TY - JOUR T1 - Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. JF - Arterioscler Thromb Vasc Biol Y1 - 2002 A1 - Kuller, Lewis A1 - Arnold, Alice A1 - Tracy, Russell A1 - Otvos, James A1 - Burke, Greg A1 - Psaty, Bruce A1 - Siscovick, David A1 - Freedman, David S A1 - Kronmal, Richard KW - Aged KW - Aging KW - Cardiovascular System KW - Case-Control Studies KW - Cohort Studies KW - Coronary Disease KW - Female KW - Health Status KW - Humans KW - Lipoproteins, HDL KW - Lipoproteins, LDL KW - Lipoproteins, VLDL KW - Magnetic Resonance Spectroscopy KW - Male KW - Nuclear Magnetic Resonance, Biomolecular KW - Risk Factors KW - Sex Factors AB -

OBJECTIVES: Relationships between incident cardiovascular disease and lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy were evaluated in the Cardiovascular Health Study (CHS) in a nested case-cohort analysis.

METHODS AND RESULTS: The case group consisted of 434 participants with incident myocardial infarction (MI) and angina diagnosed after entry to the study (1990 to 1995) and the comparison group, 249 "healthy" participants with no prevalent clinical or subclinical disease. By univariate analysis, the median levels for healthy participants versus participants with incident MI and angina were 0 versus 7 mg% for small low density lipoprotein (LDL), 1501 versus 1680 nmol/L for the number of LDL particles, and 21.6 versus 21.3 for LDL size, and these values were significantly different between "healthy" participants and those with incident MI and angina for women but not men. The levels of less dense LDL, which is most of the total LDL cholesterol among women, was not related to incident MI and angina. For women, large high density lipoprotein cholesterol (HDLc), but not small HDLc, levels were significantly higher for healthy participants compared with levels for participants with MI and angina. For men and women, levels of total and very low density lipoprotein triglycerides were higher for the case group than for the healthy group. In multivariate models for women that included triglycerides and HDLc, the number of LDL particles (but not LDL size) remained significantly related to MI and angina.

CONCLUSIONS: Small LDL, the size of LDL particles, and the greater number of LDL particles are related to incident coronary heart disease among older women.

VL - 22 IS - 7 U1 - https://www.ncbi.nlm.nih.gov/pubmed/12117734?dopt=Abstract ER - TY - JOUR T1 - Weight-modification trials in older adults: what should the outcome measure be? JF - Curr Control Trials Cardiovasc Med Y1 - 2002 A1 - Diehr, Paula A1 - Newman, Anne B A1 - Jackson, Sharon A A1 - Kuller, Lewis A1 - Powe, Neil AB -

BACKGROUND: Overweight older adults are often counseled to lose weight, even though there is little evidence of excess mortality in that age group. Overweight and underweight may be more associated with health status than with mortality, but few clinical trials of any kind have been based on maximizing years of healthy life (YHL), as opposed to years of life (YOL). OBJECTIVE: This paper examines the relationship of body mass index (BMI) to both YHL and YOL. Results were used to determine whether clinical trials of weight-modification based on improving YHL would be more powerful than studies based on survival. DESIGN: We used data from a cohort of 4,878 non-smoking men and women aged 65-100 at baseline (mean age 73) and followed 7 years. We estimated mean YHL and YOL in four categories of BMI: underweight, normal, overweight, and obese. RESULTS: Subjects averaged 6.3 YOL and 4.6 YHL of a possible 7 years. Both measures were higher for women and whites. For men, none of the BMI groups was significantly different from the normal group on either YOL or YHL. For women, the obese had significantly lower YHL (but not YOL) than the normals, and the underweight had significantly lower YOL and YHL. The overweight group was not significantly different from the normal group on either measure. CONCLUSIONS: Clinical trials of weight loss interventions for obese older women would require fewer participants if YHL rather than YOL was the outcome measure. Interventions for obese men or for the merely overweight are not likely to achieve differences in either YOL or YHL. Evaluations of interventions for the underweight (which would presumably address the causes of their low weight) may be conducted efficiently using either outcome measure.

VL - 3 IS - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/11985775?dopt=Abstract ER - TY - JOUR T1 - The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study. JF - Ophthalmology Y1 - 2003 A1 - Wong, Tien Yin A1 - Klein, Ronald A1 - Sharrett, A Richey A1 - Manolio, Teri A A1 - Hubbard, Larry D A1 - Marino, Emily K A1 - Kuller, Lewis A1 - Burke, Gregory A1 - Tracy, Russell P A1 - Polak, Joseph F A1 - Gottdiener, John S A1 - Siscovick, David S KW - Aged KW - Aged, 80 and over KW - Blood Pressure KW - Coronary Artery Disease KW - Cross-Sectional Studies KW - Female KW - Humans KW - Hypertension KW - Male KW - Prevalence KW - Retinal Diseases KW - Retinal Vessels KW - Risk Factors KW - United States AB -

PURPOSE: To describe the prevalence of retinal microvascular characteristics and their associations with atherosclerosis in elderly, nondiabetic persons.

DESIGN AND PARTICIPANTS: Population-based, cross-sectional study comprising 2050 men and women aged 69 to 97 years without diabetes, living in four communities.

METHODS: Participants underwent retinal photography and standardized grading of retinal microvascular characteristics, including retinopathy (e.g., microaneurysms, retinal hemorrhages), focal arteriolar narrowing, and arteriovenous nicking. In addition, calibers of retinal arterioles and venules were measured on digitized photographs to obtain an estimate of generalized arteriolar narrowing. Atherosclerosis and its risk factors were obtained from clinical examination and laboratory investigations.

MAIN OUTCOME MEASURES: Prevalence of retinal microvascular abnormalities and their associations with measures of atherosclerosis.

RESULTS: The prevalence of retinal microvascular abnormalities was 8.3% for retinopathy, 9.6% for focal arteriolar narrowing, and 7.7% for arteriovenous nicking. All retinal lesions were associated with hypertension (odds ratios [OR] were 1.8 for retinopathy, 2.1 for focal arteriolar narrowing, 1.5 for arteriovenous nicking, and 1.7 for generalized arteriolar narrowing). After controlling for age, gender, race, mean arterial blood pressure, and antihypertensive medication use, retinopathy was associated with prevalent coronary heart disease (OR, 1.7), prevalent myocardial infarction (OR, 1.7), prevalent stroke (OR, 2.0), presence of carotid artery plaque (OR, 1.9), and increased intima-media thickness of the common carotid (OR, 2.3; fourth vs. first quartile) and internal carotid (OR, 1.8; fourth vs. first quartile) arteries. In contrast, focal arteriolar narrowing, arteriovenous nicking, and generalized arteriolar narrowing were not associated with any measures of atherosclerosis.

