@article {1467, title = {Prevalence and correlates of snoring and observed apneas in 5,201 older adults.}, journal = {Sleep}, volume = {19}, year = {1996}, month = {1996 Sep}, pages = {531-8}, abstract = {

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

}, keywords = {Activities of Daily Living, Age Factors, Aged, Cardiovascular Diseases, Comorbidity, Female, Humans, Incidence, Lung Diseases, Male, Narcolepsy, Prevalence, Random Allocation, Sex Factors, Sleep Apnea Syndromes, Snoring}, issn = {0161-8105}, author = {Enright, P L and Newman, A B and Wahl, P W and Manolio, T A and Haponik, E F and Boyle, P J} } @article {1459, title = {Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {16}, year = {1996}, month = {1996 Aug}, pages = {963-70}, abstract = {

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

}, keywords = {Aged, Anthropometry, Aortic Aneurysm, Abdominal, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Humans, Male, Middle Aged, Pilot Projects, Prevalence, Reproducibility of Results, Risk Factors, Smoking, Ultrasonography, United States}, issn = {1079-5642}, author = {Alcorn, H G and Wolfson, S K and Sutton-Tyrrell, K and Kuller, L H and O{\textquoteright}Leary, D} } @article {660, title = {Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.}, journal = {Stroke}, volume = {32}, year = {2001}, month = {2001 Sep}, pages = {1939-46}, abstract = {

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

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

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

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

}, keywords = {Aged, Aging, Alcohol Drinking, Atrophy, Brain, Brain Diseases, Cerebral Infarction, Comorbidity, Demography, Female, Health Surveys, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Odds Ratio, Prospective Studies, Sensitivity and Specificity, United States}, issn = {1524-4628}, doi = {10.1161/hs0901.095723}, author = {Mukamal, K J and Longstreth, W T and Mittleman, M A and Crum, R M and Siscovick, D S} } @article {667, title = {Coronary artery calcification in older adults to age 99: prevalence and risk factors.}, journal = {Circulation}, volume = {104}, year = {2001}, month = {2001 Nov 27}, pages = {2679-84}, abstract = {

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

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

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

}, keywords = {Age Distribution, Age Factors, Aged, Aged, 80 and over, Black People, Calcinosis, Calcium, Cohort Studies, Comorbidity, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Demography, Female, Humans, Logistic Models, Male, Predictive Value of Tests, Prevalence, Risk Factors, Sex Distribution, Sex Factors, Tomography, X-Ray Computed, White People}, issn = {1524-4539}, doi = {10.1161/hc4601.099464}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Feldman, A and Edmundowicz, D and Kuller, L H} } @article {638, title = {The role of comorbidity in the assessment of intermittent claudication in older adults.}, journal = {J Clin Epidemiol}, volume = {54}, year = {2001}, month = {2001 Mar}, pages = {294-300}, abstract = {

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

}, keywords = {Aged, Angina Pectoris, Arterial Occlusive Diseases, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Diabetes Mellitus, Female, Humans, Intermittent Claudication, Leg, Male, Prevalence, Sensitivity and Specificity, Surveys and Questionnaires}, issn = {0895-4356}, doi = {10.1016/s0895-4356(00)00308-5}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Polak, J F and Kuller, L H} } @article {692, title = {Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Jun}, pages = {1636-44}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Depression, Disease Progression, Female, Health Surveys, Humans, Incidence, Logistic Models, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Odds Ratio, United States}, issn = {1524-4628}, doi = {10.1161/01.str.0000018405.59799.d5}, author = {Steffens, David C and Krishnan, K Ranga Rama and Crump, Casey and Burke, Gregory L} } @article {690, title = {No association of plasma prothrombin concentration or the G20210A mutation with incident cardiovascular disease: results from the Cardiovascular Health Study.}, journal = {Thromb Haemost}, volume = {87}, year = {2002}, month = {2002 Apr}, pages = {614-21}, abstract = {

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{\textquoteright} 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}, issn = {0340-6245}, author = {Smiles, Adam M and Jenny, Nancy S and Tang, Zhonghua and Arnold, Alice and Cushman, Mary and Tracy, Russell P} } @article {702, title = {Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.}, journal = {JAMA}, volume = {288}, year = {2002}, month = {2002 Sep 25}, pages = {1475-83}, abstract = {

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

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

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

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

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

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

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

}, keywords = {Aged, Aggression, Anxiety, Behavioral Symptoms, Cognition Disorders, Comorbidity, Cross-Sectional Studies, Delusions, Dementia, Depression, Feeding and Eating Disorders, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Prevalence, Sleep Wake Disorders}, issn = {0098-7484}, doi = {10.1001/jama.288.12.1475}, author = {Lyketsos, Constantine G and Lopez, Oscar and Jones, Beverly and Fitzpatrick, Annette L and Breitner, John and DeKosky, Steven} } @article {733, title = {Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Apr 22}, pages = {2021-4}, abstract = {

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

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

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

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Brain Ischemia, Cardiovascular Diseases, Cohort Studies, Comorbidity, Coronary Disease, European Continental Ancestry Group, Follow-Up Studies, Gene Frequency, Humans, Incidence, Linkage Disequilibrium, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Assessment, Stroke, United States}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000065231.07729.92}, author = {Heckbert, Susan R and Hindorff, Lucia A and Edwards, Karen L and Psaty, Bruce M and Lumley, Thomas and Siscovick, David S and Tang, Zhonghua and Durda, J Peter and Kronmal, Richard A and Tracy, Russell P} } @article {741, title = {C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Jul 15}, pages = {166-70}, abstract = {

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

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

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

}, keywords = {Aged, Brain Ischemia, C-Reactive Protein, California, Carotid Arteries, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Maryland, North Carolina, Odds Ratio, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000079160.07364.6A}, author = {Cao, Jie J and Thach, Chau and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis H and Chaves, Paulo H M and Polak, Joseph F and Sutton-Tyrrell, Kim and Herrington, David M and Price, Thomas R and Cushman, Mary} } @article {798, title = {APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Aug 24}, pages = {664-8}, abstract = {

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}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000134671.99649.32}, author = {Gottlieb, D J and DeStefano, A L and Foley, D J and Mignot, E and Redline, S and Givelber, R J and Young, T} } @article {768, title = {The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture.}, journal = {Arch Intern Med}, volume = {164}, year = {2004}, month = {2004 Feb 23}, pages = {406-18}, abstract = {

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}, issn = {0003-9926}, doi = {10.1001/archinte.164.4.406}, author = {Redline, Susan and Kirchner, H Lester and Quan, Stuart F and Gottlieb, Daniel J and Kapur, Vishesh and Newman, Anne} } @article {794, title = {The relationship of cardiovascular risk factors to microalbuminuria in older adults with or without diabetes mellitus or hypertension: the cardiovascular health study.}, journal = {Am J Kidney Dis}, volume = {44}, year = {2004}, month = {2004 Jul}, pages = {25-34}, abstract = {

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}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2004.03.022}, author = {Barzilay, Joshua I and Peterson, Do and Cushman, Mary and Heckbert, Susan R and Cao, Jie J and Blaum, Caroline and Tracy, Russell P and Klein, Ronald and Herrington, David M} } @article {752, title = {Sleep apnea and markers of vascular endothelial function in a large community sample of older adults.}, journal = {Am J Respir Crit Care Med}, volume = {169}, year = {2004}, month = {2004 Feb 01}, pages = {354-60}, abstract = {

