Glucose, blood pressure, and lipid control in older people with and without diabetes mellitus: the Cardiovascular Health Study. - Smith, Nicholas L; Savage, Peter J; Heckbert, Susan R; Barzilay, Joshua I; Bittner, Vera A; Kuller, Lewis H; Psaty, Bruce M (J Am Geriatr Soc, 2002)
OBJECTIVES: To determine the prevalence of cardiovascular risk-factor treatment and control in older adults with normal fasting glucose, impaired fasting glucose, and diabetes mellitus and whether those with diabetes mellitus had better risk factor control than older adults with normal fasting glucose. DESIGN: Secondary analysis of data from population-based, prospective cohort study of risk factors for cardio-vascular and cerebrovascular disease in older people (Cardiovascular Health Study). SETTING: Community-based. PARTICIPANTS: Community-dwelling adults aged 65 and older. MEASUREMENTS: Fasting plasma glucose, serum cholesterol and its subfractions, systolic and diastolic blood pressures, and body mass index. RESULTS: There were 579 (18%) cohort members with diabetes mellitus (77% receiving antidiabetic medication, 23% with fasting glucose > or =126 mg/dL and no treatment), 213 (6%) with impaired fasting glucose, and 2,582 (77%)with normal fasting glucose. Of diabetic participants, 12% had recommended fasting glucose levels of less than 110 mg/dL. Of participants with hypertension, a larger proportion of diabetic participants than nondiabetic participants (89% versus 75%, P < .01) was treated with antihypertensive agents, but a smaller proportion of diabetic participants had recommended blood pressure levels of 129/85 mmHg or lower than nondiabetic participants had recommended blood pressure levels of 139/89 mmHg or lower (27% vs 48%, P < .01). Diabetic dyslipidemic participants were treated less often with lipid-lowering therapy (26% versus 55%, P < .01) and achieved recommended low-density lipoprotein goals less often (8%versus 54%, P < .01) than nondiabetic dyslipidemic participants. CONCLUSIONS: Overall, treatment and control of cardiovascular risk factors were suboptimal in this older population, especially among those with diabetes mellitus. Optimizing risk-factor control can improve health outcomes in older adults with and without diabetes mellitus.
Keywords: Age Factors; Aged; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Prevalence; Prospective Studies; Risk Factors

In the elderly, interleukin-6 plasma levels and the -174G>C polymorphism are associated with the development of cardiovascular disease. - Jenny, Nancy S; Tracy, Russell P; Ogg, Malcolm S; Luong, Le Ahn; Kuller, Lewis H; Arnold, Alice M; Sharrett, A Richey; Humphries, Steve E (Arterioscler Thromb Vasc Biol, 2002)
OBJECTIVE: Interleukin (IL)-6-mediated inflammation is involved in cardiovascular disease (CVD). We assessed IL-6 levels and the -174G>C genotype in a case-control study of men and women (average age 73 years) within the Cardiovascular Health Study. METHODS AND RESULTS: Cases included incident angina, myocardial infarction (MI), and stroke (5-year follow-up), prevalent MI, and MRI-detectable infarcts. A control group and a group free of subclinical CVD were used for comparison. The -174C allele was associated with higher C-reactive protein (11% higher, P=0.02), fibrinogen (3% higher, P=0.02), and IL-6 (5% higher; P=0.16). IL-6 was associated with increased atherosclerosis when the control group was compared with the group free of subclinical CVD. No further association with CVD events was found when case groups were compared with the control group. Compared with its absence, presence of the -174C allele was associated with risk of MRI infarcts (odds ratio 1.5). CONCLUSIONS: IL-6 levels differentiated those with subclinical CVD from those without. Although the -174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis.
Keywords: Age Factors; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cytosine; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Guanine; Health Surveys; Humans; Inflammation; Interleukin-6; Linear Models; Male; Polymorphism, Genetic; Predictive Value of Tests; Promoter Regions, Genetic

Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. - Kop, Willem J; Gottdiener, John S; Tangen, Catherine M; Fried, Linda P; McBurnie, Mary Ann; Walston, Jeremy; Newman, Anne; Hirsch, Calvin; Tracy, Russell P (Am J Cardiol, 2002)
Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.
Keywords: Aged; Blood Chemical Analysis; Blood Coagulation Factors; Cardiovascular Diseases; Depression; Female; Humans; Inflammation; Male; Risk Factors

Left atrial dimensions determined by M-mode echocardiography in black and white older (> or =65 years) adults (The Cardiovascular Health Study). - Manolio, Teri A; Gottdiener, John S; Tsang, Teresa S M; Gardin, Julius M (Am J Cardiol, 2002)
Stroke and atrial fibrillation are common and serious illnesses in the elderly, the risks of which are substantially increased by left atrial (LA) enlargement. Despite growing recognition of the importance of LA enlargement, the distribution and correlates of LA dimension in the elderly have not been well defined. A total of 3,882 women and men aged >65 years were studied. Increased LA dimension was independently associated with increased weight, mitral annular calcium, regional wall motion abnormalities, mitral early peak inflow velocity, and left ventricular (LV) fractional shortening. Increased LA dimension was negatively associated with aortic leaflet thickening. The relation with LV fractional shortening was curvilinear with a nadir at 35% to 40%. LA dimension in black men was approximately 1.9 mm less than in white men in multivariate analyses. Adjustment for spirometric lung volumes and chest dimensions appeared to diminish the race-LA dimension relation. Thus, LA dimension is strongly associated with weight and with several echocardiographic valvular abnormalities; its relation with LV fractional shortening is U-shaped with a nadir at the borderline of LV functional impairment.
Keywords: African Continental Ancestry Group; Age Factors; Aged; Blood Flow Velocity; Body Weight; Cardiovascular Diseases; Echocardiography; Electrocardiography; European Continental Ancestry Group; Evidence-Based Medicine; Female; Heart Atria; Heart Ventricles; Humans; Male; Multivariate Analysis; Prospective Studies; Risk Factors; Statistics as Topic; Ventricular Function, Left

Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions. - Rautaharju, Pentti M; Zhang, Zhu-Ming (J Cardiovasc Electrophysiol, 2002)
INTRODUCTION: Normal limits for QT traditionally are derived as mean +/- 2*SD, with rate adjustment done by dividing QT values by power functions such as RR 1/2 (proportional scaling). METHODS AND RESULTS: We evaluated procedures for deriving normal limits by comparing adjusted QT distributions versus heart rate using ECG data of 11,739 normal men and women aged > or = 40 years. QT decreased as predicted by many power functions with heart rate but its SD remained relatively unchanged. Consequently, proportional scaling induced rate-dependent distortion of normal limits. Furthermore, QT distributions by heart rate were variably skewed and non-normal. Therefore, normal limits expressed as mean +/- 2*SD were misleading. Omission of regression intercept was an additional reason for failure of Bazett's and Fridericia's formulas. Regularized normal limits for adjusted QT (Qta) were obtained with linear instead of proportional scaling of type QTa = QT + k1*(1 - RR(k2)), for instance, with k2 = 0.5, k1 = 0.360 for males and 0.353 for females, or with k2 = 0.42, k1 = 0.414 for males and 0.420 for females. With linear scaling, QTa = 460 msec was established as the upper 2% normal limit, with 32 msec as the limit for a significant QTa increase from reference ECG in serial comparison. CONCLUSION: Traditional procedures for establishment of normal limits failed because of proportional scaling, assumption of normal QT distribution, or omission of regression intercept. Percentile distributions of linearly scaled adjusted QT produced regularized rate invariant normal limits within normal sinus rates.
Keywords: Adult; Aged; Aged, 80 and over; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Prognosis; Reference Values; Sex Characteristics

Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study. - Boland, Lori L; Shahar, Eyal; Iber, Conrad; Knopman, David S; Kuo, Tracy F; Nieto, F Javier (J Sleep Res, 2002)
Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.
Keywords: Aged; Body Mass Index; Brain; Cognition Disorders; Cohort Studies; Female; Humans; Hypoxia; Male; Middle Aged; Neuropsychological Tests; Oxygen; Polysomnography; Severity of Illness Index; Sleep Apnea, Central

No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study. - Smiles, Adam M; Jenny, Nancy S; Tang, Zhonghua; Arnold, Alice; Cushman, Mary; Tracy, Russell P (Thromb Haemost, 2002)
Prothrombin is a key factor in blood clotting, a process intimately involved in thrombotic disease. We assessed prothrombin levels and G20210A genotype in a case-control study within the Cardiovascular Health Study. Cases included angina, myocardial infarction, stroke, and the presence of MRI-detectable infarcts (n approximately 250 each). Population-based controls free of clinical cardiovascular disease (CVD) (n approximately 500) and a subset free of clinical and subclinical CVD (n approximately 250) were used for comparison. The 20210 A allele, frequency 2.9%, was associated with higher mean prothrombin levels: 166.3 vs. 139.5 microg/ml (P <0.001). Significant correlates of prothrombin included gender, plasma lipids, other vitamin K-dependent proteins, and inflammatory markers, but not race, smoking, hypertension, diabetes, measures of subclinical CVD, or markers of procoagulant activity. Compared to controls, neither genotype nor prothrombin level was associated with any CVD case group. We conclude that, in the elderly, neither prothrombin level nor 20210 genotype were associated with either CVD risk factors or events. This is consistent with the lack of association of prothrombin levels with measures of underlying CVD or procoagulant markers.
Keywords: 3' Untranslated Regions; Aged; Aged, 80 and over; Alleles; Angina Pectoris; Blood Proteins; Cardiovascular Diseases; Case-Control Studies; Comorbidity; Diabetes Mellitus; Female; Genetic Predisposition to Disease; Humans; Hyperlipidemias; Hypertension; Male; Mutation; Myocardial Infarction; Obesity; Promoter Regions, Genetic; Prothrombin; Risk Factors; Smoking; Stroke; Vermont

Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. - Kuller, Lewis; Arnold, Alice; Tracy, Russell; Otvos, James; Burke, Greg; Psaty, Bruce; Siscovick, David; Freedman, David S; Kronmal, Richard (Arterioscler Thromb Vasc Biol, 2002)
OBJECTIVES: Relationships between incident cardiovascular disease and lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy were evaluated in the Cardiovascular Health Study (CHS) in a nested case-cohort analysis. METHODS AND RESULTS: The case group consisted of 434 participants with incident myocardial infarction (MI) and angina diagnosed after entry to the study (1990 to 1995) and the comparison group, 249 "healthy" participants with no prevalent clinical or subclinical disease. By univariate analysis, the median levels for healthy participants versus participants with incident MI and angina were 0 versus 7 mg% for small low density lipoprotein (LDL), 1501 versus 1680 nmol/L for the number of LDL particles, and 21.6 versus 21.3 for LDL size, and these values were significantly different between "healthy" participants and those with incident MI and angina for women but not men. The levels of less dense LDL, which is most of the total LDL cholesterol among women, was not related to incident MI and angina. For women, large high density lipoprotein cholesterol (HDLc), but not small HDLc, levels were significantly higher for healthy participants compared with levels for participants with MI and angina. For men and women, levels of total and very low density lipoprotein triglycerides were higher for the case group than for the healthy group. In multivariate models for women that included triglycerides and HDLc, the number of LDL particles (but not LDL size) remained significantly related to MI and angina. CONCLUSIONS: Small LDL, the size of LDL particles, and the greater number of LDL particles are related to incident coronary heart disease among older women.
Keywords: Aged; Aging; Cardiovascular System; Case-Control Studies; Cohort Studies; Coronary Disease; Female; Health Status; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Magnetic Resonance Spectroscopy; Male; Nuclear Magnetic Resonance, Biomolecular; Risk Factors; Sex Factors

Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study. - Gottdiener, John S; McClelland, Robyn L; Marshall, Robert; Shemanski, Lynn; Furberg, Curt D; Kitzman, Dalane W; Cushman, Mary; Polak, Joseph; Gardin, Julius M; Gersh, Bernard J; Aurigemma, Gerard P; Manolio, Teri A (Ann Intern Med, 2002)
BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function. OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons. DESIGN: Population-based longitudinal study of coronary heart disease and stroke. SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland. PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community. MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality. RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category. CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.
Keywords: Aged; Cause of Death; Echocardiography; Female; Heart Failure; Humans; Longitudinal Studies; Male; Myocardial Infarction; Prevalence; Prognosis; Risk Factors; Stroke; Ventricular Dysfunction, Right; Ventricular Function, Left

Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. - Young, Terry; Shahar, Eyal; Nieto, F Javier; Redline, Susan; Newman, Anne B; Gottlieb, Daniel J; Walsleben, Joyce A; Finn, Laurel; Enright, Paul; Samet, Jonathan M (Arch Intern Med, 2002)
BACKGROUND: Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. METHODS: The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. RESULTS: Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. CONCLUSIONS: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.
Keywords: Adult; Age Factors; Aged; Aged, 80 and over; Cohort Studies; Continental Population Groups; Female; Humans; Male; Middle Aged; Obesity; Predictive Value of Tests; Residence Characteristics; Risk Factors; Sex Factors; Sleep Apnea Syndromes; Snoring

Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. - Lyketsos, Constantine G; Lopez, Oscar; Jones, Beverly; Fitzpatrick, Annette L; Breitner, John; DeKosky, Steven (JAMA, 2002)
CONTEXT: Mild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI. OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study. DESIGN: Cross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia. MAIN OUTCOME MEASURE: Prevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms. RESULTS: Of the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P =.02). CONCLUSIONS: Neuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.
Keywords: Aged; Aggression; Anxiety; Behavioral Symptoms; Cognition Disorders; Comorbidity; Cross-Sectional Studies; Delusions; Dementia; Depression; Feeding and Eating Disorders; Female; Humans; Longitudinal Studies; Male; Neuropsychological Tests; Prevalence; Sleep Wake Disorders

Prevalence of renovascular disease in the elderly: a population-based study. - Hansen, Kimberley J; Edwards, Matthew S; Craven, Timothy E; Cherr, Gregory S; Jackson, Sharon A; Appel, Richard G; Burke, Gregory L; Dean, Richard H (J Vasc Surg, 2002)
PURPOSE: The purpose of this investigation was to estimate the population-based prevalence of renovascular disease (RVD), defined as > or = 60% diameter-reducing renal artery stenosis or occlusion, and to define its associations with age, gender, race, and other potential risk factors among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a multicenter, longitudinal cohort study of cardiovascular disease risk factors, morbidity, and mortality among free-living adults of more than 65 years of age. As part of an ancillary investigation, participants in the Forsyth County cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD. RVD was defined as stenosis with a focal renal artery peak systolic velocity exceeding 1.8 m/s in the main renal artery and defined as occlusion when an imaged renal artery lacked a Doppler signal. Demographic and atherosclerotic risk factor data were gathered as part of the baseline CHS examination. Univariable tests of association were performed with chi(2) and Student t tests and logistic regression analysis. Multivariate associations were examined with logistic regression analysis. RESULTS: Eight hundred seventy CHS participants underwent RDS. Of these examinations, 834 (96%) were technically adequate to define the presence or absence of RVD. The RDS study cohort had a mean age of 77.2 +/- 4.9 years and consisted of 63% women and 37% men. Participant race was 76% white and 23% African American. The overall prevalence rate of RVD was 6.8%. Among the 57 patients with RVD, 50 (88%) had unilateral disease and seven (12%) had bilateral disease. Seven cases were seen of renal artery occlusion, including one case with contralateral renal artery stenosis. The mean ages of patients with and without RVD were 78.7 +/- 5.7 years and 77.1 +/- 4.9 years (P =.018). RVD was present in 5.5% of women and 9.1% of men (P =.053). RVD was present in 6.9% of white participants and 6.7% of African American participants (P =.933). Multivariate analysis revealed increasing participant age (P =.028; odds ratio, 1.34; 95% CI, 1.03, 1.73), high-density lipoprotein cholesterol levels of less than 40 mg/dL (P =.003; odds ratio, 2.63; 95% CI, 1.40, 4.93), and increasing systolic blood pressure (P =.007; odds ratio, 1.44; 95% CI, 1.10, 1.87) to be significantly and independently associated with the presence of RVD. CONCLUSION: This investigation provides the first population-based estimate of the prevalence of RVD among free-living, elderly black and white Americans. RVD was present in 6.8% of the study cohort. RVD showed no association with ethnicity. However, its presence was significantly and independently associated with increasing age, low high-density lipoprotein cholesterol levels, and increasing systolic blood pressure.
Keywords: Age Factors; Aged; Aged, 80 and over; Cohort Studies; Ethnic Groups; Female; Humans; Longitudinal Studies; Male; Prevalence; Prospective Studies; Renal Artery; Renal Artery Obstruction; Risk Factors; Sex Factors; Ultrasonography, Doppler, Duplex

Racial differences in coronary artery calcification in older adults. - Newman, Anne B; Naydeck, Barbara L; Whittle, Jeff; Sutton-Tyrrell, Kim; Edmundowicz, Daniel; Kuller, Lewis H (Arterioscler Thromb Vasc Biol, 2002)
Reports on race-related differences in coronary artery calcium (CAC) are just beginning to emerge and have not been well studied in the elderly. This study was undertaken to assess whether such differences exist and the relationship between CAC and cardiovascular risk factors in a cohort of elderly community-dwelling adults. CAC was measured by using electron-beam tomography in 614 adults (aged 67 to 99 years), of whom 59% were women and 23% were black. The median CAC score was lower in blacks than in whites for men (159 versus 787, respectively; P<0.001) and for women (134 versus 233, respectively; P=0.02) after adjustment for age, cardiovascular disease, and risk factors for cardiovascular disease, although this difference was stronger and remained significant among men only. Lower CAC scores were also observed in the subgroup of blacks with a history of myocardial infarction. The lower CAC scores in blacks compared with whites observed in this study is consistent with either a lower prevalence of coronary artery disease or a lower extent of calcification of coronary artery disease.
Keywords: Age Factors; Aged; Calcinosis; Cohort Studies; Coronary Artery Disease; Female; Humans; Logistic Models; Male; Risk Factors; Sex Factors; Tomography, X-Ray Computed

The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study. - Klein, Ronald; Marino, Emily K; Kuller, Lewis H; Polak, Joseph F; Tracy, Russell P; Gottdiener, John S; Burke, Gregory L; Hubbard, Larry D; Boineau, Robin (Br J Ophthalmol, 2002)
AIMS: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes. METHODS: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45 degrees colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system. RESULTS: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86). CONCLUSION: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.
Keywords: Age of Onset; Aged; Aged, 80 and over; Arteriosclerosis; Black People; Blood Pressure; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Longitudinal Studies; Male; Odds Ratio; Prospective Studies; Regression Analysis; Risk Factors; Time Factors; White People

The relationship between chronically disrupted sleep and healthcare use. - Kapur, Vishesh K; Redline, Susan; Nieto, F Javier; Young, Terry B; Newman, Anne B; Henderson, Jeffrey A (Sleep, 2002)
STUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population. DESIGN: Cross-sectional study. SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies. INTERVENTIONS: N/A. MEASUREMENTS: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data. RESULTS: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS. CONCLUSIONS: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.
Keywords: Adult; Chronic Disease; Cohort Studies; Community Health Services; Cross-Sectional Studies; Disorders of Excessive Somnolence; Female; Health Status; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Polysomnography; Prevalence; Severity of Illness Index; Sleep Apnea, Obstructive; Sleep Deprivation

Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults. - Newman, Anne B; Naydeck, Barbara L; Sutton-Tyrrell, Kim; Edmundowicz, Daniel; O'Leary, Daniel; Kronmal, Richard; Burke, Gregory L; Kuller, Lewis H (Arterioscler Thromb Vasc Biol, 2002)
BACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown. METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures. CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.
Keywords: Aged; Aged, 80 and over; Calcinosis; Cardiovascular Diseases; Carotid Stenosis; Cohort Studies; Coronary Artery Disease; Demography; Female; Humans; Male; Prevalence; Risk Factors; Sensitivity and Specificity; Sex Factors; Tomography, X-Ray Computed; Tunica Intima; Tunica Media

Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study. - Wong, T Y; Hubbard, L D; Klein, R; Marino, E K; Kronmal, R; Sharrett, A R; Siscovick, D S; Burke, G; Tielsch, J M (Br J Ophthalmol, 2002)
AIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people. METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised. RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes. CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Cohort Studies; Diabetic Retinopathy; Eye; Female; Humans; Male; Microcirculation; Prospective Studies; Retina; Retinal Diseases

Serum potassium level and dietary potassium intake as risk factors for stroke. - Green, D M; Ropper, A H; Kronmal, R A; Psaty, B M; Burke, G L (Neurology, 2002)
BACKGROUND: Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. METHODS: The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. RESULTS: Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. CONCLUSIONS: A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.
Keywords: Aged; Cohort Studies; Confidence Intervals; Diuretics; Humans; Linear Models; Male; Potassium; Potassium, Dietary; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke

Short-term variability of respiration and sleep during unattended nonlaboratory polysomnography--the Sleep Heart Health Study. [corrected]. - Quan, Stuart F; Griswold, Michael E; Iber, Conrad; Nieto, F Javier; Rapoport, David M; Redline, Susan; Sanders, Mark; Young, Terry (Sleep, 2002)
STUDY OBJECTIVES: To determine the short-term variability of indices of disturbed respiration and sleep during 2 nights of unattended nonlaboratory polysomnography conducted several months apart. DESIGN: Participants were randomly selected using a block design with stratification on preliminary estimates of 2 criteria: respiratory disturbance index [RDI3% (apnea or hypopnea events associated with > or = 3% O2 desaturation): < 15/hour total sleep time, > or = 15/hour total sleep time] and sleep efficiency (SEff: < 85% and > or = 85%). The RDI and sleep data from initial and repeated polysomnography were compared. SETTING: NA. PARTICIPANTS: A subset of 99 participants in the Sleep Heart Health Study who agreed to have a repeat polysomnogram within 4 months of their original study. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Acceptable repeat polysomnograms were obtained in 91 subjects (mean study interval: 77 +/- 18 [sd] days; range: 31-112 days). There was no significant bias in RDI between study nights using several different RDI definitions including RDI3% and RDI4% (apnea or hypopnea events associated with > or = 4% O2 desaturation). Variability between studies estimated using intraclass correlations (ICC) ranged from 0.77 to 0.81. For subjects with a RDI3% < 15, variability increased as a function of increasing RDI, but for those with a RDI3% > or = 15, variability was constant. Body mass index, SEff, gender, or age did not directly predict RDI variability. Using RDI4% cutpoints of < or = 5, < or = 10 and < or = 15 events per hour of sleep demonstrated that 79.1%, 85.7%, and 87.9% of subjects, respectively, had the same classification of SDB status on both nights of study. There also was no significant bias in sleep staging, sleep efficiency, or arousal index between studies. However, variability was greater with ICC values ranging from 0.37 (% time in REM) to 0.76 (arousal index). CONCLUSION: In the Sleep Heart Health Study, accurate estimates of the severity of sleep-disordered breathing and the quality of sleep were obtained from a single night of unattended nonlaboratory polysomnography. These findings may be applicable to other large epidemiologic studies provided that similar recording techniques and quality-assurance procedures are followed.
Keywords: Adult; Aged; Aged, 80 and over; Apnea; Arousal; Body Mass Index; Circadian Rhythm; Electrocardiography; Electromyography; Electrooculography; Female; Humans; Male; Middle Aged; Oxygen Consumption; Polysomnography; Respiration; Sleep Apnea Syndromes; Sleep Stages; Time Factors

A stroke prediction score in the elderly: validation and Web-based application. - Lumley, Thomas; Kronmal, Richard A; Cushman, Mary; Manolio, Teri A; Goldstein, Steven (J Clin Epidemiol, 2002)
The objective of this study was to construct a prediction model for predicting stroke in an elderly U.S. population, and to assess the accuracy in this population of other previously published prediction models. The subjects were participants in the Cardiovascular Health Study: 2,495 men and 3,393 women age 65 years and older at baseline, and followed for 6.3 years. Among 5,711 participants free of baseline stroke, 399 strokes occurred. Sex-specific prediction equations were constructed using study variables that were most importantly related to incident stroke: age, systolic blood pressure, diabetes, ECG diagnosis of atrial fibrillation or left ventricular hypertrophy, confirmed history of cardiovascular disease, diabetes, time to walk 15 ft, and serum creatinine. The prediction rule was implemented as a risk score and in a Web-based interactive Java applet. Overall, the model predicted 5-year stroke risks ranging from less than 1 to 59%. The 20% of subjects in the highest predicted risk group had a 5-year actual stroke incidence rate of 15%, while the 20% lowest risk group had a 1% incidence. Risk scores from two other studies performed well in these study participants. Effective discrimination between low and high stroke risk in the elderly was possible in this cohort with data that are easy to obtain. Evaluation of the generalizability and clinical usefulness of this prediction model requires further research.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Female; Follow-Up Studies; Humans; Incidence; Male; Models, Cardiovascular; Predictive Value of Tests; Risk Factors; ROC Curve; Stroke; United States

Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study. - Lemaitre, Rozenn N; Psaty, Bruce M; Heckbert, Susan R; Kronmal, Richard A; Newman, Anne B; Burke, Gregory L (Arch Intern Med, 2002)
BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol. METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years' follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for confounding variables. RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline. CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.
Keywords: Aged; Cholesterol, LDL; Coronary Disease; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Incidence; Male; Multivariate Analysis; Proportional Hazards Models; Risk Factors; United States

Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study. - Psaty, Bruce M; Manolio, Teri A; Smith, Nicholas L; Heckbert, Susan R; Gottdiener, John S; Burke, Gregory L; Weissfeld, Joel; Enright, Paul; Lumley, Thomas; Powe, Neil; Furberg, Curt D (Arch Intern Med, 2002)
BACKGROUND: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention. OBJECTIVE: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications. RESULTS: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37% at baseline to 49% in 1999. The 51% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5% in 1990 to 51.1% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased. CONCLUSIONS: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers--the preferred agents since 1993 according to the recommendations of the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure--remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure.
Keywords: Age Factors; Aged; Antihypertensive Agents; Awareness; Cohort Studies; Drug Therapy; Female; Health Knowledge, Attitudes, Practice; Humans; Hypertension; Male; Prospective Studies; Time Factors

Underdiagnosis of sleep apnea syndrome in U.S. communities. - Kapur, Vishesh; Strohl, Kingman P; Redline, Susan; Iber, Conrad; O'Connor, George; Nieto, Javier (Sleep Breath, 2002)
We hypothesize that clinical recognition rates for obstructive sleep apnea-hypoapnea syndrome (OSAHS) are influenced by comorbidity and demographic factors. Data on medical disorders, symptoms of sleep disorders, and cardiovascular risk factors gathered from 15,699 individuals in the Sleep Heart Health Study were compared. Participants were classified into three groups: those with a self-reported physician diagnosis of OSAHS, those with self-reported physician-diagnosed and -treated OSAHS, and those reporting both frequent snoring and daytime sleepiness (two-symptom group). Among all participants, 4.1% reported two symptoms (range across sites: 1.55 to 7.23%), whereas 1.6% reported a physician diagnosis of OSAHS (range: 0.66 to 2.88%) and 0.6% reported physician diagnosis and treatment (range: 0.11 to 0.88%). Recognized OSAHS groups were similar to the two-symptom group in age, having a sleeping partner, measured blood pressure, total cholesterol, and race. In a logistic model that included age along with characteristics found to vary significantly among the three groups (gender, body mass index [BMI], high-density lipoprotein cholesterol levels, hypertension), only male gender and BMI were increased in those with physician-diagnosed and -treated OSAHS. We conclude that disparities (especially in women and in those with lower BMI) exist between current recognition rates for OSAHS and the estimated prevalence by symptom report across the United States.
Keywords: Diagnosis, Differential; Diagnostic Errors; Female; Humans; Male; Middle Aged; Prevalence; Sleep Apnea Syndromes; United States

The 6-min walk test: a quick measure of functional status in elderly adults. - Enright, Paul L; McBurnie, Mary Ann; Bittner, Vera; Tracy, Russell P; McNamara, Robert; Arnold, Alice; Newman, Anne B (Chest, 2003)
OBJECTIVES: To determine the correlates of the total 6-min walk distance (6MWD) in a population sample of adults > or = 68 years old. METHODS: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular Health Study cohort during their seventh annual examination. RESULTS: Of the 3,333 participants with a clinic visit, 2,281 subjects (68%) performed the 6MWT. There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general correlates of a shorter 6MWD in linear regression models in women and men included the following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression, and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV(1) in women; and the use of digitalis in men. Approximately 30% of the variance in 6MWD was explained by the linear regression models. Newly described bivariate associations of a shorter 6MWD included impaired activities of daily living; self-reported poor health; less education; nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes; and higher levels of C-reactive protein, fibrinogen, or WBC count. CONCLUSIONS: Most community-dwelling elderly persons can quickly and safely perform this functional status test in the outpatient clinic setting. The test may be used clinically to measure the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis, diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older adults. Expected values should be adjusted for the patient's age, gender, height, and weight.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Exercise Test; Female; Humans; Ischemic Attack, Transient; Linear Models; Male; Mass Screening; Sensitivity and Specificity; Stroke; United States; Walking

Alcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Kronmal, Richard A; Mittleman, Murray A; O'Leary, Daniel H; Polak, Joseph F; Cushman, Mary; Siscovick, David S (Arterioscler Thromb Vasc Biol, 2003)
OBJECTIVE: The association of alcohol use with atherosclerosis is inconsistent in previous studies. METHODS AND RESULTS: For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07+/-0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07+/-0.05-mm higher IMT than abstainers (P quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24+/-0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22%. CONCLUSIONS: Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.
Keywords: Aged; Alcohol Drinking; Cardiovascular Diseases; Carotid Artery Diseases; Cross-Sectional Studies; Female; Health Surveys; Humans; Longitudinal Studies; Male; Prospective Studies

The association between the length of the QT interval and mortality in the Cardiovascular Health Study. - Robbins, John; Nelson, Jennifer Clark; Rautaharju, Pentti M; Gottdiener, John S (Am J Med, 2003)
PURPOSE: A long QT interval is a risk factor for arrhythmic events and sudden death. Whether moderate QT prolongation is associated with clinical events in community-dwelling elderly patients is uncertain. METHODS: We measured the QT interval in a population-based sample of 5888 men and women at least 65 years of age who were participants in the Cardiovascular Health Study. The association between Bazett's rate-corrected QT (QTc, in ms) and mortality during the subsequent 10 years was evaluated. We stratified participants by the presence or absence of coronary heart disease status at baseline, and adjusted for coronary heart disease risk factors. RESULTS: The rates of all-cause and coronary heart disease mortality were greater in participants with longer QTc intervals. Among participants without known coronary heart disease, those whose QTc interval was >450 ms were at increased risk of all-cause mortality (relative risk [RR] = 1.34; 95% confidence interval [CI]: 1.07 to 1.67) and coronary heart disease mortality (RR = 1.6; 95% CI: 1.0 to 2.5) when compared with participants whose QTc interval was <410 ms. The associations were stronger among those with known coronary heart disease (RR for all-cause mortality = 2.3; 95% CI: 1.6 to 3.3; and RR for coronary heart disease mortality = 2.0; 95% CI: 1.1 to 3.7). CONCLUSIONS: The QT interval from the standard electrocardiograms is of value for identification of elderly persons at increased risk of coronary heart disease and total mortality. A QTc interval >450 ms should prompt clinical evaluation and possible interventions to reduce the risk of coronary events.
Keywords: Aged; Arrhythmias, Cardiac; Cause of Death; Coronary Disease; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Male; Randomized Controlled Trials as Topic; Risk Factors; Statistics as Topic; Survival Analysis; United States