CONCLUSIONS: Retinal microvascular abnormalities are common in older persons without diabetes and are related to hypertension. Retinopathy is associated with prevalent coronary heart disease, stroke, and carotid artery thickening, but focal and generalized arteriolar narrowing and arteriovenous nicking are not related to most measures of atherosclerosis. These data suggest that retinal microvascular abnormalities reflect processes associated with hypertension but distinct from atherosclerosis.

VL - 110 IS - 4 U1 - https://www.ncbi.nlm.nih.gov/pubmed/12689883?dopt=Abstract ER - TY - JOUR T1 - Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals. JF - J Am Soc Nephrol Y1 - 2004 A1 - Fried, Linda A1 - Solomon, Cam A1 - Shlipak, Michael A1 - Seliger, Stephen A1 - Stehman-Breen, Catherine A1 - Bleyer, Anthony J A1 - Chaves, Paolo A1 - Furberg, Curt A1 - Kuller, Lewis A1 - Newman, Anne KW - Aged KW - Biomarkers KW - C-Reactive Protein KW - Creatinine KW - Factor VII KW - Female KW - Fibrinogen KW - Follow-Up Studies KW - Glomerular Filtration Rate KW - Hemoglobins KW - Humans KW - Leukocyte Count KW - Linear Models KW - Longitudinal Studies KW - Male KW - Predictive Value of Tests KW - Prospective Studies KW - Renal Insufficiency KW - Serum Albumin KW - Thrombosis AB -

Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.

VL - 15 IS - 12 U1 - https://www.ncbi.nlm.nih.gov/pubmed/15579522?dopt=Abstract ER - TY - JOUR T1 - Association of beta-blocker use with mortality among patients with congestive heart failure in the Cardiovascular Health Study (CHS). JF - Am Heart J Y1 - 2005 A1 - Chan, Jeannie D A1 - Rea, Thomas D A1 - Smith, Nicholas L A1 - Siscovick, David A1 - Heckbert, Susan R A1 - Lumley, Thomas A1 - Chaves, Paulo A1 - Furberg, Curt D A1 - Kuller, Lewis A1 - Psaty, Bruce M KW - Adrenergic beta-Antagonists KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Female KW - Follow-Up Studies KW - Heart Failure KW - Humans KW - Male AB -

BACKGROUND: In clinical trials, beta-blocker therapy reduces all-cause mortality among people with congestive heart failure (CHF) characterized by depressed systolic function, but few trials included large numbers of elderly participants. This study assessed the association between beta-blocker therapy and mortality among community-dwelling older adults with CHF.

METHODS: The Cardiovascular Health Study (CHS) is a longitudinal, population-based study of adults aged > or = 65 years. Recruitment began in 1989 with follow-up extending through June 2000 or death. Cox proportional hazard regression models were used to assess the association between beta-blocker therapy and all-cause mortality among 950 participants who developed new-onset CHF.

RESULTS: beta-Blocker users (n = 157) were more likely than nonusers (n = 793) to have treated hypertension, clinical coronary artery disease, and valvular disease at the time of CHF diagnosis. Death occurred in 67 users and 446 nonusers during a median follow-up of 2.3 years. Compared with nonuse, use of beta-blockers was associated with a multivariable adjusted hazard ratio (HR) of 0.74 (95% CI 0.56-0.98) for all-cause mortality. Among the 520 participants who had left ventricular ejection fraction assessed within 90 days after CHF diagnosis, the risk for all cause mortality associated with beta-blocker use did not differ significantly between those with ejection fraction of < 40% and those with ejection fraction of > or = 40% (HR 0.56, 95% CI 0.27-1.13; HR 0.82, 95% CI 0.56-1.22, respectively; interaction P = .34).

CONCLUSIONS: This observational study suggests that beta-blocker treatment is associated with a reduced risk of all-cause mortality among community-dwelling older adults with CHF.

VL - 150 IS - 3 U1 - https://www.ncbi.nlm.nih.gov/pubmed/16169325?dopt=Abstract ER - TY - JOUR T1 - The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: the Cardiovascular Health Study. JF - Atherosclerosis Y1 - 2006 A1 - Cao, Jie J A1 - Barzilay, Joshua I A1 - Peterson, Do A1 - Manolio, Teri A A1 - Psaty, Bruce M A1 - Kuller, Lewis A1 - Wexler, Jason A1 - Bleyer, Anthony J A1 - Cushman, Mary KW - Aged KW - Aged, 80 and over KW - Albuminuria KW - Atherosclerosis KW - Cardiovascular Diseases KW - Coronary Disease KW - Diabetes Mellitus KW - Female KW - Humans KW - Hypertension KW - Male KW - Peripheral Vascular Diseases KW - Prevalence KW - Risk Factors KW - Stroke KW - United States AB -

PURPOSE: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events.

METHODS: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >or=65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass.

RESULTS: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]).

CONCLUSION: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease.

VL - 187 IS - 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/16242696?dopt=Abstract ER - TY - JOUR T1 - CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. JF - Hum Mol Genet Y1 - 2006 A1 - Conley, Yvette P A1 - Jakobsdottir, Johanna A1 - Mah, Tammy A1 - Weeks, Daniel E A1 - Klein, Ronald A1 - Kuller, Lewis A1 - Ferrell, Robert E A1 - Gorin, Michael B KW - Aged KW - Aged, 80 and over KW - Case-Control Studies KW - Cohort Studies KW - Complement Factor H KW - Eye Proteins KW - Female KW - Genetic Predisposition to Disease KW - Humans KW - Intracellular Signaling Peptides and Proteins KW - Macular Degeneration KW - Male KW - Membrane Proteins KW - Proteins AB -

