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Eur Heart J. 2019 Jun 13. pii: ehz388. doi: 10.1093/eurheartj/ehz388. [Epub ahead of print]

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

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Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, SE Stockholm, Sweden.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Heart and Vascular Theme - Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Edinburgh Clinical Trials Unit, Usher, Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
MRC Biostatistics Unit, University of Cambridge, UK.



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.


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.


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.


Adiposity; Body composition; Body mass index; Cardiovascular disease; Mendelian randomization; Obesity


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