@article {738, title = {The association between time since last meal and blood pressure in older adults: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {51}, year = {2003}, month = {2003 Jun}, pages = {824-8}, abstract = {

OBJECTIVES: To demonstrate a postprandial hypotensive (PPH) phenomenon in older adults.

DESIGN: Observational, prospective cohort study composed of baseline and nine follow-up visits.

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

PARTICIPANTS: Five thousand eight hundred eighty-eight community-dwelling adults aged 65 and older.

MEASUREMENTS: Blood pressure and time since last meal were recorded synchronously at baseline and at follow-up clinic visits. Generalized estimating equations were used to estimate associations between time since last meal and blood pressure and to adjust variance estimates to account for repeated blood pressure measures within subjects across fasting times.

RESULTS: Mean systolic and diastolic blood pressures were lower in the first hour after the last meal and were progressively higher through the fourth hour after the last meal than blood pressures measured immediately after the last meal (0 hour: 133.7/68.8 mmHg; 1st hour: 130.1/66.6 mmHg; 4th hour: 136.5/71.1 mmHg). Changes were significant for systolic and diastolic measures (P <.001 for both). Exploratory analyses suggested that the systolic PPH association was more pronounced in women. Little evidence was found that the degree of systolic or diastolic PPH varied by age, race, prevalent cardiovascular disease, heart rate, ejection fraction, treated hypertension or diabetes mellitus, or body mass index.

CONCLUSION: These data support previous observations that there is a significant drop in blood pressure within 1 hour after a meal in older adults. Time since last meal may be an important factor to consider when measuring blood pressure in older adults, and perhaps national standards need to be set.

}, keywords = {Aged, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Eating, Female, Humans, Hypotension, Male, Postprandial Period, Prospective Studies, Risk Factors, Time Factors}, issn = {0002-8614}, doi = {10.1046/j.1365-2389.2003.51264.x}, author = {Smith, Nicholas L and Psaty, Bruce M and Rutan, Gale H and Lumley, Thomas and Yanez, David and Chaves, Paulo H M and Kronmal, Richard A} } @article {741, title = {C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Jul 15}, pages = {166-70}, abstract = {

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

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

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

}, keywords = {Aged, Brain Ischemia, C-Reactive Protein, California, Carotid Arteries, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Maryland, North Carolina, Odds Ratio, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000079160.07364.6A}, author = {Cao, Jie J and Thach, Chau and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis H and Chaves, Paulo H M and Polak, Joseph F and Sutton-Tyrrell, Kim and Herrington, David M and Price, Thomas R and Cushman, Mary} } @article {740, title = {Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.}, journal = {J Womens Health (Larchmt)}, volume = {12}, year = {2003}, month = {2003 May}, pages = {341-50}, abstract = {

BACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.

METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).

RESULTS: At baseline, 62\% were never users, 26\% were past users, and 12\% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95\% confidence interval [95\% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).

CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Heart Failure, Humans, Incidence, Life Style, Middle Aged, Multivariate Analysis, Obesity, Osteoporosis, Postmenopausal, Proportional Hazards Models, Prospective Studies, Risk, Risk Factors, United States, Women{\textquoteright}s Health}, issn = {1540-9996}, doi = {10.1089/154099903765448853}, author = {Rea, Thomas D and Psaty, Bruce M and Heckbert, Susan R and Cushman, Mary and Meilahn, Elaine and Olson, Jean L and Lemaitre, Rozenn N and Smith, Nicholas L and Sotoodehnia, Nona and Chaves, Paulo H M} } @article {804, title = {Risk of congestive heart failure in an elderly population treated with peripheral alpha-1 antagonists.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1648-54}, abstract = {

OBJECTIVES: To compare the risk of congestive heart failure (CHF) in elderly individuals treated with any peripheral alpha-1 antagonist for hypertension with any thiazide, test whether the risk persists in subjects without cardiovascular disease (CVD) at baseline, and examine CHF risk in normotensive men with prostatism treated with alpha antagonists.

DESIGN: Prospective cohort study.

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

PARTICIPANTS: A total of 5,888 community-dwelling subjects aged 65 and older.

MEASUREMENTS: Adjudicated incident CHF.

RESULTS: The 3,105 participants with treated hypertension were at risk for CHF; 22\% of men and 8\% of women took alpha antagonists during follow-up. The age-adjusted risk of CHF in those receiving monotherapy treated with alpha antagonists was 1.90 (95\% confidence interval=1.03-3.50) compared with thiazides. In subjects without CVD at baseline receiving monotherapy, women taking an alpha antagonist had a 3.6 times greater age-adjusted risk of CHF, whereas men had no difference in risk. Adjustment for systolic blood pressure attenuated statistical differences in risk. There were 930 men without hypertension at risk for CHF; 5\% used alpha antagonists during follow-up, with no observed increase in CHF risk.

CONCLUSION: Subjects receiving alpha antagonist monotherapy for hypertension had a two to three times greater risk of incident CHF, also seen in lower-risk subjects, but differences in blood pressure control partly explained this.

}, keywords = {Adrenergic alpha-Antagonists, Aged, Antihypertensive Agents, Benzothiadiazines, Blood Pressure, Cohort Studies, Diuretics, Female, Heart Failure, Humans, Hypertension, Male, Risk Factors, Sodium Chloride Symporter Inhibitors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52456.x}, author = {Bryson, Chris L and Smith, Nicholas L and Kuller, Lewis H and Chaves, Paulo H M and Manolio, Teri A and Lewis, William and Boyko, Edward J and Furberg, Curt D and Psaty, Bruce M} } @article {778, title = {Subclinical cardiovascular disease in older adults: insights from the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 May-Jun}, pages = {137-51}, abstract = {

Knowledge about the epidemiology of subclinical cardiovascular disease (SCVD) in older adults may hold the key for improved opportunities for primary prevention of cardiovascular disease (CVD), a top clinical and public health priority. This review reports findings on the prevalence of SCVD and the ability of SCVD measures to predict incident and adverse outcomes from one of the largest (N=5888) and most comprehensive prospective observational studies on SCVD in older adults, the Cardiovascular Health Study. According to a composite index that combined SCVD measures from different vascular beds, the overall prevalence of SCVD was 37\%, making it as common as clinically overt CVD in older adults. SCVD measures strongly predicted incident CVD, stroke, mortality, frailty, and physical and cognitive decline, even after adjustment for traditional CVD risk factors. Ongoing research will address the potential use of SCVD for clinical decision making in older adults.

}, keywords = {Aged, Cardiovascular Diseases, Coronary Artery Disease, Heart Failure, Humans, Longitudinal Studies, Prevalence, Risk Assessment, Risk Factors}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02120.x}, author = {Chaves, Paulo H M and Kuller, Lewis H and O{\textquoteright}Leary, Daniel H and Manolio, Teri A and Newman, Anne B} } @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 {864, title = {A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Oct 24}, pages = {2214-20}, abstract = {

BACKGROUND: Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear.

METHODS: Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities.

RESULTS: A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5\%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95\% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95\% CI, 1.25-1.62) and 1.24 (95\% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95\% CI, 1.15-1.54) and 1.17 (95\% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95\% CI, 1.38-1.78) and 1.38 (95\% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations.

