肥胖作为心血管疾病的一个病因：一项孟德尔随机化研究。
Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.
作者信息
Hägg Sara, Fall Tove, Ploner Alexander, Mägi Reedik, Fischer Krista, Draisma Harmen H M, Kals Mart, de Vries Paul S, Dehghan Abbas, Willems Sara M, Sarin Antti-Pekka, Kristiansson Kati, Nuotio Marja-Liisa, Havulinna Aki S, de Bruijn Renée F A G, Ikram M Arfan, Kuningas Maris, Stricker Bruno H, Franco Oscar H, Benyamin Beben, Gieger Christian, Hall Alistair S, Huikari Ville, Jula Antti, Järvelin Marjo-Riitta, Kaakinen Marika, Kaprio Jaakko, Kobl Michael, Mangino Massimo, Nelson Christopher P, Palotie Aarno, Samani Nilesh J, Spector Tim D, Strachan David P, Tobin Martin D, Whitfield John B, Uitterlinden André G, Salomaa Veikko, Syvänen Ann-Christine, Kuulasmaa Kari, Magnusson Patrik K, Esko Tõnu, Hofman Albert, de Geus Eco J C, Lind Lars, Giedraitis Vilmantas, Perola Markus, Evans Alun, Ferrières Jean, Virtamo Jarmo, Kee Frank, Tregouet David-Alexandre, Arveiler Dominique, Amouyel Philippe, Gianfagna Francesco, Brambilla Paolo, Ripatti Samuli, van Duijn Cornelia M, Metspalu Andres, Prokopenko Inga, McCarthy Mark I, Pedersen Nancy L, Ingelsson Erik
机构信息
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, Estonian Genome Center, University of Tartu, Tartu, Estonia, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands, Institute of Mathematical Statistics, University of Tartu, Tartu, Estonia, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, Leiden, The Netherlands, Department of Genetic Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands, Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland, National Institute for Health and Welfare, Helsinki, Finland, Department of Neurology, and Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands, Inspectorate for Health Care, The Hague, The Netherlands, Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia, Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany, Division of Epidemiology, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK, Center for Life Course and Systems Epidemiology, University of Oulu, Oulu, Finland, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland, Department of Children, Young People and Families, National Institute for Health and Welfare, Oulu, Finland, MRC Health Protection Agency (HPE) Centre for Environment and Health, Imperial College London, London, UK, Unit of Primary Care, Oulu University Hospital, Oulu, Finland, Hjelt Institute, University of Helsinki,
出版信息
Int J Epidemiol. 2015 Apr;44(2):578-86. doi: 10.1093/ije/dyv094. Epub 2015 May 27.
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 (β = 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.
背景
在流行病学研究中，体重指数（BMI）所表明的肥胖与心血管疾病风险相关。我们旨在使用孟德尔随机化（MR）方法研究这些关联是否为因果关系。
方法
在ENGAGE联盟的9项前瞻性随访研究中，对多达22193名个体进行了研究，其中有3062例心血管事件，研究了BMI与心血管结局[冠心病（CHD）、心力衰竭和缺血性中风]的关联，以及基因评分（32个BMI单核苷酸多态性）与BMI和心血管结局的关联。我们在MR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与冠心病发病（BMI每增加1个标准差，风险比[HR]=1.20，95%置信区间[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）和缺血性中风（HR = 1.15，95% CI，1.06 - 1.24，P = 0.0008）之间存在强关联。基因评分与BMI密切相关（每增加一个等位基因，BMI增加0.030个标准差，95% CI，0.028 - 0.033，P = 3×10⁻¹⁰⁷）。分析表明肥胖对心力衰竭（BMI每增加1个标准差，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）的发生有因果效应。使用ENGAGE和CARDIoGRAMplusC4D数据进行的额外横断面分析显示肥胖对冠心病有因果效应。
结论
使用MR方法，我们支持肥胖导致冠心病、心力衰竭以及此前未证实的缺血性中风这一假设。
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