@article {695, title = {Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Jun 24}, pages = {1395-400}, abstract = {

BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol.

METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years{\textquoteright} follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95\% confidence intervals (CIs), adjusted for confounding variables.

RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95\% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95\% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline.

CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.

}, keywords = {Aged, Cholesterol, LDL, Coronary Disease, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hypolipidemic Agents, Incidence, Male, Multivariate Analysis, Proportional Hazards Models, Risk Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.162.12.1395}, author = {Lemaitre, Rozenn N and Psaty, Bruce M and Heckbert, Susan R and Kronmal, Richard A and Newman, Anne B and Burke, Gregory L} } @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 {750, title = {Regional and racial differences in the prevalence of physician-diagnosed essential tremor in the United States.}, journal = {Mov Disord}, volume = {18}, year = {2003}, month = {2003 Sep}, pages = {1035-40}, abstract = {

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

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Essential Tremor, European Continental Ancestry Group, Female, Humans, Male, Physicians, Prevalence, United States}, issn = {0885-3185}, doi = {10.1002/mds.10492}, author = {Louis, Elan D and Fried, Linda P and Fitzpatrick, Annette L and Longstreth, William T and Newman, Anne B} } @article {803, title = {The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1639-47}, abstract = {

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults.

DESIGN: A prospective population-based study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later.

MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.

RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95\% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality.

CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.

}, keywords = {African Americans, African Continental Ancestry Group, Aged, Female, Health Surveys, Humans, Incidence, Lipids, Male, Mortality, Myocardial Infarction, Population Surveillance, Prospective Studies, Risk Factors, Stroke, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52455.x}, author = {Psaty, Bruce M and Anderson, Melissa and Kronmal, Richard A and Tracy, Russell P and Orchard, Trevor and Fried, Linda P and Lumley, Thomas and Robbins, John and Burke, Greg and Newman, Anne B and Furberg, Curt D} } @article {775, title = {The presence of frailty in elderly persons with chronic renal insufficiency.}, journal = {Am J Kidney Dis}, volume = {43}, year = {2004}, month = {2004 May}, pages = {861-7}, abstract = {

BACKGROUND: Frailty has been defined as a tool to define individuals who lack functional reserve and are at risk for functional decline. We hypothesized that chronic renal insufficiency (CRI) would be associated with a greater prevalence of frailty and disability in the elderly.

METHODS: This cross-sectional analysis used baseline data collected from the Cardiovascular Health Study, which enrolled 5,888 community-dwelling adults aged 65 years or older from 4 clinical centers in the United States. Renal insufficiency is defined as a serum creatinine level of 1.3 mg/dL or greater (> or =115 micromol/L) in women and 1.5 mg/dL or greater (> or =133 micromol/L) in men. Frailty is defined by the presence of 3 of the following abnormalities: unintentional weight loss, self-reported exhaustion, measured weakness, slow walking speed, and low physical activity. Disability is defined as any self-reported difficulty with activities of daily living.

RESULTS: Among 5,808 participants with creatinine levels measured at entry, 15.9\% of men (n = 394) and 7.6\% of women (n = 254) had CRI. Prevalences of frailty (15\% versus 6\%; P < 0.001) and disability (12\% versus 7\%; P = 0.001) were greater in participants with CRI compared with those with normal renal function. After multivariate adjustment for comorbidity, CRI remained significantly associated with frailty (odds ratio, 1.76; 95\% confidence interval, 1.28 to 2.41), but not disability (odds ratio, 1.26; 95\% confidence interval, 0.94 to 1.69).

CONCLUSION: Elderly persons with CRI have a high prevalence of frailty, which may signal their risk for progression to adverse health outcomes. If confirmed in other studies, identification of frailty in patients with CRI may warrant special interventions to preserve their independence, quality of life, and survival.

}, keywords = {Activities of Daily Living, Aged, Cross-Sectional Studies, Female, Frail Elderly, Humans, Kidney Failure, Chronic, Male, United States}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2003.12.049}, author = {Shlipak, Michael G and Stehman-Breen, Catherine and Fried, Linda F and Song, Xiao and Siscovick, David and Fried, Linda P and Psaty, Bruce M and Newman, Anne B} } @article {792, title = {Self-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Jul}, pages = {1174-9}, abstract = {

OBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults.

DESIGN: Cross-sectional and longitudinal analyses.

SETTING: Four U.S. communities.

PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated.

MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline.

RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95\% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25\% higher risk in consumers of 14 or more drinks per week (95\% CI=3-52\%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity.

CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.

}, keywords = {Accidental Falls, Aged, Alcohol Drinking, Chi-Square Distribution, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Male, Regression Analysis, Risk Factors, Self Disclosure, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52318.x}, author = {Mukamal, Kenneth J and Mittleman, Murray A and Longstreth, W T and Newman, Anne B and Fried, Linda P and Siscovick, David S} } @article {829, title = {Coronary artery calcium: associations with brain magnetic resonance imaging abnormalities and cognitive status.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {609-15}, abstract = {

OBJECTIVES: To evaluate the association between coronary atherosclerosis and subclinical brain magnetic resonance imaging (MRI) abnormalities and between coronary atherosclerosis and abnormal cognitive function (dementia/mild cognitive impairment).

DESIGN: Cross-sectional.

SETTING: The Cardiovascular Health Study (CHS), an epidemiological study of risk factors for cardiovascular disease in older adults.

PARTICIPANTS: Four hundred nine men and women, mean age 79, recruited from the Pittsburgh center of the CHS.

MEASUREMENTS: Coronary atherosclerosis was defined according to the level of coronary artery calcification (CAC), as measured using electronic beam tomography. Subclinical brain MRI abnormalities included ventricular enlargement, white matter hyperintensities, and number of subcortical brain infarcts. Brain MRI and CAC measurements were performed between 1998 and 2000 at the Pittsburgh center of the CHS. Prevalence of brain MRI abnormalities and abnormal cognitive status were examined across quartiles of the CAC score, before and after controlling for age. Multivariate logistic regression models were used to assess whether CAC level was associated with abnormalities of brain MRI or abnormal cognitive status.

RESULTS: Older adults with high CAC scores were more likely to have more-severe brain MRI abnormalities, including subcortical infarction and high white matter hyperintensities. The associations between CAC and ventricular enlargement showed a similar but not significant trend. The presence of any of the MRI abnormalities attenuated the association between CAC and abnormal cognitive status.

CONCLUSION: Older adults with higher levels of CAC were more likely to have more-severe brain MRI abnormalities and abnormal cognitive status.

