@article {686, title = {Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Apr 22}, pages = {893-900}, abstract = {

BACKGROUND: Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis.

METHODS: The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater.

RESULTS: Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95\% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased.

CONCLUSIONS: A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Continental Population Groups, Female, Humans, Male, Middle Aged, Obesity, Predictive Value of Tests, Residence Characteristics, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Snoring}, issn = {0003-9926}, doi = {10.1001/archinte.162.8.893}, author = {Young, Terry and Shahar, Eyal and Nieto, F Javier and Redline, Susan and Newman, Anne B and Gottlieb, Daniel J and Walsleben, Joyce A and Finn, Laurel and Enright, Paul and Samet, Jonathan M} } @article {682, title = {Racial differences in coronary artery calcification in older adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Mar 01}, pages = {424-30}, abstract = {

Reports on race-related differences in coronary artery calcium (CAC) are just beginning to emerge and have not been well studied in the elderly. This study was undertaken to assess whether such differences exist and the relationship between CAC and cardiovascular risk factors in a cohort of elderly community-dwelling adults. CAC was measured by using electron-beam tomography in 614 adults (aged 67 to 99 years), of whom 59\% were women and 23\% were black. The median CAC score was lower in blacks than in whites for men (159 versus 787, respectively; P<0.001) and for women (134 versus 233, respectively; P=0.02) after adjustment for age, cardiovascular disease, and risk factors for cardiovascular disease, although this difference was stronger and remained significant among men only. Lower CAC scores were also observed in the subgroup of blacks with a history of myocardial infarction. The lower CAC scores in blacks compared with whites observed in this study is consistent with either a lower prevalence of coronary artery disease or a lower extent of calcification of coronary artery disease.

}, keywords = {Age Factors, Aged, Calcinosis, Cohort Studies, Coronary Artery Disease, Female, Humans, Logistic Models, Male, Risk Factors, Sex Factors, Tomography, X-Ray Computed}, issn = {1524-4636}, doi = {10.1161/hq0302.105357}, author = {Newman, Anne B and Naydeck, Barbara L and Whittle, Jeff and Sutton-Tyrrell, Kim and Edmundowicz, Daniel and Kuller, Lewis H} } @article {688, title = {The relationship between chronically disrupted sleep and healthcare use.}, journal = {Sleep}, volume = {25}, year = {2002}, month = {2002 May 01}, pages = {289-96}, abstract = {

STUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population.

DESIGN: Cross-sectional study.

SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies.

INTERVENTIONS: N/A.

MEASUREMENTS: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90\% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data.

RESULTS: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6\%-9\% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18\% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS.

CONCLUSIONS: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.

}, keywords = {Adult, Chronic Disease, Cohort Studies, Community Health Services, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Health Status, Humans, Male, Middle Aged, Patient Acceptance of Health Care, Polysomnography, Prevalence, Severity of Illness Index, Sleep Apnea, Obstructive, Sleep Deprivation}, issn = {0161-8105}, author = {Kapur, Vishesh K and Redline, Susan and Nieto, F Javier and Young, Terry B and Newman, Anne B and Henderson, Jeffrey A} } @article {704, title = {Relationship between coronary artery calcification and other measures of subclinical cardiovascular disease in older adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Oct 01}, pages = {1674-9}, abstract = {

BACKGROUND: In the Cardiovascular Health Study, subclinical cardiovascular disease (CVD) predicted CVD events in older adults. The extent to which this measure or its components reflect calcified coronary disease is unknown.

METHODS AND RESULTS: Coronary artery calcium (CAC) was assessed with electron beam tomography in 414 participants without clinical CVD and examined using cut points (CAC> or =400 and CAC> or =800) and the log(CAC); 274 had subclinical CVD by ankle-arm index, ECG, or carotid ultrasound. Cut points for subclinical disease as previously defined in the Cardiovascular Health Study were examined as well as continuous measures to produce receiver operating characteristic curve curves. A low ankle-arm index was highly specific for a high CAC score. The internal carotid artery intima-media thickness was most strongly correlated with CAC (r=0.30) and was significantly related to both CAC cut points and to the log(CAC) score independently of all other measures.

CONCLUSIONS: In these community-dwelling older adults without clinical CVD, internal carotid artery intima-media thickness was most closely related to CAC. However, 17.5\% of those with a CAC> or =400 would be missed in the ascertainment of subclinical atherosclerosis using the previously published composite of subclinical atherosclerosis. Prospective follow-up will determine whether the CAC score improves prediction of CVD events over other noninvasive measures.

}, keywords = {Aged, Aged, 80 and over, Calcinosis, Cardiovascular Diseases, Carotid Stenosis, Cohort Studies, Coronary Artery Disease, Demography, Female, Humans, Male, Prevalence, Risk Factors, Sensitivity and Specificity, Sex Factors, Tomography, X-Ray Computed, Tunica Intima, Tunica Media}, issn = {1524-4636}, doi = {10.1161/01.atv.0000033540.89672.24}, author = {Newman, Anne B and Naydeck, Barbara L and Sutton-Tyrrell, Kim and Edmundowicz, Daniel and O{\textquoteright}Leary, Daniel and Kronmal, Richard and Burke, Gregory L and Kuller, Lewis H} } @article {725, title = {The 6-min walk test: a quick measure of functional status in elderly adults.}, journal = {Chest}, volume = {123}, year = {2003}, month = {2003 Feb}, pages = {387-98}, abstract = {

OBJECTIVES: To determine the correlates of the total 6-min walk distance (6MWD) in a population sample of adults > or = 68 years old.

METHODS: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular Health Study cohort during their seventh annual examination.

RESULTS: Of the 3,333 participants with a clinic visit, 2,281 subjects (68\%) performed the 6MWT. There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general correlates of a shorter 6MWD in linear regression models in women and men included the following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression, and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV(1) in women; and the use of digitalis in men. Approximately 30\% of the variance in 6MWD was explained by the linear regression models. Newly described bivariate associations of a shorter 6MWD included impaired activities of daily living; self-reported poor health; less education; nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes; and higher levels of C-reactive protein, fibrinogen, or WBC count.

CONCLUSIONS: Most community-dwelling elderly persons can quickly and safely perform this functional status test in the outpatient clinic setting. The test may be used clinically to measure the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis, diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older adults. Expected values should be adjusted for the patient{\textquoteright}s age, gender, height, and weight.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Exercise Test, Female, Humans, Ischemic Attack, Transient, Linear Models, Male, Mass Screening, Sensitivity and Specificity, Stroke, United States, Walking}, issn = {0012-3692}, doi = {10.1378/chest.123.2.387}, author = {Enright, Paul L and McBurnie, Mary Ann and Bittner, Vera and Tracy, Russell P and McNamara, Robert and Arnold, Alice and Newman, Anne B} } @article {715, title = {Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease.}, journal = {Am J Respir Crit Care Med}, volume = {167}, year = {2003}, month = {2003 Jan 01}, pages = {7-14}, abstract = {

Neither the association between obstructive airways disease (OAD) and sleep apnea-hypopnea (SAH) nor the sleep consequences of each disorder alone and together have been characterized in an adult community setting. Our primary aims were (1) to determine if there is an association between OAD and SAH and (2) identify predictors of oxyhemoglobin desaturation during sleep in persons having OAD with and without SAH. Polysomnography and spirometry results from 5,954 participants in the Sleep Heart Health Study were analyzed. OAD was defined by a FEV1/FVC value less than 70\%. Assessment of SAH prevalence in OAD was performed using thresholds of respiratory disturbance index (RDI) greater than 10 and greater than 15. A total of 1,132 participants had OAD that was predominantly mild (FEV1/FVC 63.81 +/- 6.56\%, mean +/- SD). SAH was not more prevalent in participants with OAD than in those without OAD (22.32 versus 28.86\%, with and without OAD, respectively, at RDI threshold values greater than 10; and 13.97 versus 18.63\%, with and without OAD, respectively, at RDI threshold value greater than 15). In the absence of SAH, the adjusted odds ratio for sleep desaturation (> 5\% total sleep time with saturation < 90\%) was greater than 1.9 when FEV1/FVC was less than 65\%. Participants with both OAD and SAH had greater sleep perturbation and desaturation than those with one disorder. Generally mild OAD alone was associated with minimally altered sleep quality. We conclude that (1) there is no association between generally mild OAD and SAH; (2) exclusive of SAH and after adjusting for demographic factors and awake oxyhemoglobin saturation, an FEV1/FVC value less than 65\% is associated with increased risk of sleep desaturation; (3) desaturation is greater in persons with both OAD and SAH compared with each of these alone; and (4) individuals with generally mild OAD and without SAH in the community have minimally perturbed sleep.

}, keywords = {Aged, Cohort Studies, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Oxyhemoglobins, Polysomnography, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Sleep, Sleep Apnea, Obstructive, Spirometry, Vital Capacity}, issn = {1073-449X}, doi = {10.1164/rccm.2203046}, author = {Sanders, Mark H and Newman, Anne B and Haggerty, Catherine L and Redline, Susan and Lebowitz, Michael and Samet, Jonathan and O{\textquoteright}Connor, George T and Punjabi, Naresh M and Shahar, Eyal} } @article {776, title = {Sleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study.}, journal = {Sleep}, volume = {27}, year = {2004}, month = {2004 Mar 15}, pages = {293-8}, abstract = {

STUDY OBJECTIVES: To describe the distribution of nocturnal sleep characteristics and reports of daytime sleepiness in a large well-defined group of healthy adults.

DESIGN: The Sleep Heart Health Study is a multicenter study examining sleep and cardiopulmonary parameters through nocturnal polysomnography in adults enrolled in geographically distinct cardiovascular cohorts.

SETTING: Community setting.

PARTICIPANTS: 470 subjects enrolled in the Sleep Heart Health Study (n = 6440) were selected as a {\textquoteright}normative{\textquoteright} group based on screening of health conditions and daily habits that could interfere with sleep.

