@article {1441, title = {Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group.}, journal = {Circulation}, volume = {88}, year = {1993}, month = {1993 Sep}, pages = {837-45}, abstract = {

BACKGROUND: Peripheral arterial disease measured noninvasively by the ankle-arm index (AAI) is common in older adults, largely asymptomatic, and associated with clinically manifest cardiovascular disease (CVD). The criteria for an abnormal AAI have varied in previous studies. To determine whether there is an inverse dose-response relation between the AAI and clinical CVD, subclinical disease, and risk factors, we examined the relation of the AAI to cardiovascular risk factors, other noninvasive measures of subclinical atherosclerosis using carotid ultrasound, echocardiography and electrocardiography, and clinical CVD.

METHODS AND RESULTS: The AAI was measured in 5084 participants > or = 65 years old at the baseline examination of the Cardiovascular Health Study. All subjects had detailed assessment of prevalent CVD, measures of cardiovascular risk factors, and noninvasive measures of disease. Participants were stratified by baseline clinical CVD status and AAI (< 0.8, > or = 0.8 to < 0.9, > or = 0.9 to < 1.0, > or = 1.0 to < 1.5). Analyses tested for a dose-response relation of the AAI with clinical CVD, risk factors, and subclinical disease. The cumulative frequency of a low AAI was 7.4\% of participants < 0.8, 12.4\% < 0.9, and 23.6\% < 1.0. participants with an AAI < 0.8 were more than twice as likely as those with an AAI of 1.0 to 1.5 to have a history of myocardial infarction, angina, congestive heart failure, stroke, or transient ischemic attack (all P < .01). In participants free of clinical CVD at baseline, the AAI was inversely related to history of hypertension, history of diabetes, and smoking, as well as systolic blood pressure, serum creatinine, fasting glucose, fasting insulin, measures of pulmonary function, and fibrinogen level (all P < .01). Risk factor associations with the AAI were similar in men and women free of CVD except for serum total and low-density lipoprotein cholesterol, which were inversely associated with AAI level only in women. Risk factors associated with an AAI of < 1.0 in multivariate analysis included smoking (odds ratio [OR], 2.55), history of diabetes (OR, 3.84), increasing age (OR, 1.54), and nonwhite race (OR, 2.36). In the 3372 participants free of clinical CVD, other noninvasive measures of subclinical CVD, including carotid stenosis by duplex scanning, segmental wall motion abnormalities by echocardiogram, and major ECG abnormalities were inversely related to the AAI (all P < .01).

CONCLUSIONS: There was an inverse dose-response relation of the AAI with CVD risk factors and subclinical and clinical CVD among older adults. The lower the AAI, the greater the increase in CVD risk; however, even those with modest, asymptomatic reductions in the AAI (0.8 to 1.0) appear to be at increased risk of CVD.

}, keywords = {Aged, Ankle, Arm, Arteriosclerosis, Blood Pressure Determination, Cardiovascular Diseases, Female, Humans, Male, Multivariate Analysis, Peripheral Vascular Diseases, Population Surveillance, Predictive Value of Tests, Risk Factors}, issn = {0009-7322}, author = {Newman, A B and Siscovick, D S and Manolio, T A and Polak, J and Fried, L P and Borhani, N O and Wolfson, S K} } @article {1436, title = {Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {3}, year = {1993}, month = {1993 Jul}, pages = {358-66}, abstract = {

Few large-scale epidemiologic studies have enrolled older adults; hence, little is known about the feasibility of recruiting this group for long-term population-based studies. In this article we present the recruitment experience of the Cardiovascular Health Study (CHS), a population-based, longitudinal study of cardiovascular diseases in adults 65 years and older. Participants were sampled from the Health Care Financing Administration{\textquoteright}s (HCFA) Medicare eligibility lists in four US communities. Letters were mailed to 11,955 sampled individuals. Persons recruited were required to complete an extensive home interview and then a 4-hour in-clinic examination. Excluded were persons who were expected to be able to complete the baseline examination and who were not expected to return for the 3-year follow-up. Some 3654 participants were recruited from those randomly selected from the Medicare sampling frame. In addition, 1547 other age-eligible persons living in the household with the sampled individuals also participated, yielding a total of 5201 participants. Of those who were contacted, 9.6\% were ineligible and 34.9\% refused participation. Among those eligible, 38.6\% refused and 57.3\% were enrolled (the remaining did not refuse but were not enrolled before the recruitment ended). Data from a subsample indicate that compared to those who were ineligible or who refused, enrolled participants were younger, more highly educated, more likely to be married, and less likely to report limitations in activity. Compared to those who were eligible but refused, enrolled participants were less likely to have high blood pressure and stroke and more likely to have quit smoking and to perceive their health status as very good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Epidemiologic Methods, Female, Humans, Male}, issn = {1047-2797}, author = {Tell, G S and Fried, L P and Hermanson, B and Manolio, T A and Newman, A B and Borhani, N O} } @article {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 {1417, title = {Physical disability in older adults: a physiological approach. Cardiovascular Health Study Research Group.}, journal = {J Clin Epidemiol}, volume = {47}, year = {1994}, month = {1994 Jul}, pages = {747-60}, abstract = {

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

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Chronic Disease, Disabled Persons, Factor Analysis, Statistical, Female, Geriatric Assessment, Humans, Logistic Models, Male, Outcome Assessment (Health Care), Risk Factors, Sex Factors, Socioeconomic Factors, United States}, issn = {0895-4356}, author = {Fried, L P and Ettinger, W H and Lind, B and Newman, A B and Gardin, J} } @article {1414, title = {Black-white differences in subclinical cardiovascular disease among older adults: the Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {J Clin Epidemiol}, volume = {48}, year = {1995}, month = {1995 Sep}, pages = {1141-52}, abstract = {

Cardiovascular and all-cause mortality are higher in black than white Americans, but racial differences in clinical and subclinical cardiovascular disease (CVD) have not been examined in older adults. Clinical and subclinical CVD and its risk factors were compared in 4926 white and 244 black men and women aged 65 years and older. Black participants had lower socioeconomic status and generally higher prevalences of CVD and its risk factors, except for adverse lipid profiles. Common carotid wall thickness was greater in black than white women, and ankle-arm blood pressure ratios were lower in black women and men (p < 0.01). After adjustment for CVD risk factors, common carotid walls were significantly thicker and ankle-arm ratios were lower in blacks than whites of both sexes, while internal carotid walls were significantly thinner in black women. Racial differences in clinical and subclinical CVD in older adults are similar to those reported in younger populations and do not appear to be explained by CVD risk factors.