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}, issn = {1073-449X}, doi = {10.1164/rccm.200306-756OC}, author = {Nieto, F Javier and Herrington, David M and Redline, Susan and Benjamin, Emelia J and Robbins, John A} } @article {801, title = {Stroke risk factors and loss of high cognitive function.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Sep 14}, pages = {793-9}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Aging, Cognition Disorders, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Higher Nervous Activity, Humans, Incidence, Male, Risk Assessment, Risk Factors, Sampling Studies, Sensitivity and Specificity, Severity of Illness Index, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000137014.36689.7f}, author = {Elkins, J S and O{\textquoteright}Meara, E S and Longstreth, W T and Carlson, M C and Manolio, T A and Johnston, S C} } @article {854, title = {Associations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study.}, journal = {Am J Kidney Dis}, volume = {46}, year = {2005}, month = {2005 Aug}, pages = {214-24}, abstract = {

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}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2005.05.005}, author = {Edwards, Matthew S and Wilson, David B and Craven, Timothy E and Stafford, Jeanette and Fried, Linda F and Wong, Tien Y and Klein, Ronald and Burke, Gregory L and Hansen, Kimberley J} } @article {838, title = {Determinants of vascular dementia in the Cardiovascular Health Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1548-52}, abstract = {

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{\textquoteright}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{\textquoteright}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{\textquoteright}s Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer{\textquoteright}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}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000160115.55756.DE}, author = {Kuller, L H and Lopez, O L and Jagust, W J and Becker, J T and DeKosky, S T and Lyketsos, C and Kawas, C and Breitner, J C S and Fitzpatrick, A and Dulberg, C} } @article {853, title = {Hospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Jul}, pages = {1108-16}, abstract = {

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}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53352.x}, author = {O{\textquoteright}Meara, Ellen S and White, Mark and Siscovick, David S and Lyles, Mary F and Kuller, Lewis H} } @article {871, title = {Progression and regression of sleep-disordered breathing with changes in weight: the Sleep Heart Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Nov 14}, pages = {2408-13}, abstract = {

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

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

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

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

}, keywords = {Body Weights and Measures, Causality, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Linear Models, Male, Middle Aged, Obesity, Odds Ratio, Sex Distribution, Sleep Apnea Syndromes, United States, Weight Gain, Weight Loss}, issn = {0003-9926}, doi = {10.1001/archinte.165.20.2408}, author = {Newman, Anne B and Foster, Greg and Givelber, Rachel and Nieto, F Javier and Redline, Susan and Young, Terry} } @article {819, title = {Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {207-13}, abstract = {

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

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

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

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

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cohort Studies, Comorbidity, Coronary Disease, Female, Geriatric Assessment, Heart Function Tests, Humans, Hypertension, Renovascular, Incidence, Kidney Function Tests, Male, Multivariate Analysis, Probability, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate, Ultrasonography, Doppler, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.207}, author = {Edwards, Matthew S and Craven, Timothy E and Burke, Gregory L and Dean, Richard H and Hansen, Kimberley J} } @article {860, title = {Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Sep 27}, pages = {835-42}, abstract = {

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}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000176058.09848.bb}, author = {Kaplan, R C and Tirschwell, D L and Longstreth, W T and Manolio, T A and Heckbert, S R and Lefkowitz, D and El-Saed, A and Psaty, B M} } @article {878, title = {10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {71-8}, abstract = {

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

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

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

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

}, keywords = {African Continental Ancestry Group, Aged, Blood Chemical Analysis, Cardiovascular Diseases, Comorbidity, Coronary Disease, Echocardiography, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Multivariate Analysis, Prevalence, Proportional Hazards Models, Regression Analysis, Risk Factors, Sex Distribution, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.71}, author = {Kuller, Lewis H and Arnold, Alice M and Psaty, Bruce M and Robbins, John A and O{\textquoteright}Leary, Daniel H and Tracy, Russell P and Burke, Gregory L and Manolio, Teri A and Chaves, Paolo H M} } @article {905, title = {The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {48}, year = {2006}, month = {2006 Jul 18}, pages = {305-11}, abstract = {

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}, issn = {1558-3597}, doi = {10.1016/j.jacc.2006.02.066}, author = {Bryson, Chris L and Mukamal, Kenneth J and Mittleman, Murray A and Fried, Linda P and Hirsch, Calvin H and Kitzman, Dalane W and Siscovick, David S} } @article {915, title = {Association of usual sleep duration with hypertension: the Sleep Heart Health Study.}, journal = {Sleep}, volume = {29}, year = {2006}, month = {2006 Aug}, pages = {1009-14}, abstract = {

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}, issn = {0161-8105}, doi = {10.1093/sleep/29.8.1009}, author = {Gottlieb, Daniel J and Redline, Susan and Nieto, F Javier and Baldwin, Carol M and Newman, Anne B and Resnick, Helaine E and Punjabi, Naresh M} } @article {896, title = {Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {113}, year = {2006}, month = {2006 May 09}, pages = {2177-85}, abstract = {

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

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

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Carotid Artery, Common, Cohort Studies, Comorbidity, Coronary Disease, Diabetes Mellitus, Electrocardiography, Female, Follow-Up Studies, Forecasting, Heart Failure, Heart Ventricles, Hospitalization, Humans, Hyperlipidemias, Hypertension, Male, Multivariate Analysis, Myocardial Infarction, Organ Size, Predictive Value of Tests, Risk Factors, Sampling Studies, Tunica Intima, Tunica Media, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.105.610352}, author = {Pearte, Camille A and Furberg, Curt D and O{\textquoteright}Meara, Ellen S and Psaty, Bruce M and Kuller, Lewis and Powe, Neil R and Manolio, Teri} } @article {924, title = {Clinical course of mesenteric artery stenosis in elderly americans.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Oct 23}, pages = {2095-100}, abstract = {

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}, issn = {0003-9926}, doi = {10.1001/archinte.166.19.2095}, author = {Wilson, David B and Mostafavi, Kian and Craven, Timothy E and Ayerdi, Juan and Edwards, Matthew S and Hansen, Kimberley J} } @article {879, title = {Costs for heart failure with normal vs reduced ejection fraction.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {112-8}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Comorbidity, Echocardiography, Health Care Costs, Heart Failure, Humans, Incidence, Medicare, Prevalence, Prospective Studies, Regression Analysis, Statistics, Nonparametric, Stroke Volume, Systole, United States, Ventricular Function, Left}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.112}, author = {Liao, Lawrence and Jollis, James G and Anstrom, Kevin J and Whellan, David J and Kitzman, Dalane W and Aurigemma, Gerard P and Mark, Daniel B and Schulman, Kevin A and Gottdiener, John S} } @article {891, title = {Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study.}, journal = {Arch Gen Psychiatry}, volume = {63}, year = {2006}, month = {2006 Mar}, pages = {273-9}, abstract = {

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

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

DESIGN: Prospective, population-based, longitudinal study.

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

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

MAIN OUTCOME MEASURE: Diagnosis of MCI.