MEASUREMENTS AND RESULTS: Home-based nocturnal polysomnography was obtained on all participants and centrally scored for sleep and respiratory parameters. Demographic and health-related data were obtained and updated at the time of the home visit. Sleep efficiency decreased by 1.6\% for each 10 years of increased age. Sleep time decreased by 0.1 hours (6.0 minutes) for each 10-year age increase and was longer in women. The arousal index increased by 0.8 for each 10-year increase in age and was lower by 1.4 in women. Women had a lower mean percentage of stage 1 and stage 2 sleep. Mean percentage of slow-wave sleep was higher in women (by 6.7\%). Percentage of slow-wave sleep decreased with increased age for men only (by 1.9\% for each 10-year age change).

CONCLUSIONS: Data suggest a clear lessening in the quantity and quality of sleep with age that appears to be more rapid in males compared to females.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Circadian Rhythm, Cohort Studies, Disorders of Excessive Somnolence, Female, Health Status, Humans, Male, Middle Aged, Polysomnography, Sleep, Sleep Stages, Surveys and Questionnaires}, issn = {0161-8105}, doi = {10.1093/sleep/27.2.293}, author = {Walsleben, Joyce A and Kapur, Vishesh K and Newman, Anne B and Shahar, Eyal and Bootzin, Richard R and Rosenberg, Carl E and O{\textquoteright}Connor, George and Nieto, F Javier} } @article {842, title = {Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.}, journal = {Atherosclerosis}, volume = {181}, year = {2005}, month = {2005 Jul}, pages = {175-83}, abstract = {

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

}, keywords = {Aged, Aging, Carboxypeptidase B2, Cause of Death, Cohort Studies, Female, Genotype, Health Status, Humans, Inflammation, Longevity, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Polymorphism, Genetic, Promoter Regions, Genetic, Prospective Studies, Risk Factors, Thrombosis}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2005.01.028}, author = {Reiner, Alexander P and Diehr, Paula and Browner, Warren S and Humphries, Stephen E and Jenny, Nancy S and Cushman, Mary and Tracy, Russell P and Walston, Jeremy and Lumley, Thomas and Newman, Anne B and Kuller, Lewis H and Psaty, Bruce M} } @article {873, title = {Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Dec 12-26}, pages = {2666-70}, abstract = {

BACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined.

METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR).

RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43\% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21\% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95\% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses.

CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.

}, keywords = {Aged, Cohort Studies, Cystatin C, Cystatins, Female, Health Surveys, Humans, Longitudinal Studies, Male, Peripheral Vascular Diseases, Predictive Value of Tests, Risk Factors, ROC Curve, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.22.2666}, author = {O{\textquoteright}Hare, Ann M and Newman, Anne B and Katz, Ronit and Fried, Linda F and Stehman-Breen, Catherine O and Seliger, Stephen L and Siscovick, David S and Shlipak, Michael G} } @article {852, title = {Dementia and Alzheimer{\textquoteright}s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Jul}, pages = {1101-7}, abstract = {

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

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. communities.

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Dementia, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Peripheral Vascular Diseases, Risk Factors}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53360.x}, author = {Newman, Anne B and Fitzpatrick, Annette L and Lopez, Oscar and Jackson, Sharon and Lyketsos, Constantine and Jagust, William and Ives, Diane and DeKosky, Steven T and Kuller, Lewis H} } @article {865, title = {Kidney function as a predictor of noncardiovascular mortality.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3728-35}, abstract = {

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95\% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Cohort Studies, Confidence Intervals, Creatinine, Cystatin C, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Longitudinal Studies, Male, Probability, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Survival Analysis, United States}, issn = {1046-6673}, doi = {10.1681/ASN.2005040384}, author = {Fried, Linda F and Katz, Ronit and Sarnak, Mark J and Shlipak, Michael G and Chaves, Paulo H M and Jenny, Nancy Swords and Stehman-Breen, Catherine and Gillen, Dan and Bleyer, Anthony J and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {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 {846, title = {Statin use and the risk of incident dementia: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {62}, year = {2005}, month = {2005 Jul}, pages = {1047-51}, abstract = {

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia.

OBJECTIVE: To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs).

DESIGN: Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 participants free of dementia at baseline.

MAIN OUTCOME MEASURES: Using Cox proportional hazards regression analysis, we estimated the risk of incident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses included the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach.

RESULTS: Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95\% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95\% CI, 0.76-1.91), mixed Alzheimer disease and vascular dementia (HR, 0.87; 95\% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95\% CI, 0.61-3.06). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95\% CI, 0.46-1.02) for all-cause dementia and 0.56 (95\% CI, 0.35-0.92) for any Alzheimer disease.

CONCLUSIONS: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Dementia, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipidemias, Male}, issn = {0003-9942}, doi = {10.1001/archneur.62.7.1047}, author = {Rea, Thomas D and Breitner, John C and Psaty, Bruce M and Fitzpatrick, Annette L and Lopez, Oscar L and Newman, Anne B and Hazzard, William R and Zandi, Peter P and Burke, Gregory L and Lyketsos, Constantine G and Bernick, Charles and Kuller, Lewis H} } @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 {866, title = {Quantitative measures of gait characteristics indicate prevalence of underlying subclinical structural brain abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {26}, year = {2006}, month = {2006}, pages = {52-60}, abstract = {

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

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Dementia, Female, Gait, Gait Disorders, Neurologic, Humans, Hypertension, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Stroke, United States}, issn = {0251-5350}, doi = {10.1159/000089240}, author = {Rosano, Caterina and Brach, Jennifer and Longstreth, William T and Newman, Anne B} } @article {987, title = {Gait variability and the risk of incident mobility disability in community-dwelling older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Sep}, pages = {983-8}, abstract = {

BACKGROUND: Gait speed is a strong predictor of incident walking disability. The objective was to determine if gait variability adds to the prediction of incident mobility disability independent of gait speed.

METHODS: Participants included 379 older adults (mean age = 79 years; 78\% Caucasian, and 40\% men) in the Cardiovascular Health Study at the Pittsburgh site. All could ambulate independently and reported no difficulty walking a half mile. Gait characteristics were determined from a 4-meter computerized walkway. For each gait parameter, variability was defined as the standard deviation from the individual steps from two passes. Incident walking disability was obtained by phone interview every 6 months for 54 months and was defined as new difficulty walking a half mile or inability to walk a half mile.

RESULTS: Of the 379 participants, 222 (58.6\%) developed incident mobility disability. In unadjusted Cox proportional hazards models gait speed, mean step length, mean stance time, and stance time variability were associated with incident mobility disability. After adjusting for gait speed, demographics, chronic conditions, prescription medications, health status, and physical activity level, only stance time variability remained an important indicator of disability. In the adjusted model, an increase in stance time variability of 0.01 seconds was associated with a 13\% higher incidence of mobility disability (hazard ratio 1.13, 95\% confidence interval, 1.01-1.27).

CONCLUSIONS: Stance time variability is an independent predictor of future mobility disability. Future efforts are needed to determine whether interventions that decrease stance time variability will also delay mobility disability.

}, keywords = {Aged, Aged, 80 and over, Aging, Cohort Studies, Female, Gait, Gait Disorders, Neurologic, Humans, Male, Mobility Limitation, Prospective Studies, Risk Factors, Walking}, issn = {1079-5006}, doi = {10.1093/gerona/62.9.983}, author = {Brach, Jennifer S and Studenski, Stephanie A and Perera, Subashan and VanSwearingen, Jessie M and Newman, Anne B} } @article {972, title = {Relationship of uric acid with progression of kidney disease.}, journal = {Am J Kidney Dis}, volume = {50}, year = {2007}, month = {2007 Aug}, pages = {239-47}, abstract = {

BACKGROUND: Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 5,808 participants of the Cardiovascular Health Study.

PREDICTOR: Uric acid levels.

OUTCOMES \& MEASUREMENTS: Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m(2) per year or greater (>or=0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation.

RESULTS: Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m(2) (<1.00 mL/s) of 7\%, 14\%, 12\%, 25\%, and 42\% for quintiles 1 (6.90 mg/dL [>410 micromol/L]), respectively. In comparison, there was only a modest, but significant, association between quintiles of uric acid levels and progression of kidney function decrease, with adjusted odds ratios of 1.0, 0.88 (95\% confidence interval [CI], 0.64 to 1.21), 1.23 (95\% CI, 0.87 to 1.75), 1.47 (95\% CI, 1.04 to 2.07), and 1.49 (95\% CI, 1.00 to 2.22) for quintiles 1 through 5, respectively. No significant association was found between uric acid level and incident CKD (adjusted odds ratio, 1.00; 95\% CI, 0.89 to 1.14).

LIMITATIONS: Measurements of albuminuria were not available.

CONCLUSIONS: Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Cross-Sectional Studies, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Prospective Studies, Uric Acid}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2007.05.013}, author = {Chonchol, Michel and Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Newman, Anne B and Siscovick, David S and Kestenbaum, Bryan and Carney, Jan Kirk and Fried, Linda F} } @article {1049, title = {Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Sep}, pages = {1618-25}, abstract = {

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

DESIGN: Observational cohort study.

SETTING: Community.

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

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

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

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

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Brain Diseases, Cause of Death, Cohort Studies, Disability Evaluation, Discrimination Learning, Female, Gait, Humans, Male, Memory, Short-Term, Mobility Limitation, Neuropsychological Tests, Pattern Recognition, Visual, Psychometrics, Psychomotor Performance, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01856.x}, author = {Rosano, Caterina and Newman, Anne B and Katz, Ronit and Hirsch, Calvin H and Kuller, Lewis H} } @article {986, title = {Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {197}, year = {2008}, month = {2008 Apr}, pages = {922-30}, abstract = {

Common polymorphisms in the CRP gene are associated with plasma CRP levels in population-based studies, but associations with age-related events are uncertain. A previous study of CRP haplotypes in older adults was broadened to include longevity and cause-specific mortality (all-cause, noncardiovascular (non-CV), and cardiovascular (CV)). Common haplotypes were inferred from four tagSNPs in 4512 whites and five tagSNPs in 812 blacks from the Cardiovascular Health Study, a longitudinal cohort of adults over age 65. Exploratory analyses addressed early versus late mortality. CRP haplotypes were not associated with all-cause mortality or longevity overall in either population, but associations with all-cause mortality differed during early and late periods. In blacks, the haplotype tagged by 3872A (rs1205) was associated with increased risk of non-CV mortality, relative to other haplotypes (adjusted hazard ratio for each additional copy: 1.42, 95\% CI: 1.07, 1.87). Relative to other haplotypes, this haplotype was associated with decreased risk of early but not decreased risk of late CV mortality in blacks; among whites, a haplotype tagged by 2667C (rs1800947) gave similar but nonsignificant findings. If confirmed, CRP genetic variants may be weakly associated with CV and non-CV mortality in older adults, particularly in self-identified blacks.