}, keywords = {African Continental Ancestry Group, Aged, Cardiovascular Diseases, Carotid Arteries, European Continental Ancestry Group, Female, Geriatric Assessment, Humans, Male, Multivariate Analysis, Prevalence, Regression Analysis, Risk Factors, Sex Factors}, issn = {0895-4356}, author = {Manolio, T A and Burke, G L and Psaty, B M and Newman, A B and Haan, M and Powe, N and Tracy, R P and O{\textquoteright}Leary, D H} } @article {1451, title = {Ischemic episodes in 24-h ambulatory electrocardiograms of elderly persons: the Cardiovascular Health Study.}, journal = {Int J Cardiol}, volume = {51}, year = {1995}, month = {1995 Sep}, pages = {165-75}, abstract = {

We examined correlates of ischemic episodes in 24-h ambulatory electrocardiograms (ECG) in a sample of 1511 men and women 65 years old and older. Ischemic episodes had a high prevalence period during early afternoon and also during morning hours after awakening, and the overall prevalence was 13\% in men and 9\% in women (P < 0.001 for gender difference). The prevalence was 9.6\% in participants with no history of myocardial infarction and no major or minor resting ECG abnormalities. In multivariate analysis by logistic regression, being on digitalis medication was associated with over a three-fold risk of ischemic episodes, with an odds ratio (95\% confidence limits) of 3.21 (1.80 to 5.74). Left ventricular hypertrophy by ECG and atrial fibrillation had almost a three-fold excess risk of ischemic episodes, with odds ratios 2.81 (1.37 to 5.74) and 2.63 (1.17 to 5.91), respectively. Isolated ST-T abnormalities had almost a two-fold excess of ischemic episodes, with an odds ratio of 1.89 (1.01 to 3.54). Being overweight was associated with a 33\% reduced likelihood of ischemic episodes after adjustment for other factors, with an odds ratio of 0.67 (0.46 to 0.98). It is concluded that the prevalence of silent ischemic episodes is high in older men and women.

}, keywords = {Age Factors, Aged, Arrhythmias, Cardiac, Atrial Fibrillation, California, Circadian Rhythm, Digitalis Glycosides, Electrocardiography, Electrocardiography, Ambulatory, Female, Health Surveys, Humans, Hypertrophy, Left Ventricular, Logistic Models, Male, Maryland, Multivariate Analysis, Myocardial Infarction, Myocardial Ischemia, North Carolina, Obesity, Odds Ratio, Pennsylvania, Prevalence, Risk Factors, Sex Characteristics}, issn = {0167-5273}, author = {Rautaharju, P M and Manolio, T A and Furberg, C D and Siscovick, D and Newman, A B and Borhani, N O and Gardin, J M} } @article {1467, title = {Prevalence and correlates of snoring and observed apneas in 5,201 older adults.}, journal = {Sleep}, volume = {19}, year = {1996}, month = {1996 Sep}, pages = {531-8}, abstract = {

The objectives of this study were to describe the prevalence of snoring, observed apneas, and daytime sleepiness in older men and women, and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases (CVD). A cross-sectional design was employed to study sleep problems, CVD, general health, psychosocial factors, and medication use. The subjects were participants in the Cardiovascular Health Study, which included 5,201 adults, aged 65 and older, who were recruited from a random sample of Medicare enrollees in four U.S. communities. Study measures employed were sleep questions, echocardiography, carotid ultrasound, resting electrocardiogram, cognitive function, cardiopulmonary symptoms and diseases, depression, independent activities of daily living (IADLs), and benzodiazepine use. Thirty-three percent of the men and 19\% of the women reported loud snoring, which was less frequent in those over age 75. Snoring was positively associated with younger age, marital status, and alcohol use in men, and obesity, diabetes, and arthritis in women. Snoring was not associated, however, with cardiovascular risk factors or clinical CVD in men or women. Observed apneas were reported much less frequently (13\% of men and 4\% women) than snoring, and they were associated with alcohol use, chronic bronchitis, and marital status in men. Observed apneas were associated with depression and diabetes in women. In both men and women, daytime sleepiness was associated with poor health, advanced age, and IADL limitations. The conclusions of the study were that loud snoring, observed apneas, and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Cardiovascular Diseases, Comorbidity, Female, Humans, Incidence, Lung Diseases, Male, Narcolepsy, Prevalence, Random Allocation, Sex Factors, Sleep Apnea Syndromes, Snoring}, issn = {0161-8105}, author = {Enright, P L and Newman, A B and Wahl, P W and Manolio, T A and Haponik, E F and Boyle, P J} } @article {1491, title = {The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Dec}, pages = {1423-33}, abstract = {

OBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults.

DESIGN: Cross-sectional study.

SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older.

PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension.

MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings).

RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors.

CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.

