#3-12E. The True Culprit: Inflammation vs. Antibodies in RA Cardiovascular Risk (Ann Rheum Dis, 2025)

Is the presence of anticitrullinated protein antibodies (ACPAs) an independent cardiovascular risk factor, or is systemic inflammation the actual driver of excess mortality in rheumatoid arthritis (RA)? This episode examines a pivotal 2025 study that analyzed data from two large coronary artery disease (CAD) cohorts and two early RA cohorts to disentangle these mechanisms. The researchers demonstrated that ACPA prevalence was not elevated in non-RA CAD patients, nor was it associated with mortality in that group. Crucially, while ACPA positivity in RA patients initially appeared linked to higher mortality, statistical joint modeling revealed that this association was nullified after adjusting for C-reactive protein (CRP) levels over time, identifying chronic inflammation as the primary mediator of cardiovascular death12. Critical appraisal of this study requires noting the heterogeneity of ACPA assays used and the reliance on annual CRP measurements, which provide only a rough estimate of cumulative inflammatory burden3. For clinicians, these findings strongly suggest that improving long-term survival in ACPA-positive patients depends less on the antibody profile itself and more on rigorously suppressing continuous inflammation4.

Citation: DERKSEN, V.F.A.M. and VAN DER WOUDE, D. Inflammation rather than anticitrullinated protein antibodies is associated with cardiovascular mortality in RA: insights from rheumatoid arthritis and coronary artery disease cohorts. Annals of the Rheumatic Diseases. 2025. DOI: 10.1016/j.ard.2025.11.023

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.