Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus
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Published:2017-06-13
Issue:24
Volume:135
Page:2373-2388
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ISSN:0009-7322
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Container-title:Circulation
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language:en
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Short-container-title:Circulation
Author:
Dale Caroline E.1, Fatemifar Ghazaleh1, Palmer Tom M.1, White Jon1, Prieto-Merino David1, Zabaneh Delilah1, Engmann Jorgen E.L.1, Shah Tina1, Wong Andrew1, Warren Helen R.1, McLachlan Stela1, Trompet Stella1, Moldovan Max1, Morris Richard W.1, Sofat Reecha1, Kumari Meena1, Hyppönen Elina1, Jefferis Barbara J.1, Gaunt Tom R.1, Ben-Shlomo Yoav1, Zhou Ang1, Gentry-Maharaj Aleksandra1, Ryan Andy1, Mutsert Renée de1, Noordam Raymond1, Caulfield Mark J.1, Jukema J. Wouter1, Worrall Bradford B.1, Munroe Patricia B.1, Menon Usha1, Power Chris1, Kuh Diana1, Lawlor Debbie A.1, Humphries Steve E.1, Mook-Kanamori Dennis O.1, Sattar Naveed1, Kivimaki Mika1, Price Jacqueline F.1, Davey Smith George1, Dudbridge Frank1, Hingorani Aroon D.1, Holmes Michael V.1, Casas Juan P.1
Affiliation:
1. From Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, United Kingdom (C.E.D., G.F., D.P.-M., A.D.H., J.P.C.); Department of Mathematics and Statistics, Lancaster University, United Kingdom (T.M.P.); UCLGenetics Institute, University College London, United Kingdom (J.W.); Applied Statistical Methods in Medical Research Group, Universidad Catolica de San Antonio de Murcia, Spain (D.P.-M.); Social Genetic & Developmental Psychiatry,...
Abstract
Background:
The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease.
Methods:
Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.
Results:
Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28–1.71), similar to findings for BMI (1 SD≈4.6 kg/m
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; OR for CHD, 1.36; 95% CI, 1.22–1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03–1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38–2.42) and OR, 1.98 (95% CI, 1.41–2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%–77% per 1 SD).
Conclusions:
Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
279 articles.
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