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

Derksen, VFAM; Lindschou, J; Winkel, P; Delgado, GE; de Moel, EC; Huizinga, TWJ; März, W; Jakobsen, JC; van der Helm-Van Mil, AHM; Toes, REM; Ajeganova, S; Gluud, C; Leipe, J; van der Woude, D; CLARICOR Trial Group and the LURIC Study Group

doi:10.1016/j.ard.2025.11.023

Rheumatoid arthritis

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

Ann Rheum DisPublished 25 Dec 2025Cohort study

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Authors' conclusion

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.

Study context

Population: Patients with coronary artery disease (CAD) without RA (2 CAD cohorts) and patients with RA (2 RA cohorts)follow-up 8.2–11.8 years

Exposure: ACPA-positive vs ACPA-negative; role of C-reactive protein (CRP) in ACPA–mortality association in RA
LUdwigshafen Risk and Cardiovascular Healthn = 2,189 patients and 656 controls
CLARIthromycin for patients with stable CORonary heart diseasen = 959
EACn = 764
BARFOTn = 794
Outcome: ACPA prevalence in CAD without RA and association of anticitrullinated protein antibodies (ACPAs) with all-cause mortality; role of CRP in ACPA–(cardiovascular) mortality association in RA

Methodological detailsmulticentre cohorts: 2 CAD cohorts and 2 RA cohorts, multivariable Cox proportional hazards models, joint models

Multicentre cohorts: 2 CAD cohorts and 2 RA cohorts
Multivariable Cox proportional hazards models
Joint models

Main finding

As reported in the abstract

Indirect effect HR (CRP) (95% CI)

EAC

1.24(1.14–1.34)

BARFOT

1.33(1.24–1.42)

ACPA prevalence low in both CAD cohorts: 0.9% and 4.6%

Observational data: associations, not effects.

Reference

Authors: Derksen VFAM, Lindschou J, Winkel P, Delgado GE, de Moel EC, Huizinga TWJ, et al.
All 15 authors
Derksen VFAM, Lindschou J, Winkel P, Delgado GE, de Moel EC, Huizinga TWJ, März W, Jakobsen JC, van der Helm-Van Mil AHM, Toes REM, Ajeganova S, Gluud C, Leipe J, van der Woude D, CLARICOR Trial Group and the LURIC Study Group
Journal: Annals of the Rheumatic Diseases
Published: 25 Dec 2025
DOI: 10.1016/j.ard.2025.11.023
PubMed: 41453823

Topic: Rheumatoid arthritis

Exposure definitions

LUdwigshafen Risk and Cardiovascular Health: CAD cohort: patients with CAD without RA, and controls
CLARIthromycin for patients with stable CORonary heart disease: CAD cohort: patients with stable CAD without RA
EAC: Early Arthritis Clinic RA cohort
BARFOT: Better Anti-rheumatic Farmaco-therapy RA cohort

Key notes

No association between seropositivity and all-cause mortality in CAD cohorts
In RA, association between ACPA positivity and all-cause mortality no longer significant after adjustment for CRP

More notes

CRP significantly associated with all-cause and cardiovascular mortality in RA

Original publication

Inflammation rather than anticitrullinated protein antibodies is associated with cardiovascular mortality in RA: insights from rheumatoid arthritis and coronary artery disease cohorts. Ann Rheum Dis. Published 25 December 2025. doi:10.1016/j.ard.2025.11.023

Read the original article ↗

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