Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study

Haoyi Weng; Haobo Li; Zhu Zhang; Yu Zhang; Linfeng Xi; Di Zhang; Chao Deng; Dingyi Wang; Ruoyan Chen; Gang Chen; Senwei Tang; Xianbo Zuo; Peiran Yang; Zhenguo Zhai; Chen Wang

doi:10.1016/j.lanwpc.2023.100848

Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study

Lancet Reg Health West Pac. 2023 Jul 26:39:100848. doi: 10.1016/j.lanwpc.2023.100848. eCollection 2023 Oct.

Authors

Haoyi Weng¹, Haobo Li^{2

3}, Zhu Zhang², Yu Zhang^{2

4}, Linfeng Xi^{2

4}, Di Zhang¹, Chao Deng⁵, Dingyi Wang⁶, Ruoyan Chen¹, Gang Chen¹, Senwei Tang¹, Xianbo Zuo⁷, Peiran Yang⁸, Zhenguo Zhai², Chen Wang²

Affiliations

¹ Shenzhen WeGene Clinical Laboratory, China; WeGene, Shenzhen Zaozhidao Technology Co. Ltd, China; Hunan Provincial Key Lab on Bioinformatics, School of Computer Science and Engineering, Central South University, China.
² National Center for Respiratory Medicine, China; State Key Laboratory of Respiratory Health and Multimorbidity, China; National Clinical Research Center for Respiratory Diseases, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, China; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, China.
³ China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China.
⁴ China-Japan Friendship Hospital, Capital Medical University, China.
⁵ SJTU-Yale Joint Center for Biostatistics and Data Science, Shanghai Jiao Tong University, China.
⁶ Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, China; National Center for Respiratory Medicine, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, China; National Clinical Research Center for Respiratory Diseases, China.
⁷ Department of Dermatology, China-Japan Friendship Hospital, China; Department of Pharmacy, China-Japan Friendship Hospital, China.
⁸ State Key Laboratory of Respiratory Health and Multimorbidity, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China; National Center for Respiratory Medicine, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China.

Abstract

Background: Serum uric acid (SUA) levels have been associated with an increased risk and recurrence of venous thromboembolism (VTE) in European populations, but the potential causal relationship remains unclear. Large-scale studies on the association between SUA and VTE in East Asian populations are lacking, despite the high prevalence of hyperuricemia in this region. To address this, we conducted a cohort analysis and a two-sample Mendelian randomization (MR) study in East Asian populations.

Methods: We collected data on VTE patients from the China Pulmonary Thromboembolism Registry Study (CURES) and compared them to controls obtained from the China Health and Retirement Longitudinal Survey (CHARLS). Propensity score matching (PSM) and cubic-spline models were applied to assess the effect of SUA on VTE risk while adjusting for multiple covariates. We also performed two-sample MR analyses to infer potential causality based on summary statistics from Genome-wide Association Studies (GWAS) of SUA and VTE in the East Asian population.

Findings: We found that the SUA levels were higher in VTE patients (317.95 mmol/L) compared to the general population (295.75 mmol/L), and SUA ≥ 325 mmol/L was associated with an increased risk of VTE recurrence (P-value = 0.0001). The univariable MR suggested a causal relationship between elevated SUA and higher VTE risk (P_{inverse variance weighted} < 0.05), and multivariable MR showed that elevated SUA levels continued to promote the development of VTE after adjusting for multiple covariates (P_{multivariable residual} < 0.05). Sensitivity analyses produced similar results for these estimations.

Interpretation: Our study provides evidence supporting a robust positive association between SUA and VTE in the East Asian population, and MR analyses suggest that this association is likely to be causal. Our findings underscore the importance of monitoring SUA levels in VTE prevention and call for urgent action to address the growing burden of hyperuricemia in the Asia-Pacific region.

Funding: This research was funded by Beijing Nova Program (No. Z211100002121057), National Natural Science Foundation of China (No. 82100065 and No. 62350004), CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-061 and No. 2021-1-I2M-001), Elite Medical Professionals project of China-Japan Friendship Hospital (No. ZRJY2021-QM12), National Key Research and Development Project (No. 2021YFF1201200 and No. 2022YFC3341004).

Keywords: Causal relationship; Mendelian randomization; Serum uric acid; Venous thromboembolism.