The association between time since last meal and blood pressure in older adults: the cardiovascular health study. - Smith, Nicholas L; Psaty, Bruce M; Rutan, Gale H; Lumley, Thomas; Yanez, David; Chaves, Paulo H M; Kronmal, Richard A (J Am Geriatr Soc, 2003)
OBJECTIVES: To demonstrate a postprandial hypotensive (PPH) phenomenon in older adults. DESIGN: Observational, prospective cohort study composed of baseline and nine follow-up visits. SETTING: Cardiovascular Health Study, an epidemiological study of risk factors for cardiovascular disease in older adults. PARTICIPANTS: Five thousand eight hundred eighty-eight community-dwelling adults aged 65 and older. MEASUREMENTS: Blood pressure and time since last meal were recorded synchronously at baseline and at follow-up clinic visits. Generalized estimating equations were used to estimate associations between time since last meal and blood pressure and to adjust variance estimates to account for repeated blood pressure measures within subjects across fasting times. RESULTS: Mean systolic and diastolic blood pressures were lower in the first hour after the last meal and were progressively higher through the fourth hour after the last meal than blood pressures measured immediately after the last meal (0 hour: 133.7/68.8 mmHg; 1st hour: 130.1/66.6 mmHg; 4th hour: 136.5/71.1 mmHg). Changes were significant for systolic and diastolic measures (P <.001 for both). Exploratory analyses suggested that the systolic PPH association was more pronounced in women. Little evidence was found that the degree of systolic or diastolic PPH varied by age, race, prevalent cardiovascular disease, heart rate, ejection fraction, treated hypertension or diabetes mellitus, or body mass index. CONCLUSION: These data support previous observations that there is a significant drop in blood pressure within 1 hour after a meal in older adults. Time since last meal may be an important factor to consider when measuring blood pressure in older adults, and perhaps national standards need to be set.
Keywords: Aged; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Eating; Female; Humans; Hypotension; Male; Postprandial Period; Prospective Studies; Risk Factors; Time Factors

Body composition in the elderly: the influence of nutritional factors and physical activity. - Mitchell, D; Haan, M N; Steinberg, F M; Visser, M (J Nutr Health Aging, 2003)
BACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio. OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue. DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition. RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes. CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.
Keywords: Absorptiometry, Photon; Aged; Aged, 80 and over; Aging; Body Composition; Cohort Studies; Cross-Sectional Studies; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Exercise; Female; Humans; Male; Walking

Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. - Mozaffarian, Dariush; Lemaitre, Rozenn N; Kuller, Lewis H; Burke, Gregory L; Tracy, Russell P; Siscovick, David S (Circulation, 2003)
BACKGROUND: Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk. METHODS AND RESULTS: In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged > or =65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years' mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk. CONCLUSIONS: Among adults aged > or =65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.
Keywords: Aged; Animals; Arrhythmias, Cardiac; Diet; Eating; Fatty Acids, Omega-3; Female; Fishes; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Prospective Studies; Risk; Tuna

Cereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals. - Mozaffarian, Dariush; Kumanyika, Shiriki K; Lemaitre, Rozenn N; Olson, Jean L; Burke, Gregory L; Siscovick, David S (JAMA, 2003)
CONTEXT: People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population. OBJECTIVE: To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons. DESIGN: Prospective cohort study conducted from 1989 to June 2000. SETTING AND PARTICIPANTS: Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire. MAIN OUTCOME MEASURE: Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction). RESULTS: During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend =.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend =.98) nor vegetable fiber intake (P for trend =.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources. CONCLUSIONS: Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber.
Keywords: Aged; Cardiovascular Diseases; Dietary Fiber; Edible Grain; Female; Fruit; Humans; Male; Nutrition Assessment; Prospective Studies; Risk; Vegetables

C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. - Cao, Jie J; Thach, Chau; Manolio, Teri A; Psaty, Bruce M; Kuller, Lewis H; Chaves, Paulo H M; Polak, Joseph F; Sutton-Tyrrell, Kim; Herrington, David M; Price, Thomas R; Cushman, Mary (Circulation, 2003)
BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT. METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95% CI 0.92 to 1.53), 1.05 (95% CI 0.81 to 1.37), and 1.60 (95% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT. CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.
Keywords: Aged; Brain Ischemia; C-Reactive Protein; California; Carotid Arteries; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Maryland; North Carolina; Odds Ratio; Pennsylvania; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke; Tunica Intima; Tunica Media; Ultrasonography

Diabetes and sleep disturbances: findings from the Sleep Heart Health Study. - Resnick, Helaine E; Redline, Susan; Shahar, Eyal; Gilpin, Adele; Newman, Anne; Walter, Robert; Ewy, Gordon A; Howard, Barbara V; Punjabi, Naresh M (Diabetes Care, 2003)
OBJECTIVE: To test the hypothesis that diabetes is independently associated with sleep-disordered breathing (SDB), and in particular that diabetes is associated with sleep abnormalities of a central, rather than obstructive, nature. RESEARCH DESIGN AND METHODS: Using baseline data from the Sleep Heart Health Study (SHHS), we related diabetes to 1). the respiratory disturbance index (RDI; number of apneas plus hypopneas per h of sleep); 2). obstructive apnea index (OAI; >or=3 apneas/h of sleep associated with obstruction of the upper airway); 3). percent of sleep time < 90% O(2) saturation; 4). central apnea index (CAI; >or=3 apneas [without respiratory effort]/h sleep); 5). occurrence of a periodic breathing (Cheyne Stokes) pattern; and 6) sleep stages. Initial analyses excluding persons with prevalent cardiovascular disease (CVD) were repeated including these participants. RESULTS: Of the 5874 participants included in this report, 692 (11.8%) reported diabetes or were taking oral hypoglycemic medications or insulin and 1002 had prevalent CVD. Among the 4872 persons without CVD, 470 (9.6%) had diabetes. Diabetic participants had worse CVD risk factor profiles than their nondiabetic counterparts, including higher BMI, waist and neck circumferences, triglycerides, higher prevalence of hypertension, and lower HDL cholesterol (P < 0.001, all). Descriptive analyses indicated differences between diabetic and nondiabetic participants in RDI, sleep stages, sleep time <90% O(2) saturation, CAI, and periodic breathing (P < 0.05, all). However, multivariable regression analyses that adjusted for age, sex, BMI, race, and neck circumference eliminated these differences for all sleep measures except percent time in rapid eye movement (REM) sleep (19.0% among diabetic vs. 20.1% among nondiabetic subjects, P < 0.001) and prevalence of periodic breathing (odds ratio [OR] for diabetic subjects versus nondiabetic subjects 1.80, 95% CI 1.02-3.15). Additionally, adjusted analyses showed diabetes was associated with nonstatistically significant elevations in the odds of an increased central breathing index (OR 1.42, 95% CI 0.80-2.55). Addition to the analysis of the 1002 persons with prevalent CVD (including 222 people with diabetes) did not materially change these results. CONCLUSIONS: These data suggest that diabetes is associated with periodic breathing, a respiratory abnormality associated with abnormalities in the central control of ventilation. Some sleep disturbances may result from diabetes through the deleterious effects of diabetes on central control of respiration. The high prevalence of SDB in diabetes, although largely explained by obesity and other confounders, suggests the presence of a potentially treatable risk factor for CVD in the diabetic population.
Keywords: Aged; Diabetes Mellitus; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Risk Factors; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Early age-related maculopathy in the cardiovascular health study. - Klein, Ronald; Klein, Barbara E K; Marino, Emily K; Kuller, Lewis H; Furberg, Curt; Burke, Gregory L; Hubbard, Larry D (Ophthalmology, 2003)
OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes. DESIGN: Population-based cohort study. PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998. METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES: Early ARM. RESULTS: Early ARM was present in 15.5% and late ARM in 1.3% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1%) compared with whites (18.2%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM. CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Arteriosclerosis; Blood Pressure; C-Reactive Protein; California; Cohort Studies; Diet; European Continental Ancestry Group; Female; Humans; Hypertension; Leukocyte Count; Longitudinal Studies; Macular Degeneration; Male; Mid-Atlantic Region; North Carolina; Prevalence; Prospective Studies; Risk Factors; Serum Albumin

Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. - Shlipak, Michael G; Fried, Linda F; Crump, Casey; Bleyer, Anthony J; Manolio, Teri A; Tracy, Russell P; Furberg, Curt D; Psaty, Bruce M (Circulation, 2003)
BACKGROUND: Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. METHODS AND RESULTS: The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar. CONCLUSION: Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.
Keywords: Aged; alpha-2-Antiplasmin; Biomarkers; Blood Coagulation Factors; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Creatinine; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Humans; Inflammation; Interleukin-6; Male; Prospective Studies; Renal Insufficiency; Risk Factors

Evaluation of dementia in the cardiovascular health cognition study. - Lopez, Oscar L; Kuller, Lewis H; Fitzpatrick, Annette; Ives, Diane; Becker, James T; Beauchamp, Norman (Neuroepidemiology, 2003)
OBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS). METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists. RESULTS: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer's disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women. CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.
Keywords: Age Distribution; Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Dementia; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Prevalence; Risk Factors; Sex Distribution

Fibrin fragment D-dimer and the risk of future venous thrombosis. - Cushman, Mary; Folsom, Aaron R; Wang, Lu; Aleksic, Nena; Rosamond, Wayne D; Tracy, Russell P; Heckbert, Susan R (Blood, 2003)
Plasma D-dimer concentration rises more than 100-fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in 2 prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21 690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (P for trend <.0001). Following added adjustment for sex, race, body mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIII coagulant activity (factor VIII:c), these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (P for trend <.0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio, 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow-up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis.
Keywords: Aged; Body Mass Index; Cohort Studies; Continental Population Groups; Factor V; Factor VIII; Female; Fibrin Fibrinogen Degradation Products; Humans; Longitudinal Studies; Male; Middle Aged; Odds Ratio; Prospective Studies; Prothrombin; Risk Factors; Venous Thrombosis

Imputation of missing longitudinal data: a comparison of methods. - Engels, Jean Mundahl; Diehr, Paula (J Clin Epidemiol, 2003)
BACKGROUND AND OBJECTIVES: Missing information is inevitable in longitudinal studies, and can result in biased estimates and a loss of power. One approach to this problem is to impute the missing data to yield a more complete data set. Our goal was to compare the performance of 14 methods of imputing missing data on depression, weight, cognitive functioning, and self-rated health in a longitudinal cohort of older adults. METHODS: We identified situations where a person had a known value following one or more missing values, and treated the known value as a "missing value." This "missing value" was imputed using each method and compared to the observed value. Methods were compared on the root mean square error, mean absolute deviation, bias, and relative variance of the estimates. RESULTS: Most imputation methods were biased toward estimating the "missing value" as too healthy, and most estimates had a variance that was too low. Imputed values based on a person's values before and after the "missing value" were superior to other methods, followed by imputations based on a person's values before the "missing value." Imputations that used no information specific to the person, such as using the sample mean, had the worst performance. CONCLUSIONS: We conclude that, in longitudinal studies where the overall trend is for worse health over time and where missing data can be assumed to be primarily related to worse health, missing data in a longitudinal sequence should be imputed from the available longitudinal data for that person.
Keywords: Aged; Analysis of Variance; Bias; Coronary Disease; Data Interpretation, Statistical; Depression; Female; Health Status; Humans; Longitudinal Studies; Male; Research Design; Risk Factors; Stroke; United States

Inflammation as a risk factor for atrial fibrillation. - Aviles, Ronnier J; Martin, David O; Apperson-Hansen, Carolyn; Houghtaling, Penny L; Rautaharju, Pentti; Kronmal, Richard A; Tracy, Russell P; Van Wagoner, David R; Psaty, Bruce M; Lauer, Michael S; Chung, Mina K (Circulation, 2003)
BACKGROUND: The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort. METHODS AND RESULTS: CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9+/-1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P=0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P=0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P<0.001). CONCLUSIONS: CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.
Keywords: Aged; Atrial Fibrillation; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Inflammation; Longitudinal Studies; Male; Risk Factors

Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly. - Crainich, P; Jenny, N S; Tang, Z; Arnold, A M; Kuller, L H; Manolio, T; Sharrett, A R; Tracy, R P (J Thromb Haemost, 2003)
Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.
Keywords: African Continental Ancestry Group; Aged; Alleles; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; European Continental Ancestry Group; Female; Genotype; Homozygote; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Promoter Regions, Genetic; Risk

Lp(a) lipoprotein, vascular disease, and mortality in the elderly. - Ariyo, Abraham A; Thach, Chau; Tracy, Russell (N Engl J Med, 2003)
BACKGROUND: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults. METHODS: In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line. RESULTS: Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation. CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.
Keywords: Aged; Coronary Disease; Female; Humans; Incidence; Lipoprotein(a); Male; Mortality; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Stroke; Survival Analysis; United States; Vascular Diseases

Multiple imputation of baseline data in the cardiovascular health study. - Arnold, Alice M; Kronmal, Richard A (Am J Epidemiol, 2003)
Most epidemiologic studies will encounter missing covariate data. Software packages typically used for analyzing data delete any cases with a missing covariate to perform a complete case analysis. The deletion of cases complicates variable selection when different variables are missing on different cases, reduces power, and creates the potential for bias in the resulting estimates. Recently, software has become available for producing multiple imputations of missing data that account for the between-imputation variability. The implementation of the software to impute missing baseline data in the setting of the Cardiovascular Health Study, a large, observational study, is described. Results of exploratory analyses using the imputed data were largely consistent with results using only complete cases, even in a situation where one third of the cases were excluded from the complete case analysis. There were few differences in the exploratory results across three imputations, and the combined results from the multiple imputations were very similar to results from a single imputation. An increase in power was evident and variable selection simplified when using the imputed data sets.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Analysis of Variance; Cardiovascular Diseases; Cause of Death; Cohort Studies; Data Collection; Data Interpretation, Statistical; Epidemiologic Studies; Female; Humans; Linear Models; Male; Mathematical Computing; Models, Statistical; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Software; Survival Analysis; United States; Ventricular Remodeling

n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. - Lemaitre, Rozenn N; King, Irena B; Mozaffarian, Dariush; Kuller, Lewis H; Tracy, Russell P; Siscovick, David S (Am J Clin Nutr, 2003)
BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults. OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults. DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event. RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction. CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.
Keywords: Aged; alpha-Linolenic Acid; Biomarkers; Case-Control Studies; Cohort Studies; Coronary Disease; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Incidence; Male; Myocardial Infarction; Odds Ratio; Phospholipids; Prevalence; Prospective Studies; Risk Factors

Perceptions and implications of received spousal care: evidence from the Caregiver Health Effects Study. - Martire, Lynn M; Schulz, Richard; Wrosch, Carsten; Newsom, Jason T (Psychol Aging, 2003)
The experiences of older care recipients have received far less theoretical and empirical attention than those of their family caregivers. In this study of 91 care recipients, the authors assessed perceptions of the amount, timing, and manner of spousal assistance; the amount of strain experienced from receiving care; and psychological well-being. Although female care recipients were more likely to report dissatisfaction with the manner in which assistance was provided, there were few gender differences in perceptions of care overall. In a stringent test of the hypothesis that perceived quality of spousal care affects recipient well-being, the authors found that poorer quality of care was related to increased depressive symptoms and a decreased sense of mastery 1 year later. These longitudinal effects were independent of the recipient's physical disability, marital quality, and care-receiving strain as well as the caregiver's well-being. These findings argue for a comprehensive assessment of the care-receiving experience that includes both care-recipient and caregiver perspectives.
Keywords: Aged; Caregivers; Chronic Disease; Disabled Persons; Family Health; Female; Health Status; Humans; Longitudinal Studies; Male; Mental Health; Quality of Health Care; Research Design; Spouses

Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. - Lopez, Oscar L; Jagust, William J; DeKosky, Steven T; Becker, James T; Fitzpatrick, Annette; Dulberg, Corinne; Breitner, John; Lyketsos, Constantine; Jones, Beverly; Kawas, Claudia; Carlson, Michelle; Kuller, Lewis H (Arch Neurol, 2003)
OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study. DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort. SETTING: Multicenter population study. PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI. MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type. RESULTS: The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%. CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Dementia; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Memory Disorders; Neuropsychological Tests; Pennsylvania; Population; Psychiatric Status Rating Scales

The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study. - Wong, Tien Yin; Klein, Ronald; Sharrett, A Richey; Manolio, Teri A; Hubbard, Larry D; Marino, Emily K; Kuller, Lewis; Burke, Gregory; Tracy, Russell P; Polak, Joseph F; Gottdiener, John S; Siscovick, David S (Ophthalmology, 2003)
PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons. DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities. METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations. MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis. RESULTS: The prevalence of retinal microvascular abnormalities was 8.3% for retinopathy, 9.6% for focal arteriolar narrowing, and 7.7% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis. CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Prevalence; Retinal Diseases; Retinal Vessels; Risk Factors; United States

A prospective analysis of risk factors for white matter disease in the brain stem: the Cardiovascular Health Study. - Ding, Jingzhong; Nieto, F Javier; Beauchamp, Norman J; Longstreth, W T; Manolio, Teri A; Hetmanski, Jacqueline B; Fried, Linda P (Neuroepidemiology, 2003)
BACKGROUND AND PURPOSE: White matter disease (WMD) in the brain stem may be a predictor of poor clinical outcome, independent of WMD in the periventricular and subcortical areas of the brain. Many cardiovascular risk factors such as older age, hypertension, and smoking have been suggested as risk factors for WMD in the periventricular and subcortical areas of the brain. However, no epidemiologic study has examined the associations between cardiovascular risk factors and WMD in the brain stem. METHODS: A total of 789 participants, aged 65 years or older, from the Cardiovascular Health Study constituted the present study population. WMD, defined as hyperintensive lesions on magnetic resonance imaging (MRI), in the brain stem was measured in 1992/1993 and 1997/1998. RESULTS: Of the 789 participants, 212 (26.9%) had WMD in the brain stem in 1997/1998. In multivariate logistic regression analysis, the presence of WMD in the brain stem in 1997/1998 was significantly associated with several variables measured in 1992/1993: an increase by 5 years of age (OR = 1.51, 95% CI: 1.25-1.83), a 10-pack-years increase in smoking (OR = 1.12, 95% CI: 1.04-1.21), a 0.1-liter increase in first-second forced expiratory volume (OR = 0.95, 95% CI: 0.92-0.99), a 1 micromol/l increase in fibrinogen level (OR = 1.13, 95% CI: 1.03-1.23), and MRI infarction (OR = 2.58, 95% CI: 1.78-3.74). Excluding those (n = 167) with WMD in the brain stem in 1992/1993, the pattern remained. Hypertension was not associated with WMD in the brain stem. CONCLUSIONS: Increased age, smoking, lower forced expiratory volume, increased fibrinogen level, and MRI infarction, but not hypertension, may be independent risk factors for WMD in the brain stem in older adults.
Keywords: Age Factors; Aged; Brain Diseases; Brain Infarction; Brain Stem; Cardiovascular Diseases; Female; Fibrinogen; Forced Expiratory Volume; Humans; Magnetic Resonance Imaging; Male; Prospective Studies; Regression Analysis; Risk Factors; Smoking

Prospective study of alcohol consumption and risk of dementia in older adults. - Mukamal, Kenneth J; Kuller, Lewis H; Fitzpatrick, Annette L; Longstreth, W T; Mittleman, Murray A; Siscovick, David S (JAMA, 2003)
CONTEXT: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. OBJECTIVE: To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. MAIN OUTCOME MEASURES: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. RESULTS: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term =.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. CONCLUSIONS: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.
Keywords: Aged; Alcohol Drinking; Apolipoprotein E4; Apolipoproteins E; Brain; Case-Control Studies; Dementia; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prospective Studies; Risk

Prospective study of fibrinolytic markers and venous thromboembolism. - Folsom, Aaron R; Cushman, Mary; Heckbert, Susan R; Rosamond, Wayne D; Aleksic, Nena (J Clin Epidemiol, 2003)
Prior research has conflicted on whether increased levels of plasma fibrinolytic factors may identify patients at risk of venous thromboembolism (VTE). We therefore performed a nested case-control study of VTE within two prospective population-based studies. In 308 participants who developed VTE and 640 controls, we measured PAI-1 antigen, tPA/PAI-1 complex, plasmin-alpha 2-antiplasmin (PAP), and the PAI-1 -675 4G/5G promoter polymorphism on pre-event blood samples. There was no overall association between any of these fibrinolytic variables and VTE, after adjustment for age or for multiple VTE risk factors. There was weak evidence for an interaction of PAP with elevated factor VIIIc and elevated D-dimer in augmenting VTE risk. We conclude that, for the most part, these fibrinolytic markers do not identify healthy subjects at risk for VTE.
Keywords: Aged; alpha-2-Antiplasmin; Antifibrinolytic Agents; Biomarkers; Caenorhabditis elegans Proteins; Case-Control Studies; Female; Fibrinolysin; Fibrinolysis; Humans; Male; Middle Aged; Odds Ratio; Plasminogen Activator Inhibitor 1; Prognosis; Prospective Studies; Protein-Tyrosine Kinases; Risk Factors; Thromboembolism; Venous Thrombosis

Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study. - Aleksic, N; Folsom, A R; Cushman, M; Heckbert, S R; Tsai, M Y; Wu, K K (J Thromb Haemost, 2003)
Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.
Keywords: Age Factors; Aged; Amino Acid Substitution; Case-Control Studies; Female; Genotype; Humans; Incidence; Male; Polymorphism, Genetic; Prevalence; Prospective Studies; Risk Factors; Thromboembolism; Thrombomodulin; Venous Thrombosis

Regional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States. - Louis, Elan D; Fried, Linda P; Fitzpatrick, Annette L; Longstreth, William T; Newman, Anne B (Mov Disord, 2003)
For reasons that are unclear, prevalence estimates of essential tremor (ET) differ considerably across the United States. Separate communities have never been sampled within the framework of the same study to substantiate these differences. We estimated the prevalence of physician-diagnosed ET in the elderly in four communities in the United States in whom the same screening questions were used, and examined whether this prevalence differed between Caucasians and African Americans. The Cardiovascular Health Study recruited a sample of Medicare beneficiaries >/=65 years of age from four communities in different regions of the United States. In 1998 to 1999, 3,494 participants (mean age, 80.0 years; range, 70-103 years) answered a 12-question screen for ET, including the question, "has a doctor diagnosed you as having familial tremor or benign essential tremor?" Fifty-four participants reported that a doctor had diagnosed them as having ET (1.5%; 95% confidence interval, [CI], 1.1-2.0%). Prevalence was similar across the four communities (1.1-2.0%). A larger proportion of Caucasians than African Americans reported a diagnosis of ET (1.7% vs. 0.4%; odds ratio = 4.9; 95% CI, 1.2-20.2; P = 0.028). In a logistic regression analysis, physician-diagnosed ET was associated with Caucasian ethnicity (P = 0.038) but not with age, gender, education, mental status or depression scores, income, smoking status, or alcohol consumption. When a standardized screening question was used, the proportion of participants with physician-diagnosed ET was similar across four communities, suggesting that the prevalence of this condition may be less variable than is often reported. Caucasians were five times more likely to have physician-diagnosed ET than were African Americans. This study does not provide an explanation for this difference, which deserves further study.
Keywords: African Continental Ancestry Group; Aged; Aged, 80 and over; Essential Tremor; European Continental Ancestry Group; Female; Humans; Male; Physicians; Prevalence; United States

The relation of dietary patterns to future survival, health, and cardiovascular events in older adults. - Diehr, Paula; Beresford, Shirley A A (J Clin Epidemiol, 2003)
BACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns. METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later. RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large. CONCLUSIONS: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes.
Keywords: Aged; Cardiovascular Diseases; Cluster Analysis; Diet; Energy Intake; Female; Follow-Up Studies; Health Status; Humans; Incidence; Linear Models; Male; Nutritional Physiological Phenomena; Survival Rate

Relationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study. - Edwards, Matthew S; Hansen, Kimberley J; Craven, Timothy E; Cherr, Gregory S; Bleyer, Anthony J; Burke, Gregory L; Dean, Richard H (Am J Kidney Dis, 2003)
BACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS). METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination. RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041). CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.
Keywords: Aged; Blood Pressure; Female; Humans; Hypertension; Kidney; Kidney Diseases; Male; Prospective Studies; Ultrasonography, Doppler, Duplex; Vascular Diseases

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. - Fried, Linda F; Shlipak, Michael G; Crump, Casey; Bleyer, Anthony J; Gottdiener, John S; Kronmal, Richard A; Kuller, Lewis H; Newman, Anne B (J Am Coll Cardiol, 2003)
OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level > or =1.5 mg/dl in men or > or =1.3 mg/dl in women. RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.
Keywords: Aged; Cardiovascular Diseases; Confidence Intervals; Creatinine; Female; Heart Failure; Humans; Intermittent Claudication; Kidney Failure, Chronic; Male; Odds Ratio; Predictive Value of Tests; Survival Analysis

Risk factors for dementia in the cardiovascular health cognition study. - Kuller, Lewis H; Lopez, Oscar L; Newman, Anne; Beauchamp, Norman J; Burke, Greg; Dulberg, Corinne; Fitzpatrick, Annette; Fried, Linda; Haan, Mary N (Neuroepidemiology, 2003)
BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.
Keywords: Aged; Aged, 80 and over; Apolipoproteins E; Cardiovascular Diseases; Cognition Disorders; Dementia; Female; Genotype; Humans; Magnetic Resonance Imaging; Male; Odds Ratio; Predictive Value of Tests; Proportional Hazards Models; Risk Factors

Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2. - Lopez, Oscar L; Jagust, William J; Dulberg, Corinne; Becker, James T; DeKosky, Steven T; Fitzpatrick, Annette; Breitner, John; Lyketsos, Constantine; Jones, Beverly; Kawas, Claudia; Carlson, Michelle; Kuller, Lewis H (Arch Neurol, 2003)
OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.
Keywords: Aged; Apolipoprotein E4; Apolipoproteins E; Brain; Cardiovascular Diseases; Cognition Disorders; Cohort Studies; Depressive Disorder; Female; Humans; Logistic Models; Longitudinal Studies; Magnetic Resonance Imaging; Male; Mood Disorders; Pennsylvania; Population; Risk Factors

Serum homocysteine, thermolabile variant of methylene tetrahydrofolate reductase (MTHFR), and venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology (LITE). - Tsai, Albert W; Cushman, Mary; Tsai, Michael Y; Heckbert, Susan R; Rosamond, Wayne D; Aleksic, Nena; Yanez, N David; Psaty, Bruce M; Folsom, Aaron R (Am J Hematol, 2003)
We sought to examine prospectively the association of serum homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T gene polymorphism with risk of venous thromboembolism (VTE). We studied these relationships in a nested case-control study of 303 VTE cases and 635 matched controls from a population-based cohort of 21,680 adults from six U.S. communities. The highest quintile of serum homocysteine carried a non-statistically significant adjusted odds ratio of 1.55 (95% CI, 0.93-2.58) compared to the lowest quintile in the overall cohort but a significant association among adults aged 45-64 years (OR = 2.05, 95% CI, 1.10-3.83) and an inverse association in those > or = 65 years of age. Carriers of the MTHFR C677T polymorphism were not at higher risk for VTE than those with normal genotype (OR = 0.74, 95% CI = 0.56-0.98). Our prospective data showed, at most, a weak relationship between homocysteine and VTE risk, with associations larger among younger participants. MTHFR C677T was not a risk factor for VTE.
Keywords: Aged; Aging; Animals; Case-Control Studies; Cohort Studies; Factor V; Female; Genotype; Homocysteine; Humans; Longitudinal Studies; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Odds Ratio; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Prospective Studies; Risk Factors; Venous Thrombosis

Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. - Sanders, Mark H; Newman, Anne B; Haggerty, Catherine L; Redline, Susan; Lebowitz, Michael; Samet, Jonathan; O'Connor, George T; Punjabi, Naresh M; Shahar, Eyal (Am J Respir Crit Care Med, 2003)
Neither the association between obstructive airways disease (OAD) and sleep apnea-hypopnea (SAH) nor the sleep consequences of each disorder alone and together have been characterized in an adult community setting. Our primary aims were (1) to determine if there is an association between OAD and SAH and (2) identify predictors of oxyhemoglobin desaturation during sleep in persons having OAD with and without SAH. Polysomnography and spirometry results from 5,954 participants in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC value less than 70%. Assessment of SAH prevalence in OAD was performed using thresholds of respiratory disturbance index (RDI) greater than 10 and greater than 15. A total of 1,132 participants had OAD that was predominantly mild (FEV1/FVC 63.81 +/- 6.56%, mean +/- SD). SAH was not more prevalent in participants with OAD than in those without OAD (22.32 versus 28.86%, with and without OAD, respectively, at RDI threshold values greater than 10; and 13.97 versus 18.63%, with and without OAD, respectively, at RDI threshold value greater than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation (> 5% total sleep time with saturation < 90%) was greater than 1.9 when FEV1/FVC was less than 65%. Participants with both OAD and SAH had greater sleep perturbation and desaturation than those with one disorder. Generally mild OAD alone was associated with minimally altered sleep quality. We conclude that (1) there is no association between generally mild OAD and SAH; (2) exclusive of SAH and after adjusting for demographic factors and awake oxyhemoglobin saturation, an FEV1/FVC value less than 65% is associated with increased risk of sleep desaturation; (3) desaturation is greater in persons with both OAD and SAH compared with each of these alone; and (4) individuals with generally mild OAD and without SAH in the community have minimally perturbed sleep.
Keywords: Aged; Cohort Studies; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oxyhemoglobins; Polysomnography; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sleep; Sleep Apnea, Obstructive; Spirometry; Vital Capacity