}, keywords = {Aged, Brain, Calcinosis, Cognition Disorders, Coronary Artery Disease, Cross-Sectional Studies, Dementia, Female, Humans, Logistic Models, Magnetic Resonance Imaging, Male, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53208.x}, author = {Rosano, Caterina and Naydeck, Barbara and Kuller, Lewis H and Longstreth, William T and Newman, Anne B} } @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 {827, title = {Cystatin C concentration as a risk factor for heart failure in older adults.}, journal = {Ann Intern Med}, volume = {142}, year = {2005}, month = {2005 Apr 05}, pages = {497-505}, abstract = {

BACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.

OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.

DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.

SETTING: Adults 65 years of age or older from 4 communities in the United States.

PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.

MEASUREMENTS: Incident heart failure.

RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17\%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95\% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).

LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.

CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.

}, keywords = {Aged, Biomarkers, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney, Kidney Function Tests, Male, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-142-7-200504050-00008}, author = {Sarnak, Mark J and Katz, Ronit and Stehman-Breen, Catherine O and Fried, Linda F and Jenny, Nancy Swords and Psaty, Bruce M and Newman, Anne B and Siscovick, David and Shlipak, Michael G} } @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 {830, title = {Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {649-54}, abstract = {

OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance.

DESIGN: Longitudinal analysis, average follow-up time: 4.0 years.

SETTING: Cardiovascular Health Study (CHS).

PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4).

MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand).

RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35\% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22\% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26\% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed.

CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Brain, Female, Follow-Up Studies, Gait, Humans, Incidence, Magnetic Resonance Imaging, Male, Proportional Hazards Models, Psychomotor Disorders, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53214.x}, author = {Rosano, Caterina and Kuller, Lewis H and Chung, Hyoju and Arnold, Alice M and Longstreth, William T and Newman, Anne B} } @article {895, title = {Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {97}, year = {2006}, month = {2006 May 01}, pages = {1281-6}, abstract = {

In the elderly, mitral annular calcification (MAC) and aortic valve sclerosis (AVS) are associated with increased cardiovascular morbidity and mortality. Aortic annular calcification (AAC) commonly occurs with MAC. However, the prognostic value of AAC, singly or in combination with MAC and AVS, for incident cardiovascular disease and mortality is unknown. From the Cardiovascular Health Study, we analyzed 3,782 participants (76 +/- 5 years of age, 60\% women) who had an echocardiogram at the 1994 to 1995 examination and who were prospectively followed for an average of 6.6 years (range 0.01 to 8.5). All 3 calcification categories were associated with incident congestive heart failure (MAC: hazard ratio [HR] 1.71, 95\% confidence interval [CI] 1.35 to 2.18, AAC: HR 1.62, 95\% CI 1.28 to 2.06, and AVS: HR 1.50, 95\% CI 1.19 to 1.89) and death. A stronger association with incident cardiovascular disease and mortality was observed with a larger number of calcification categories and with increased MAC severity. Moreover, in the participants with prevalent cardiovascular disease at echocardiographic examination (n = 1,054), MAC and AAC were still associated with cardiovascular mortality (MAC: HR 1.91, 95\% CI 1.04 to 3.50; AAC: HR 2.11, 95\% CI 1.16 to 3.85) even in fully adjusted models. In conclusion, MAC, AAC, and AVS are associated with a significant risk of incident congestive heart failure, cardiovascular and all-cause mortalities, and worse outcome in older patients with preexisting cardiovascular disease. Elderly patients with these findings represent a high-risk group and may require close medical attention.

}, keywords = {Aged, Aortic Valve, Calcinosis, Echocardiography, Female, Follow-Up Studies, Heart Failure, Heart Valve Diseases, Humans, Male, Mitral Valve, Prospective Studies, Risk Factors, Sclerosis, Severity of Illness Index, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2005.11.065}, author = {Barasch, Eddy and Gottdiener, John S and Marino Larsen, Emily K and Chaves, Paulo H M and Newman, Anne B} } @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 {953, title = {The effect of different public health interventions on longevity, morbidity, and years of healthy life.}, journal = {BMC Public Health}, volume = {7}, year = {2007}, month = {2007 Apr 05}, pages = {52}, abstract = {

BACKGROUND: Choosing cost-effective strategies for improving the health of the public is difficult because the relative effects of different types of interventions are not well understood. The benefits of one-shot interventions may be different from the benefits of interventions that permanently change the probability of getting sick, recovering, or dying. Here, we compare the benefits of such types of public health interventions.

METHODS: We used multi-state life table methods to estimate the impact of five types of interventions on mortality, morbidity (years of life in fair or poor health), and years of healthy life (years in excellent, very good, or good health).

RESULTS: A one-shot intervention that makes all the sick persons healthy at baseline would increase life expectancy by 3 months and increase years of healthy life by 6 months, in a cohort beginning at age 65. An equivalent amount of improvement can be obtained from an intervention that either decreases the probability of getting sick each year by 12\%, increases the probability of a sick person recovering by 16\%, decreases the probability that a sick person dies by 15\%, or decreases the probability that a healthy person dies by 14\%. Interventions aimed at keeping persons healthy increased longevity and years of healthy life, while decreasing morbidity and medical expenditures. Interventions focused on preventing mortality had a greater effect on longevity, but had higher future morbidity and medical expenditures. Results differed for older and younger cohorts and depended on the value to society of an additional year of sick life.

CONCLUSION: Interventions that promote health and prevent disease performed well, but other types of intervention were sometimes better. The value to society of interventions that increase longevity but also increase morbidity needs further research. More comprehensive screening and treatment of new Medicare enrollees might improve their health and longevity without increasing future medical expenditures.

}, keywords = {Actuarial Analysis, Cost-Benefit Analysis, Disease Management, Health Priorities, Health Promotion, Health Services, Health Status, Humans, Life Expectancy, Medicare, Models, Biological, Morbidity, United States, United States Public Health Service}, issn = {1471-2458}, doi = {10.1186/1471-2458-7-52}, author = {Diehr, Paula and Derleth, Ann and Cai, Liming and Newman, Anne B} } @article {948, title = {Ethnic-specific prevalence of peripheral arterial disease in the United States.}, journal = {Am J Prev Med}, volume = {32}, year = {2007}, month = {2007 Apr}, pages = {328-33}, abstract = {

BACKGROUND: Individuals diagnosed with peripheral arterial disease (PAD) are at increased risk for future functional limitations as well as cardiovascular morbidity and mortality. The aim of this study was to estimate the age-, gender-, and ethnic-specific burden of PAD in the United States for the year 2000.

