PLoS Med：荟萃分析确认BMI与心脏病的风险关系

（图片来源：Medpage Today）

英国布里斯托大学的Nicholas J. Timpson博士等人近日在《公共科学图书馆·医学》（PLoS Medicine）杂志发表论文称，身体质量指数（BMI）升高可增大发生缺血性心脏病的风险。

研究者称，如果将遗传因素考虑进去，BMI每升高4 kg/m2 ，发生缺血性心脏病的风险将增大52%（95%可信区间为1.12至2.05）。

之前已有多项观察性研究表明，高BMI与缺血性心脏病之间存在某种联系，但由于混杂、逆向因果关系、以及偏倚的影响，其因果关系一直未得到证实。因此Timpson等使用孟德尔方法进行了该研究。

孟德尔法与随机化试验类似，但其危险因素相关基因型的随机化发生在概念阶段。

该研究共包括75627名丹麦白人，这些研究对象分别来自于3个不同的研究。研究者前瞻性地分析了缺血性心脏病的发生率与3个基因型和BMI的关系，3个基因型分别为FTO（rs9939609）、MC4R（rs17782313）、TMEM18（rs6548238）。

对这3个研究的Meta分析表明，BMI每升高1个标准差（即4 kg/m2），发生缺血性心脏病的风险增高26%（95%可信区间为1.19至1.34）。每个肥胖相关性等位基因与BMI升高0.28 kg/m2 相关（95%可信区间为0.22至0.34），没有该等位基因者与有全部6个肥胖相关性等位基因者相差1.68 kg/m2 。每个肥胖相关性等位基因可使发生缺血性心脏病的风险升高3%，因此有全部6个等位基因者发生缺血性心脏病的风险比没有等位基因者高20%，这与上述结论一致。

该研究中，可能产生混杂的因素如性别、年龄、吸烟和饮酒史、经济收入等，均与BMI和缺血性心脏病不相关。

最后研究者指出，这项发现对于关乎民族健康的指导性政策有重要意义。

doi:10.1371/journal.pmed.1001212
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The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach

Børge G. Nordestgaard, Tom M. Palmer,Marianne Benn, Jeppe Zacho, Anne Tybjærg-Hansen, George Davey Smith, Nicholas J. Timpson.

Background Adiposity, assessed as elevated body mass index (BMI), is associated with increased risk of ischemic heart disease (IHD); however, whether this is causal is unknown. We tested the hypothesis that positive observational associations between BMI and IHD are causal. Methods and Findings In 75,627 individuals taken from two population-based and one case-control study in Copenhagen, we measured BMI, ascertained 11,056 IHD events, and genotyped FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238). Using genotypes as a combined allele score in instrumental variable analyses, the causal odds ratio (OR) between BMI and IHD was estimated and compared with observational estimates. The allele score-BMI and the allele score-IHD associations used to estimate the causal OR were also calculated individually. In observational analyses the OR for IHD was 1.26 (95% CI 1.19–1.34) for every 4 kg/m2 increase in BMI. A one-unit allele score increase associated with a 0.28 kg/m2 (95 CI% 0.20–0.36) increase in BMI and an OR for IHD of 1.03 (95% CI 1.01–1.05) (corresponding to an average 1.68 kg/m2 BMI increase and 18% increase in the odds of IHD for those carrying all six BMI increasing alleles). In instrumental variable analysis using the same allele score the causal IHD OR for a 4 kg/m2 increase in BMI was 1.52 (95% CI 1.12–2.05). Conclusions For every 4 kg/m2 increase in BMI, observational estimates suggested a 26% increase in odds for IHD while causal estimates suggested a 52% increase. These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia, and type 2 diabetes. This work has important policy implications for public health, given the continuous nature of the BMI-IHD association and the modifiable nature of BMI. This analysis demonstrates the value of observational studies and their ability to provide unbiased results through inclusion of genetic data avoiding confounding, reverse causation, and bias.