Age-related maculopathy (ARM) is an important cause of visual impairment in the elderly population. It is of crucial importance to identify genetic factors and their interactions with environmental exposures for this disorder. This study was aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in independent cohorts collected using different ascertainment schemes. The study used a case-control design with subjects originally recruited through the Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS). CFH was significantly associated with ARM in both cohorts (P VL - 15 IS - 21 U1 - https://www.ncbi.nlm.nih.gov/pubmed/17000705?dopt=Abstract ER - TY - JOUR T1 - Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study. JF - Circulation Y1 - 2006 A1 - Pearte, Camille A A1 - Furberg, Curt D A1 - O'Meara, Ellen S A1 - Psaty, Bruce M A1 - Kuller, Lewis A1 - Powe, Neil R A1 - Manolio, Teri KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Carotid Artery, Common KW - Cohort Studies KW - Comorbidity KW - Coronary Disease KW - Diabetes Mellitus KW - Electrocardiography KW - Female KW - Follow-Up Studies KW - Forecasting KW - Heart Failure KW - Heart Ventricles KW - Hospitalization KW - Humans KW - Hyperlipidemias KW - Hypertension KW - Male KW - Multivariate Analysis KW - Myocardial Infarction KW - Organ Size KW - Predictive Value of Tests KW - Risk Factors KW - Sampling Studies KW - Tunica Intima KW - Tunica Media KW - United States AB -

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

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

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

VL - 113 IS - 18 U1 - https://www.ncbi.nlm.nih.gov/pubmed/16651468?dopt=Abstract ER - TY - JOUR T1 - Cardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68-102: the Cardiovascular Health Study. JF - Atherosclerosis Y1 - 2008 A1 - Cao, Jie J A1 - Biggs, Mary L A1 - Barzilay, Joshua A1 - Konen, Joseph A1 - Psaty, Bruce M A1 - Kuller, Lewis A1 - Bleyer, Anthony J A1 - Olson, Jean A1 - Wexler, Jason A1 - Summerson, John A1 - Cushman, Mary KW - Aged KW - Aged, 80 and over KW - Albuminuria KW - Biomarkers KW - Cohort Studies KW - Coronary Disease KW - Cross-Sectional Studies KW - Female KW - Health Surveys KW - Humans KW - Male KW - Predictive Value of Tests KW - Risk AB -

BACKGROUND: Elevated urinary albumin excretion (UAE) is associated with the risk of cardiovascular disease (CVD) and all-cause mortality. We tested the hypothesis that elevated UAE improves cardiovascular risk stratification in an elderly cohort aged 68-102 years.

METHODS: We evaluated UAE in 3112 participants of the Cardiovascular Health Study who attended the 1996-1997 examination and had median follow up of 5.4 years. Elevated UAE was defined as urinary albumin to creatinine ratio > or =30 microg/mg. Microalbuminuria and macroalbuminuria were defined as urinary albumin to creatinine ratio 30-300 microg/mg and >300 microg/mg, respectively. Outcomes included CVD (myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox proportional hazards models were used to assess the risk of outcomes associated with elevated UAE.

RESULTS: The prevalence of elevated UAE was 14.3%, 17.1% and 26.9% in those aged 68-74, 75-84 and 85-102 years, respectively. CVD incidence and all-cause mortality were doubled (7.2% and 8.1% per year) in those with microalbuminuria and tripled (11.1% and 12.3% per year) in those with macroalbuminuria compared to those with normal UAE (3.3% and 3.8% per year). The increased CVD and mortality risks were observed in all age groups after adjustment for conventional risk factors. The adjusted population attributable risk percent of CVD and all-cause mortality for elevated UAE was 11% and 12%, respectively. When participants were cross-classified by UAE and Framingham Risk Score categories, the 5-year cumulative incidence of coronary heart disease among participants with elevated UAE and a 5-year predicted risk of 5-10% was 20%, substantially higher than 6.3% in those with UAE <30m microg/mg.

CONCLUSION: Elevated UAE was associated with an increased risk of CVD and all-cause mortality in all age groups from 68 to 102 years. Combining elevated UAE with the Framingham risk scores may improve risk stratification for CVD in the elderly.

VL - 197 IS - 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/17875308?dopt=Abstract ER - TY - JOUR T1 - High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly. JF - Am Heart J Y1 - 2008 A1 - Kaplan, Robert C A1 - McGinn, Aileen P A1 - Pollak, Michael N A1 - Kuller, Lewis A1 - Strickler, Howard D A1 - Rohan, Thomas E A1 - Cappola, Anne R A1 - Xue, XiaoNan A1 - Psaty, Bruce M KW - Aged KW - Aged, 80 and over KW - Female KW - Heart Failure KW - Humans KW - Incidence KW - Insulin-Like Growth Factor Binding Protein 1 KW - Insulin-Like Growth Factor Binding Protein 3 KW - Insulin-Like Growth Factor I KW - Male KW - Predictive Value of Tests KW - Prospective Studies KW - Risk Factors AB -

BACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.

METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.

RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.

CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.

VL - 155 IS - 6 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18513511?dopt=Abstract ER - TY - JOUR T1 - Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults. JF - Growth Horm IGF Res Y1 - 2008 A1 - Rajpathak, Swapnil N A1 - McGinn, Aileen P A1 - Strickler, Howard D A1 - Rohan, Thomas E A1 - Pollak, Michael A1 - Cappola, Anne R A1 - Kuller, Lewis A1 - Xue, XiaoNan A1 - Newman, Anne B A1 - Strotmeyer, Elsa S A1 - Psaty, Bruce M A1 - Kaplan, Robert C KW - Aged KW - Aged, 80 and over KW - Cohort Studies KW - Cross-Sectional Studies KW - Female KW - Glucose Intolerance KW - Humans KW - Inflammation KW - Insulin-Like Growth Factor Binding Proteins KW - Male KW - Signal Transduction KW - Somatomedins AB -

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

VL - 18 IS - 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/17904401?dopt=Abstract ER - TY - JOUR T1 - Item response theory facilitated cocalibrating cognitive tests and reduced bias in estimated rates of decline. JF - J Clin Epidemiol Y1 - 2008 A1 - Crane, Paul K A1 - Narasimhalu, Kaavya A1 - Gibbons, Laura E A1 - Mungas, Dan M A1 - Haneuse, Sebastien A1 - Larson, Eric B A1 - Kuller, Lewis A1 - Hall, Kathleen A1 - van Belle, Gerald KW - Aged KW - Aged, 80 and over KW - Cognition Disorders KW - Dementia KW - Disease Progression KW - Epidemiologic Methods KW - Female KW - Humans KW - Male KW - Neuropsychological Tests KW - Psychometrics AB -

OBJECTIVE: To cocalibrate the Mini-Mental State Examination, the Modified Mini-Mental State, the Cognitive Abilities Screening Instrument, and the Community Screening Instrument for Dementia using item response theory (IRT) to compare screening cut points used to identify cases of dementia from different studies, to compare measurement properties of the tests, and to explore the implications of these measurement properties on longitudinal studies of cognitive functioning over time.

