Abstract Aims The causal role of adiposity for several cardiovascular diseases (CVDs) is unclear. Our primary aim was to apply the Mendelian randomization design to investigate the associations of body mass index (BMI) with 13 CVDs and arterial hypertension. We also assessed the roles of fat mass and fat-free mass on the same outcomes. Methods and results Single-nucleotide polymorphisms associated with BMI and fat mass and fat-free mass indices were used as instrumental variables to estimate the associations with the cardiovascular conditions among 367 703 UK Biobank participants. After correcting for multiple testing, genetically predicted BMI was significantly positively associated with eight outcomes, including and with decreasing magnitude of association: aortic valve stenosis, heart failure, deep vein thrombosis, arterial hypertension, peripheral artery disease, coronary artery disease, atrial fibrillation, and pulmonary embolism. The odds ratio (OR) per 1 kg/m2 increase in BMI ranged from 1.06 [95% confidence interval (CI) 1.02–1.11; P = 2.6 × 10−3] for pulmonary embolism to 1.13 (95% CI 1.05–1.21; P = 1.2 × 10−3) for aortic valve stenosis. There was suggestive evidence of positive associations of genetically predicted fat mass index with nine outcomes (P < 0.05). The strongest magnitude of association was with aortic valve stenosis (OR per 1 kg/m2 increase in fat mass index 1.46, 95% CI 1.13–1.88; P = 3.9 × 10−3). There was suggestive evidence of inverse associations of fat-free mass index with atrial fibrillation, ischaemic stroke, and abdominal aortic aneurysm. Conclusion This study provides evidence that higher BMI and particularly fat mass index are associated with increased risk of aortic valve stenosis and most other cardiovascular conditions.

中文翻译：

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英国生物银行中与 14 种心血管疾病相关的体重指数和身体成分：孟德尔随机研究


摘要 目的 肥胖与多种心血管疾病 (CVD) 的因果关系尚不清楚。我们的主要目的是应用孟德尔随机化设计来研究体重指数 (BMI) 与 13 种 CVD 和动脉高血压的关联。我们还评估了脂肪量和去脂量对相同结果的作用。方法和结果 与 BMI、脂肪质量和无脂肪质量指数相关的单核苷酸多态性被用作工具变量，以估计 367 703 名英国生物银行参与者与心血管疾病的关联。经过多次测试校正后，基因预测的 BMI 与八种结果呈显着正相关，包括主动脉瓣狭窄、心力衰竭、深静脉血栓形成、动脉高血压、外周动脉疾病、冠状动脉疾病、心房颤动、和肺栓塞。 BMI 每增加 1 kg/m2，优势比 (OR) 范围为 1.06 [95% 置信区间 (CI) 1.02–1.11；对于肺栓塞，P = 2.6 × 10−3]；对于主动脉瓣狭窄，P = 1.13（95% CI 1.05–1.21；P = 1.2 × 10−3）。有暗示性证据表明基因预测的脂肪质量指数与九个结果呈正相关（P< 0.05）。关联性最强的是主动脉瓣狭窄（脂肪质量指数每增加 1 kg/m2，OR 为 1.46，95% CI 1.13–1.88；P = 3.9 × 10−3）。有证据表明，去脂体重指数与心房颤动、缺血性中风和腹主动脉瘤呈负相关。结论 这项研究提供的证据表明，较高的 BMI，尤其是脂肪质量指数与主动脉瓣狭窄和大多数其他心血管疾病的风险增加相关。