METHODS: Data were collected from seven community-based studies that assessed subjects for the presence of PAD using the ankle-brachial index (ABI). Using standardized weighting criteria, age-, gender-, and ethnic-specific prevalence rates were computed and then multiplied by the corresponding 2000 Census population totals to estimate the burden of PAD in the United States for that year. Evidence-based adjustments for studies which did not consider possible subclavian stenosis, prior revascularization for PAD, or both were employed.

RESULTS: In 2000, it is conservatively estimated that at least 6.8 million (5.8\%) individuals aged 40 years or older had PAD based on an ABI of less than 0.9 or previous revascularization for PAD, and that that there are an additional 1.7 million Americans with PAD but "normal" ABIs. Including this group gives a total of 8.5 million (7.2\%) individuals with PAD.

CONCLUSIONS: Roughly one in 16 individuals residing in the United States in 2000 who were aged 40 years and older had PAD. Clinicians are encouraged to screen for the presence of PAD using the ABI.

}, keywords = {Adult, Aged, Aged, 80 and over, Databases as Topic, Female, Humans, Male, Middle Aged, Peripheral Vascular Diseases, United States}, issn = {0749-3797}, doi = {10.1016/j.amepre.2006.12.010}, author = {Allison, Matthew A and Ho, Elena and Denenberg, Julie O and Langer, Robert D and Newman, Anne B and Fabsitz, Richard R and Criqui, Michael H} } @article {960, title = {Focal atrophy and cerebrovascular disease increase dementia risk among cognitively normal older adults.}, journal = {J Neuroimaging}, volume = {17}, year = {2007}, month = {2007 Apr}, pages = {148-55}, abstract = {

BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer{\textquoteright}s disease (AD) among cognitively normal older adults.

METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60\% women, 81\% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD.

RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95\% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95\% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions.

CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.

}, keywords = {Aged, Alzheimer Disease, Analysis of Variance, Atrophy, Cerebrovascular Disorders, Cognition, Female, Humans, Logistic Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Temporal Lobe, United States}, issn = {1051-2284}, doi = {10.1111/j.1552-6569.2007.00093.x}, author = {Rosano, Caterina and Aizenstein, Howard J and Wu, Minjie and Newman, Anne B and Becker, James T and Lopez, Oscar L and Kuller, Lewis H} } @article {1002, title = {Gait variability is associated with subclinical brain vascular abnormalities in high-functioning older adults.}, journal = {Neuroepidemiology}, volume = {29}, year = {2007}, month = {2007}, pages = {193-200}, abstract = {

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

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

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

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

}, keywords = {Accidental Falls, Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebral Infarction, Comorbidity, Female, Gait Disorders, Neurologic, Geriatric Assessment, Health Surveys, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mobility Limitation, Neurodegenerative Diseases, Neurologic Examination, Risk Factors, United States}, issn = {1423-0208}, doi = {10.1159/000111582}, author = {Rosano, Caterina and Brach, Jennifer and Studenski, Stephanie and Longstreth, W T and Newman, Anne B} } @article {994, title = {Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {167}, year = {2008}, month = {2008 Jan 01}, pages = {34-41}, abstract = {

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95\% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95\% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95\% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

}, keywords = {Aged, Alcohol Drinking, Female, Follow-Up Studies, Health Surveys, Humans, Intermittent Claudication, Male, Prevalence, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwm274}, author = {Mukamal, Kenneth J and Kennedy, Margaret and Cushman, Mary and Kuller, Lewis H and Newman, Anne B and Polak, Joseph and Criqui, Michael H and Siscovick, David S} } @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 {1006, title = {Coronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old.}, journal = {Am J Cardiol}, volume = {101}, year = {2008}, month = {2008 Jan 15}, pages = {186-92}, abstract = {

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95\% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95\% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

}, keywords = {Aged, Aged, 80 and over, Carotid Artery Diseases, Carotid Artery, Common, Carotid Artery, Internal, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, ROC Curve, Severity of Illness Index, Survival Analysis, Ultrasonography, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2007.07.075}, author = {Newman, Anne B and Naydeck, Barbara L and Ives, Diane G and Boudreau, Robert M and Sutton-Tyrrell, Kim and O{\textquoteright}Leary, Daniel H and Kuller, Lewis H} } @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 {1021, title = {Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Apr}, pages = {652-60}, abstract = {

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults.

DESIGN: Cohort study.

SETTING/PARTICIPANTS: One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study.

MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality.

RESULTS: Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95\% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95\% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties.

CONCLUSION: In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Enzyme-Linked Immunosorbent Assay, Fasting, Female, Follow-Up Studies, Hand Strength, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Survival Rate, United States, Walking}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01637.x}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Xue, XiaoNan and Kritchevsky, Stephen B and Newman, Anne B and Psaty, Bruce M} } @article {1000, title = {Weight, mortality, years of healthy life, and active life expectancy in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Jan}, pages = {76-83}, abstract = {

OBJECTIVES: To determine whether weight categories predict subsequent mortality and morbidity in older adults.

DESIGN: Multistate life tables, using data from the Cardiovascular Health Study, a longitudinal population-based cohort of older adults.

SETTING: Data were provided by community-dwelling seniors in four U.S. counties: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.

PARTICIPANTS: Five thousand eight hundred eighty-eight adults aged 65 and older at baseline.

MEASUREMENTS: The age- and sex-specific probabilities of transition from one health state to another and from one weight category to another were estimated. From these probabilities, future life expectancy, years of healthy life, active life expectancy, and the number of years spent in each weight and health category after age 65 were estimated.

RESULTS: Women who are healthy and of normal weight at age 65 have a life expectancy of 22.1 years. Of that, they spend, on average, 9.6 years as overweight or obese and 5.3 years in fair or poor health. For both men and women, being underweight at age 65 was associated with worse outcomes than being normal weight, whereas being overweight or obese was rarely associated with worse outcomes than being normal weight and was sometimes associated with significantly better outcomes.

CONCLUSION: Similar to middle-aged populations, older adults are likely to be or to become overweight or obese, but higher weight is not associated with worse health in this age group. Thus, the number of older adults at a "healthy" weight may be much higher than currently believed.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Body Mass Index, Body Weight, Female, Health Status Indicators, Humans, Life Expectancy, Life Style, Male, Prognosis, Risk Factors, Sex Factors, Survival Rate, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01500.x}, author = {Diehr, Paula and O{\textquoteright}Meara, Ellen S and Fitzpatrick, Annette and Newman, Anne B and Kuller, Lewis and Burke, Gregory} } @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 {1083, title = {Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {179}, year = {2009}, month = {2009 Jun 15}, pages = {1159-64}, abstract = {

RATIONALE: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.

OBJECTIVES: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.

METHODS: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.