"Successful aging": effect of subclinical cardiovascular disease. - Newman, Anne B; Arnold, Alice M; Naydeck, Barbara L; Fried, Linda P; Burke, Gregory L; Enright, Paul; Gottdiener, John; Hirsch, Calvin; O'Leary, Daniel; Tracy, Russell (Arch Intern Med, 2003)
BACKGROUND: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined. METHODS: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning. RESULTS: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself. CONCLUSIONS: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.
Keywords: Aged; Aged, 80 and over; Aging; C-Reactive Protein; Cardiovascular Diseases; Female; Health Status; Humans; Longitudinal Studies; Male; Quality of Life; Regression Analysis; Risk Factors

Transitions in spousal caregiving. - Burton, Lynda C; Zdaniuk, Bozena; Schulz, Richard; Jackson, Sharon; Hirsch, Calvin (Gerontologist, 2003)
PURPOSE: This study describes transitions over 5 years among community-dwelling elderly spouses into and within caregiving roles and associated health outcomes. DESIGN AND METHODS: Participants in the Caregiver Health Effects Study (n = 818) were interviewed four times over 5 years with changes in their caregiving status described. Analyses of the effect on health outcomes of transitions were performed on those for whom four observations were available (n = 428). RESULTS: Only half (49.5%) of noncaregivers at baseline remained noncaregivers at 5-year follow-up. The remainder experienced one or more transitions, including moving into the caregiving role, their own or their spouse's death, or placement of their spouse in a long-term care facility. The trajectory of health outcomes associated with caregiving was generally downward. Those who transitioned to heavy caregiving had more symptoms of depression, and poorer self-reported health and health behaviors. IMPLICATIONS: Transitions into and within the caregiving role should be monitored for adverse health effects on the caregiver, with interventions tailored to the individual's location in the caregiving trajectory.
Keywords: Adaptation, Psychological; Aged; Aged, 80 and over; Caregivers; Female; Health Behavior; Health Status; Humans; Long-Term Care; Male; Residence Characteristics; Spouses; Stress, Psychological; Time Factors

Variation in symptoms of sleep-disordered breathing with race and ethnicity: the Sleep Heart Health Study. - O'Connor, George T; Lind, Bonnie K; Lee, Elisa T; Nieto, F Javier; Redline, Susan; Samet, Jonathan M; Boland, Lori L; Walsleben, Joyce A; Foster, Gregory L (Sleep, 2003)
STUDY OBJECTIVES: To examine the relation of sleep-related symptoms to race and ethnicity in a diverse sample of middle-aged and older men and women. DESIGN: Cross-sectional questionnaire survey. SETTING: In the initial phase of the Sleep Heart Health Study, men and women enrolled in participating epidemiologic cohort studies were surveyed. PARTICIPANTS: 13,194 men and women 40 years of age and older, including 11,517 non-Hispanic white, 648 black, 643 American Indian, 296 Hispanic, and 90 Asian-Pacific Islander. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: After adjustment for BMI and other factors, frequent snoring was more common among Hispanic women (odds ratio (OR) = 2.25, 95% confidence interval (CI) = 1.48, 3.42) and black women (OR = 1.55, 95% Ci = 1.13, 2.13) than among non-Hispanic white women. Hispanic men were significantly more likely to report frequent snoring than non-Hispanic white men (OR = 2.30, 95% CI = 1.43, 3.69). Black, American Indian, and Asian men did not differ significantly from white men in snoring prevalence. American Indian women were significantly more likely to report breathing pauses during sleep than their white, non-Hispanic counterparts (OR = 1.52, 95% CI 1.03, 2.24), although polysomnography data on a subset of the sample suggested that the association between this symptom reported on questionnaire and objective evidence of sleep-disordered breathing may be weaker among American Indians than among other groups. Mean Epworth Sleepiness Scale scores were slightly higher in black men and women than in their white, non-hispanic counterparts. CONCLUSIONS: Frequent snoring was more common among black and Hispanic women and Hispanic men than among their white non-Hispanic counterparts, even after adjusting for BMI and other factors. Further research including polysomnography and objective measurements of sleepiness is needed to assess the physiologic and clinical significance of these findings.
Keywords: Adult; Cross-Sectional Studies; Electroencephalography; Electrooculography; Ethnic Groups; Female; Heart Rate; Humans; Male; Polysomnography; Severity of Illness Index; Sleep Apnea Syndromes; Snoring; Surveys and Questionnaires

Alcohol consumption and inflammatory markers in older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Cushman, Mary; Mittleman, Murray A; Tracy, Russell P; Siscovick, David S (Atherosclerosis, 2004)
OBJECTIVE: We sought to determine the relation of alcohol intake and systemic inflammation in a population-based sample of older adults. METHODS AND RESULTS: As part of the Cardiovascular Health Study (CHS), 5865 adults aged 65 years and older reported their intake of beer, wine, and liquor. We determined white blood cell count (WBC), factor VIII coagulant activity (factor VIIIc), and levels of C-reactive protein (CRP), fibrinogen, and albumin as markers of systemic inflammation. Among participants without confirmed cardiovascular disease, alcohol consumption was inversely associated with WBC, factor VIIIc, and fibrinogen level, and positively associated with albumin concentration in multivariate analyses. We found no consistent modification of these results by sex, obesity, or beverage type. The relation of alcohol use and CRP levels was significantly modified by apoE genotype (P interaction 0.03), with a positive association among participants with an apoE4 allele (P = 0.05), but a trend toward an inverse association among those without an apoE4 allele (P = 0.15). CONCLUSIONS: Alcohol intake is associated with lower levels of inflammatory markers in older adults free of cardiovascular disease.
Keywords: Aged; Aged, 80 and over; Alcohol Drinking; Apolipoproteins E; C-Reactive Protein; Coronary Artery Disease; Female; Fibrinogen; Geriatric Assessment; Humans; Inflammation Mediators; Leukocyte Count; Logistic Models; Longitudinal Studies; Male; Probability; Prospective Studies; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study. - Gottlieb, D J; DeStefano, A L; Foley, D J; Mignot, E; Redline, S; Givelber, R J; Young, T (Neurology, 2004)
BACKGROUND: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association. METHODS: A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship. RESULTS: At least one APOE epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without. CONCLUSION: The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.
Keywords: Adult; Age Distribution; Aged; Aged, 80 and over; Alleles; Apolipoprotein E4; Apolipoproteins E; Cardiovascular Diseases; Cohort Studies; Comorbidity; Female; Genetic Predisposition to Disease; Genotype; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Obesity; Polysomnography; Sleep Apnea, Obstructive; Smoking

Assessment of prolonged QT and JT intervals in ventricular conduction defects. - Rautaharju, Pentti M; Zhang, Zhu-Ming; Prineas, Ron; Heiss, Gerardo (Am J Cardiol, 2004)
The JT interval or Bazett's QTc - QRS has been advocated for detection of prolonged repolarization in ventricular conduction defects (VCDs). However, the use of neither JT nor QTc - QRS has been validated, and normal limits for rate-adjusted JT have not been established for VCDs or for normal ventricular conduction. Functional relations among RR, JT, and QT intervals were evaluated in 11,739 adult men and women with normal ventricular conduction and in 1,251 subjects with major VCD. The results showed that JT adjustment obtained as QTc - QRS retained a strong residual correlation with ventricular rate (r = 0.54), making its use ill-advised. In contrast, QT adjustment as a linear function of the RR interval for VCD as QT(RR,QRS) = QT - 155 x (60/heart rate - 1) - 0.93 x (QRS - 139) + k, with k = -22 ms for men and -34 ms for women, removed the rate dependence and produced upper 2% and 5% normal limits at 460 and 450 ms, respectively, which are identical to those in normal conduction. As an alternative, equally effective linear JT adjustment formulas were derived, including newly required normal standards. Thus, detection of prolonged repolarization in VCD requires the use of the JT interval or a bivariate model for QT with RR and QRS intervals as covariates.
Keywords: Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Bundle-Branch Block; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged

Associates of bone mineral density in older African Americans. - Robbins, John; Hirsch, Calvin; Cauley, Jane (J Natl Med Assoc, 2004)
OBJECTIVES: To assess correlates of bone mineral density (BMD) in older African Americans. PARTICIPANTS: 189 women and 115 men over age 64. METHODS: Variables investigated: BMD by dual X-ray absorptiometry (DXA), medications, cardiovascular disease risk factors, demographic, lifestyle factors and functional status. Variables showing univariate correlation with BMD (p < or = 0.1) were entered into sex-stratified linear regression models. RESULTS: Age range 67-96 (mean 75). The mean BMD (gm/ cm2 +/- standard deviation) is reported for three sites. Total body: 1.03 (+/- 0.12) in women, 1.21 (+/- 0.11) in men. Spine: 1.05 (+/- 0.24) in women, 1.22 (+/- 0.26) in men. Total hip: 0.85 (+/- 0.15) in women, 1.04 (+/- 0.17) in men. Gender was significantly associated with BMD (t-test, p < 0.001). The R2 for tested variables were highly significant only for weight. Age was only significant for total hip in women (p < 0.05). Each kilogram of weight change was associated with a 5.3-6.8 mg/cm2 change in BMD. CONCLUSIONS: In a population-based cohort of older African Americans, average BMD was significantly greater in men than women. Weight accounted for most of the explained variability (R2) in BMD; age added little to the overall R2. Lower-weight, older African-American men and women are at significantly increased risk for low BMD and, thus, likely to be at greater risk for osteoporotic fracture.
Keywords: Aged; Body Weight; Bone Density; Cross-Sectional Studies; Female; Humans; Male; Osteoporosis; Risk Factors

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study. - Psaty, Bruce M; Anderson, Melissa; Kronmal, Richard A; Tracy, Russell P; Orchard, Trevor; Fried, Linda P; Lumley, Thomas; Robbins, John; Burke, Greg; Newman, Anne B; Furberg, Curt D (J Am Geriatr Soc, 2004)
OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.
Keywords: African Americans; African Continental Ancestry Group; Aged; Female; Health Surveys; Humans; Incidence; Lipids; Male; Mortality; Myocardial Infarction; Population Surveillance; Prospective Studies; Risk Factors; Stroke; United States

The association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study. - Barzilay, Joshua I; Kronmal, Richard A; Gottdiener, John S; Smith, Nicholas L; Burke, Gregory L; Tracy, Russell; Savage, Peter J; Carlson, Michelle (J Am Coll Cardiol, 2004)
OBJECTIVES: The purpose of this study was to determine if fasting glucose levels are an independent risk factor for congestive heart failure (CHF) in elderly individuals with diabetes mellitus (DM) with or without coronary heart disease (CHD). BACKGROUND: Diabetes mellitus and CHF frequently coexist in the elderly. It is not clear whether fasting glucose levels in the setting of DM are a risk factor for incident CHF in the elderly. METHODS: A cohort of 829 diabetic participants, age > or =65 years, without prevalent CHF, was followed for five to eight years. The Cox proportional hazards modeling was used to determine the risk of CHF by fasting glucose levels. The cohort was categorized by the presence or absence of prevalent CHD. RESULTS: For a 1 standard deviation (60.6 mg/dl) increase in fasting glucose, the adjusted hazard ratios for incident CHF among participants without CHD at baseline, with or without an incident myocardial infarction (MI) or CHD event on follow-up, was 1.41 (95% confidence interval 1.24 to 1.61; p < 0.0001). Among those with prevalent CHD at baseline, with or without another incident MI or CHD event on follow-up, the corresponding adjusted hazard ratio was 1.27 (95% confidence interval 1.02 to 1.58; p < 0.05). CONCLUSIONS: Among older adults with DM, elevated fasting glucose levels are a risk factor for incident CHF. The relationship of fasting glucose to CHF differs somewhat by the presence or absence of prevalent CHD.
Keywords: Aged; Biomarkers; Blood Glucose; Blood Pressure; Coronary Disease; Diabetes Mellitus; Diabetic Angiopathies; Fasting; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Proportional Hazards Models; Risk Factors; Statistics as Topic; Stroke Volume; Ventricular Function, Left

The association of personal and neighborhood socioeconomic indicators with subclinical cardiovascular disease in an elderly cohort. The cardiovascular health study. - Nordstrom, Cheryl K; Diez Roux, Ana V; Jackson, Sharon A; Gardin, Julius M (Soc Sci Med, 2004)
There has been recent interest in determining whether neighborhood characteristics are related to the cardiovascular health of residents. However, there are no data regarding the relationship between neighborhood socioeconomic status (SES) and prevalence of subclinical cardiovascular disease (CVD) in the elderly. We related personal SES (education, income, and occupation type) and neighborhood socioeconomic characteristics (a block-group score summing six variables reflecting neighborhood income and wealth, education, and occupation) to the prevalence of subclinical CVD (asymptomatic peripheral vascular disease or carotid atherosclerosis, electrocardiogram or echocardiogram abnormalities, and/or positive responses to Rose Questionnaire claudication or angina pectoris) among 3545 persons aged 65 and over, without prevalent CVD, in the Cardiovascular Health Study. Sixty percent of participants had at least one indicator of subclinical disease. Compared to those without, those with subclinical disease had significantly lower education, income, and neighborhood scores and were more likely to have blue-collar jobs. After adjustment for age, gender, and race, those in the lowest SES groups had increased prevalence of subclinical disease compared with those in the highest SES groups (OR = 1.50; 95% CI 1.21, 1.86 for income; OR = 1.41; 95% CI 1.18, 1.69 for education; OR = 1.39; 95% CI 1.16, 1.67 for block-group score). Those reporting a blue-collar lifetime occupation had greater prevalence of subclinical disease relative to those reporting a white-collar occupation (OR = 1.29; 95% CI 1.02-1.59). After adjustment for behavioral and biomedical risk factors, all of these associations were reduced. Neighborhood score tended to remain inversely associated with subclinical disease after adjustment for personal socioeconomic indicators but associations were not statistically significant. Personal income and blue-collar occupation remained significantly associated with subclinical disease after simultaneous adjustment for neighborhood score and education. Personal and neighborhood socioeconomic indicators were associated with subclinical disease prevalence in this elderly cohort. These relationships were reduced after controlling for traditional CVD risk factors.
Keywords: Aged; California; Cardiovascular Diseases; Cohort Studies; Female; Geography; Humans; Male; Maryland; Medicare; North Carolina; Pennsylvania; Residence Characteristics; Risk Factors; Social Class; Socioeconomic Factors; Surveys and Questionnaires

Associations between gender and measures of daytime somnolence in the Sleep Heart Health Study. - Baldwin, Carol M; Kapur, Vishesh K; Holberg, Catharine J; Rosen, Carol; Nieto, F Javier (Sleep, 2004)
STUDY OBJECTIVES: To examine the relationship of gender to subjective measures of sleepiness, including the Epworth Sleepiness Scale (ESS), in a community-based population. DESIGN: A cross-sectional study. SETTING/PARTICIPANTS: Multicenter Sleep Heart Health Study participants (N = 6.440, 52% women) recruited from ongoing cohort studies. INTERVENTIONS: N/A. MEASUREMENTS: Scores from the ESS, Sleep Heart Health Study daytime sleepiness and feeling unrested questions, polysomnography results (respiratory disturbance index at 4% desaturation), as well as data on difficulty initiating and maintaining sleep, insufficient sleep, sedative use, alcohol use, cardiovascular or respiratory disease, frequent awakening due to leg cramps. RESULTS: Women reported feeling sleepy as often as men did (odds ratio [OR] = 1.06; confidence interval [CI], 0.86-1.32), but women were less likely to have an ESS score > 10 (adjusted OR = 0.77; CI, 0.66-0.90) and more likely to report feeling unrested (adjusted OR = 1.39; CI, 1.14-1.69) than men. In men, the ESS score was more strongly correlated with reports of feeling unrested or sleepy compared to women. CONCLUSIONS: Men and women answer questions on sleepiness differently. Findings indicate that using the ESS to detect subjective sleepiness is more likely to identify men with sleepiness. Since the ESS is more strongly related to other subjective measures in men, the ESS may be a more sensitive measure of subjective sleepiness in men than in women.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Disorders of Excessive Somnolence; Female; Health Status; Humans; Hypertension; Male; Middle Aged; Polysomnography; Severity of Illness Index; Sex Factors

Associations between renovascular disease and prevalent cardiovascular disease in the elderly: a population-based study. - Edwards, Matthew S; Hansen, Kimberley J; Craven, Timothy E; Bleyer, Anthony J; Burke, Gregory L; Levy, Pavel J; Dean, Richard H (Vasc Endovascular Surg, 2004)
Atherosclerotic renovascular disease (RVD) is a suspected contributor to the morbidity and mortality of cardiovascular disease (CVD) through its potential effects on blood pressure and excretory renal function as well as through its associations with other forms of CVD. However, population-based data regarding the associations between the presence of RVD and prevalent CVD are lacking. The Cardiovascular Health Study (CHS) is a prospective, multicenter cohort study of CVD among elderly Americans. As part of an ancillary study, participants in the Forsyth County, North Carolina, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to establish the presence or absence of RVD (defined as any focal peak systolic velocity >/= 1.8 m/second or the absence of a Doppler-shifted signal from an imaged artery). Demographic, risk factor, and prevalent CVD data were obtained from the CHS coordinating center and matched with ancillary study participants. Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African-Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/-4.9 years underwent RDS examination. RVD was present in 57 participants (6.8%). Overall, clinical and/or subclinical manifestations of CVD were present in 603 participants (72.3%) at the time of RDS. Participants with RVD demonstrated a significantly greater prevalence of angina (p = 0.002), previous myocardial infarction (p < 0.001), >/= 25% diameter-reducing internal carotid artery stenosis (p = 0.010), increased carotid intimal medial thickness (p = 0.003), and major electrocardiographic abnormalities (p = 0.013). Following adjustment for demographics and cardiovascular risk factors, the presence of RVD demonstrated a significant and independent association with prevalent coronary artery disease but not with prevalent cerebrovascular or lower extremity vascular disease. These results suggest important population-based associations between RVD and both clinical and subclinical manifestations of CVD, especially coronary artery disease.
Keywords: Aged; Arteriosclerosis; Cardiovascular Diseases; Cohort Studies; Humans; Hypertension, Renovascular; Longitudinal Studies; Male; Multivariate Analysis; Prevalence; Prospective Studies; Renal Artery Obstruction; Ultrasonography; United States

Barriers to health care access among the elderly and who perceives them. - Fitzpatrick, Annette L; Powe, Neil R; Cooper, Lawton S; Ives, Diane G; Robbins, John A (Am J Public Health, 2004)
OBJECTIVES: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries. METHODS: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study. RESULTS: The questionnaires were completed by 4889 (91.1%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor's lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors. CONCLUSIONS: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.
Keywords: Aged; Aged, 80 and over; Chi-Square Distribution; Female; Health Behavior; Health Services Accessibility; Humans; Logistic Models; Male; Medicare; Patients; Surveys and Questionnaires; United States

The Cardiovascular Health Study: risk factors, subclinical disease, and clinical cardiovascular disease in older adults. - Newman, Anne B; Siscovick, David (Am J Geriatr Cardiol, 2004)
Keywords: Aged; Cardiovascular Diseases; Female; Geriatric Assessment; Humans; Male; Risk Factors

Chronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study. - Shlipak, Michael G; Fried, Linda F; Stehman-Breen, Catherine; Siscovick, David; Newman, Anne B (Am J Geriatr Cardiol, 2004)
In the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community-dwelling elderly adults. Defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men, CRI was present in 647 (11%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64% in participants with CRI and 43% in those without CRI (odds ratio, 2.34; 95% confidence interval, 1.96-2.80). The incidence of cardiovascular disease events during follow-up was 3% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7% per year in those with creatinine > or =1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C-reactive protein, fibrinogen, and interleukin-6) and hemostatic (factor VII, factor VIII, plasmin-antiplasmin product, and D-dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.
Keywords: Aged; Blood Coagulation Factors; Cardiovascular Diseases; Chronic Disease; Creatinine; Cystatin C; Cystatins; Female; Fibrinogen; Geriatric Assessment; Humans; Incidence; Male; Prevalence; Renal Insufficiency; Risk Factors

Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. - Johnston, S Claiborne; O'Meara, Ellen S; Manolio, Teri A; Lefkowitz, David; O'Leary, Daniel H; Goldstein, Steven; Carlson, Michelle C; Fried, Linda P; Longstreth, W T (Ann Intern Med, 2004)
BACKGROUND: Whether carotid artery disease is a cause of cognitive impairment in persons who have not had stroke is unknown. If this is the case, diminished performance on the Modified Mini-Mental State Examination should be more common in persons with left carotid artery disease than in those with right carotid artery disease. OBJECTIVE: To determine whether left carotid artery disease is associated with cognitive impairment. DESIGN: Cross-sectional and cohort study. SETTING: Four U.S. communities participating in the Cardiovascular Health Study. PATIENTS: 4006 right-handed men and women 65 years of age or older without history of stroke, transient ischemic attack, or carotid endarterectomy. MEASUREMENTS: Internal carotid artery stenosis and intima-media thickness of the common carotid artery were assessed by using duplex ultrasonography. Cognitive impairment was defined as a score less than 80 on the Modified Mini-Mental State Examination, and cognitive decline was defined as an average decrease of more than 1 point annually in Modified Mini-Mental State Examination score during up to 5 years of follow-up. Multivariate logistic regression models were used to estimate the risk for cognitive impairment and decline associated with left internal carotid artery stenosis and intima-media thickness, after adjustment for measures of right-sided disease and risk factors for vascular disease. RESULTS: After adjustment for right-sided stenosis, high-grade (> or =75% narrowing of diameter) stenosis of the left internal carotid artery (32 patients) was associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1] compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to 6.3]). Intima-media thickness of the left common carotid artery was associated with cognitive impairment and decline in univariate analysis, but this effect did not persist after adjustment. CONCLUSIONS: Cognitive impairment and decline are associated with asymptomatic high-grade stenosis of the left internal carotid artery. The persistence of the association after adjustment for right-sided stenosis indicates that the association is not due to underlying vascular risk factors or atherosclerosis in general.
Keywords: Aged; Carotid Stenosis; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Neuropsychological Tests; Odds Ratio; Risk Factors; Tunica Intima

Congestive heart failure in the elderly: the Cardiovascular Health Study. - Mathew, Sunil T; Gottdiener, John S; Kitzman, Dalane; Aurigemma, Gerard (Am J Geriatr Cardiol, 2004)
Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.
Keywords: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Diagnosis, Differential; Female; Geriatric Assessment; Heart Atria; Heart Failure; Heart Rate; Humans; Incidence; Male; Prevalence; Risk Factors; Stroke Volume; United States; Ventricular Dysfunction, Left

Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. - Cushman, Mary; Tsai, Albert W; White, Richard H; Heckbert, Susan R; Rosamond, Wayne D; Enright, Paul; Folsom, Aaron R (Am J Med, 2004)
PURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States. METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review. RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48% (175/366) of events. The 28-day case-fatality rate was 11% (29/265) after a first venous thromboembolism and 25% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7% per year (95% confidence interval [CI]: 4.5% to 10.9% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95% CI: 2.0 to 41.7). CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.
Keywords: Aged; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms; Population Surveillance; Pulmonary Embolism; Recurrence; Risk Factors; Survival Rate; Venous Thrombosis

The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture. - Redline, Susan; Kirchner, H Lester; Quan, Stuart F; Gottlieb, Daniel J; Kapur, Vishesh; Newman, Anne (Arch Intern Med, 2004)
BACKGROUND: Polysomnography is used to assess sleep quality and to gauge the functional effect of sleep disorders. Few population-based data are available to estimate the variation in sleep architecture across the population and the extent to which sleep-disordered breathing (SDB), a common health condition, contributes to poor sleep independent of other factors. The objective of this study was to describe the population variability in sleep quality and to quantify the independent associations with SDB. METHODS: Cross-sectional analyses were performed on data from 2685 participants, aged 37 to 92 years, in a community-based multicenter cohort study. Dependent measures included the percentage time in each sleep stage, the arousal index, and sleep efficiency. Independent measures were age, sex, ethnicity, comorbidity status, and the respiratory disturbance index. RESULTS: Lighter sleep was found in men relative to women and in American Indians and blacks relative to other ethnic groups. Increasing age was associated with impaired sleep in men, with less consistent associations in women. Notably, women had, on average, 106% more slow wave sleep. Sleep-disordered breathing was associated with poorer sleep; however, these associations were generally smaller than associations with sex, ethnicity, and age. Current smokers had lighter sleep than ex-smokers or never smokers. Obesity had little effect on sleep. CONCLUSIONS: Sleep architecture varies with sex, age, ethnicity, and SDB. Individual assessment of the effect of SDB on sleep quality needs to account for other host characteristics. Men, but not women, show evidence of poorer sleep with aging, suggesting important sex differences in sleep physiology.
Keywords: Adult; Age Factors; Aged; Aged, 80 and over; Body Mass Index; Comorbidity; Female; Humans; Male; Middle Aged; Multivariate Analysis; Sex Factors; Sleep; Sleep Apnea Syndromes

Incidence and prevalence of dementia in the Cardiovascular Health Study. - Fitzpatrick, Annette L; Kuller, Lewis H; Ives, Diane G; Lopez, Oscar L; Jagust, William; Breitner, John C S; Jones, Beverly; Lyketsos, Constantine; Dulberg, Corinne (J Am Geriatr Soc, 2004)
OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort. DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia. SETTING: Four U.S. communities. PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years. MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD and Alzheimer's Disease Diagnostic and Treatment Center's State of California criteria for VaD. RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0%) than men (14.7%). CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.
Keywords: African Americans; Age Distribution; Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Dementia; Dementia, Vascular; Education; European Continental Ancestry Group; Female; Humans; Incidence; Longitudinal Studies; Male; Prevalence; Proportional Hazards Models; Risk Factors; Sex Distribution; United States

Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study. - Drazner, Mark H; Rame, J Eduardo; Marino, Emily K; Gottdiener, John S; Kitzman, Dalane W; Gardin, Julius M; Manolio, Teri A; Dries, Daniel L; Siscovick, David S (J Am Coll Cardiol, 2004)
OBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF). BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF. METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF. RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8% in quartile 1, 4.4% in quartile 2, 7.5% in quartile 3, and 14.1% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF. CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.
Keywords: Aged; Body Surface Area; Coronary Artery Disease; Diastole; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Longitudinal Studies; Male; Multivariate Analysis; Prospective Studies; Risk Factors; Sensitivity and Specificity; Statistics as Topic; Stroke Volume; Ventricular Dysfunction, Left

Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. - Fried, Linda; Solomon, Cam; Shlipak, Michael; Seliger, Stephen; Stehman-Breen, Catherine; Bleyer, Anthony J; Chaves, Paolo; Furberg, Curt; Kuller, Lewis; Newman, Anne (J Am Soc Nephrol, 2004)
Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.
Keywords: Aged; Biomarkers; C-Reactive Protein; Creatinine; Factor VII; Female; Fibrinogen; Follow-Up Studies; Glomerular Filtration Rate; Hemoglobins; Humans; Leukocyte Count; Linear Models; Longitudinal Studies; Male; Predictive Value of Tests; Prospective Studies; Renal Insufficiency; Serum Albumin; Thrombosis

Mesenteric artery disease in the elderly. - Hansen, Kimberley J; Wilson, David B; Craven, Timothy E; Pearce, Jeffrey D; English, William P; Edwards, Matthew S; Ayerdi, Juan; Burke, Gregory L (J Vasc Surg, 2004)
PURPOSE: The purpose of this study was to estimate the population-based prevalence of mesenteric artery stenosis (MAS) and occlusion among independent elderly Americans. METHOD: As part of an ancillary investigation to the Cardiovascular Health Study (CHS), participants in the Forsyth County, NC cohort had visceral duplex sonography of the celiac arteries and superior mesenteric arteries (SMAs). Critical MAS was defined by celiac peak systolic velocity >or=2.0 m/s and/or SMA peak systolic velocity >or=2.7 m/s. Occlusion of either vessel was defined by lack of a Doppler-shifted signal within the imaged artery. Demographic data, blood pressures, and blood lipid levels were collected as part of the baseline CHS examination. Participants' weights were measured at baseline and before the duplex exam. Univariate tests of association were performed with two-way contingency tables, Student t tests, and Fisher exact tests. Multivariate associations were examined with logistic regression analysis. RESULTS: A total of 553 CHS participants had visceral duplex sonography technically adequate to define the presence or absence of MAS. The study group had a mean age of 77.2 +/- 4.9 years and comprised 63% women and 37% men. Participant race was 76% white and 23% African-American. Ninety-seven participants (17.5%) had MAS. There was no significant difference in age, race, gender, body mass index, blood pressure, cholesterol, or low-density lipoproteins for participants with or without MAS. Forward stepwise variable selection found renal artery stenosis (P =.008; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.31, 6.21) and high-density lipoprotein >40 (P =.02; OR, 3.03; 95% CI, 1.17, 7.81) significantly associated with MAS in a multivariate logistic regression model. Eighty-three of the 97 participants with MAS (15.0% of the cohort) had isolated celiac stenosis. Seven participants (1.3% of the cohort) had combined celiac and SMA stenosis. Five participants (0.9% of the cohort) had isolated SMA stenosis. Two participants (0.4% of the cohort) had celiac occlusion. Considering all participants with MAS, there was no association with weight change. However, SMA stenosis and celiac occlusion demonstrated an independent association with annualized weight loss (P =.028; OR, 1.54; 95% CI, 1.05, 2.26) and with renal artery stenosis (P =.001; OR, 9.48; 95% CI, 2.62, 34.47). CONCLUSION: This investigation provides the first population-based estimate of the prevalence of MAS among independent elderly Americans. MAS existed in 17.5% of the study cohort. The majority had isolated celiac disease. SMA stenosis and celiac artery occlusion demonstrated a significant and independent association with weight loss and concurrent renal artery disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Arteriosclerosis; Celiac Artery; Cohort Studies; Female; Humans; Male; Mesenteric Arteries; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Prevalence; Ultrasonography, Doppler, Duplex; Weight Loss

Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. - Seliger, Stephen L; Siscovick, David S; Stehman-Breen, Catherine O; Gillen, Daniel L; Fitzpatrick, Annette; Bleyer, Anthony; Kuller, Lew H (J Am Soc Nephrol, 2004)
Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.
Keywords: Aged; Alzheimer Disease; Cardiovascular Diseases; Creatinine; Dementia; Dementia, Vascular; Female; Humans; Kidney; Kidney Diseases; Male; Muscles; Proportional Hazards Models

