Investigating the causal relationship between rheumatoid arthritis and cardiovascular disease: A Mendelian randomization study.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.