Abstract
Several observational studies have suggested an association between rheumatoid arthritis (RA) and abnormalities of ventricular structure and function, yet the causal relationship remains unclear. This study aimed to assess the causal association between seropositive and seronegative RA and ventricular structure and function via Mendelian randomization (MR). Genetic data were derived from a genome-wide association study (GWAS) of seropositive and seronegative RA conducted within the FinnGen study, and a GWAS of 16 biventricular functional and structural cardiac magnetic resonance (CMR) measurements involving subjects from the UK Biobank. Inverse variance weighting (IVW) served as the primary analytical strategy to determine the causal associations between seropositive RA, seronegative RA, and ventricular CMR parameters. The MR-Egger, weighted median (WME), weighted mode (WM), and sample mode (SM) methods were employed as supplementary analyses. Additionally, the direct effects of RA on ventricular structure and function were further explored via multivariate MR (MVMR). IVW methods demonstrated that genetically predicted seropositive RA was significantly associated with a reduced left ventricular (LV) stroke volume (adjusted without body surface area (BSA) and systolic blood pressure (SBP)) (OR = 0.635; 95%CI 0.482–0.837; P = 0.001). MVMR analysis indicated that seropositive RA could influence LV stroke volume independently of traditional cardiovascular disease risk factors (OR = 0.695; 95%CI 0.512–0.942; P = 0.019). Sensitivity analyses yielded robust and reliable results. Our genetic analyses revealed a significant causal relationship between the development of seropositive RA and reduced LV stroke volume, offering valuable insights into the prevention and treatment of adverse cardiovascular events in patients with RA.