Neighbourhood environments and mortality in an elderly cohort: results from the cardiovascular health study. - Diez Roux, Ana V; Borrell, Luisa N; Haan, Mary; Jackson, Sharon A; Schultz, Richard (J Epidemiol Community Health, 2004)
BACKGROUND: It has been postulated that neighbourhood conditions are related to the health of the elderly population but longitudinal studies are rare and confounding by individual level variables remains a possibility. METHODS: Data were obtained from the cardiovascular health study, a population based study of adults aged 65 years and older. Census block groups were used as proxies for neighbourhoods. A summary score was used to characterise the neighbourhood socioeconomic environment. Information on personal socioeconomic indicators, cardiovascular disease prevalence, and cardiovascular risk factors was obtained from the baseline examination. Proportional hazards regression and propensity score matching were used to control for individual level variables. RESULTS: Over the eight year follow up there were 1346 deaths among the 5074 participants, of which 43% were attributable to cardiovascular disease. Among white participants, living in the most disadvantaged neighbourhood group was associated with higher rates of cardiovascular death, after adjustment for income, education, and occupation (hazard ratio (HR) 1.5, 95% confidence intervals (CI) 1.2 to 1.9). No neighbourhood differences were observed for non-cardiovascular deaths. Estimates for black participants were 1.3 (95% CI 0.7 to 2.3) for cardiovascular deaths and 1.4 (95% CI 0.8 to 2.4) for non-cardiovascular deaths, but sample size was small. In white participants, associations of neighbourhood characteristics with cardiovascular mortality persisted after adjustment for prevalent baseline disease and cardiovascular risk factors. The use of propensity score matching led to similar results (HR for the lowest compared with the highest neighbourhood score group: 1.6 95% CI 1.1 to 2.5, controlling for personal socioeconomic indicators). CONCLUSION: Neighbourhood disadvantage is related to rates of cardiovascular death in elderly white adults.
Keywords: African Americans; Aged; Cardiovascular Diseases; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Income; Male; Poverty Areas; Residence Characteristics; Risk Factors; Socioeconomic Factors; United States

Plasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons: the Cardiovascular Health Study. - Longstreth, W T; Katz, Ronit; Olson, Jean; Bernick, Charles; Carr, J Jeffrey; Malinow, M René; Hess, David L; Cushman, Mary; Schwartz, Stephen M (Arch Neurol, 2004)
BACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI). DESIGN: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype. RESULTS: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P =.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P =.07 for linear trend). CONCLUSION: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.
Keywords: Aged; Aging; Brain; Brain Infarction; Female; Homocysteine; Humans; Magnetic Resonance Imaging; Male; Odds Ratio; Radiography; Risk Factors

Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset. - Saxton, J; Lopez, O L; Ratcliff, G; Dulberg, C; Fried, L P; Carlson, M C; Newman, A B; Kuller, L (Neurology, 2004)
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

Predictors of falling cholesterol levels in older adults: the Cardiovascular Health Study. - Manolio, Teri A; Cushman, Mary; Gottdiener, John S; Dobs, Adrian; Kuller, Lewis H; Kronmal, Richard A (Ann Epidemiol, 2004)
PURPOSE: To estimate 4-year change in serum total cholesterol levels in a population-based sample of older adults and identify independent predictors of cholesterol decline. METHODS: Prospective study of 2837 adults aged 65 years and older with serum cholesterol measured in 1992-1993 and 1996-1997. RESULTS: Mean serum cholesterol levels declined 6.3 mg/dl between the two examinations. Declines were greater in white (-7.3 mg/dl) than black (-1.4 mg/dl) participants and in those in good/excellent health (-0.9 mg/dl) vs. fair/poor health (-3.1 mg/dl; both p < 0.01). Factors associated with greater decline on multivariate analysis included age, male gender, and higher white cell count, albumin, and baseline cholesterol. Cholesterol levels declined 2.0 mg/dl per 6 year increment in baseline age and 6.8 mg/dl more in men than women after adjustment for other factors. C-reactive protein levels were unrelated to cholesterol change. CONCLUSION: Declining cholesterol levels were associated with male gender, advanced age, weight loss, and white blood cell count but not with C-reactive protein levels. The role of declining cholesterol synthesis, due to as yet undefined age-related changes or to cytokine-mediated reductions related to illness, should be examined to help clarify the mechanisms of the sometimes marked declines in cholesterol levels observed at advanced ages.
Keywords: African Americans; Age Factors; Aged; Cardiovascular Diseases; Cholesterol; European Continental Ancestry Group; Female; Forecasting; Health Status; Humans; Male; Medicare; Prospective Studies; Risk Factors; Sex Distribution; Sex Factors; United States

The presence of frailty in elderly persons with chronic renal insufficiency. - Shlipak, Michael G; Stehman-Breen, Catherine; Fried, Linda F; Song, Xiao; Siscovick, David; Fried, Linda P; Psaty, Bruce M; Newman, Anne B (Am J Kidney Dis, 2004)
BACKGROUND: Frailty has been defined as a tool to define individuals who lack functional reserve and are at risk for functional decline. We hypothesized that chronic renal insufficiency (CRI) would be associated with a greater prevalence of frailty and disability in the elderly. METHODS: This cross-sectional analysis used baseline data collected from the Cardiovascular Health Study, which enrolled 5,888 community-dwelling adults aged 65 years or older from 4 clinical centers in the United States. Renal insufficiency is defined as a serum creatinine level of 1.3 mg/dL or greater (> or =115 micromol/L) in women and 1.5 mg/dL or greater (> or =133 micromol/L) in men. Frailty is defined by the presence of 3 of the following abnormalities: unintentional weight loss, self-reported exhaustion, measured weakness, slow walking speed, and low physical activity. Disability is defined as any self-reported difficulty with activities of daily living. RESULTS: Among 5,808 participants with creatinine levels measured at entry, 15.9% of men (n = 394) and 7.6% of women (n = 254) had CRI. Prevalences of frailty (15% versus 6%; P < 0.001) and disability (12% versus 7%; P = 0.001) were greater in participants with CRI compared with those with normal renal function. After multivariate adjustment for comorbidity, CRI remained significantly associated with frailty (odds ratio, 1.76; 95% confidence interval, 1.28 to 2.41), but not disability (odds ratio, 1.26; 95% confidence interval, 0.94 to 1.69). CONCLUSION: Elderly persons with CRI have a high prevalence of frailty, which may signal their risk for progression to adverse health outcomes. If confirmed in other studies, identification of frailty in patients with CRI may warrant special interventions to preserve their independence, quality of life, and survival.
Keywords: Activities of Daily Living; Aged; Cross-Sectional Studies; Female; Frail Elderly; Humans; Kidney Failure, Chronic; Male; United States

Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131). - Scuteri, Angelo; Manolio, Teri A; Marino, Emily K; Arnold, Alice M; Lakatta, Edward G (J Am Coll Cardiol, 2004)
OBJECTIVES: We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT). BACKGROUND: Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease. METHOD: Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM). RESULTS: Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95% confidence interval [CI] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95% CI 1.16 to 1.75) compared with CGP1 (normal). CONCLUSIONS: Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT.
Keywords: Aged; Cardiovascular Diseases; Carotid Arteries; Female; Humans; Hypertrophy; Incidence; Male; Predictive Value of Tests; Prevalence; Prospective Studies; Ultrasonography

The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the cardiovascular health study. - Barzilay, Joshua I; Peterson, Do; Cushman, Mary; Heckbert, Susan R; Cao, Jie J; Blaum, Caroline; Tracy, Russell P; Klein, Ronald; Herrington, David M (Am J Kidney Dis, 2004)
BACKGROUND: Microalbuminuria is a risk factor for coronary heart disease (CHD). It occurs most commonly in the settings of diabetes and hypertension. The mechanisms by which it increases CHD risk are uncertain. METHODS: We examined the cross-sectional association of microalbuminuria with a broad range of CHD risk factors in 3 groups of adults aged 65 years or older with and without microalbuminuria: those with (1) no diabetes or hypertension (n = 1,098), (2) hypertension only (n = 1,450), and (3) diabetes with or without hypertension (n = 465). RESULTS: Three factors were related to microalbuminuria in all 3 groups: age, elevated systolic blood pressure, and markers of systemic inflammation. In patients with neither diabetes nor hypertension, increasing C-reactive protein levels were associated with microalbuminuria (odds ratio per 1-mg/L increase, 1.46; 95% confidence interval [CI], 1.15 to 1.84). Among those with diabetes, an increase in white blood cell (WBC) count was associated with microalbuminuria (odds ratio per 1,000-cell/mL increase, 2.57; 95% CI, 1.12 to 5.89). Among those with hypertension, an increase in WBC count (odds ratio per 1,000-cell/mL increase, 1.83; 95% CI, 1.04 to 3.23) and fibrinogen level (odds ratio per 10-mg/dL increase, 1.02; 95% CI, 1.00 to 1.05) were significantly associated with microalbuminuria. In all 3 groups, prevalent CHD was related to an elevated WBC count. In none of the 3 groups was brachial artery reactivity to ischemia, an in vivo marker of endothelial function, related to microalbuminuria. CONCLUSION: Microalbuminuria is associated with age, systolic blood pressure, and markers of inflammation. These associations reflect potential mechanisms by which microalbuminuria is related to CHD risk.
Keywords: Age Distribution; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Brachial Artery; Comorbidity; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypertension; Inflammation; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Risk Factors; Smoking; Ultrasonography

The relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort. - Kronmal, Richard A; Barzilay, Joshua I; Tracy, Russell P; Savage, Peter J; Orchard, Trevor J; Burke, Gregory L (J Clin Endocrinol Metab, 2004)
It is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6-9 yr. All were free of CHD at baseline. There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43-150 microU/ml (258-900 pmol/liter)] had an adjusted 30% increased relative risk (95% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 microU/ml (<120 pmol/liter)]. Those in the fourth interval [151-400 microU/ml (906-2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3-13.1; P < 0.0001). Approximately 15% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels. Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.
Keywords: Aged; Cohort Studies; Coronary Disease; Diabetes Mellitus, Type 1; Fasting; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Male; Radioimmunoassay; Risk Factors

Respiratory muscle strength and the risk of incident cardiovascular events. - van der Palen, J; Rea, T D; Manolio, T A; Lumley, T; Newman, A B; Tracy, R P; Enright, P L; Psaty, B M (Thorax, 2004)
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

Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists. - Bryson, Chris L; Smith, Nicholas L; Kuller, Lewis H; Chaves, Paulo H M; Manolio, Teri A; Lewis, William; Boyko, Edward J; Furberg, Curt D; Psaty, Bruce M (J Am Geriatr Soc, 2004)
OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists. DESIGN: Prospective cohort study. SETTING: Four U.S. sites: Washington County, Maryland; Allegheny County, Pennsylvania; Sacramento County, California; and Forsyth County, North Carolina. PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older. MEASUREMENTS: Adjudicated incident CHF. RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22% of men and 8% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5% used alpha antagonists during follow-up, with no observed increase in CHF risk. CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.
Keywords: Adrenergic alpha-Antagonists; Aged; Antihypertensive Agents; Benzothiadiazines; Blood Pressure; Cohort Studies; Diuretics; Female; Heart Failure; Humans; Hypertension; Male; Risk Factors; Sodium Chloride Symporter Inhibitors; United States

Self-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study. - Mukamal, Kenneth J; Mittleman, Murray A; Longstreth, W T; Newman, Anne B; Fried, Linda P; Siscovick, David S (J Am Geriatr Soc, 2004)
OBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Four U.S. communities. PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated. MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline. RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25% higher risk in consumers of 14 or more drinks per week (95% CI=3-52%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity. CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.
Keywords: Accidental Falls; Aged; Alcohol Drinking; Chi-Square Distribution; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Regression Analysis; Risk Factors; Self Disclosure; United States

Sleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study. - Walsleben, Joyce A; Kapur, Vishesh K; Newman, Anne B; Shahar, Eyal; Bootzin, Richard R; Rosenberg, Carl E; O'Connor, George; Nieto, F Javier (Sleep, 2004)
STUDY OBJECTIVES: To describe the distribution of nocturnal sleep characteristics and reports of daytime sleepiness in a large well-defined group of healthy adults. DESIGN: The Sleep Heart Health Study is a multicenter study examining sleep and cardiopulmonary parameters through nocturnal polysomnography in adults enrolled in geographically distinct cardiovascular cohorts. SETTING: Community setting. PARTICIPANTS: 470 subjects enrolled in the Sleep Heart Health Study (n = 6440) were selected as a 'normative' group based on screening of health conditions and daily habits that could interfere with sleep. MEASUREMENTS AND RESULTS: Home-based nocturnal polysomnography was obtained on all participants and centrally scored for sleep and respiratory parameters. Demographic and health-related data were obtained and updated at the time of the home visit. Sleep efficiency decreased by 1.6% for each 10 years of increased age. Sleep time decreased by 0.1 hours (6.0 minutes) for each 10-year age increase and was longer in women. The arousal index increased by 0.8 for each 10-year increase in age and was lower by 1.4 in women. Women had a lower mean percentage of stage 1 and stage 2 sleep. Mean percentage of slow-wave sleep was higher in women (by 6.7%). Percentage of slow-wave sleep decreased with increased age for men only (by 1.9% for each 10-year age change). CONCLUSIONS: Data suggest a clear lessening in the quantity and quality of sleep with age that appears to be more rapid in males compared to females.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Circadian Rhythm; Cohort Studies; Disorders of Excessive Somnolence; Female; Health Status; Humans; Male; Middle Aged; Polysomnography; Sleep; Sleep Stages; Surveys and Questionnaires

Sleep apnea and markers of vascular endothelial function in a large community sample of older adults. - Nieto, F Javier; Herrington, David M; Redline, Susan; Benjamin, Emelia J; Robbins, John A (Am J Respir Crit Care Med, 2004)
Clinical studies have suggested that sleep apnea is associated with impaired brachial artery flow-mediated dilation, a surrogate of endothelial dysfunction. We examined this question among older participants in the baseline examination of the Sleep Heart Health/Cardiovascular Health Study cohort (n = 1,037, age 68 years or older, 56% female). Indices of sleep apnea, derived from 12-channel home polysomnography, were the apnea-hypopnea index (average number of apneas/hypopneas per hour) and the hypoxemia index (percentage of time below 90% O2 saturation). Baseline arterial diameter and percentage of flow-mediated dilation were measured by ultrasound. Sleep apnea measures were associated with baseline diameter and the percentage of flow-mediated dilation, although these associations were weakened after adjustment for other cardiovascular risk factors, particularly body mass index. However, a statistically significant linear association between the hypoxemia index and baseline diameter was observed even after adjustment for body mass index and other confounders (p < 0.01). The associations were stronger among participants who were younger than 80 years and among those who with hypertension. This study adds to the growing body of evidence linking sleep apnea with vascular dysfunction in older subjects. Whether these relationships are entirely independent of obesity is unclear. This association might be one of the mechanisms explaining the relationship between sleep apnea, hypertension, and cardiovascular disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Brachial Artery; Cardiovascular Diseases; Cohort Studies; Comorbidity; Endothelium, Vascular; Female; Humans; Hypertension; Linear Models; Male; Polysomnography; Prevalence; Probability; Residence Characteristics; Risk Assessment; Sampling Studies; Severity of Illness Index; Sleep Apnea Syndromes; Ultrasonography, Doppler

Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. - Punjabi, Naresh M; Shahar, Eyal; Redline, Susan; Gottlieb, Daniel J; Givelber, Rachel; Resnick, Helaine E (Am J Epidemiol, 2004)
Clinic-based studies suggest that sleep-disordered breathing (SDB) is associated with glucose intolerance and insulin resistance. However, in the available studies, researchers have not rigorously controlled for confounding variables to assess the independent relation between SDB and impaired glucose metabolism. The objective of this study was to determine whether SDB was associated with glucose intolerance and insulin resistance among community-dwelling subjects (n=2,656) participating in the Sleep Heart Health Study (1994-1999). SDB was characterized with the respiratory disturbance index and measurements of oxygen saturation during sleep. Fasting and 2-hour glucose levels measured during an oral glucose tolerance test were used to assess glycemic status. Relative to subjects with a respiratory disturbance index of less than 5.0 events/hour (the reference category), subjects with mild SDB (5.0-14.9 events/hour) and moderate to severe SDB (> or =15 events/hour) had adjusted odds ratios of 1.27 (95% confidence interval: 0.98, 1.64) and 1.46 (95% confidence interval: 1.09, 1.97), respectively, for fasting glucose intolerance (p for trend < 0.01). Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, body mass index, and waist circumference. The results of this study suggest that SDB is independently associated with glucose intolerance and insulin resistance and may lead to type 2 diabetes mellitus.
Keywords: Aged; Blood Gas Analysis; Body Constitution; Body Mass Index; Cohort Studies; Confounding Factors, Epidemiologic; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Linear Models; Male; Middle Aged; Multivariate Analysis; Oxyhemoglobins; Polysomnography; Research Design; Risk Factors; Severity of Illness Index; Sleep Apnea Syndromes

Stroke risk factors and loss of high cognitive function. - Elkins, J S; O'Meara, E S; Longstreth, W T; Carlson, M C; Manolio, T A; Johnston, S C (Neurology, 2004)
BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition. METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS). RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction). CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.
Keywords: Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Higher Nervous Activity; Humans; Incidence; Male; Risk Assessment; Risk Factors; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Stroke; United States

Survival associated with two sets of diagnostic criteria for congestive heart failure. - Schellenbaum, Gina D; Rea, Thomas D; Heckbert, Susan R; Smith, Nicholas L; Lumley, Thomas; Roger, Veronique L; Kitzman, Dalane W; Taylor, Herman A; Levy, Daniel; Psaty, Bruce M (Am J Epidemiol, 2004)
Congestive heart failure (CHF) definitions vary across epidemiologic studies. The Framingham Heart Study criteria include CHF signs and symptoms assessed by a physician panel. In the Cardiovascular Health Study, a committee of physicians adjudicated CHF diagnoses, confirmed by signs, symptoms, clinical tests, and/or medical therapy. The authors used data from the Cardiovascular Health Study, a population-based cohort study of 5,888 elderly US adults, to compare CHF incidence and survival patterns following onset of CHF as defined by Framingham and/or Cardiovascular Health Study criteria. They constructed an inception cohort of nonfatal, hospitalized CHF patients. Of 875 participants who had qualifying CHF hospitalizations between 1989 and 2000, 54% experienced a first CHF event that fulfilled both sets of diagnostic criteria (concordant), 31% fulfilled only the Framingham criteria (Framingham only), and 15% fulfilled only the Cardiovascular Health Study criteria (Cardiovascular Health Study only). No significant survival difference was found between the Framingham-only group (hazard ratio = 0.87, 95% confidence interval: 0.71, 1.07) or the Cardiovascular Health Study-only group (hazard ratio = 0.89, 95% confidence interval: 0.68, 1.15) and the concordant group (referent). Compared with Cardiovascular Health Study central adjudication, Framingham criteria for CHF identified a larger group of participants with incident CHF, but all-cause mortality rates were similar across these diagnostic classifications.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Diagnosis, Differential; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Prognosis; Severity of Illness Index; Survival Analysis

Time trends in the use of beta-blockers and other pharmacotherapies in older adults with congestive heart failure. - Smith, Nicholas L; Chan, Jeannie D; Rea, Thomas D; Wiggins, Kerri L; Gottdiener, John S; Lumley, Thomas; Psaty, Bruce M (Am Heart J, 2004)
BACKGROUND: Evidence supporting pharmacotherapy of congestive heart failure (CHF) has grown substantially over the past decade and includes large, placebo-controlled trials with mortality end points. We describe beta-blocker and other medication temporal treatment trends of CHF in the Cardiovascular Health Study, a community-based cohort study of 5888 adults > or =65 years of age. METHODS: Prescription medication data were collected from hospital discharge summaries for incident CHF events and at in-study annual clinic visits for prevalent CHF cases from 1989 to 2000. Change in use of agents over time was estimated by using generalized estimating equations while adjusting for potential confounding factors of age, sex, race, and cardiovascular and pulmonary comorbidities. RESULTS: Among 1033 incident CHF events, beta-blocker use after diagnosis increased an average of 2.4 percentage points annually (95% CI, 1.5 to 3.4 points) from 1989 to 2000. The increasing trend was consistent throughout follow-up. Among participants with coronary disease and/or hypertension and among those with low ejection fractions (<45%), beta-blocker use remained flat from 1989 to 1994 and increased 4.7 points annually (2.5 to 6.9) and 10.0 points annually (6.1 to 13.8), respectively, from 1995 to 2000. Among participants without coronary disease or hypertension, there was no overall increase in use. Use of renin-angiotensin system inhibitors increased 2.3 points annually (1.0 to 3.5), digoxin use decreased 2.4 points annually (-3.6 to -1.1), and loop diuretic use remained flat between 1989 and 2000. In general, treatment trends were similar for prevalent CHF. CONCLUSIONS: Treatment of CHF has changed gradually in the 1990s and may in part reflect the influence of CHF clinical trial evidence.
Keywords: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies; Drug Therapy; Drug Therapy, Combination; Female; Heart Failure; Humans; Male; Multivariate Analysis; Prevalence

Traditional and novel risk factors in older adults: cardiovascular risk assessment late in life. - Mukamal, Kenneth J; Kronmal, Richard A; Tracy, Russell P; Cushman, Mary; Siscovick, David S (Am J Geriatr Cardiol, 2004)
As a population-based, longitudinal study of nearly 6000 older American adults, the Cardiovascular Health Study provides an excellent opportunity to assess the roles of traditional and novel cardiovascular risk factors in the development of coronary heart disease. Cardiovascular Health Study investigators have analyzed both traditional risk factors, such as diabetes, hypertension, and smoking, and new risk factors, such as hemostatic factors, inflammatory markers, exposure to infectious agents, and genetic determinants. These analyses have led to several important conclusions. First, older adults without previous cardiovascular events have a tremendous burden of subclinical vascular disease, which may change how physicians view risk factor modification in this age group. Second, some traditional cardiovascular risk factors lose importance as predictors of cardiovascular disease among older adults. Third, even modest elevations in fasting blood glucose or systolic blood pressure-below the levels used to define diabetes or hypertension-may have prognostic implications. Fourth, novel cardiovascular risk factors may add further information about cardiovascular disease risk in older adults. Promising potential candidates identified in the Cardiovascular Health Study include markers of hemostatic activation, fibrinogen, factor VIII coagulant activity, C-reactive protein, and exposure to herpes simplex virus-1 and possibly chlamydia. Future Cardiovascular Health Study investigations will help to clarify which combination of traditional and newer risk factors provides the best estimate of cardiovascular risk for older adults.
Keywords: Aged; Blood Coagulation Factors; Cardiovascular Diseases; Cohort Studies; Diabetes Complications; Female; Genetic Predisposition to Disease; Humans; Hypertension; Infections; Inflammation; Lipids; Longitudinal Studies; Male; Obesity; Predictive Value of Tests; Risk Factors; Smoking; United States

White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. - Kuller, Lewis H; Longstreth, W T; Arnold, Alice M; Bernick, Charles; Bryan, R Nick; Beauchamp, Norman J (Stroke, 2004)
BACKGROUND AND PURPOSE: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors. METHODS: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.
Keywords: Aged; Brain; Female; Humans; Leukoaraiosis; Magnetic Resonance Imaging; Male; Radiography; Risk Factors; Stroke

Age-dependent associations between sleep-disordered breathing and hypertension: importance of discriminating between systolic/diastolic hypertension and isolated systolic hypertension in the Sleep Heart Health Study. - Haas, Donald C; Foster, Gregory L; Nieto, F Javier; Redline, Susan; Resnick, Helaine E; Robbins, John A; Young, Terry; Pickering, Thomas G (Circulation, 2005)
BACKGROUND: Sleep-disordered breathing (SDB) is associated with hypertension in the middle-aged. The association is less clear in older persons. Most middle-aged hypertensives have systolic/diastolic hypertension, whereas isolated systolic hypertension (ISH) is common among persons over 60 years. Mechanistically, only systolic/diastolic hypertension is expected to be associated with SDB, but few studies of SDB and hypertension distinguish systolic/diastolic hypertension from ISH. Prior investigations may have underestimated an association between SDB and systolic/diastolic hypertension in the elderly by categorizing individuals with ISH as simply hypertensive. METHODS AND RESULTS: We conducted cross-sectional analyses of 6120 participants in the Sleep Heart Health Study, stratified by age: 40 to 59 (n=2477) and > or =60 years. Outcome measures included apnea-hypopnea index (AHI; average number of apneas plus hypopneas per hour of sleep), systolic/diastolic hypertension (> or =140 and > or =90 mm Hg), and ISH (> or =140 and <90 mm Hg). With adjustment for covariates, ISH was not associated with SDB in either age category. In those aged<60 years, AHI was significantly associated with higher odds of systolic/diastolic hypertension (AHI 15 to 29.9, OR=2.38 [95% CI 1.30 to 4.38]; AHI > or =30, OR=2.24 [95% CI 1.10 to 4.54]). Among those aged > or =60 years, no adjusted association between AHI and systolic/diastolic hypertension was found. CONCLUSIONS: SDB is associated with systolic/diastolic hypertension in those aged <60 years. No association was found between SDB and systolic/diastolic hypertension in those aged > or =60 years or between SDB and ISH in either age category. These findings have implications for SDB screening and treatment. Distinguishing between hypertensive subtypes reveals a stronger association between SDB and hypertension for those aged <60 years than previously reported.
Keywords: Adult; Age Factors; Aged; Antihypertensive Agents; Cross-Sectional Studies; Diastole; Female; Humans; Hypertension; Male; Middle Aged; Risk Factors; Sleep Apnea Syndromes; Sleep Apnea, Central; Systole

Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study. - Mukamal, Kenneth J; Chung, Hyoju; Jenny, Nancy S; Kuller, Lewis H; Longstreth, W T; Mittleman, Murray A; Burke, Gregory L; Cushman, Mary; Beauchamp, Norman J; Siscovick, David S (Stroke, 2005)
BACKGROUND AND PURPOSE: The association of light to moderate alcohol consumption with risk of ischemic stroke remains uncertain, as are the roles of potentially mediating factors and modification by apolipoprotein E (apoE) genotype. METHODS: We studied the prospective association of alcohol consumption and risk of ischemic stroke among 4410 participants free of cardiovascular disease at baseline in the Cardiovascular Health Study, a population-based cohort study of older adults from 4 US communities. Participants reported their consumption of alcoholic beverages yearly. RESULTS: During an average follow-up period of 9.2 years, 434 cases of incident ischemic stroke occurred. Compared with long-term abstainers, the multivariate relative risks of ischemic stroke were 0.85 (95% CI, 0.63 to 1.13), 0.75 (95% CI, 0.53 to 1.06), 0.82 (95% CI, 0.51 to 1.30), and 1.03 (95% CI, 0.68 to 1.57) among consumers of <1, 1 to 6, 7 to 13, and > or =14 drinks per week (P quadratic trend 0.06). ApoE genotype appeared to modify the alcohol-ischemic stroke relationship (P interaction 0.08), with generally lower risks among drinkers than abstainers in apoE4-negative participants but higher risks among drinkers than abstainers among apoE4-positive participants. We could not identify candidate mediators among lipid, inflammatory, and prothrombotic factors. CONCLUSIONS: In this study of older adults, the association of alcohol use and risk of ischemic stroke was U-shaped, with modestly lower risk among consumers of 1 to 6 drinks per week. However, apoE genotype may modify this association, and even moderate alcohol intake may be associated with an increased risk of ischemic stroke among apoE4-positive older adults.
Keywords: Aged; Alcohol Drinking; Apolipoproteins E; Brain Infarction; Brain Ischemia; Cohort Studies; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Inflammation; Ischemia; Lipids; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Prospective Studies; Risk; Risk Factors; Stroke; Substance-Related Disorders; Thrombosis; Time Factors; Vascular Diseases

Association between screening for osteoporosis and the incidence of hip fracture. - Kern, Lisa M; Powe, Neil R; Levine, Michael A; Fitzpatrick, Annette L; Harris, Tamara B; Robbins, John; Fried, Linda P (Ann Intern Med, 2005)
BACKGROUND: Because direct evidence for the effectiveness of screening is lacking, guidelines disagree on whether people should be screened for osteoporosis. OBJECTIVE: To determine whether population-based screening for osteoporosis in older adults is associated with fewer incident hip fractures than usual medical care. DESIGN: Nonconcurrent cohort study. SETTING: Population-based cohort enrolled in the Cardiovascular Health Study (CHS) from 4 states (California, Pennsylvania, Maryland, and North Carolina). PATIENTS: 3107 adults 65 years of age and older who attended their CHS study visits in 1994-1995. MEASUREMENTS: 31 participant characteristics (including demographic characteristics, medical histories, medications, and physical examination findings) and incident hip fractures over 6 years of follow-up. INTERVENTION: Bone density scans (dual-energy x-ray absorptiometry [DEXA] at the hip) for participants in California and Pennsylvania (n = 1422) and usual care for participants in Maryland and North Carolina (n = 1685). RESULTS: The incidence of hip fractures per 1000 person-years was 4.8 in the screened group and 8.2 in the usual care group. Screening was associated with a statistically significant lower hazard of hip fracture than usual care after adjustment for sex and propensity to be screened (Cox proportional hazard ratio, 0.64 [95% CI, 0.41 to 0.99]). LIMITATIONS: The mechanism of the association was unclear. A small unmeasured confounder that decreased the hazard of hip fracture could diminish or erase the observed association. CONCLUSIONS: Use of hip DEXA scans to screen for osteoporosis in older adults was associated with 36% fewer incident hip fractures over 6 years compared with usual medical care. Further research is needed to explore the mechanism of this association.
Keywords: Absorptiometry, Photon; Aged; Aged, 80 and over; Cohort Studies; Female; Hip Fractures; Humans; Incidence; Male; Mass Screening; Osteoporosis; Risk Factors; Sensitivity and Specificity

Association of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS). - Chan, Jeannie D; Rea, Thomas D; Smith, Nicholas L; Siscovick, David; Heckbert, Susan R; Lumley, Thomas; Chaves, Paulo; Furberg, Curt D; Kuller, Lewis; Psaty, Bruce M (Am Heart J, 2005)
BACKGROUND: In clinical trials, beta-blocker therapy reduces all-cause mortality among people with congestive heart failure (CHF) characterized by depressed systolic function, but few trials included large numbers of elderly participants. This study assessed the association between beta-blocker therapy and mortality among community-dwelling older adults with CHF. METHODS: The Cardiovascular Health Study (CHS) is a longitudinal, population-based study of adults aged > or = 65 years. Recruitment began in 1989 with follow-up extending through June 2000 or death. Cox proportional hazard regression models were used to assess the association between beta-blocker therapy and all-cause mortality among 950 participants who developed new-onset CHF. RESULTS: beta-Blocker users (n = 157) were more likely than nonusers (n = 793) to have treated hypertension, clinical coronary artery disease, and valvular disease at the time of CHF diagnosis. Death occurred in 67 users and 446 nonusers during a median follow-up of 2.3 years. Compared with nonuse, use of beta-blockers was associated with a multivariable adjusted hazard ratio (HR) of 0.74 (95% CI 0.56-0.98) for all-cause mortality. Among the 520 participants who had left ventricular ejection fraction assessed within 90 days after CHF diagnosis, the risk for all cause mortality associated with beta-blocker use did not differ significantly between those with ejection fraction of < 40% and those with ejection fraction of > or = 40% (HR 0.56, 95% CI 0.27-1.13; HR 0.82, 95% CI 0.56-1.22, respectively; interaction P = .34). CONCLUSIONS: This observational study suggests that beta-blocker treatment is associated with a reduced risk of all-cause mortality among community-dwelling older adults with CHF.
Keywords: Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Female; Follow-Up Studies; Heart Failure; Humans; Male

