Xie Xintong, Wei Guangliang, Tang Zhenboyang, Chen Huidong, Lin Xiru, Huang Chunyan, Yu Hao, He Youxian, Li Mengxiang, Zhang Xue, He Chengsong, He Yue, Chen Jie
Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People's Republic of China.
Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
Clin Rheumatol. 2025 Mar;44(3):1057-1067. doi: 10.1007/s10067-025-07357-4. Epub 2025 Feb 6.
Previous research has revealed a positive correlation between rheumatoid arthritis (RA) and cardiovascular diseases, but the causal relationship is unclear. This study applies Mendelian randomization to examine whether RA causally contributes to the likelihood of various cardiovascular diseases, such as heart failure, coronary artery disease, and atrial fibrillation.
Using genome-wide association data, we conducted a univariable MR (UVMR) analysis to evaluate the causal impact of RA on CVD, primarily utilizing the inverse variance weighted method. Additional MR methods were used to test the robustness of the results. Multivariable MR (MVMR) was applied to explore potential confounders.
In the European population, genetically predicted RA had a harmful causal effect on HF, with the IVW analysis indicating an OR of 1.06 (95% CI: 1.02-1.10, P < 0.01) based on 23 SNPs. No causal relationships were found between RA and other CVDs. The MVMR analysis did not identify significant causal impact of rheumatoid arthritis on HF after controlling for traditional risk factors. In the Asian population, RA was associated with an adverse effect on AF, with the IVW method reporting an OR of 1.20 (95% CI: 1.01-1.41, P = 0.03) for 5 SNPs. No other CVD relationships were found.
Our MR analysis indicates that genetic susceptibility to rheumatoid arthritis increases the likelihood of heart failure in European populations and atrial fibrillation in East Asian populations. However, established CVD risk factors, such as smoking, overweight, and physical inactivity, remain critically important in the management of RA. Key Points • Multiple studies have highlighted a marked increase in the cardiovascular event risk among individuals with RA. However, additional RCTs are needed for confirmation. • We applied Mendelian randomization to explore the potential causal relationship between rheumatoid arthritis and cardiovascular conditions. The findings demonstrated a causal link between RA and heart failure among European populations, as well as an association between RA and atrial fibrillation in East Asian groups. • Further adjustments using multivariable Mendelian randomization to account for the influence of traditional cardiovascular risk factors revealed that the causal association between RA and heart failure disappeared.
先前的研究揭示了类风湿关节炎（RA）与心血管疾病之间存在正相关，但因果关系尚不清楚。本研究应用孟德尔随机化方法来检验RA是否因果性地增加了各种心血管疾病的发病可能性，如心力衰竭、冠状动脉疾病和心房颤动。
利用全基因组关联数据，我们进行了单变量孟德尔随机化（UVMR）分析，以评估RA对心血管疾病的因果影响，主要采用逆方差加权法。还使用了其他孟德尔随机化方法来检验结果的稳健性。应用多变量孟德尔随机化（MVMR）来探索潜在的混杂因素。
在欧洲人群中，基因预测的RA对心力衰竭有有害的因果效应，基于23个单核苷酸多态性（SNP）的逆方差加权分析显示比值比（OR）为1.06（95%置信区间：1.02 - 1.10，P < 0.01）。未发现RA与其他心血管疾病之间存在因果关系。在控制传统危险因素后，MVMR分析未发现类风湿关节炎对心力衰竭有显著的因果影响。在亚洲人群中，RA与心房颤动的不良影响相关，基于5个SNP的逆方差加权法报告的OR为1.20（95%置信区间：1.01 - 1.41，P = 0.03）。未发现与其他心血管疾病的关系。
我们的孟德尔随机化分析表明，类风湿关节炎的遗传易感性增加了欧洲人群患心力衰竭和东亚人群患心房颤动的可能性。然而，已确定的心血管疾病危险因素，如吸烟、超重和身体活动不足，在类风湿关节炎的管理中仍然至关重要。要点 • 多项研究强调类风湿关节炎患者心血管事件风险显著增加。然而，需要更多随机对照试验来证实。 • 我们应用孟德尔随机化来探索类风湿关节炎与心血管疾病之间的潜在因果关系。研究结果表明欧洲人群中RA与心力衰竭之间存在因果联系，以及东亚人群中RA与心房颤动之间存在关联。 • 使用多变量孟德尔随机化进一步调整以考虑传统心血管危险因素的影响后发现，RA与心力衰竭之间的因果关联消失。