MEASUREMENTS AND MAIN RESULTS: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95\% confidence interval, 0.93-2.47) does not exclude the possibility of a modest association.

CONCLUSIONS: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded.

}, keywords = {Adult, Blood Pressure, Confidence Intervals, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Middle Aged, Odds Ratio, Polysomnography, Prognosis, Prospective Studies, Risk Factors, Sleep Apnea Syndromes, Time Factors, United States}, issn = {1535-4970}, doi = {10.1164/rccm.200712-1809OC}, author = {O{\textquoteright}Connor, George T and Caffo, Brian and Newman, Anne B and Quan, Stuart F and Rapoport, David M and Redline, Susan and Resnick, Helaine E and Samet, Jonathan and Shahar, Eyal} } @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 {1097, title = {Using telephone and informant assessments to estimate missing Modified Mini-Mental State Exam scores and rates of cognitive decline. The cardiovascular health study.}, journal = {Neuroepidemiology}, volume = {33}, year = {2009}, month = {2009}, pages = {55-65}, abstract = {

AIM: To estimate an equivalent to the Modified Mini-Mental State Exam (3MSE), and to compare changes in the 3MSE with and without the estimated scores.

METHODS: Comparability study on a subset of 405 participants, aged >or=70 years, from the Cardiovascular Health Study (CHS), a longitudinal study in 4 United States communities. The 3MSE, the Telephone Interview for Cognitive Status (TICS) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered within 30 days of one another. Regression models were developed to predict the 3MSE score from the TICS and/or IQCODE, and the predicted values were used to estimate missing 3MSE scores in longitudinal follow-up of 4,274 CHS participants.

RESULTS: The TICS explained 67\% of the variability in 3MSE scores, with a correlation of 0.82 between predicted and observed scores. The IQCODE alone was not a good estimate of 3MSE score, but improved the model fit when added to the TICS model. Using estimated 3MSE scores classified more participants with low cognition, and rates of decline were greater than when only the observed 3MSE scores were considered.

CONCLUSIONS: 3MSE scores can be reliably estimated from the TICS, with or without the IQCODE. Incorporating these estimates captured more cognitive decline in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Interviews as Topic, Longitudinal Studies, Male, Predictive Value of Tests, Psychiatric Status Rating Scales, Regression Analysis, Risk Factors, ROC Curve, United States}, issn = {1423-0208}, doi = {10.1159/000215830}, author = {Arnold, Alice M and Newman, Anne B and Dermond, Norma and Haan, Mary and Fitzpatrick, Annette} } @article {1210, title = {Association between adiposity in midlife and older age and risk of diabetes in older adults.}, journal = {JAMA}, volume = {303}, year = {2010}, month = {2010 Jun 23}, pages = {2504-12}, abstract = {

CONTEXT: Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults.

OBJECTIVE: To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older.

DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later.

MAIN OUTCOME MEASURE: Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater.

RESULTS: Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95\% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95\% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95\% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95\% CI, 2.8-6.4) for weight, 4.0 (95\% CI, 2.6-6.0) for fat mass, 4.2 (95\% CI, 2.8-6.2) for waist circumference, 2.4 (95\% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95\% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (+/-2 kg), those who gained the most weight from 50 years of age to baseline (> or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95\% CI, 1.9-4.3) and 2.0 (95\% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95\% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less.

CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes.

}, keywords = {Adiposity, Age Factors, Aged, Body Mass Index, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States, Weight Gain}, issn = {1538-3598}, doi = {10.1001/jama.2010.843}, author = {Biggs, Mary L and Mukamal, Kenneth J and Luchsinger, Jos{\'e} A and Ix, Joachim H and Carnethon, Mercedes R and Newman, Anne B and de Boer, Ian H and Strotmeyer, Elsa S and Mozaffarian, Dariush and Siscovick, David S} } @article {1094, title = {Body weight dynamics and their association with physical function and mortality in older adults: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Jan}, pages = {63-70}, abstract = {

BACKGROUND: To estimate the associations of weight dynamics with physical functioning and mortality in older adults.

METHODS: Longitudinal cohort study using prospectively collected data on weight, physical function, and health status in four U.S. Communities in the Cardiovascular Health Study. Included were 3,278 participants (2,013 women and 541 African Americans), aged 65 or older at enrollment, who had at least five weight measurements. Weight was measured at annual clinic visits between 1992 and 1999, and summary measures of mean weight, coefficient of variation, average annual weight change, and episodes of loss and gain (cycling) were calculated. Participants were followed from 1999 to 2006 for activities of daily living (ADL) difficulty, incident mobility limitations, and mortality.

RESULTS: Higher mean weight, weight variability, and weight cycling increased the risk of new onset of ADL difficulties and mobility limitations. After adjustment for risk factors, the hazard ratio (95\% confidence interval) for weight cycling for incident ADL impairment was 1.28 (1.12, 1.47), similar to that for several comorbidities in our model, including cancer and diabetes. Lower weight, weight loss, higher variability, and weight cycling were all risk factors for mortality, after adjustment for demographic risk factors, height, self-report health status, and comorbidities.

CONCLUSIONS: Variations in weight are important indicators of future physical limitations and mortality in the elderly and may reflect difficulties in maintaining homeostasis throughout older ages. Monitoring the weight of an older person for fluctuations or episodes of both loss and gain is an important aspect of geriatric care.

}, keywords = {Activities of Daily Living, Age Factors, Aged, 80 and over, Body Weight, Cardiovascular Diseases, Female, Follow-Up Studies, Health Status, Humans, Longevity, Male, Prospective Studies, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glp050}, author = {Arnold, Alice M and Newman, Anne B and Cushman, Mary and Ding, Jingzhong and Kritchevsky, Stephen} } @article {1168, title = {Cardiovascular disease is associated with greater incident dehydroepiandrosterone sulfate decline in the oldest old: the cardiovascular health study all stars study.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Mar}, pages = {421-6}, abstract = {

OBJECTIVES: To describe cross-sectional and longitudinal associations with dehydroepiandrosterone sulfate (DHEAS) and change in DHEAS with age.

DESIGN: Longitudinal cohort study.

SETTING: Pittsburgh, Pennsylvania.

PARTICIPANTS: Cardiovascular Health Study All Stars study participants assessed in 2005/06 (N=989, mean age 85.2, 63.5\% women, 16.5\% African American).

MEASUREMENTS: Health characteristics were assessed in 2005/06 according to DHEAS level, mean DHEAS and DHEAS change across age categories were tested, and linear and logistic regression was used to identify factors present in 1996/97 associated with continuous and categorical DHEAS change.