Association of sleep time with diabetes mellitus and impaired glucose tolerance. - Gottlieb, Daniel J; Punjabi, Naresh M; Newman, Ann B; Resnick, Helaine E; Redline, Susan; Baldwin, Carol M; Nieto, F Javier (Arch Intern Med, 2005)
BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index. RESULTS: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded. CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.
Keywords: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus; Disease Progression; Female; Glucose Intolerance; Humans; Male; Middle Aged; Odds Ratio; Prevalence; Prospective Studies; Sleep; Surveys and Questionnaires; Time Factors; United States

Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study. - Edwards, Matthew S; Wilson, David B; Craven, Timothy E; Stafford, Jeanette; Fried, Linda F; Wong, Tien Y; Klein, Ronald; Burke, Gregory L; Hansen, Kimberley J (Am J Kidney Dis, 2005)
BACKGROUND: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals. METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling. RESULTS: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function. CONCLUSION: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.
Keywords: African Americans; Aged; Aged, 80 and over; Aging; Antihypertensive Agents; Capillaries; Cohort Studies; Comorbidity; Creatinine; Diabetes Mellitus; Disease Progression; European Continental Ancestry Group; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Photography; Prospective Studies; Proteinuria; Retina; Retinal Diseases; Retinal Vessels

Associations of sleep-disordered breathing and cerebral changes on MRI. - Robbins, John; Redline, Susan; Ervin, Ann; Walsleben, Joyce A; Ding, Jingzhong; Nieto, F Javier (J Clin Sleep Med, 2005)
STUDY OBJECTIVES: Population-based studies have demonstrated associations between sleep-disordered breathing (SDB), hypertension, and cardiovascular disease; few large-scale studies have examined associations of SDB with objective measures of cerebrovascular disease. This study tested the significance of associations of SDB with evidence of brain injury or ischemia determined by cerebral magnetic resonance imaging (MRI) studies. DESIGN: Cross-sectional and longitudinal analyses in a nested sample of Cardiovascular Health Study participants in the Sleep Heart Health Study. PARTICIPANTS: The 843 individuals (mean age 77, SD 4.3 years, 58% women) who had MRI studies as part of the Cardiovascular Health Study before and after polysomnography obtained as part of the Sleep Heart Health Study. MEASUREMENTS: A 12-channel polysomnogram was used to derive indexes of sleep-disordered breathing. Repeated MRI measurements provided indexes of infarct (presence and size) and white matter disease. Logistic regression analyses were used to model MRI changes of infarct-like lesions and white matter disease as a function of age, baseline white matter grade, and indexes of central and obstructive sleep-disordered breathing. RESULTS: Individuals who showed progression in white matter disease compared to those who did not were significantly more likely to show a Cheyne-Stokes respiration pattern and to have an increased number of central but not obstructive apneas. CONCLUSIONS: An association between change in white matter grade and measures of central sleep apnea was demonstrated that was consistent with a causal pathway in which central sleep apnea contributes to the progression of white matter disease; alternatively, central sleep apnea may be a marker of subclinical cerebrovascular or cardiovascular disease.
Keywords: Aged; Brain; Cerebral Infarction; Cerebrovascular Circulation; Female; Humans; Magnetic Resonance Imaging; Male; Polysomnography; Severity of Illness Index; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4. - Huang, T L; Zandi, P P; Tucker, K L; Fitzpatrick, A L; Kuller, L H; Fried, L P; Burke, G L; Carlson, M C (Neurology, 2005)
OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.
Keywords: Aged; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Cohort Studies; Dementia; Dietary Fats, Unsaturated; Fatty Acids, Omega-3; Feeding Behavior; Female; Fish Oils; Fish Products; Food, Formulated; Genetic Predisposition to Disease; Humans; Incidence; Male; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires

beta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study. - Hindorff, Lucia A; Heckbert, Susan R; Psaty, Bruce M; Lumley, Thomas; Siscovick, David S; Herrington, David M; Edwards, Karen L; Tracy, Russell P (Am J Hypertens, 2005)
BACKGROUND: Common Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) have been associated with hypertension and coronary disease. This analysis of older adults in the Cardiovascular Health Study examined whether these polymorphisms were associated with blood pressure (BP), subclinical atherosclerosis, and, among treated hypertensive individuals, differences in coronary disease risk according to antihypertensive drug class. METHODS: Altogether, 5249 participants (4441 white and 808 African American, median follow-up time 10.2 years) were genotyped for both polymorphisms. Ankle-arm index (AAI), carotid intima-media thickness (IMT), and brachial flow-mediated dilation were measured cross-sectionally. All estimates were adjusted for ethnicity. RESULTS: Relative to Gln27 homozygotes, carrying the Glu27 allele was not associated with new-onset hypertension (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.87 to 1.16), BP control (odds ratio [OR] = 0.97, 95% CI = 0.89 to 1.06), AAI (mean difference 0.0042 +/- 0.0052), carotid IMT (mean difference 0.0044 +/- 0.02 mm), or brachial flow-mediated dilation (mean difference in baseline diameter -0.028 +/- 0.036 mm; the most marked of three measures). Among treated hypertensive individuals, coronary disease risk was similar in Glu27 carriers relative to Gln27 homozygotes in subgroups defined by use of beta-blockers (HR = 1.09, 95% CI = 0.64 to 1.87) or other antihypertensive medications (HR = 1.00, 95% CI = 0.78 to 1.28). Results were similar for the Arg16Gly polymorphism. CONCLUSIONS: The association of beta(2)AR genotype with coronary disease previously reported in this older adult population is not likely to be explained by BP levels, subclinical atherosclerosis, or antihypertensive treatment. Other measures of vascular response, gene-gene or gene-environment interactions, or characteristics developing earlier in life may mediate the association between beta(2)AR genotype and coronary disease and merit further research.
Keywords: African Americans; Antihypertensive Agents; Arteriosclerosis; Coronary Artery Disease; European Continental Ancestry Group; Female; Genotype; Homozygote; Humans; Hypertension; Incidence; Male; Middle Aged; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Risk Factors

Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies. - Wong, Tien Yin; Larsen, Emily K Marino; Klein, Ronald; Mitchell, Paul; Couper, David J; Klein, Barbara E K; Hubbard, Larry D; Siscovick, David S; Sharrett, A Richey (Ophthalmology, 2005)
OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years). METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli. RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3% (n = 39 cases) and 0.2% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95% CI, 2.60-12.16), body mass index (OR, 3.88; 95% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95% CI, 1.44-6.84), systolic BP (OR, 3.46; 95% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound. CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.
Keywords: Aged; Aged, 80 and over; Arterioles; Blood Pressure; Cardiovascular Diseases; Carotid Stenosis; Coronary Artery Disease; Cross-Sectional Studies; Embolism; Female; Fibrinogen; Humans; Hypertension; Lipoprotein(a); Male; Meta-Analysis as Topic; Middle Aged; Retinal Artery; Retinal Vein Occlusion; Risk Factors

Classification of vascular dementia in the Cardiovascular Health Study Cognition Study. - Lopez, O L; Kuller, L H; Becker, J T; Jagust, W J; DeKosky, S T; Fitzpatrick, A; Breitner, J; Lyketsos, C; Kawas, C; Carlson, M (Neurology, 2005)
OBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study. METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI. RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer's Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD). CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cerebral Arteries; Cohort Studies; Dementia, Vascular; Diagnosis, Differential; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Stroke; United States

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study. - Reiner, Alexander P; Diehr, Paula; Browner, Warren S; Humphries, Stephen E; Jenny, Nancy S; Cushman, Mary; Tracy, Russell P; Walston, Jeremy; Lumley, Thomas; Newman, Anne B; Kuller, Lewis H; Psaty, Bruce M (Atherosclerosis, 2005)
Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.
Keywords: Aged; Aging; Carboxypeptidase B2; Cause of Death; Cohort Studies; Female; Genotype; Health Status; Humans; Inflammation; Longevity; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Promoter Regions, Genetic; Prospective Studies; Risk Factors; Thrombosis

Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status. - Rosano, Caterina; Naydeck, Barbara; Kuller, Lewis H; Longstreth, William T; Newman, Anne B (J Am Geriatr Soc, 2005)
OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment). DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults. PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS. MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status. RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status. CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.
Keywords: Aged; Brain; Calcinosis; Cognition Disorders; Coronary Artery Disease; Cross-Sectional Studies; Dementia; Female; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Risk Factors; United States

The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study. - Lenze, Eric J; Schulz, Richard; Martire, Lynn M; Zdaniuk, Bozena; Glass, Thomas; Kop, Willem J; Jackson, Sharon A; Reynolds, Charles F (J Am Geriatr Soc, 2005)
OBJECTIVES: To examine the relationship between persistently high depressive symptoms and long-term changes in functional disability in elderly persons. DESIGN: A community-based, prospective, observational study. SETTING: Participant data from the Cardiovascular Health Study. PARTICIPANTS: From the overall sample of 5,888 subjects, three types of participants were identified for this study: (1) persistently depressed individuals, who experienced an onset of depressive symptoms that persisted over 4 years (n=119); (2) temporarily depressed individuals, who experienced an onset of depressive symptoms that resolved over time (n=259); and (3) nondepressed individuals, with persistently low depressive symptoms throughout the follow-up period who were matched on baseline activity of daily living (ADL) scores, sex, and age to the previous two groups combined (n=378). MEASUREMENTS: Four consecutive years of data were assessed: validated measures of depression (10-item CES-D), functional disability (10-item ADL/instrumental ADL measure), physical performance, medical illness, and cognition. RESULTS: The persistently depressed group showed a greater linear increase in functional disability ratings than the temporarily depressed and nondepressed groups. This association between persistent depression and functional disability was robust even when controlling for baseline demographic and clinical/performance measures, including cognition. The persistently depressed group had an adjusted odds ratio (OR) of 5.27 (95% confidence interval (CI) 3.03-9.16) for increased functional disability compared with the nondepressed group over 3 years of follow-up, whereas the temporarily depressed group had an adjusted OR of 2.39 (95% CI=1.55-3.69) compared with the nondepressed group. CONCLUSION: Persistently elevated depressive symptoms in elderly persons are associated with a steep trajectory of worsening functional disability, generating the hypothesis that treatments for late-life depression need to be assessed on their efficacy in maintaining long-term functional status as well as remission of depressive symptoms. These results also demonstrate the need for studies to differentiate between persistent and temporary depressive symptoms when examining their relationship to disability.
Keywords: Activities of Daily Living; Aged; Case-Control Studies; Depressive Disorder; Disabled Persons; Female; Humans; Longitudinal Studies; Male; Multivariate Analysis; Risk; United States

C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. - Cushman, Mary; Arnold, Alice M; Psaty, Bruce M; Manolio, Teri A; Kuller, Lewis H; Burke, Gregory L; Polak, Joseph F; Tracy, Russell P (Circulation, 2005)
BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available. METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33% in men and 17% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20%; the incidences were 31% and 10% for elevated and normal CRP levels, respectively. CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Coronary Disease; Female; Humans; Incidence; Inflammation; Male; Myocardial Infarction; Predictive Value of Tests; Risk Factors

Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study. - O'Hare, Ann M; Newman, Anne B; Katz, Ronit; Fried, Linda F; Stehman-Breen, Catherine O; Seliger, Stephen L; Siscovick, David S; Shlipak, Michael G (Arch Intern Med, 2005)
BACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined. METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR). RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses. CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.
Keywords: Aged; Cohort Studies; Cystatin C; Cystatins; Female; Health Surveys; Humans; Longitudinal Studies; Male; Peripheral Vascular Diseases; Predictive Value of Tests; Risk Factors; ROC Curve; United States

Cystatin C and subclinical brain infarction. - Seliger, Stephen L; Longstreth, W T; Katz, Ronit; Manolio, Teri; Fried, Linda F; Shlipak, Michael; Stehman-Breen, Catherine O; Newman, Anne; Sarnak, Mark; Gillen, Daniel L; Bleyer, Anthony; Siscovick, David S (J Am Soc Nephrol, 2005)
Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.
Keywords: Age Factors; Aged; Aged, 80 and over; Biomarkers; Brain Infarction; Confidence Intervals; Creatinine; Cross-Sectional Studies; Cystatin C; Cystatins; Disease Progression; Female; Geriatric Assessment; Humans; Incidence; Ischemic Attack, Transient; Magnetic Resonance Imaging; Male; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Factors; Survival Analysis

Cystatin C and the risk of death and cardiovascular events among elderly persons. - Shlipak, Michael G; Sarnak, Mark J; Katz, Ronit; Fried, Linda F; Seliger, Stephen L; Newman, Anne B; Siscovick, David S; Stehman-Breen, Catherine (N Engl J Med, 2005)
BACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community. METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c). RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes. CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.
Keywords: Aged; Biomarkers; Cardiovascular Diseases; Cerebrospinal Fluid Proteins; Creatinine; Cystatin C; Cystatins; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Male; Mortality; Multivariate Analysis; Prognosis; Risk

Cystatin C concentration as a risk factor for heart failure in older adults. - Sarnak, Mark J; Katz, Ronit; Stehman-Breen, Catherine O; Fried, Linda F; Jenny, Nancy Swords; Psaty, Bruce M; Newman, Anne B; Siscovick, David; Shlipak, Michael G (Ann Intern Med, 2005)
BACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function. OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure. DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months. SETTING: Adults 65 years of age or older from 4 communities in the United States. PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine. MEASUREMENTS: Incident heart failure. RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]). LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear. CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.
Keywords: Aged; Biomarkers; Creatinine; Cystatin C; Cystatins; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Incidence; Kidney; Kidney Function Tests; Male; Risk Factors; United States

Cystatin-C and inflammatory markers in the ambulatory elderly. - Shlipak, Michael G; Katz, Ronit; Cushman, Mary; Sarnak, Mark J; Stehman-Breen, Catherine; Psaty, Bruce M; Siscovick, David; Tracy, Russell P; Newman, Anne; Fried, Linda (Am J Med, 2005)
PURPOSE: Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels. METHODS: This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes. RESULTS: After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5. CONCLUSIONS: The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.
Keywords: Age Factors; Aged; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Cystatin C; Cystatins; Female; Fibrinogen; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Predictive Value of Tests; Sensitivity and Specificity

Cystatin-C and mortality in elderly persons with heart failure. - Shlipak, Michael G; Katz, Ronit; Fried, Linda F; Jenny, Nancy Swords; Stehman-Breen, Catherine O; Newman, Anne B; Siscovick, David; Psaty, Bruce M; Sarnak, Mark J (J Am Coll Cardiol, 2005)
OBJECTIVES: We sought to evaluate cystatin-C, a novel measure of renal function, as a predictor of mortality in elderly persons with heart failure (HF) and to compare it with creatinine. BACKGROUND: Renal function is an important prognostic factor in patients with HF, but creatinine levels, which partly reflect muscle mass, may be insensitive for detecting renal insufficiency. METHODS: A total of 279 Cardiovascular Health Study participants with prevalent HF and measures of serum cystatin-C and creatinine were followed for mortality outcomes over a median of 6.5 years. RESULTS: Median creatinine and cystatin-C levels were 1.05 mg/dl and 1.26 mg/l. Each standard deviation increase in cystatin-C (0.35 mg/l) was associated with a 31% greater adjusted mortality risk (95% confidence interval [CI] 20% to 43%, p < 0.001), whereas each standard deviation increase in creatinine (0.39 mg/dl) was associated with a 17% greater adjusted mortality risk (95% CI 1% to 36%, p = 0.04). When both measures were combined in a single adjusted model, cystatin-C remained associated with elevated mortality risk (hazard ratio 1.60, 95% CI 1.32 to 1.94), whereas creatinine levels appeared associated with lower risk (hazard ratio 0.73, 95% CI 0.57 to 0.95). CONCLUSIONS: Cystatin-C is a stronger predictor of mortality than creatinine in elderly persons with HF. If confirmed in future studies, this new marker of renal function could improve risk stratification in patients with HF.
Keywords: Age Factors; Aged; Aged, 80 and over; Creatinine; Cystatin C; Cystatins; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Male; Pilot Projects; Predictive Value of Tests; Risk Assessment; Survival Analysis

Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. - Newman, Anne B; Fitzpatrick, Annette L; Lopez, Oscar; Jackson, Sharon; Lyketsos, Constantine; Jagust, William; Ives, Diane; DeKosky, Steven T; Kuller, Lewis H (J Am Geriatr Soc, 2005)
OBJECTIVES: To determine whether coronary artery disease, peripheral arterial disease (PAD), or noninvasive markers of cardiovascular disease (CVD) predict the onset of dementia and Alzheimer's disease (AD). DESIGN: Longitudinal cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Men and women (N=3,602) with a brain magnetic resonance imaging (MRI) scan but no dementia were followed for 5.4 years. Participants with stroke were excluded. MEASUREMENTS: Neurologists and psychiatrists classified incident cases of dementia and subtype using neuropsychological tests, examination, medical records and informant interviews. CVD was defined at the time of the MRI scan. Noninvasive tests of CVD were assessed within 1 year of the MRI. Apolipoprotein E allele status, age, race, sex, education, Mini-Mental State Examination score, and income were assessed as potential confounders. RESULTS: The incidence of dementia was higher in those with prevalent CVD, particularly in the subgroup with PAD. The rate of AD was 34.4 per 1,000 person-years for those with a history of CVD, versus 22.2 per 1,000 person-years without a history of CVD (adjusted hazard ratio (HR)=1.3, 95% confidence interval (CI)=1.0-1.7). Rates of AD were highest in those with PAD (57.4 vs 23.7 per 100 person-years, adjusted HR=2.4, 95% CI=1.4-4.2). Results were similar with further exclusion of those with vascular dementia from the AD group. A gradient of increasing risk was noted with the extent of vascular disease. CONCLUSION: Older adults with CVD other than stroke had a higher risk of dementia and AD than did those without CVD. The risk was highest in people with PAD, suggesting that extensive peripheral atherosclerosis is a risk factor for AD.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Dementia; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Peripheral Vascular Diseases; Risk Factors

Determinants of vascular dementia in the Cardiovascular Health Cognition Study. - Kuller, L H; Lopez, O L; Jagust, W J; Becker, J T; DeKosky, S T; Lyketsos, C; Kawas, C; Breitner, J C S; Fitzpatrick, A; Dulberg, C (Neurology, 2005)
OBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia. METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. RESULTS: Approximately 44% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke. CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer's Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.
Keywords: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Cardiovascular Diseases; Cerebral Arteries; Cerebral Infarction; Cohort Studies; Comorbidity; Continental Population Groups; Dementia, Vascular; Female; Humans; Lateral Ventricles; Magnetic Resonance Imaging; Male; Nerve Fibers, Myelinated; Neuropsychological Tests; Risk Factors; Sex Factors

Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study. - Quan, Stuart F; Katz, Ronit; Olson, Jean; Bonekat, William; Enright, Paul L; Young, Terry; Newman, Anne (Am J Med Sci, 2005)
BACKGROUND: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well. METHODS: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination 1 to 4 years later. RESULTS: Annualized incidence and nonremission rates were the following: TFA (2.8% and 15.4%), FA (12.3% and 22.7%), and EDS (4.4% and 13.4%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining nonremission was much more limited. CONCLUSIONS: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression.
Keywords: Aged; Cardiovascular Diseases; Cohort Studies; Depression; Female; Health Status; Humans; Incidence; Logistic Models; Male; Odds Ratio; Prevalence; Risk Factors; Sex Factors; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires

Fish consumption and stroke risk in elderly individuals: the cardiovascular health study. - Mozaffarian, Dariush; Longstreth, W T; Lemaitre, Rozenn N; Manolio, Teri A; Kuller, Lewis H; Burke, Gregory L; Siscovick, David S (Arch Intern Med, 2005)
BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.
Keywords: Age Distribution; Aged; Aged, 80 and over; Animals; Cohort Studies; Confidence Intervals; Diet; Fatty Acids, Omega-3; Female; Fish Oils; Fishes; Humans; Incidence; Male; Multivariate Analysis; Probability; Proportional Hazards Models; Risk Assessment; Seafood; Sensitivity and Specificity; Sex Distribution; Stroke; Surveys and Questionnaires; Survival Rate; United States

Fish intake and risk of incident heart failure. - Mozaffarian, Dariush; Bryson, Chris L; Lemaitre, Rozenn N; Burke, Gregory L; Siscovick, David S (J Am Coll Cardiol, 2005)
OBJECTIVES: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF). BACKGROUND: The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown. METHODS: Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated. RESULTS: During 12 years' follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to 0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% CI = 0.52 to 0.91), and 32% lower risk with intake > or =5 times/week (HR = 0.68, 95% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37% lower risk in the highest quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest. CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.
Keywords: Aged; Animals; Cohort Studies; Cooking; Diet; Diet Surveys; Disease-Free Survival; Female; Fishes; Heart Failure; Humans; Incidence; Male; Risk Factors; United States

Haptoglobin phenotype, sleep-disordered breathing, and the prevalence of cardiovascular disease: the Sleep Heart Health Study. - Levy, Andrew P; Zhang, Lin; Miller-Lotan, Rachel; Redline, Susan; O'Connor, George T; Quan, Stuart F; Resnick, Helaine E (Sleep, 2005)
BACKGROUND: Diabetes is an independent risk factor for cardiovascular disease, and there is growing evidence that sleep-disordered breathing also may increase the risk of cardiovascular disease. The mechanism responsible for increased susceptibility of people with diabetes to cardiovascular disease is thought to share several features with sleep-disordered breathing, notably increased oxidative stress. We recently demonstrated that a particular haptoglobin phenotype that is associated with differential antioxidant activity is an independent risk factor for cardiovascular disease in individuals with diabetes. We therefore sought to determine whether sleep-disordered breathing and cardiovascular disease are more strongly associated among people with the unfavorable haptoglobin phenotype. METHODS: We tested this hypothesis in 2612 middle-aged and older participants from the Sleep Heart Health Study. Haptoglobin phenotyping was performed by gel electrophoresis. Respiratory disturbance index was assessed by standard methods. Logistic regression analysis was performed to estimate the association between haptoglobin phenotype and cardiovascular disease, adjusting for known cardiovascular risk factors (age, sex, diabetes, smoking, lipid levels, and hypertension). Possible modification by haptoglobin phenotype of the association of sleep-disordered breathing with cardiovascular disease prevalence was explored by examining interaction terms. RESULTS: We found no significant association between haptoglobin phenotype and prevalent cardiovascular disease in this cohort, nor were significant interactions found between haptoglobin phenotype and sleep-disordered breathing on the prevalence of cardiovascular disease. CONCLUSIONS: Sleep-disordered breathing did not appear to interact with haptoglobin phenotype in modifying the association with prevalent cardiovascular disease in the Sleep Heart Health Study. These findings could be due to the absence of association or to survivor bias in these cross-sectional analyses.
Keywords: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Bypass; Cross-Sectional Studies; Female; Haptoglobins; Humans; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Phenotype; Polysomnography; Prevalence; Sleep Apnea Syndromes

Hospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival. - O'Meara, Ellen S; White, Mark; Siscovick, David S; Lyles, Mary F; Kuller, Lewis H (J Am Geriatr Soc, 2005)
OBJECTIVES: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality. DESIGN: Prospective observational study. SETTING: The Cardiovascular Health Study (CHS) in four U.S. communities. PARTICIPANTS: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years. MEASUREMENTS: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death. RESULTS: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2-12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1-6.0) during the first year after hospitalization and 2.6 (95% CI=2.2-3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1-4.8) and 2.0 (95% CI=1.6-2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function. CONCLUSION: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.
Keywords: Aged; Aged, 80 and over; Cognition; Comorbidity; Diabetes Complications; Female; Hospitalization; Humans; Male; Mortality; Pneumonia; Prospective Studies; Respiratory Physiological Phenomena; Risk Factors; Smoking

Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. - Longstreth, W T; Arnold, Alice M; Beauchamp, Norman J; Manolio, Teri A; Lefkowitz, David; Jungreis, Charles; Hirsch, Calvin H; O'Leary, Daniel H; Furberg, Curt D (Stroke, 2005)
BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade. RESULTS: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk. CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.
Keywords: Aged; Brain; Cardiovascular Diseases; Cognition Disorders; Female; Humans; Incidence; Leukoaraiosis; Longitudinal Studies; Magnetic Resonance Imaging; Male; Risk Factors; Stroke

Incidence of cardiovascular disease in older Americans: the cardiovascular health study. - Arnold, Alice M; Psaty, Bruce M; Kuller, Lewis H; Burke, Gregory L; Manolio, Teri A; Fried, Linda P; Robbins, John A; Kronmal, Richard A (J Am Geriatr Soc, 2005)
OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans. DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events. SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS). PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American). MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD. RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95% confidence interval (CI)=36.4-43.1) in men and 22.3 (95% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95% CI=13.0-16.6) and 13.7 (95% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9% with each year of age over 65 and was greater than 6% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians. CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.
Keywords: African Americans; Age Distribution; Aged; Aged, 80 and over; Cardiovascular Diseases; European Continental Ancestry Group; Female; Geriatric Assessment; Humans; Incidence; Longitudinal Studies; Male; Sex Distribution; Survival Rate; United States

Kidney function as a predictor of noncardiovascular mortality. - Fried, Linda F; Katz, Ronit; Sarnak, Mark J; Shlipak, Michael G; Chaves, Paulo H M; Jenny, Nancy Swords; Stehman-Breen, Catherine; Gillen, Dan; Bleyer, Anthony J; Hirsch, Calvin; Siscovick, David; Newman, Anne B (J Am Soc Nephrol, 2005)
Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.
Keywords: Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Cohort Studies; Confidence Intervals; Creatinine; Cystatin C; Cystatins; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Kidney Function Tests; Longitudinal Studies; Male; Probability; Proportional Hazards Models; Risk Assessment; Severity of Illness Index; Survival Analysis; United States

Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study. - Podewils, Laura Jean; Guallar, Eliseo; Kuller, Lewis H; Fried, Linda P; Lopez, Oscar L; Carlson, Michelle; Lyketsos, Constantine G (Am J Epidemiol, 2005)
Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Apolipoproteins E; Dementia; Dementia, Vascular; Female; Genotype; Humans; Male; Motor Activity; Proportional Hazards Models; Prospective Studies; Risk Factors; United States

Polysomnographic predictors of blood pressure and hypertension: is one index best? - Redline, Susan; Min, Nancy I; Shahar, Eyal; Rapoport, David; O'Connor, George (Sleep, 2005)
STUDY OBJECTIVES: Numerous indexes derived from polysomnography are available to characterize sleep-disordered breathing, with no consensus over which measures best predict clinical outcomes. This study addresses the relative merits of using alternative polysomnography indexes by characterizing the consistency and strength of the association of each index with blood pressure and hypertension. DESIGN: Cross-sectional analyses of the association of alternative polysomnography indexes with blood pressure and hypertension were performed in construction and validation data sets. Linear and logistic regression models were used to identify the best variable sets. PATIENTS: Data were obtained from 6433 men and women (age 62.9 +/- 11.0 years, 52.8% women) who participated in the Sleep Heart Health Study. RESULTS: In multivariable models, most indexes showed weak linear associations with systolic, with slightly stronger associations for diastolic blood pressure, and the log odds of hypertension. No single index showed consistent superiority over others. Systolic blood pressure, diastolic blood pressure, and hypertension each were associated with distinct sets of polysomnography variables. Slightly more-consistent associations were demonstrated for indexes that included hypopneas that were linked with either a 3% or 4% desaturation level than indexes that did not require hypopneas to have linked desaturation. For indexes that combined apneas and hypopneas, there was no evidence that linking obstructive apneas to desaturation or arousal altered prediction compared with counting all apneas. CONCLUSION: In summary, using a rigorous cross-validation assessment, we did not identify a clear superiority of any single index for blood pressure or hypertension prediction. Detailed analyses of alternative definitions of the respiratory disturbance index support current scoring guidelines, where desaturation criteria are recommended for hypopneas but not apneas.
Keywords: Blood Pressure; Cross-Sectional Studies; Female; Humans; Hypertension; Male; Middle Aged; Polysomnography; Predictive Value of Tests; Reproducibility of Results; Severity of Illness Index; Sleep Apnea, Obstructive

Population structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study. - Reiner, Alexander P; Ziv, Elad; Lind, Denise L; Nievergelt, Caroline M; Schork, Nicholas J; Cummings, Steven R; Phong, Angie; Burchard, Esteban González; Harris, Tamara B; Psaty, Bruce M; Kwok, Pui-Yan (Am J Hum Genet, 2005)
U.S. populations are genetically admixed, but surprisingly little empirical data exists documenting the impact of such heterogeneity on type I and type II error in genetic-association studies of unrelated individuals. By applying several complementary analytical techniques, we characterize genetic background heterogeneity among 810 self-identified African American subjects sampled as part of a multisite cohort study of cardiovascular disease in older adults. On the basis of the typing of 24 ancestry-informative biallelic single-nucleotide-polymorphism markers, there was evidence of substantial population substructure and admixture. We used an allele-sharing-based clustering algorithm to infer evidence for four genetically distinct subpopulations. Using multivariable regression models, we demonstrate the complex interplay of genetic and socioeconomic factors on quantitative phenotypes related to cardiovascular disease and aging. Blood glucose level correlated with individual African ancestry, whereas body mass index was associated more strongly with genetic similarity. Blood pressure, HDL cholesterol level, C-reactive protein level, and carotid wall thickness were not associated with genetic background. Blood pressure and HDL cholesterol level varied by geographic site, whereas C-reactive protein level differed by occupation. Both ancestry and genetic similarity predicted the number and quality of years lived during follow-up, but socioeconomic factors largely accounted for these associations. When the 24 genetic markers were tested individually, there were an excess number of marker-trait associations, most of which were attenuated by adjustment for genetic ancestry. We conclude that the genetic demography underlying older individuals who self identify as African American is complex, and that controlling for both genetic admixture and socioeconomic characteristics will be required in assessing genetic associations with chronic-disease-related traits in African Americans. Complementary methods that identify discrete subgroups on the basis of genetic similarity may help to further characterize the complex biodemographic structure of human populations.
Keywords: African Americans; Aged; Aging; Algorithms; Cardiovascular Diseases; Cohort Studies; Female; Genetics, Population; Genotype; Humans; Male; Models, Genetic; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Risk Factors; Socioeconomic Factors

