POS0874 The effect of inflammation on cardiovascular risk in rheumatoid arthritis varies according to sex and anticitrullinated protein antibody status.
Karpouzas, G van Riel, P Myasoedova, E Gonzalez-Gay, MA Corrales Martinez, A Rantapaa Dahlqvist, S Sfikakis, PP Dessein, P Hitchon, C Pascual, V
Karpouzas, G
van Riel, P
Myasoedova, E
Gonzalez-Gay, MA
Corrales Martinez, A
Rantapaa Dahlqvist, S
Sfikakis, PP
Dessein, P
Hitchon, C
Pascual, V
Affiliation
Harbor-UCLA Medical Centre; The Lundquist Institute for Biomedical Innovation; The Dudley Group NHS Foundation Trust et al
Other Contributors
Publication date
2025/06/01
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
Background: Disease activity associates with cardiovascular risk in rheumatoid arthritis (RA). Females with RA exhibit higher disease activity than males. Yet, males with RA incur greater cardiovascular risk compared to females. We therefore hypothesized that the impact of disease activity on cardiovascular risk may differ between males and females. Also, anticitrullinated protein antibody (ACPA) positive RA patients experience greater cardiovascular morbidity and mortality compared to negative ones. Moreover, ACPA associated with higher disease activity and lower remission rates. Hence, we posited that the effect of inflammation on cardiovascular risk may vary across ACPA positive and negative patients. Lastly, male sex was linked to better clinical outcomes in ACPA negative but not ACPA positive RA. Objective(s): Therefore, we here explored whether the relationship between disease activity and cardiovascular risk in RA varied across sex and ACPA status. Method(s): We evaluated 4008 RA patients free of cardiovascular disease upon enrollment in An InTernationAl Consortium for Cardiovascular disease in RA (ATACC-RA). The outcome was major adverse cardiovascular events (MACE) defined as nonfatal myocardial infarction, nonfatal stroke, or CV death. Missing data were imputed using multiple imputation by chain equations with 10 iterations. Multivariable Cox models stratified by center risk assessed the impact of disease activity score on 28-joint counts with C-reactive protein (DAS28CRP), sex, ACPA positivity, as well as the two- and three-way interactions of DAS28CRP with ACPA and/or sex on risk of MACE after adjusting for age, diabetes, hypertension, family history of CV disease, smoking, total cholesterol to high-density lipoprotein ratio, and RA duration. Result(s): Over 23,279 patient years, 193 MACE were recorded. Upon multivariable adjustment, there were main effects of DAS28CRP (HR 1.17, 95% CI 1.03-1.32, p=0.017), male sex (HR 1.83, 95% CI 1.37-2.43, p<0.001), and ACPA positivity (HR 1.38, 95% CI 1.01-1.90, p=0.043) on MACE risk in the entire cohort. A three-way interaction between DAS28CRP, sex, and ACPA was significant (p=0.034), indicating that the impact of RA activity on MACE risk varied according to sex and ACPA status. Specifically, among ACPA negative patients, the DAS28CRP x Sex interaction was significant (p=0.022) such that disease activity associated with MACE risk in males (HR 1.57, 95% CI 1.14-2.16, p=0.006) but not females (HR 0.96, 95% CI 0.72-1.29, p=0.790, Figures 1 and 2). Among ACPA positive patients, the DAS28CRP x Sex interaction (p=0.929) and main effect of DAS28CRP (HR 1.13, 95% CI 0.97-1.31, p=0.124) were not significant, while that of sex was (HR 1.61, 95% CI 1.15-2.27, p=0.006). Considering the ACPA x DAS28CRP interaction stratified by sex, ACPA modified the effect of DAS28CRP on MACE risk in males (p=0.004), with DAS28CRP associating with MACE in ACPA negative (as above) but not positive patients (HR 1.14, 95% CI 0.94-1.37, p=0.189). Among females the ACPA x DAS28CRP interaction (p=0.523) and DAS28CRP main effect (HR 1.10, 95% CI 0.91-1.34, p=0.319) were not significant but that of ACPA was (HR 1.57, 95% CI 1.02-2.42, p=0.039). Conclusion(s): Among ACPA negative patients, higher RA activity associated with greater risk of MACE only in males, whereas in ACPA positive DAS28CRP was not associated with MACE risk, but male sex was. Among females, DAS28CRP was not associated with MACE risk but ACPA presence was. REFERENCES: NIL. [Figure presented][Figure presented] Acknowledgements: NIL. Disclosure of Interests: George Karpouzas Scipher, Janssen, Scipher, Pfizer, Piet van Riel: None declared, Elena Myasoedova: None declared, Miguel Angel Gonzalez-Gay: None declared, Alfonso Corrales Martinez: None declared, Solbritt Rantapaa Dahlqvist: None declared, Petros P. Sfikakis: None declared, Patrick Dessein: None declared, Carol Hitchon: None declared, Virginia Pascual: None declared, Irazu Contreras-Yanez: None declared, Iris J. Colunga-Pedraza: None declared, Dionicio A. Galarza-Delgado: None declared, Jose R. Azpiri-Lopez: None declared, Anne Grete Semb: None declared, Durga Prasanna Misra: None declared, Patrick Durez: None declared, Brian Bridal-Logstrup: None declared, Ellen-Margrethe Hauge: None declared, George Kitas: None declared, Sarah Ormseth: None declared. � The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.Copyright � 2025 � Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by Elsevier Inc.
Citation
G. Karpouzas, P. van Riel, E. Myasoedova, M.�. Gonz�lez-Gay, A. Corrales Martinez, S. Rantap�� Dahlqvist, P.P. Sfikakis, P. Dessein, C. Hitchon, V. Pascual, I. Contreras-Y��ez, I.J. Colunga-Pedraza, D.A. Galarza-Delgado, J.R. Azpiri-Lopez, A.G. Semb, D.P. Misra, P. Durez, B. Bridal-Logstrup, E.M. Hauge, G. Kitas, S. Ormseth, POS0874 The effect of inflammation on cardiovascular risk in rheumatoid arthritis varies according to sex and anticitrullinated protein antibody status, Annals of the Rheumatic Diseases, Volume 84, Supplement 1, 2025, Pages 1011-1012, ISSN 0003-4967, https://doi.org/10.1016/j.ard.2025.06.229.