Rheumatoid arthritis increases risk of atherosclerosis: A Mendelian randomization study

Understanding of the relationship between rheumatoid arthritis (RA) and atherosclerosis (AS) remains limited by the shortcomings of previous observational studies. This study investigated the causal relationship between RA and AS risks using Mendelian randomization (MR) analysis. Genetic data related to RA and AS were sourced from the genome-wide association studies database and FinnGen Biobank gene database, respectively. Standard screening metrics were applied and palindromic single nucleotide polymorphisms were processed. The initial analysis employed the inverse-variance weighted method for MR analysis, with other methods used as supplementary methods. Multiple sensitivity analyses, including MR-Egger and MR-PRESSO, were used to ensure the robustness of the study. The RA-related dataset included a total of 13,108,512 single nucleotide polymorphisms, involving a sample size of 58,284, of which 14,361 were case groups. The datasets of coronary AS, peripheral AS, cerebral AS, and AS excluding coronary AS, cerebral AS, and peripheral atherosclerosis (ASE) involved in the study contained sample sizes of 296,542, 236,794, 284,385, and 299,827, respectively. The MR results indicated a positive causal relationship between genetically determined RA and the risk of coronary AS (odds ratio [OR] = 1.025, 95% confidence interval [CI]: 1.003-1.047, P = .023), peripheral AS (OR = 1.071, 95% CI: 1.034-1.110, P < .001), and ASE (OR = 1.045, 95% CI: 1.013-1.078, P = .006), whereas no significant causal relationship with cerebral AS was observed. This study provided new evidence from a genetic evidence perspective that RA increases the risk of AS, revealing insights into early screening and preventive interventions for cardiovascular disease in RA patients.