Predictors of heartburn during sleep in a large prospective cohort study. - Fass, Ronnie; Quan, Stuart F; O'Connor, George T; Ervin, Ann; Iber, Conrad (Chest, 2005)
BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study. METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep. CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.
Keywords: Aged; Body Mass Index; Carbonated Beverages; Cohort Studies; Educational Status; Female; Gastroesophageal Reflux; Heartburn; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Sleep; Surveys and Questionnaires

Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study. - Newman, Anne B; Foster, Greg; Givelber, Rachel; Nieto, F Javier; Redline, Susan; Young, Terry (Arch Intern Med, 2005)
BACKGROUND: The relationship of weight changes to the incidence, progression, and remission of sleep-disordered breathing (SDB) is not well defined. This study aims to determine the relationship between change in weight and progression or remission of SDB by polysomnography. METHODS: We performed a longitudinal cohort study of the cardiovascular consequences of sleep apnea in diverse US communities. Sleep apnea and polysomnographic indicators of SDB were assessed 5 years apart. RESULTS: A total of 2968 men and women (mean age, 62 years) participated in the study. Men were more likely to have an increase in Respiratory Disturbance Index (RDI) with a given increase in weight than were women, and this was not explained by differences in starting weight, waist circumference, age, or ethnicity. In a linear regression analysis, both men and women had a greater increase in RDI with weight gain than a decrease in RDI with weight loss. In a categorical analysis of larger degrees of change, this sex difference was also evident. Associations were similar in diverse ethnic groups. However, SDB progressed over time, even in those with stable weight. CONCLUSION: Modest changes in weight were related to an increase or decrease in SDB, and this association was stronger in men than in women.
Keywords: Body Weights and Measures; Causality; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Humans; Linear Models; Male; Middle Aged; Obesity; Odds Ratio; Sex Distribution; Sleep Apnea Syndromes; United States; Weight Gain; Weight Loss

A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. - Zakai, Neil A; Katz, Ronit; Hirsch, Calvin; Shlipak, Michael G; Chaves, Paulo H M; Newman, Anne B; Cushman, Mary (Arch Intern Med, 2005)
BACKGROUND: Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear. METHODS: Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities. RESULTS: A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95% CI, 1.25-1.62) and 1.24 (95% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95% CI, 1.15-1.54) and 1.17 (95% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95% CI, 1.38-1.78) and 1.38 (95% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations. CONCLUSIONS: Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations.
Keywords: Age Factors; Aged; Anemia; California; Female; Follow-Up Studies; Health Status; Hemoglobins; Humans; Male; Maryland; Multivariate Analysis; North Carolina; Observation; Pennsylvania; Prospective Studies; Risk Factors; Severity of Illness Index; Survival Rate

Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin. - Chen, Chu; Lewis, S Kay; Voigt, Lynda; Fitzpatrick, Annette; Plymate, Stephen R; Weiss, Noel S (Cancer, 2005)
BACKGROUND: There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case-control study within the Cardiovascular Health Study cohort. METHODS: In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n=174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1-9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age. RESULTS: Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95% confidence interval [95% CI], 0.43-1.38), 0.73 (95% CI, 0.41-1.30), and 0.67 (95% CI, 0.37-1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels <4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95% CI, 0.49-1.68), 0.47 (95% CI, 0.25-0.94), and 0.65 (95% CI, 0.35-1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical. CONCLUSIONS: The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk.
Keywords: Aged; Aged, 80 and over; Carcinoma; Case-Control Studies; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Prostatic Neoplasms; Risk Factors

Renal duplex parameters, blood pressure, and renal function in elderly people. - Pearce, Jeffrey D; Edwards, Matthew S; Craven, Timothy E; English, William P; Mondi, Matthew M; Reavis, Scott W; Hansen, Kimberley J (Am J Kidney Dis, 2005)
BACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans. METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques. RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine. CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.
Keywords: African Americans; Aged; Aging; Arteriosclerosis; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Creatinine; Cross-Sectional Studies; Diastole; Disease Progression; European Continental Ancestry Group; Female; Humans; Hypertension, Renovascular; Kidney; Kidney Diseases; Kidney Function Tests; Male; Renal Artery; Renal Artery Obstruction; Renal Circulation; Risk Factors; Sampling Studies; Systole; Ultrasonography, Doppler, Duplex; United States

Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study. - Edwards, Matthew S; Craven, Timothy E; Burke, Gregory L; Dean, Richard H; Hansen, Kimberley J (Arch Intern Med, 2005)
BACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans. METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization. RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure. CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.
Keywords: Age Distribution; Aged; Aged, 80 and over; Analysis of Variance; Cohort Studies; Comorbidity; Coronary Disease; Female; Geriatric Assessment; Heart Function Tests; Humans; Hypertension, Renovascular; Incidence; Kidney Function Tests; Male; Multivariate Analysis; Probability; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Rate; Ultrasonography, Doppler; United States

Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. - Kennedy, Margaret; Solomon, Cam; Manolio, Teri A; Criqui, Michael H; Newman, Anne B; Polak, Joseph F; Burke, Gregory L; Enright, Paul; Cushman, Mary (Arch Intern Med, 2005)
BACKGROUND: An ankle-brachial index (ABI) of less than 0.9 is a noninvasive measure of lower extremity arterial disease and a predictor of cardiovascular events. Little information is available on longitudinal change in ABI or on risk factors for declining ABI in a community-based population. METHODS: To assess risk factors for ABI decline, we studied 5888 participants in the Cardiovascular Health Study cohort (men and women 65 years or older). We measured ABI in 1992-1993 and again in 1998-1999. At baseline, we excluded individuals with an ABI less than 0.9, ABI greater than 1.4, or confirmed symptomatic lower extremity arterial disease (n = 823). The group with ABI decline included 218 participants with decline greater than 0.15 and to 0.9 or less. The comparison group comprised the remaining 2071 participants with follow-up ABI. RESULTS: The percentage of participants with ABI decline was 9.5% over 6 years of follow-up. The mean +/- SD decline was 0.33 +/- 0.12 in cases of ABI decline and 0.02 +/- 0.13 in non-cases. Independent predictors of ABI decline, reported as odds ratios, were age, 1.96 (95% confidence interval [CI], 1.42-2.71) for 75 to 84 years and 3.79 (95% CI, 1.36-10.5) for those older than 85 years compared with those younger than 75 years; current cigarette use, 1.74 (95% CI, 1.02-2.96); hypertension, 1.64 (95% CI, 1.18-2.28); diabetes, 1.77 (95% CI, 1.14-2.76); higher low-density lipoprotein cholesterol level, 1.60 (95% CI, 1.03-2.51), and lipid-lowering drug use 1.74 (95% CI, 1.05-2.89). CONCLUSION: Worsening lower extremity arterial disease, assessed as ABI decline, occurred in 9.5% of this elderly cohort over 6 years and was associated with modifiable vascular disease risk factors.
Keywords: Aged; Aged, 80 and over; Ankle; Brachial Artery; Cardiovascular Diseases; Female; Humans; Male; Peripheral Vascular Diseases; Risk Assessment; Risk Factors

Sleepiness in patients with moderate to severe sleep-disordered breathing. - Kapur, Vishesh K; Baldwin, Carol M; Resnick, Helaine E; Gottlieb, Daniel J; Nieto, F Javier (Sleep, 2005)
BACKGROUND: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15). DESIGN: Cross-sectional study. SETTING: The Sleep Heart Health Study. PARTICIPANTS: Sleep Heart Health Study participants (N = 6440). MEASUREMENTS AND RESULTS: Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not. CONCLUSIONS: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.
Keywords: Aged; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Oxygen; Polysomnography; Prevalence; Risk Factors; Severity of Illness Index; Sleep Apnea Syndromes; Sleep Arousal Disorders; Sleep Stages; Surveys and Questionnaires

Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses. - Stein, Phyllis K; Domitrovich, Peter P; Hui, Nelson; Rautaharju, Pentti; Gottdiener, John (J Cardiovasc Electrophysiol, 2005)
OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly. METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality. RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04). CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.
Keywords: Aged; Aged, 80 and over; Algorithms; Arrhythmia, Sinus; Cohort Studies; Diagnosis, Computer-Assisted; Electrocardiography; Female; Heart Rate; Humans; Male; Models, Cardiovascular; Nonlinear Dynamics; Numerical Analysis, Computer-Assisted; Prevalence; Proportional Hazards Models; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; United States

Statin use and the risk of incident dementia: the Cardiovascular Health Study. - Rea, Thomas D; Breitner, John C; Psaty, Bruce M; Fitzpatrick, Annette L; Lopez, Oscar L; Newman, Anne B; Hazzard, William R; Zandi, Peter P; Burke, Gregory L; Lyketsos, Constantine G; Bernick, Charles; Kuller, Lewis H (Arch Neurol, 2005)
BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia. OBJECTIVE: To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs). DESIGN: Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 participants free of dementia at baseline. MAIN OUTCOME MEASURES: Using Cox proportional hazards regression analysis, we estimated the risk of incident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses included the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach. RESULTS: Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia and 0.56 (95% CI, 0.35-0.92) for any Alzheimer disease. CONCLUSIONS: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.
Keywords: Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Dementia; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Male

Statins and cognitive function in the elderly: the Cardiovascular Health Study. - Bernick, C; Katz, R; Smith, N L; Rapp, S; Bhadelia, R; Carlson, M; Kuller, L (Neurology, 2005)
OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults. METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.
Keywords: Aged; Aged, 80 and over; Aging; Anticholesteremic Agents; Atrophy; Brain; Cholesterol; Cognition Disorders; Cohort Studies; Dementia; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Longitudinal Studies; Male; Memory Disorders; Nootropic Agents; Treatment Outcome

Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults. - Rosano, Caterina; Kuller, Lewis H; Chung, Hyoju; Arnold, Alice M; Longstreth, William T; Newman, Anne B (J Am Geriatr Soc, 2005)
OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance. DESIGN: Longitudinal analysis, average follow-up time: 4.0 years. SETTING: Cardiovascular Health Study (CHS). PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4). MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand). RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed. CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.
Keywords: Activities of Daily Living; Aged; Aged, 80 and over; Brain; Female; Follow-Up Studies; Gait; Humans; Incidence; Magnetic Resonance Imaging; Male; Proportional Hazards Models; Psychomotor Disorders; Risk Factors; United States

Survival following dementia onset: Alzheimer's disease and vascular dementia. - Fitzpatrick, Annette L; Kuller, Lewis H; Lopez, Oscar L; Kawas, Claudia H; Jagust, William (J Neurol Sci, 2005)
Survival following the onset of dementia has been reported to vary from 3 to over 9 years. We examined mortality in 3602 participants of the Cardiovascular Health (CHS) Cognition Study in four US communities evaluated for dementia incidence between 1992 and 1999 and followed for 6.5 years. By June 2000, 33 of 62 (53.2%) participants who developed vascular dementia (VaD) had died compared to 79 of 245 (32.2%) with Alzheimer's disease (AD), 66 of 151 (43.7%) with both AD and VaD, and 429 of 2318 (18.5%) with normal cognition. Using Cox proportional hazards regression with a time-dependent covariate for dementia status adjusted for age, gender and race, individuals with VaD were more than four times as likely to die during follow-up than those with normal cognition (HR: 4.4, 95% CI: 3.1-6.3). The hazard ratios were 2.1 (95% CI: 1.6-2.7) for AD and 2.5 (95% CI: 1.9-3.3) for both types. Adjusted accelerated life models estimated median survival from dementia onset to death as 3.9 years for those with VaD, 7.1 years for AD, 5.4 years for mixed dementia, and 11.0 years for matched controls with normal cognition. While persons with VaD died primarily from cerebrovascular disease, those with AD/mixed dementia died more frequently from dementia/failure to thrive.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Brain; Capillaries; Cerebral Amyloid Angiopathy; Cerebrovascular Circulation; Cerebrovascular Disorders; Female; Frontal Lobe; Humans; Male; Middle Aged; Prospective Studies

Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly. - Kaplan, R C; Tirschwell, D L; Longstreth, W T; Manolio, T A; Heckbert, S R; Lefkowitz, D; El-Saed, A; Psaty, B M (Neurology, 2005)
BACKGROUND: The authors studied mortality, vascular events, and preventive therapies following ischemic stroke among adults aged > or =65 years. METHODS: The authors identified 546 subjects with first ischemic stroke during 1989 to 2001 among Cardiovascular Health Study participants. Deaths, recurrent strokes, and coronary heart disease (CHD) events were identified over 3.2 years (median) follow-up. RESULTS: During the first year of follow-up, rates were 105.4/1,000 for recurrent stroke and 59.3/1,000 for CHD. After the first year, the stroke rate was 52.0/1,000 and the CHD rate was 46.5/1,000. Cardioembolic strokes had the highest mortality (185.4/1,000) and recurrence rates (86.6/1,000). Lacunar strokes had the lowest mortality (119.3/1,000) and recurrence rates (43.0/1,000). Age and male sex predicted death and CHD, but not recurrence. Outcomes did not differ by race. Following stroke, 47.8% used aspirin and 13.5% used other antiplatelet agents; 52.6% of patients with atrial fibrillation used warfarin; 31.3% of hyperlipidemic subjects, 57.0% of diabetic patients, and 81.5% of hypertensive patients were drug-treated; and 40.0% of hypertensive patients had blood pressure (BP) <140/90 mm Hg. Older subjects were less likely to use lipid-lowering therapy, women were less likely to have BP <140/90 mm Hg, and low-income subjects were less likely to use diabetes medications. CONCLUSIONS: Recurrent strokes were nearly twice as frequent as coronary heart disease (CHD) events during the first year after initial stroke, but stroke and CHD rates were similar after the first year. Preventive drug therapies were underused, which may reflect clinical uncertainty due to the lack of clinical trials among the elderly. Utilization was lower among the oldest patients, women, and low-income individuals.
Keywords: Age Factors; Aged; Aged, 80 and over; Aging; Anticoagulants; Antihypertensive Agents; Brain Ischemia; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Utilization; Female; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Male; Mortality; Prospective Studies; Recurrence; Sex Factors; Stroke; Treatment Outcome

Weight loss, muscle strength, and angiotensin-converting enzyme inhibitors in older adults with congestive heart failure or hypertension. - Schellenbaum, Gina D; Smith, Nicholas L; Heckbert, Susan R; Lumley, Thomas; Rea, Thomas D; Furberg, Curt D; Lyles, Mary F; Psaty, Bruce M (J Am Geriatr Soc, 2005)
OBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor use may be associated with weight maintenance and sustained muscle strength (measured by grip strength) in older adults. DESIGN: Data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults, were used. SETTING: Subjects were recruited from four U.S. sites beginning in 1989; this analysis included data through 2001. PARTICIPANTS: CHS participants with congestive heart failure (CHF) or treated hypertension. MEASUREMENTS: The exposure, current ACE inhibitor use, was ascertained by medication inventory at annual clinic visits; the outcomes were weight change and grip-strength change during the following year. Multivariate linear regression was used, accounting for correlations between observations on the same participant over time. RESULTS: The average annual weight change was -0.38 kg in 2,834 participants (14,443 person-years) with treated hypertension and -0.62 kg in 342 participants (980 person-years) with CHF. ACE inhibitor use was associated with less annual weight loss after adjustment for potential confounders: a difference of 0.17 kg (95% confidence interval (CI)=0.05-0.29) in those with treated hypertension and 0.29 kg (95% CI=-0.25-0.83) in those with CHF. There was no evidence of association between ACE inhibitor use and grip-strength change. CONCLUSION: ACE inhibitor use may be associated with weight maintenance, but not maintenance of muscle strength, in older adults with treated hypertension.
Keywords: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Female; Hand Strength; Heart Failure; Humans; Hypertension; Male; Multivariate Analysis; Outcome Assessment, Health Care; Prospective Studies; Statistics as Topic; United States; Weight Loss

10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study. - Kuller, Lewis H; Arnold, Alice M; Psaty, Bruce M; Robbins, John A; O'Leary, Daniel H; Tracy, Russell P; Burke, Gregory L; Manolio, Teri A; Chaves, Paolo H M (Arch Intern Med, 2006)
BACKGROUND: The incidence of coronary heart disease (CHD) is very high among individuals 65 years or older. METHODS: We evaluated the relationships between measurements of subclinical disease at baseline (1989-1990) and at the third-year follow-up examination (1992-1993) and subsequent incidence of cardiovascular disease and total mortality as of June 2001. Approximately 61% of the participants without clinical cardiovascular disease at baseline had subclinical disease based on our previously described criteria from the Cardiovascular Health Study. RESULTS: The incidence of CHD was substantially increased for participants with subclinical disease compared with those who had no subclinical disease: 30.5 per 1000 person-years with and 16.3 per 1000 person-years without for white individuals, and 31.2 per 1000 person-years with and 12.5 per 1000 person-years without for black individuals. The risk persisted over the entire follow-up period. Incidence rates were higher for men than for women with or without subclinical disease, but there was little difference in rates for black individuals and white individuals. CONCLUSIONS: In multivariable models, subclinical disease at baseline remained a significant predictor of CHD in both men and women; the hazard ratios (95% confidence intervals) of their relative risks were 1.64 (1.30-2.06) and 1.49 (1.21-1.84), respectively. The presence of subclinical disease substantially increased the risk of subsequent CHD for participants with hypertension, diabetes mellitus, or elevated C-reactive protein. In summary, subclinical disease is very prevalent among older individuals, is independently associated with risk of CHD even over a 10-year follow-up period, and substantially increases the risk of CHD among participants with hypertension or diabetes mellitus.
Keywords: African Continental Ancestry Group; Aged; Blood Chemical Analysis; Cardiovascular Diseases; Comorbidity; Coronary Disease; Echocardiography; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Incidence; Male; Multivariate Analysis; Prevalence; Proportional Hazards Models; Regression Analysis; Risk Factors; Sex Distribution; United States

Adjusted mortality after hip fracture: From the cardiovascular health study. - Robbins, John A; Biggs, Mary L; Cauley, Jane (J Am Geriatr Soc, 2006)
OBJECTIVES: To estimate the risk of death associated with hip fracture (HFx), stratifying by sex and time since fracture. DESIGN: Prospective cohort study compared participants with and without hip fracture, matched on sex, age, race, recruitment period, and time since enrollment. SETTING: The Cardiovascular Health Study, a more-than-15-year longitudinal study of 5,888 older individuals from four U.S. sites. PARTICIPANTS: Three hundred seventy-nine individuals with HFx were compared with 1,134 without HFx. MEASUREMENTS: Extended Cox models were used to estimate mortality hazard ratios (HRs) for different periods after fracture, adjusting for prefracture health. RESULTS: Age- and race-adjusted excess mortality was 9% in women and 24% in men 1 year after fracture, and 24% in women and 26% men 5 years postfracture. Multivariable-adjusted HRs of mortality associated with HFx in women were 7.1 (95% confidence interval (CI) = 2.3-21.5), 2.1 (95% CI = 1.0-4.1), 1.4 (95% CI = 1.1-2.0), and 1.0 (95% CI = 0.6-1.5) for 0 to 1 months, 2 to 6 months, 7 months to 4 years, and 5 to 8 years, respectively, after index date. In men, respective HRs for the same time periods were 39.9 (95% CI = 5.2-308.7), 3.8 (95% CI = 1.4-10.3), 1.1 (95% CI = 0.7-1.8), and 1.0 (95% CI = 0.3-2.7). HRs adjusted for age and race were 20% to 40% higher. CONCLUSION: The risk of mortality was highest in the first 6 months after HFx. In men, the risk of death approximated that of men without HFx after 6 months; in women, a moderately greater risk persisted through the fourth year. Although the mortality pattern was different in women and men, excess mortality 5 years postfracture was similar for both sexes.
Keywords: Aged; Cohort Studies; Female; Health Status; Health Surveys; Hip Fractures; Humans; Male; Mortality; Multicenter Studies as Topic; Proportional Hazards Models; Sex Distribution; Time Factors; United States

African ancestry, socioeconomic status, and kidney function in elderly African Americans: a genetic admixture analysis. - Peralta, Carmen A; Ziv, Elad; Katz, Ronit; Reiner, Alex; Burchard, Esteban González; Fried, Linda; Kwok, Pui-Yan; Psaty, Bruce; Shlipak, Michael (J Am Soc Nephrol, 2006)
Kidney disease is a major public health problem in the United States that affects African Americans disproportionately. The relative contribution of environmental and genetic factors to the increased burden of kidney disease among African Americans is unknown. The associations of genetic African ancestry and socioeconomic status with kidney function were studied cross-sectionally and longitudinally among 736 community-dwelling African Americans who were aged >65 yr and participating in the Cardiovascular Health Study. Genetic African ancestry was determined by genotyping 24 biallelic ancestry-informative markers and combining this information statistically to generate an estimate of ancestry for each individual. Kidney function was evaluated by cystatin C and estimated GFR (eGFR) using the Modification of Diet in Renal Disease equation. Longitudinal changes in serum creatinine and eGFR were estimated using baseline and follow-up values. In cross-sectional analyses, there was no association between genetic African ancestry and either measure of kidney function (P = 0.36 for cystatin C and 0.68 for eGFR). African ancestry was not associated with change in serum creatinine > or =0.05 mg/dl per yr (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.83 to 1.06) or with change in eGFR > or =3 ml/min per 1.73 m(2) per yr (OR 1.02; 95% CI 0.92 to 1.13). In contrast, self reported African-American race was strongly associated with increased risk for kidney disease progression compared with white individuals for change in creatinine (OR 1.77; 95% CI 1.33 to 2.36) and for change in eGFR (OR 3.21; 95% CI 2.54 to 4.06). Among self-identified African Americans, low income (< US dollars 8000/yr) was strongly associated with prevalent kidney dysfunction by cystatin C >1.29 g/dl (adjusted OR 2.7; 95% CI 1.0 to 7.5) or by eGFR <60 ml/min per 1.73 m(2) (adjusted OR 3.2; 95% CI 1.1 to 9.4) compared with those with incomes >US dollars 35,000/yr. Alleles that are known to be present more frequently in the African ancestral group were not associated with kidney dysfunction or kidney disease progression. Rather, kidney dysfunction in elderly African Americans seems more attributable to differences in environmental and social factors.
Keywords: African Americans; Aged; Creatinine; Cross-Sectional Studies; Cystatin C; Cystatins; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Linear Models; Longitudinal Studies; Male; Social Class

Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study. - Mukamal, Kenneth J; Chung, Hyoju; Jenny, Nancy S; Kuller, Lewis H; Longstreth, W T; Mittleman, Murray A; Burke, Gregory L; Cushman, Mary; Psaty, Bruce M; Siscovick, David S (J Am Geriatr Soc, 2006)
OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71-1.14), 0.93 (95% CI=0.73-1.20), 0.76 (95% CI=0.53-1.10), and 0.58 (95% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.
Keywords: Aged; Alcohol Drinking; Apolipoproteins E; Beer; Cohort Studies; Coronary Disease; Female; Genotype; Health Behavior; Humans; Incidence; Male; Residence Characteristics; Risk Assessment; Socioeconomic Factors; United States; Wine

Alcohol consumption in older adults and Medicare costs. - Mukamal, Kenneth J; Lumley, Thomas; Luepker, Russell V; Lapin, Pauline; Mittleman, Murray A; McBean, A Marshall; Crum, Rosa M; Siscovick, David S (Health Care Financ Rev, 2006)
We determined the relationship of alcohol consumption and Medicare costs among 4,392 participants in the Cardiovascular Health Study (CHS), a longitudinal, population-based cohort study of adults age 65 or over in four U.S. communities. We assessed 5-year Parts A and B costs and self-reported intake of beer, wine, and liquor at baseline. Among both sexes, total costs were approximately $2,000 lower among consumers of > 1-6 drinks per week than abstainers. The lower costs associated with moderate drinking were most apparent among participants with cardiovascular disease (CVD) and for hospitalization costs for CVD among healthy participants. Former drinkers had the highest costs.
Keywords: Aged; Alcohol Drinking; Cardiovascular Diseases; Female; Health Expenditures; Hospitalization; Humans; Longitudinal Studies; Male; Medicare; United States

The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. - Bryson, Chris L; Mukamal, Kenneth J; Mittleman, Murray A; Fried, Linda P; Hirsch, Calvin H; Kitzman, Dalane W; Siscovick, David S (J Am Coll Cardiol, 2006)
OBJECTIVES: We investigated the association between alcohol consumption and incident congestive heart failure (CHF) both overall and after adjusting for incident myocardial infarction (MI). BACKGROUND: Moderate alcohol consumption has been associated with lower risk of CHF and MI. METHODS: The Cardiovascular Health study, a prospective cohort study of cardiovascular disease risk factors and outcomes, followed 5,888 subjects > or =65 years old for 7 to 10 years. Cox models were used to estimate the adjusted risk of CHF by reported alcohol consumption. RESULTS: There were 5,595 subjects at baseline at risk for incident CHF with alcohol data and 1,056 events during follow-up. Compared with abstainers, the adjusted risk of CHF was lower among subjects who reported consuming 1 to 6 drinks per week (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67 to 1.00, p = 0.05) and 7 to 13 drinks per week (HR 0.66, 95% CI 0.47 to 0.91, p = 0.01). Time-dependent adjustment for incident MI altered only slightly the association between moderate alcohol consumption and CHF (for 1 to 6 drinks per week, HR 0.84, 95% CI 0.65 to 1.04; for 7 to 13 drinks per week, HR 0.69, 95% CI 0.49 to 0.99). Baseline former drinkers had a higher risk of CHF than abstainers (HR 1.51, p < 0.01), but those who quit during the study did not have a higher risk (HR 0.83, 95% CI 0.66 to 1.03). CONCLUSIONS: Moderate alcohol use is associated with a lower risk of incident CHF among older adults, even after accounting for incident MI and other factors.
Keywords: Aged; Alcohol Drinking; Chi-Square Distribution; Comorbidity; Female; Heart Failure; Humans; Life Style; Male; Multicenter Studies as Topic; Myocardial Infarction; Proportional Hazards Models; Risk Factors; Smoking

The association of markers of inflammation with weight change in older adults: the Cardiovascular Health Study. - Barzilay, J I; Forsberg, C; Heckbert, S R; Cushman, M; Newman, A B (Int J Obes (Lond), 2006)
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

The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study. - Cao, Jie J; Barzilay, Joshua I; Peterson, Do; Manolio, Teri A; Psaty, Bruce M; Kuller, Lewis; Wexler, Jason; Bleyer, Anthony J; Cushman, Mary (Atherosclerosis, 2006)
PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events. METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass. RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]). CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.
Keywords: Aged; Aged, 80 and over; Albuminuria; Atherosclerosis; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Female; Humans; Hypertension; Male; Peripheral Vascular Diseases; Prevalence; Risk Factors; Stroke; United States

Association of nocturnal arrhythmias with sleep-disordered breathing: The Sleep Heart Health Study. - Mehra, Reena; Benjamin, Emelia J; Shahar, Eyal; Gottlieb, Daniel J; Nawabit, Rawan; Kirchner, H Lester; Sahadevan, Jayakumar; Redline, Susan (Am J Respir Crit Care Med, 2006)
RATIONALE: Sleep-disordered breathing recurrent intermittent hypoxia and sympathetic nervous system activity surges provide the milieu for cardiac arrhythmia development. OBJECTIVE: We postulate that the prevalence of nocturnal cardiac arrhythmias is higher among subjects with than without sleep-disordered breathing. METHODS: The prevalence of arrhythmias was compared in two samples of participants from the Sleep Heart Health Study frequency-matched on age, sex, race/ethnicity, and body mass index: (1) 228 subjects with sleep-disordered breathing (respiratory disturbance index>or=30) and (2) 338 subjects without sleep-disordered breathing (respiratory disturbance index<5). RESULTS: Atrial fibrillation, nonsustained ventricular tachycardia, and complex ventricular ectopy (nonsustained ventricular tachycardia or bigeminy or trigeminy or quadrigeminy) were more common in subjects with sleep-disordered breathing compared with those without sleep-disordered breathing: 4.8 versus 0.9% (p=0.003) for atrial fibrillation; 5.3 versus 1.2% (p=0.004) for nonsustained ventricular tachycardia; 25.0 versus 14.5% (p=0.002) for complex ventricular ectopy. Compared with those without sleep-disordered breathing and adjusting for age, sex, body mass index, and prevalent coronary heart disease, individuals with sleep-disordered breathing had four times the odds of atrial fibrillation (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.03-15.74), three times the odds of nonsustained ventricular tachycardia (OR, 3.40; 95% CI, 1.03-11.20), and almost twice the odds of complex ventricular ectopy (OR, 1.74; 95% CI, 1.11-2.74). A significant relation was also observed between sleep-disordered breathing and ventricular ectopic beats/h (p<0.0003) considered as a continuous outcome. CONCLUSIONS: Individuals with severe sleep-disordered breathing have two- to fourfold higher odds of complex arrhythmias than those without sleep-disordered breathing even after adjustment for potential confounders.
Keywords: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Circadian Rhythm; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Polysomnography; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; Sleep; Sleep Apnea, Obstructive

Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. - Lange, Leslie A; Carlson, Christopher S; Hindorff, Lucia A; Lange, Ethan M; Walston, Jeremy; Durda, J Peter; Cushman, Mary; Bis, Joshua C; Zeng, Donglin; Lin, Danyu; Kuller, Lewis H; Nickerson, Deborah A; et al. (JAMA, 2006)
CONTEXT: C-reactive protein (CRP) is an inflammation protein that may play a role in the pathogenesis of cardiovascular disease (CVD). OBJECTIVE: To assess whether polymorphisms in the CRP gene are associated with plasma CRP, carotid intima-media thickness (CIMT), and CVD events. DESIGN, SETTING, AND PARTICIPANTS: In the prospective, population-based Cardiovascular Health Study, 4 tag single-nucleotide polymorphisms (SNPs) (1919A/T, 2667G/C, 3872G/A, 5237A/G) were genotyped in 3941 white (European American) participants and 5 tag SNPs (addition of 790A/T) were genotyped in 700 black (African American) participants, aged 65 years or older, all of whom were without myocardial infarction (MI) or stroke before study entry. Median follow-up was 13 years (1989-2003). MAIN OUTCOME MEASURES: Baseline CIMT; occurrence of MI, stroke, and CVD mortality during follow-up. RESULTS: In white participants, 461 incident MIs, 491 incident strokes, and 490 CVD-related deaths occurred; in black participants, 67 incident MIs, 78 incident strokes, and 75 CVD-related deaths occurred. The 1919T and 790T alleles were associated with higher CRP levels in white and black participants, respectively. The 3872A allele was associated with lower CRP levels in both populations, and the 2667C allele was associated with lower CRP levels in white participants only. There was no association between CIMT and any CRP gene polymorphism in either population. In white participants, the 1919T allele was associated with increased risk of stroke for TT vs AA (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.87) and for CVD mortality (HR, 1.40; 95% CI, 1.10-1.90). In black participants, homozygosity for the 790T allele was associated with a 4-fold increased risk of MI compared with homozygosity for the 790A allele (95% CI, 1.58-10.53). The minor alleles of the 2 SNPs associated with lower plasma CRP concentration in white participants (2667C and 3872A) were associated with decreased risk of CVD mortality. CONCLUSIONS: Genetic variation in the CRP gene is associated with plasma CRP levels and CVD risk in older adults.
Keywords: African Continental Ancestry Group; Aged; C-Reactive Protein; Cardiovascular Diseases; Carotid Arteries; European Continental Ancestry Group; Female; Genotype; Humans; Male; Myocardial Infarction; Polymorphism, Single Nucleotide; Proportional Hazards Models; Risk; Stroke; Tunica Intima