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

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

}, keywords = {Aged, Cerebrovascular Disorders, Cognition Disorders, Comorbidity, Dementia, Dementia, Vascular, Depressive Disorder, Female, Follow-Up Studies, Geriatric Assessment, Humans, Longitudinal Studies, Male, Prospective Studies, Psychiatric Status Rating Scales, Risk Factors, Sampling Studies, Vascular Diseases}, issn = {0003-990X}, doi = {10.1001/archpsyc.63.3.273}, author = {Barnes, Deborah E and Alexopoulos, George S and Lopez, Oscar L and Williamson, Jeff D and Yaffe, Kristine} } @article {906, title = {Heart failure at the end of life: symptoms, function, and medical care in the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {15}, year = {2006}, month = {2006 Jul-Aug}, pages = {217-25}, abstract = {

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}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2006.05196.x}, author = {Sullivan, Mark D and O{\textquoteright}Meara, Ellen S} } @article {949, title = {Are microvascular abnormalities in the retina associated with depression symptoms? The Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {15}, year = {2007}, month = {2007 Apr}, pages = {335-43}, abstract = {

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

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

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

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

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

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

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

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

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {1002, title = {Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {29}, year = {2007}, month = {2007}, pages = {193-200}, abstract = {

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

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

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

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

}, keywords = {Accidental Falls, Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebral Infarction, Comorbidity, Female, Gait Disorders, Neurologic, Geriatric Assessment, Health Surveys, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mobility Limitation, Neurodegenerative Diseases, Neurologic Examination, Risk Factors, United States}, issn = {1423-0208}, doi = {10.1159/000111582}, author = {Rosano, Caterina and Brach, Jennifer and Studenski, Stephanie and Longstreth, W T and Newman, Anne B} } @article {946, title = {Ventricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {49}, year = {2007}, month = {2007 Mar 06}, pages = {972-81}, abstract = {

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

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

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

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

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

}, keywords = {Age Distribution, Aged, Body Size, Case-Control Studies, Cohort Studies, Comorbidity, Continental Population Groups, Echocardiography, Female, Heart Failure, Heart Ventricles, Humans, Hypertension, Longitudinal Studies, Male, Multivariate Analysis, Prevalence, Regression Analysis, Risk Factors, Sex Distribution, Stroke Volume, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2006.10.061}, author = {Maurer, Mathew S and Burkhoff, Daniel and Fried, Linda P and Gottdiener, John and King, Donald L and Kitzman, Dalane W} } @article {1024, title = {Incident physical disability in people with lower extremity peripheral arterial disease: the role of cardiovascular disease.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Jun}, pages = {1037-44}, abstract = {

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

DESIGN: Observational cohort study.

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

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

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

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

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

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Cohort Studies, Comorbidity, Disability Evaluation, Female, Gait, Geriatric Assessment, Humans, Lower Extremity, Male, Mobility Limitation, Peripheral Vascular Diseases, Proportional Hazards Models, Risk Assessment, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01719.x}, author = {Brach, Jennifer S and Solomon, Cam and Naydeck, Barbara L and Sutton-Tyrrell, Kim and Enright, Paul L and Jenny, Nancy Swords and Chaves, Paulo M and Newman, Anne B} } @article {1037, title = {A physiologic index of comorbidity: relationship to mortality and disability.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {63}, year = {2008}, month = {2008 Jun}, pages = {603-9}, abstract = {

BACKGROUND: In older adults, there is often substantial undiagnosed chronic disease detectable on noninvasive testing, not accounted for by most comorbidity indices. We developed a simple physiologic index of comorbidity by scoring five noninvasive tests across the full range of values. We examined the predictive validity of this index for mortality and disability.

METHODS: There were 2928 (mean age 74.5 years, 60\% women, 85\% white, and 15\% black) participants in the Cardiovascular Health Study (1992-1993) who had carotid ultrasound, pulmonary function testing, brain magnetic resonance scan, serum cystatin-C, and fasting glucose. These were combined into a single physiologic index of comorbid chronic disease on a scale of 0-10. Cox proportional hazard models were used to predict mortality, mobility limitation, and activities of daily living (ADL) difficulty after a maximum of 9 years.

RESULTS: The range of the physiologic index was quite broad, with very few individuals having total scores of either 0 or 10. Those with an index of 7-10 had a hazard ratio of 3.80 (95\% confidence interval, 2.82-5.13) for mortality compared to those with scores of 0-2, after adjustment for demographics, behavioral risk factors, and clinically diagnosed conditions. Associations with mobility limitation and ADL difficulty were also significant. The index explained about 40\% of the age effect on mortality risk.

CONCLUSION: Older adults with low levels of markers of chronic disease are rather rare but have remarkably good health outcomes. The ability of such an index to distinguish usual from low risk might provide an opportunity to better understand optimal health in old age.

}, keywords = {Activities of Daily Living, Aged, Comorbidity, Disabled Persons, Female, Health Status, Humans, Male, Mobility Limitation, Mortality, Predictive Value of Tests, Proportional Hazards Models}, issn = {1079-5006}, doi = {10.1093/gerona/63.6.603}, author = {Newman, Anne B and Boudreau, Robert M and Naydeck, Barbara L and Fried, Linda F and Harris, Tamara B} } @article {1025, title = {Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 May 06}, pages = {1664-71}, abstract = {

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

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

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

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Cerebrovascular Disorders, Comorbidity, Cross-Sectional Studies, Cystatin C, Cystatins, Female, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Models, Statistical, Neuropsychological Tests, Peptide Fragments, Predictive Value of Tests, Prospective Studies, Reference Values, Risk Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000306696.82017.66}, author = {Lopez, O L and Kuller, L H and Mehta, P D and Becker, J T and Gach, H M and Sweet, R A and Chang, Y F and Tracy, R and DeKosky, S T} } @article {1051, title = {Sleep disordered breathing and hypertension: does self-reported sleepiness modify the association?}, journal = {Sleep}, volume = {31}, year = {2008}, month = {2008 Aug}, pages = {1127-32}, abstract = {

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

DESIGN: Cross-sectional.

SETTING: Multicenter study.

PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study.

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

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

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

}, keywords = {Aged, Antihypertensive Agents, Comorbidity, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Health Surveys, Humans, Hypertension, Male, Middle Aged, Odds Ratio, Oxygen, Polysomnography, Sleep Apnea, Obstructive, United States}, issn = {0161-8105}, author = {Kapur, Vishesh K and Resnick, Helaine E and Gottlieb, Daniel J} } @article {1113, title = {External validity of the cardiovascular health study: a comparison with the Medicare population.}, journal = {Med Care}, volume = {47}, year = {2009}, month = {2009 Aug}, pages = {916-23}, abstract = {

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

OBJECTIVE: To assess the external validity of the CHS.

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

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

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

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

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

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Humans, Male, Medicare, Randomized Controlled Trials as Topic, Reproducibility of Results, Socioeconomic Factors, United States}, issn = {1537-1948}, doi = {10.1097/MLR.0b013e318197b104}, author = {DiMartino, Lisa D and Hammill, Bradley G and Curtis, Lesley H and Gottdiener, John S and Manolio, Teri A and Powe, Neil R and Schulman, Kevin A} } @article {1076, title = {Insomnia did not predict incident hypertension in older adults in the cardiovascular health study.}, journal = {Sleep}, volume = {32}, year = {2009}, month = {2009 Jan}, pages = {65-72}, abstract = {

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

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

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

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

INTERVENTIONS: none.

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

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

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

}, keywords = {African Americans, Aged, Cohort Studies, Comorbidity, European Continental Ancestry Group, Female, Follow-Up Studies, Health Surveys, Humans, Hypertension, Male, Prospective Studies, Risk Factors, Sleep Initiation and Maintenance Disorders, United States}, issn = {0161-8105}, author = {Phillips, Barbara and B{\r u}zkov{\'a}, Petra and Enright, Paul} } @article {1125, title = {Longitudinal evaluation of sleep-disordered breathing and sleep symptoms with change in quality of life: the Sleep Heart Health Study (SHHS).}, journal = {Sleep}, volume = {32}, year = {2009}, month = {2009 Aug}, pages = {1049-57}, abstract = {

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

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

SETTING: Multicenter study.

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

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

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

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

}, keywords = {Aged, Attitude to Health, Cohort Studies, Comorbidity, Disease Progression, Disorders of Excessive Somnolence, Female, Humans, Longitudinal Studies, Male, Middle Aged, Polysomnography, Quality of Life, Sleep Apnea, Obstructive, Sleep Initiation and Maintenance Disorders}, issn = {0161-8105}, author = {Silva, Graciela E and An, Ming-Wen and Goodwin, James L and Shahar, Eyal and Redline, Susan and Resnick, Helaine and Baldwin, Carol M and Quan, Stuart F} } @article {1075, title = {Long-term function in an older cohort--the cardiovascular health study all stars study.}, journal = {J Am Geriatr Soc}, volume = {57}, year = {2009}, month = {2009 Mar}, pages = {432-40}, abstract = {

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

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. communities.

