Inflammation rather than anticitrullinated protein antibodies is associated with cardiovascular mortality in RA: insights from rheumatoid arthritis and coronary artery disease cohorts

Derksen, V.F.A.M.; Lindschou, J.; Winkel, P.; Delgado, G.E.; Moel, E.C.D.; Huizinga, T.W.J.; ... ; LURIC Study Grp (2026)

Article / Letter to editor

Objectives: Anticitrullinated protein antibodies (ACPAs) are associated with increased mortality in patients with rheumatoid arthritis (RA). Previous data suggest ACPAs might be associated with worse disease outcomes in patients without RA with coronary artery disease (CAD). Therefore, we investigated ACPA prevalence and its association with mortality in patients with CAD without RA. Furthermore, the role of systemic inflammation in the relation between ACPAs and mortality was investigated in RA.

Methods: The prevalence of ACPAs in patients with CAD without RA was investigated in 2 CAD cohorts (LUdwigshafen Risk and Cardiovascular Health n = 2189 patients and 656 controls; CLARIthromycin for patients with stable CORonary heart disease n = 959 patients) using a commercial enzyme-linked immunosorbent assay. Multivariable Cox proportional hazards models were performed to investigate the association between ACPAs and all-cause mortality. In 2 RA cohorts (Early Arthritis Clinic [EAC] n = 764; Better Anti-rheumatic Farmaco-therapy [BAR-FOT] n = 794), joint models were applied to investigate the role of C-reactive protein (CRP) on the association between ACPAs and (cardiovascular) mortality.

Results: Average follow-up time in the cohorts ranged between 8.2 and 11.8 years. In both CAD cohorts, ACPA prevalence was low (0.9% and 4.6%), and no association was found between seropositivity and all-cause mortality. In patients with RA, the association between ACPA positivity and all-cause mortality was no longer significant after adjustment for CRP. In contrast, CRP was significantly associated with all-cause and cardiovascular mortality in RA (indirect effect hazard ratio [95% CI]: EAC 1.24 [1.14-1.34], BARFOT 1.33 [1.24-1.42]).

Conclusions: ACPA prevalence is not increased in patients with CAD without RA. In RA, the association between ACPA positivity and increased (cardiovascular) mortality was primarily explained by CRP. This highlights the impact of chronic inflammation on cardiovascular outcomes in RA.

• All authors: Derksen, V.F.A.M.; Lindschou, J.; Winkel, P.; Delgado, G.E.; Moel, E.C.D.; Huizinga, T.W.J.; März, W.; Jakobsen, J.C.; Helm-Van Mil, A.H.M. van der; Toes, R.E.M.; Gluud, C.; Leipe, J.; Woude, D. van der; CLARICOR Trial Grp; LURIC Study Grp
• Date: 2026-03-01
• Journal: Annals of the Rheumatic Diseases
• Volume: 85
• Issue: 3
• Pages: 425 - 434
• DOI: doi:10.1016/j.ard.2025.11.023