CONCLUSIONS: Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations.

}, keywords = {Age Factors, Aged, Anemia, California, Female, Follow-Up Studies, Health Status, Hemoglobins, Humans, Male, Maryland, Multivariate Analysis, North Carolina, Observation, Pennsylvania, Prospective Studies, Risk Factors, Severity of Illness Index, Survival Rate}, issn = {0003-9926}, doi = {10.1001/archinte.165.19.2214}, author = {Zakai, Neil A and Katz, Ronit and Hirsch, Calvin and Shlipak, Michael G and Chaves, Paulo H M and Newman, Anne B and Cushman, Mary} } @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 {874, title = {Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS).}, journal = {Am Heart J}, volume = {151}, year = {2006}, month = {2006 Jan}, pages = {39-47}, abstract = {

BACKGROUND: Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population.

METHODS: We used 2-dimensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60\% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons.

RESULTS: Mitral annular calcification was found in 1640 (42 \%) subjects, AAC in 1710 (44 \%), AVS in 2114 (54 \%), and all 3 combined in 662 (17 \%). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95\% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC.

CONCLUSIONS: In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile.

}, keywords = {Aged, Aortic Valve, Calcinosis, Female, Heart Valve Diseases, Humans, Male, Mitral Valve, Prevalence, Prospective Studies, Risk Factors, Sclerosis, Ultrasonography}, issn = {1097-6744}, doi = {10.1016/j.ahj.2005.03.052}, author = {Barasch, Eddy and Gottdiener, John S and Larsen, Emily K Marino and Chaves, Paulo H M and Newman, Anne B and Manolio, Teri A} } @article {887, title = {Comparison of mortality risk for electrocardiographic abnormalities in men and women with and without coronary heart disease (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {97}, year = {2006}, month = {2006 Feb 01}, pages = {309-15}, abstract = {

Mortality risk associated with electrocardiographic (ECG) abnormalities has been commonly reported to be lower in women than in men. We compared coronary heart disease (CHD) and all-cause mortality risk for ECG variables during a mean 9.1-year follow-up in 4,912 participants in the Cardiovascular Health Study who were > or = 65 years of age. The hypothesis was that mortality risk for ECG abnormalities is not lower in women than in men. Five ECG variables were significant mortality predictors in Cox regression models that were adjusted for demographic, clinical, and medication variables. Gender differences were significant and mortality risk was higher in women for ECG estimates of left ventricular mass for both end points and for nondipolar QRS voltage for all-cause mortality. When evaluated simultaneously in multiple ECG variable risk models in subgroups that were stratified by baseline CHD status, no gender difference was significant. In the latter models, ST depression was a strong predictor of CHD mortality in groups with and without previous CHD. Other significant ECG predictors were previous myocardial infarction in the previous CHD group and nondipolar QRS voltage in the CHD-free group. Four ECG abnormalities were significant predictors of all-cause mortality in the CHD-free group, with risk increases of 18\% to 50\%. The risk of all-cause mortality in the previous CHD group was significantly increased for ST depression (by 64\%), the ECG estimate of left ventricular mass (by 48\%), and previous myocardial infarction (by 34\%). In conclusion, we found no evidence that the relative risk of mortality for ECG abnormalities is lower in women than in men.

}, keywords = {Aged, Coronary Disease, Electrocardiography, Female, Humans, Male, Risk}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2005.08.046}, author = {Rautaharju, Pentti M and Ge, Sijian and Nelson, Jennifer C and Marino Larsen, Emily K and Psaty, Bruce M and Furberg, Curt D and Zhang, Zhu-Ming and Robbins, John and Gottdiener, John S and Chaves, Paulo H M} } @article {1008, title = {Higher levels of inflammation factors and greater insulin resistance are independently associated with higher heart rate and lower heart rate variability in normoglycemic older individuals: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Feb}, pages = {315-21}, abstract = {

OBJECTIVES: To explore the relationship between (1) insulin resistance and inflammation factors with (2) higher heart rate (HR) and lower heart rate variability (HRV) in normoglycemic older adults.

DESIGN: Cross-sectional population-based study.

PARTICIPANTS: Five hundred forty-five adults aged 65 and older with normoglycemia (fasting glucose <100 mg/dL) who participated in the Cardiovascular Health Study.

MEASUREMENTS: Serum levels of three inflammation proteins (C-reactive protein (CRP), interleukin 6 (IL-6), and fibrinogen); insulin resistance, quantified according to the homeostasis assessment model (HOMA-IR); HR; and four representative measures of HRV (the standard deviation of normal beat to beat intervals (SDNN), the root mean square of successive differences (rMSSD), very low frequency power (VLF), and the low- to high-frequency power ratio (LF/HF)) derived from 24-hour Holter recordings.

RESULTS: High CRP and IL-6 levels were associated with higher HR and lower SDNN and VLF after adjustment for multiple covariates, including HOMA-IR and clinical cardiovascular disease. High IL-6 was also associated with lower LF/HF. Significant univariate inverse relationships between HOMA-IR and HR and HRV were also found, but the strengths of these relationships were attenuated after adjustment for inflammation factors.

CONCLUSION: Increased levels of inflammation markers and HOMA-IR are associated with higher HR and lower HRV. These findings suggest that inflammation may contribute to the pathogenesis of cardiovascular autonomic decline in older adults.

}, keywords = {Aged, C-Reactive Protein, Cardiovascular Diseases, Cross-Sectional Studies, Electrocardiography, Ambulatory, Female, Fibrinogen, Heart Rate, Humans, Inflammation Mediators, Insulin Resistance, Interleukin-6, Male, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01564.x}, author = {Stein, Phyllis K and Barzilay, Joshua I and Chaves, Paulo H M and Traber, Jennifer and Domitrovich, Peter P and Heckbert, Susan R and Gottdiener, John S} } @article {1042, title = {Novel measures of heart rate variability predict cardiovascular mortality in older adults independent of traditional cardiovascular risk factors: the Cardiovascular Health Study (CHS).}, journal = {J Cardiovasc Electrophysiol}, volume = {19}, year = {2008}, month = {2008 Nov}, pages = {1169-74}, abstract = {

UNLABELLED: Novel HRV Predicts CV Mortality in the Elderly.

BACKGROUND: It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties of heart rate variability identify older adults at increased risk of cardiovascular death (CVdth).

METHODS: Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people >or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset [TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low = <10, mid = 10-20, and high >20) and adjusted for prevalent clinical cardiovascular disease (CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs).

RESULTS: CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum, low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS; 2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth (RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group. Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9, high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2).

CONCLUSIONS: The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among older adults even after adjustment for conventional CVD risk measures and the presence of CVD.