STUDY DESIGN AND SETTING: We used cross-sectional data from three large (n>1000) community-based studies of cognitive functioning in the elderly. We used IRT to cocalibrate the scales and performed simulations of longitudinal studies.

RESULTS: Screening cut points varied quite widely across studies. The four tests have curvilinear scaling and varied levels of measurement precision, with more measurement error at higher levels of cognitive functioning. In longitudinal simulations, IRT scores always performed better than standard scoring, whereas a strategy to account for varying measurement precision had mixed results.

CONCLUSION: Cocalibration allows direct comparison of cognitive functioning in studies using any of these four tests. Standard scoring appears to be a poor choice for analysis of longitudinal cognitive testing data. More research is needed into the implications of varying levels of measurement precision.

VL - 61 IS - 10 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18455909?dopt=Abstract ER - TY - JOUR T1 - Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults. JF - J Am Geriatr Soc Y1 - 2008 A1 - Kaplan, Robert C A1 - McGinn, Aileen P A1 - Pollak, Michael N A1 - Kuller, Lewis A1 - Strickler, Howard D A1 - Rohan, Thomas E A1 - Xue, XiaoNan A1 - Kritchevsky, Stephen B A1 - Newman, Anne B A1 - Psaty, Bruce M KW - Activities of Daily Living KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Cardiovascular Diseases KW - Enzyme-Linked Immunosorbent Assay KW - Fasting KW - Female KW - Follow-Up Studies KW - Hand Strength KW - Humans KW - Incidence KW - Insulin-Like Growth Factor Binding Protein 1 KW - Insulin-Like Growth Factor Binding Protein 3 KW - Insulin-Like Growth Factor I KW - Male KW - Middle Aged KW - Prognosis KW - Prospective Studies KW - Risk Factors KW - Survival Rate KW - United States KW - Walking AB -

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

DESIGN: Cohort study.

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

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

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

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

VL - 56 IS - 4 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18312313?dopt=Abstract ER - TY - JOUR T1 - Weight, mortality, years of healthy life, and active life expectancy in older adults. JF - J Am Geriatr Soc Y1 - 2008 A1 - Diehr, Paula A1 - O'Meara, Ellen S A1 - Fitzpatrick, Annette A1 - Newman, Anne B A1 - Kuller, Lewis A1 - Burke, Gregory KW - Activities of Daily Living KW - Aged KW - Aged, 80 and over KW - Body Mass Index KW - Body Weight KW - Female KW - Health Status Indicators KW - Humans KW - Life Expectancy KW - Life Style KW - Male KW - Prognosis KW - Risk Factors KW - Sex Factors KW - Survival Rate KW - United States AB -

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

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

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

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

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

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

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

VL - 56 IS - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18031486?dopt=Abstract ER - TY - JOUR T1 - Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study. JF - Arch Intern Med Y1 - 2009 A1 - Sink, Kaycee M A1 - Leng, Xiaoyan A1 - Williamson, Jeff A1 - Kritchevsky, Stephen B A1 - Yaffe, Kristine A1 - Kuller, Lewis A1 - Yasar, Sevil A1 - Atkinson, Hal A1 - Robbins, Mike A1 - Psaty, Bruce A1 - Goff, David C KW - Aged KW - Angiotensin-Converting Enzyme Inhibitors KW - Blood-Brain Barrier KW - Cognition KW - Dementia KW - Female KW - Follow-Up Studies KW - Humans KW - Hypertension KW - Incidence KW - Male KW - Prospective Studies KW - Risk Factors AB -

BACKGROUND: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control.

METHODS: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs).

RESULTS: Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs.

CONCLUSIONS: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

VL - 169 IS - 13 U1 - http://www.ncbi.nlm.nih.gov/pubmed/19597068?dopt=Abstract ER - TY - JOUR T1 - Change in cardiovascular risk factors with progression of kidney disease. JF - Am J Nephrol Y1 - 2009 A1 - Fried, Linda F A1 - Katz, Ronit A1 - Cushman, Mary A1 - Sarnak, Mark A1 - Shlipak, Michael G A1 - Kuller, Lewis A1 - Newman, Anne B KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - C-Reactive Protein KW - Cholesterol, HDL KW - Creatinine KW - Diabetes Mellitus KW - Factor VIII KW - Female KW - Follow-Up Studies KW - Humans KW - Hypertension, Renal KW - Interleukin-6 KW - Logistic Models KW - Male KW - Prevalence KW - Renal Insufficiency, Chronic KW - Risk Factors KW - Vasculitis AB -

BACKGROUND: Prior studies evaluating the relationship of kidney disease with cardiovascular risk factors have been limited by their cross-sectional design. We evaluated the change in lipids, inflammatory and procoagulant biomarkers with decline in kidney function in a nested case-cohort study in the Cardiovascular Health Study, a community-based study of adults aged >65 years.

METHODS: Individuals with an increase in serum creatinine >or=0.3 mg/dl (baseline to 3 years later, n = 207) were matched to controls of similar age, race, gender, diabetes and baseline serum creatinine, but whose change in creatinine was <0.3 mg/dl. Baseline and change in risk factors were analyzed with conditional logistic regression.

RESULTS: Changes in C-reactive protein were similar. In contrast, cases had larger increases in fibrinogen (OR 1.38 per standard deviation, 95% confidence interval 1.08-1.76) and factor VIII [1.38 (1.10-1.72)] and larger decreases in HDL [OR 0.80 (0.64, 1.00)]. Change in interleukin-6 was greater in cases than controls, but this did not persist after multivariate adjustment. However, in linear regression, change in interleukin-6 was correlated with change in creatinine.

CONCLUSION: Cardiovascular risk factors and kidney function may change concurrently. This could lead to an increased risk of cardiovascular disease as kidney function worsens.

VL - 29 IS - 4 U1 - https://www.ncbi.nlm.nih.gov/pubmed/18948687?dopt=Abstract ER - TY - JOUR T1 - Depressed mood is not a risk factor for incident dementia in a community-based cohort. JF - Am J Geriatr Psychiatry Y1 - 2009 A1 - Becker, James T A1 - Chang, Yue-Fang A1 - Lopez, Oscar L A1 - Dew, Mary Amanda A1 - Sweet, Robert A A1 - Barnes, Deborah A1 - Yaffe, Kristine A1 - Young, Jeffrey A1 - Kuller, Lewis A1 - Reynolds, Charles F KW - Aged KW - Aged, 80 and over KW - Alzheimer Disease KW - Cognition Disorders KW - Dementia KW - Depression KW - Female KW - Follow-Up Studies KW - Humans KW - Incidence KW - Longitudinal Studies KW - Magnetic Resonance Imaging KW - Male KW - Mental Status Schedule KW - Prospective Studies KW - Psychiatric Status Rating Scales KW - Residence Characteristics KW - Risk Factors AB -

OBJECTIVES: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals.

