Adiposity as a cause of cardiovascular disease: a Mendelian randomization study
Adiposity as a cause of cardiovascular disease: a Mendelian randomization study
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DOI：
10.1093/ije/dyv094
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发表时间：
2015-04-01
影响因子：
7.7
通讯作者：
Ingelsson, Erik
中科院分区：
文献类型：
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作者：
Haegg, Sara;Fall, Tove;Ingelsson, Erik
背景：流行病学研究表明，体重指数（BMI）显示的肥胖与心血管疾病的风险相关。我们的目的是调查这些关联是否有因果关系，使用孟德尔随机化（MR）方法。方法：研究了BMI与心血管结局[冠心病、心力衰竭和缺血性卒中]的关系，以及遗传评分（32个BMI单核苷酸多态性）与BMI和心血管结局的关系，这些研究来自ENGAGE联盟的9项前瞻性随访研究，涉及多达22 193例3062例心血管事件。我们在磁共振框架中使用随机效应荟萃分析来提供肥胖对心血管结局影响的因果估计。结果：在观察性分析中，BMI与冠心病的发生率（每sd BMI增加，HR = 1.20, 95% CI, 1.12-1.28, P = 1.9.10(-7)）、心力衰竭（HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)）和缺血性卒中（HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008）有很强的相关性。遗传评分与BMI呈显著相关（β = 0.030 sd -每增加一个等位基因BMI增加，95% CI, 0.028-0.033, P = 3.10(-107)）。分析表明，肥胖对心力衰竭（每sd BMI增加的HR = 1.93, 95% CI, 1.12-3.30, P = 0.017）和缺血性中风（HR = 1.83, 95% CI, 1.05-3.20, P = 0.034）的发展有因果关系。使用ENGAGE和CARDIoGRAMplusC4D数据进行的其他横断面分析显示，肥胖对冠心病有因果关系。结论：使用MR方法，我们为肥胖导致冠心病、心力衰竭和缺血性中风的假设提供了支持。
Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (beta = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.