}, keywords = {Aged, Aged, 80 and over, Arrhythmias, Cardiac, Death, Sudden, Cardiac, Electrocardiography, Ambulatory, Female, Heart Rate, Humans, Male, Maryland, Reproducibility of Results, Risk Assessment, Risk Factors, Sensitivity and Specificity, Survival Analysis, Survival Rate}, issn = {1540-8167}, doi = {10.1111/j.1540-8167.2008.01232.x}, author = {Stein, Phyllis K and Barzilay, Joshua I and Chaves, Paulo H M and Mistretta, Stephanie Q and Domitrovich, Peter P and Gottdiener, John S and Rich, Michael W and Kleiger, Robert E} } @article {1069, title = {Heart rate variability and its changes over 5 years in older adults.}, journal = {Age Ageing}, volume = {38}, year = {2009}, month = {2009 Mar}, pages = {212-8}, abstract = {

PURPOSE: to characterise the association between age, ageing and heart rate variability (HRV) in older individuals, 585 adults age >65 years with two 24-h Holter recordings in the Cardiovascular Health Study were studied.

METHODS: heart rate (HR), ventricular premature contractions (VPCs), atrial premature contractions (APCs), frequency-domain, ratio-based and non-linear HRV and heart rate turbulence (HRT) were examined cross-sectionally by 5-year age groups and prospectively over 5 years. Analyses adjusted for gender, lower versus elevated cardiovascular (CV) risk and for the change in CV risk.

RESULTS: HR declined, and VPCs and APCs increased per 5-year increase in age. Frequency-domain HRV decreased more at 65-69, less at 70-74 and minimally at > or =75 years, independent of CVD risk or change in CVD risk. Ratio and non-linear HRV continued to decline to > or =75 years old. Ratio HRV and HRT slope were more strongly related to CVD risk than frequency-domain HRV.

CONCLUSIONS: cardiac autonomic function, assessed by frequency-domain HRV, declines most at 65-70 and levels off at age >75. The decline is independent of CVD risk or change in CVD risk. Ratio-based and non-linear HRV and HRT slope continued to change with increasing age and were more closely related to CVD risk than frequency-domain HRV.

}, keywords = {Age Distribution, Aged, Aging, Atrial Premature Complexes, Autonomic Nervous System, Cardiovascular Diseases, Cross-Sectional Studies, Electrocardiography, Ambulatory, Female, Heart Rate, Humans, Hypertension, Male, Nonlinear Dynamics, Prevalence, Prospective Studies, Risk Factors, Ventricular Premature Complexes}, issn = {1468-2834}, doi = {10.1093/ageing/afn292}, author = {Stein, Phyllis K and Barzilay, Joshua I and Chaves, Paulo H M and Domitrovich, Peter P and Gottdiener, John S} } @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 {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 {1269, title = {Hypertension, white matter hyperintensities, and concurrent impairments in mobility, cognition, and mood: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {123}, year = {2011}, month = {2011 Mar 01}, pages = {858-65}, abstract = {

BACKGROUND: Our objective was to investigate the association between hypertension and concurrent impairments in mobility, cognition, and mood; the role of brain white matter hyperintensities in mediating this association; and the impact of these impairments on disability and mortality in elderly hypertensive individuals.

METHODS AND RESULTS: -Blood pressure, gait speed, digit symbol substitution test, and the Center for Epidemiological Studies Depression Scale were measured yearly (1992-1999) on 4700 participants in the Cardiovascular Health Study (age: 74.7, 58\% women, 17\% blacks, 68\% hypertension, 3600 had brain magnetic resonance imaging in 1992-1993, survival data 1992-2005). Using latent profile analysis at baseline, we found that 498 (11\%) subjects had concurrent impairments and 3086 (66\%) were intact on all 3 measures. Between 1992 and 1999, 651 (21\%) became impaired in all 3 domains. Hypertensive individuals were more likely to be impaired at baseline (odds ratio 1.23, 95\% confidence interval 1.04 to 1.42, P=0.01) and become impaired during the follow-up (hazard ratio=1.3, 95\% confidence interval 1.02 to 1.66, P=0.037). A greater degree of white matter hyperintensities was associated with impairments in the 3 domains (P=0.007) and mediated the association with hypertension (P=0.19 for hypertension after adjusting for white matter hyperintensities in the model, 21\% hazard ratio change). Impairments in the 3 domains increased subsequent disability with hypertension (P<0.0001). Hypertension mortality also was increased in those impaired (compared with unimpaired hypertensive individuals: HR=1.10, 95\% confidence interval 1.04 to 1.17, P=0.004).

CONCLUSIONS: Hypertension increases the risk of concurrent impairments in mobility, cognition, and mood, which increases disability and mortality. This association is mediated in part by microvascular brain injury.

}, keywords = {Aged, Aged, 80 and over, Brain, Cognition Disorders, Female, Humans, Hypertension, Kaplan-Meier Estimate, Longitudinal Studies, Magnetic Resonance Imaging, Male, Microcirculation, Mobility Limitation, Mood Disorders, Nerve Fibers, Myelinated, Retrospective Studies, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.978114}, author = {Hajjar, Ihab and Quach, Lien and Yang, Frances and Chaves, Paulo H M and Newman, Anne B and Mukamal, Kenneth and Longstreth, Will and Inzitari, Marco and Lipsitz, Lewis A} } @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 {1338, title = {Surrogate screening models for the low physical activity criterion of frailty.}, journal = {Aging Clin Exp Res}, volume = {23}, year = {2011}, month = {2011 Jun}, pages = {209-16}, abstract = {

BACKGROUND AND AIMS: Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women{\textquoteright}s Health and Aging Study (WHAS).

METHODS: Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality.

RESULTS: Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive.

CONCLUSIONS: We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

}, keywords = {Activities of Daily Living, Aged, Cohort Studies, Exercise, Female, Follow-Up Studies, Frail Elderly, Geriatric Assessment, Humans, Leisure Activities, Logistic Models, Male, Motor Activity, Prospective Studies, Surveys and Questionnaires, Women{\textquoteright}s Health}, issn = {1594-0667}, author = {Eckel, Sandrah P and Bandeen-Roche, Karen and Chaves, Paulo H M and Fried, Linda P and Louis, Thomas A} } @article {1366, title = {Long-term assessment of inflammation and healthy aging in late life: the Cardiovascular Health Study All Stars.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {67}, year = {2012}, month = {2012 Sep}, pages = {970-6}, abstract = {

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

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

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

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

}, keywords = {Aged, Aged, 80 and over, Aging, C-Reactive Protein, Cardiovascular Diseases, Cognition, Cohort Studies, Cross-Sectional Studies, Female, Humans, Inflammation, Inflammation Mediators, Interleukin-6, Longitudinal Studies, Male, Risk Factors, Vermont}, issn = {1758-535X}, doi = {10.1093/gerona/glr261}, author = {Jenny, Nancy S and French, Benjamin and Arnold, Alice M and Strotmeyer, Elsa S and Cushman, Mary and Chaves, Paulo H M and Ding, Jingzhong and Fried, Linda P and Kritchevsky, Stephen B and Rifkin, Dena E and Sarnak, Mark J and Newman, Anne B} } @article {1400, title = {Modification of the association between ambient air pollution and lung function by frailty status among older adults in the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {176}, year = {2012}, month = {2012 Aug 01}, pages = {214-23}, abstract = {

The susceptibility of older adults to the health effects of air pollution is well-recognized. Advanced age may act as a partial surrogate for conditions associated with aging. The authors investigated whether gerontologic frailty (a clinical health status metric) modified the association between ambient level of ozone or particulate matter with an aerodynamic diameter less than 10 {\textmu}m and lung function in 3,382 older adults using 7 years of follow-up data (1990-1997) from the Cardiovascular Health Study and its Environmental Factors Ancillary Study. Monthly average pollution and annual frailty assessments were related to up to 3 repeated measurements of lung function using cumulative summaries of pollution and frailty histories that accounted for duration as well as concentration. Frailty history was found to modify long-term associations of pollutants with forced vital capacity. For example, the decrease in forced vital capacity associated with a 70-ppb/month greater cumulative sum of monthly average ozone exposure was 12.3 mL (95\% confidence interval: 10.4, 14.2) for a woman who had spent the prior 7 years prefrail or frail as compared with 4.7 mL (95\% confidence interval: 3.8, 5.6) for a similar woman who was robust during all 7 years (interaction P < 0.001).