}, keywords = {Adrenergic beta-Antagonists, Aged, Aged, 80 and over, Antihypertensive Agents, Brain, Calcium Channel Blockers, Cognition, Cohort Studies, Cross-Sectional Studies, Diuretics, Female, Geriatric Assessment, Humans, Magnetic Resonance Imaging, Male, Risk Factors}, issn = {0002-8614}, author = {Heckbert, S R and Longstreth, W T and Psaty, B M and Murros, K E and Smith, N L and Newman, A B and Williamson, J D and Bernick, C and Furberg, C D} } @article {1473, title = {Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Jan}, pages = {1-7}, abstract = {

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

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

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cross-Sectional Studies, Depression, Female, Geriatric Assessment, Health Surveys, Humans, Male, Prevalence, Psychotropic Drugs, Random Allocation, Risk Factors, Sex Factors, Sleep Wake Disorders, Social Support, Surveys and Questionnaires, United States}, issn = {0002-8614}, author = {Newman, A B and Enright, P L and Manolio, T A and Haponik, E F and Wahl, P W} } @article {1497, title = {Correlates of daytime sleepiness in 4578 elderly persons: the Cardiovascular Health Study.}, journal = {Sleep}, volume = {21}, year = {1998}, month = {1998}, pages = {27-36}, abstract = {

OBJECTIVES: To describe the prevalence of self-reported daytime sleepiness in older men and women and to describe their relationships with demographic factors, nocturnal complaints, health status, and cardiovascular diseases (CVD).

DESIGN: Cross-sectional survey and clinical exam.

SETTING: Participants in the Cardiovascular Health Study, 4578 adults aged 65 and older, recruited from a random sample of non-institutionalized Medicare enrollees in four U.S. communities.

MEASURES: Daytime sleepiness measured by the Epworth Sleepiness Scale (ESS), magnetic resonance imaging of the brain (MRI), cognitive function tests, and standardized questionnaires for cardiopulmonary symptoms and diseases, depressive symptoms, social support, activities of daily living, physical activity, and current medications.

RESULTS: Approximately 20\% of the participants reported that they were "usually sleepy in the daytime". Although elderly black men were less likely to report frequent awakenings than those in the other three race and gender groups, they had significantly higher mean ESS scores. The following were independently associated with higher ESS scores in gender-specific models: non-white race, depression, loud snoring, awakening with dyspnea or snorting, frequent nocturnal awakenings, medications used to treat congestive heart failure, non-use of sleeping pills, a sedentary lifestyle, and limitation of activities of daily living in both men and women; additional correlates included hip circumference and current smoking in men, and hayfever in women. The following were not independently associated with ESS in the models: age, education, use of wine or beer to aid sleep, use of tricyclic antidepressants, long- or short-acting benzodiazepines, asthma, angina, myocardial infarction, congestive heart failure itself, forced vital capacity, social support, cognitive function, or MRI evidence of global brain atrophy or white matter abnormality.

CONCLUSIONS: Daytime sleepiness is common in the elderly, probably due to nocturnal disturbances such as frequent awakenings and snoring. The occasional use of sleeping pills for insomnia is associated with reduced daytime sleepiness in the elderly, while the use of medications for congestive heart failure is associated with daytime sleepiness. Surprisingly, anatomic abnormalities such as evidence of previous strokes and brain atrophy (as seen on brain MRI scans) were not associated with daytime sleepiness in these non-institutionalized elderly persons.

}, keywords = {Activities of Daily Living, Age Distribution, Aged, Aged, 80 and over, Brain, Cardiovascular Diseases, Circadian Rhythm, Cognition Disorders, Cohort Studies, Continental Population Groups, Cross-Sectional Studies, Disorders of Excessive Somnolence, Electrocardiography, Female, Health Status, Health Surveys, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Prevalence, Sex Distribution}, issn = {0161-8105}, author = {Whitney, C W and Enright, P L and Newman, A B and Bonekat, W and Foley, D and Quan, S F} } @article {1498, title = {Risk factors for 5-year mortality in older adults: the Cardiovascular Health Study.}, journal = {JAMA}, volume = {279}, year = {1998}, month = {1998 Feb 25}, pages = {585-92}, abstract = {

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

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

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

SETTING: Four US communities.

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

MAIN OUTCOME MEASURES: Five-year mortality.

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

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

}, keywords = {African Americans, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Health Surveys, Humans, Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, United States}, issn = {0098-7484}, author = {Fried, L P and Kronmal, R A and Newman, A B and Bild, D E and Mittelmark, M B and Polak, J F and Robbins, J A and Gardin, J M} } @article {1513, title = {Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {158}, year = {1998}, month = {1998 Sep 14}, pages = {1761-8}, abstract = {

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

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

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

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

}, keywords = {Aged, Anticholesteremic Agents, Cholesterol, LDL, Cohort Studies, Female, Humans, Hypercholesterolemia, Male, Prevalence, Risk Factors, United States}, issn = {0003-9926}, author = {Lemaitre, R N and Furberg, C D and Newman, A B and Hulley, S B and Gordon, D J and Gottdiener, J S and McDonald, R H and Psaty, B M} } @article {586, title = {Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Mar}, pages = {538-45}, abstract = {

Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3\%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7\%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95\% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Ankle, Arm, Blood Pressure Determination, Cardiovascular Diseases, Cohort Studies, Female, Humans, Hypertension, Male, Predictive Value of Tests, Risk Factors, Sex Distribution, Survival Analysis}, issn = {1079-5642}, doi = {10.1161/01.atv.19.3.538}, author = {Newman, A B and Shemanski, L and Manolio, T A and Cushman, M and Mittelmark, M and Polak, J F and Powe, N R and Siscovick, D} } @article {1521, title = {Stroke risk in an elderly population with atrial fibrillation.}, journal = {J Gen Intern Med}, volume = {14}, year = {1999}, month = {1999 Jan}, pages = {56-9}, abstract = {

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke varies widely depending on coexistent vascular disease. We assessed the stroke rate and predictive value of two published schemes for stroke risk stratification in a population-derived cohort of 259 elderly people with nonvalvular AF followed for a median of 5.3 years. The rate of ischemic stroke was 2.8\% per year (95\% confidence interval [CI] 1.9, 3.9). Thirty-one percent were predicted to be at low risk, and their stroke rate was 1.7\% per year (95\% CI 0.6, 3.8). Many people with AF in this population-derived cohort had relatively low rates of stroke. Further studies to reliably stratify stroke risk in patients with AF are needed.

