Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.
Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis.
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DOI：
10.1161/circulationaha.116.026560
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发表时间：
2017-06-13
期刊：
影响因子：
37.8
通讯作者：
Casas JP
中科院分区：
文献类型：
--
作者：
Dale CE;Fatemifar G;Palmer TM;White J;Prieto-Merino D;Zabaneh D;Engmann JEL;Shah T;Wong A;Warren HR;McLachlan S;Trompet S;Moldovan M;Morris RW;Sofat R;Kumari M;Hyppönen E;Jefferis BJ;Gaunt TR;Ben-Shlomo Y;Zhou A;Gentry-Maharaj A;Ryan A;UCLEB Consortium; METASTROKE Consortium;Mutsert R;Noordam R;Caulfield MJ;Jukema JW;Worrall BB;Munroe PB;Menon U;Power C;Kuh D;Lawlor DA;Humphries SE;Mook-Kanamori DO;Sattar N;Kivimaki M;Price JF;Davey Smith G;Dudbridge F;Hingorani AD;Holmes MV;Casas JP
不同的肥胖测量方法对心血管疾病病因的影响尚不清楚。在本文中，我们量化和对比了中心性肥胖（腰臀比调整BMI (WHRadjBMI)）和一般性肥胖（身体质量指数（BMI））与心脏代谢疾病的因果关系。BMI的97个独立单核苷酸多态性（snp）和WHRadjBMI的49个snp被用于对14项前瞻性研究进行孟德尔随机化分析，这些研究补充了CARDIoGRAMplusC4D的冠心病数据（总计66,842例）、METASTROKE的卒中数据（12,389例缺血性卒中）、DIAGRAM的2型糖尿病（T2D）数据（34,840例）和GLGC（213,500名参与者）联盟的脂质数据。主要结局为冠心病、T2D和主要脑卒中亚型；二次分析包括18个心脏代谢特征。WHRadjBMI每高一个标准差（1SD~0.08单位）与冠心病风险增加48%相关（冠心病的比值比[OR]: 1.48; 95%CI: 1.28 ~ 1.71），与BMI的结果相似（1SD~4.6kg/m2；冠心病的比值比：1.36;95%CI: 1.22 ~ 1.52）。只有WHRadjBMI增加了缺血性卒中的风险（OR 1.32; 95%CI 1.03-1.70）。对于T2D，两种测量方法都有很大的影响：WHRadjBMI和BMI每高1SD， OR分别为1.82 （95%CI 1.38-2.42）和1.98 （95%CI 1.41-2.78）。WHRadjBMI和BMI均与较高的左室肥厚、血糖特征、白细胞介素-6和循环脂质有关。WHRadjBMI也与颈动脉内膜-中膜厚度升高相关（39%;95%CI: 9%-77% / 1SD）。全身性和中心性肥胖对冠心病和T2D均有因果影响。中心性肥胖可能对中风风险有更大的影响。未来对肥胖对健康造成的负担的估计应包括中枢性和一般性肥胖的测量。
Implications of different adiposity measures on cardiovascular disease aetiology remain unclear. In this paper we quantify and contrast causal associations of central adiposity (waist:hip ratio adjusted for BMI (WHRadjBMI)) and general adiposity (body mass index (BMI)) with cardiometabolic disease. 97 independent single nucleotide polymorphisms (SNPs) for BMI and 49 SNPs for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with CHD data from CARDIoGRAMplusC4D (combined total 66,842 cases), stroke from METASTROKE (12,389 ischaemic stroke cases), type 2 diabetes (T2D) from DIAGRAM (34,840 cases), and lipids from GLGC (213,500 participants) consortia. Primary outcomes were CHD, T2D, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. Each one standard deviation (SD) higher WHRadjBMI (1SD~0.08 units) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD: 1.48; 95%CI: 1.28-1.71), similar to findings for BMI (1SD~4.6kg/m2; OR for CHD: 1.36; 95%CI: 1.22-1.52). Only WHRadjBMI increased risk of ischaemic stroke (OR 1.32; 95%CI 1.03-1.70). For T2D, 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 1SD higher WHRadjBMI and BMI respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycaemic traits, interleukin-6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95%CI: 9%-77% per 1SD). Both general and central adiposity have causal effects on CHD and T2D. 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.