}, keywords = {Aged, Air Pollution, Cardiovascular Diseases, Female, Forced Expiratory Volume, Frail Elderly, Geriatric Assessment, Humans, Male, Prospective Studies, Respiratory Function Tests, Sex Factors, Smoking, Time Factors, United States, Vital Capacity}, issn = {1476-6256}, doi = {10.1093/aje/kws001}, author = {Eckel, Sandrah P and Louis, Thomas A and Chaves, Paulo H M and Fried, Linda P and Margolis, And Helene G} } @article {1351, title = {Retinal microvascular signs and disability in the Cardiovascular Health Study.}, journal = {Arch Ophthalmol}, volume = {130}, year = {2012}, month = {2012 Mar}, pages = {350-6}, abstract = {

OBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL).

DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25\% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.

RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1\% vs 7.1\%; adjusted hazard ratio, 1.45; 95\% confidence interval, 1.24-1.69; P~<~.001). There was no evidence of interaction by advanced carotid atherosclerosis (P~>~.10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.

CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.

}, keywords = {Activities of Daily Living, Aged, Carotid Artery Diseases, Cognition Disorders, Diagnostic Techniques, Ophthalmological, Disability Evaluation, Follow-Up Studies, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Microcirculation, Predictive Value of Tests, Prevalence, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Smoking}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2011.360}, author = {Kim, Dae Hyun and Chaves, Paulo H M and Newman, Anne B and Klein, Ronald and Sarnak, Mark J and Newton, Elizabeth and Strotmeyer, Elsa S and Burke, Gregory L and Lipsitz, Lewis A} } @article {1564, title = {Soluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {33}, year = {2013}, month = {2013 Jan}, pages = {158-64}, abstract = {

OBJECTIVE: CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.

METHODS AND RESULTS: We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.

CONCLUSIONS: CD14 independently predicts risk mortality in older adults.

}, keywords = {African Americans, Age Factors, Aged, Biomarkers, Cardiovascular Diseases, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Hexosyltransferases, Humans, Incidence, Inflammation Mediators, Linear Models, Lipopolysaccharide Receptors, Logistic Models, Male, Membrane Proteins, Multivariate Analysis, Phenotype, Polymorphism, Single Nucleotide, Principal Component Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.112.300421}, author = {Reiner, Alex P and Lange, Ethan M and Jenny, Nancy S and Chaves, Paulo H M and Ellis, Jaclyn and Li, Jin and Walston, Jeremy and Lange, Leslie A and Cushman, Mary and Tracy, Russell P} } @article {6363, title = {Prognostic implications of microvascular and macrovascular abnormalities in older adults: cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Dec}, pages = {1495-502}, abstract = {

BACKGROUND: Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.

METHODS: This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009).

RESULTS: At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95\% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease.

CONCLUSIONS: Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Aging, Ankle Brachial Index, Disability Evaluation, Electrocardiography, Female, Follow-Up Studies, Forecasting, Humans, Life Expectancy, Magnetic Resonance Imaging, Male, Microcirculation, Prognosis, Prospective Studies, Risk Factors, Vascular Malformations}, issn = {1758-535X}, doi = {10.1093/gerona/glu074}, author = {Kim, Dae Hyun and Grodstein, Francine and Newman, Anne B and Chaves, Paulo H M and Odden, Michelle C and Klein, Ronald and Sarnak, Mark J and Patel, Kushang V and Lipsitz, Lewis A} } @article {7017, title = {Vitamin D and the risk of dementia and Alzheimer disease.}, journal = {Neurology}, volume = {83}, year = {2014}, month = {2014 Sep 2}, pages = {920-8}, abstract = {

OBJECTIVE: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.

METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria.

RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95\% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (>=25 to <50 nmol/L) were 2.25 (95\% CI: 1.23-4.13) and 1.53 (95\% CI: 1.06-2.21) compared to participants with sufficient concentrations (>=50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95\% CI: 1.02-4.83) and 1.69 (95\% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

CONCLUSION: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.

}, keywords = {Aged, Alzheimer Disease, Dementia, Female, Follow-Up Studies, Humans, Incidence, Male, Proportional Hazards Models, Risk Factors, United States, Vitamin D, Vitamin D Deficiency}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000000755}, author = {Littlejohns, Thomas J and Henley, William E and Lang, Iain A and Annweiler, Cedric and Beauchet, Olivier and Chaves, Paulo H M and Fried, Linda and Kestenbaum, Bryan R and Kuller, Lewis H and Langa, Kenneth M and Lopez, Oscar L and Kos, Katarina and Soni, Maya and Llewellyn, David J} } @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 {6935, title = {Cardiovascular and Mortality Outcomes in the Elderly With Impaired Cardiac and Pulmonary Function: The Cardiovascular Health Study (CHS).}, journal = {J Am Heart Assoc}, volume = {4}, year = {2015}, month = {2015 Dec}, abstract = {

BACKGROUND: Impaired pulmonary function (IPF) and left ventricular systolic dysfunction (LVSD) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of IPF and LVSD with heart failure, cardiovascular mortality and all-cause mortality, and their impact on risk classification using a continuous net reclassification index.

METHODS AND RESULTS: We followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years. LVSD was defined as LV ejection fraction <55\%. IPF was defined as: forced expiratory volume in 1 second:forced vital capacity <70\%, and predicted forced expiratory volume in 1 second <80\%. Outcomes included heart failure hospitalization, cardiovascular mortality, all-cause mortality, and composite outcome. LVSD was detected in 128 subjects (6\%), IPF in 441 (19\%) and both in 38 (2\%). Compared to those without LVSD or IPF, there was a significantly increased cardiovascular risk for groups of LVSD only, IPF only, and LVSD plus IPF, adjusted hazard ratio (95\% CI) 2.1 (1.5-3.0), 1.7 (1.4-2.1), and 3.2 (2.0-5.1) for HF; 1.8 (1.2-2.6), 1.4 (1.1-1.8), and 2.8 (1.7-4.7) for cardiovascular mortality; 1.3 (1.0-1.8), 1.7 (1.4-1.9), and 2.1 (1.5-3.0) for all-cause mortality, and 1.6 (1.3-2.1), 1.7 (1.5-1.9), and 2.4 (1.7-3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when IPF was added to the adjusted model with LVSD or LVSD to IPF.