}, keywords = {Aged, Atrial Fibrillation, Cerebrovascular Disorders, Cohort Studies, Humans, Male, Poisson Distribution, Proportional Hazards Models, Risk Factors}, issn = {0884-8734}, author = {Feinberg, W M and Kronmal, R A and Newman, A B and Kraut, M A and Bovill, E G and Cooper, L and Hart, R G} } @article {599, title = {Temporal trends in the use of anticoagulants among older adults with atrial fibrillation.}, journal = {Arch Intern Med}, volume = {159}, year = {1999}, month = {1999 Jul 26}, pages = {1574-8}, abstract = {

BACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.

METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.

RESULTS: The use of warfarin increased 4-fold from 13\% in 1990 to 50\% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.

CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50\% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.

}, keywords = {Aged, Anticoagulants, Aspirin, Atrial Fibrillation, Cerebrovascular Disorders, Drug Therapy, Electrocardiography, Female, Humans, Incidence, Male, Prevalence, Treatment Outcome, Warfarin}, issn = {0003-9926}, doi = {10.1001/archinte.159.14.1574}, author = {Smith, N L and Psaty, B M and Furberg, C D and White, R and Lima, J A and Newman, A B and Manolio, T A} } @article {601, title = {Underdiagnosis and undertreatment of asthma in the elderly. Cardiovascular Health Study Research Group.}, journal = {Chest}, volume = {116}, year = {1999}, month = {1999 Sep}, pages = {603-13}, abstract = {

OBJECTIVE: To describe the clinical correlates of asthma in a community-based sample of elderly persons.

PARTICIPANTS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study.

MEASUREMENTS: Standardized respiratory, sleep, and quality-of-life (QOL) questions, a medication inventory, spirometry, and ambulatory peak flow.

RESULTS: Four percent of the participants reported a current diagnosis of asthma (definite asthma), while another 4\% reported at least one attack of wheezing accompanied by chest tightness or dyspnea during the previous 12 months (probable asthma). Smokers and those with congestive heart failure were excluded from the subsequent analyses, leaving 2,527 participants. Of those who had definite asthma, 40\% were taking a sympathomimetic bronchodilator, 30\% inhaled corticosteroids, 21\% theophylline, and 18\% oral corticosteroids; 39\% were taking no asthma medications. The participants with definite or probable asthma were much more likely than the others to have a family history of asthma, childhood respiratory problems, a history of workplace exposures, dyspnea on exertion, hay fever, chronic bronchitis, nocturnal symptoms, and daytime sleepiness. They were also more likely to report poor general health, symptoms of depression, and limitation of activities of daily living. There was little difference in the morbidity and QOL of participants with recent asthma-like symptoms who had received the diagnosis of asthma versus those who had not.

CONCLUSIONS: Asthma in elderly persons is associated with a lower QOL and considerable morbidity when compared with those who do not have asthma symptoms. Asthma is underdiagnosed in this group and is often associated with allergic triggers; inhaled corticosteroids are underutilized.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Asthma, Female, Humans, Male, Peak Expiratory Flow Rate, Quality of Life, Risk Factors, Spirometry, Vital Capacity}, issn = {0012-3692}, doi = {10.1378/chest.116.3.603}, author = {Enright, P L and McClelland, R L and Newman, A B and Gottlieb, D J and Lebowitz, M D} } @article {613, title = {Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.}, journal = {JAMA}, volume = {283}, year = {2000}, month = {2000 Apr 12}, pages = {1829-36}, abstract = {

CONTEXT: Sleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.

OBJECTIVE: To assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.

DESIGN AND SETTING: Cross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.

PARTICIPANTS: A total of 6132 subjects recruited from ongoing population-based studies (aged > or = 40 years; 52.8\% female).

MAIN OUTCOME MEASURES: Apnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a > or = 30\% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a > or = 4\% drop in oxyhemoglobin saturation) [corrected], obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90\% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.

RESULTS: Mean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (> or = 30 per hour) with the lowest category (< 1.5 per hour), was 1.37 (95\% confidence interval [CI], 1.03-1.83; P for trend = .005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90\% oxygen saturation (> or = 12\% vs < 0.05\%) was 1.46 (95\% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.

CONCLUSION: Our findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

}, keywords = {Adult, Aged, Cohort Studies, Cross-Sectional Studies, Female, Humans, Hypertension, Logistic Models, Male, Middle Aged, Obesity, Polysomnography, Sleep Apnea Syndromes, Snoring}, issn = {0098-7484}, doi = {10.1001/jama.283.14.1829}, author = {Nieto, F J and Young, T B and Lind, B K and Shahar, E and Samet, J M and Redline, S and D{\textquoteright}Agostino, R B and Newman, A B and Lebowitz, M D and Pickering, T G} } @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 {610, title = {Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 Feb}, pages = {115-23}, abstract = {

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

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

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

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

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Heart Failure, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Odds Ratio, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Stages, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb03901.x}, author = {Newman, A B and Spiekerman, C F and Enright, P and Lefkowitz, D and Manolio, T and Reynolds, C F and Robbins, J} } @article {640, title = {Associations of subclinical cardiovascular disease with frailty.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M158-66}, abstract = {

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

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

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

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

}, keywords = {Aged, Ankle, Arm, Black or African American, Blood Pressure, Brain, Cardiovascular Diseases, Carotid Artery Diseases, Cerebral Infarction, Cerebrovascular Disorders, Cohort Studies, Echocardiography, Electrocardiography, Frail Elderly, Health Status, Heart Failure, Humans, Magnetic Resonance Imaging, United States, Vascular Diseases}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m158}, author = {Newman, A B and Gottdiener, J S and McBurnie, M A and Hirsch, C H and Kop, W J and Tracy, R and Walston, J D and Fried, L P} } @article {630, title = {Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.}, journal = {Ann Intern Med}, volume = {134}, year = {2001}, month = {2001 Feb 06}, pages = {182-90}, abstract = {

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

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

DESIGN: Longitudinal cohort study.

