The spectrum of cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis: a nationwide case-control postmortem study

OBJECTIVE: To examine cardiovascular pathology in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) vs. population-based controls, and its association with cause of death. METHODS: A case-control postmortem study was performed in Australia using the National Coronial Information System (2000-2025). SLE/RA cases were identified via keyword/ICD-10 code search. Controls were selected from motor vehicle accident deaths (3:1 ratio). Cardiovascular findings/histology were extracted from autopsy reports. Associations between SLE/RA and cardiovascular findings/outcomes using logistic regression (odds ratios (OR), 95% confidence intervals (CI)). RESULTS: 363 cases (240 RA&123 SLE) and 123 controls of similar age (cases 63y (IQR 53-72), vs. controls 59y (47-73), p=0.166) and sex (female 69% vs. controls 75%, p=0.235) were included. Adjusting for age, sex and BMI, myocardial fibrosis (SLE OR3.66, 95%CI2.00-6.72, p<0.001; RA OR3.96, 95%CI2.37-6.60, p<0.001), myocardial inflammation (SLE OR14.79, 95%CI3.35-65.37, p<0.001; RA OR6.35, 95%CI1.44-28.09, p=0.015) and cardiomegaly (SLE OR5.70, 95%CI2.99-10.86, p<0.001; RA OR3.50, 95%CI2.02-6.08, p<0.001) were more frequent in SLE and RA, as were coronary artery disease (CAD; SLE OR2.46, 95%CI1.34-4.51, p=0.004; RA OR2.56, 95%CI1.54-4.27, p<0.001) and microvascular disease (SLE OR10.28, 95%CI2.28- 46.31; RA OR6.74, 95%CI1.53-29.57, p=0.012). Associations between cardiovascular findings and SLE/RA status were strongest in under-60s, and persisted after adjusting for CAD. Cardiovascular death was associated with myocardial fibrosis (SLE OR2.35, 95%CI1.02-5.43, p=0.045; RA OR3.62, 95%CI1.81-7.27, p<0.001), cardiomegaly (SLE OR3.77, 95%CI1.71-8.27, p=0.001; RA OR2.52, 95%CI1.44-4.43, p=0.001) and CAD (SLE OR4.12, 95%CI1.76-9.66, p=0.001; RA OR12.71, 95%CI6.59-24.49, p<0.001); and microvascular disease (OR5.26, 95%CI1.40-19.77, p=0.014) and valvular pathology (OR2.68, 95%CI1.11-6.43, p=0.028) in SLE only. CONCLUSION: This unique dataset identified increased atherosclerotic, inflammatory and fibrotic cardiovascular disease in SLE and RA, particularly in younger individuals. These pathologies were frequently associated with cardiovascular death.