Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Epidemiology and Population Health

Effect of visceral adipose tissue mass on coronary artery disease and heart failure: A Mendelian randomization study

International Journal of Obesity volume 46, pages 2102–2106 (2022)Cite this article

Subjects

Abstract

Objectives

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).

Methods

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.

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.

Conclusion

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A directed acyclic graph of the Mendelian randomization study.
Fig. 2: Associations between VAT mass and coronary artery disease (CAD).
Fig. 3: Associations between VAT mass and myocardial infarction (MI) and heart failure (HF).

Similar content being viewed by others

Data availability

The GWAS data used in our MR analysis were publicly available (Supplementary Table 1).

References

  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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:1301–13.

    Article  PubMed  Google Scholar 

  6. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev Off J Int Assoc Stud Obes. 2010;11:11–8.

    Article  Google Scholar 

  7. McFarlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86:713–8.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Falconer DS MT. Introduction to Quantitative Genetics. 4th edition Harlow, Essex, UK: Longman 1996.

  23. Burgess S, Thompson SG. Bias in causal estimates from Mendelian randomization studies with weak instruments. Stat Med. 2011;30:1312–23.

    Article  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:377–89.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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.

    Article  Google Scholar 

  31. 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.

    Article  Google Scholar 

  32. 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.

    Article  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

    Article  Google Scholar 

  36. Nuttall FQ. Body mass index: obesity, bmi, and health: a critical review. Nutr Today. 2015;50:117–28.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 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.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

  40. Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:251–60.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ohman MK, Wright AP, Wickenheiser KJ, Luo W, Eitzman DT. Visceral adipose tissue and atherosclerosis. Curr Vasc Pharmacol. 2009;7:169–79.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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.

Funding

This study was supported by the Natural Science Basic Research Program of Shaanxi (No. 2021JQ-395).

Author information

Authors and Affiliations

  1. Department of Cardiovascular Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Qiang Chen, Yang Gao & Tao Shi

  2. Department of Clinical Research Center, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Yanhua Wu & Bin Yan

  3. Departments of Anaesthesiology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Zhanqin Zhang

Authors
  1. Qiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanhua Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhanqin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tao Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QC and BY raised the idea for the study. QC, YW, YG, ZZ, TS, and BY contributed to the study design, writing and review of the report. BY and QC did the data analysis. BY handled supervision in our study. All authors approved the final version of the report.

Corresponding author

Correspondence to Bin Yan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-022-01216-x

Search

Advanced search

Quick links