DESIGN: Longitudinal and observational.

SETTING: Community-based cohort study.

PARTICIPANTS: A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years).

MEASUREMENTS: The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams.

RESULTS: The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood.

CONCLUSION: Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.

VL - 17 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/19634208?dopt=Abstract ER - TY - JOUR T1 - Prevalence of hearing loss in Black and White elders: results of the Cardiovascular Health Study. JF - J Speech Lang Hear Res Y1 - 2009 A1 - Pratt, Sheila R A1 - Kuller, Lewis A1 - Talbott, Evelyn O A1 - McHugh-Pemu, Kathleen A1 - Buhari, Alhaji M A1 - Xu, Xiaohui KW - African Americans KW - Aged KW - Aged, 80 and over KW - Aging KW - Auditory Threshold KW - Cardiovascular Diseases KW - Cohort Studies KW - Cross-Sectional Studies KW - European Continental Ancestry Group KW - Female KW - Hearing Loss KW - Hearing Tests KW - Humans KW - Male KW - Occupations KW - Prevalence KW - Sex Characteristics KW - Smoking KW - Socioeconomic Factors KW - United States AB -

PURPOSE: The goal of this study was to determine the impact of age, gender, and race on the prevalence and severity of hearing loss in elder adults, aged 72-96 years, after accounting for income, education, smoking, and clinical and subclinical cardiovascular disease. Methods Air-conduction thresholds for standard and extended high-frequency pure-tones were obtained from a cohort of 548 (out of 717) elderly adults (ages 72-96 years) who were recruited during the Year 11 clinical visit (1999-2000) of the Cardiovascular Health Study (CHS) at the Pittsburgh, Pennsylvania site. Participant smoking, income, education, and cardiovascular disease histories were obtained from the CHS database and were included as factors.

RESULTS: Hearing loss was more common and more severe for the participants in their 80s than for those in their 70s-the men more than the women and the White participants more than the Black participants. The inclusion of education, income, smoking, and cardiovascular disease (clinical and subclinical) histories as factors did not substantively impact the overall results.

CONCLUSION: Although the data reported in this article were cross-sectional and a cohort phenomenon might have been operational, they suggested that hearing loss is more substantive in the 8th than the 7th decade of life and that race and gender influence this decline in audition. Given the high prevalence in the aging population and the differences across groups, there is a clear need to understand the nature and causes of hearing loss across various groups in order to improve prevention and develop appropriate interventions.

VL - 52 IS - 4 U1 - https://www.ncbi.nlm.nih.gov/pubmed/19380605?dopt=Abstract ER - TY - JOUR T1 - Combined association of lipids and blood pressure in relation to incident cardiovascular disease in the elderly: the cardiovascular health study. JF - Am J Hypertens Y1 - 2010 A1 - Wong, Nathan D A1 - Lopez, Victor A A1 - Roberts, Craig S A1 - Solomon, Henry A A1 - Burke, Gregory L A1 - Kuller, Lewis A1 - Tracy, Russell A1 - Yanez, David A1 - Psaty, Bruce M KW - Age Factors KW - Aged KW - Aged, 80 and over KW - Blood Pressure KW - Cardiovascular Diseases KW - Cholesterol, HDL KW - Cholesterol, LDL KW - Diabetes Mellitus KW - Female KW - Health Surveys KW - Humans KW - Likelihood Functions KW - Lipids KW - Male KW - Proportional Hazards Models KW - Sex Factors KW - Smoking KW - Socioeconomic Factors KW - United States AB -

BACKGROUND: Hypertension and dyslipidemia are highly prevalent in the elderly. We studied the combined impact of both conditions on cardiovascular disease (CVD) events.

METHODS: We studied 4,311 participants aged 65-98 (61.2% female) from the Cardiovascular Health Study (CHS), a longitudinal epidemiologic study, with no prior CVD. We evaluated the relation of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or non-HDL-cholesterol combined with blood pressure (BP) categories to incident CVD-including coronary heart disease (CHD) (angina, myocardial infarction (MI), angioplasty, coronary bypass surgery, or CHD death), stroke, claudication, and CVD death over 15 years.

RESULTS: CVD incidence (per 1,000 person years) ranged from 38.4 when BP <120/80 mm Hg and LDL-C <100 mg/dl to 94.8 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl, and from 28.9 when BP <120/80 mm Hg and HDL >60 mg/dl to 87.1 for a BP >or=160/100 and HDL-C <40 mg/dl. Compared with those with BP <120/80 mm Hg with either LDL-C <100 mg/dl or HDL-C >60 mg/dl, hazard ratios (HRs) for CVD events were 2.1 when BP >or=160/100 mm Hg and LDL-C >or=160 mg/dl and 2.1 when BP >or=160/100 and HDL-C <40 mg/dl (all P < 0.01), with similar results for non-HDL-C. Elevated BP was associated with increased risk across all lipid levels. Increased LDL-C added risk mainly when BP <140/90 mm Hg, but lower HDL-C also predicted CVD in those with higher BP.

CONCLUSION: Increased BP confers increased risks for CVD in elderly persons across all lipid levels. Although increased LDL-C added risk mainly when BP <140/90 mm Hg, low HDL-C added risk also in those with hypertension. These results document the importance of combined hypertension and dyslipidemia.

VL - 23 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/19927131?dopt=Abstract ER - TY - JOUR T1 - Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study. JF - Am J Geriatr Psychiatry Y1 - 2011 A1 - Emanuel, James E A1 - Lopez, Oscar L A1 - Houck, Patricia R A1 - Becker, James T A1 - Weamer, Elise A A1 - Demichele-Sweet, Mary Ann A A1 - Kuller, Lewis A1 - Sweet, Robert A KW - Aged KW - Alzheimer Disease KW - Chi-Square Distribution KW - Female KW - Follow-Up Studies KW - Humans KW - Longitudinal Studies KW - Male KW - Neuropsychological Tests KW - Psychiatric Status Rating Scales KW - Psychotic Disorders KW - Time Factors AB -

OBJECTIVE: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI).

DESIGN: : The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data.

SETTING: Community.