CONCLUSIONS: While risk of cardiovascular outcomes was the highest among elderly with both LVSD and IPF, risk was comparable between subjects with IPF alone and those with LVSD alone. This observation, combined with improved risk classification by adding IPF to LVSD or LVSD to IPF, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Heart Diseases, Heart Failure, Hospitalization, Humans, Kaplan-Meier Estimate, Lung Diseases, Male, Mortality, Prospective Studies, Respiratory Function Tests, Risk Assessment, Risk Factors, Stroke Volume, United States, Ventricular Dysfunction, Left}, issn = {2047-9980}, doi = {10.1161/JAHA.115.002308}, author = {Waheed, Salman and Chaves, Paulo H M and Gardin, Julius M and Cao, Jie Jane} } @article {6852, title = {Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {63}, year = {2015}, month = {2015 Sep}, pages = {1886-93}, abstract = {

OBJECTIVES: To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function

DESIGN: Cross-sectional analysis of the Cardiovascular Health Study (1998-1999).

SETTING: Community.

PARTICIPANTS: Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5).

MEASUREMENTS: Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand)

RESULTS: Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95\% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95\% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95\% CI = -0.24 to -0.08 vs -0.13, 95\% CI = -0.20 to -0.06; physical function: -0.15, 95\% CI = -0.22 to -0.08 vs -0.12, 95\% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function.

CONCLUSION: Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication.

}, keywords = {Aged, Aged, 80 and over, Cognition, Cross-Sectional Studies, Female, Humans, Male, Neuropsychological Tests, Vascular Malformations}, issn = {1532-5415}, doi = {10.1111/jgs.13594}, author = {Kim, Dae Hyun and Grodstein, Francine and Newman, Anne B and Chaves, Paulo H M and Odden, Michelle C and Klein, Ronald and Sarnak, Mark J and Lipsitz, Lewis A} } @article {6770, title = {Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults.}, journal = {Kidney Int}, volume = {88}, year = {2015}, month = {2015 Nov}, pages = {1126-34}, abstract = {

Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30\% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23\% lower odds of eGFR decline (odds ratio 0.77 (95\% CI 0.62-0.96)) and a 10\% lower risk of mortality (hazard ratio 0.90 (95\% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Creatinine, Disease Progression, Female, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney Failure, Chronic, Male, Proportional Hazards Models, Uromodulin}, issn = {1523-1755}, doi = {10.1038/ki.2015.192}, author = {Garimella, Pranav S and Biggs, Mary L and Katz, Ronit and Ix, Joachim H and Bennett, Michael R and Devarajan, Prasad and Kestenbaum, Bryan R and Siscovick, David S and Jensen, Majken K and Shlipak, Michael G and Chaves, Paulo H M and Sarnak, Mark J} } @article {7247, title = {Can a Healthy Lifestyle Compress the Disabled Period in Older Adults?}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Oct}, pages = {1952-1961}, abstract = {

OBJECTIVES: To determine whether lifestyle factors, measured late in life, could compress the disabled period toward the end of life.

DESIGN: Community-based cohort study of older adults followed from 1989 to 2015.

SETTING: Four U.S. communities.

PARTICIPANTS: Community-living men and women aged 65 and older (N = 5,248, mean age 72.7 {\textpm} 5.5, 57\% female, 15.2\% minority) who were not wheelchair dependent and were able to give informed consent at baseline.

MEASUREMENTS: Multiple lifestyle factors, including smoking, alcohol consumption, physical activity, diet, body mass index (BMI), social networks, and social support, were measured at baseline. Activities of daily living (ADLs) were assessed at baseline and throughout follow-up. Years of life (YoL) was defined as years until death. Years of able life (YAL) was defined as years without any ADL difficulty. YAL/YoL\%, the proportion of life lived able, was used to indicate the relative compression or expansion of the disabled period.

RESULTS: The average duration of disabled years was 4.5 (out of 15.4 mean YoL) for women and 2.9 (out of 12.4 mean YoL) for men. In a multivariable model, obesity was associated with 7.3 percentage points (95\% confidence interval (CI) = 5.4-9.2) lower YAL/YoL\% than normal weight. Scores in the lowest quintile of the Alternate Healthy Eating Index were associated with a 3.7\% (95\% CI = 1.6-5.9) lower YAL/YoL\% than scores in the highest quintile. Every 25 blocks walked in a week was associated with 0.5 percentage points (95\% CI = 0.3-0.8) higher YAL/YoL\%.

CONCLUSION: The effects of healthy lifestyle factors on the proportion of future life lived free of disability indicate that the disabled period can be compressed, given the right combination of these factors.

}, issn = {1532-5415}, doi = {10.1111/jgs.14314}, author = {Jacob, Mini E and Yee, Laura M and Diehr, Paula H and Arnold, Alice M and Thielke, Stephen M and Chaves, Paulo H M and Gobbo, Liana Del and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {6999, title = {Vitamin D and Memory Decline: Two Population-Based Prospective Studies.}, journal = {J Alzheimers Dis}, volume = {50}, year = {2016}, month = {2016}, pages = {1099-108}, abstract = {

BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown.

OBJECTIVE: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline.

METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey{\textquoteright}s Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively.

RESULTS: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95\% CI: -0.06 to 0.01) and -0.10 SD (95\% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95\% CI: -0.01 to 0.02) and -0.01 SD (95\% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34).

CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.

}, issn = {1875-8908}, doi = {10.3233/JAD-150811}, author = {Ku{\'z}ma, El{\.z}bieta and Soni, Maya and Littlejohns, Thomas J and Ranson, Janice M and van Schoor, Natasja M and Deeg, Dorly J H and Comijs, Hannie and Chaves, Paulo H M and Kestenbaum, Bryan R and Kuller, Lewis H and Lopez, Oscar L and Becker, James T and Langa, Kenneth M and Henley, William E and Lang, Iain A and Ukoumunne, Obioha C and Llewellyn, David J} } @article {7126, title = {Vitamin D and Risk of Neuroimaging Abnormalities.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016}, pages = {e0154896}, abstract = {

Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer{\textquoteright}s disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged >=65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95\% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (>=25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (>=50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0154896}, author = {Littlejohns, Thomas J and Kos, Katarina and Henley, William E and Lang, Iain A and Annweiler, Cedric and Beauchet, Olivier and Chaves, Paulo H M and Kestenbaum, Bryan R and Kuller, Lewis H and Langa, Kenneth M and Lopez, Oscar L and Llewellyn, David J} } @article {7344, title = {Bone Mineral Density and Risk of Heart Failure in Older Adults: The Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {6}, year = {2017}, month = {2017 Mar 13}, abstract = {

BACKGROUND: Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density (BMD) and heart failure (HF) risk remains insufficiently studied.

METHODS AND RESULTS: We investigated whether BMD measured by dual-energy x-ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55\% women) developed HF during the median follow-up of 10.5~years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF, with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95\% CI, 1.01-1.26] per 0.1~g/cm(2) decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95\% CI, 0.59-0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95\% CI, 1.39-5.74]) compared with normal BMD.

CONCLUSIONS: Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways.

