Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study

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.

Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

“…These conclusions are based on traditional observational studies which are subject to confounding and reverse causality, which are minimized in this MR design. Though a recent MR analysis showed obesity is a key risk factor for cardiovascular disease [3], our study shows obesity is not a consistent risk factor for cancer. This has future implications for public health measures for cancer prevention and screening.…”

“…Obesity is a global epidemic [1], with 20% of the world's population predicted to be obese by 2025 [2]. Multiple studies have demonstrated that obesity is associated with increased risk of cardiovascular [3] [4], liver [5], and musculoskeletal disease [6]. The relationship between obesity and cancer risk has been subject to extensive investigation.…”

Mendelian Randomization Study of Obesity and Cerebrovascular Disease

“…Two prior genetic studies have investigated the relationship between obesity and ICH and did not identify any significant associations . To our knowledge, no study has investigated distinct effects between lobar and nonlobar ICH.…”

“…Two prior genetic studies have investigated the relationship between obesity and ICH and did not identify any significant associations. 6,7 To our knowledge, no study has investigated distinct effects between lobar and nonlobar ICH. In contrast to ischemic stroke, epidemiologic studies have reported conflicting results on the association between obesity and ICH risk, with 1 study reporting an increased prevalence of obesity in patients hospitalized for ICH 39 and another showing that ICH cases have lower BMI.…”

“…Mendelian randomization (MR) is an instrumental variable analysis approach that has been deployed in genetic epidemiology to determine whether associations of co‐occurring traits reflect a causal relationship or simple correlation . Two previous analyses applied MR to show that central adiposity increases risk of ischemic stroke, among other cardiovascular phenotypes . Leveraging the most updated genome‐wide association study (GWAS) data for body fat distribution and obesity, stroke, and additional cerebrovascular disease traits, we aimed to (1) determine the degree to which different cerebrovascular disease subtypes are affected by obesity traits, (2) clarify which obesity trait (waist‐to‐hip ratio [WHR] or BMI) best explains any increased risk of stroke, and (3) assess the role of potential mediators of any identified causal effects.…”