POS0874 THE EFFECT OF INFLAMMATION ON CARDIOVASCULAR RISK IN RHEUMATOID ARTHRITIS VARIES ACCORDING TO SEX AND ANTICITRULLINATED PROTEIN ANTIBODY STATUS
Bibliographic record
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. Objectives: Therefore, we here explored whether the relationship between disease activity and cardiovascular risk in RA varied across sex and ACPA status. Methods: We evaluated 4008 RA patients free of cardiovascular disease upon enrollment in An InTernation A l 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. Results: 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 × 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 × 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: 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 . Acknowledgements: NIL . Disclosure of Interests: George Karpouzas Scipher, Janssen, Scipher, Pfizer, Piet van Riel: None declared, Elena Myasoedova: None declared, Miguel Ángel González-Gay: None declared, Alfonso Corrales Martinez: None declared, Solbritt Rantapää Dahlqvist: None declared, Petros P. Sfikakis: None declared, Patrick Dessein: None declared, Carol Hitchon: None declared, Virginia Pascual: None declared, Irazú Contreras-Yáñez: 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.017 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".