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

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

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

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

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Attention, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Comorbidity, Cross-Sectional Studies, Female, Follow-Up Studies, Gait, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Male, Memory, Short-Term, Mental Status Schedule, Proportional Hazards Models, Psychometrics, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.02152.x}, author = {Newman, Anne B and Arnold, Alice M and Sachs, Michael C and Ives, Diane G and Cushman, Mary and Strotmeyer, Elsa S and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Fried, Linda P and Robbins, John} } @article {1105, title = {Polysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study.}, journal = {Sleep}, volume = {32}, year = {2009}, month = {2009 Jun}, pages = {772-8}, abstract = {

STUDY OBJECTIVES: Sleep disturbance is the primary clinical morbidity of restless legs syndrome (RLS). To date, sleep disturbance in RLS has been measured in (1) clinical samples with polysomnography (PSG) or (2) population-based samples by self-report. The objective of this study was to analyze sleep by PSG in a population-based sample with symptoms of RLS.

DESIGN: Cross-sectional observational study.

SETTING: Community-based.

PARTICIPANTS: 3433 older men and women.

INTERVENTIONS: None.

MEASUREMENTS AND RESULTS: RLS was evaluated using an 8-item self-administered questionnaire based on NIH diagnostic criteria and required symptoms occurring > or = five times per month and associated with at least moderate distress. Health-related quality of life (HRQOL) was determined using the SF-36. Unattended, in-home PSG was performed. Data were assessed using general linear models with adjustment for demographic, health-related variables, and apnea-hypopnea index (AHI). Subjects with RLS had longer adjusted mean sleep latency (39.8 vs 26.4 min, P < 0.0001) and higher arousal index (20.1 vs 18.0, P = 0.0145) than those without RLS. Sleep latency increased progressively as the frequency of RLS symptoms increased from 5-15 days per month to 6-7 days per week. No differences in sleep stage percentages were observed between participants with and without RLS. Subjects with RLS also reported poorer HRQOL in all physical domains as well as in the Mental Health and Vitality domains.

CONCLUSIONS: These novel PSG data from a nonclinical, community-based sample of individuals with RLS document sleep disturbance in the home even in individuals with intermittent symptoms.

}, keywords = {Adult, Aged, Cohort Studies, Comorbidity, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Polysomnography, Prospective Studies, Quality of Life, Restless Legs Syndrome, Sleep Initiation and Maintenance Disorders, Statistics as Topic}, issn = {0161-8105}, author = {Winkelman, John W and Redline, Susan and Baldwin, Carol M and Resnick, Helaine E and Newman, Anne B and Gottlieb, Daniel J} } @article {1162, title = {Association of Holter-based measures including T-wave alternans with risk of sudden cardiac death in the community-dwelling elderly: the Cardiovascular Health Study.}, journal = {J Electrocardiol}, volume = {43}, year = {2010}, month = {2010 May-Jun}, pages = {251-9}, abstract = {

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

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

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

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

}, keywords = {Comorbidity, Coronary Artery Disease, Death, Sudden, Cardiac, Electrocardiography, Ambulatory, Female, Humans, Male, Prevalence, Prognosis, Reproducibility of Results, Risk Assessment, Risk Factors, Sensitivity and Specificity, Survival Analysis, Survival Rate, United States, Ventricular Premature Complexes}, issn = {1532-8430}, doi = {10.1016/j.jelectrocard.2009.12.009}, author = {Stein, Phyllis K and Sanghavi, Devang and Sotoodehnia, Nona and Siscovick, David S and Gottdiener, John} } @article {1216, title = {Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression.}, journal = {Psychosom Med}, volume = {72}, year = {2010}, month = {2010 Sep}, pages = {626-35}, abstract = {

OBJECTIVE: To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression.

METHODS: Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 {\textpm} 4.6 years; 59.1\% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA(1)) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates.

RESULTS: Depression was associated with ANS dysfunction (DFA(1), p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95\% confidence interval, 1.23-2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95\% confidence interval, 1.05-2.83) when adjusting for independent HRV and inflammation predictors (DFA(1), heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7\% (p < .001).

CONCLUSION: Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures.

}, keywords = {Aged, Autonomic Nervous System Diseases, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cause of Death, Cohort Studies, Comorbidity, Depressive Disorder, Electrocardiography, Female, Follow-Up Studies, Heart Rate, Humans, Inflammation, Interleukin-6, Leukocyte Count, Male, Risk Factors}, issn = {1534-7796}, doi = {10.1097/PSY.0b013e3181eadd2b}, author = {Kop, Willem J and Stein, Phyllis K and Tracy, Russell P and Barzilay, Joshua I and Schulz, Richard and Gottdiener, John S} } @article {1220, title = {Chronic medical conditions and the sex-based disparity in disability: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Dec}, pages = {1325-31}, abstract = {

BACKGROUND: Older women experience disability more commonly than their male peers. This disparity may be due, in part, to sex-based differences in the prevalence or the disabling effects of common medical conditions. The objectives of this analysis were to (a) quantify the extent to which excess disability in women is explained by higher prevalence of selected medical conditions and (b) evaluate whether the same conditions have differing effects on disability in men and women.

METHODS: We analyzed cross-sectional data from 5,888 community-dwelling older men and women. Disability was defined as difficulty with greater than or equal to one activity of daily living. Thirteen medical conditions were assessed by self-report, testing, or record review.

RESULTS: Controlling for age, race, education, and marital status, women were more likely to experience disability (odds ratio = 1.70, 95\% confidence interval = 1.36-2.11). Higher prevalence of arthritis and obesity in women explained 30.2\% and 12.9\%, respectively, of the sex-based difference in disability rates, whereas male prevalent diseases like vascular conditions and emphysema narrowed the disability gap. Women with arthritis, hearing problems, coronary artery disease, congestive heart failure, stroke, and claudication were more likely to exhibit disability compared with men with the same conditions (p < .001).

CONCLUSIONS: Efforts to lessen sex-based inequality in disability should focus on reducing the prevalence of arthritis and obesity. Future generations may see greater functional disparity if rates of vascular disease and emphysema rise among women. Several conditions were more often associated with disability in women, suggesting additional sex-based differences in the disablement process.

}, keywords = {Aged, Arthritis, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Comorbidity, Cross-Sectional Studies, Disabled Persons, Emphysema, Female, Hearing Disorders, Humans, Male, Obesity, Prevalence, Sex Distribution}, issn = {1758-535X}, doi = {10.1093/gerona/glq139}, author = {Whitson, Heather E and Landerman, Lawrence R and Newman, Anne B and Fried, Linda P and Pieper, Carl F and Cohen, Harvey Jay} } @article {1276, title = {High blood pressure accelerates gait slowing in well-functioning older adults over 18-years of follow-up.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Mar}, pages = {390-7}, abstract = {

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

DESIGN: Longitudinal cohort study.

SETTING: Cardiovascular Health Study.