PARTICIPANTS: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-∊ (APOE) genotyping.

MEASUREMENTS: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status.

RESULTS: : Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis.

CONCLUSIONS: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.

VL - 19 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20808116?dopt=Abstract ER - TY - JOUR T1 - Adiposity and cognitive decline in the cardiovascular health study. JF - Neuroepidemiology Y1 - 2013 A1 - Luchsinger, José A A1 - Biggs, Mary L A1 - Kizer, Jorge R A1 - Barzilay, Joshua A1 - Fitzpatrick, Annette A1 - Newman, Anne A1 - Longstreth, William T A1 - Lopez, Oscar A1 - Siscovick, David A1 - Kuller, Lewis KW - Adiposity KW - Aged KW - Aged, 80 and over KW - Body Mass Index KW - Cardiovascular Diseases KW - Cognition Disorders KW - Electric Impedance KW - Female KW - Humans KW - Male KW - Risk Factors KW - Waist Circumference KW - Waist-Hip Ratio AB -

BACKGROUND: Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis, body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study.

METHODS: Cognitive performance was assessed with the modified Mini-Mental State Examination, the Digit Symbol Substitution Test, and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline.

RESULTS: The final sample was comprised of 2,681 women (57.9%) and 1,949 men (42.1%) aged 73 ± 5.2 and 73.9 ± 5.6 years, respectively. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease.

CONCLUSIONS: Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by preexisting conditions.

VL - 40 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23445925?dopt=Abstract ER - TY - JOUR T1 - Insulin resistance and risk of incident heart failure: Cardiovascular Health Study. JF - Circ Heart Fail Y1 - 2013 A1 - Banerjee, Dipanjan A1 - Biggs, Mary L A1 - Mercer, Laina A1 - Mukamal, Kenneth A1 - Kaplan, Robert A1 - Barzilay, Joshua A1 - Kuller, Lewis A1 - Kizer, Jorge R A1 - Djoussé, Luc A1 - Tracy, Russell A1 - Zieman, Susan A1 - Lloyd-Jones, Donald A1 - Siscovick, David A1 - Carnethon, Mercedes KW - Aged KW - Female KW - Heart Atria KW - Heart Failure KW - Heart Ventricles KW - Humans KW - Incidence KW - Insulin KW - Insulin Resistance KW - Male KW - Middle Aged KW - Myocardial Infarction KW - Organ Size KW - Proportional Hazards Models KW - Prospective Studies AB -

BACKGROUND: Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance as compared with matched controls. Insulin resistance leads to structural abnormalities in the heart, such as increased left atrial size, left ventricular mass, and alterations in transmitral velocity that can precede the diagnosis of HF. It is not known whether insulin resistance precedes the development of HF or whether the relationship between insulin resistance and HF is present among adults with HF caused by nonischemic heart disease.

METHODS AND RESULTS: We examined 4425 participants (60% women) from the Cardiovascular Health Study after excluding those with HF, myocardial infarction, or treated diabetes mellitus at baseline. We used Cox proportional hazards models to estimate the relative risk of incident HF associated with fasting insulin measured at study entry. There were 1216 cases of incident HF (1103 without antecedent myocardial infarction) during a median follow-up of 12 years (maximum, 19 years). Fasting insulin levels were positively associated with the risk of incident HF (hazard ratio, 1.10; 95% confidence interval, 1.05-1.15, per SD change) when adjusted for age, sex, race, field center, physical activity, smoking, alcohol intake, high-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure, and waist circumference. The association between fasting insulin levels and incident HF was similar for HF without antecedent myocardial infarction (hazard ratio, 1.10; 95% confidence interval, 1.05-1.15). Measures of left atrial size, left ventricular mass, and peak A velocity at baseline were associated both with fasting insulin levels and with HF; however, additional statistical adjustment for these parameters did not completely attenuate the insulin-HF estimate (hazard ratio, 1.08; 95% confidence interval, 1.03-1.14 per 1-SD increase in fasting insulin).

CONCLUSIONS: Fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF in Cardiovascular Health Study participants, including those without an antecedent myocardial infarction.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

VL - 6 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23575256?dopt=Abstract ER - TY - JOUR T1 - Association Between 6-Minute Walk Test and All-Cause Mortality, Coronary Heart Disease-Specific Mortality, and Incident Coronary Heart Disease. JF - J Aging Health Y1 - 2014 A1 - Yazdanyar, Ali A1 - Aziz, Michael M A1 - Enright, Paul L A1 - Edmundowicz, Daniel A1 - Boudreau, Robert A1 - Sutton-Tyrell, Kim A1 - Kuller, Lewis A1 - Newman, Anne B AB -

OBJECTIVE: To examine the association between 6-min walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults.

METHOD: We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants without prevalent cardiovascular disease with a 6 MWT.

RESULTS: During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, and 504 deaths of which 100 were coronary heart disease-related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 m: hazard ratio [HR] = 1.7; 95% confidence interval [CI] = [1.2, 2.5]; <290 m: HR = 2.1; 95% CI = [1.4, 3.0]). The adjusted risk of coronary heart disease mortality incident events among those with a 6 MWT < 290 m was not significant.

DISCUSSION: Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling older adults.

VL - 26 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24695552?dopt=Abstract ER - TY - JOUR T1 - Insulinlike growth factor binding protein-1 and ghrelin predict health outcomes among older adults: CHS cohort. JF - J Clin Endocrinol Metab Y1 - 2016 A1 - Kaplan, Robert C A1 - Strizich, Garrett A1 - Aneke-Nash, Chino A1 - Dominguez-Islas, Clara A1 - Bůzková, Petra A1 - Strickler, Howard A1 - Rohan, Thomas A1 - Pollak, Michael A1 - Kuller, Lewis A1 - Kizer, Jorge R A1 - Cappola, Anne A1 - Li, Christopher I A1 - Psaty, Bruce M A1 - Newman, Anne AB -

CONTEXT: Multiple diseases may explain the association of the growth hormone / insulinlike growth factor-I (GH/IGF-I) axis with longevity.

OBJECTIVE: To relate circulating GH/IGF-I system protein levels with major health events.

DESIGN: Cohort study Setting: Four US communities Participants: Adults (n=2268) 65 years and older free of diabetes and cardiovascular disease.

MEASUREMENTS: We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiologic covariates.

RESULTS: During 13,930 person-years of follow-up, 48.1% individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-h ghrelin were associated with a 27% higher (95% CI: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-h IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite endpoint. Similarly, higher mortality was significantly associated with higher fasting and 2-h ghrelin level, and with 2-h IGFBP-1 level. When examined together, 2-h post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels.

