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Cited by 436Genetic Associations and EpidemiologyCardiovascular Disease and AdiposityObesity, Physical Activity, Diet

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

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Larsson, Susanna C, Bäck, Magnus, Rees, Jessica M B, Mason, Amy M, Burgess, Stephen·2020·European Heart Journal
DOI 10.1093/eurheartj/ehz388PMC PMC6945523
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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.

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  • Obesity increases risk of thromboembolism, which has also been confirmed genetically.

    “Obesity increases risk of thromboembolism, which has also been confirmed genetically.107”

    From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [107]

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Authors
Larsson, S. C., Bäck, M., Rees, J. M. B., Mason, A. M., & Burgess, S.
Affiliations
  • Uppsala University (SE)
  • Karolinska University Hospital (SE)
  • University of Cambridge (GB)
Corresponding author
Larsson, Susanna C
ORCID
Venue
European Heart Journal
Publisher
Oxford University Press (OUP)
Published
2019-06-13
Volume
41
Issue
2
Pages
221-226
ISSN
  • 0195-668X (ISSN-L)
  • 1522-9645
DOI
10.1093/eurheartj/ehz388
PMC
PMC6945523
OpenAlex
W2950769483
Cited by
436
References
7
Citations by year
2026: 37 · 2025: 65 · 2024: 68 · 2023: 64 · 2022: 70 · 2021: 71 · 2020: 51 · 2019: 9
FWCI
30.44
Type
journal article
Language
en
Open access
Licence
Locations
  • European Heart Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • Swedish Research Council for Health, Working Life and Welfare
  • Swedish Research Council
  • Wellcome Trust
  • Royal Society (204623/Z/16/Z)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
Keywords
body mass index, adiposity, cardiovascular disease, fat mass index, fat-free mass index, aortic stenosis, hypertension, coronary artery disease, atrial fibrillation, deep vein thrombosis, pulmonary embolism, heart failure, peripheral arterial disease, ischemic stroke, abdominal aortic aneurysm, genetic instruments, causal relationship
MeSH terms
Adult, Aged, Cardiovascular Diseases, Female, United Kingdom, Humans, Male, Middle Aged, Obesity, Risk Factors, Body Mass Index, Incidence, Biological Specimen Banks, Risk Assessment, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis

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