}, issn = {2047-9980}, doi = {10.1161/JAHA.116.004344}, author = {Fohtung, Raymond B and Brown, David L and Koh, William J H and Bartz, Traci M and Carbone, Laura D and Civitelli, Roberto and Stein, Phyllis K and Chaves, Paulo H M and Kestenbaum, Bryan R and Kizer, Jorge R} } @article {7544, title = {Late-Life Depressive Symptoms as Partial Mediators in the Associations between Subclinical Cardiovascular Disease with Onset of Mild Cognitive Impairment and Dementia.}, journal = {Am J Geriatr Psychiatry}, year = {2017}, month = {2017 Nov 20}, abstract = {

OBJECTIVE: To study whether depression contributes to the association between subclinical cardiovascular disease (CVD) and dementia, and identify the contribution{\textquoteright}s magnitude.

METHODS: Among participants from the Cardiovascular Health Study Cognition Study who did not have baseline CVD-related events (N = 2,450), causal mediation methodology was implemented to examine whether late-life depressive symptoms, defined as 10-item Center for Epidemiologic Studies-Depression (mCES-D) Scale scores >=8 from 2 to 3 years after baseline, partially mediated the association of baseline subclinical CVD (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) with mild cognitive impairment (MCI)/dementia onset occurring between 5 and 10 years from baseline. The total effect was decomposed into direct and indirect effects (via late-life depressive symptoms), obtained from an accelerated failure time model with weights derived from multivariable logistic regression of late-life depressive symptoms on subclinical CVD. Analyses were adjusted by baseline covariates: age, race, sex, poverty status, marital status, body mass index, smoking status, ApoE4 status, and mCES-D.

RESULTS: Participants contributed 20,994 person-years of follow-up with a median follow-up time of 9.4 years. Subclinical CVD was associated with 12\% faster time to MCI/dementia (time ratio [TR]: 0.88; 95\% CI: 0.83, 0.93). The total effect of subclinical CVD on MCI/dementia onset was decomposed into a direct effect (TR: 0.95, 95\% CI: 0.92, 0.98) and indirect effect (TR: 0.92, 95\% CI: 0.88, 0.97); 64.5\% of the total effect was mediated by late-life depressive symptoms.

CONCLUSIONS: These data suggest late-life depressive symptoms partially mediate the association of subclinical CVD with MCI/dementia onset.

}, issn = {1545-7214}, doi = {10.1016/j.jagp.2017.11.004}, author = {Armstrong, Nicole M and Carlson, Michelle C and Schrack, Jennifer and Xue, Qian-Li and Carnethon, Mercedes R and Rosano, Caterina and Chaves, Paulo H M and Gross, Alden L} } @article {7545, title = {Role of Late-Life Depression in the Association of Subclinical Cardiovascular Disease With All-Cause Mortality: Cardiovascular Health Study.}, journal = {J Aging Health}, year = {2017}, month = {2017 Nov 01}, pages = {898264317744921}, abstract = {

OBJECTIVES: To evaluate whether late-life depression mediates the association of subclinical cardiovascular disease (CVD) with all-cause mortality.

METHOD: Using data from 3,473 Cardiovascular Health Study participants, the Cox proportional hazards model was used to examine the direct and indirect (via late-life depression) effects of the association between baseline subclinical CVD and all-cause mortality with weights derived from multivariable logistic regression of late-life depression on subclinical CVD.

RESULTS: Subclinical CVD led to a higher risk of all-cause mortality (hazard ratio [HR] = 1.51, 95\% confidence interval, [CI] = [1.42, 1.94]). Total effect of subclinical CVD on all-cause mortality was decomposed into direct (HR = 1.41, 95\% CI = [1.37, 1.58]) and indirect (HR = 1.07, 95\% CI = [1.01, 1.23]) effects; 16.3\% of the total effect of subclinical CVD on all-cause mortality was mediated by late-life depression.

DISCUSSION: Late-life depression accounts for little, if any, of the association between subclinical CVD, a risk factor of all-cause mortality, and all-cause mortality.

}, issn = {1552-6887}, doi = {10.1177/0898264317744921}, author = {Armstrong, Nicole M and Carlson, Michelle C and Xue, Qian-Li and Schrack, Jennifer and Carnethon, Mercedes R and Chaves, Paulo H M and Gross, Alden L} } @article {7656, title = {Social Network Trajectories in Myocardial Infarction Versus Ischemic Stroke.}, journal = {J Am Heart Assoc}, volume = {7}, year = {2018}, month = {2018 Apr 13}, abstract = {

BACKGROUND: Changes in social networks are rarely examined before and after various diseases because of insufficient data. CHS (The Cardiovascular Health Study) offers an opportunity to compare social network trajectories surrounding well-adjudicated myocardial infarction (MI) or stroke events. We tested the hypothesis that social networks will be stable after MI and decrease after stroke.

METHODS AND RESULTS: We examined trajectories of the Lubben Social Network Scale score (LSNS, range 0-50) before and after vascular events over 11~years. The LSNS assesses engagement in family networks, friends{\textquoteright} networks, and social supports. We used a linear mixed model with repeated measures and fixed effects to compare the change in social network score before and after events in 395 people with MI and 382 with ischemic stroke. Over a mean of 12.4~years of follow-up for MI and 11.1~years for stroke, we examined an average of 4 social network scores for each participant. We controlled for sociodemographics, baseline cognitive function, and comorbidities. The participants{\textquoteright} mean age was 73.5, 51\% were women, and 88\% were non-Hispanic white. After MI, the social network trajectory remained stable compared with the baseline trajectory (-0.06 points per year, adjusted =0.2356). After stroke, the social network trajectory declined compared with the baseline trajectory (-0.14 points per year, adjusted =0.0364).

CONCLUSIONS: Social networks remained stable after MI and declined after stroke. This small and persistent decline after adjustment for potential confounders is notable because it deviates from stable network trajectories found in CHS participants and is specific to stroke.

}, issn = {2047-9980}, doi = {10.1161/JAHA.117.008029}, author = {Dhand, Amar and Longstreth, W T and Chaves, Paulo H M and Dhamoon, Mandip S} } @article {8007, title = {Association of serum uromodulin with mortality and cardiovascular disease in the elderly-the Cardiovascular Health Study.}, journal = {Nephrol Dial Transplant}, year = {2019}, month = {2019 Mar 21}, abstract = {

BACKGROUND: Uromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.

METHODS: We measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants{\textquoteright} demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5\% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.

RESULTS: The mean age was 78 {\textpm} 5 years, 40\% were male, sUMOD level was 127 {\textpm} 64 ng/mL, eGFR was 63 mL/min/1.73~m2 and 42\% had CKD defined as eGFR <60 mL/min/1.73~m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95\% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95\% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95\% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95\% CI 0.70-1.01)].

CONCLUSION: Higher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.