CONCLUSIONS: Circulating IGFBP-1 and ghrelin measured during an OGTT predict major health events and death in older adults, which may explain the influence of the GH-IGF-axis on lifespan and health.

ER - TY - JOUR T1 - The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study. JF - J Clin Endocrinol Metab Y1 - 2017 A1 - Aneke-Nash, Chino S A1 - Xue, XiaoNan A1 - Qi, Qibin A1 - Biggs, Mary L A1 - Cappola, Anne A1 - Kuller, Lewis A1 - Pollak, Michael A1 - Psaty, Bruce M A1 - Siscovick, David A1 - Mukamal, Kenneth A1 - Strickler, Howard D A1 - Kaplan, Robert C KW - Aged KW - Aged, 80 and over KW - Biomarkers KW - Blood Glucose KW - Cardiovascular Diseases KW - Cohort Studies KW - Diabetes Mellitus KW - Female KW - Humans KW - Incidence KW - Insulin-Like Growth Factor Binding Protein 3 KW - Insulin-Like Growth Factor I KW - Longitudinal Studies KW - Male KW - New England KW - Prospective Studies KW - Risk AB -

Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.

Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.

Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged ≥65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.

Setting: General community.

Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.

Interventions: Not applicable.

Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) ≥126 mg/dL, non-FPG ≥200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare & Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.

Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.

Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

VL - 102 IS - 12 ER - TY - JOUR T1 - Association of Coronary Artery Calcium Score vs Age With Cardiovascular Risk in Older Adults: An Analysis of Pooled Population-Based Studies. JF - JAMA Cardiol Y1 - 2017 A1 - Yano, Yuichiro A1 - O'Donnell, Christopher J A1 - Kuller, Lewis A1 - Kavousi, Maryam A1 - Erbel, Raimund A1 - Ning, Hongyan A1 - D'Agostino, Ralph A1 - Newman, Anne B A1 - Nasir, Khurram A1 - Hofman, Albert A1 - Lehmann, Nils A1 - Dhana, Klodian A1 - Blankstein, Ron A1 - Hoffmann, Udo A1 - Möhlenkamp, Stefan A1 - Massaro, Joseph M A1 - Mahabadi, Amir-Abbas A1 - Lima, João A C A1 - Ikram, M Arfan A1 - Jöckel, Karl-Heinz A1 - Franco, Oscar H A1 - Liu, Kiang A1 - Lloyd-Jones, Donald A1 - Greenland, Philip AB -

Importance: Besides age, other discriminators of atherosclerotic cardiovascular disease (ASCVD) risk are needed in older adults.

Objectives: To examine the predictive ability of coronary artery calcium (CAC) score vs age for incident ASCVD and how risk prediction changes by adding CAC score and removing only age from prediction models.

Design, Setting, and Participants: We conducted an analysis of pooled US population-based studies, including the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study. Results were compared with 2 European cohorts, the Rotterdam Study and the Heinz Nixdorf Recall Study. Participants underwent CAC scoring between 1998 and 2006 using cardiac computed tomography. The participants included adults older than 60 years without known ASCVD at baseline.

Exposures: Coronary artery calcium scores.

Main Outcomes and Measures: Incident ASCVD events including coronary heart disease (CHD) and stroke.

Results: The study included 4778 participants from 3 US cohorts, with a mean age of 70.1 years; 2582 (54.0%) were women, and 2431 (50.9%) were nonwhite. Over 11 years of follow-up (44 152 person-years), 405 CHD and 228 stroke events occurred. Coronary artery calcium score (vs age) had a greater association with incident CHD (C statistic, 0.733 vs 0.690; C statistics difference, 0.043; 95% CI of difference, 0.009-0.075) and modestly improved prediction of incident stroke (C statistic, 0.695 vs 0.670; C statistics difference, 0.025; 95% CI of difference, -0.015 to 0.064). Adding CAC score to models including traditional cardiovascular risk factors, with only age being removed, provided improved discrimination for incident CHD (C statistic, 0.735 vs 0.703; C statistics difference, 0.032; 95% CI of difference, 0.002-0.062) but not for stroke. Coronary artery calcium score was more likely than age to provide higher category-free net reclassification improvement among participants who experienced an ASCVD event (0.390; 95% CI, 0.312-0.467 vs 0.08; 95% CI -0.001 to 0.181) and to result in more accurate reclassification of risk for ASCVD events among these individuals. The findings were similar in the 2 European cohorts (n = 4990).

Conclusions and Relevance: Coronary artery calcium may be an alternative marker besides age to better discriminate between lower and higher CHD risk in older adults. Whether CAC score can assist in guiding the decision to initiate statin treatment for primary prevention in older adults requires further investigation.

ER - TY - JOUR T1 - Examining the causal mediating role of brain pathology on the relationship between diabetes and cognitive impairment: the Cardiovascular Health Study. JF - J R Stat Soc Ser A Stat Soc Y1 - 2020 A1 - Andrews, Ryan M A1 - Shpitser, Ilya A1 - Lopez, Oscar A1 - Longstreth, William T A1 - Chaves, Paulo H M A1 - Kuller, Lewis A1 - Carlson, Michelle C AB -

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.

