Association between rheumatoid arthritis and blood lipid levels: An integrated epidemiological observational analysis and Mendelian randomization study.

Background: The association between rheumatoid arthritis (RA) and blood lipids remains controversial.

Objective: This study aimed to investigate the association between RA and blood lipids by integrating observational and Mendelian randomization (MR) analyses.

Methods: The association between the prevalence of RA and blood lipid levels was examined using data from the National Health and Nutrition Examination Survey (NHANES) (n = 24,345). Subsequently, the causality between RA and lipid and apolipoprotein levels was inferred in a 2-sample MR framework. Genetic instruments for RA (13,261 RA cases and 43,823 controls), lipids (n = 121,577), and apolipoproteins (n = 121,577) were obtained from large-scale genome-wide association studies. The statistical significance of the MR effect estimates was determined using a false discovery rate (FDR) with a <5% threshold to adjust for multiple testing.

Results: In the NHANES cohort, RA was associated with lower total cholesterol (TC) (β -0.08; 95% CI -0.15, -0.02) and low-density lipoprotein cholesterol (LDL-C) (β -0.11; 95% CI -0.18, -0.05) levels after adjusting for potential confounders. In the 2-sample MR analyses, genetic liability to RA was associated with lower levels of TC (β -0.013; 95% CI -0.022, -0.004, FDR 0.011), LDL-C (β -0.017; 95% CI -0.027, -0.008, FDR 0.003), and apolipoprotein B (Apo B) (β -0.016; 95% CI -0.028, -0.004, FDR 0.015).

Conclusion: RA is causally associated with lower TC, LDL-C, and Apo B levels. Clinicians should cautiously interpret lower atherogenic lipid levels in patients with RA, as these may indicate underlying disease processes.