The association of race with frailty: the cardiovascular health study. - Hirsch, Calvin; Anderson, Melissa L; Newman, Anne; Kop, Willem; Jackson, Sharon; Gottdiener, John; Tracy, Russell; Fried, Linda P (Ann Epidemiol, 2006)
PURPOSE: Frailty, which has been conceptualized as a state of decreased physiologic reserve contributing to functional decline, has a prevalence among older African Americans that is twice that in older whites. This study assesses the independent contribution of race to frailty. METHODS: We evaluated 786 African-American and 4491 white participants of the Cardiovascular Health Study (CHS). Frailty is defined as meeting three or more of five criteria derived from CHS measures: lowest quintile for grip strength, self-reported exhaustion, unintentional weight loss of 10 lbs or greater in 1 year, slowest quintile for gait speed, and lowest quintile for physical activity. Controlling for age, sex, comorbidity, socioeconomic factors, and race, multinomial logistic regression estimated the odds ratio (OR) of prefrail (one or two criteria) to not frail and frail to not frail. RESULTS: Among African Americans, 8.7% of men and 15.0% of women were frail compared with 4.6% and 6.8% of white men and women, respectively. In adjusted models, nonobese African Americans had a fourfold greater odds of frailty compared with whites. The increased OR of frailty associated with African-American race was less pronounced among those who were obese or disabled. CONCLUSION: African-American race is associated independently with frailty.
Keywords: African Americans; Aged; Asthenia; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; European Continental Ancestry Group; Female; Frail Elderly; Health Status; Humans; Male; Middle Aged; Motor Activity; Odds Ratio; United States; Weight Loss

Association of usual sleep duration with hypertension: the Sleep Heart Health Study. - Gottlieb, Daniel J; Redline, Susan; Nieto, F Javier; Baldwin, Carol M; Newman, Anne B; Resnick, Helaine E; Punjabi, Naresh M (Sleep, 2006)
STUDY OBJECTIVES: Limited experimental data suggest that sleep restriction acutely elevates blood pressure; however, little is known about the relationship between usual sleep duration and hypertension. This study assesses the relationship between usual sleep duration and hypertension in a community-based cohort. DESIGN: Cross-sectional observational study. SETTING: The Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. PARTICIPANTS: Two thousand eight hundred thirteen men and 3097 women, aged 40 to 100 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Usual weekday and weekend sleep durations were obtained by questionnaire, and their weighted average were categorized as less than 6, 6 to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication to treat hypertension. The relationship between sleep duration and hypertension was examined using categorical logistic regression with adjustment for age, sex, race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7 to less than 8 hours per night, those sleeping less than 6 and between 6 and 7 hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping between 8 and 9 and 9 or more hours per night had adjusted odds ratios for hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p < .0001 for association of sleep duration with hypertension). These associations persisted when analyses were further adjusted for caffeine and alcohol consumption, current smoking, insomnia symptoms, depression symptoms, sleep efficiency, and prevalent diabetes mellitus or cardiovascular disease. CONCLUSIONS: Usual sleep duration above or below the median of 7 to less than 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night.
Keywords: Adult; Aged; Aged, 80 and over; Body Mass Index; Cohort Studies; Comorbidity; Cross-Sectional Studies; Female; Health Surveys; Humans; Hypertension; Male; Middle Aged; Odds Ratio; Prospective Studies; Sleep; Sleep Apnea, Obstructive; Sleep Deprivation; Statistics as Topic

Beta2-adrenergic receptor genetic variants and risk of sudden cardiac death. - Sotoodehnia, Nona; Siscovick, David S; Vatta, Matteo; Psaty, Bruce M; Tracy, Russell P; Towbin, Jeffrey A; Lemaitre, Rozenn N; Rea, Thomas D; Durda, J Peter; Chang, Joel M; Lumley, Thomas S; Kuller, Lewis H; et al. (Circulation, 2006)
BACKGROUND: Sympathetic activation influences the risk of ventricular arrhythmias and sudden cardiac death (SCD), mediated in part by the beta2-adrenergic receptor (B2AR). We investigated whether variation in the B2AR gene is associated with SCD risk. METHODS AND RESULTS: In this study, 4441 white and 808 black Cardiovascular Health Study (CHS) participants were followed up prospectively for SCD and genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated in 155 case and 144 control white subjects in a population-based case-control study of SCD, the Cardiac Arrest Blood Study (CABS). In CHS, Gly16 and Gln27 allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events occurred in white and black participants, respectively. The Gln27Glu variant was associated with SCD risk (P=0.008 for general model). SCD risk was higher in Gln27 homozygous participants than in Glu27 carriers (ethnicity-adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P=0.003). The increased risk did not differ significantly between white (HR, 1.62; 95% CI, 1.18 to 2.23) and black (HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the confidence interval was wide in blacks. In the CABS replication study, Gln27 homozygous participants similarly had higher SCD risk than Glu27 carriers (odds ratio, 1.64; 95% CI, 1.02 to 2.63; P=0.040). Gly16Arg was not associated with SCD risk in either study. CONCLUSIONS: Gln27 homozygous individuals have an increased risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role in SCD in humans. Study of genetic variation within the B2AR gene may help identify those at increased SCD risk.
Keywords: African Continental Ancestry Group; Aged; Case-Control Studies; Death, Sudden, Cardiac; European Continental Ancestry Group; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Glutamine; Haplotypes; Homozygote; Humans; Male; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2; Reproducibility of Results

Blood pressure level and outcomes in adults aged 65 and older with prior ischemic stroke. - Kaplan, Robert C; Tirschwell, David L; Longstreth, W T; Manolio, Teri A; Heckbert, Susan R; LeValley, Aaron J; Lefkowitz, David; El-Saed, Aiman; Psaty, Bruce M (J Am Geriatr Soc, 2006)
OBJECTIVES: To examine the association between blood pressure (BP) levels and long-term stroke outcomes in elderly stroke survivors. DESIGN: Observational study. SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling adults. PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age 78.6) who sustained a nonfatal first ischemic stroke. MEASUREMENTS: BP levels assessed at prestroke and poststroke CHS visits were examined as predictors of stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs), and mortality. RESULTS: Higher poststroke BP level, assessed 261.6 days (mean) after stroke, was associated with higher risk of stroke recurrence over 5.4 years (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence was 1.42 (95% confidence interval (CI) = 1.03-1.99) per standard deviation (SD) of systolic BP (P = .04) and 1.39 (95% CI = 1.01-1.91) per SD of diastolic BP (P = .04). Mortality was significantly greater in patients with low or high poststroke BP than in those with intermediate BP. Poststroke BP was not associated with risk of CHD or CVE, although further analyses suggested that high systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP did not predict poststroke outcomes. CONCLUSION: In this observational study of adults aged 65 and older assessed approximately 8 months after stroke, low BP was associated with favorable risk of recurrent stroke, although high and low poststroke BP levels were associated with greater mortality. Long-term antihypertensive trials in older stroke survivors would increase knowledge about the benefits of lowering BP in this population.
Keywords: Aged; Aged, 80 and over; Blood Pressure; Brain Ischemia; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Prospective Studies; Recurrence; Stroke; Survival Rate

Body mass index is not a good predictor of bone density: results from WHI, CHS, and EPIDOS. - Robbins, John; Schott, Anne-Marie; Azari, Rahman; Kronmal, Richard (J Clin Densitom, 2006)
Body mass index (BMI) is often used to predict bone mineral density (BMD). This may be flawed. Large epidemiologic studies with BMI and BMD data were analyzed. Weight alone is a better predictor of BMD than BMI. Thus, when selecting individuals for dual-energy X-ray absorptiometry, weight should be used instead of BMI. Low body mass index (BMI) is frequently suggested as one of the factors that indicates the need for bone mineral density (BMD) screening for osteoporosis. The inclusion of the height-squared term in the denominator of this predictive factor is taken on faith or from other data, but it may not be reasonable in this case. We used data from three large epidemiologic studies to test the BMI, height, and weight as predictors of BMD: (1) the Women's Health Initiative (WHI) with 11,390 women; (2) the Cardiovascular Health Study (CHS) with 1,578 men and women; (3) and EPIDOS with 7,598 women. Dual-energy X-ray absorptiometry data on one or more BMD sites, the total hip, the femoral neck, and the lumbar spine from the three studies, as well as height and weight were examined. Correlation coefficients for BMI and weight with BMD were compared. Log transformed models were evaluated to compare the strengths of the models. The result of weight alone was a much better predictor of BMD for all sites in the three studies than BMI. Taller participants had larger BMDs than would have been predicted by BMI. In conclusion, BMIs should not be used to select individuals for BMD screening. A regression model using weight alone or weight and height is a better predictor of BMD in all three populations.
Keywords: Absorptiometry, Photon; Aged; Aged, 80 and over; Biometry; Body Height; Body Mass Index; Body Weight; Bone Density; Female; France; Humans; Male; United States

Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study). - Barasch, Eddy; Gottdiener, John S; Marino Larsen, Emily K; Chaves, Paulo H M; Newman, Anne B (Am J Cardiol, 2006)
In the elderly, mitral annular calcification (MAC) and aortic valve sclerosis (AVS) are associated with increased cardiovascular morbidity and mortality. Aortic annular calcification (AAC) commonly occurs with MAC. However, the prognostic value of AAC, singly or in combination with MAC and AVS, for incident cardiovascular disease and mortality is unknown. From the Cardiovascular Health Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60% women) who had an echocardiogram at the 1994 to 1995 examination and who were prospectively followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification categories were associated with incident congestive heart failure (MAC: hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95% CI 1.28 to 2.06, and AVS: HR 1.50, 95% CI 1.19 to 1.89) and death. A stronger association with incident cardiovascular disease and mortality was observed with a larger number of calcification categories and with increased MAC severity. Moreover, in the participants with prevalent cardiovascular disease at echocardiographic examination (n = 1,054), MAC and AAC were still associated with cardiovascular mortality (MAC: HR 1.91, 95% CI 1.04 to 3.50; AAC: HR 2.11, 95% CI 1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are associated with a significant risk of incident congestive heart failure, cardiovascular and all-cause mortalities, and worse outcome in older patients with preexisting cardiovascular disease. Elderly patients with these findings represent a high-risk group and may require close medical attention.
Keywords: Aged; Aortic Valve; Calcinosis; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heart Valve Diseases; Humans; Male; Mitral Valve; Prospective Studies; Risk Factors; Sclerosis; Severity of Illness Index; United States

CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. - Conley, Yvette P; Jakobsdottir, Johanna; Mah, Tammy; Weeks, Daniel E; Klein, Ronald; Kuller, Lewis; Ferrell, Robert E; Gorin, Michael B (Hum Mol Genet, 2006)
Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P</=0.00001). A meta-analysis confirmed that the risk allele in the heterozygous or homozygous state (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers susceptibility. LOC387715 was also significantly associated with ARM in both cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4, respectively) confers susceptibility. Both CFH and LOC387715 showed an allele-dose effect on the ARM risk, individuals homozygous at either locus were at more than two-fold risk compared to those heterozygous. PLEKHA1, which is closely linked to LOC387715, was significantly associated with ARM status in the AREDS cohort, but not the CHS cohort and ELOVL4 was not significantly associated with ARM in either cohort. Joint action of CFH and LOC387715 was best described by independent multiplicative effect without significant interaction in both cohorts. Interaction of both genes with cigarette smoking was insignificant in both cohorts. This study provides additional support for the CFH and LOC387715 genes in ARM susceptibility via the evaluation of cohorts that had different ascertainment schemes regarding ARM status and through the meta-analyses.
Keywords: Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Complement Factor H; Eye Proteins; Female; Genetic Predisposition to Disease; Humans; Intracellular Signaling Peptides and Proteins; Macular Degeneration; Male; Membrane Proteins; Proteins

Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study. - Pearte, Camille A; Furberg, Curt D; O'Meara, Ellen S; Psaty, Bruce M; Kuller, Lewis; Powe, Neil R; Manolio, Teri (Circulation, 2006)
BACKGROUND: Although >80% of annual coronary heart disease (CHD) deaths occur in adults aged >65 years and the population is aging rapidly, CHD event fatality and its predictors in the elderly have not been well described. METHODS AND RESULTS: The first myocardial infarction (MI) or CHD death among the 5888 adults aged > or =65 years occurring during enrollment in the Cardiovascular Health Study during 1989-2001 was identified and adjudicated. Characteristics measured at examinations before the event were examined for associations with case fatality (death before hospitalization or hospital discharge) and for differences in predictors by demographics or clinical history. During a median follow-up of 8.2 years, 985 CHD events occurred, of which 30% were fatal. Case fatality decreased slightly over time, ranging from 28% to 30% per year in the early 1990s versus 23% by 2000-2001; with adjustment for age at MI and gender, there was a 6% lower odds of fatality with each successive year (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.90 to 0.98). Case fatality was similar by race and gender but higher with age and prior CHD (MI, angina, or revascularization). When considered alone, many subclinical disease measures, such as common carotid intima-media thickness, ankle-arm index, left ventricular mass by ECG, and a major ECG abnormality, and traditional risk factors, such as diabetes and hypertension, were associated with fatality. In multivariable analysis, independent predictors of fatality were prior congestive heart failure (OR, 3.20; 95% CI, 2.32 to 4.41), prior CHD rather than only history of MI (OR, 2.51; 95% CI, 1.84 to 3.43), diabetes (OR, 1.66; 95% CI, 1.10 to 2.31), and age (OR, 1.21 per 5 years; 95% CI, 1.07 to 1.37), adjusted for gender and each other. Prior congestive heart failure, regardless of left ventricular systolic function, age, gender, or prior CHD, conferred a > or =3-fold increased risk of fatality in almost all subgroups. CONCLUSIONS: Among community-dwelling older adults, CHD case fatality remains substantial, with easily identifiable risk factors that may be different from those that predict incident disease. In the elderly in whom the risk/benefit of therapies may be influenced by multiple competing comorbidities and care needs, risk stratification possibly may be improved further by focusing more aggressive care on specific patients, especially those with a history of congestive heart failure or prior CHD.
Keywords: Age Factors; Aged; Aged, 80 and over; Carotid Artery, Common; Cohort Studies; Comorbidity; Coronary Disease; Diabetes Mellitus; Electrocardiography; Female; Follow-Up Studies; Forecasting; Heart Failure; Heart Ventricles; Hospitalization; Humans; Hyperlipidemias; Hypertension; Male; Multivariate Analysis; Myocardial Infarction; Organ Size; Predictive Value of Tests; Risk Factors; Sampling Studies; Tunica Intima; Tunica Media; United States

Cigarette smoking and nocturnal sleep architecture. - Zhang, Lin; Samet, Jonathan; Caffo, Brian; Punjabi, Naresh M (Am J Epidemiol, 2006)
Cigarette smoking has been associated with a high prevalence of sleep-related complaints. However, its effects on sleep architecture have not been fully examined. The primary objective of this investigation was to assess the impact of cigarette smoking on sleep architecture. Polysomnography was used to characterize sleep architecture among 6,400 participants of the Sleep Heart Health Study (United States, 1994-1999). Sleep parameters included total sleep time, latency to sleep onset, sleep efficiency, and percentage of time in each sleep stage. The study sample consisted of 2,916 never smokers, 2,705 former smokers, and 779 current smokers. Compared with never smokers, current smokers had a longer initial sleep latency (5.4 minutes, 95% confidence interval (CI): 2.9, 7.9) and less total sleep time (14.0 minutes, 95% CI: 6.4, 21.7). Furthermore, relative to never smokers, current smokers also had more stage 1 sleep (relative proportion = 1.24, 95% CI: 1.14, 1.33) and less slow wave sleep (relative proportion = 0.86, 95% CI: 0.78, 0.95). Finally, no differences in sleep architecture were noted between former and never smokers. The results of this study show that cigarette smoking is independently associated with disturbances in sleep architecture, including a longer latency to sleep onset and a shift toward lighter stages of sleep. Nicotine in cigarette smoke and acute withdrawal from it may contribute to disturbances in sleep architecture.
Keywords: Aged; Arousal; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Polysomnography; Prevalence; Regression Analysis; Risk Factors; Sleep Stages; Sleep Wake Disorders; Smoking; United States

Clinical course of mesenteric artery stenosis in elderly americans. - Wilson, David B; Mostafavi, Kian; Craven, Timothy E; Ayerdi, Juan; Edwards, Matthew S; Hansen, Kimberley J (Arch Intern Med, 2006)
BACKGROUND: To examine prospectively the relationship between stenosis or occlusion of the celiac and superior mesenteric arteries and symptoms of chronic intestinal ischemia in free-living elderly patients in the United States. METHODS: As part of an ancillary study to the Cardiovascular Health Study, participants in the Forsyth County (North Carolina) cohort underwent visceral duplex ultrasonography of the celiac and superior mesenteric arteries. Critical mesenteric artery stenosis (MAS) or occlusion was defined by Doppler flow ultrasound-derived criteria. Clinical outcomes were assessed at annual follow-up examinations and review of death certificates. Multivariate associations between the presence of MAS and all-cause mortality and adverse cardiovascular events were analyzed. Participants with MAS were contacted to determine the presence of symptoms consistent with chronic intestinal ischemia. RESULTS: Of 553 participants who underwent visceral duplex ultrasonography, 97 (17.5%) had disease of the celiac or superior mesenteric artery. At a mean follow-up of 6(1/2) years, 20 participants with MAS (20.6%) and 93 without MAS (20.4%) had died (relative risk, 1.01; 95% confidence interval, 0.66-1.55). No deaths were attributed to intestinal infarction. No association existed between the presence of MAS and prevalent cardiovascular disease, all-cause mortality, or adverse cardiovascular events. A questionnaire was completed by 71% of the surviving participants with MAS. No participant reported symptoms or weight loss consistent with chronic intestinal ischemia. CONCLUSIONS: Mesenteric artery stenosis was a common finding in free-living elderly patients. At long-term follow-up, the presence of asymptomatic MAS was not associated with death or adverse cardiovascular events. Participants with asymptomatic MAS by duplex ultrasonographic criteria did not experience intestinal infarction or develop chronic intestinal ischemia.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Comorbidity; Female; Humans; Male; Mesenteric Arteries; Mesenteric Vascular Occlusion; Proportional Hazards Models; Prospective Studies; Radiography; Risk Factors; Surveys and Questionnaires; Ultrasonography

Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS). - Barasch, Eddy; Gottdiener, John S; Larsen, Emily K Marino; Chaves, Paulo H M; Newman, Anne B; Manolio, Teri A (Am Heart J, 2006)
BACKGROUND: Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population. METHODS: We used 2-dimensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons. RESULTS: Mitral annular calcification was found in 1640 (42 %) subjects, AAC in 1710 (44 %), AVS in 2114 (54 %), and all 3 combined in 662 (17 %). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC. CONCLUSIONS: In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile.
Keywords: Aged; Aortic Valve; Calcinosis; Female; Heart Valve Diseases; Humans; Male; Mitral Valve; Prevalence; Prospective Studies; Risk Factors; Sclerosis; Ultrasonography

Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study). - Rautaharju, Pentti M; Ge, Sijian; Nelson, Jennifer C; Marino Larsen, Emily K; Psaty, Bruce M; Furberg, Curt D; Zhang, Zhu-Ming; Robbins, John; Gottdiener, John S; Chaves, Paulo H M (Am J Cardiol, 2006)
Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18% to 50%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64%), the ECG estimate of left ventricular mass (by 48%), and previous myocardial infarction (by 34%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.
Keywords: Aged; Coronary Disease; Electrocardiography; Female; Humans; Male; Risk

Congestive heart failure incidence and prognosis: case identification using central adjudication versus hospital discharge diagnoses. - Schellenbaum, Gina D; Heckbert, Susan R; Smith, Nicholas L; Rea, Thomas D; Lumley, Thomas; Kitzman, Dalane W; Roger, Veronique L; Taylor, Herman A; Psaty, Bruce M (Ann Epidemiol, 2006)
PURPOSE: We compared hospitalized congestive heart failure (CHF) incidence and prognosis estimates using hospital discharge diagnoses or central adjudication. METHODS: We used the Cardiovascular Health Study (CHS), a population-based cohort study of 5888 elderly adults. A physician committee adjudicated potential CHF events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A CHF discharge diagnosis included any of these ICD-9 codes in any position: 428, 425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by discharge diagnosis, adjudication, or both. RESULTS: Incidence rates for hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and 17.1 per 1000 person-years using central adjudication. Compared to the group identified as having CHF by both methods, the group with only a discharge diagnosis (hazard ratio=0.77, 95% confidence interval=0.65-0.91) and the group with central adjudication only (hazard ratio=0.72, 95% confidence interval=0.55-0.94) had lower mortality rates. CONCLUSIONS: In the elderly, studies using only discharge diagnoses, as compared to central adjudication, may estimate higher rates of incident hospitalized CHF. Mortality following CHF onset may be similar for these methods and higher if both methods are used together.
Keywords: Aged; Aged, 80 and over; Cohort Studies; Female; Heart Failure; Humans; Incidence; Male; Patient Discharge; Prognosis

A cross-sectional study of vitamin C and cognitive function in older adults: the differential effects of gender. - Sato, R; Helzlsouer, K J; Comstock, G W; Hoffman, S C; Norkus, E P; Fried, L P (J Nutr Health Aging, 2006)
Previous studies have suggested that vitamin C status may be associated with cognitive function in community-dwelling populations. However, this has not been consistent across all studies due to methodological differences. This cross-sectional study assessed the association between vitamin C and cognitive function in 544 community-dwelling older adults aged 65 or older who participated in both the Cardiovascular Health Study (CHS) and the CLUE II study in 1989. Three percent of the subjects had low plasma vitamin C concentrations (< 40 mg/dL) and 15% had low total vitamin C intake (< 60 mg/day). Most participants (96.7 percent) had normal cognitive function. In the unadjusted analyses, the highest fifth of plasma vitamin C concentration was associated with better Digit Symbol Substitution Test (DSST) scores and marginally associated with Mini-Mental State Examination (MMSE) compared to the lowest fifth. Total vitamin C intake, measured by Block's food frequency questionnaire, was generally associated with higher MMSE scores, though it was not significant. Adjusting for numerous factors did not substantially change results. In a stratified analysis by gender, higher plasma concentrations or intake were associated with higher MMSE scores for men but not for women. These mixed results do not provide strong evidence of an association between vitamin C concentrations or intake and cognitive function.
Keywords: Aged; Aging; Ascorbic Acid; Cognition; Cross-Sectional Studies; Diet; Female; Health Surveys; Humans; Male; Mental Status Schedule; Nutrition Surveys; Nutritional Requirements; Sex Factors; Surveys and Questionnaires

Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. - Barnes, Deborah E; Alexopoulos, George S; Lopez, Oscar L; Williamson, Jeff D; Yaffe, Kristine (Arch Gen Psychiatry, 2006)
CONTEXT: Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons. OBJECTIVES: To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease. DESIGN: Prospective, population-based, longitudinal study. SETTING: Random sample of adults 65 years or older recruited from 4 US communities. PARTICIPANTS: Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria. MAIN OUTCOME MEASURE: Diagnosis of MCI. RESULTS: Depressive symptoms at baseline were associated with increased risk of MCI (10.0%, 13.3%, and 19.7% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics. CONCLUSION: Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.
Keywords: Aged; Cerebrovascular Disorders; Cognition Disorders; Comorbidity; Dementia; Dementia, Vascular; Depressive Disorder; Female; Follow-Up Studies; Geriatric Assessment; Humans; Longitudinal Studies; Male; Prospective Studies; Psychiatric Status Rating Scales; Risk Factors; Sampling Studies; Vascular Diseases

Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans. - Mozaffarian, Dariush; Prineas, Ronald J; Stein, Phyllis K; Siscovick, David S (J Am Coll Cardiol, 2006)
OBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk. BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects. METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories. RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88). CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.
Keywords: Aged; Animals; Atrioventricular Node; Cross-Sectional Studies; Diet; Electrocardiography; Fatty Acids, Omega-3; Female; Fishes; Heart; Heart Rate; Humans; Male; Ventricular Function

Education, cognitive test scores, and black-white differences in dementia risk. - Shadlen, Marie-Florence; Siscovick, David; Fitzpatrick, Annette L; Dulberg, Corinne; Kuller, Lewis H; Jackson, Sharon (J Am Geriatr Soc, 2006)
OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups. DESIGN: Longitudinal, 6-year follow-up. PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study. MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes. RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5-2.4 and 95% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE. CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.
Keywords: African Continental Ancestry Group; Aged; Cognition; Dementia; Educational Status; European Continental Ancestry Group; Female; Follow-Up Studies; Humans; Incidence; Male; Psychological Tests; Retrospective Studies; Risk Factors; United States

Factors associated with geographic variations in stroke incidence among older populations in four US communities. - El-Saed, Aiman; Kuller, Lewis H; Newman, Anne B; Lopez, Oscar; Costantino, Joseph; McTigue, Kathleen; Cushman, Mary; Kronmal, Richard (Stroke, 2006)
BACKGROUND AND PURPOSE: In the Cardiovascular Health Study (CHS), we previously observed lower stroke incidence in Allegheny County, PA compared with the other 3 study sites. The purpose of this study was to study possible reasons for the lower stroke incidence in Allegheny County. METHODS: CHS participants 65 years or older who were stroke-free at baseline (n=5639) were followed between 1989 to 1990 and 2000 for the development of stroke. Risk factors at baseline and their subsequent control were compared among both groups. Site-specific hazard ratios for stroke incidence were calculated using Cox regression models. RESULTS: The unadjusted hazard ratio for total stroke incidence in Forsyth County, NC; Sacramento County, CA; and Washington County, MD combined compared with Allegheny County, PA was 1.74 (95% CI: 1.42, 2.14). After adjustment for age and other traditional risk factors, there was modest reduction of the excess hazard in non-Allegheny sites compared with Allegheny County (hazard ratio=1.52, 95% CI: 1.17, 1.98). Between baseline and the seventh-year visits, control of hypertension, diabetes, lipids, smoking, atrial fibrillation and transient ischemic attack were similar across sites. White matter grade > or = 3 on the baseline brain MRI was less common in Allegheny County (25.8% versus 36.3%, respectively; P<0.001) and accounted for 25% of the excess hazard in non-Allegheny sites compared with Allegheny County. CONCLUSIONS: Site differences in stroke risk factors at baseline and subsequent control only partially explain site differences in stroke incidence. White matter grade as a possible integrated measure of exposure and control of risk factors may help in explaining geographic variations in stroke incidence.
Keywords: Aged; Brain; California; Female; Humans; Incidence; Magnetic Resonance Imaging; Male; Maryland; North Carolina; Pennsylvania; Proportional Hazards Models; Risk Assessment; Risk Factors; Stroke

Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States). - Sieh, Weiva; Edwards, Karen L; Fitzpatrick, Annette L; Srinouanprachanh, Sengkeo L; Farin, Fred M; Monks, Stephanie A; Kronmal, Richard A; Eaton, David L (Cancer Causes Control, 2006)
OBJECTIVE: To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk. METHODS: We conducted a case-control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989-2000. We genotyped 193 cases and 391 controls for the PSA -252 G/A and -158 G/A SNPs and the AR CAG microsatellite, and developed methods to directly determine proximal PSA promoter haplotypes. Exact logistic regression was used to estimate odds ratios and significance levels. RESULTS: No significant associations were observed between PSA diplotype and prostate cancer overall. Short (< 20) AR CAG repeat lengths were associated with modest increases in the risk of prostate cancer (OR, 1.46; 95% CI, 0.97-2.19; p = 0.071) that were significant for advanced disease (OR, 1.82; 95% CI, 1.02-3.26; p = 0.044). Men who possessed two copies of the PSA*2 (-252G/-158G) haplotype and short AR CAG repeat lengths had a 4-fold (95% CI, 1.05-20.75; exact p = 0.040) increased risk of prostate cancer, and a 7-fold (95% CI, 1.25-39.78; exact p = 0.026) increased risk of advanced disease. CONCLUSIONS: We found evidence that the PSA*2*2 diplotype in combination with short AR CAG alleles increases a man's risk of developing prostate cancer. These findings support an etiologic role in prostate cancer of genetic interactions between polymorphisms that increase AR transactivation strength and those that alter the regulatory regions of target genes such as PSA that are responsive to androgen stimulation.
Keywords: Aged; Biomarkers, Tumor; Case-Control Studies; Cohort Studies; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Polymorphism, Genetic; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; United States

Geographic variations in stroke incidence and mortality among older populations in four US communities. - El-Saed, Aiman; Kuller, Lewis H; Newman, Anne B; Lopez, Oscar; Costantino, Joseph; McTigue, Kathleen; Cushman, Mary; Kronmal, Richard (Stroke, 2006)
BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability in the US. There is limited data on geographic variations in stroke incidence among older US populations who experience the majority of stroke burden. The purpose of this study was to compare stroke incidence and mortality rates in 4 US communities. METHODS: Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n=5639) were followed for 10 or 7 years in predominantly white (n=5002) and black (n=637) participants, respectively. Incident stroke was validated by a stroke adjudication committee after ascertainment at annual visits, interim telephone contacts, and review of Medicare hospitalization data. RESULTS: The 2000 US population age and sex standardized total stroke incidence rate for all CHS participants was 17.7 per 1000 person-years (95% CI: 15.9, 19.5). The rate was significantly lower in Allegheny County, Pennsylvania 9.6/1000 person-years (95% CI: 7.7, 11.5) than Forsyth County, North Carolina 19.2/1000 person-years (95% CI: 15.6, 22.8), Sacramento County, California 20.7/1000 person-years (95% CI: 16.9, 24.5), and Washington County, Maryland 19.8/1000 person-years (95% CI: 16.1, 23.5). The lower stroke incidence rate in Allegheny County was consistent in gender, race, and age groups. Though not statistically significant, stroke mortality was also lower in Allegheny County than other 3 sites. The 1-month case fatality rate was similar in the 4 sites for all strokes, and by stroke types. CONCLUSIONS: Understanding geographic variations in stroke incidence may be an important step in improving preventive practices of stroke.
Keywords: Aged; Aged, 80 and over; California; Female; Humans; Incidence; Male; Maryland; North Carolina; Pennsylvania; Stroke