RESULTS: Mean +/- standard deviation DHEAS was 0.555 +/- 0.414 microg/mL in 1996/97 and 0.482 +/- 0.449 microg/mL in 2005/06 for women and 0.845 +/- 0.520 microg/mL in 1996/97 and 0.658 +/- 0.516 microg/mL in 2005/06 for men. In 2005/06, DHEAS was lower in women and subjects with cardiovascular disease (CVD) and chronic pulmonary disease and higher for African Americans and subjects with hypertension and high cholesterol. Mean DHEAS change was greater in men (-0.200 microg/mL) than in women (-0.078 microg/mL) (P<.001). Each 1-year increase in age attenuated the effect of male sex by 0.01 microg/mL (P=.009), abolishing the sex difference in DHEAS change by age 79. Presence of CVD before the study period was associated with greater absolute DHEAS change (beta=-0.04 microg/mL, P=.04) and with the fourth quartile of DHEAS change versus the first to third quartiles (odds ratio=1.46, 95\% confidence interval=1.03-2.05).

CONCLUSION: DHEAS change continues into very old age, is not homogenous, is affected by sex, and is associated with prevalent CVD. Future studies should investigate factors that might accelerate DHEAS decline.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Dehydroepiandrosterone Sulfate, Female, Humans, Longitudinal Studies, Male, Multivariate Analysis, Regression Analysis, Sex Distribution, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.02724.x}, author = {Sanders, Jason L and Boudreau, Robert M and Cappola, Anne R and Arnold, Alice M and Robbins, John and Cushman, Mary and Newman, Anne B} } @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 {1232, title = {Geriatric impairments and disability: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Sep}, pages = {1686-92}, abstract = {

OBJECTIVES: To determine the relative importance of geriatric impairments (in muscle strength, physical capacity, cognition, vision, hearing, and psychological status) and chronic diseases in predicting subsequent functional disability in longitudinal analyses.

DESIGN: Longitudinal data from the Cardiovascular Health Study were analyzed. Multivariable Cox hazards regression modeling was used to analyze associations between time-dependent predictors and onset of disability in activities of daily living (ADLs) and mobility.

SETTING: Four communities across the United States (Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Allegheny County, PA).

PARTICIPANTS: Five thousand eight hundred eighty-eight elderly persons.

MEASUREMENTS: Data were collected annually through in-person examinations.

RESULTS: ADL disability developed in 15\% of participants and mobility disability in 30\%. A single multivariable model was developed that included demographics, marital status, body mass index, and number of impairments and diseases. The hazard ratios (HRs) of having one, two, and three or more geriatric impairments (vs none) for the outcome of ADL disability were 2.12 (95\% confidence interval (CI)=1.63-2.75), 4.25 (95\% CI=3.30-5.48), and 7.87 (95\% CI=6.10-10.17), respectively, and for having one, two, and three or more chronic diseases were 1.75 (95\% CI=1.41-2.19), 2.45 (95\% CI=1.95-3.07), and 3.26 (95\% CI=2.53-4.19), respectively. Similarly, the HRs of having one, two, and three or more impairments for the outcome of mobility disability were 1.48 (95\% CI=1.27-1.73), 2.08 (95\% CI=1.77-2.45), and 3.70 (95\% CI=3.09-4.42), respectively, and for having one, two, and three or more diseases were 2.06 (95\% CI=1.76-2.40), 2.80 (95\% CI=2.36-3.31), and 4.20 (95\% CI=3.44-5.14), respectively.

CONCLUSION: Number of geriatric impairments was more strongly associated than number of chronic diseases with subsequent ADL disability and nearly as strongly associated with the subsequent mobility disability.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Cardiac Rehabilitation, Cardiovascular Diseases, Disabled Persons, Female, Follow-Up Studies, Geriatric Assessment, Health Status, Humans, Male, Morbidity, Retrospective Studies, Risk Factors, Time Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03022.x}, author = {Chaudhry, Sarwat I and McAvay, Gail and Ning, Yuming and Allore, Heather G and Newman, Anne B and Gill, Thomas M} } @article {1185, title = {Long-term retention of older adults in the Cardiovascular Health Study: implications for studies of the oldest old.}, journal = {J Am Geriatr Soc}, volume = {58}, year = {2010}, month = {2010 Apr}, pages = {696-701}, abstract = {

OBJECTIVES: To describe retention according to age and visit type (clinic, home, telephone) and to determine characteristics associated with visit types for a longitudinal epidemiological study in older adults.

DESIGN: Longitudinal cohort study.

SETTING: Four U.S. clinical sites.

PARTICIPANTS: Five thousand eight hundred eighty-eight Cardiovascular Health Study (CHS) participants aged 65 to 100 at 1989/90 or 1992/93 enrollment (58.6\% female; 15.7\% black). CHS participants were contacted every 6 months, with annual assessments through 1999 and in 2005/06 for the All Stars Study visit of the CHS cohort (aged 77-102; 66.5\% female; 16.6\% black).

MEASUREMENTS: All annual contacts through 1999 (n=43,772) and for the 2005/06 visit (n=1,942).

RESULTS: CHS had 43,772 total participant contacts from 1989 to 1999: 34,582 clinic visits (79.0\%), 2,238 refusals (5.1\%), 4,401 telephone visits (10.1\%), 1,811 home visits (4.1\%), and 740 other types (1.7\%). In 2005/06, the All Stars participants of the CHS cohort had 36.6\% clinic, 22.3\% home, and 41.1\% telephone visits. Compared with participants aged 65 to 69, odds ratios of not attending a CHS clinic visit were 1.82 (95\% confidence interval (CI)=1.54-2.13), 2.94 (95\% CI=2.45-3.57), 4.55 (95\% CI=3.70-5.56), and 9.09 (95\% CI=7.69-11.11) for those aged 70 to 74, 75 to 79, 80 to 84, and 85 and older, respectively, in sex-adjusted regression. In multivariable regression, participants with a 2005/06 clinic visit were younger, more likely to be male and in good health, and had had better cognitive and physical function 7 years earlier than participants with other visit types. Participants with home, telephone, and missing visits were similar on characteristics measured 7 years earlier.

