东亚人群中尿酸与静脉血栓栓塞风险的关联：一项队列研究和孟德尔随机化研究
Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study.
作者信息
Weng Haoyi, Li Haobo, Zhang Zhu, Zhang Yu, Xi Linfeng, Zhang Di, Deng Chao, Wang Dingyi, Chen Ruoyan, Chen Gang, Tang Senwei, Zuo Xianbo, Yang Peiran, Zhai Zhenguo, Wang Chen
机构信息
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.
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.
出版信息
Lancet Reg Health West Pac. 2023 Jul 26;39:100848. doi: 10.1016/j.lanwpc.2023.100848. eCollection 2023 Oct.
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 ( = 0.0001). The univariable MR suggested a causal relationship between elevated SUA and higher VTE risk ( < 0.05), and multivariable MR showed that elevated SUA levels continued to promote the development of VTE after adjusting for multiple covariates ( < 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).
背景
在欧洲人群中，血清尿酸（SUA）水平与静脉血栓栓塞症（VTE）风险增加及复发相关，但潜在因果关系仍不明确。尽管该地区高尿酸血症患病率很高，但缺乏关于东亚人群中SUA与VTE关联的大规模研究。为解决这一问题，我们在东亚人群中进行了一项队列分析和两项样本孟德尔随机化（MR）研究。
方法
我们收集了来自中国肺血栓栓塞症注册研究（CURES）的VTE患者数据，并与从中国健康与养老追踪调查（CHARLS）获得的对照组进行比较。应用倾向评分匹配（PSM）和三次样条模型来评估SUA对VTE风险的影响，同时对多个协变量进行调整。我们还基于东亚人群SUA和VTE的全基因组关联研究（GWAS）的汇总统计数据进行了两项样本MR分析，以推断潜在因果关系。
结果
我们发现，VTE患者的SUA水平（317.95 mmol/L）高于普通人群（295.75 mmol/L），且SUA≥325 mmol/L与VTE复发风险增加相关（ = 0.0001）。单变量MR表明SUA升高与较高的VTE风险之间存在因果关系（ < 0.05），多变量MR显示，在调整多个协变量后，SUA水平升高继续促进VTE的发展（ < 0.？5）。敏感性分析对这些估计产生了相似的结果。
解读
我们的研究提供了证据，支持东亚人群中SUA与VTE之间存在强有力的正相关，并且MR分析表明这种关联可能是因果关系。我们的研究结果强调了在VTE预防中监测SUA水平的重要性，并呼吁采取紧急行动应对亚太地区日益增加的高尿酸血症负担。
资金
本研究由北京新星计划（项目编号：Z211100002121057）、国家自然科学基金（项目编号：82100065和62350004）、中国医学科学院医学创新基金（项目编号：2021-I2M-1-061和2021-1-I2M-001）、中日友好医院优秀医学人才项目（项目编号：ZRJY2021-QM12）、国家重点研发计划（项目编号：2021YFF1201200和2022YFC3341004）资助。
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