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Wannamethee S.G.,University College London | Welsh P.,University of Glasgow | Whincup P.H.,St Georges, University of London | Sawar N.,University of Cambridge | And 4 more authors.
European Journal of Cardiovascular Prevention and Rehabilitation | Year: 2011

Background: Raised adiponectin is associated with increased rather than decreased risk of cardiovascular disease (CVD) and mortality at older age. We examined whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction, may help explain this relationship. Methods and results: A prospective study of 2879 men aged 60-79 years with no history of CVD at baseline followed-up for a mean of 9 years during which there were 196 major coronary heart disease events (fatal and non-fatal myocardial infarction) and 667 deaths (including 225 CVD deaths), whereas adiponectin concentration was inversely associated with several conventional CVD risk factors; it was significantly and positively associated with NT-proBNP concentration. After adjustment for several vascular risk factors, including renal function and muscle mass, relative risks associated with a top third versus bottom third comparison of adiponectin concentration were 1.51 (1.02-2.23) for coronary heart disease, 1.67 (1.15-2.41) for CVD mortality and 1.41 (1.13-1.95) for all cause mortality. Upon further adjustment for NT-proBNP, these relative risks attenuated to 1.31 (0.88-1.94), 1.31 (0.90-1.91) and 1.26 (1.01-1.59), respectively. Conclusion: We show for the first time that concomitantly elevated NT-proBNP concentration, at least, partially explains the apparently positive relationship between adiponectin concentration and risk of CVD and mortality in asymptomatic elderly men. © The European Society of Cardiology 2011. Source


Danielsen R.,Reykjavik University | Aspelund T.,Icelandic Heart Association Research Institute | Aspelund T.,University of Iceland | Harris T.B.,U.S. National Institute on Aging | And 2 more authors.
International Journal of Cardiology | Year: 2014

Methods and results Echocardiography and computed tomography (CT) data from individuals who participated in the AGES-Reykjavik study were used. Echocardiography data from 685 individuals (58% females) aged 67-95 years were available. In both sexes combined, the prevalence for severe AS, defined as an aortic valve area index of < 0.6 cm2/m2, in the age groups < 70, 70-79 and ≤80 years was 0.92%, 2.4% and 7.3%, respectively. A ROC analysis on the relation between the echocardiography data and the aortic valve calcium score on CT defined a score ≤500 to be indicative of severe AS. Subsequently, in a CT study cohort of 5256 individuals the prevalence of severe AS in the same age groups was 0.80%, 4.0% and 9.5%, respectively. Overall, the prevalence of severe AS by echocardiography and CT in individuals ≤70 years was 4.3% and 5.9%, respectively. A prediction on the number of elderly ≤70 years for the coming decades demonstrated that patients with severe AS will have increased 2.4 fold by the year 2040 and will more than triple by the year 2060. Conclusion This study, in a cohort of elderly individuals representative of the general population in a Nordic country, predicts that AS will be a large health problem in the coming decades.Aims To evaluate the prevalence of significant aortic valve stenosis (AS) in a randomly selected study population of elderly individuals representing the general population of Iceland. Furthermore, to predict the number of individuals likely to have severe AS in the future. © 2014 Elsevier Ireland Ltd. All rights reserved. Source


Murphy R.A.,U.S. National Institute on Aging | Nalls M.A.,U.S. National Institute on Aging | Keller M.,U.S. National Institute on Aging | Keller M.,Temple University | And 9 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Most genome-wide association studies are confined to middle-Aged populations. It is unclear whether associations between single nucleotide polymorphisms (SNPs) and obesity persist in old age. We aimed to relate 10 body mass index (BMI)-Associated SNPs to weight, BMI, % fat, visceral and subcutaneous adipose tissue in Health ABC and AGES-Reykjavik comprising 4,846 individuals of European Ancestry, and 1,139 African Americans over age 65. SNPs were scaled using effect estimates from candidate SNPs. In Health ABC, a SNP near GNPDA2 was modestly associated with weight and SAT area (p =. 008, p =. 001). Risk score (sum of scaled SNPs) was associated with weight, BMI, and SAT area (p <. 0001 for all), but neither GNPDA2 nor risk score was associated with weight, BMI, visceral adippose tissue, subcutaneous adipose tissue, or % fat in AGES-Reykjavik. In African Americans, a SNP near SEC16B was weakly associated with weight (p =. 04). In this sample of older adults, no BMI-Associated SNPs were associated with weight or adiposity. © 2012 Published by Oxford University Press on behalf of the Gerontological Society of America 2012. Source


Murphy R.A.,U.S. National Institute on Aging | Reinders I.,U.S. National Institute on Aging | Garcia M.E.,U.S. National Institute on Aging | Eiriksdottir G.,Icelandic Heart Association Research Institute | And 5 more authors.
Diabetes Care | Year: 2014

OBJECTIVE: Studies in type 2 diabetes report both increased mortality for normal weight and no evidence of an obesity paradox. We aimed to examine whether adipose tissue, muscle size, and physical function, which are known to vary by weight, mediate associations between BMI and mortality. RESEARCH DESIGN AND METHODS: The AGES-Reykjavik cohort comprised participants aged 66-96 years with diabetes defined by fasting glucose, medications, or self-report. BMI was determined from measured height and weight and classified as normal (18.5-24.9 kg/m2, n = 117), overweight (25.0-29.9 kg/m2, n = 293, referent group) or obese (≥30.0 kg/m2, n = 227). Thigh muscle area and intermuscular, visceral, and subcutaneous adipose tissues were assessed with computed tomography. Function was assessed from gait speed and knee extensor strength. Hazard ratios (HRs) and 95% CIs were estimated by Cox proportional hazards regression adjusted for demographics and diabetes-related risk factors. RESULTS: Themedian follow-upwas 6.66 years, and there were 85, 59, and 44 deaths among normal weight, overweight, and obese participants, respectively. There was no mortality risk for obese participants and an increased risk among normal weight comparedwith overweight participants (HR 1.72 [95% CI 1.12-2.64]). Associations remained with adjustment for adipose tissues and knee extensor strength; however, mortality risk for normal weight was attenuated following adjustment for thigh muscle (HR 1.36 [95% CI 0.87-2.11]) and gait speed (HR 1.44 [95% CI 0.91-2.27]). Linear regression confirmed with bootstrapping indicated that thigh muscle size mediated 46% of the relationship between normal weight and mortality. CONCLUSIONS: Normal weight participants had elevated mortality risk compared with overweight participants. This paradoxical association was mediated in part by muscle size. © 2014 by the American Diabetes Association. Source


Smith J.G.,Lund University | Smith J.G.,Skane University Hospital | Smith J.G.,The Broad Institute of MIT and Harvard | Smith J.G.,Harvard University | And 32 more authors.
JAMA - Journal of the American Medical Association | Year: 2014

IMPORTANCE Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. Copyright 2014 American Medical Association. All rights reserved.OBJECTIVE To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease.DESIGN, SETTING, AND PARTICIPANTS Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study-Reykjavik (2000-2012; n = 3120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28 461).MAIN OUTCOMES AND MEASURES Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS.RESULTS The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P =.02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P =.007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P=.02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P =.03) and aortic stenosis (P =.009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P =.02).CONCLUSIONS AND RELEVANCE Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation. Source

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