CONCLUSION: Offering home, telephone, and proxy visits are essential to optimizing follow-up of aging cohorts. Home visits increased in-person retention from 36.5\% to 58.8\% and diversified the cohort with respect to age, health, and physical functioning.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Ambulatory Care Facilities, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Epidemiologic Studies, Female, Geriatric Assessment, House Calls, Humans, Logistic Models, Longitudinal Studies, Male, Multivariate Analysis, Patient Dropouts, Patient Selection, Research Subjects, Telephone, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.02770.x}, author = {Strotmeyer, Elsa S and Arnold, Alice M and Boudreau, Robert M and Ives, Diane G and Cushman, Mary and Robbins, John A and Harris, Tamara B and Newman, Anne B} } @article {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 {1326, title = {Association of body mass index with peripheral arterial disease in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {174}, year = {2011}, month = {2011 Nov 01}, pages = {1036-43}, abstract = {

The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)(2)) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged >= 65 years at baseline (1989-1990 or 1992-1993). Ankle brachial index was measured, and participants reported their history of PAD procedures. Participants were followed longitudinally for adjudicated incident PAD events. At baseline, mean BMI was 26.6 (standard deviation, 4.6), and 776 participants (14\%) had prevalent PAD. During 13.2 (median) years of follow-up through June 30, 2007, 276 incident PAD events occurred. In cross-sectional analysis, each 5-unit increase in BMI was inversely associated with PAD (prevalence ratio (PR) = 0.92, 95\% confidence interval (CI): 0.85, 1.00). However, among persons in good health who had never smoked, the direction of association was opposite (PR = 1.20, 95\% CI: 0.94, 1.52). Similar results were observed between BMI calculated using weight at age 50 years and PAD prevalence (PR = 1.30, 95\% CI: 1.11, 1.51) and between BMI at baseline and incident PAD events occurring during follow-up (hazard ratio = 1.32, 95\% CI: 1.00, 1.76) among never smokers in good health. Greater BMI is associated with PAD in older persons who remain healthy and have never smoked. Normal weight maintenance may decrease PAD incidence and associated comorbidity in older age.

}, keywords = {Aged, Ankle Brachial Index, Body Mass Index, Cross-Sectional Studies, Health Status, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Obesity, Peripheral Arterial Disease, Prevalence, Sex Factors, Smoking, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwr228}, author = {Ix, Joachim H and Biggs, Mary L and Kizer, Jorge R and Mukamal, Kenneth J and Djouss{\'e}, Luc and Zieman, Susan J and de Boer, Ian H and Nelson, Tracy L and Newman, Anne B and Criqui, Michael H and Siscovick, David S} } @article {1286, title = {Chronic kidney disease in octogenarians.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Jun}, pages = {1410-7}, abstract = {

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

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

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

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

}, keywords = {Age Factors, Aged, 80 and over, Analysis of Variance, Biomarkers, Cardiovascular Diseases, Chi-Square Distribution, Chronic Disease, Creatinine, Cross-Sectional Studies, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Logistic Models, Male, Models, Biological, Prevalence, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.08801010}, author = {Shastri, Shani and Tighiouart, Hocine and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {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 {1296, title = {Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Oct}, pages = {1100-7}, abstract = {

BACKGROUND: Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.

METHODS: We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).

RESULTS: Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95\% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels >=20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p = .043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p = .55), as compared with smaller changes for both.

CONCLUSION: Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

}, keywords = {Adiponectin, Aged, 80 and over, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Chi-Square Distribution, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Interleukin-6, Male, Mortality, Predictive Value of Tests, Risk Factors, Sensitivity and Specificity, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glr098}, author = {Kizer, Jorge R and Arnold, Alice M and Jenny, Nancy S and Cushman, Mary and Strotmeyer, Elsa S and Ives, Diane G and Ding, Jingzhong and Kritchevsky, Stephen B and Chaves, Paulo H M and Hirsch, Calvin H and Newman, Anne B} } @article {1264, title = {Patterns and predictors of recovery from exhaustion in older adults: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Feb}, pages = {207-13}, abstract = {

OBJECTIVES: To estimate the likelihood of, and factors associated with, recovery from exhaustion in older adults.

DESIGN: Secondary analysis of a cohort study.

SETTING: Six annual examinations in four U.S. communities.

PARTICIPANTS: Four thousand five hundred eighty-four men and women aged 69 and older.

MEASUREMENTS: Exhaustion was considered present when a participant responded "a moderate amount" or "most of the time" to either of two questions: "How often have you had a hard time getting going?" and "How often does everything seem an effort?"

RESULTS: Of the 964 participants who originally reported exhaustion, 634 (65.8\%) were exhaustion free at least once during follow-up. When data from all time points were considered, 48\% of those who reported exhaustion were exhaustion free the following year. After adjustment for age, sex, race, education, and marital status, 1-year recovery was less likely in individuals with worse self-rated health and in those who were taking six or more medications or were obese, depressed, or had musculoskeletal pain or history of stroke. In proportional hazards models, the following risk factors were associated with more persistent exhaustion over 5 years: poor self-rated health, six or more medications, obesity, and depression. Recovery was not less likely in participants with a history of cancer or heart disease.

CONCLUSION: Exhaustion is common in old age but is dynamic, even in those with a history of cancer and congestive heart failure. Recovery is especially likely in seniors who have a positive perception of their overall health, take few medications, and are not obese or depressed. These findings support the notion that resiliency is associated with physical and psychological well-being.

}, keywords = {Aged, Aging, Cardiovascular Physiological Phenomena, Exercise Test, Exercise Tolerance, Female, Follow-Up Studies, Geriatric Assessment, Health Status, Humans, Male, Predictive Value of Tests, Recovery of Function, Retrospective Studies, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2010.03238.x}, author = {Whitson, Heather E and Thielke, Stephen and Diehr, Paula and O{\textquoteright}Hare, Ann M and Chaves, Paulo H M and Zakai, Neil A and Arnold, Alice and Chaudhry, Sarwat and Ives, Diane and Newman, Anne B} } @article {1352, title = {Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {59}, year = {2011}, month = {2011 Oct}, pages = {1793-801}, abstract = {

OBJECTIVES: To examine the association between 25-hydroxyvitamin D (25(OH)D) and physical function in adults of advanced age.

DESIGN: Cross-sectional and longitudinal analysis of physical function over 3~years of follow-up in the Cardiovascular Health Study All Stars.

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

PARTICIPANTS: Community-dwelling adults aged 77 to 100 (N~=~988).

MEASUREMENTS: Serum 25-hydroxyvitamin D 25(OH)D), Short Physical Performance Battery (SPPB), and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADLs) disability were assessed at baseline and every 6~months over 3~years of follow-up.

RESULTS: Almost one-third (30.8\%) of participants were deficient in 25(OH)D (<20~ng/mL). SPPB scores were lower in those with deficient 25(OH)D (mean (standard error) 6.53~(0.24)) than in those with sufficient 25(OH)D (>=30~ng/mL) (7.15~(0.25)) after adjusting for sociodemographic characteristics, season, health behaviors, and chronic conditions (P~=~.006). Grip strength adjusted for body size was also lower in those with deficient 25(OH)D than in those with sufficient 25(OH)D (24.7~(0.6)~kg vs 26.0~(0.6)~kg, P~=~.02). Participants with deficient 25(OH)D were more likely to have prevalent mobility (OR~=~1.44, 95\% confidence interval (CI))~=~0.96-2.14) and ADL disability (OR~=~1.51, 95\% CI~=~1.01-2.25) at baseline than those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at greater risk of incident mobility disability over 3~years of follow-up (hazard ratio~=~1.56, 95\% CI~=~1.06-2.30).