}, keywords = {African Americans, Aged, C-Reactive Protein, Cardiovascular Diseases, Cause of Death, Cohort Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Linear Models, Longevity, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2007.08.012}, author = {Hindorff, Lucia A and Rice, Kenneth M and Lange, Leslie A and Diehr, Paula and Halder, Indrani and Walston, Jeremy and Kwok, Pui and Ziv, Elad and Nievergelt, Caroline and Cummings, Steven R and Newman, Anne B and Tracy, Russell P and Psaty, Bruce M and Reiner, Alexander P} } @article {1009, title = {Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study.}, journal = {Arch Neurol}, volume = {65}, year = {2008}, month = {2008 Jan}, pages = {89-93}, abstract = {

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

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

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

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

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

}, keywords = {African Americans, Age Factors, Aged, Alzheimer Disease, Apolipoprotein E4, Cognition, Cohort Studies, Confidence Intervals, Dementia, Vascular, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Genotype, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors}, issn = {0003-9942}, doi = {10.1001/archneurol.2007.29}, author = {Irie, Fumiko and Fitzpatrick, Annette L and Lopez, Oscar L and Kuller, Lewis H and Peila, Rita and Newman, Anne B and Launer, Lenore J} } @article {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 {991, title = {Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults.}, journal = {Growth Horm IGF Res}, volume = {18}, year = {2008}, month = {2008 Apr}, pages = {166-73}, abstract = {

Increasing evidence suggests that the insulin-like growth factor (IGF)-axis may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women > or = 65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95\% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95\% CI: 0.26, 0.64; p-trend: <0.01) for IFG. We did not find any significant association between IGF-I and glucose intolerance in this study and the association for IGFBP-3 was less clear. However, low levels of IGF-I and IGFBP-3 were associated with increased levels of markers of inflammation including C-reactive protein and interleukin-6 levels. We conclude that among adults > or = 65 years, low IGFBP-1 levels are associated with increased prevalence of glucose intolerance. We did not confirm prior associations of low IGF-I with glucose intolerance in this cohort of older individuals.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Cross-Sectional Studies, Female, Glucose Intolerance, Humans, Inflammation, Insulin-Like Growth Factor Binding Proteins, Male, Signal Transduction, Somatomedins}, issn = {1096-6374}, doi = {10.1016/j.ghir.2007.08.004}, author = {Rajpathak, Swapnil N and McGinn, Aileen P and Strickler, Howard D and Rohan, Thomas E and Pollak, Michael and Cappola, Anne R and Kuller, Lewis and Xue, XiaoNan and Newman, Anne B and Strotmeyer, Elsa S and Psaty, Bruce M and Kaplan, Robert C} } @article {1018, title = {Sleep-disordered breathing and cardiovascular disease: an outcome-based definition of hypopneas.}, journal = {Am J Respir Crit Care Med}, volume = {177}, year = {2008}, month = {2008 May 15}, pages = {1150-5}, abstract = {

RATIONALE: Epidemiologic studies on the consequences of sleep-disordered breathing invariably use the apnea-hypopnea index as the primary measure of disease severity. Although hypopneas constitute a majority of disordered breathing events, significant controversy remains about the best criteria used to define these events.

OBJECTIVES: The current investigation sought to assess the most appropriate definition for hypopneas that would be best correlated with cardiovascular disease.

METHODS: A community sample of middle-aged and older adults was recruited as part of the Sleep Heart Health Study. Full-montage polysomnography was conducted and hypopneas were defined using different thresholds of oxyhemoglobin desaturation with and without arousals. Prevalent cardiovascular disease was assessed based on self-report. Logistic regression analysis was used to characterize the independent association between the hypopnea index and prevalent cardiovascular disease.

MEASUREMENTS AND MAIN RESULTS: Using a sample of 6,106 adults with complete data on cardiovascular disease status and polysomnography, the current study found that hypopneas associated with an oxyhemoglobin desaturation of 4\% or more were associated with prevalent cardiovascular disease independent of confounding covariates. The adjusted prevalent odds ratios for quartiles of the hypopnea index using a 4\% desaturation criterion were as follows: 1.00 (<1.10 events/h), 1.10 (1.01-3.20 events/h), 1.33 (3.21-7.69 events/h), and 1.41 (>7.69 events/h). Hypopnea measures based on less than 4\% oxyhemoglobin desaturation or presence of arousals showed no association with cardiovascular disease.

CONCLUSIONS: Hypopneas comprise a significant component of sleep-disordered breathing in the general community. By varying the criteria for defining hypopneas, this study demonstrates that hypopneas with a desaturation of at least 4\% are independently associated with cardiovascular disease. In contrast, no association was observed between cardiovascular disease and hypopneas associated with milder desaturations or arousals.

}, keywords = {Aged, Apnea, Cardiovascular Diseases, Cohort Studies, Female, Humans, Male, Middle Aged, Odds Ratio, Oxyhemoglobins, Polysomnography, Sleep Apnea Syndromes, Terminology as Topic}, issn = {1535-4970}, doi = {10.1164/rccm.200712-1884OC}, author = {Punjabi, Naresh M and Newman, Anne B and Young, Terry B and Resnick, Helaine E and Sanders, Mark H} } @article {1053, title = {Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The Cardiovascular Health study.}, journal = {J Am Coll Cardiol}, volume = {52}, year = {2008}, month = {2008 Sep 30}, pages = {1152-9}, abstract = {

OBJECTIVES: The goal of this study was to determine whether subclinical thyroid dysfunction was associated with incident heart failure (HF) and echocardiogram abnormalities.

BACKGROUND: Subclinical hypothyroidism and hyperthyroidism have been associated with cardiac dysfunction. However, long-term data on the risk of HF are limited.

METHODS: We studied 3,044 adults>or=65 years of age who initially were free of HF in the Cardiovascular Health Study. We compared adjudicated HF events over a mean 12-year follow-up and changes in cardiac function over the course of 5 years among euthyroid participants, those with subclinical hypothyroidism (subdivided by thyroid-stimulating hormone [TSH] levels: 4.5 to 9.9, >or=10.0 mU/l), and those with subclinical hyperthyroidism.

RESULTS: Over the course of 12 years, 736 participants developed HF events. Participants with TSH>or=10.0 mU/l had a greater incidence of HF compared with euthyroid participants (41.7 vs. 22.9 per 1,000 person years, p=0.01; adjusted hazard ratio: 1.88; 95\% confidence interval: 1.05 to 3.34). Baseline peak E velocity, which is an echocardiographic measurement of diastolic function associated with incident HF in the CHS cohort, was greater in those patients with TSH>or=10.0 mU/l compared with euthyroid participants (0.80 m/s vs. 0.72 m/s, p=0.002). Over the course of 5 years, left ventricular mass increased among those with TSH>or=10.0 mU/l, but other echocardiographic measurements were unchanged. Those patients with TSH 4.5 to 9.9 mU/l or with subclinical hyperthyroidism had no increase in risk of HF.

CONCLUSIONS: Compared with euthyroid older adults, those adults with TSH>or=10.0 mU/l have a moderately increased risk of HF and alterations in cardiac function but not older adults with TSH<10.0 mU/l. Clinical trials should assess whether the risk of HF might be ameliorated by thyroxine replacement in individuals with TSH>or=10.0 mU/l.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Echocardiography, Female, Heart, Heart Failure, Heart Function Tests, Humans, Hyperthyroidism, Hypertrophy, Left Ventricular, Hypothyroidism, Male, Risk Factors, Time Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2008.07.009}, author = {Rodondi, Nicolas and Bauer, Douglas C and Cappola, Anne R and Cornuz, Jacques and Robbins, John and Fried, Linda P and Ladenson, Paul W and Vittinghoff, Eric and Gottdiener, John S and Newman, Anne B} } @article {1130, title = {Association of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {54}, year = {2009}, month = {2009 Sep 22}, pages = {1176-84}, abstract = {

OBJECTIVES: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.

BACKGROUND: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.

METHODS: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.

RESULTS: Among 4,513 participants, 23\% had CKD, 13\% had a low ABI, and 3\% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95\% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95\% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.

CONCLUSIONS: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.

}, keywords = {Aged, Aged, 80 and over, Ankle Brachial Index, C-Reactive Protein, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Lipids, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2009.06.017}, author = {Ix, Joachim H and Katz, Ronit and de Boer, Ian H and Kestenbaum, Brian R and Allison, Matthew A and Siscovick, David S and Newman, Anne B and Sarnak, Mark J and Shlipak, Michael G and Criqui, Michael H} } @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 {1103, title = {Sleep-disordered breathing and frailty in the Cardiovascular Health Study Cohort.}, journal = {Am J Epidemiol}, volume = {170}, year = {2009}, month = {2009 Jul 15}, pages = {193-202}, abstract = {

Sleep-disordered breathing (SDB) is associated with pathophysiology that may influence the development and progression of frailty. Using data collected in 1995-1996, the authors explored the relation between SDB and components of frailty among 1,042 participants of the Cardiovascular Health Study. Diagnosis of SDB was based on the results of overnight polysomnography, and severe SDB was defined as an apnea-hypopnea index of >30 per hour of sleep. Slow walking speed, low grip strength, exhaustion, low physical activity, and unexplained weight loss were referred to as frailty indicator variables. There were 584 (56\%) female and 458 (44\%) male participants, and the mean age was 77 (standard deviation, 4) years. There was independent association between severe SDB and 1 or more frailty indicator variables (adjusted odds ratio = 4.85, 95\% confidence interval: 1.40, 16.78), slow walking speed (adjusted odds ratio = 2.67, 95\% confidence interval: 1.04, 6.84), and low grip strength (adjusted odds ratio = 3.29, 95\% confidence interval: 1.36, 7.96) among female study participants. The finding of an independent association between SDB and frailty indicator variables among older women could have important implications in interventions aimed at preventing or delaying the progression of frailty.

