Body and Fat Mass Associated with Increased Risk of Cardiovascular Disease

by | Jul 8, 2019 | 2019, Cardiovascular Health

Written by Angeline A. De Leon, Staff Writer. Using a Mendelian randomization design, researchers demonstrated that higher BMI and particularly fat mass index are associated with increased risk of aortic valve stenosis and most other cardiovascular conditions.

cardiovascular health - sliderA rich body of evidence has established body mass index (BMI), along with smoking, poor diet, and alcohol 1, as a strong predictor of cardiovascular disease 2,3. Reports estimate that over two thirds of deaths caused by high BMI are a form of CVD 1. Despite strong evidence suggesting BMI as a causal risk factor for a variety of CVDs, the role of BMI as a risk factor in other forms of CVDs, including aortic valve stenosis, aortic aneurysm, intracerebral hemorrhages, and pulmonary embolism, is less certain and has only been studied using observational study designs 4-6. To this end, researchers in Sweden (2019) evaluated the association of BMI (representing overall adiposity) to arterial hypertension and 13 CVDs, including aortic valve stenosis, heart failure, ischemic stroke, and coronary artery disease 7. Importantly, investigators employed a Mendelian randomization study design, an epidemiological method used to determine a causal link between a modifiable risk factor (BMI) and an observed clinical outcome (CVD). The roles of fat mass and fat-free mass indices were also examined on the same outcomes in the present study.

In a group of 367,703 community-dwelling adults (aged 40 to 69 years) registered with the UK Biobank, 96 single-nucleotide polymorphisms (SNPs, a variation in a single base pair in a DNA sequence) associated with BMI (at the genome-wide significance threshold p < 5 x 10-8) were used as instrument variables to estimate associations with 14 cardiovascular conditions. For fat mass and fat-free mass indices, 82 SNPs associated with body composition were used to estimate associations with CVD among 362, 499 UK Biobank participants.

After correcting for multiple testing, analyses indicated that genetically predicted BMI was positively linked to 8 of 14 assessed cardiovascular conditions: 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 genetically predicted 1 kg/m2 increase of BMI ranged from 1.06 (95% Confidence Interval: 1.02 to 1.11, p = 2.6 x 10-3) for pulmonary embolism to 1.13 (95% CI: 1.05 to 1.21, p = 1.2 x 10-3) for aortic valve stenosis. Results also revealed significant inverse associations of genetically predicted fat mass index with 9 of the 14 cardiovascular outcomes (p < 0.05), with the strongest magnitude of association between fat mass index and aortic valve stenosis (OR per 1 kg/m2 increase in fat mass index: 1.46, 95% CI: 1.13 to 1.88, p = 3.9 x 10-3).

General findings coincide with previous research identifying BMI as a causal risk factor for CVDs 3-6. Along with BMI, fat mass index, in particular, was found to be associated with increased risk of the majority of cardiovascular outcomes, with the strongest positive association relating to aortic valve stenosis. Fat-free mass index showed only suggestive evidence of inverse associations with atrial fibrillation, ischemic stroke, and abdominal aortic aneurysm. The primary strength of the current study is its ability to evaluate the causal role of adiposity measures in a range of cardiovascular conditions within the same cohort using a Mendelian randomization study design. A limitation to be noted is the potential for pleiotropic effects, the association of a genetic variant with more than one phenotype, which could limit the current study’s ability to establish direct causality between the SNPs associated with BMI and the various cardiovascular conditions. Nonetheless, the present study contributes to the understanding of how adiposity measures relate to a range of CVDs whose association to BMI was previously unclear. Future studies are needed to examine the mechanisms underlying the associations between BMI and each CVD outcome.

Source: Larsson SC, Back M, Rees JMB, et al. Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: A Mendelian randomization study. European Heart Journal. 2019: 0-8. DOI: 10.1093/eurheartj/ehz388.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).

Posted July 8, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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