Cardiovascular risk and all-cause mortality across low-density lipoprotein cholesterol levels in seropositive rheumatoid arthritis: a nationwide cohort study

OBJECTIVE: To assess cardiovascular disease (CVD) and all-cause mortality risk in patients with seropositive rheumatoid arthritis (RA) compared with matched controls, and examine whether low-density lipoprotein cholesterol (LDL-C) levels influence these risks. METHOD: This nationwide retrospective cohort study used Korean National Health Insurance Service data. Adults newly diagnosed with seropositive RA between 2010 and 2017 were matched 1:5 to non-RA controls by age, sex, and health screening year. Participants were followed from the index date until death or the end of 2019. The primary outcome was composite CVD [stroke or coronary heart disease (CHD)]; secondary outcomes included stroke, CHD, and all-cause mortality. LDL-C levels were categorized into clinically relevant strata. Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models, accounting for demographic, clinical, and lifestyle factors. Interaction terms assessed LDL-C level effect modification. RESULTS: Among 15 385 patients with seropositive RA and 76 727 matched controls (mean age 55.4 years; 26.7% male), RA was associated with significantly increased risks of CVD [adjusted HR 1.33, 95% confidence interval (CI) 1.25-1.41], stroke (1.16, 1.08-1.26), CHD (1.49, 1.38-1.62), and all-cause mortality (1.93, 1.81-2.05), with no statistically significant interaction between RA status and LDL-C category for any outcome. CONCLUSION: In this large national cohort, seropositive RA was independently associated with increased cardiovascular event and all-cause mortality risks, regardless of LDL-C level. These findings suggest that conventional LDL-C-based risk stratification may be insufficient for patients with RA, and support broader risk management approaches.