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Cardiovascular System, Cohort Studies, Confidence Intervals, Exercise Tolerance, Female, Frail Elderly, Hand Strength, Humans, Logistic Models, Male, Mobility Limitation, Models, Statistical, Motor Activity, Muscle Strength, Odds Ratio, Polysomnography, Psychometrics, Risk Factors, Sleep Apnea, Obstructive, Weight Loss}, issn = {1476-6256}, doi = {10.1093/aje/kwp108}, author = {Endeshaw, Yohannes W and Unruh, Mark L and Kutner, Michael and Newman, Anne B and Bliwise, Donald L} } @article {1124, title = {Total and cause-specific mortality in the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Dec}, pages = {1251-61}, abstract = {

BACKGROUND: Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.

METHODS: A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.

RESULTS: Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E epsilon4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.

CONCLUSIONS: In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cause of Death, Chronic Disease, Cohort Studies, Female, Geriatric Assessment, Health Surveys, Humans, Kaplan-Meier Estimate, Male, Probability, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp127}, author = {Newman, Anne B and Sachs, Michael C and Arnold, Alice M and Fried, Linda P and Kronmal, Richard and Cushman, Mary and Psaty, Bruce M and Harris, Tamara B and Robbins, John A and Burke, Gregory L and Kuller, Lewis H and Lumley, Thomas} } @article {1123, title = {Trajectories of dehydroepiandrosterone sulfate predict mortality in older adults: the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {64}, year = {2009}, month = {2009 Dec}, pages = {1268-74}, abstract = {

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) has been proposed as an antiaging hormone, but its importance is unclear. Assessment of an individual{\textquoteright}s ability to maintain a DHEAS set point, through examination of multiple DHEAS levels over time, may provide insight into biologic aging.

METHODS: Using Cox proportional hazard models, we examined the relationship between DHEAS trajectory patterns and all-cause death in 950 individuals aged >or=65 years who were enrolled in the Cardiovascular Health Study and had DHEAS levels measured at three to six time points.

RESULTS: Overall, there was a slight decline in DHEAS levels over time (-0.013 microg/mL/y). Three trajectory components were examined: slope, variability, and baseline DHEAS. When examined individually, a steep decline or extreme variability in DHEAS levels was associated with higher mortality (p < .001 for each), whereas baseline DHEAS level was not. In adjusted models including all three components, steep decline (hazard ratio [HR] 1.75, confidence interval [CI] 1.32-2.33) and extreme variability (HR 1.89, CI 1.47-2.43) remained significant predictors of mortality, whereas baseline DHEAS level remained unpredictive of mortality (HR 0.97 per standard deviation, CI 0.88-1.07). The effect of trajectory pattern was more pronounced in men than in women. Individuals with both a steep decline and extreme variability in DHEAS levels had a significantly higher death rate than those with neither pattern (141 vs 48 deaths per 1,000 person-years, p < .001).

CONCLUSIONS: Our data show significant heterogeneity in the individual trajectories of DHEAS levels and suggest that these trajectories provide important biologic information about the rate of aging, whereas the DHEAS level itself does not.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Cardiovascular Diseases, Cause of Death, Cohort Studies, Dehydroepiandrosterone Sulfate, Female, Geriatric Assessment, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Sex Factors, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp129}, author = {Cappola, Anne R and O{\textquoteright}Meara, Ellen S and Guo, Wensheng and Bartz, Traci M and Fried, Linda P and Newman, Anne B} } @article {1190, title = {Association between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.}, journal = {Nephron Clin Pract}, volume = {115}, year = {2010}, month = {2010}, pages = {c114-21}, abstract = {

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

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

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

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

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Residence Characteristics}, issn = {1660-2110}, doi = {10.1159/000312874}, author = {Rifkin, Dena E and Katz, Ronit and Fried, Linda F and Kestenbaum, Bryan and Jenny, Nancy Swords and Newman, Anne B and Siscovick, David S and Shlipak, Michael G and Sarnak, Mark J} } @article {1214, title = {Change in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Nov}, pages = {1208-14}, abstract = {

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

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

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

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

}, keywords = {Adiponectin, Age Factors, Aged, Aging, Analysis of Variance, Cardiovascular Diseases, Cause of Death, Chi-Square Distribution, Cohort Studies, Cross-Sectional Studies, Female, Health Status, Humans, Linear Models, Male, Physical Fitness, Proportional Hazards Models, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glq122}, author = {Kizer, Jorge R and Arnold, Alice M and Strotmeyer, Elsa S and Ives, Diane G and Cushman, Mary and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Hirsch, Calvin H and Newman, Anne B} } @article {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 {1147, title = {CRP gene variation and risk of community-acquired pneumonia.}, journal = {Respirology}, volume = {15}, year = {2010}, month = {2010 Jan}, pages = {160-4}, abstract = {

BACKGROUND AND OBJECTIVE: CRP has several potentially antibacterial effects, and variation in the CRP gene is known to influence CRP levels. Whether this variation influences risk of infection, and hence whether CRP has anti-infective activity in humans, is uncertain.

METHODS: We evaluated a series of haplotype-tagging single nucleotide polymorphisms among 5374 individuals in the Cardiovascular Health Study, a cohort of older adults from four communities, who were followed for community-acquired pneumonia for 12-13 years. Secondarily, we evaluated whether these polymorphisms varied among men in the Health Professionals Follow-up Study who self-reported pneumonia on biennial questionnaires.

RESULTS: There were 581 (507 white and 74 black) Cardiovascular Health Study participants with incident hospitalizations for pneumonia. No single nucleotide polymorphism or haplotypes were associated with risk among white Cardiovascular Health Study participants. Among black participants, the haplotype tagged by A790T was associated with lower risk of incident pneumonia (hazard ratio 0.5; 95\% confidence interval: 0.3-0.9) and with higher CRP levels. In Health Professionals Follow-up Study, a separate haplotype was associated with less frequent self-reported pneumonia but not with circulating CRP levels.

CONCLUSIONS: Some genetic variants in CRP may be associated with risk of pneumonia, but haplotypes associated with risk are variably associated with baseline CRP levels. If CRP is a relevant component of innate immunity in humans, the inducibility or tissue-specificity of expression may be at least as important as chronic circulating levels.

}, keywords = {African Americans, Aged, Aged, 80 and over, Body Mass Index, C-Reactive Protein, Cohort Studies, Community-Acquired Infections, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Pneumonia, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Smoking}, issn = {1440-1843}, doi = {10.1111/j.1440-1843.2009.01661.x}, author = {Mukamal, Kenneth J and Pai, Jennifer K and O{\textquoteright}Meara, Ellen S and Tracy, Russell P and Psaty, Bruce M and Kuller, Lewis H and Newman, Anne B and Yende, Sachin and Curhan, Gary C and Siscovick, David S and Rimm, Eric B} } @article {1179, title = {A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 May}, pages = {478-87}, abstract = {

BACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity.

METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort.

RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage.

CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Alleles, Cohort Studies, Confidence Intervals, Female, Genome-Wide Association Study, Genotype, Humans, Longevity, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide}, issn = {1758-535X}, doi = {10.1093/gerona/glq028}, author = {Newman, Anne B and Walter, Stefan and Lunetta, Kathryn L and Garcia, Melissa E and Slagboom, P Eline and Christensen, Kaare and Arnold, Alice M and Aspelund, Thor and Aulchenko, Yurii S and Benjamin, Emelia J and Christiansen, Lene and D{\textquoteright}Agostino, Ralph B and Fitzpatrick, Annette L and Franceschini, Nora and Glazer, Nicole L and Gudnason, Vilmundur and Hofman, Albert and Kaplan, Robert and Karasik, David and Kelly-Hayes, Margaret and Kiel, Douglas P and Launer, Lenore J and Marciante, Kristin D and Massaro, Joseph M and Miljkovic, Iva and Nalls, Michael A and Hernandez, Dena and Psaty, Bruce M and Rivadeneira, Fernando and Rotter, Jerome and Seshadri, Sudha and Smith, Albert V and Taylor, Kent D and Tiemeier, Henning and Uh, Hae-Won and Uitterlinden, Andr{\'e} G and Vaupel, James W and Walston, Jeremy and Westendorp, Rudi G J and Harris, Tamara B and Lumley, Thomas and van Duijn, Cornelia M and Murabito, Joanne M} } @article {1219, title = {Physical activity and years of healthy life in older adults: results from the cardiovascular health study.}, journal = {J Aging Phys Act}, volume = {18}, year = {2010}, month = {2010 Jul}, pages = {313-34}, abstract = {

Little is known about how many years of life and disability-free years seniors can gain through exercise. Using data from the Cardiovascular Health Study, the authors estimated the extra years of life and self-reported healthy life (over 11 years) and years without impairment in activities of daily living (over 6 years) associated with quintiles of physical activity (PA) in older adults from different age groups. They estimated PA from the Minnesota Leisure Time Activities Questionnaire. Multivariable linear regression adjusted for health-related covariates. The relative gains in survival and years of healthy life (YHL) generally were proportionate to the amount of PA, greater among those 75+, and higher in men. Compared with being sedentary, the most active men 75+ had 1.49 more YHL (95\% CI: 0.79, 2.19), and the most active women 75+ had 1.06 more YHL (95\% CI: 0.44, 1.68). Seniors over age 74 experience the largest relative gains in survival and healthy life from physical activity.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Exercise, Female, Health Behavior, Health Status, Humans, Leisure Activities, Life Style, Male, Quality-Adjusted Life Years, Sex Factors}, issn = {1063-8652}, author = {Hirsch, Calvin H and Diehr, Paula and Newman, Anne B and Gerrior, Shirley A and Pratt, Charlotte and Lebowitz, Michael D and Jackson, Sharon A} } @article {1194, title = {Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {3}, year = {2010}, month = {2010 Jul}, pages = {495-502}, abstract = {

BACKGROUND: The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.