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

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

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

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

}, keywords = {Aged, Antihypertensive Agents, Comorbidity, Female, Follow-Up Studies, Gait, Geriatric Assessment, Humans, Hypertension, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Statistics, Nonparametric}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03282.x}, author = {Rosano, Caterina and Longstreth, William T and Boudreau, Robert and Taylor, Christopher A and Du, Yan and Kuller, Lewis H and Newman, Anne B} } @article {1265, title = {Leukocyte telomere length and mortality in the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Apr}, pages = {421-9}, abstract = {

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

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

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

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

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

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

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

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

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

}, keywords = {Acute Kidney Injury, Aged, Chronic Disease, Cohort Studies, Comorbidity, Depression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Longitudinal Studies, Male}, issn = {1555-905X}, doi = {10.2215/CJN.03840510}, author = {Kop, Willem J and Seliger, Stephen L and Fink, Jeffrey C and Katz, Ronit and Odden, Michelle C and Fried, Linda F and Rifkin, Dena E and Sarnak, Mark J and Gottdiener, John S} } @article {1255, title = {Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults.}, journal = {J Cardiovasc Electrophysiol}, volume = {22}, year = {2011}, month = {2011 Feb}, pages = {122-7}, abstract = {

INTRODUCTION: We examined whether heart rate turbulence (HRT) and C-reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk.

METHODS AND RESULTS: One thousand two hundred and seventy-two individuals, age >= 65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low-risk group [HR 7.9, 95\% confidence interval (CI) 2.8-22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95\% CI 1.5-4.0, P = 0.016] and [HR 2.7, 95\% CI 1.2-5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low-risk individuals [HR 2.5, 95\% CI 1.3-5.1, P = 0.009]. Among low risk, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT.

CONCLUSIONS: Abnormal HRT independently adds to risk stratification of low, intermediate and high-risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk.

}, keywords = {Aged, C-Reactive Protein, Cardiovascular Diseases, Comorbidity, Electrocardiography, Ambulatory, Female, Humans, Incidence, Male, Risk Assessment, Risk Factors, Statistics as Topic, Survival Analysis, Survival Rate, United States, Ventricular Premature Complexes}, issn = {1540-8167}, doi = {10.1111/j.1540-8167.2010.01967.x}, author = {Stein, Phyllis K and Barzilay, Joshua I} } @article {1350, title = {Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {58}, year = {2011}, month = {2011 Dec}, pages = {1021-8}, abstract = {

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >=20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >=65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7\% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95\% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.

}, keywords = {Aged, Cardiovascular Diseases, Comorbidity, Death, Sudden, Cardiac, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Kidney, Male, Middle Aged, Minerals, Parathyroid Hormone, Proportional Hazards Models, Risk Factors, Socioeconomic Factors, United States, Vitamin D}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.111.179135}, author = {Deo, Rajat and Katz, Ronit and Shlipak, Michael G and Sotoodehnia, Nona and Psaty, Bruce M and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and de Boer, Ian H and Enquobahrie, Daniel and Siscovick, David and Kestenbaum, Bryan} } @article {6087, title = {Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Aug 28}, pages = {1040-9}, abstract = {

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events.

METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1\%) had subclinical hypothyroidism and 648 (2.6\%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95\% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95\% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95\% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95\% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95\% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors.

CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH >=10 and <0.10 mIU/L.

}, keywords = {Adult, Aged, Aged, 80 and over, Comorbidity, Female, Follow-Up Studies, Heart Failure, Humans, Hypothyroidism, Male, Middle Aged, Prospective Studies, Risk, Risk Factors, Sensitivity and Specificity, Thyrotropin, Thyroxine}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.096024}, author = {Gencer, Bari{\c s} and Collet, Tinh-Hai and Virgini, Vanessa and Bauer, Douglas C and Gussekloo, Jacobijn and Cappola, Anne R and Nanchen, David and den Elzen, Wendy P J and Balmer, Philippe and Luben, Robert N and Iacoviello, Massimo and Triggiani, Vincenzo and Cornuz, Jacques and Newman, Anne B and Khaw, Kay-Tee and Jukema, J Wouter and Westendorp, Rudi G J and Vittinghoff, Eric and Aujesky, Drahomir and Rodondi, Nicolas} } @article {6827, title = {Association of functional polymorphism rs2231142 (Q141K) in the ABCG2 gene with serum uric acid and gout in 4 US populations: the PAGE Study.}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, month = {2013 May 1}, pages = {923-32}, abstract = {

A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 {\texttimes} 10(-67), P = 3.98 {\texttimes} 10(-5), P = 6.97 {\texttimes} 10(-9), and P = 5.33 {\texttimes} 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 {\texttimes} 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 {\texttimes} 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 {\texttimes} 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout.

}, keywords = {Adult, African Americans, Age Distribution, ATP-Binding Cassette Transporters, Comorbidity, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genetics, Population, Genome-Wide Association Study, Gout, Hormone Replacement Therapy, Humans, Indians, North American, Male, Mexican Americans, Middle Aged, Neoplasm Proteins, Polymorphism, Genetic, Postmenopause, Sex Distribution, United States, Uric Acid}, issn = {1476-6256}, doi = {10.1093/aje/kws330}, author = {Zhang, Lili and Spencer, Kylee L and Voruganti, V Saroja and Jorgensen, Neal W and Fornage, Myriam and Best, Lyle G and Brown-Gentry, Kristin D and Cole, Shelley A and Crawford, Dana C and Deelman, Ewa and Franceschini, Nora and Gaffo, Angelo L and Glenn, Kimberly R and Heiss, Gerardo and Jenny, Nancy S and K{\"o}ttgen, Anna and Li, Qiong and Liu, Kiang and Matise, Tara C and North, Kari E and Umans, Jason G and Kao, W H Linda} } @article {6002, title = {Atrial fibrillation and cognitive decline: a longitudinal cohort study.}, journal = {Neurology}, volume = {81}, year = {2013}, month = {2013 Jul 09}, pages = {119-25}, abstract = {

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

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

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

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Luria-Nebraska Neuropsychological Battery, Male, Predictive Value of Tests}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31829a33d1}, author = {Thacker, Evan L and McKnight, Barbara and Psaty, Bruce M and Longstreth, W T and Sitlani, Colleen M and Dublin, Sascha and Arnold, Alice M and Fitzpatrick, Annette L and Gottesman, Rebecca F and Heckbert, Susan R} } @article {5997, title = {Effects of respiratory and non-respiratory factors on disability among older adults with airway obstruction: the Cardiovascular Health Study.}, journal = {COPD}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {588-96}, abstract = {

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

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

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

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

}, keywords = {Activities of Daily Living, Aged, Cognition Disorders, Cohort Studies, Comorbidity, Depression, Diabetes Mellitus, Disease Progression, Dyspnea, Female, Heart Failure, Humans, Linear Models, Longitudinal Studies, Male, Muscle Weakness, Myocardial Ischemia, Osteoporosis, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Spirometry}, issn = {1541-2563}, doi = {10.3109/15412555.2013.781148}, author = {Locke, Emily and Thielke, Stephen and Diehr, Paula and Wilsdon, Anthony G and Barr, R Graham and Hansel, Nadia and Kapur, Vishesh K and Krishnan, Jerry and Enright, Paul and Heckbert, Susan R and Kronmal, Richard A and Fan, Vincent S} } @article {6193, title = {Epidemiology and long-term clinical and biologic risk factors for pneumonia in community-dwelling older Americans: analysis of three cohorts.}, journal = {Chest}, volume = {144}, year = {2013}, month = {2013 Sep}, pages = {1008-1017}, abstract = {

BACKGROUND: Preventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals.

METHODS: This was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization.

RESULTS: The crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15\%). The 30-day and 1-year mortality were 16.5\% and 31.5\%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38\% of pneumonia cases occurred in adults \< 65 years of age. The 30-day and 1-year mortality were 12.5\% and 25.7\% in those \< 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance.

CONCLUSIONS: Pneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Community-Acquired Infections, Comorbidity, Female, Follow-Up Studies, Hospitalization, Humans, Incidence, Male, Middle Aged, Pneumonia, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, Time Factors}, issn = {1931-3543}, doi = {10.1378/chest.12-2818}, author = {Yende, Sachin and Alvarez, Karina and Loehr, Laura and Folsom, Aaron R and Newman, Anne B and Weissfeld, Lisa A and Wunderink, Richard G and Kritchevsky, Stephen B and Mukamal, Kenneth J and London, Stephanie J and Harris, Tamara B and Bauer, Doug C and Angus, Derek C} } @article {5854, title = {Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.}, journal = {Ann Epidemiol}, volume = {23}, year = {2013}, month = {2013 Mar}, pages = {106-11}, abstract = {

PURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age.

METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.

RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95\% confidence interval [CI], 0.1, 4.4), 5.1 (95\% CI, 4.1, 6.1), and 6.9 (95\%~CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80~years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95\% CI, 3.5, 6.3), 7.1 (95\% CI, 6.0, 8.3), 8.9 (95\% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.

CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Causality, Cholesterol, LDL, Cohort Studies, Comorbidity, Cross-Sectional Studies, Cystatin C, Female, Humans, Hypertension, Kidney Function Tests, Male, Netherlands, Obesity, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Smoking, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2012.12.004}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Fried, Linda F and Newman, Anne B and Katz, Ronit and Satterfield, Suzanne and Harris, Tamara B and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {6064, title = {Plasma free fatty acids and risk of heart failure: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {6}, year = {2013}, month = {2013 Sep 01}, pages = {964-9}, abstract = {

BACKGROUND: Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes mellitus and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF).

METHODS AND RESULTS: To test the hypothesis that plasma concentration of FFAs is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and >65 years old from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per SD of FFAs. During a median follow-up of 10.5 years, a total of 1286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12\% (95\% confidence interval, 6\%-19\%) higher risk of HF. Controlling for time-varying diabetes mellitus and coronary heart disease did not change the results (hazard ratio per SD, 1.16 [95\% confidence interval, 1.09-1.23]).

CONCLUSIONS: A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biological mechanisms by which FFAs may influence the risk of HF and determine whether FFAs could serve as a novel pharmacological target for HF prevention.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Fatty Acids, Nonesterified, Female, Heart Failure, Humans, Incidence, Kaplan-Meier Estimate, Linear Models, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.113.000521}, author = {Djouss{\'e}, Luc and Benkeser, David and Arnold, Alice and Kizer, Jorge R and Zieman, Susan J and Lemaitre, Rozenn N and Tracy, Russell P and Gottdiener, John S and Mozaffarian, Dariush and Siscovick, David S and Mukamal, Kenneth J and Ix, Joachim H} } @article {5851, title = {Risk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {61}, year = {2013}, month = {2013 Feb 12}, pages = {635-42}, chapter = {635}, abstract = {

OBJECTIVES: This study sought to identify risk factors for the occurrence of all-cause hospital admissions among older persons after heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors for admission when evaluated in the context of other relevant clinical data.

BACKGROUND: Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk for hospital admission after heart failure diagnosis. With the aging of the population with heart failure, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common.

METHODS: The study population included participants with a new diagnosis of heart failure in the Cardiovascular Health Study, a longitudinal study of community-living older persons. Data were collected through annual examinations and medical-record reviews. Geriatric conditions assessed were slow gait, muscle weakness (defined as weak grip), cognitive impairment, and depressive symptoms. Anderson-Gill regression modeling was used to determine the predictors of hospital admission after heart failure diagnosis.

RESULTS: Of the 758 participants with a new diagnosis of heart failure, the mean rate of hospital admission was 7.9 per 10 person-years (95\% CI: 7.4 to 8.4). Independent risk factors for hospital admission included diabetes mellitus (HR: 1.36; 95\% CI: 1.13 to 1.64), New York Heart Association functional class III or IV (HR: 1.32; 95\% CI: 1.11 to 1.57), chronic kidney disease (HR: 1.32; 95\% CI: 1.14 to 1.53), slow gait (HR: 1.28; 95\% CI: 1.06 to 1.55), depressed ejection fraction (HR: 1.25; 95\% CI: 1.04 to 1.51), depression (HR: 1.23; 95\% CI: 1.05 to 1.45), and muscle weakness (HR: 1.19; 95\% CI: 1.00 to 1.42).

CONCLUSIONS: Geriatric conditions are important, and potentially modifiable, risk factors for hospital admission in heart failure that should be routinely assessed at the time of heart failure diagnosis.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Comorbidity, Effect Modifier, Epidemiologic, Female, Geriatric Assessment, Health Surveys, Heart Failure, Hospitalization, Humans, Longitudinal Studies, Male, Mental Competency, Risk Assessment, Risk Factors, Severity of Illness Index, Stroke Volume, Time-to-Treatment, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2012.11.027}, author = {Chaudhry, Sarwat I and McAvay, Gail and Chen, Shu and Whitson, Heather and Newman, Anne B and Krumholz, Harlan M and Gill, Thomas M} } @article {6424, title = {Association of kidney disease measures with ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective community-based cohorts.}, journal = {Stroke}, volume = {45}, year = {2014}, month = {2014 Jul}, pages = {1925-31}, abstract = {

BACKGROUND AND PURPOSE: Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke.

METHODS: We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression.

RESULTS: Among 29,595 participants (mean age, 61 [SD 12.5] years; 46\% men; 17\% black), 1261 developed stroke (12\% hemorrhagic) during 280,549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95\% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure.

CONCLUSIONS: Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations.

}, keywords = {Aged, Albuminuria, Brain Ischemia, Comorbidity, Female, Glomerular Filtration Rate, Humans, Intracranial Hemorrhages, Kidney Diseases, Male, Middle Aged, Netherlands, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.114.004900}, author = {Mahmoodi, Bakhtawar K and Yatsuya, Hiroshi and Matsushita, Kunihiro and Sang, Yinying and Gottesman, Rebecca F and Astor, Brad C and Woodward, Mark and Longstreth, W T and Psaty, Bruce M and Shlipak, Michael G and Folsom, Aaron R and Gansevoort, Ron T and Coresh, Josef} } @article {6399, title = {Fibroblast growth factor-23 and incident atrial fibrillation: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS).}, journal = {Circulation}, volume = {130}, year = {2014}, month = {2014 Jul 22}, pages = {298-307}, abstract = {

BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a hormone that promotes urinary phosphate excretion and regulates vitamin D metabolism. Circulating FGF-23 concentrations increase markedly in chronic kidney disease and are associated with increased risk of clinical cardiovascular events. FGF-23 may promote atrial fibrillation (AF) by inducing left ventricular hypertrophy and diastolic and left atrial dysfunction.

METHODS AND RESULTS: We tested the associations of circulating FGF-23 concentration with incident AF among 6398 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 1350 participants in the Cardiovascular Health Study (CHS), all free of clinical cardiovascular disease at baseline. Over a median of 7.7 and 8.0 years of follow-up, we observed 291 and 229 incident AF events in MESA and CHS, respectively. In multivariable Cox proportional hazards models, each 2-fold-higher FGF-23 concentration was associated with a 41\% higher risk of incident AF in MESA (hazard ratio, 1.41; 95\% confidence interval, 1.13-1.76; P=0.003) and a 30\% higher risk of incident AF in CHS (hazard ratio, 1.30; 95\% confidence interval, 1.05-1.61; P=0.016) after adjustment for potential confounding characteristics, including kidney disease. Serum phosphate concentration was significantly associated with incident AF in MESA (hazard ratio, 1.15 per 0.5 mg/dL; 95\% confidence interval, 1.02-1.31; P=0.023) but not CHS. In MESA, an association of low estimated glomerular filtration rate with incident AF was partially attenuated by adjustment for FGF-23.

