Aldi and Zhang, Qunyuan and Wild, Philipp S and Scott, Rodney J and Holliday, Elizabeth G and Org, Elin and Viigimaa, Margus and Bandinelli, Stefania and Metter, Jeffrey E and Lupo, Antonio and Trabetti, Elisabetta and Sorice, Rossella and D{\"o}ring, Angela and Lattka, Eva and Strauch, Konstantin and Theis, Fabian and Waldenberger, Melanie and Wichmann, H-Erich and Davies, Gail and Gow, Alan J and Bruinenberg, Marcel and Stolk, Ronald P and Kooner, Jaspal S and Zhang, Weihua and Winkelmann, Bernhard R and Boehm, Bernhard O and Lucae, Susanne and Penninx, Brenda W and Smit, Johannes H and Curhan, Gary and Mudgal, Poorva and Plenge, Robert M and Portas, Laura and Persico, Ivana and Kirin, Mirna and Wilson, James F and Mateo Leach, Irene and van Gilst, Wiek H and Goel, Anuj and Ongen, Halit and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Imboden, Medea and von Eckardstein, Arnold and Cucca, Francesco and Nagaraja, Ramaiah and Piras, Maria Grazia and Nauck, Matthias and Schurmann, Claudia and Budde, Kathrin and Ernst, Florian and Farrington, Susan M and Theodoratou, Evropi and Prokopenko, Inga and Stumvoll, Michael and Jula, Antti and Perola, Markus and Salomaa, Veikko and Shin, So-Youn and Spector, Tim D and Sala, Cinzia and Ridker, Paul M and K{\"a}h{\"o}nen, Mika and Viikari, Jorma and Hengstenberg, Christian and Nelson, Christopher P and Meschia, James F and Nalls, Michael A and Sharma, Pankaj and Singleton, Andrew B and Kamatani, Naoyuki and Zeller, Tanja and Burnier, Michel and Attia, John and Laan, Maris and Klopp, Norman and Hillege, Hans L and Kloiber, Stefan and Choi, Hyon and Pirastu, Mario and Tore, Silvia and Probst-Hensch, Nicole M and V{\"o}lzke, Henry and Gudnason, Vilmundur and Parsa, Afshin and Schmidt, Reinhold and Whitfield, John B and Fornage, Myriam and Gasparini, Paolo and Siscovick, David S and Polasek, Ozren and Campbell, Harry and Rudan, Igor and Bouatia-Naji, Nabila and Metspalu, Andres and Loos, Ruth J F and van Duijn, Cornelia M and Borecki, Ingrid B and Ferrucci, Luigi and Gambaro, Giovanni and Deary, Ian J and Wolffenbuttel, Bruce H R and Chambers, John C and M{\"a}rz, Winfried and Pramstaller, Peter P and Snieder, Harold and Gyllensten, Ulf and Wright, Alan F and Navis, Gerjan and Watkins, Hugh and Witteman, Jacqueline C M and Sanna, Serena and Schipf, Sabine and Dunlop, Malcolm G and T{\"o}njes, Anke and Ripatti, Samuli and Soranzo, Nicole and Toniolo, Daniela and Chasman, Daniel I and Raitakari, Olli and Kao, W H Linda and Ciullo, Marina and Fox, Caroline S and Caulfield, Mark and Bochud, Murielle and Gieger, Christian} } @article {6593, title = {Relationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals.}, journal = {J Alzheimers Dis}, volume = {44}, year = {2015}, month = {2015}, pages = {319-28}, abstract = {

Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Brain, Cerebrovascular Disorders, Female, Humans, Image Processing, Computer-Assisted, Logistic Models, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Peripheral Vascular Diseases, Predictive Value of Tests, Retrospective Studies, White Matter}, issn = {1875-8908}, doi = {10.3233/JAD-141077}, author = {Riverol, Mario and Becker, James T and Lopez, Oscar L and Raji, Cyrus A and Thompson, Paul M and Carmichael, Owen T and Gach, H Michael and Longstreth, William T and Fried, Linda and Tracy, Russell P and Kuller, Lewis H} }