Sex and anticitrullinated protein antibodies modify the relationship between inflammation and cardiovascular risk in rheumatoid arthritis
Karpouzas, George A Pascual-Ramos, Virginia Gonzalez-Gay, Miguel A Misra, Durga P Myasoedova, Elena Rantapää-Dahlqvist, Solbritt Sfikakis, Petros Dessein, Patrick Hitchon, Carol A Galarza-Delgado, Dionicio
Karpouzas, George A
Pascual-Ramos, Virginia
Gonzalez-Gay, Miguel A
Misra, Durga P
Myasoedova, Elena
Rantapää-Dahlqvist, Solbritt
Sfikakis, Petros
Dessein, Patrick
Hitchon, Carol A
Galarza-Delgado, Dionicio
Abstract
OBJECTIVES: Female sex and anticitrullinated protein antibodies (ACPA) are associated with higher disease activity in rheumatoid arthritis (RA). Since disease-related inflammation is linked to cardiovascular risk, we explored whether sex and ACPA influenced the association between disease activity at study entry and cardiovascular risk in established RA.
METHODS: We evaluated 4008 patients with prevalent RA from an international observational cohort enrolled between 1985 and 2012. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction and stroke) and ischaemic cardiovascular events (iCVE: MACE, angina, revascularisation, transient ischaemic attack and peripheral arterial disease). Follow-up accrued from enrolment until the first event or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, sex, ACPA and their interactions.
RESULTS: We documented 193 MACE and 299 iCVE. Disease activity and sex were associated with MACE (all p≤0.017) and iCVE (p≤0.005) but ACPA was only associated with MACE (p=0.043). A three-way interaction on MACE (p=0.034) but not iCVE was noted. Among ACPA-negative patients, disease activity was associated with MACE in males (HR 1.57 (95% CI 1.14 to 2.16)) but not females (p-for-interaction=0.022). Among ACPA-positive patients, neither the disease activity x sex interaction (p=0.929), nor main effect of disease activity on MACE (p=0.124) was significant, but male sex was (HR 1.61 (95% CI 1.15 to 2.27)). Among females, neither disease activity x ACPA interaction (p=0.523) nor disease activity (p=0.319) was significant for MACE, but ACPA was (HR 1.57 (95% CI 1.02 to 2.42)).
CONCLUSIONS: The effect of disease activity at enrolment on cardiovascular risk in prevalent RA varies across patient groups with different sex and ACPA characteristics.
MIDER Authors
Date
2026-02-02
Type
Article
Subject
Arthritis, Autoantibodies, Cardiovascular Diseases
Collections
Citation
Karpouzas GA, Pascual-Ramos V, Gonzalez-Gay MA, Misra DP, Myasoedova E, Rantapää-Dahlqvist S, Sfikakis P, Dessein P, Hitchon CA, Galarza-Delgado D, Van Riel P, Semb AG, Hauge EM, Kitas GD, Ormseth SR; An inTernationAl Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Sex and anticitrullinated protein antibodies modify the relationship between inflammation and cardiovascular risk in rheumatoid arthritis. RMD Open. 2026 Feb 2;12(1):e006420. doi: 10.1136/rmdopen-2025-006420
Journal / Source Title
RMD open
DOI
10.1136/rmdopen-2025-006420
PMID
41629127
Publisher
BMJ Publishing Group
Publisher’s URL
https://rmdopen.bmj.com/