The Association Between Red Cell Distribution Width and Rheumatoid Arthritis: Insights from Cross-Sectional and Mendelian Randomization Studies

Background This study aimed to explore the association and causal relationship between red cell distribution width (RDW) and rheumatoid arthritis (RA).Methods This study analyzed RA patients aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. A multivariable weighted logistic regression model was adopted to evaluate the relationship between RDW and RA. In addition, MR analysis was performed, primarily using the Inverse Variance Weighted (IVW) method to assess the causal relationship between RDW and RA.Results A total of 5,496 participants were included in the cross-sectional analysis. Compared to the lowest quartile (≤12.3%), RDW levels in the highest quartile (≥13.6%) were significantly associated with the risk of RA (Odds Ratio [OR]: 1.71; 95% Confidence Interval [CI]: 1.06-2.75). Moreover, the restricted cubic splines (RCS) model identified a linear relationship between RDW levels and RA. Subgroup and sensitivity analysis results were stable. MR analysis indicates a positive causal relationship between RDW and the risk of RA (OR: 1.11; 95% CI: 1.05–1.17). Lastly, MR-Egger regression and MR-PRESSO test results revealed the absence of pleiotropy.Conclusion This cross-sectional observational analysis identified a significant positive association between RDW and RA, with the results from MR studies supporting its causal role.