}, issn = {1460-2385}, doi = {10.1093/ndt/gfz008}, author = {Steubl, Dominik and B{\r u}zkov{\'a}, Petra and Garimella, Pranav S and Ix, Joachim H and Devarajan, Prasad and Bennett, Michael R and Chaves, Paulo H M and Shlipak, Michael G and Bansal, Nisha and Sarnak, Mark J} } @article {8047, title = {Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.}, journal = {Circulation}, volume = {139}, year = {2019}, month = {2019 May 21}, pages = {2422-2436}, abstract = {

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95\% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.118.038908}, author = {Marklund, Matti and Wu, Jason H Y and Imamura, Fumiaki and Del Gobbo, Liana C and Fretts, Amanda and de Goede, Janette and Shi, Peilin and Tintle, Nathan and Wennberg, Maria and Aslibekyan, Stella and Chen, Tzu-An and de Oliveira Otto, Marcia C and Hirakawa, Yoichiro and Eriksen, Helle H{\o}jmark and Kr{\"o}ger, Janine and Laguzzi, Federica and Lankinen, Maria and Murphy, Rachel A and Prem, Kiesha and Samieri, Cecilia and Virtanen, Jyrki and Wood, Alexis C and Wong, Kerry and Yang, Wei-Sin and Zhou, Xia and Baylin, Ana and Boer, Jolanda M A and Brouwer, Ingeborg A and Campos, Hannia and Chaves, Paulo H M and Chien, Kuo-Liong and de Faire, Ulf and Djouss{\'e}, Luc and Eiriksdottir, Gudny and El-Abbadi, Naglaa and Forouhi, Nita G and Michael Gaziano, J and Geleijnse, Johanna M and Gigante, Bruna and Giles, Graham and Guallar, Eliseo and Gudnason, Vilmundur and Harris, Tamara and Harris, William S and Helmer, Catherine and Hellenius, Mai-Lis and Hodge, Allison and Hu, Frank B and Jacques, Paul F and Jansson, Jan-H{\r a}kan and Kalsbeek, Anya and Khaw, Kay-Tee and Koh, Woon-Puay and Laakso, Markku and Leander, Karin and Lin, Hung-Ju and Lind, Lars and Luben, Robert and Luo, Juhua and McKnight, Barbara and Mursu, Jaakko and Ninomiya, Toshiharu and Overvad, Kim and Psaty, Bruce M and Rimm, Eric and Schulze, Matthias B and Siscovick, David and Skjelbo Nielsen, Michael and Smith, Albert V and Steffen, Brian T and Steffen, Lyn and Sun, Qi and Sundstr{\"o}m, Johan and Tsai, Michael Y and Tunstall-Pedoe, Hugh and Uusitupa, Matti I J and van Dam, Rob M and Veenstra, Jenna and Monique Verschuren, W M and Wareham, Nick and Willett, Walter and Woodward, Mark and Yuan, Jian-Min and Micha, Renata and Lemaitre, Rozenn N and Mozaffarian, Dariush and Riserus, Ulf} } @article {7982, title = {Discrepancy in Frailty Identification: Move beyond Predictive Validity.}, journal = {J Gerontol A Biol Sci Med Sci}, year = {2019}, month = {2019 Feb 21}, abstract = {

BACKGROUND: To evaluate the discordance in frailty classification between the frailty index (FI) and the physical frailty phenotype (PFP) and identify factors discriminating those with discordant frailty classification from each other and from those for whom the assessments agree.

METHODS: A prospective observational study of older adults aged 65 and older selected from Medicare eligibility lists in four US communities (n=5,362). The PFP was measured by the Cardiovascular Health Study PFP. Subjects meeting >=3 of the 5 criteria were deemed frail. The FI was calculated as the proportion of deficits in an a priori selected set of 48 measures and subjects were classified as frail if FI>0.35.

RESULTS: The prevalence of frailty was 7.0\% by the PFP and 8.3\% by the FI. Of the 730 deemed frail by either instrument, only 12\% were in agreement; whereas 39\% were classified as frail by PFP but not FI; and 48\% were classified as frail by FI but not PFP. Participants aged 65-72 or greater disease burden were mostly likely to be characterized as being FI-frail but not PFP-frail. The associations of frailty with age and mortality was stronger when frailty was measured by the PFP rather than the FI.

CONCLUSIONS: Despite comparable frailty prevalence between the PFP and the FI, there was substantial discordance in individual-level classification, with highest agreement existing only in the most vulnerable subset. These findings suggest that there are clinically important contexts in which PFP and FI cannot be used interchangeably.

}, issn = {1758-535X}, doi = {10.1093/gerona/glz052}, author = {Xue, Qian-Li and Tian, Jing and Walston, Jeremy D and Chaves, Paulo H M and Newman, Anne B and Bandeen-Roche, Karen} } @article {8620, title = {Association of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.}, journal = {JAMA Intern Med}, volume = {180}, year = {2020}, month = {2020 05 01}, pages = {676-686}, abstract = {

Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain.

Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers.

Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018.

Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years.

Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis.

Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2\% were female, 65.9\% were non-Hispanic white, and 49.6\% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7\%]) had accelerated decreases in FEV1 (4.1 mL/y; 95\% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95\% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95\% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95\% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95\% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3\%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95\% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0\%) and never smokers (6.7\%), was associated with adverse respiratory health outcomes.

Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Asthma, Bronchitis, Chronic, Female, Humans, Lung, Male, Middle Aged, Prospective Studies, Respiratory Function Tests, Smokers, Smoking, Young Adult}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2020.0104}, author = {Balte, Pallavi P and Chaves, Paulo H M and Couper, David J and Enright, Paul and Jacobs, David R and Kalhan, Ravi 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, Benjamin M and Smith, Lewis J and White, Wendy B and Yende, Sachin and Oelsner, Elizabeth C} } @article {8824, title = {Examining the causal mediating role of brain pathology on the relationship between diabetes and cognitive impairment: the Cardiovascular Health Study.}, journal = {J R Stat Soc Ser A Stat Soc}, volume = {183}, year = {2020}, month = {2020 Oct}, pages = {1705-1726}, abstract = {

The paper examines whether leads to incident mild cognitive impairment and dementia through brain hypoperfusion and white matter disease. We performed inverse odds ratio weighted causal mediation analyses to decompose the effect of diabetes on cognitive impairment into direct and indirect effects, and we found that approximately a third of the total effect of diabetes is mediated through vascular-related brain pathology. Our findings lend support for a common aetiological hypothesis regarding incident cognitive impairment, which is that diabetes increases the risk of clinical cognitive impairment in part by impacting the vasculature of the brain.

}, issn = {0964-1998}, doi = {10.1111/rssa.12570}, author = {Andrews, Ryan M and Shpitser, Ilya and Lopez, Oscar and Longstreth, William T and Chaves, Paulo H M and Kuller, Lewis and Carlson, Michelle C} } @article {8487, title = {Intact and C-Terminal FGF23 Assays-Do Kidney Function, Inflammation, and Low Iron Influence Relationships With Outcomes?}, journal = {J Clin Endocrinol Metab}, volume = {105}, year = {2020}, month = {2020 Dec 01}, abstract = {

CONTEXT: Higher fibroblast growth factor-23 (FGF23) concentrations are associated with heart failure and mortality in diverse populations, but the strengths of associations differ markedly depending up on which assay is used.

OBJECTIVE: We sought to evaluate whether iron deficiency, inflammation, or kidney function account for differences in the strengths of associations between these 2 FGF23 assays with clinical outcomes.