SETTING: Four communities in the United States.

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal, Aortic Rupture, Cardiovascular Diseases, Disease Progression, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Proportional Hazards Models, Risk Factors, Ultrasonography, United States}, issn = {0003-4819}, doi = {10.7326/0003-4819-134-3-200102060-00008}, author = {Newman, A B and Arnold, A M and Burke, G L and O{\textquoteright}Leary, D H and Manolio, T A} } @article {667, title = {Coronary artery calcification in older adults to age 99: prevalence and risk factors.}, journal = {Circulation}, volume = {104}, year = {2001}, month = {2001 Nov 27}, pages = {2679-84}, abstract = {

BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied.

METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60\%) were women, and 143 (23\%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31\% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile.

CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

}, keywords = {Age Distribution, Age Factors, Aged, Aged, 80 and over, Black People, Calcinosis, Calcium, Cohort Studies, Comorbidity, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Demography, Female, Humans, Logistic Models, Male, Predictive Value of Tests, Prevalence, Risk Factors, Sex Distribution, Sex Factors, Tomography, X-Ray Computed, White People}, issn = {1524-4539}, doi = {10.1161/hc4601.099464}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Feldman, A and Edmundowicz, D and Kuller, L H} } @article {639, title = {Frailty in older adults: evidence for a phenotype.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M146-56}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Disabled Persons, Fatigue, Female, Frail Elderly, Humans, Incidence, Male, Muscle Weakness, Phenotype, Prevalence, Sex Distribution, United States, Weight Loss}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m146}, author = {Fried, L P and Tangen, C M and Walston, J and Newman, A B and Hirsch, C and Gottdiener, J and Seeman, T and Tracy, R and Kop, W J and Burke, G and McBurnie, M A} } @article {679, title = {Gait variability in community-dwelling older adults.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Dec}, pages = {1646-50}, abstract = {

OBJECTIVES: To describe gait variability at usual and fast walking speeds in community-dwelling older adults and to describe the effects of increasing gait speed on gait variability.

DESIGN: Cross-sectional, descriptive study.

SETTING: The Cardiovascular Health Study at the University of Pittsburgh.

PARTICIPANTS: Ninety-five community-living older adults, 54 women and 41 men, age 65 and older (mean age +/- standard deviation 79.4 +/- 3.37).

MEASUREMENTS: Gait measured at participant{\textquoteright}s usual and fast walking speed collected using an instrumented walkway. Step-length and step-width variability were determined using the coefficient of variation.

RESULTS: Step-length variability was greatest in those who walked the slowest (r = -0.66, P < .001); step-width variability was smallest in those who walked the slowest (r -0.37, P < .001). Individuals who could not increase their walking speed (<0.10 m/second) on command had an increase in step-length variability and a decrease in step-width variability, whereas those who could increase their speed (>0.10 m/second) had an increase in step-width variability when walking at a faster speed.

CONCLUSIONS: Step-length and step-width variability have opposite associations with gait speed in older adults. Improvement in step-length and step-width variability with attempted acceleration might be a key factor to examine in future studies of disability risk and therapeutic interventions.

}, keywords = {Aged, Aged, 80 and over, Aging, Body Height, Body Weight, Cross-Sectional Studies, Disability Evaluation, Female, Gait, Humans, Male, Residence Characteristics, Risk Factors, Time Factors, Walking}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.t01-1-49274.x}, author = {Brach, J S and Berthold, R and Craik, R and VanSwearingen, J M and Newman, A B} } @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 {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 {638, title = {The role of comorbidity in the assessment of intermittent claudication in older adults.}, journal = {J Clin Epidemiol}, volume = {54}, year = {2001}, month = {2001 Mar}, pages = {294-300}, abstract = {

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5\% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

}, keywords = {Aged, Angina Pectoris, Arterial Occlusive Diseases, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Diabetes Mellitus, Female, Humans, Intermittent Claudication, Leg, Male, Prevalence, Sensitivity and Specificity, Surveys and Questionnaires}, issn = {0895-4356}, doi = {10.1016/s0895-4356(00)00308-5}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Polak, J F and Kuller, L H} } @article {636, title = {Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {163}, year = {2001}, month = {2001 Jan}, pages = {19-25}, abstract = {

Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-living individuals who underwent overnight, unattended polysomnography at home. Sleep-disordered breathing was quantified by the apnea-hypopnea index (AHI)-the average number of apneas and hypopneas per hour of sleep. Mild to moderate disordered breathing during sleep was highly prevalent in the sample (median AHI: 4.4; interquartile range: 1.3 to 11.0). A total of 1,023 participants (16\%) reported at least one manifestation of CVD (myocardial infarction, angina, coronary revascularization procedure, heart failure, or stroke). The multivariable-adjusted relative odds (95\% CI) of prevalent CVD for the second, third, and fourth quartiles of the AHI (versus the first) were 0.98 (0.77-1.24), 1.28 (1.02-1.61), and 1.42 (1.13-1.78), respectively. Sleep-disordered breathing was associated more strongly with self-reported heart failure and stroke than with self-reported coronary heart disease: the relative odds (95\% CI) of heart failure, stroke, and coronary heart disease (upper versus lower AHI quartile) were 2.38 (1.22-4.62), 1.58 (1.02- 2.46), and 1.27 (0.99-1.62), respectively. These findings are compatible with modest to moderate effects of sleep-disordered breathing on heterogeneous manifestations of CVD within a range of AHI values that are considered normal or only mildly elevated.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Sleep Apnea Syndromes}, issn = {1073-449X}, doi = {10.1164/ajrccm.163.1.2001008}, author = {Shahar, E and Whitney, C W and Redline, S and Lee, E T and Newman, A B and Nieto, F J and O{\textquoteright}Connor, G T and Boland, L L and Schwartz, J E and Samet, J M} } @article {683, title = {Weight change in old age and its association with mortality.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Oct}, pages = {1309-18}, abstract = {

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

DESIGN: Longitudinal observational cohort study.