METHODS AND RESULTS: Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5\%) participants developed heart failure over 5 years versus 364 (6.8\%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2\% versus 2.8\%, 9.0\% versus 7.0\%, 15.9\% versus 13.7\%, and 24.6\% versus 30.8\% for the <5\%, 5\% to 10\%, 10\% to 20\%, and >20\% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95\% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5\% to 10\% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.

CONCLUSIONS: The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Confidence Intervals, Disease Progression, Echocardiography, Doppler, Female, Heart Failure, Humans, Incidence, Male, Models, Statistical, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Survival Analysis, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.109.904300}, author = {Kalogeropoulos, Andreas and Psaty, Bruce M and Vasan, Ramachandran S and Georgiopoulou, Vasiliki and Smith, Andrew L and Smith, Nicholas L and Kritchevsky, Stephen B and Wilson, Peter W F and Newman, Anne B and Harris, Tamara B and Butler, Javed} } @article {1230, title = {Chronic kidney disease and the risk of end-stage renal disease versus death.}, journal = {J Gen Intern Med}, volume = {26}, year = {2011}, month = {2011 Apr}, pages = {379-85}, abstract = {

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

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

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

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic, Longitudinal Studies, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Treatment Outcome}, issn = {1525-1497}, doi = {10.1007/s11606-010-1511-x}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and Shlipak, Michael G and Sarnak, Mark J and Stehman-Breen, Catherine and Seliger, Stephen and Siscovick, David and Newman, Anne B and Fried, Linda} } @article {1259, title = {Gait speed and survival in older adults.}, journal = {JAMA}, volume = {305}, year = {2011}, month = {2011 Jan 05}, pages = {50-8}, abstract = {

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates.

OBJECTIVE: To evaluate the relationship between gait speed and survival.

DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6\%, women; and 79.8\%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s.

MAIN OUTCOME MEASURES: Survival rates and life expectancy.

RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8\% (confidence interval [CI], 79.6\%-88.8\%) and 10-year survival rate was 59.7\% (95\% CI, 46.5\%-70.6\%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95\% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19\% to 87\% in men and from 35\% to 91\% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization.

CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

}, keywords = {Aged, Cohort Studies, Female, Gait, Geriatric Assessment, Humans, Life Expectancy, Male, Survival Analysis, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1923}, author = {Studenski, Stephanie and Perera, Subashan and Patel, Kushang and Rosano, Caterina and Faulkner, Kimberly and Inzitari, Marco and Brach, Jennifer and Chandler, Julie and Cawthon, Peggy and Connor, Elizabeth Barrett and Nevitt, Michael and Visser, Marjolein and Kritchevsky, Stephen and Badinelli, Stefania and Harris, Tamara and Newman, Anne B and Cauley, Jane and Ferrucci, Luigi and Guralnik, Jack} } @article {1263, title = {Health and function of participants in the Long Life Family Study: A comparison with other cohorts.}, journal = {Aging (Albany NY)}, volume = {3}, year = {2011}, month = {2011 Jan}, pages = {63-76}, abstract = {

Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts. Pulse pressure and triglycerides were lower, high density lipids were higher, and a perceptual speed task and gait speed were better in LLFS. Age-specific comparisons showed differences that would be consistent with a higher peak, later onset of decline or slower rate of change across age in LLFS participants. These findings suggest several priority phenotypes for inclusion in future genetic analysis to identify loci contributing to exceptional survival.

}, keywords = {Aged, Aged, 80 and over, Aging, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Female, Gait, Humans, Longevity, Male, Middle Aged, Psychomotor Performance, Research Design}, issn = {1945-4589}, doi = {10.18632/aging.100242}, author = {Newman, Anne B and Glynn, Nancy W and Taylor, Christopher A and Sebastiani, Paola and Perls, Thomas T and Mayeux, Richard and Christensen, Kaare and Zmuda, Joseph M and Barral, Sandra and Lee, Joseph H and Simonsick, Eleanor M and Walston, Jeremy D and Yashin, Anatoli I and Hadley, Evan} } @article {1323, title = {Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque.}, journal = {Nat Genet}, volume = {43}, year = {2011}, month = {2011 Sep 11}, pages = {940-7}, abstract = {

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 {\texttimes} 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

}, keywords = {Adult, Aged, Aging, Atherosclerosis, Carotid Intima-Media Thickness, Cohort Studies, Coronary Artery Disease, European Continental Ancestry Group, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Heart, Humans, Middle Aged, Phenotype, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1546-1718}, doi = {10.1038/ng.920}, author = {Bis, Joshua C and Kavousi, Maryam and Franceschini, Nora and Isaacs, Aaron and Abecasis, Goncalo R and Schminke, Ulf and Post, Wendy S and Smith, Albert V and Cupples, L Adrienne and Markus, Hugh S and Schmidt, Reinhold and Huffman, Jennifer E and Lehtim{\"a}ki, Terho and Baumert, Jens and M{\"u}nzel, Thomas and Heckbert, Susan R and Dehghan, Abbas and North, Kari and Oostra, Ben and Bevan, Steve and Stoegerer, Eva-Maria and Hayward, Caroline and Raitakari, Olli and Meisinger, Christa and Schillert, Arne and Sanna, Serena and V{\"o}lzke, Henry and Cheng, Yu-Ching and Thorsson, Bolli and Fox, Caroline S and Rice, Kenneth and Rivadeneira, Fernando and Nambi, Vijay and Halperin, Eran and Petrovic, Katja E and Peltonen, Leena and Wichmann, H Erich and Schnabel, Renate B and D{\"o}rr, Marcus and Parsa, Afshin and Aspelund, Thor and Demissie, Serkalem and Kathiresan, Sekar and Reilly, Muredach P and Taylor, Kent and Uitterlinden, Andre and Couper, David J and Sitzer, Matthias and K{\"a}h{\"o}nen, Mika and Illig, Thomas and Wild, Philipp S and Orr{\`u}, Marco and L{\"u}demann, Jan and Shuldiner, Alan R and Eiriksdottir, Gudny and White, Charles C and Rotter, Jerome I and Hofman, Albert and Seissler, Jochen and Zeller, Tanja and Usala, Gianluca and Ernst, Florian and Launer, Lenore J and D{\textquoteright}Agostino, Ralph B and O{\textquoteright}Leary, Daniel H and Ballantyne, Christie and Thiery, Joachim and Ziegler, Andreas and Lakatta, Edward G and Chilukoti, Ravi Kumar and Harris, Tamara B and Wolf, Philip A and Psaty, Bruce M and Polak, Joseph F and Li, Xia and Rathmann, Wolfgang and Uda, Manuela and Boerwinkle, Eric and Klopp, Norman and Schmidt, Helena and Wilson, James F and Viikari, Jorma and Koenig, Wolfgang and Blankenberg, Stefan and Newman, Anne B and Witteman, Jacqueline and Heiss, Gerardo and Duijn, Cornelia van and Scuteri, Angelo and Homuth, Georg and Mitchell, Braxton D and Gudnason, Vilmundur and O{\textquoteright}Donnell, Christopher J} } @article {1359, title = {Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Feb 01}, pages = {100-12}, abstract = {

BACKGROUND: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

METHODS AND RESULTS: Continuous ABI and PAD (ABI <=0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (≈60\% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46{\texttimes}10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65{\texttimes}10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6{\texttimes}10(-5)), CYBA (rs3794624, P=6.3{\texttimes}10(-5)), and rs1122608 (LDLR, P=0.0026).