DESIGN: Case cohort study from the Cardiovascular Health Study.

SETTING: A total of 844 community-dwelling individuals aged 65 years or older with and without chronic kidney disease were followed for 10 years.

OUTCOMES: Outcomes included death, incident heart failure (HF), and incident myocardial infarction (MI). Exposure was baseline intact and C-terminal FGF23. Using modified Cox models, adjusting sequentially we tested whether observed associations of each assay with outcomes were attenuated by iron status, inflammation, kidney function, or their combinations.

RESULTS: FGF23 measured by either assay was associated with mortality in unadjusted analysis (intact FGF23 hazard ratio [HR] per 2-fold higher 1.45; 95\% CI, 1.25-1.68; C-terminal FGF23 HR 1.38; 95\% CI, 1.26-1.50). Adjustment for kidney function completely attenuated associations of intact FGF23 with mortality (HR 1.00; 95\% CI, 0.85-1.17), but had much less influence on the association of C-terminal FGF23, for which results remained significant after adjustment (HR 1.15; 95\% CI, 1.04-1.28). Attenuation was much less with adjustment for iron status or inflammation. Results were similar for the HF end point. Neither C-terminal or intact FGF23 was associated with MI risk.

CONCLUSIONS: The relationship of FGF23 with clinical end points is markedly different depending on the type of FGF23 assay used. The associations of biologically active FGF23 with clinical end points may be confounded by kidney disease, and thus much weaker than previously thought.

}, issn = {1945-7197}, doi = {10.1210/clinem/dgaa665}, author = {Sharma, Shilpa and Katz, Ronit and Bullen, Alexander L and Chaves, Paulo H M and de Leeuw, Peter W and Kroon, Abraham A and Houben, Alfons J H M and Shlipak, Michael G and Ix, Joachim H} } @article {8626, title = {Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.}, journal = {JAMA Netw Open}, volume = {3}, year = {2020}, month = {2020 10 01}, pages = {e2023242}, abstract = {

Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.

Objective: To assess performance of the PCE across clinical BMI categories.

Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020.

Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (>=35).

Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D{\textquoteright}Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE.

Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7\%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0\%) were in the underweight category, 9937 individuals (26.6\%) were in the normal weight category, 13 601 individuals (36.4\%) were in the overweight category, 7783 individuals (20.9\%) were in the mild obesity category, and 5630 individuals (15.1\%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1\% (2.5\%-15.4\%), and 3709 individuals (9.9\%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95\% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95\% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk >=20\%. The PCE C statistic overall was 0.760 (95\% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95\% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95\% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95\% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95\% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95\% CI, 0.753-0.767) with or without added metrics.

Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

}, keywords = {Adult, Aged, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Correlation of Data, Female, Humans, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2020.23242}, author = {Khera, Rohan and Pandey, Ambarish and Ayers, Colby R and Carnethon, Mercedes R and Greenland, Philip and Ndumele, Chiadi E and Nambi, Vijay and Seliger, Stephen L and Chaves, Paulo H M and Safford, Monika M and Cushman, Mary and Xanthakis, Vanessa and Vasan, Ramachandran S and Mentz, Robert J and Correa, Adolfo and Lloyd-Jones, Donald M and Berry, Jarett D and de Lemos, James A and Neeland, Ian J} } @article {9248, title = {Sex- and race-specific associations of bone mineral density with incident heart failure and its subtypes in older adults.}, journal = {J Am Geriatr Soc}, year = {2022}, month = {2022 Nov 05}, abstract = {

BACKGROUND: Previous studies have suggested an association between bone mineral density (BMD) and heart failure (HF) risk that may be race-dependent.

METHODS: We evaluated the relationship between BMD and incident HF in a cohort of older adults, the Health, Aging, and Body Composition (Health ABC) study (n~=~2835), and next performed a pooled analysis involving a second older cohort, the Cardiovascular Health Study (n~=~1268). Hip BMD was measured by dual-energy X-ray absorptiometry in both cohorts and spine BMD by computed tomography in a subset from Health ABC.

RESULTS: In Health ABC, lower BMD at the total hip was associated with higher incident HF in Black women after multivariable adjustment. Similar associations were found for BMD at the femoral neck and spine. In both cohorts, pooled analysis again revealed an association between lower total hip BMD and increased risk of HF in Black women (HR~=~1.41 per 0.1-g/cm decrement [95\% CI~=~1.23-1.62]), and showed the same to be true for White men (HR~=~1.12 [1.03-1.21]). There was a decreased risk of HF in Black men (HR 0.80 [0.70-0.91]), but no relationship in White women. The associations were numerically stronger with HFpEF for Black women and White men, and with HFrEF for Black men. Findings were similar for femoral neck BMD. Sensitivity analyses delaying HF follow-up by 2 years eliminated the association in Black men.

CONCLUSIONS: Lower BMD was associated with higher risk of HF and especially HFpEF in older Black women and White men, highlighting the need for additional investigation into underlying mechanisms.

}, issn = {1532-5415}, doi = {10.1111/jgs.18121}, author = {Gao, Hans and Patel, Sheena and Fohtung, Raymond B and Cawthon, Peggy M and Newman, Anne B and Cauley, Jane A and Carbone, Laura and Chaves, Paulo H M and Stein, Phyllis K and Civitelli, Roberto and Kizer, Jorge R} } @article {9284, title = {Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.}, journal = {Atherosclerosis}, year = {2023}, month = {2023 Jan 29}, abstract = {

BACKGROUND AND AIMS: Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons.

METHODS: We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992-1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998-1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI.

RESULTS: Mean age was 74.8 years, 59\% were female, and 17\% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95\%CI~=~1.06-2.13, p~=~0.02) across extreme tertiles, and 1.14 (95\%CI~=~0.99-1.31, p~=~0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95\%CI~=~0.69-1.32, p~=~0.76) across extreme tertiles, and 1.03 (95\%CI~=~0.89-1.20, p~=~0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up.

CONCLUSIONS: Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2023.01.020}, author = {Ahiawodzi, Peter and Solaru, Khendi White and Chaves, Paulo H M and Ix, Joachim H and Kizer, Jorge R and Tracy, Russell P and Newman, Anne and Siscovick, David and Djouss{\'e}, Luc and Mukamal, Kenneth J} } @article {9615, title = {Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.}, journal = {ESC Heart Fail}, year = {2024}, month = {2024 Feb 26}, abstract = {

AIMS: Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function.

METHODS: In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N~=~414 total HF cases]) aged >= 65~years without HF (41\% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3\%), "functional iron deficiency" (7.7\%), "iron deficiency" (11.8\%), "mixed iron deficiency" (5.6\%), "high iron" (9.3\%) and "non-classified" (38.1\%), consistent with prior studies.

RESULTS: Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2).

CONCLUSIONS: Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

}, issn = {2055-5822}, doi = {10.1002/ehf2.14724}, author = {Sharma, Shilpa and Katz, Ronit and Chaves, Paulo H M and Hoofnagle, Andrew N and Kizer, Jorge R and Bansal, Nisha and Ganz, Tomas and Ix, Joachim H} }