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CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(03): 347-361
DOI: 10.1055/a-1980-8852
Stroke, Systemic or Venous Thromboembolism

Genetic Predisposition of Both Waist Circumference and Hip Circumference Increased the Risk of Venous Thromboembolism

Jiayu Wang‡   *
1   Department of Cardiology, The Second Hospital of Shandong University, Jinan, China
,
Jiangshan Tan‡   *
2   Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Lu Hua
2   Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
,
Qiping Sheng
1   Department of Cardiology, The Second Hospital of Shandong University, Jinan, China
,
Xianwei Huang
3   Department of Emergency, The First Affiliated Hospital of Xiamen University, Xiamen, China
,
Ping Liu
1   Department of Cardiology, The Second Hospital of Shandong University, Jinan, China
› Author Affiliations Funding This study and this research group were supported by grants from the Science and Technology Innovation Project of Jinan City (No. 201602153; No. 202019193), the Major Research and Development Project of Shandong Province (No. ZR2020MH041), the Natural Fund Project of Shandong Province (No. G201703080074), the project of the Central Government Guides Local Science and Technology Development (2021Szvup073), the National Natural Science Foundation of China (No. 81170274; No. 82170462), and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences (NCRC2020007).
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Abstract

Background Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. Observational studies have shown an observational association between obesity and venous thromboembolism (VTE). As a type of VTE, pulmonary embolism (PE) is also associated with obesity. However, it is unclear whether the observed associations are causal or caused by confounding bias or reverse causality.

Methods We performed a two-sample test by obtaining the exposure dataset of waist circumference (WC) and hip circumference (HC) from the Neale Laboratory Consortium's genome-wide association study summary data and the summary-level outcome data of VTE and PE from FinnGen Biobank of European ancestry to determine the causal effect of WC and HC on VTE and PE.

Results All three Mendelian randomization methods displayed a positive association between WC/HC and VTE/PE. WC and HC were positively associated with VTE (odds ratio [OR] = 1.803 per 1 standard deviation [SD] increase in WC, 95% confidence interval [CI] = 1.393–2.333; p < 0.001; OR = 1.479 per 1 SD increase in HC, 95% CI = 1.219–1.796; p < 0.001, respectively). Furthermore, we found a causal association between genetically predicted WC/HC and a higher risk of PE (OR = 1.929 per 1 SD increase in WC, 95% CI = 1.339–2.778, p < 0.001; OR = 1.431 per 1 SD increase in HC, 95% CI =1.095–1.869; p = 0.009, respectively).

Conclusion There is a significant causal relationship between WC/HC and VTE/PE, which is consistent with observational studies. Taking measures to reduce WC/HC of obesity may help reduce the incidence of VTE/PE.

Keywords

waist circumference - hip circumference - venous thromboembolism - Mendelian randomization study - obesity

Contribution to the Field Statement

Obesity, especially abdominal obesity, is an independent indicator of increased cardiovascular risk. There have been observational studies that showed an observational association between obesity and venous thromboembolism. As a type of venous thromboembolism, pulmonary embolism is also associated with obesity. But it is unclear whether the observed association is causal or caused by confounding bias or reverse causality. To verify and compare the effects of waist circumstance and hip circumstance on venous thromboembolism and life-threatening pulmonary embolism, we used the method of Mendelian randomization study to analysis the exposure data from the Neale Laboratory Consortium's GWAS summary data and the summary-level outcome data from FinnGen Biobank of European ancestry. Then we found a causal association between genetically predicted waist circumstance/hip circumstance and higher risk of pulmonary embolism, and compared with hip circumstance, waist circumstance is a better anthropometric index to predict venous thromboembolism in obese patients. This conclusion is consistent with observational studies. But compared with observational studies, our findings provide evidence of significant causality between waist circumstance/hip circumstance and venous thromboembolism/pulmonary embolism. Based on the above conclusions, we make the case that taking measures to reduce waist circumstance/hip circumstance of obesity may help reduce the incidence of venous thromboembolism.


Author Contributions

Project design and interpretation: J.T. and P.L.; data curation: J.T. and J.W.; statistical analysis: J.T.; methodology: J.T. and P.L.; validation: P.L., Q.S., and X.H.; writing—original draft: J.T. and J.W.; review, revision, and editing: P.L., J.T., and L.H. All authors have read and agreed to the published version of the manuscript.


* These authors have contributed equally to this work and share authorship.


Supplementary Material



Publication History

Received: 25 June 2022

Accepted: 11 November 2022

Accepted Manuscript online:
16 November 2022

Article published online:
05 January 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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