CONCLUSIONS: Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Alleles, Ankle Brachial Index, Chromosomes, Human, Pair 9, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p15, Female, Genome-Wide Association Study, Genotype, HapMap Project, Humans, Logistic Models, Male, Middle Aged, Peripheral Vascular Diseases, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Sex Factors}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.111.961292}, author = {Murabito, Joanne M and White, Charles C and Kavousi, Maryam and Sun, Yan V and Feitosa, Mary F and Nambi, Vijay and Lamina, Claudia and Schillert, Arne and Coassin, Stefan and Bis, Joshua C and Broer, Linda and Crawford, Dana C and Franceschini, Nora and Frikke-Schmidt, Ruth and Haun, Margot and Holewijn, Suzanne and Huffman, Jennifer E and Hwang, Shih-Jen and Kiechl, Stefan and Kollerits, Barbara and Montasser, May E and Nolte, Ilja M and Rudock, Megan E and Senft, Andrea and Teumer, Alexander and van der Harst, Pim and Vitart, Veronique and Waite, Lindsay L and Wood, Andrew R and Wassel, Christina L and Absher, Devin M and Allison, Matthew A and Amin, Najaf and Arnold, Alice and Asselbergs, Folkert W and Aulchenko, Yurii and Bandinelli, Stefania and Barbalic, Maja and Boban, Mladen and Brown-Gentry, Kristin and Couper, David J and Criqui, Michael H and Dehghan, Abbas and den Heijer, Martin and Dieplinger, Benjamin and Ding, Jingzhong and D{\"o}rr, Marcus and Espinola-Klein, Christine and Felix, Stephan B and Ferrucci, Luigi and Folsom, Aaron R and Fraedrich, Gustav and Gibson, Quince and Goodloe, Robert and Gunjaca, Grgo and Haltmayer, Meinhard and Heiss, Gerardo and Hofman, Albert and Kieback, Arne and Kiemeney, Lambertus A and Kolcic, Ivana and Kullo, Iftikhar J and Kritchevsky, Stephen B and Lackner, Karl J and Li, Xiaohui and Lieb, Wolfgang and Lohman, Kurt and Meisinger, Christa and Melzer, David and Mohler, Emile R and Mudnic, Ivana and Mueller, Thomas and Navis, Gerjan and Oberhollenzer, Friedrich and Olin, Jeffrey W and O{\textquoteright}Connell, Jeff and O{\textquoteright}Donnell, Christopher J and Palmas, Walter and Penninx, Brenda W and Petersmann, Astrid and Polasek, Ozren and Psaty, Bruce M and Rantner, Barbara and Rice, Ken and Rivadeneira, Fernando and Rotter, Jerome I and Seldenrijk, Adrie and Stadler, Marietta and Summerer, Monika and Tanaka, Toshiko and Tybjaerg-Hansen, Anne and Uitterlinden, Andr{\'e} G and van Gilst, Wiek H and Vermeulen, Sita H and Wild, Sarah H and Wild, Philipp S and Willeit, Johann and Zeller, Tanja and Zemunik, Tatijana and Zgaga, Lina and Assimes, Themistocles L and Blankenberg, Stefan and Boerwinkle, Eric and Campbell, Harry and Cooke, John P and de Graaf, Jacqueline and Herrington, David and Kardia, Sharon L R and Mitchell, Braxton D and Murray, Anna and M{\"u}nzel, Thomas and Newman, Anne B and Oostra, Ben A and Rudan, Igor and Shuldiner, Alan R and Snieder, Harold and van Duijn, Cornelia M and V{\"o}lker, Uwe and Wright, Alan F and Wichmann, H-Erich and Wilson, James F and Witteman, Jacqueline C M and Liu, Yongmei and Hayward, Caroline and Borecki, Ingrid B and Ziegler, Andreas and North, Kari E and Cupples, L Adrienne and Kronenberg, Florian} } @article {1391, title = {Cardiovascular physiology in premotor Parkinson{\textquoteright}s disease: a neuroepidemiologic study.}, journal = {Mov Disord}, volume = {27}, year = {2012}, month = {2012 Jul}, pages = {988-95}, abstract = {

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

}, keywords = {Aged, Antiparkinson Agents, Cardiovascular Physiological Phenomena, Carotid Stenosis, Cohort Studies, Data Interpretation, Statistical, Dizziness, Electrocardiography, Female, Heart Rate, Hospitalization, Humans, Longitudinal Studies, Male, Movement Disorders, Neurologic Examination, Parkinson Disease, Risk, Ultrasonography}, issn = {1531-8257}, doi = {10.1002/mds.24979}, author = {Jain, Samay and Ton, Thanh G and Perera, Subashan and Zheng, Yan and Stein, Phyllis K and Thacker, Evan and Strotmeyer, Elsa S and Newman, Anne B and Longstreth, Will T} } @article {1366, title = {Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {67}, year = {2012}, month = {2012 Sep}, pages = {970-6}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Aging, C-Reactive Protein, Cardiovascular Diseases, Cognition, Cohort Studies, Cross-Sectional Studies, Female, Humans, Inflammation, Inflammation Mediators, Interleukin-6, Longitudinal Studies, Male, Risk Factors, Vermont}, issn = {1758-535X}, doi = {10.1093/gerona/glr261}, author = {Jenny, Nancy S and French, Benjamin and Arnold, Alice M and Strotmeyer, Elsa S and Cushman, Mary and Chaves, Paulo H M and Ding, Jingzhong and Fried, Linda P and Kritchevsky, Stephen B and Rifkin, Dena E and Sarnak, Mark J and Newman, Anne B} } @article {6084, title = {Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts.}, journal = {Circ Cardiovasc Genet}, volume = {5}, year = {2012}, month = {2012 Dec}, pages = {639-46}, abstract = {

BACKGROUND: The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.

METHODS AND RESULTS: We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 {\texttimes} 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 {\texttimes} 10(-8)).

CONCLUSIONS: This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.

}, keywords = {Adult, African Americans, Cohort Studies, Electrocardiography, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.112.963991}, author = {Butler, Anne M and Yin, Xiaoyan and Evans, Daniel S and Nalls, Michael A and Smith, Erin N and Tanaka, Toshiko and Li, Guo and Buxbaum, Sarah G and Whitsel, Eric A and Alonso, Alvaro and Arking, Dan E and Benjamin, Emelia J and Berenson, Gerald S and Bis, Josh C and Chen, Wei and Deo, Rajat and Ellinor, Patrick T and Heckbert, Susan R and Heiss, Gerardo and Hsueh, Wen-Chi and Keating, Brendan J and Kerr, Kathleen F and Li, Yun and Limacher, Marian C and Liu, Yongmei and Lubitz, Steven A and Marciante, Kristin D and Mehra, Reena and Meng, Yan A and Newman, Anne B and Newton-Cheh, Christopher and North, Kari E and Palmer, Cameron D and Psaty, Bruce M and Quibrera, P Miguel and Redline, Susan and Reiner, Alex P and Rotter, Jerome I and Schnabel, Renate B and Schork, Nicholas J and Singleton, Andrew B and Smith, J Gustav and Soliman, Elsayed Z and Srinivasan, Sathanur R and Zhang, Zhu-Ming and Zonderman, Alan B and Ferrucci, Luigi and Murray, Sarah S and Evans, Michele K and Sotoodehnia, Nona and Magnani, Jared W and Avery, Christy L} } @article {1545, title = {Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.}, journal = {Arch Intern Med}, volume = {172}, year = {2012}, month = {2012 May 28}, pages = {799-809}, abstract = {

BACKGROUND: Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.

METHODS: Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.

RESULTS: Of 52 674 participants, 2188 (4.2\%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95\% CI, 1.06-1.46), CHD mortality (HR,1.29; 95\% CI, 1.02-1.62), CHD events (HR, 1.21; 95\%CI, 0.99-1.46), and AF (HR, 1.68; 95\% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5\% for total mortality to 41.5\% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03).

CONCLUSION: Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.

}, keywords = {Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Atrial Fibrillation, Cause of Death, Cohort Studies, Coronary Artery Disease, Female, Humans, Hyperthyroidism, Male, Middle Aged, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Analysis, Switzerland, Thyroid Function Tests, Thyrotropin, Young Adult}, issn = {1538-3679}, doi = {10.1001/archinternmed.2012.402}, author = {Collet, Tinh-Hai and Gussekloo, Jacobijn and Bauer, Douglas C and den Elzen, Wendy P J and Cappola, Anne R and Balmer, Philippe and Iervasi, Giorgio and Asvold, Bj{\o}rn O and Sgarbi, Jos{\'e} A and V{\"o}lzke, Henry and Gencer, Bari{\c s} and Maciel, Rui M B and Molinaro, Sabrina and Bremner, Alexandra and Luben, Robert N and Maisonneuve, Patrick and Cornuz, Jacques and Newman, Anne B and Khaw, Kay-Tee and Westendorp, Rudi G J and Franklyn, Jayne A and Vittinghoff, Eric and Walsh, John P and Rodondi, Nicolas} } @article {5999, title = {Blood pressure components and decline in kidney function in community-living older adults: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Aug}, pages = {1037-44}, abstract = {

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

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

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

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

}, keywords = {Aged, Blood Pressure, Cohort Studies, Cystatin C, Diastole, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Logistic Models, Longitudinal Studies, Male, Pulse, Renal Insufficiency, Chronic, Systole}, issn = {1941-7225}, doi = {10.1093/ajh/hpt067}, author = {Rifkin, Dena E and Katz, Ronit and Chonchol, Michel and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Siscovick, David S and Peralta, Carmen A} } @article {5992, title = {Decline in health for older adults: five-year change in 13 key measures of standardized health.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {68}, year = {2013}, month = {2013 Sep}, pages = {1059-67}, abstract = {

BACKGROUND: The health of older adults declines over time, but there are many ways of measuring health. It is unclear whether all health measures decline at the same rate or whether some aspects of health are less sensitive to aging than others.

METHODS: We compared the decline in 13 measures of physical, mental, and functional health from the Cardiovascular Health Study: hospitalization, bed days, cognition, extremity strength, feelings about life as a whole, satisfaction with the purpose of life, self-rated health, depression, digit symbol substitution test, grip strength, activities of daily living, instrumental activities of daily living, and gait speed. Each measure was standardized against self-rated health. We compared the 5-year change to see which of the 13 measures declined the fastest and the slowest.

RESULTS: The 5-year change in standardized health varied from a decline of 12 points (out of 100) for hospitalization to a decline of 17 points for gait speed. In most comparisons, standardized health from hospitalization and bed days declined the least, whereas health measured by activities of daily living, instrumental activities of daily living, and gait speed declined the most. These rankings were independent of age, sex, mortality patterns, and the method of standardization.

CONCLUSIONS: All of the health variables declined, on average, with advancing age, but at significantly different rates. Standardized measures of mental health, cognition, quality of life, and hospital utilization did not decline as fast as gait speed, activities of daily living, and instrumental activities of daily living. Public health interventions to address problems with gait speed, activities of daily living, and instrumental activities of daily living may help older adults to remain healthier in all dimensions.

}, keywords = {Activities of Daily Living, Aged, Aging, Cohort Studies, Female, Gait, Health Status, Health Status Indicators, Hospitalization, Humans, Longitudinal Studies, Male, Mental Health, Quality of Life, Self Report, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt038}, author = {Diehr, Paula H and Thielke, Stephen M and Newman, Anne B and Hirsch, Calvin and Tracy, Russell} } @article {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 {5998, title = {The QT interval and risk of incident atrial fibrillation.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {1562-8}, abstract = {

BACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.

OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.

METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.

RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95\% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95\% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95\% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.

CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF.