CONCLUSION: Higher circulating FGF-23 concentration is associated with incident AF and may, in part, explain the link between chronic kidney disease and AF.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Comorbidity, Ethnic Groups, Female, Fibroblast Growth Factor 3, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Hypertrophy, Left Ventricular, Male, Middle Aged, Phosphates, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk Factors, United States, Ventricular Dysfunction, Left, Ventricular Remodeling, Vitamin D}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.113.005499}, author = {Mathew, Jehu S and Sachs, Michael C and Katz, Ronit and Patton, Kristen K and Heckbert, Susan R and Hoofnagle, Andrew N and Alonso, Alvaro and Chonchol, Michel and Deo, Rajat and Ix, Joachim H and Siscovick, David S and Kestenbaum, Bryan and de Boer, Ian H} } @article {6564, title = {What do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.}, journal = {J Am Soc Echocardiogr}, volume = {27}, year = {2014}, month = {2014 Sep}, pages = {998-1005.e2}, abstract = {

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

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

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

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

}, keywords = {Aged, Cardiovascular Diseases, Carotid Intima-Media Thickness, Carotid Stenosis, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Male, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Stroke, Survival Rate}, issn = {1097-6795}, doi = {10.1016/j.echo.2014.06.013}, author = {Gardin, Julius M and Bartz, Traci M and Polak, Joseph F and O{\textquoteright}Leary, Daniel H and Wong, Nathan D} } @article {6669, title = {Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease.}, journal = {JAMA}, volume = {313}, year = {2015}, month = {2015 Jan 20}, pages = {264-74}, abstract = {

IMPORTANCE: The risk of cardiovascular disease (CVD) after infection is poorly understood.

OBJECTIVE: To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD.

DESIGN, SETTINGS, AND PARTICIPANTS: We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, >=65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status.

EXPOSURES: Hospitalization for pneumonia.

MAIN OUTCOMES AND MEASURES: Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease).

RESULTS: Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95\% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95\% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95\% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95\% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95\% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95\% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95\% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95\% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant.

CONCLUSIONS AND RELEVANCE: Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.

}, keywords = {Aged, Atherosclerosis, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Male, Middle Aged, Pneumonia, Risk Factors}, issn = {1538-3598}, doi = {10.1001/jama.2014.18229}, author = {Corrales-Medina, Vicente F and Alvarez, Karina N and Weissfeld, Lisa A and Angus, Derek C and Chirinos, Julio A and Chang, Chung-Chou H and Newman, Anne and Loehr, Laura and Folsom, Aaron R and Elkind, Mitchell S and Lyles, Mary F and Kronmal, Richard A and Yende, Sachin} } @article {6811, title = {Association of Cardiometabolic Multimorbidity With Mortality.}, journal = {JAMA}, volume = {314}, year = {2015}, month = {2015 Jul 7}, pages = {52-60}, abstract = {

IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing.

OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.

EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy.

RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95\% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95\% CI, 2.0-2.2) in those with stroke, 2.0 (95\% CI, 1.9-2.2) in those with MI, 3.7 (95\% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95\% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95\% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95\% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

}, keywords = {Adult, Aged, Comorbidity, Diabetes Mellitus, Female, Humans, Life Expectancy, Male, Middle Aged, Mortality, Myocardial Infarction, Risk Factors, Stroke}, issn = {1538-3598}, doi = {10.1001/jama.2015.7008}, author = {Di Angelantonio, Emanuele and Kaptoge, Stephen and Wormser, David and Willeit, Peter and Butterworth, Adam S and Bansal, Narinder and O{\textquoteright}Keeffe, Linda M and Gao, Pei and Wood, Angela M and Burgess, Stephen and Freitag, Daniel F and Pennells, Lisa and Peters, Sanne A and Hart, Carole L and H{\r a}heim, Lise Lund and Gillum, Richard F and Nordestgaard, B{\o}rge G and Psaty, Bruce M and Yeap, Bu B and Knuiman, Matthew W and Nietert, Paul J and Kauhanen, Jussi and Salonen, Jukka T and Kuller, Lewis H and Simons, Leon A and van der Schouw, Yvonne T and Barrett-Connor, Elizabeth and Selmer, Randi and Crespo, Carlos J and Rodriguez, Beatriz and Verschuren, W M Monique and Salomaa, Veikko and Sv{\"a}rdsudd, Kurt and van der Harst, Pim and Bj{\"o}rkelund, Cecilia and Wilhelmsen, Lars and Wallace, Robert B and Brenner, Hermann and Amouyel, Philippe and Barr, Elizabeth L M and Iso, Hiroyasu and Onat, Altan and Trevisan, Maurizio and D{\textquoteright}Agostino, Ralph B and Cooper, Cyrus and Kavousi, Maryam and Welin, Lennart and Roussel, Ronan and Hu, Frank B and Sato, Shinichi and Davidson, Karina W and Howard, Barbara V and Leening, Maarten J G and Leening, Maarten and Rosengren, Annika and D{\"o}rr, Marcus and Deeg, Dorly J H and Kiechl, Stefan and Stehouwer, Coen D A and Nissinen, Aulikki and Giampaoli, Simona and Donfrancesco, Chiara and Kromhout, Daan and Price, Jackie F and Peters, Annette and Meade, Tom W and Casiglia, Edoardo and Lawlor, Debbie A and Gallacher, John and Nagel, Dorothea and Franco, Oscar H and Assmann, Gerd and Dagenais, Gilles R and Jukema, J Wouter and Sundstr{\"o}m, Johan and Woodward, Mark and Brunner, Eric J and Khaw, Kay-Tee and Wareham, Nicholas J and Whitsel, Eric A and Nj{\o}lstad, Inger and Hedblad, Bo and Wassertheil-Smoller, Sylvia and Engstr{\"o}m, Gunnar and Rosamond, Wayne D and Selvin, Elizabeth and Sattar, Naveed and Thompson, Simon G and Danesh, John} } @article {6768, title = {Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {542-50}, abstract = {

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

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

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

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

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

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Cohort Studies, Comorbidity, Coronary Disease, Female, Heart Failure, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Peripheral Arterial Disease, Physical Fitness, Prevalence, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.03.004}, author = {Murad, Khalil and Goff, David C and Morgan, Timothy M and Burke, Gregory L and Bartz, Traci M and Kizer, Jorge R and Chaudhry, Sarwat I and Gottdiener, John S and Kitzman, Dalane W} } @article {6822, title = {Empirically Derived Trajectories to Dementia Over 15 Years of Follow-up Identified by Using Mixed Membership Models.}, journal = {Am J Epidemiol}, volume = {182}, year = {2015}, month = {2015 Aug 15}, pages = {366-74}, abstract = {

Alzheimer disease is the most common form of dementia in the elderly, and the complex relationships among risk factors produce highly variable natural histories from normal cognition through the prodromal stage of mild cognitive impairment (MCI) to clinical dementia. We used a novel statistical approach, mixed membership trajectory models, to capture the variety of such pathways in 652 participants in the Cardiovascular Health Study Cognition Study over 22 years of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with a peak probability of MCI between 95 and 100 years of age and only a 50\% probability of dementia by age 100; an "intermediate" profile with a peak probability of MCI between 85 and 90 years of age and progression to dementia between 90 and 95 years; and an "unhealthy" profile with a peak probability of progressing to MCI between ages 75 and 80 years and to dementia between the ages of 80 and 85 years. Hypertension, education, race, and the ϵ4 allele of the apolipoprotein E gene all affected the closeness of an individual to 1 or more of the canonical trajectories. These results provide new insights into the natural history of Alzheimer disease and evidence for a potential difference in the pathophysiology of the development of dementia.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Cardiovascular Diseases, Comorbidity, Dementia, Diabetes Mellitus, Disease Progression, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Mild Cognitive Impairment, Neuroimaging, Prevalence, Proportional Hazards Models, Risk Factors, Sex Distribution}, issn = {1476-6256}, doi = {10.1093/aje/kwv051}, author = {Lecci, Fabrizio and Junker, Brian and Kuller, Lewis H and Lopez, Oscar L and Becker, James T} } @article {6662, title = {Fibroblast growth factor 23 and sudden versus non-sudden cardiac death: the Cardiovascular Health Study.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Jul}, pages = {40-6}, abstract = {

BACKGROUND: Elevated fibroblast growth factor 23 (FGF-23) concentrations are associated with greater risk of cardiovascular events and mortality, especially among people with chronic kidney disease (CKD). Because individuals with CKD are at an increased risk of sudden cardiac death (SCD), we sought to understand whether FGF-23 level is a stronger risk factor for SCD versus non-SCD.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 3,244 participants 65 years or older in the community-based Cardiovascular Health Study.

