Background/Purpose: Patients with rheumatoid arthritis (RA) experience premature mortality, largely due to cardiovascular (CV) disease. The increased CV risk is due to both the underlying systemic inflammation and the interaction between RA and traditional CV risk factors. Individual CV risk assessment in RA patients is complex because tools validated for the general population have not been adapted to account for disease activity. The use of biomarkers may help to refine risk stratification. The aim of this study was to evaluate the predictive value of two cardiac biomarkers for major CV events in RA patients.

Methods: This prospective cohort study included patients from the ESPOIR cohort who met the 2010 ACR/EULAR classification criteria for RA and had no prior history of CV events at baseline. Serum levels of high-sensitivity cardiac troponin T (Hs-cTnT, a marker of myocardial injury) and soluble ST2 (a marker of inflammation and myocardial fibrosis) were measured at baseline using electrochemiluminescence and ELISA, respectively. The primary outcome was the occurrence of major CV events (myocardial infarction, ischemic stroke, and CV death) during the observation period.

Results: We analyzed 559 patients (425 women, 76%) with available data and biomarker measurements. The mean (SD) age was 49 (12) years, and the mean (SD) disease duration was 104 (211) days. Among these patients, 228 (41%) and 253 (45%) were positive for rheumatoid factors and anti-CCP antibodies, respectively, and 218 (39%) had bone erosions. The mean (SD) DAS28 was 5.26 (1.27).Thirty-three major CV events were identified over a mean (SD) follow-up of 130 (34) months. Baseline mean (SD) Hs-cTnT and ST2 levels were 6.5 (13.8) pg/mL and 5.2 (1.3) ng/mL, respectively, and both correlated with age (r=0.53, p < 0.001 and r=0.22, p < 0.001) and the Framingham risk score (r=0.63, p < 0.001 and r=0.18, p=0.003). Mean ST2 levels were significantly higher in patients with at least two CV risk factors (22.3 (18.8) vs. 15.8 (11.5) ng/mL, p < 0.001).The area under the curve (AUC) for Hs-cTnT in predicting major CV events was 0.71 (p=0.002), with a sensitivity of 72% and specificity of 60% at a threshold of 4.9 pg/mL. The AUC for ST2 was 0.69 (p=0.019), with a sensitivity of 97% and specificity of 32% at a threshold of 9.7 ng/mL. Elevated levels of Hs-cTnT ( >4.9 pg/mL) and ST2 ( >9.7 ng/mL) were predictive of major CV events (hazard ratios [HR]: 2.59, 95% confidence interval [CI] 1.31–5.13 and 3.23, 95% CI 1.43–7.27, respectively). The predictive value was higher when both biomarkers were elevated (HR 3.49, 95% CI 1.68–7.24). This combination remained predictive after adjusting for DAS28, CRP, methotrexate exposure, and traditional CV risk factors (adjusted HR 2.22, 95% CI 1.01–4.92).

Conclusion: These two cardiac biomarkers were identified as predictors of major CV events in this prospective RA cohort. The combination of Hs-cTnT and ST2 may improve CV risk stratification in RA patients. Adding these biomarkers to non-specific CV risk scores could better identify patients requiring advanced CV evaluation.

Figure 1: Kaplan-Meier curve illustrating CV event-free survival based on Hs-cTnT and ST2 concentrations.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cardiac-biomarkers-and-prediction-of-major-cardiovascular-events-in-rheumatoid-arthritis-results-from-the-espoir-cohort/