}, keywords = {Aged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Humans, Incidence, Long QT Syndrome, Male, Middle Aged, Risk Factors}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2013.07.023}, author = {Mandyam, Mala C and Soliman, Elsayed Z and Alonso, Alvaro and Dewland, Thomas A and Heckbert, Susan R and Vittinghoff, Eric and Cummings, Steven R and Ellinor, Patrick T and Chaitman, Bernard R and Stocke, Karen and Applegate, William B and Arking, Dan E and Butler, Javed and Loehr, Laura R and Magnani, Jared W and Murphy, Rachel A and Satterfield, Suzanne and Newman, Anne B and Marcus, Gregory M} } @article {6581, title = {Brain imaging findings in elderly adults and years of life, healthy life, and able life over the ensuing 16 years: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {62}, year = {2014}, month = {2014 Oct}, pages = {1838-43}, abstract = {

OBJECTIVES: To determine whether elderly people with different patterns of magnetic resonance imaging (MRI) findings have different long-term outcomes.

DESIGN: Longitudinal cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals aged 65 and older were recruited (N = 5,888); 3,660 of these underwent MRI, and 3,230 without a stroke before MRI were included in these analyses.

MEASUREMENTS: Cluster analysis of brain MRI findings was previously used to define five clusters: normal, atrophy, simple infarct, leukoaraiosis, and complex infarct. Participants were subsequently classified as healthy if they rated their health as excellent, very good, or good and as able if they did not report any limitations in activities of daily living (ADLs). Mean years of life (YoL), years of healthy life (YHL), and years of able life (YAL) were calculated over 16 years after the MRI and compared between clusters using unadjusted and adjusted regression analyses.

RESULTS: Mean age of participants was 75.0. With 16 years of follow-up, mean YoL was 11.3; YHL, 8.0; and YAL, 8.4. Outcomes differed significantly between clusters. With or without adjustments, outcomes were all significantly better in the normal than complex infarct cluster. The three remaining clusters had intermediate results, significantly different from the normal and complex infarct clusters but not usually from one another. Over 16 years of follow-up, participants in the complex infarct cluster (n = 368) spent the largest percentage of their 8.4 years alive being sick (38\%) and not able (38\%).

CONCLUSION: Findings on MRI scans in elderly adults are associated not only with long-term survival, but also with long-term self-rated health and limitation in ADLs. The combination of infarcts and leukoaraiosis carried the worst prognosis, presumably reflecting small vessel disease.

}, keywords = {Activities of Daily Living, Aged, Atrophy, Brain, Brain Infarction, Cohort Studies, Disability Evaluation, Female, Health Status, Humans, Leukoaraiosis, Longevity, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prognosis, Regression Analysis, United States}, issn = {1532-5415}, doi = {10.1111/jgs.13068}, author = {Longstreth, W T and Diehr, Paula H and Yee, Laura M and Newman, Anne B and Beauchamp, Norman J} } @article {6000, title = {Do changes in circulating biomarkers track with each other and with functional changes in older adults?}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Feb}, pages = {174-81}, abstract = {

BACKGROUND: It is unclear if changes in proposed circulating biomarkers of aging are strongly correlated to each other or functional change. We tested if biomarker changes track with each other and with functional measures over 9 years in older adults.

METHODS: Dehydroepiandrosterone sulfate (DHEAS), adiponectin, insulin-like growth factor 1 (IGF-1), IGF binding proteins 1 (IGFBP-1) and 3 (IGFBP-3), interleukin-6 (IL-6), cholesterol, and function (gait speed, grip strength, Modified Mini Mental Status Exam [3MSE] and Digit Symbol Substitution Test [DSST] scores) were measured in 1996-1997 and 2005-2006 in the Cardiovascular Health Study All Stars study (N = 901, mean [standard deviation, SD] age 85.3 [3.6] years in 2005-2006). Adjusted Pearson correlations illustrated if biomarkers tracked together. Multivariable linear regression demonstrated if biomarker changes tracked with functional changes.

RESULTS: Correlations among biomarker changes were mostly <0.2. In models with each biomarker entered separately, a 1-SD increase biomarker change was associated with change in function as follows: grip strength (DHEAS β = 0.61kg, p = .001; IL-6 β = -0.46kg, p = .012; cholesterol men β = 0.79kg, p = .016); gait speed (DHEAS β = 0.02 meters per second, p = .039; IL-6 β = -0.018 meters per second, p = .049); and DSST score (DHEAS women β = 1.46, p = .004; IL-6 β = -0.83, p = .027). When biomarkers were entered in the same model, significant associations remaining were as follows: grip strength (DHEAS β = 0.54kg, p = .005; IL-6 β = -0.43kg, p = .022); 3MSE score (IGF-1 β = 0.96, p = .04; IGFBP-3 β = -1.07, p = .024); and DSST score (DHEAS women β = 1.27, p = .012; IL-6 β = -0.80, p = .04).

CONCLUSION: Changes in biomarkers were poorly correlated, supporting a model of stochastic, independent change across systems. DHEAS and IL-6 tracked most closely with function, illustrating that changes in inflammation and sex steroids may play dominant roles in changes of these functional outcomes.

}, keywords = {Adiponectin, Aged, Aged, 80 and over, Aging, Biomarkers, Cholesterol, Cognition, Cohort Studies, Dehydroepiandrosterone Sulfate, Female, Gait, Hand Strength, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Interleukin-6, Male, Neuropsychological Tests, Psychomotor Performance, Time Factors}, issn = {1758-535X}, doi = {10.1093/gerona/glt088}, author = {Sanders, Jason L and Ding, Victoria and Arnold, Alice M and Kaplan, Robert C and Cappola, Anne R and Kizer, Jorge R and Boudreau, Robert M and Cushman, Mary and Newman, Anne B} } @article {6589, title = {Subclinical vascular disease burden and longer survival.}, journal = {J Am Geriatr Soc}, volume = {62}, year = {2014}, month = {2014 Sep}, pages = {1692-8}, abstract = {

OBJECTIVES: To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer.

DESIGN: Cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals born between June 30, 1918, and June 30, 1921 (N~=~2,082; aged 70-75 at baseline (1992-93)).

MEASUREMENTS: A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older.

RESULTS: A 1-point lower SVD score was associated with 1.22 greater odds (95\% confidence interval~=~1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking.

CONCLUSION: A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival.

}, keywords = {Aged, Aged, 80 and over, C-Reactive Protein, Carotid Intima-Media Thickness, Cohort Studies, Cystatin C, Depression, Diabetes Mellitus, Electrocardiography, Female, Humans, Inflammation, Kidney Diseases, Male, Smoking, Survival Analysis, United States, Vascular Diseases}, issn = {1532-5415}, doi = {10.1111/jgs.13018}, author = {Odden, Michelle C and Yee, Laura M and Arnold, Alice M and Sanders, Jason L and Hirsch, Calvin and DeFilippi, Christopher and Kizer, Jorge R and Inzitari, Marco and Newman, Anne B} } @article {6737, title = {Changes in insulin-like growth factor-I and its binding proteins are associated with diabetes mellitus in older adults.}, journal = {J Am Geriatr Soc}, volume = {63}, year = {2015}, month = {2015 May}, pages = {902-9}, abstract = {

OBJECTIVES: To determine whether changes in insulin-like growth factor (IGF) protein levels are greater in participants with type 2 diabetes mellitus or worsening glycemia than in normoglycemic individuals over a 9-year follow-up period.

DESIGN: Retrospective analysis of a cohort study.

SETTING: Participants were recruited from North Carolina, California, Maryland, and Pennsylvania.

PARTICIPANTS: Cardiovascular Health Study All Stars participants, a cohort study of community-dwelling adults aged 65 and older (N=897).

MEASUREMENTS: Plasma IGF-I, IGF binding protein (IGFBP)-1, and IGFBP-3 levels were assessed and American Diabetes Association cut-points for impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and diabetes mellitus were used to classify participants at baseline (1996-97) and follow-up (2005-06).

RESULTS: At baseline, mean age was 76.3{\textpm}3.6, and 18.5\% had diabetes mellitus. Participants with IFG alone and IGT plus IFG had higher IGF-I levels and lower IGFBP-1 levels than those with normoglycemia or diabetes mellitus. The greatest percentage change in IGF levels occurred in those who had diabetes mellitus at baseline (9-year changes: -9.3\% for IGF-I, 59.7\% for IGFBP-1, -13.4\% for IGFBP-3), the smallest in individuals who remained normoglycemic at follow-up (9-year changes: -3.7\% for IGF-I, 25.6\% for IGFBP-1, -6.4\% for IGFBP-3), and intermediate in those who were normoglycemic but developed IFG at follow-up.

CONCLUSION: Degrees of glycemic impairment are associated with varying degrees of change in IGF protein levels. The changes observed in the diabetes mellitus group have been previously shown to be associated with heart failure, cancer, and noncancer mortality.

}, keywords = {Aged, Blood Glucose, Cohort Studies, Diabetes Mellitus, Type 2, Female, Humans, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Retrospective Studies}, issn = {1532-5415}, doi = {10.1111/jgs.13390}, author = {Aneke-Nash, Chino S and Parrinello, Christina M and Rajpathak, Swapnil N and Rohan, Thomas E and Strotmeyer, Elsa S and Kritchevsky, Stephen B and Psaty, Bruce M and B{\r u}zkov{\'a}, Petra and Kizer, Jorge R and Newman, Anne B and Strickler, Howard D and Kaplan, Robert C} } @article {6550, title = {GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {70}, year = {2015}, month = {2015 Jan}, pages = {110-8}, abstract = {

BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15\% to 25\%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.

METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age >=90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.

RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 {\texttimes} 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 {\texttimes} 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85{\texttimes}10(-10)).

CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages >=90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

}, keywords = {Aged, Aged, 80 and over, Apolipoproteins E, Cell Adhesion Molecules, Cohort Studies, Female, Forkhead Box Protein O3, Forkhead Transcription Factors, Genome-Wide Association Study, Humans, Longevity, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Kainic Acid}, issn = {1758-535X}, doi = {10.1093/gerona/glu166}, author = {Broer, Linda and Buchman, Aron S and Deelen, Joris and Evans, Daniel S and Faul, Jessica D and Lunetta, Kathryn L and Sebastiani, Paola and Smith, Jennifer A and Smith, Albert V and Tanaka, Toshiko and Yu, Lei and Arnold, Alice M and Aspelund, Thor and Benjamin, Emelia J and De Jager, Philip L and Eirkisdottir, Gudny and Evans, Denis A and Garcia, Melissa E and Hofman, Albert and Kaplan, Robert C and Kardia, Sharon L R and Kiel, Douglas P and Oostra, Ben A and Orwoll, Eric S and Parimi, Neeta and Psaty, Bruce M and Rivadeneira, Fernando and Rotter, Jerome I and Seshadri, Sudha and Singleton, Andrew and Tiemeier, Henning and Uitterlinden, Andr{\'e} G and Zhao, Wei and Bandinelli, Stefania and Bennett, David A and Ferrucci, Luigi and Gudnason, Vilmundur and Harris, Tamara B and Karasik, David and Launer, Lenore J and Perls, Thomas T and Slagboom, P Eline and Tranah, Gregory J and Weir, David R and Newman, Anne B and van Duijn, Cornelia M and Murabito, Joanne M} } @article {6596, title = {Multisystem physiologic impairments and changes in gait speed of older adults.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {70}, year = {2015}, month = {2015 Mar}, pages = {319-24}, abstract = {

BACKGROUND: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals.

METHODS: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95\% confidence intervals (CI) by category of index were calculated using mixed effects models.

RESULTS: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95\% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95\% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95\% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95\% CI: -0.014, -0.006).

CONCLUSIONS: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Brain, Cardiovascular Physiological Phenomena, Cohort Studies, Female, Gait, Geriatric Assessment, Glucose, Health Status Indicators, Humans, Kidney, Lung, Male, Sensitivity and Specificity, Time Factors}, issn = {1758-535X}, doi = {10.1093/gerona/glu176}, author = {Rosso, Andrea L and Sanders, Jason L and Arnold, Alice M and Boudreau, Robert M and Hirsch, Calvin H and Carlson, Michelle C and Rosano, Caterina and Kritchevsky, Stephen B and Newman, Anne B} } @article {6771, title = {Resting heart rate and risk of incident heart failure: three prospective cohort studies and a systematic meta-analysis.}, journal = {J Am Heart Assoc}, volume = {4}, year = {2015}, month = {2015 Jan}, pages = {e001364}, abstract = {

BACKGROUND: The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned.

METHODS AND RESULTS: RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95\% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95\% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95\% CI: 1.19 to 1.64).

CONCLUSIONS: There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Aging, Cohort Studies, Female, Heart Failure, Heart Rate, Humans, Incidence, Japan, Male, Predictive Value of Tests, Prospective Studies, Rest, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate}, issn = {2047-9980}, doi = {10.1161/JAHA.114.001364}, author = {Khan, Hassan and Kunutsor, Setor and Kalogeropoulos, Andreas P and Georgiopoulou, Vasiliki V and Newman, Anne B and Harris, Tamara B and Bibbins-Domingo, Kirsten and Kauhanen, Jussi and Gheorghiade, Mihai and Fonarow, Gregg C and Kritchevsky, Stephen B and Laukkanen, Jari A and Butler, Javed} } @article {6798, title = {Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.}, journal = {JAMA Intern Med}, volume = {175}, year = {2015}, month = {2015 Jun}, pages = {1037-47}, abstract = {

IMPORTANCE: Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).

OBJECTIVE: To assess the association between differences in thyroid function within the reference range and CHD risk.

DESIGN, SETTING, AND PARTICIPANTS: Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.

EXPOSURES: Thyroid function as expressed by serum thyrotropin levels at baseline.

MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.

RESULTS: Among 55,412 individuals, 1813 people (3.3\%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5\%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95\% CI, 0.90-1.04) for CHD mortality and 1.00 (95\% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95\% CI, 0.74-1.20]) and CHD events (0.97 [95\% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.

CONCLUSIONS AND RELEVANCE: Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

}, keywords = {Cohort Studies, Coronary Disease, Humans, Hypothyroidism, Thyrotropin}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2015.0930}, author = {Asvold, Bj{\o}rn O and Vatten, Lars J and Bj{\o}ro, Trine and Bauer, Douglas C and Bremner, Alexandra and Cappola, Anne R and Ceresini, Graziano and den Elzen, Wendy P J and Ferrucci, Luigi and Franco, Oscar H and Franklyn, Jayne A and Gussekloo, Jacobijn and Iervasi, Giorgio and Imaizumi, Misa and Kearney, Patricia M and Khaw, Kay-Tee and Maciel, Rui M B and Newman, Anne B and Peeters, Robin P and Psaty, Bruce M and Razvi, Salman and Sgarbi, Jos{\'e} A and Stott, David J and Trompet, Stella and Vanderpump, Mark P J and V{\"o}lzke, Henry and Walsh, John P and Westendorp, Rudi G J and Rodondi, Nicolas} } @article {7161, title = {Gait Speed Predicts Incident Disability: A Pooled Analysis.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Jan}, pages = {63-71}, abstract = {

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking {\textonequarter} - {\textonehalf} mile or climbing 10 steps within 3 years.

RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10\% to 1\% in men, and from 15\% to 1\% in women, while mobility difficulty trended from 47\% to 4\% in men and 40\% to 6\% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.

CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Gait, Geriatric Assessment, Humans, Independent Living, Male, Mobility Limitation, Predictive Value of Tests, Prognosis, Psychomotor Performance, Risk Assessment, Risk Factors, ROC Curve, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv126}, author = {Perera, Subashan and Patel, Kushang V and Rosano, Caterina and Rubin, Susan M and Satterfield, Suzanne and Harris, Tamara and Ensrud, Kristine and Orwoll, Eric and Lee, Christine G and Chandler, Julie M and Newman, Anne B and Cauley, Jane A and Guralnik, Jack M and Ferrucci, Luigi and Studenski, Stephanie A} } @article {7493, title = {Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults.}, journal = {Stroke}, volume = {48}, year = {2017}, month = {2017 Jul}, pages = {1818-1826}, abstract = {

BACKGROUND AND PURPOSE: Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke.

METHODS: In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (>=5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations).

RESULTS: Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only.

CONCLUSIONS: Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Brain Ischemia, Cohort Studies, Female, Follow-Up Studies, Frail Elderly, Humans, Male, Recovery of Function, Risk Factors, Stroke, Survival Rate}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.117.016726}, author = {Winovich, Divya Thekkethala and Longstreth, William T and Arnold, Alice M and Varadhan, Ravi and Zeki Al Hazzouri, Adina and Cushman, Mary and Newman, Anne B and Odden, Michelle C} } @article {8572, title = {Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study.}, journal = {Am J Hypertens}, volume = {30}, year = {2017}, month = {2017 Feb}, pages = {151-158}, abstract = {

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

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

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

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

}, keywords = {Aged, Aging, Blood Pressure, Blood Pressure Determination, Body Composition, California, Cohort Studies, Female, Health Status, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Office Visits, Prognosis, Retrospective Studies, Risk Factors, Stroke, Survival Rate}, issn = {1941-7225}, doi = {10.1093/ajh/hpw106}, author = {Wu, Chenkai and Shlipak, Michael G and Stawski, Robert S and Peralta, Carmen A and Psaty, Bruce M and Harris, Tamara B and Satterfield, Suzanne and Shiroma, Eric J and Newman, Anne B and Odden, Michelle C} } @article {8712, title = {Total carotenoid intake is associated with reduced loss of grip strength and gait speed over time in adults: The Framingham Offspring Study.}, journal = {Am J Clin Nutr}, volume = {113}, year = {2021}, month = {2021 02 02}, pages = {437-445}, abstract = {

BACKGROUND: Lower antioxidant serum concentrations have been linked to declines in lean mass and physical function in older adults. Yet population data on the effect of dietary antioxidants on loss of muscle strength and physical function are lacking.

OBJECTIVE: We sought to determine the association of antioxidant intake [vitamin C, vitamin E, and total and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein~+~zeaxanthin)] with annualized change in grip strength and gait speed in adults from the Framingham Offspring study.

METHODS: This prospective cohort study included participants with a valid FFQ at the index examination and up to 2 prior examinations and at >=2 measures of primary outcomes: grip strength (n~=~2452) and/or gait speed (n~=~2422) measured over 3 subsequent examinations. Annualized change in grip strength (kg/y) and change in gait speed (m/s/y) over the follow-up period were used. Linear regression was used to calculate β coefficients and P values, adjusting for covariates.

RESULTS: Mean {\textpm} SD age of participants was 61 {\textpm} 9 y (range: 33-88 y). Median intakes (IQR, mg/d) of vitamin C, vitamin E, and total carotenoid across available examinations were 209.2 (133.1-394.2), 27.1 (7.4-199.0), and 15.3 (10.4-21.3), respectively. The mean follow-up time was \~{}12 {\textpm} 2 y (range: 4.5-15.4 y). In the sex-combined sample, higher intakes of total carotenoids, lycopene, and lutein~+~zeaxanthin were associated with increased annualized change in grip strength [β (SE) per 10-mg higher intake/d, range: 0.0316 (0.0146) to 0.1223 (0.0603) kg/y)]. All antioxidants except for vitamin C were associated with faster gait speed [β (SE) per 10-mg higher intake/d, range: 0.00008 (0.00004) to 0.0187 (0.0081) m/s/y].

CONCLUSIONS: Higher antioxidant intake was associated with increase in grip strength and faster gait speed in this cohort of adults. This finding highlights the need for a randomized controlled trial of dietary antioxidants and their effect on muscle strength and physical function.

}, keywords = {Adult, Aged, Aged, 80 and over, Carotenoids, Cohort Studies, Diet, Female, Hand Strength, Humans, Male, Middle Aged, Prospective Studies, Walking Speed}, issn = {1938-3207}, doi = {10.1093/ajcn/nqaa288}, author = {Sahni, Shivani and Dufour, Alyssa B and Fielding, Roger A and Newman, Anne B and Kiel, Douglas P and Hannan, Marian T and Jacques, Paul F} }