Low-Density Lipoprotein Cholesterol and the Risk of Rheumatoid Arthritis: A Prospective Study in a Chinese Cohort

Objective: This study aimed to investigate whether low-density lipoprotein cholesterol (LDL-C) concentration was associated with the risk of rheumatoid arthritis (RA) in Chinese adults. Methods: The study included the 97,411 participants in the Kailuan Study without RA, with complete baseline LDL-C data, and who did not use lipid-lowering medications at baseline or during follow-up. We used Cox proportional hazards modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to baseline LDL-C tertiles, adjusting for age, sex, body mass index, HDL-C, triglycerides, diabetes, hypertension, alcohol consumption, and smoking. We also calculated the HR and 95% CI of RA using updated LDL-C measurements prior to the end of follow-up, adjusting for covariates. Results: We identified 97 incident RA cases between 2006 and 2018. After adjusting for potential confounders, updated LDL-C concentration-rather than baseline LDL-C-was inversely associated with RA risk. The adjusted HR of RA was 0.64 (95% CI: 0.38, 1.09; p-trend = 0.10) comparing the two extreme baseline LDL-C tertiles, and 0.38 (95% CI: 0.22, 0.64; p-trend < 0.01) comparing the two extreme tertiles of the updated LDL-C concentrations. Conclusions: In this prospective study, high LDL-C concentrations, when measured closest to RA diagnosis or the end of follow-up, were associated with a low risk of RA. These findings highlight the changes in LDL-C prior to RA diagnosis, and the importance of including lipid analyses into studies of the pathogenesis of RA.