TOPLINE:

In patients with coronary artery disease without rheumatoid arthritis (RA), no association was found between anti-citrullinated protein antibody (ACPA) seropositivity and mortality. In patients with RA, C-reactive protein (CRP) over time was associated with ACPA seropositivity, and the associations between ACPAs and all-cause mortality and between ACPAs and cardiovascular mortality may have been mediated by CRP.

METHODOLOGY:

• Researchers analyzed data from two coronary artery disease cohorts, comprising patients with coronary artery disease without RA, to assess the prevalence of ACPAs and other autoantibodies and their link with mortality:
  • Nearly 959 patients with acute myocardial infarction or angina pectoris from the CLARICOR trial
  • Nearly 2189 patients with coronary artery disease and 656 control individuals from the LURIC study
• Data from two early RA cohorts, the Leiden Early Arthritis Clinic (EAC; n = 764) and the Better Anti-rheumatic Farmacotherapy (BARFOT; n = 794), were used to assess the role of systemic inflammation in the relationship between ACPAs and mortality.
• The prevalence of ACPAs was measured using enzyme-linked immunosorbent assay or other assays.
• The association between ACPAs and all-cause mortality was assessed, and a sub-analysis of cardiovascular mortality was limited to 575 patients.
• Joint models were applied to RA cohorts to explore the role of CRP in the relationship between ACPAs and mortality. The indirect effect of CRP on mortality was calculated in these joint models to assess mediation effects.

TAKEAWAY:

• In the CLARICOR and LURIC cohorts, 4.6% and 0.9% of patients with coronary artery disease without RA tested ACPA-positive, respectively. No significant difference in all-cause mortality was observed between ACPA-positive and ACPA-negative patients with coronary artery disease without RA in these two cohorts.
• In the EAC and BARFOT RA cohorts, ACPA positivity was associated with an increased risk for all-cause mortality (adjusted hazard ratio [HR], 1.66; 95% CI, 1.17-2.37 and adjusted HR, 1.50; 95% CI, 1.13-1.99, respectively). However, this association was not significant after including CRP in the joint models.
• CRP over time was associated with ACPA positivity; a significant indirect effect of logCRP on mortality was observed (HR, 1.24; 95% CI, 1.14-1.34 and HR, 1.33; 95% CI, 1.24-1.42 for both the EAC and BARFOT cohorts, respectively).
• The indirect effect of logCRP over time on cardiovascular mortality was also significant.

IN PRACTICE:

“[I]n contrast to seronegative RA, in patients with ACPA-positive RA, the ongoing chronic inflammatory process seems to be especially critical in the development of CVD [cardiovascular disease] and is therefore an important therapeutic target to improve long-term outcomes for these seropositive patients with RA,” the authors of the study wrote.

SOURCE:

The study was led by Veerle F.A.M. Derksen, MSc, Leiden University Medical Center, Leiden, Netherlands. It was published online on December 25, 2025, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The number of ACPA-positive patients with coronary artery disease was limited. Variability in antibody testing methods across cohorts could lead to differences in positivity rates. Population-specific control groups were available only in the LURIC study.

DISCLOSURES:

One author reported receiving support from a Dutch Research Council Vidi grant. Another author reported receiving support from the Swedish Rheumatism Association. A third author disclosed receiving grants and personal fees from multiple pharmaceutical companies, including Aegerion Pharmaceuticals, Amgen, and Sanofi. Abbott, Germany, provided an unrestricted grant for Alinity i anti-CCP and rheumatoid factor immunoglobulin M assays. INOVA supplied diagnostic autoantibody kits free of charge.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.