PREDICTOR: Plasma FGF-23 concentrations.

OUTCOMES: We assessed SCD and non-SCD in these analyses. SCD was adjudicated rigorously and was defined as a sudden pulseless condition of cardiac origin in a previously stable person occurring out of hospital or in the emergency department.

MEASUREMENTS: We estimated associations of baseline FGF-23 concentrations with SCD and non-SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, comorbid conditions, and kidney function. We also tested whether associations differed by CKD status.

RESULTS: During a median follow-up of 8.1 years, there were 118 adjudicated SCD and 570 non-SCD events. After multivariable adjustment for demographics, cardiovascular risk factors, comorbid conditions, and parameters of kidney function, higher FGF-23 concentrations were an independent risk factor for non-SCD (HR [per doubling], 1.17; 95\% CI, 1.06-1.30). However, elevated FGF-23 concentrations were not associated independently with SCD (HR [per doubling], 1.07; 95\% CI, 0.85-1.35). In stratified analysis by CKD status (36.5\% of cohort), doubling of FGF-23 concentrations was associated independently with non-SCD (adjusted HR, 1.26; 95\% CI, 1.10-1.45). A similar magnitude of association was observed between FGF-23 level and SCD in the CKD subgroup; however, it was not significant (HR, 1.20; 95\% CI, 0.89-1.62).

LIMITATIONS: Limited power to detect moderate-sized effects between FGF-23 level and SCD in both the primary and stratified analyses.

CONCLUSIONS: In this population-based study, FGF-23 level elevations were associated independently with non-SCD. Among individuals with CKD, the associations between FGF-23 level and SCD and non-SCD were similar.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Death, Sudden, Cardiac, Electrocardiography, Female, Fibroblast Growth Factors, Follow-Up Studies, Heart Arrest, Heart Diseases, Humans, Kaplan-Meier Estimate, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Sympathetic Nervous System, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2014.10.025}, author = {Deo, Rajat and Katz, Ronit and de Boer, Ian H and Sotoodehnia, Nona and Kestenbaum, Bryan and Mukamal, Kenneth J and Chonchol, Michel and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G and Ix, Joachim H} } @article {6826, title = {LV Mass as a Predictor of CVD Events in~Older Adults With and Without Metabolic Syndrome and Diabetes.}, journal = {JACC Cardiovasc Imaging}, volume = {8}, year = {2015}, month = {2015 Sep}, pages = {1007-15}, abstract = {

OBJECTIVES: The purpose of this study was to examine the prognostic significance of left ventricular (LV) mass for cardiovascular disease (CVD) events in older adults with and without metabolic syndrome (MetS) and diabetes mellitus (DM).

BACKGROUND: MetS and DM are associated with increased CVD risk, but it is unclear in these groups whether subclinical CVD as shown by increased LV mass improves risk prediction compared to standard risk factors in older individuals.

METHODS: We studied 3,724 adults (mean 72.4 {\textpm} 5.4 years of age, 61.0\% female, 4.4\% African-American) from the Cardiovascular Health Study who had MetS but not DM or had DM alone or had neither condition. Cox regression was used to examine the association of LV mass, (alone and indexed by height and body surface area [BSA]) as determined by echocardiography, with CVD events, including coronary heart disease (CHD), stroke, heart failure (HF), and CVD death, as well as total mortality. We also assessed the added prediction, discriminative value, and net reclassification improvement (NRI) for clinical utility of LV mass compared to standard risk factors.

RESULTS: Over a mean follow-up of 14.2 {\textpm} 6.3 years, 2,180 subjects experienced CVD events, including 986 CVD deaths. After adjustment for age, sex and standard risk factors, LV mass was positively associated with CVD events in those with MetS (hazard ratio [HR]: 1.4, p~< 0.001) and without MetS (HR: 1.4, p~< 0.001), but not DM (HR: 1.0, p~= 0.62), with similar findings for LV mass indexed for height or BSA. Adding LV mass to standard risk factors moderately improved the prediction accuracy in the overall sample and MetS group from changes in C-statistics (p~< 0.05). Categorical-free net reclassification improvement increased significantly by 17\% to 19\% in those with MetS. Findings were comparable for CHD, CVD mortality, and total mortality.

CONCLUSIONS: LV mass is associated with increased CVD risk and provides modest added prediction and clinical utility compared to standard risk factors in older persons with and without MetS but not with DM.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Comorbidity, Diabetes Mellitus, Female, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Logistic Models, Male, Metabolic Syndrome X, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1876-7591}, doi = {10.1016/j.jcmg.2015.04.019}, author = {Hoang, Khiet and Zhao, Yanglu and Gardin, Julius M and Carnethon, Mercedes and Mukamal, Ken and Yanez, David and Wong, Nathan D} } @article {6796, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {602-12}, abstract = {

BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.

STUDY DESIGN: Meta-analysis of cohort studies.

SETTING \& POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.

SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.

PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.

OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.

LIMITATIONS: AKI identified by diagnostic code.

CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

}, keywords = {Acute Kidney Injury, Adult, Aged, Comorbidity, Diabetes Mellitus, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.338}, author = {James, Matthew T and Grams, Morgan E and Woodward, Mark and Elley, C Raina and Green, Jamie A and Wheeler, David C and de Jong, Paul and Gansevoort, Ron T and Levey, Andrew S and Warnock, David G and Sarnak, Mark J} } @article {6876, title = {Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0132321}, abstract = {

BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.

METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.

RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.

CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

}, keywords = {Adult, Age Distribution, Aged, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, HDL, Cholesterol, LDL, Comorbidity, Continental Population Groups, Diabetes Mellitus, Dyslipidemias, Ethnic Groups, Female, Follow-Up Studies, Global Health, Humans, Hypertension, Incidence, Linear Models, Male, Middle Aged, Myocardial Infarction, Prevalence, Proportional Hazards Models, Risk Factors, Smoking, Stroke}, issn = {1932-6203}, doi = {10.1371/journal.pone.0132321}, author = {Gijsberts, Crystel M and Groenewegen, Karlijn A and Hoefer, Imo E and Eijkemans, Marinus J C and Asselbergs, Folkert W and Anderson, Todd J and Britton, Annie R and Dekker, Jacqueline M and Engstr{\"o}m, Gunnar and Evans, Greg W and de Graaf, Jacqueline and Grobbee, Diederick E and Hedblad, Bo and Holewijn, Suzanne and Ikeda, Ai and Kitagawa, Kazuo and Kitamura, Akihiko and de Kleijn, Dominique P V and Lonn, Eva M and Lorenz, Matthias W and Mathiesen, Ellisiv B and Nijpels, Giel and Okazaki, Shuhei and O{\textquoteright}Leary, Daniel H and Pasterkamp, Gerard and Peters, Sanne A E and Polak, Joseph F and Price, Jacqueline F and Robertson, Christine and Rembold, Christopher M and Rosvall, Maria and Rundek, Tatjana and Salonen, Jukka T and Sitzer, Matthias and Stehouwer, Coen D A and Bots, Michiel L and den Ruijter, Hester M} }