CONCLUSION: Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability in community-dwelling older adults. Moreover, vitamin D deficiency predicted incident mobility disability.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Female, Follow-Up Studies, Geriatric Assessment, Health Surveys, Humans, Male, Mobility Limitation, Muscle Strength, Physical Fitness, Proportional Hazards Models, Reference Values, United States, Vitamin D, Vitamin D Deficiency}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2011.03601.x}, author = {Houston, Denise K and Tooze, Janet A and Davis, Cralen C and Chaves, Paulo H M and Hirsch, Calvin H and Robbins, John A and Arnold, Alice M and Newman, Anne B and Kritchevsky, Stephen B} } @article {1370, title = {Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.}, journal = {Vasc Med}, volume = {17}, year = {2012}, month = {2012 Apr}, pages = {85-93}, abstract = {

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95\% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95\% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Fasting, Female, Health Surveys, Humans, Incidence, Insulin, Insulin Resistance, Logistic Models, Longitudinal Studies, Male, Odds Ratio, Peripheral Arterial Disease, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1477-0377}, doi = {10.1177/1358863X11436195}, author = {Britton, Kathryn A and Mukamal, Kenneth J and Ix, Joachim H and Siscovick, David S and Newman, Anne B and de Boer, Ian H and Thacker, Evan L and Biggs, Mary L and Gaziano, J Michael and Djouss{\'e}, Luc} } @article {1395, title = {Kidney function and mortality in octogenarians: Cardiovascular Health Study All Stars.}, journal = {J Am Geriatr Soc}, volume = {60}, year = {2012}, month = {2012 Jul}, pages = {1201-7}, abstract = {

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

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: Community.

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

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

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

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

}, keywords = {Aged, 80 and over, Analysis of Variance, Cardiovascular Diseases, Chi-Square Distribution, Creatinine, Cystatin C, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Hypertension, Kidney Diseases, Male, Prevalence, Proportional Hazards Models, Retrospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2012.04046.x}, author = {Shastri, Shani and Katz, Ronit and Rifkin, Dena E and Fried, Linda F and Odden, Michelle C and Peralta, Carmen A and Chonchol, Michel and Siscovick, David and Shlipak, Michael G and Newman, Anne B and Sarnak, Mark J} } @article {1357, title = {Predicting late-life disability and death by the rate of decline in physical performance measures.}, journal = {Age Ageing}, volume = {41}, year = {2012}, month = {2012 Mar}, pages = {155-61}, abstract = {

BACKGROUND: the rate of performance decline may influence the risk of disability or death.

METHODS: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998-99, and the rate of performance change between 1992-93 and 1998-99, to the risk of death or disability in 2005-06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992-93 and 1998-99.

RESULTS: participants{\textquoteright} age averaged 79.4 in 1998-99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95\% CI: 1.16 -1.96) and a 1.27 RR of death (95\% CI: 1.07 -1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35\% (95\% CI: 1.13 -1.61) and death by 31\% (95\% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF.

CONCLUSION: performance trajectories independently predict death and disability.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Aged, 80 and over, Aging, Disability Evaluation, Disabled Persons, Female, Geriatric Assessment, Hand Strength, Health Surveys, Humans, Linear Models, Male, Mobility Limitation, Mortality, Motor Skills, Predictive Value of Tests, Risk Assessment, Risk Factors, Survival Analysis, Time Factors, United States, Upper Extremity, Walking}, issn = {1468-2834}, doi = {10.1093/ageing/afr151}, author = {Hirsch, Calvin Hayes and B{\r u}zkov{\'a}, Petra and Robbins, John A and Patel, Kushang V and Newman, Anne B} } @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 {6136, title = {Kidney function and prevalent and incident frailty.}, journal = {Clin J Am Soc Nephrol}, volume = {8}, year = {2013}, month = {2013 Dec}, pages = {2091-9}, abstract = {

BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: CHS enrolled community-dwelling adults age >=65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.

RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24\% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) >=90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95\% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95\% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95\% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95\% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95\% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95\% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.

CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Creatinine, Cross-Sectional Studies, Cystatin C, Fatigue, Female, Frail Elderly, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Independent Living, Kidney, Kidney Diseases, Logistic Models, Male, Motor Activity, Multivariate Analysis, Muscle Weakness, Odds Ratio, Phenotype, Prevalence, Prospective Studies, Risk Factors, Time Factors, United States, Weight Loss}, issn = {1555-905X}, doi = {10.2215/CJN.02870313}, author = {Dalrymple, Lorien S and Katz, Ronit and Rifkin, Dena E and Siscovick, David and Newman, Anne B and Fried, Linda F and Sarnak, Mark J and Odden, Michelle C and Shlipak, Michael G} } @article {5851, title = {Risk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {61}, year = {2013}, month = {2013 Feb 12}, pages = {635-42}, chapter = {635}, abstract = {

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

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

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

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

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

}, keywords = {Age Factors, Aged, Aged, 80 and over, Comorbidity, Effect Modifier, Epidemiologic, Female, Geriatric Assessment, Health Surveys, Heart Failure, Hospitalization, Humans, Longitudinal Studies, Male, Mental Competency, Risk Assessment, Risk Factors, Severity of Illness Index, Stroke Volume, Time-to-Treatment, United States}, issn = {1558-3597}, doi = {10.1016/j.jacc.2012.11.027}, author = {Chaudhry, Sarwat I and McAvay, Gail and Chen, Shu and Whitson, Heather and Newman, Anne B and Krumholz, Harlan M and Gill, Thomas M} } @article {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 {6280, title = {Heritability of and mortality prediction with a longevity phenotype: the healthy aging index.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Apr}, pages = {479-85}, abstract = {

BACKGROUND: Longevity-associated genes may modulate risk for age-related diseases and survival. The Healthy Aging Index (HAI) may be a subphenotype of longevity, which can be constructed in many studies for genetic analysis. We investigated the HAI{\textquoteright}s association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study.

METHODS: The HAI includes systolic blood pressure, pulmonary vital capacity, creatinine, fasting glucose, and Modified Mini-Mental Status Examination score, each scored 0, 1, or 2 using approximate tertiles and summed from 0 (healthy) to 10 (unhealthy). In Cardiovascular Health Study, the association with mortality and accuracy predicting death were determined with Cox proportional hazards analysis and c-statistics, respectively. In Long Life Family Study, heritability was determined with a variance component-based family analysis using a polygenic model.