VL - 183 IS - 4 ER - TY - JOUR T1 - Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry. JF - Am J Hum Genet Y1 - 2021 A1 - Graff, Mariaelisa A1 - Justice, Anne E A1 - Young, Kristin L A1 - Marouli, Eirini A1 - Zhang, Xinruo A1 - Fine, Rebecca S A1 - Lim, Elise A1 - Buchanan, Victoria A1 - Rand, Kristin A1 - Feitosa, Mary F A1 - Wojczynski, Mary K A1 - Yanek, Lisa R A1 - Shao, Yaming A1 - Rohde, Rebecca A1 - Adeyemo, Adebowale A A1 - Aldrich, Melinda C A1 - Allison, Matthew A A1 - Ambrosone, Christine B A1 - Ambs, Stefan A1 - Amos, Christopher A1 - Arnett, Donna K A1 - Atwood, Larry A1 - Bandera, Elisa V A1 - Bartz, Traci A1 - Becker, Diane M A1 - Berndt, Sonja I A1 - Bernstein, Leslie A1 - Bielak, Lawrence F A1 - Blot, William J A1 - Bottinger, Erwin P A1 - Bowden, Donald W A1 - Bradfield, Jonathan P A1 - Brody, Jennifer A A1 - Broeckel, Ulrich A1 - Burke, Gregory A1 - Cade, Brian E A1 - Cai, Qiuyin A1 - Caporaso, Neil A1 - Carlson, Chris A1 - Carpten, John A1 - Casey, Graham A1 - Chanock, Stephen J A1 - Chen, Guanjie A1 - Chen, Minhui A1 - Chen, Yii-der I A1 - Chen, Wei-Min A1 - Chesi, Alessandra A1 - Chiang, Charleston W K A1 - Chu, Lisa A1 - Coetzee, Gerry A A1 - Conti, David V A1 - Cooper, Richard S A1 - Cushman, Mary A1 - Demerath, Ellen A1 - Deming, Sandra L A1 - Dimitrov, Latchezar A1 - Ding, Jingzhong A1 - Diver, W Ryan A1 - Duan, Qing A1 - Evans, Michele K A1 - Falusi, Adeyinka G A1 - Faul, Jessica D A1 - Fornage, Myriam A1 - Fox, Caroline A1 - Freedman, Barry I A1 - Garcia, Melissa A1 - Gillanders, Elizabeth M A1 - Goodman, Phyllis A1 - Gottesman, Omri A1 - Grant, Struan F A A1 - Guo, Xiuqing A1 - Hakonarson, Hakon A1 - Haritunians, Talin A1 - Harris, Tamara B A1 - Harris, Curtis C A1 - Henderson, Brian E A1 - Hennis, Anselm A1 - Hernandez, Dena G A1 - Hirschhorn, Joel N A1 - McNeill, Lorna Haughton A1 - Howard, Timothy D A1 - Howard, Barbara A1 - Hsing, Ann W A1 - Hsu, Yu-Han H A1 - Hu, Jennifer J A1 - Huff, Chad D A1 - Huo, Dezheng A1 - Ingles, Sue A A1 - Irvin, Marguerite R A1 - John, Esther M A1 - Johnson, Karen C A1 - Jordan, Joanne M A1 - Kabagambe, Edmond K A1 - Kang, Sun J A1 - Kardia, Sharon L A1 - Keating, Brendan J A1 - Kittles, Rick A A1 - Klein, Eric A A1 - Kolb, Suzanne A1 - Kolonel, Laurence N A1 - Kooperberg, Charles A1 - Kuller, Lewis A1 - Kutlar, Abdullah A1 - Lange, Leslie A1 - Langefeld, Carl D A1 - Le Marchand, Loïc A1 - Leonard, Hampton A1 - Lettre, Guillaume A1 - Levin, Albert M A1 - Li, Yun A1 - Li, Jin A1 - Liu, Yongmei A1 - Liu, Youfang A1 - Liu, Simin A1 - Lohman, Kurt A1 - Lotay, Vaneet A1 - Lu, Yingchang A1 - Maixner, William A1 - Manson, JoAnn E A1 - McKnight, Barbara A1 - Meng, Yan A1 - Monda, Keri L A1 - Monroe, Kris A1 - Moore, Jason H A1 - Mosley, Thomas H A1 - Mudgal, Poorva A1 - Murphy, Adam B A1 - Nadukuru, Rajiv A1 - Nalls, Mike A A1 - Nathanson, Katherine L A1 - Nayak, Uma A1 - N'diaye, Amidou A1 - Nemesure, Barbara A1 - Neslund-Dudas, Christine A1 - Neuhouser, Marian L A1 - Nyante, Sarah A1 - Ochs-Balcom, Heather A1 - Ogundiran, Temidayo O A1 - Ogunniyi, Adesola A1 - Ojengbede, Oladosu A1 - Okut, Hayrettin A1 - Olopade, Olufunmilayo I A1 - Olshan, Andrew A1 - Padhukasahasram, Badri A1 - Palmer, Julie A1 - Palmer, Cameron D A1 - Palmer, Nicholette D A1 - Papanicolaou, George A1 - Patel, Sanjay R A1 - Pettaway, Curtis A A1 - Peyser, Patricia A A1 - Press, Michael F A1 - Rao, D C A1 - Rasmussen-Torvik, Laura J A1 - Redline, Susan A1 - Reiner, Alex P A1 - Rhie, Suhn K A1 - Rodriguez-Gil, Jorge L A1 - Rotimi, Charles N A1 - Rotter, Jerome I A1 - Ruiz-Narvaez, Edward A A1 - Rybicki, Benjamin A A1 - Salako, Babatunde A1 - Sale, Michèle M A1 - Sanderson, Maureen A1 - Schadt, Eric A1 - Schreiner, Pamela J A1 - Schurmann, Claudia A1 - Schwartz, Ann G A1 - Shriner, Daniel A A1 - Signorello, Lisa B A1 - Singleton, Andrew B A1 - Siscovick, David S A1 - Smith, Jennifer A A1 - Smith, Shad A1 - Speliotes, Elizabeth A1 - Spitz, Margaret A1 - Stanford, Janet L A1 - Stevens, Victoria L A1 - Stram, Alex A1 - Strom, Sara S A1 - Sucheston, Lara A1 - Sun, Yan V A1 - Tajuddin, Salman M A1 - Taylor, Herman A1 - Taylor, Kira A1 - Tayo, Bamidele O A1 - Thun, Michael J A1 - Tucker, Margaret A A1 - Vaidya, Dhananjay A1 - Van Den Berg, David J A1 - Vedantam, Sailaja A1 - Vitolins, Mara A1 - Wang, Zhaoming A1 - Ware, Erin B A1 - Wassertheil-Smoller, Sylvia A1 - Weir, David R A1 - Wiencke, John K A1 - Williams, Scott M A1 - Williams, L Keoki A1 - Wilson, James G A1 - Witte, John S A1 - Wrensch, Margaret A1 - Wu, Xifeng A1 - Yao, Jie A1 - Zakai, Neil A1 - Zanetti, Krista A1 - Zemel, Babette S A1 - Zhao, Wei A1 - Zhao, Jing Hua A1 - Zheng, Wei A1 - Zhi, Degui A1 - Zhou, Jie A1 - Zhu, Xiaofeng A1 - Ziegler, Regina G A1 - Zmuda, Joe A1 - Zonderman, Alan B A1 - Psaty, Bruce M A1 - Borecki, Ingrid B A1 - Cupples, L Adrienne A1 - Liu, Ching-Ti A1 - Haiman, Christopher A A1 - Loos, Ruth A1 - Ng, Maggie C Y A1 - North, Kari E AB -

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

VL - 108 IS - 4 ER -