Heart failure at the end of life: symptoms, function, and medical care in the Cardiovascular Health Study. - Sullivan, Mark D; O'Meara, Ellen S (Am J Geriatr Cardiol, 2006)
Among Cardiovascular Health Study participants who died from coronary heart disease, the authors compared those with incident and definite congestive heart failure (CHF) (n=60; 15%) and those with prevalent or probable CHF (n=70; 17.5%) to those with no history of CHF (n=198; 50%) concerning health status at the end of life. Both CHF groups had worse health status before death than the group without CHF. Patients in the CHF groups were more likely to use benzodiazepines (20% and 19% vs. 6%; p=0.001) and to rate their health as fair or poor (68% and 63% vs. 41%; p<0.001). They were more likely to be hospitalized (33% and 28% vs. 11%; p<0.001), to have activity restrictions (79% and 62% vs. 38%; p<0.001), and to report a wide array of physical symptoms. These data suggest that patients who die from coronary heart disease in the presence of CHF have greater need for hospice or palliative care than those with no history of CHF.
Keywords: Activities of Daily Living; Aged; Comorbidity; Coronary Disease; Female; Health Status; Heart Failure; Hospice Care; Humans; Male; Palliative Care

Kidney function predicts the rate of bone loss in older individuals: the Cardiovascular Health Study. - Fried, Linda F; Shlipak, Michael G; Stehman-Breen, Catherine; Mittalhenkle, Anuja; Seliger, Stephen; Sarnak, Mark; Robbins, John; Siscovick, David; Harris, Tamara B; Newman, Anne B; Cauley, Jane A (J Gerontol A Biol Sci Med Sci, 2006)
BACKGROUND: Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old. METHODS: Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women. RESULTS: In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women. CONCLUSION: Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.
Keywords: Absorptiometry, Photon; Aged; Bone Density; Creatinine; Cystatin C; Cystatins; Female; Hip; Humans; Kidney Diseases; Kidney Function Tests; Linear Models; Longitudinal Studies; Male; Osteoporosis; Predictive Value of Tests

Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons > or =65 years of age (the cardiovascular health study). - Gottdiener, John S; Kitzman, Dalane W; Aurigemma, Gerard P; Arnold, Alice M; Manolio, Teri A (Am J Cardiol, 2006)
The left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects > or =65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction.
Keywords: Aged; Atrial Function, Left; Case-Control Studies; Diastole; Echocardiography; Female; Heart Atria; Heart Failure; Humans; Male; Multivariate Analysis; Systole

Lipoprotein subclass and particle size differences in Afro-Caribbeans, African Americans, and white Americans: associations with hepatic lipase gene variation. - Miljkovic-Gacic, Iva; Bunker, Clareann H; Ferrell, Robert E; Kammerer, Candace M; Evans, Rhobert W; Patrick, Alan L; Kuller, Lewis H (Metabolism, 2006)
Despite a higher prevalence of coronary heart disease risk factors, men of African origin have less coronary atherosclerosis, as measured by coronary calcification, than whites. In part, this is thought to be because of the less atherogenic lipoprotein profile observed in men of African origin, characterized by lower triglycerides and higher high-density lipoprotein (HDL) cholesterol. We hypothesized that the -514C>T polymorphism in the hepatic lipase gene (LIPC) plays a significant role in determining a less atherogenic lipoprotein profile observed in men of African origin. Previously conducted studies of the LIPC -514C>T polymorphism in African Americans may have been confounded by a higher level of European admixture; in addition, the results from these studies do not necessarily apply to other African populations because gene-environment interactions may differ. Thus, we compared nuclear magnetic resonance spectroscopy-measured lipoprotein subclass patterns and LIPC -514C>T genotypes in population-based samples of older white American (n = 532) and African American (n = 97) men from the Cardiovascular Health Study to those among older, less admixed, Afro-Caribbean men (n = 205) from the Tobago Health Study. Men of African origin had a more favorable lipoprotein profile than whites. In addition, levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride, and large and small very low-density lipoprotein, small low-density lipoprotein, as well as very low-density lipoprotein particle size, were remarkably lower in Afro-Caribbean men than in either African American or white men. The frequency of the LIPC -514T allele was much higher in Afro-Caribbeans (0.57) and in African Americans (0.49) than in whites (0.20). The -514T allele in both populations of African origin, but not in whites, was associated with elevated large HDL and greater HDL size. Our findings indicate that the higher frequency of the LIPC -514T allele found in men of African origin living in different environments significantly contributes to the more favorable distribution of HDL subclasses compared with whites.
Keywords: Adult; African Americans; Age Factors; Aged; Alleles; Body Mass Index; Cardiovascular Diseases; Caribbean Region; Cohort Studies; DNA; European Continental Ancestry Group; Gene Frequency; Genetic Variation; Humans; Lipase; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Liver; Longitudinal Studies; Male; Middle Aged; Particle Size; Trinidad and Tobago; United States

Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study. - McNeill, Ann Marie; Katz, Ronit; Girman, Cynthia J; Rosamond, Wayne D; Wagenknecht, Lynne E; Barzilay, Joshua I; Tracy, Russell P; Savage, Peter J; Jackson, Sharon A (J Am Geriatr Soc, 2006)
OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD. DESIGN: Prospective cohort study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62% female, 14% black). MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L). RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95% confidence interval (CI) = 1.07-1.57), 0.94 (95% CI = 0.73-1.21), and 1.40 (95% CI = 1.12-1.76) for women and 1.35 (95% CI = 1.10-1.66), 1.51 (95% CI = 1.08-2.12), and 1.47 (95% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20% to 30% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16% to 46%) and an additional 9% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD. CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.
Keywords: African Americans; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Cardiovascular Diseases; Cohort Studies; European Continental Ancestry Group; Fasting; Female; Humans; Incidence; Male; Metabolic Syndrome; Risk Factors; Sex Factors

Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the Cardiovascular Health Study. - O'Hare, Ann M; Katz, Ronit; Shlipak, Michael G; Cushman, Mary; Newman, Anne B (Circulation, 2006)
BACKGROUND: A low ankle-arm index (AAI) is a strong predictor of mortality and cardiovascular events. A high AAI also appears to be associated with higher mortality risk in select populations. However, mortality and cardiovascular risk across the AAI spectrum have not been described in a more broadly defined population. METHODS AND RESULTS: We examined total and cardiovascular mortality and cardiovascular events across the AAI spectrum among 5748 participants in the Cardiovascular Health Study (CHS). The mean age of the sample population was 73+/-6 years, and the sample included 3289 women (57%) and 883 blacks (15%). The median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6 (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of which were cardiovascular) and 1491 cardiovascular events during follow-up. After adjustment for potential confounders, AAI measurements < or =0.60 (hazard ratio [HR] 1.82, 95% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95% CI 1.61 to 2.69), 0.71 to 0.8 (HR 1.80, 95% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95% CI 1.43 to 2.11), 0.91 to 1.0 (HR 1.40, 95% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95% CI 1.07 to 2.31) were associated with higher mortality risk from all causes compared with the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular mortality. For cardiovascular events, risk was higher at all AAI levels <1 but not for AAI levels >1.4 (HR 1.00, 95% CI 0.57 to 1.74). The association of a high AAI with mortality was stronger in men than in women and in younger than in older cohort members. CONCLUSIONS: In a cohort of community-dwelling elders, mortality risk was higher than the referent category of 1.11 to 1.2 among participants with AAI values above the traditional cutpoint of 0.9 (ie, 0.91 to 1.0 and >1.4), and the specific association of AAI with mortality varied by age and gender.
Keywords: Aged; Ankle; Arm; Blood Pressure; Body Mass Index; Cholesterol, LDL; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Peripheral Vascular Diseases; Risk Factors; Smoking

Mortality in pharmacologically treated older adults with diabetes: the Cardiovascular Health Study, 1989-2001. - Kronmal, Richard A; Barzilay, Joshua I; Smith, Nicholas L; Psaty, Bruce M; Kuller, Lewis H; Burke, Gregory L; Furberg, Curt (PLoS Med, 2006)
BACKGROUND: Diabetes mellitus (DM) confers an increased risk of mortality in young and middle-aged individuals and in women. It is uncertain, however, whether excess DM mortality continues beyond age 75 years, is related to type of hypoglycemic therapy, and whether women continue to be disproportionately affected by DM into older age. METHODS AND FINDINGS: From the Cardiovascular Health Study, a prospective study of 5,888 adults, we examined 5,372 participants aged 65 y or above without DM (91.2%), 322 with DM treated with oral hypoglycemic agents (OHGAs) (5.5%), and 194 with DM treated with insulin (3.3%). Participants were followed (1989-2001) for total, cardiovascular disease (CVD), coronary heart disease (CHD), and non-CVD/noncancer mortality. Compared with non-DM participants, those treated with OHGAs or insulin had adjusted hazard ratios (HRs) for total mortality of 1.33 (95% confidence interval [CI], 1.10 to 1.62) and 2.04 (95% CI, 1.62 to 2.57); CVD mortality, 1.99 (95% CI, 1.54 to 2.57) and 2.16 (95% CI, 1.54 to 3.03); CHD mortality, 2.47 (95% CI, 1.89 to 3.24) and 2.75 (95% CI, 1.95 to 3.87); and infectious and renal mortality, 1.35 (95% CI, 0.70 to 2.59) and 6.55 (95% CI, 4.18 to 10.26), respectively. The interaction of age (65-74 y versus > or =75 y) with DM was not significant. Women treated with OHGAs had a similar HR for total mortality to men, but a higher HR when treated with insulin. CONCLUSIONS: DM mortality risk remains high among older adults in the current era of medical care. Mortality risk and type of mortality differ between OHGA and insulin treatment. Women treated with insulin therapy have an especially high mortality risk. Given the high absolute CVD mortality in older people, those with DM warrant aggressive CVD risk factor reduction.
Keywords: Administration, Oral; Aged; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Male; Proportional Hazards Models; Prospective Studies; Risk Assessment; Sex Distribution

Neuropsychological characteristics of mild cognitive impairment subgroups. - Lopez, O L; Becker, J T; Jagust, W J; Fitzpatrick, A; Carlson, M C; DeKosky, S T; Breitner, J; Lyketsos, C G; Jones, B; Kawas, C; Kuller, L H (J Neurol Neurosurg Psychiatry, 2006)
OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study. METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition. RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits. CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.
Keywords: Aged; Aged, 80 and over; Alzheimer Disease; Amnesia; Cognition Disorders; Female; Humans; Male; Neuropsychological Tests; Psychometrics; Reference Values

Obstructive sleep apnea and plasma natriuretic peptide levels in a community-based sample. - Patwardhan, Anjali A; Larson, Martin G; Levy, Daniel; Benjamin, Emelia J; Leip, Eric P; Keyes, Michelle J; Wang, Thomas J; Gottlieb, Daniel J; Vasan, Ramachandran S (Sleep, 2006)
STUDY OBJECTIVES: We hypothesized that alterations in cardiac hemodynamics associated with obstructive sleep apnea-hypopnea (OSAH) would be reflected in higher natriuretic peptide levels. We examined the association of OSAH with natriuretic peptides in a community-based sample. DESIGN: Cross-sectional, retrospective, observational study. SETTING: Framingham Heart Study Offspring Cohort and Sleep Heart Health Study. PARTICIPANTS: Community-based sample of 623 individuals. MEASUREMENTS: Full-montage home polysomnography was used to determine apnea-hypopnea index (AHI) and percentage of time with an oxyhemoglobin saturation < 90% (PctLt90). Sensitive immunoradiometric assays were used to measure plasma B-type (BNP) and N-terminal pro-atrial natriuretic peptide (NT-ANP). Multivariable regression was used to examine the relations between natriuretic peptides and indicators of OSAH, adjusting for age, sex, body mass index, and clinical covariates. RESULTS: No statistically significant relations between OSAH indices and BNP were observed in the multivariable model. Compared with an AHI < 5, relative levels of 1.20, 0.88, and 0.91 were observed forAHI categories 5-15, 15-30, >30 events per hour, respectively. For NT-ANP, no significant relations were seen with AHI in the multivariable model (relative levels of 0.98, 0.91, and 0.90). An inverse association was observed between NT-ANP and PctLt90 in age- and sex-adjusted models (relative levels of 0.93, 0.87, and 0.80), although this association became statistically nonsignificant after adjusting for body mass index. CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels.
Keywords: Atrial Fibrillation; Body Mass Index; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptides; Obesity; Polysomnography; Prevalence; Residence Characteristics; Severity of Illness Index; Sleep Apnea, Obstructive

Obstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep Heart Health Study. - Quan, Stuart F; Wright, Ron; Baldwin, Carol M; Kaemingk, Kristine L; Goodwin, James L; Kuo, Tracy F; Kaszniak, Alfred; Boland, Lori L; Caccappolo, Elise; Bootzin, Richard R (Sleep Med, 2006)
BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients with OSAH frequently are found to have deficits in neuropsychological function. However, the nature and severity of these abnormalities in non-clinical populations is less well defined. PATIENTS AND METHODS: One hundred and forty-one participants from the Tucson, AZ and New York, NY field centers of the Sleep Heart Health Study completed a battery of neuropsychological tests for 9-40 months (mean=24 months, SD=7 months) after an unattended home polysomnogram. Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests, composite variables representing attention, executive function, MotorSpeed and processing speed were constructed from the neuropsychological test battery. RESULTS: There were no significant differences in any individual neuropsychological test or composite variable between the OSAH and CTL groups. However, when time spent with O(2) saturations less than 85% was dichotomized into those participants in the top quartile of the distribution and those in the lower three quartiles, motor speed was significantly impaired in those who were more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242, P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001) were associated with more severe oxygen desaturation even after controlling for degree of daytime sleepiness, age, gender and educational level. CONCLUSIONS: Mild to moderate OSAH has little impact on the selected measures of attention, executive function, motor speed and processing speed. However, hypoxemia adversely affects both motor and processing speed. These results suggest that in middle-aged to elderly adults the neuropsychological effects of clinically unrecognized mild to moderate OSAH are neither global nor large.
Keywords: Brain; Cognition Disorders; Continuous Positive Airway Pressure; Demography; Disorders of Excessive Somnolence; Electromyography; Electrooculography; Female; Health Status; Humans; Hypoxia; Male; Middle Aged; Neuropsychological Tests; Oxygen; Polysomnography; Severity of Illness Index; Sleep Apnea, Obstructive; Surveys and Questionnaires

Plasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: the cardiovascular health study. - Lemaitre, Rozenn N; King, Irena B; Mozaffarian, Dariush; Sotoodehnia, Nona; Rea, Thomas D; Kuller, Lewis H; Tracy, Russel P; Siscovick, David S (Circulation, 2006)
BACKGROUND: Intake of trans fatty acids is associated with increased risk of coronary heart disease. Whether different classes of trans fatty acids show similar associations is unclear. We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids. To extend these findings, we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease (IHD) and sudden cardiac death. METHODS AND RESULTS: We conducted a case-control study nested in the Cardiovascular Health Study. We identified 214 cases of fatal IHD (fatal myocardial infarction and coronary heart disease death) between 1992 and 1998. We randomly selected 214 controls, matched to cases on demographics, prevalent cardiovascular disease, and timing of blood draw. Plasma phospholipid fatty acids were assessed in blood samples collected earlier. Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD (odds ratio [OR] for interquintile range 1.68, 95% confidence interval [CI] 1.21 to 2.33) after adjustment for risk factors and trans-18:1 levels. Trans-18:1 levels above the 20th percentile were associated with lower risk (OR 0.34, 95% CI 0.18 to 0.63). In analyses limited to cases of sudden cardiac death (n=95), higher levels of trans-18:2 fatty acids were associated with higher risk (OR 2.34, 95% CI 1.27 to 4.31) and higher trans-18:1 with lower risk (OR 0.18, 95% CI 0.06 to 0.54). CONCLUSIONS: Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death. If confirmed, these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content.
Keywords: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Coronary Disease; Death, Sudden, Cardiac; Female; Humans; Male; Myocardial Ischemia; Phospholipids; Trans Fatty Acids; United States

The prevalence of the 65-kilodalton isoform of glutamic acid decarboxylase autoantibodies by glucose tolerance status in elderly patients from the cardiovascular health study. - Barinas-Mitchell, Emma; Kuller, Lewis H; Pietropaolo, Susan; Zhang, Ying-Jian; Henderson, Tyona; Pietropaolo, Massimo (J Clin Endocrinol Metab, 2006)
CONTEXT: Autoantibodies (AA) to glutamic acid decarboxylase (GAD65), a determinant of risk for autoimmune diabetes, have been found in up to 10% of patients with type 2 diabetes. In older adults, this marker may also serve as a determinant of risk for autoimmune diabetes and enhance diabetes classification. OBJECTIVE: The objective of this study was to evaluate the relationship between GAD65AA and glucose tolerance status, current diabetes treatment, and clinical measures in older adults. DESIGN: GAD65AA were measured at baseline in 3318 participants from the Cardiovascular Health Study, a cohort study of 5888 individuals 65 or older. SETTING: The population-based cohort was recruited from four U.S. sites. PATIENTS: Patients included all Cardiovascular Health Study participants with known diabetes, newly diagnosed diabetes, impaired fasting glucose, impaired glucose tolerance, and a sample of normal glucose-tolerant participants. MAIN OUTCOME MEASURES: GAD65AA, body mass index, fasting glucose and insulin levels, blood pressure, lipid levels, and diabetes treatment at baseline were measured. RESULTS: The prevalence of GAD65AA increased with decreasing glucose tolerance in both Blacks (n = 560) and Whites (n = 2730), being more pronounced in known diabetic individuals. GAD65AA were found in 2.3, 5.8, 7.8, and 8.3% of diabetic participants, reporting use of no diabetes medication, oral hypoglycemic agents, insulin only, and both oral hypoglycemic agents and insulin, respectively (P = 0.02, linear trend). Among diabetic participants, GAD65AA positivity was associated with diabetes treatment, higher fasting glucose, and lower body mass index. CONCLUSIONS: Even among older individuals with diabetes, GAD65AA may be a useful marker in identifying a subgroup of autoimmune diabetes, serve as a marker of insulin requirement, and remain stable over years.
Keywords: Aged; Aging; Autoantibodies; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glucose Intolerance; Glutamate Decarboxylase; Humans; Insulin; Isoenzymes; Lipids; Logistic Models; Male; Nutrition Surveys

Progression of atherosclerotic renovascular disease: A prospective population-based study. - Pearce, Jeffrey D; Craven, Brandon L; Craven, Timothy E; Piercy, K Todd; Stafford, Jeanette M; Edwards, Matthew S; Hansen, Kimberley J (J Vasc Surg, 2006)
OBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS). METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion. RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95% CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD. CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0% of kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and no prevalent RVD progressed to occlusion.
Keywords: Aged; Aged, 80 and over; Atherosclerosis; Blood Flow Velocity; Blood Pressure; Disease Progression; Female; Follow-Up Studies; Humans; Incidence; Male; North Carolina; Population Surveillance; Prognosis; Prospective Studies; Renal Artery Obstruction; Severity of Illness Index; Time Factors; Ultrasonography, Doppler, Duplex

Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults. - Rosano, Caterina; Brach, Jennifer; Longstreth, William T; Newman, Anne B (Neuroepidemiology, 2006)
Abnormal gait in high-functioning older adults may indicate underlying subtle structural brain abnormalities. We tested the hypothesis that temporal and spatial parameters of gait, including speed, stride length and double support time, are cross-sectionally associated with white matter hyperintensity, subcortical infarcts or brain atrophy on brain MRI. We examined 321 men and women (mean age = 78.3) participating to the Cardiovascular Health Study who were free of dementia or stroke at the time of the gait assessment. Analyses were set with gait as independent variable and brain MRIs as dependent variables. Gait measures were determined from the footfalls recorded on a 4-meter-long instrumented walking surface, the GaitMat II. Brain MRIs were examined for the presence of white matter hyperintensity (WMG, graded from 0 to 9), brain infarcts (predominantly subcortical) and ventricular enlargement (graded from 0 to 9). Slower gait, shorter stride length and longer double support times were associated with greater prevalence of white matter grade > or =3 (p = 0.02), and at least 1 brain infarct (p = 0.04) independent of age. In multivariate logistic regression models adjusted for demographics and clinical cardiovascular diseases, those with gait speed <1.02 m/s were more likely to have WMG > or =3 and at least 1 brain infarct, compared with those with faster gait - odds ratio (OR): 2.85, 95% confidence interval (95% CI): 1.35, 6.02, and OR: 2.09, 95% CI: 1.04, 4.19. Shorter stride length was also associated with greater probability of having at least 1 brain infarct (gait stride <0.88 vs. >1.10 m: OR: 3.20, 95% CI: 1.49, 6.88), while longer double support times were associated with a greater probability of having WMG > or =3 (double support time >0.19 vs. <0.14 s: OR: 2.3, 95% CI: 1.1, 4.7) independent of demographics and clinical cardiovascular diseases. Gait parameters were not significantly associated with ventricular grade. In summary, in this group of high-functioning older adults, poorer gait speed, shorter stride and longer double support time are associated with high white matter disease and subclinical strokes.
Keywords: Aged; Brain; Cerebral Infarction; Cerebral Ventricles; Cerebrovascular Disorders; Cohort Studies; Dementia; Female; Gait; Gait Disorders, Neurologic; Humans; Hypertension; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Stroke; United States

Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study. - Wong, Tien Yin; Kamineni, Aruna; Klein, Ronald; Sharrett, A Richey; Klein, Barbara E; Siscovick, David S; Cushman, Mary; Duncan, Bruce B (Arch Intern Med, 2006)
BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.
Keywords: Aged; Aged, 80 and over; Algorithms; Cardiovascular Diseases; Cohort Studies; Female; Humans; Image Processing, Computer-Assisted; Incidence; Male; Photography; Prospective Studies; Retinal Diseases; Retinal Vein; Retinal Vessels; Risk Factors; Stroke; United States

Regression dilution methods for meta-analysis: assessing long-term variability in plasma fibrinogen among 27,247 adults in 15 prospective studies. - Wood, Angela M; White, Ian; Thompson, Simon G; Lewington, Sarah; Danesh, John (Int J Epidemiol, 2006)
BACKGROUND: Within-person variability in measured values of a risk factor can bias its association with disease. The extent of this regression dilution bias for plasma fibrinogen was investigated using repeat measurement data collected at varying time intervals on 27 247 adults in 15 prospective studies. METHODS: Regression dilution ratios (RDRs) were estimated from a linear regression of repeat measurements on baseline values in each study and for each time interval, and pooled allowing for within- and between-study heterogeneity. RDRs were estimated both without and with adjustment for confounders, and factors were investigated that might influence the RDRs. RESULTS: The unadjusted overall RDR was 0.51 (95% CI: 0.47, 0.55), which decreased to 0.46 (95% CI: 0.42, 0.49) after adjustment for age, sex and measured values of other established vascular risk factors. The RDR did not vary materially by assay method, age, sex or smoking status, but decreased at higher levels of baseline fibrinogen. CONCLUSION: It is appropriate to use an RDR of 0.5 to correct approximately for regression dilution bias in plasma fibrinogen values; however, this correction factor may produce somewhat conservative hazard ratios in adjusted analyses, at higher fibrinogen concentrations and in follow-up beyond a decade. More generally, the methods described in this report have widespread applicability to quantifying regression dilution bias in repeatability data from multiple prospective studies.
Keywords: Adult; Age Factors; Bias; Cardiovascular Diseases; Female; Fibrinogen; Humans; Male; Meta-Analysis as Topic; Prospective Studies; Regression Analysis; Risk Factors; Sex Factors; Smoking; Time Factors

The sensitivity and specificity of markers for event times. - Cai, Tianxi; Pepe, Margaret Sullivan; Zheng, Yingye; Lumley, Thomas; Jenny, Nancy Swords (Biostatistics, 2006)
The statistical literature on assessing the accuracy of risk factors or disease markers as diagnostic tests deals almost exclusively with settings where the test, Y, is measured concurrently with disease status D. In practice, however, disease status may vary over time and there is often a time lag between when the marker is measured and the occurrence of disease. One example concerns the Framingham risk score (FR-score) as a marker for the future risk of cardiovascular events, events that occur after the score is ascertained. To evaluate such a marker, one needs to take the time lag into account since the predictive accuracy may be higher when the marker is measured closer to the time of disease occurrence. We therefore consider inference for sensitivity and specificity functions that are defined as functions of time. Semiparametric regression models are proposed. Data from a cohort study are used to estimate model parameters. One issue that arises in practice is that event times may be censored. In this research, we extend in several respects the work by Leisenring et al. (1997) that dealt only with parametric models for binary tests and uncensored data. We propose semiparametric models that accommodate continuous tests and censoring. Asymptotic distribution theory for parameter estimates is developed and procedures for making statistical inference are evaluated with simulation studies. We illustrate our methods with data from the Cardiovascular Health Study, relating the FR-score measured at enrollment to subsequent risk of cardiovascular events.
Keywords: Aged; Aged, 80 and over; Biomarkers; Biometry; Cardiovascular Diseases; Female; Humans; Male; Models, Statistical; Risk Factors; ROC Curve; Sensitivity and Specificity; Time Factors

Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. - Unruh, Mark L; Sanders, Mark H; Redline, Susan; Piraino, Beth M; Umans, Jason G; Hammond, Terese C; Sharief, Imran; Punjabi, Naresh M; Newman, Anne B (J Am Soc Nephrol, 2006)
Sleep-disordered breathing (SDB) has been noted commonly in hemodialysis (HD) patients, but it is not known whether this is related directly to the treatment of kidney failure with HD or to the higher prevalence of obesity and older age. Forty-six HD patients were compared with 137 participants from the Sleep Heart Health Study (SHHS) who were matched for age, gender, body mass index (BMI), and race. Home unattended polysomnography was performed and scored using similar protocols. The study sample was 62.7 +/- 10.1 yr, was predominantly male (72%) and white (63%), and had an average BMI of 28 +/- 5.3 kg/m(2). The HD sample had a higher systolic BP (137 versus 121 mmHg; P < 0.01) and a higher prevalence of diabetes (33 versus 9%; P < 0.01) and cardiovascular disease (33 versus 13%; P < 0.01) compared with the SHHS sample. The HD group had significantly less sleep time (320 versus 379 min; P < 0.0001) but similar sleep efficiency. HD patients had a higher frequency of arousals per hour (25.1 versus 17.1; P < 0.0001) and apnea-hypopneas per hour (27.2 versus 15.2; P < 0.0001) and greater percentage of the total sleep time below an oxygen saturation of 90% (7.2 versus 1.8; P < 0.0001). HD patients were more likely to have severe SDB (>30 respiratory events per hour) compared with the SHHS sample (odds ratio 4.07; 95% confidence interval 1.83 to 9.07). There was a strong association of HD with severe SDB and nocturnal hypoxemia independent of age, BMI, and the higher prevalence of chronic disease. The potential mechanisms for the higher likelihood of SDB in the HD population must be identified to provide specific prevention and therapy.
Keywords: Blood Pressure; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Renal Dialysis; Severity of Illness Index; Sleep Apnea Syndromes

Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults. - Jenny, N S; Arnold, A M; Kuller, L H; Sharrett, A R; Fried, L P; Psaty, B M; Tracy, R P (J Thromb Haemost, 2006)
BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression. OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.
Keywords: Aged; Aged, 80 and over; Angina Pectoris; Biomarkers; Cardiovascular Diseases; Female; Humans; Incidence; Intercellular Adhesion Molecule-1; Male; Mortality; Myocardial Infarction; Regression Analysis; Risk Factors; Sex Factors; Solubility; Stroke

Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study. - van der Hagen, P B; Folsom, A R; Jenny, N S; Heckbert, S R; O'Meara, E S; Reich, L M; Rosendaal, F R; Cushman, M (J Thromb Haemost, 2006)
BACKGROUND: Recent reports have suggested an association of atherosclerosis with risk of venous thrombosis. OBJECTIVE: To confirm whether subclinical atherosclerosis is a risk factor for venous thrombosis (VT) among men and women age 65 and older. METHODS: Participants of the Cardiovascular Health Study (n = 4,108) without baseline clinical cardiovascular disease, anticoagulant use or previous VT were followed for a median of 11.7 years after non-invasive assessment of subclinical atherosclerosis using carotid ultrasound (intima-media thickness and presence of plaques), ankle-brachial blood pressure index and electrocardiogram. Each event was classified as idiopathic or secondary. We used Cox proportional hazards regression to estimate the relative risk of overall and idiopathic VT for individuals with and without baseline subclinical atherosclerosis. RESULTS: There were 133 first time VT events. No subclinical atherosclerosis measures were associated with increased risk of overall or idiopathic VT. The adjusted relative risks of overall and idiopathic VT for presence of any type of subclinical disease were 0.60 (95% confidence interval 0.39-0.91) and 0.32 (0.18-0.59), respectively. Most of this association was explained by an inverse association of high-risk carotid plaques (prevalent in 54% of those at risk) with VT. CONCLUSION: Non-invasively measured subclinical atherosclerosis was not associated with increased risk of overall or idiopathic VT in this observational study. Carotid plaques and arterial events during follow up were inversely associated, a finding that requires further study.
Keywords: Aged; Aged, 80 and over; Atherosclerosis; Carotid Artery Thrombosis; Cohort Studies; Female; Humans; Male; Proportional Hazards Models; Risk Factors; Ultrasonography; Venous Thrombosis

Thyroid status, cardiovascular risk, and mortality in older adults. - Cappola, Anne R; Fried, Linda P; Arnold, Alice M; Danese, Mark D; Kuller, Lewis H; Burke, Gregory L; Tracy, Russell P; Ladenson, Paul W (JAMA, 2006)
CONTEXT: Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system. OBJECTIVE: To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication. DESIGN, SETTING, AND PARTICIPANTS: A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study. MAIN OUTCOME MEASURES: Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism. RESULTS: Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease. CONCLUSION: Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.
Keywords: Aged; Atrial Fibrillation; Cardiovascular Diseases; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Proportional Hazards Models; Risk Factors; Thyroid Gland; Thyrotropin