SETTING: Four U.S. communities.

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

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

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

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

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

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

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

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

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

}, keywords = {Age of Onset, Alzheimer Disease, Cardiovascular Diseases, Cognition Disorders, Cohort Studies, Confounding Factors, Epidemiologic, Disease Progression, Early Diagnosis, Educational Status, Female, Follow-Up Studies, Humans, Male, Memory Disorders, Neuropsychological Tests, Predictive Value of Tests, Proportional Hazards Models, Risk, Sensitivity and Specificity, Time Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000147470.58328.50}, author = {Saxton, J and Lopez, O L and Ratcliff, G and Dulberg, C and Fried, L P and Carlson, M C and Newman, A B and Kuller, L} } @article {811, title = {Respiratory muscle strength and the risk of incident cardiovascular events.}, journal = {Thorax}, volume = {59}, year = {2004}, month = {2004 Dec}, pages = {1063-7}, abstract = {

BACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained.

METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke.

RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95\% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95\% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95\% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95\% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly.

CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.

}, keywords = {Cardiovascular Diseases, Female, Follow-Up Studies, Forced Expiratory Volume, Humans, Male, Maximal Voluntary Ventilation, Prospective Studies, Respiratory Muscles, Risk Factors, Vital Capacity}, issn = {0040-6376}, doi = {10.1136/thx.2004.021915}, author = {van der Palen, J and Rea, T D and Manolio, T A and Lumley, T and Newman, A B and Tracy, R P and Enright, P L and Psaty, B M} } @article {892, title = {The association of markers of inflammation with weight change in older adults: the Cardiovascular Health Study.}, journal = {Int J Obes (Lond)}, volume = {30}, year = {2006}, month = {2006 Sep}, pages = {1362-7}, abstract = {

OBJECTIVE: Elevated levels of inflammation factors often precede weight loss and may be causally related to it. Newer studies suggest that elevated levels of inflammation factors also precede weight gain. In this study, we examined whether inflammation factors are elevated in individuals, age >or=65 years, who lost or gained >5\% weight over a 3 year follow-up period compared to those with stable weight.

SUBJECTS: In total, 3254 participants in the Cardiovascular Health Study whose weight was stable; 661 who gained >5\% weight; and 842 who lost >5\% weight.

MEASUREMENTS: C-reactive protein (CRP), fibrinogen, factor VIIIc, white blood cell (WBC) and platelet counts, and interleukin-6 (IL-6) levels.

RESULTS: As compared to participants whose weight was stable, those who lost >5\% weight had higher baseline CRP concentration (1.05 (95\% CI, 1.02, 1.08) per interquartile increase) and WBC count (1.10 (1.01, 1.19) per interquartile increase) on adjusted analyses. Those who gained >5\% weight had higher baseline CRP (1.05 (1.01, 1.08)), fibrinogen (1.13 (1.01, 1.27)), and factor VIIIc (1.15 (1.03, 1.30)).

CONCLUSIONS: Inflammation factors are associated with weight gain and weight loss in older individuals. These findings suggest that subclinical inflammation, or unknown factors associated with subclinical inflammation, contribute to weight change.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Factor VIII, Female, Fibrinogen, Humans, Inflammation, Interleukin-6, Leukocyte Count, Male, Platelet Count, Weight Gain, Weight Loss}, issn = {0307-0565}, doi = {10.1038/sj.ijo.0803306}, author = {Barzilay, J I and Forsberg, C and Heckbert, S R and Cushman, M and Newman, A B} } @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 {1039, title = {Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.}, journal = {JAMA}, volume = {300}, year = {2008}, month = {2008 Jul 09}, pages = {197-208}, abstract = {

CONTEXT: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.

OBJECTIVE: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.

DATA SOURCES: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies.

STUDY SELECTION: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality.

DATA EXTRACTION: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease.

RESULTS: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7\% (95\% confidence interval [CI], 13.3\%-24.1\%) and with normal ABI (1.11-1.40) was 4.4\% (95\% CI, 3.2\%-5.7\%) (hazard ratio [HR], 4.2; 95\% CI, 3.3-5.4). Corresponding mortalities in women were 12.6\% (95\% CI, 6.2\%-19.0\%) and 4.1\% (95\% CI, 2.2\%-6.1\%) (HR, 3.5; 95\% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95\% CI, 2.3-3.7] for men vs 3.0 [95\% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19\% of men and 36\% of women.

CONCLUSION: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Ankle, Atherosclerosis, Blood Pressure, Brachial Artery, Cardiovascular Diseases, Cohort Studies, Confidence Intervals, Female, Global Health, Humans, Male, Middle Aged, Odds Ratio, Predictive Value of Tests, Risk Assessment, Risk Factors, Severity of Illness Index}, issn = {1538-3598}, doi = {10.1001/jama.300.2.197}, author = {Fowkes, F G R and Murray, G D and Butcher, I and Heald, C L and Lee, R J and Chambless, L E and Folsom, A R and Hirsch, A T and Dramaix, M and deBacker, G and Wautrecht, J-C and Kornitzer, M and Newman, A B and Cushman, M and Sutton-Tyrrell, K and Fowkes, F G R and Lee, A J and Price, J F and D{\textquoteright}Agostino, R B and Murabito, J M and Norman, P E and Jamrozik, K and Curb, J D and Masaki, K H and Rodr{\'\i}guez, B L and Dekker, J M and Bouter, L M and Heine, R J and Nijpels, G and Stehouwer, C D A and Ferrucci, L and McDermott, M M and Stoffers, H E and Hooi, J D and Knottnerus, J A and Ogren, M and Hedblad, B and Witteman, J C and Breteler, M M B and Hunink, M G M and Hofman, A and Criqui, M H and Langer, R D and Fronek, A and Hiatt, W R and Hamman, R and Resnick, H E and Guralnik, J and McDermott, M M} } @article {1109, title = {Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.}, journal = {J Med Genet}, volume = {47}, year = {2010}, month = {2010 Jan}, pages = {1-7}, abstract = {

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD.

METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus.

RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95\% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95\% CI 1.29 to 2.76).

CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

}, keywords = {African Americans, Aged, Ankle Brachial Index, Chromosome Mapping, Chromosomes, Human, Pair 11, Female, Genetic Loci, Genotype, Humans, Male, Odds Ratio, Peripheral Vascular Diseases, Polymorphism, Single Nucleotide}, issn = {1468-6244}, doi = {10.1136/jmg.2008.064808}, author = {Scherer, M L and Nalls, M A and Pawlikowska, L and Ziv, E and Mitchell, G and Huntsman, S and Hu, D and Sutton-Tyrrell, K and Lakatta, E G and Hsueh, W-C and Newman, A B and Tandon, A and Kim, L and Kwok, P-Y and Sung, A and Li, R and Psaty, B and Reiner, A P and Harris, T} } @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 {1091, title = {Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.}, journal = {Nutr Metab Cardiovasc Dis}, volume = {20}, year = {2010}, month = {2010 Jan}, pages = {15-21}, abstract = {

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults.

METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4\% per year, 4.3\% per year and 4.6\% per year for tertile 1 (< or =5.6\%), tertile 2 (5.61-6.20\%) and tertile 3 (> or =6.21\%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95\% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95\% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest).

CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Glycated Hemoglobin A, Health Surveys, Heart Failure, Humans, Incidence, Male, Myocardial Infarction, Risk Factors, Statistics as Topic, Stroke, United States}, issn = {1590-3729}, doi = {10.1016/j.numecd.2009.02.007}, author = {Chonchol, M and Katz, R and Fried, L F and Sarnak, M J and Siscovick, D S and Newman, A B and Strotmeyer, E S and Bertoni, A and Shlipak, M G} } @article {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 {1233, title = {Post hoc Parkinson{\textquoteright}s disease: identifying an uncommon disease in the Cardiovascular Health Study.}, journal = {Neuroepidemiology}, volume = {35}, year = {2010}, month = {2010}, pages = {241-9}, abstract = {

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson{\textquoteright}s disease (PD), they typically have limited information for clinical diagnosis.

METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.

RESULTS: We identified 60 cases with prevalent PD (1.0\%; 95\% confidence interval, CI = 0.8-1.3\%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95\% CI = 0.26-0.95) and for those who smoked >=50 pack-years (OR = 0.53; 95\% CI = 0.29-0.96). Estimates for smoking were similar when >=2 data sources were required. Estimates for self-report alone were attenuated towards null.

CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cohort Studies, Female, Health Status, Humans, Incidence, Male, Odds Ratio, Parkinson Disease, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1423-0208}, doi = {10.1159/000319895}, author = {Ton, T G and Jain, S and Boudreau, R and Thacker, E L and Strotmeyer, E S and Newman, A B and Longstreth, W T and Checkoway, H} } @article {1297, title = {The risk of Parkinson disease associated with urate in a community-based cohort of older adults.}, journal = {Neuroepidemiology}, volume = {36}, year = {2011}, month = {2011}, pages = {223-9}, abstract = {

BACKGROUND/AIMS: Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults.

METHODS: The association of baseline urate ({\textmu}mol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 {\textmu}mol/l), middle (300-500 {\textmu}mol/l), and high (>500 {\textmu}mol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD.

RESULTS: Women had significantly lower urate concentrations than did men [316.8 {\textmu}mol/l (SD 88.0) vs. 367.4 {\textmu}mol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 {\textmu}mol/l (OR 1.69, 95\% CI 1.03-2.78) but not for urate >500 {\textmu}mol/l (OR 1.55, 95\% CI 0.72-3.32) in men. A negative linear term was significant for urate <500 {\textmu}mol/l, and across the entire range a convex quadratic term was significant.

CONCLUSIONS: Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk.

}, keywords = {Aged, California, Cohort Studies, Female, Humans, Male, Maryland, North Carolina, Parkinson Disease, Pennsylvania, Prospective Studies, Risk Factors, Sex Distribution, Sex Factors, Uric Acid}, issn = {1423-0208}, doi = {10.1159/000327748}, author = {Jain, S and Ton, T G and Boudreau, R M and Yang, M and Thacker, E L and Studenski, S and Longstreth, W T and Strotmeyer, E S and Newman, A B} } @article {6061, title = {Association of heat shock proteins with all-cause mortality.}, journal = {Age (Dordr)}, volume = {35}, year = {2013}, month = {2013 Aug}, pages = {1367-76}, abstract = {

Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

}, keywords = {Aged, 80 and over, Aging, Cause of Death, Forecasting, Genotype, Heat-Shock Proteins, Humans, Longevity, Promoter Regions, Genetic, Retrospective Studies, Transcription, Genetic, United States}, issn = {1574-4647}, doi = {10.1007/s11357-012-9417-7}, author = {Broer, L and Demerath, E W and Garcia, M E and Homuth, G and Kaplan, R C and Lunetta, K L and Tanaka, T and Tranah, G J and Walter, S and Arnold, A M and Atzmon, G and Harris, T B and Hoffmann, W and Karasik, D and Kiel, D P and Kocher, T and Launer, L J and Lohman, K K and Rotter, J I and Tiemeier, H and Uitterlinden, A G and Wallaschofski, H and Bandinelli, S and D{\"o}rr, M and Ferrucci, L and Franceschini, N and Gudnason, V and Hofman, A and Liu, Y and Murabito, J M and Newman, A B and Oostra, B A and Psaty, B M and Smith, A V and van Duijn, C M} } @article {6063, title = {Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Mar}, pages = {401-8}, abstract = {

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.

OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans.

METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P<=2.5{\texttimes}10(-8)).

RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98{\texttimes}10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.

CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

}, keywords = {Adult, African Americans, Aged, Arrhythmias, Cardiac, Connexin 43, Electrocardiography, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Rest, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2012.11.014}, author = {Deo, R and Nalls, M A and Avery, C L and Smith, J G and Evans, D S and Keller, M F and Butler, A M and Buxbaum, S G and Li, G and Miguel Quibrera, P and Smith, E N and Tanaka, T and Akylbekova, E L and Alonso, A and Arking, D E and Benjamin, E J and Berenson, G S and Bis, J C and Chen, L Y and Chen, W and Cummings, S R and Ellinor, P T and Evans, M K and Ferrucci, L and Fox, E R and Heckbert, S R and Heiss, G and Hsueh, W C and Kerr, K F and Limacher, M C and Liu, Y and Lubitz, S A and Magnani, J W and Mehra, R and Marcus, G M and Murray, S S and Newman, A B and Njajou, O and North, K E and Paltoo, D N and Psaty, B M and Redline, S S and Reiner, A P and Robinson, J G and Rotter, J I and Samdarshi, T E and Schnabel, R B and Schork, N J and Singleton, A B and Siscovick, D and Soliman, E Z and Sotoodehnia, N and Srinivasan, S R and Taylor, H A and Trevisan, M and Zhang, Z and Zonderman, A B and Newton-Cheh, C and Whitsel, E A} } @article {6803, title = {Development and validation of an ankle brachial index risk model for the prediction of cardiovascular events.}, journal = {Eur J Prev Cardiol}, volume = {21}, year = {2014}, month = {2014 Mar}, pages = {310-20}, abstract = {

BACKGROUND: The ankle brachial index (ABI) is related to risk of cardiovascular events independent of the Framingham risk score (FRS). The aim of this study was to develop and evaluate a risk model for cardiovascular events incorporating the ABI and FRS.

DESIGN: An analysis of participant data from 18 cohorts in which 24,375 men and 20,377 women free of coronary heart disease had ABI measured and were followed up for events.

METHODS: Subjects were divided into a development and internal validation dataset and an external validation dataset. Two models, comprising FRS and FRS + ABI, were fitted for the primary outcome of major coronary events.

RESULTS: In predicting events in the external validation dataset, C-index for the FRS was 0.672 (95\% CI 0.599 to 0.737) in men and 0.578 (95\% CI 0.492 to 0.661) in women. The FRS + ABI led to a small increase in C-index in men to 0.685 (95\% CI 0.612 to 0.749) and large increase in women to 0.690 (95\% CI 0.605 to 0.764) with net reclassification improvement (NRI) of 4.3\% (95\% CI 0.0 to 7.6\%, p = 0.050) and 9.6\% (95\% CI 6.1 to 16.4\%, p < 0.001), respectively. Restricting the FRS + ABI model to those with FRS intermediate 10-year risk of 10 to 19\% resulted in higher NRI of 15.9\% (95\% CI 6.1 to 20.6\%, p < 0.001) in men and 23.3\% (95\% CI 13.8 to 62.5\%, p = 0.002) in women. However, incorporating ABI in an improved newly fitted risk factor model had a nonsignificant effect: NRI 2.0\% (95\% CI 2.3 to 4.2\%, p = 0.567) in men and 1.1\% (95\% CI 1.9 to 4.0\%, p = 0.483) in women.

CONCLUSIONS: An ABI risk model may improve prediction especially in individuals at intermediate risk and when performance of the base risk factor model is modest.

}, keywords = {Adult, Aged, Aged, 80 and over, Ankle Brachial Index, Cardiovascular Diseases, Europe, European Continental Ancestry Group, Female, Humans, Male, Middle Aged, Models, Statistical, Predictive Value of Tests, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States, Young Adult}, issn = {2047-4881}, doi = {10.1177/2047487313516564}, author = {Fowkes, F G R and Murray, G D and Butcher, I and Folsom, A R and Hirsch, A T and Couper, D J and deBacker, G and Kornitzer, M and Newman, A B and Sutton-Tyrrell, K C and Cushman, M and Lee, A J and Price, J F and D{\textquoteright}Agostino, R B and Murabito, J M and Norman, Pe and Masaki, K H and Bouter, L M and Heine, R J and Stehouwer, C D A and McDermott, M M and Stoffers, H E J H and Knottnerus, J A and Ogren, M and Hedblad, B and Koenig, W and Meisinger, C and Cauley, J A and Franco, Oh and Hunink, M G M and Hofman, A and Witteman, J C and Criqui, M H and Langer, R D and Hiatt, W R and Hamman, R F} } @article {7124, title = {Brain natriuretic peptide and insulin resistance in older adults.}, journal = {Diabet Med}, year = {2016}, month = {2016 Apr 21}, abstract = {

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established.

METHODS: N-Terminal (NT)-proBNP was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance.

RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P~<~0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic~=~71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P~=~0.38; P~=~0.01 for comparison with the association of measured levels of NT-proBNP).

CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. This article is protected by copyright. All rights reserved.

}, issn = {1464-5491}, doi = {10.1111/dme.13139}, author = {Kim, F and Biggs, M L and Kizer, J R and Brutsaert, E F and de Fillipi, C and Newman, A B and Kronmal, R A and Tracy, R P and Gottdiener, J S and Djouss{\'e}, L and de Boer, I H and Psaty, B M and Siscovick, D S and Mukamal, K J} }