Obesity is associated with coronary artery disease (CAD) and its risk factors in observational studies. This two-sample Mendelian randomization (MR) study investigated the effect of visceral adipose tissue (VAT) mass on coronary artery disease (CAD), myocardial infarction (MI) and heart failure (HF).
Genetic variants (220 SNPs, P < 5 × 10−8) associated with VAT mass were obtained from a genome-wide association study (GWAS) in the UK Biobank. Genetic associations with CAD outcomes including CAD and myocardial infarction (MI) were obtained from the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (including up to 60,801 cases and 123,504 controls) and data on patients with HF were obtained from the HERMES Consortium (47,309 cases and 930,014 controls). The effects of VAT mass on CAD outcomes and HF were estimated using the inverse variance weighted (IVW) method. Sensitivity analysis and multi-variable MR were used to examine the stability of the IVW results.
Our results showed that genetically predicted higher VAT mass was associated with increased risk of CAD (odds ratio [OR] 1.57, 95% confidence interval [CI], 1.44–1.71; P = 7.62 × 10−24), MI (OR 1.63, 95% CI: 1.48–1.79; P = 3.76 × 10−24) and HF (OR 1.71, 95% CI: 1.60–1.83; P = 1.72 × 10−53). These findings remained significant in the sensitivity analysis and multi-variable MR.
This MR study suggests that genetic determinants of VAT mass are causally associated with CAD, MI and HF.
This is a preview of subscription content, access via your institution
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
The GWAS data used in our MR analysis were publicly available (Supplementary Table 1).
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–128.
Collaborators GBDCoD. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736–88.
Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980–2000. N Engl J Med. 2007;356:2388–98.
Rosengren A, Wedel H, Wilhelmsen L. Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality. A prospective population study. Eur Heart J. 1999;20:269–77.
Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:1301–13.
Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev Off J Int Assoc Stud Obes. 2010;11:11–8.
McFarlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86:713–8.
Tanaka T, Kishi S, Ninomiya K, Tomii D, Koseki K, Sato Y, et al. Impact of abdominal fat distribution, visceral fat, and subcutaneous fat on coronary plaque scores assessed by 320-row computed tomography coronary angiography. Atherosclerosis. 2019;287:155–61.
Marques MD, Santos RD, Parga JR, Rocha-Filho JA, Quaglia LA, Miname MH, et al. Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography. Atherosclerosis. 2010;209:481–6.
Kouli GM, Panagiotakos DB, Kyrou I, Georgousopoulou EN, Chrysohoou C, Tsigos C, et al. Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study. Nutr Metab Cardiovasc Dis. 2017;27:881–9.
Nicklas BJ, Penninx BW, Cesari M, Kritchevsky SB, Newman AB, Kanaya AM, et al. Association of visceral adipose tissue with incident myocardial infarction in older men and women: the Health, Aging and Body Composition Study. Am J Epidemiol. 2004;160:741–9.
Schousboe JT, Kats AM, Langsetmo L, Vo TN, Taylor BC, Schwartz AV, et al. Central obesity and visceral adipose tissue are not associated with incident atherosclerotic cardiovascular disease events in older men. J Am Heart Assoc. 2018;7:e009172.
Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133–63.
Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.
Larsson SC, Back M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study. Eur Heart J. 2020;41:221–6.
Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39–48.
Mahabadi AA, Massaro JM, Rosito GA, Levy D, Murabito JM, Wolf PA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30:850–6.
Karlsson T, Rask-Andersen M, Pan G, Hoglund J, Wadelius C, Ek WE, et al. Contribution of genetics to visceral adiposity and its relation to cardiovascular and metabolic disease. Nat Med. 2019;25:1390–5.
Nikpay M, Goel A, Won HH, Hall LM, Willenborg C, Kanoni S, et al. A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47:1121–30.
Shah S, Henry A, Roselli C, Lin H, Sveinbjornsson G, Fatemifar G, et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat Commun. 2020;11:163.
Cheung C-L, Tan KCB, Au PCM, Li GHY, Cheung BMY. Evaluation of GDF15 as a therapeutic target of cardiometabolic diseases in human: A Mendelian randomization study. EBioMedicine. 2019;41:85–90.
Falconer DS MT. Introduction to Quantitative Genetics. 4th edition Harlow, Essex, UK: Longman 1996.
Burgess S, Thompson SG. Bias in causal estimates from Mendelian randomization studies with weak instruments. Stat Med. 2011;30:1312–23.
Pierce BL, Ahsan H, VanderWeele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40:740–52.
Greco MF, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 2015;34:2926–40.
Bowden J, Davey, Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40:304–14.
Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377–89.
Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693–8.
Pulit SL, Stoneman C, Morris AP, Wood AR, Glastonbury CA, Tyrrell J, et al. Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. Human Mol Genet. 2019;28:166–74.
Freedland ES. Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review. Nutr Metab. 2004;1:12.
Wang Q, Zheng D, Liu J, Fang L, Li Q. Skeletal muscle mass to visceral fat area ratio is an important determinant associated with type 2 diabetes and metabolic syndrome. Diabetes Metab Syndr Obes Targets Ther. 2019;12:1399–407.
Preis SR, Massaro JM, Robins SJ, Hoffmann U, Vasan RS, Irlbeck T, et al. Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham heart study. Obesity. 2010;18:2191–8.
Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radiol. 2012;85:1–10.
Lee YH, Lee SH, Jung ES, Kim JS, Shim CY, Ko YG, et al. Visceral adiposity and the severity of coronary artery disease in middle-aged subjects with normal waist circumference and its relation with lipocalin-2 and MCP-1. Atherosclerosis. 2010;213:592–7.
Yan B, Yang J, Zhao B, Wu Y, Bai L, Ma X. Causal effect of visceral adipose tissue accumulation on the human longevity: a mendelian randomization study. Front Endocrinol (Lausanne). 2021;12:722187.
Nuttall FQ. Body mass index: obesity, bmi, and health: a critical review. Nutr Today. 2015;50:117–28.
Zhang X, Lv WQ, Qiu B, Zhang LJ, Qin J, Tang FJ, et al. Assessing causal estimates of the association of obesity-related traits with coronary artery disease using a Mendelian randomization approach. Sci Rep. 2018;8:7146.
Sanderson E, Davey Smith G, Windmeijer F, Bowden J. An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. Int J Epidemiol. 2019;48:713–27.
Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res. 2019;4:186.
Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:251–60.
Ohman MK, Wright AP, Wickenheiser KJ, Luo W, Eitzman DT. Visceral adipose tissue and atherosclerosis. Curr Vasc Pharmacol. 2009;7:169–79.
We would like to thank the High-Performance Computing Center of the First Affiliated Hospital of Xi’an Jiaotong University for assistance of data computing.
This study was supported by the Natural Science Basic Research Program of Shaanxi (No. 2021JQ-395).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Chen, Q., Wu, Y., Gao, Y. et al. Effect of visceral adipose tissue mass on coronary artery disease and heart failure: A Mendelian randomization study. Int J Obes 46, 2102–2106 (2022). https://doi.org/10.1038/s41366-022-01216-x