RESULTS: Cardiovascular Health Study participants with unhealthier index scores (7-10) had 2.62-fold (95\% confidence interval: 2.22, 3.10) greater mortality than participants with healthier scores (0-2). The HAI alone predicted death moderately well (c-statistic = 0.643, 95\% confidence interval: 0.626, 0.661, p < .0001) and slightly worse than age alone (c-statistic = 0.700, 95\% confidence interval: 0.684, 0.717, p < .0001; p < .0001 for comparison of c-statistics). Prediction increased significantly with adjustment for demographics, health behaviors, and clinical comorbidities (c-statistic = 0.780, 95\% confidence interval: 0.765, 0.794, p < .0001). In Long Life Family Study, the heritability of the HAI was 0.295 (p < .0001) overall, 0.387 (p < .0001) in probands, and 0.238 (p = .0004) in offspring.

CONCLUSION: The HAI should be investigated further as a candidate phenotype for uncovering longevity-associated genes in humans.

}, keywords = {Aged, Aging, Cardiovascular Diseases, Female, Genetic Predisposition to Disease, Genotype, Health Behavior, Humans, Longevity, Male, Phenotype, Retrospective Studies, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt117}, author = {Sanders, Jason L and Minster, Ryan L and Barmada, M Michael and Matteini, Amy M and Boudreau, Robert M and Christensen, Kaare and Mayeux, Richard and Borecki, Ingrid B and Zhang, Qunyuan and Perls, Thomas and Newman, Anne B} } @article {6243, title = {Serum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Jun}, pages = {710-6}, abstract = {

BACKGROUND: Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.

METHODS: In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 {\textpm} 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.

RESULTS: Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95\% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95\% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.

CONCLUSIONS: Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML{\textquoteright}s value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Biomarkers, Cardiac Rehabilitation, Cardiovascular Diseases, Disabled Persons, Female, Follow-Up Studies, Frail Elderly, Health Status, Humans, Incidence, Lysine, Male, Prevalence, Prognosis, Retrospective Studies, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt155}, author = {Whitson, Heather E and Arnold, Alice M and Yee, Laura M and Mukamal, Kenneth J and Kizer, Jorge R and Djouss{\'e}, Luc and Ix, Joachim H and Siscovick, David and Tracy, Russell P and Thielke, Stephen M and Hirsch, Calvin and Newman, Anne B and Zieman, Susan} } @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 {6545, title = {Association of mitochondrial DNA levels with frailty and all-cause mortality.}, journal = {J Mol Med (Berl)}, volume = {93}, year = {2015}, month = {2015 Feb}, pages = {177-186}, abstract = {

Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3\% men) from CHS and 11,509 participants (44.9\% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95\% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95\% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population.

}, keywords = {African Americans, Aged, Aged, 80 and over, Aging, DNA, Mitochondrial, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Dosage, Geriatric Assessment, Humans, Kaplan-Meier Estimate, Male, Mortality, Odds Ratio, Population Surveillance, Prospective Studies, Surveys and Questionnaires, United States}, issn = {1432-1440}, doi = {10.1007/s00109-014-1233-3}, author = {Ashar, Foram N and Moes, Anna and Moore, Ann Z and Grove, Megan L and Chaves, Paulo H M and Coresh, Josef and Newman, Anne B and Matteini, Amy M and Bandeen-Roche, Karen and Boerwinkle, Eric and Walston, Jeremy D and Arking, Dan E} } @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 {6996, title = {Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Apr}, pages = {750-6}, abstract = {

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged >=65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95\% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95\% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95\% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95\% confidence interval 1.09, 1.50).

CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.306647}, author = {Garg, Parveen K and Arnold, Alice M and Hinckley Stukovsky, Karen D and Koro, Carol and Jenny, Nancy S and Mukamal, Kenneth J and Criqui, Michael H and Furberg, Curt D and Newman, Anne B and Cushman, Mary} } @article {8402, title = {Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.}, journal = {Lancet Respir Med}, volume = {8}, year = {2020}, month = {2020 01}, pages = {34-44}, abstract = {

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease.

METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (>=17 years), two recruited middle-aged and older adults (>=45 years), and two recruited only elderly adults (>=65 years) with examinations done between 1983 and 2014. FEV decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption.

FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV decline at the median age (57 years) was 31{\textperiodcentered}01 mL per year (95\% CI 30{\textperiodcentered}66-31{\textperiodcentered}37) in sustained never-smokers, 34{\textperiodcentered}97 mL per year (34{\textperiodcentered}36-35{\textperiodcentered}57) in former smokers, and 39{\textperiodcentered}92 mL per year (38{\textperiodcentered}92-40{\textperiodcentered}92) in current smokers. With adjustment, former smokers showed an accelerated FEV decline of 1{\textperiodcentered}82 mL per year (95\% CI 1{\textperiodcentered}24-2{\textperiodcentered}40) compared to never-smokers, which was approximately 20\% of the effect estimate for current smokers (9{\textperiodcentered}21 mL per year; 95\% CI 8{\textperiodcentered}35-10{\textperiodcentered}08). Compared to never-smokers, accelerated FEV decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV decline in current smokers consuming less than five cigarettes per day (7{\textperiodcentered}65 mL per year; 95\% CI 6{\textperiodcentered}21-9{\textperiodcentered}09) was 68\% of that in current smokers consuming 30 or more cigarettes per day (11{\textperiodcentered}24 mL per year; 9{\textperiodcentered}86-12{\textperiodcentered}62), and around five times greater than in former smokers (1{\textperiodcentered}57 mL per year; 1{\textperiodcentered}00-2{\textperiodcentered}14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results.

INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage.

FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

}, keywords = {Adult, Aged, Case-Control Studies, Ex-Smokers, Female, Follow-Up Studies, Humans, Lung, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Non-Smokers, Respiratory Physiological Phenomena, Smokers, Smoking, Spirometry, United States, Young Adult}, issn = {2213-2619}, doi = {10.1016/S2213-2600(19)30276-0}, author = {Oelsner, Elizabeth C and Balte, Pallavi P and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Folsom, Aaron R and Freedman, Neal D and Jacobs, David R and Kalhan, Ravi and Mathew, Amanda R and Kronmal, Richard A and Loehr, Laura R and London, Stephanie J and Newman, Anne B and O{\textquoteright}Connor, George T and Schwartz, Joseph E and Smith, Lewis J and White, Wendy B and Yende, Sachin} }