POS0086 ROLE OF PERIPHERAL VASODILATORY FUNCTION IN PREDICTING FUTURE MAJOR CARDIOVASCULAR EVENTS IN RHEUMATOID ARTHRITIS PATIENTS: FINDINGS FROM THE PROSPECTIVE EDRA STUDY
Authors: G. L. Erre, G. D. Sanna, A. A. Mangoni, E. Gremese, M. Piga
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The added usefulness of peripheral vasodilatory capacity (PVC) in predicting future cardiovascular events over traditional cardiovascular risk factors has been recently demonstrated in the general population [1]. Similar evidence in rheumatoid arthritis (RA) patients, a population at higher risk of cardiovascular disease, is lacking. <h3>Objectives:</h3> The EDRA study (Clinical Trials.gov NCT02341066) is a multicenter prospective study evaluating the contribution of the assessment of PVC in improving risk stratification calculated using the Framingham risk score (FRS) in the RA population. <h3>Methods:</h3> Unselected consecutive RA patients free from previous cardiovascular events were enrolled between 2015 and 2018 in 3 third-level Rheumatology Units (Sassari, Cagliari, Roma, ITALY). Recorded major cardiovascular events (MACE) included myocardial infarction, heart failure hospitalization, cerebrovascular events, and all-cause mortality. Reactive hyperaemia index (RHI) was measured as a proxy of PVC by peripheral arterial tonometry (EndoPAT). Outcome-oriented optimal cut-off of RHI was determined using the surv_cutpoint function (survminer, R package). Peripheral endothelial dysfunction (PED) was defined as a PVC under the optimal cut-off value. Multivariate Cox proportional hazard analysis was calculated to evaluate the independent predictive role of PED for MACE. The FRS estimate was scaled to the length of follow-up using the exponential survival function (1-(1-FRS)^(follow-up/10). The incremental value of "FRS + PED" compared to "FRS alone" in predicting future MACE was evaluated by C-statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI) (nricens, R package). <h3>Results:</h3> Data from 652 out of the original 980 RA patients enrolled in the EDRA study were available for analysis [mean (SD)age was 64.8 ± 10 years; 74.8% were females; median(IQR) disease duration was 140(144) months; 78.9% were seropositive; mean DAS28-ESR was 3.8±1.2; no-steroid use: 61.4%; &gt;5 mg prednisone use: 12.6%; no-therapy: 4.72%; only csDMARDs: 51.4%; only bDMARDs: 21.6%; csDMARDs + bDMARDs: 22.2%)]. After 6.6(IQR 1.3) years of follow-up 52 MACE were recorded, corresponding to an incidence rate of 12 MACE per 1,000 person-years. PED was demonstrated in 204(31.3%) of the overall population. Kaplan–Meier analysis showed that PED was associated with worse MACE-free survival (P=0.0053) (Figure 2B). In multivariate Cox proportional hazard analysis, adjusted for conventional cardiovascular risk factors, and significant RA-specific variables, baseline PED was an independent predictor of future MACE [HR(95%CI), 2.58(1.34-4.93); P=0.004] (Figure 1C). Among RA descriptors, disease duration [HR(95%CI), 1.34(1.07-1.67) every 10 yrs; P=0.010], ESR [HR(95%CI), 1.24(1.08-1.43); P=0.002], and HAQ [HR(95%CI), 1.001(1.00028-1.0028); P=0.017] were significant and independent predictors of future MACE (Figure 1C). The mean(IQR), follow-up scaled, FRS-calculated risk of MACE was 7.7%(9.7). Adding PED to FRS, marginally increased the FRS, but did not significantly improve its performance [AUC(95%CI)= 0.6397 vs 0.6237 respectively) when the C-statistics was used (P=0.68). In contrast, NRI and IDI for PED+FRS compared to the FRS alone were 13.9%(-3.1 to 44.6%) and 1.8%(z 3.06, P=0.002), respectively. <h3>Conclusion:</h3> PED is an independent predictor of future MACE in the RA population, irrespective of conventional and RA-specific cardiovascular risk factors. Adding PED to FRS, appeared to increase -albeit modestly- FRS predictive power in NRI and IDI analysis. Trials with larger sample size cohorts and longer follow-up period are needed to replicate our findings, confirm the optimal cut-off of RHI in the RA population, and provide a solid background to implement early preventive strategies in RA patients at increased risk of cardiovascular events. The EDRA study has been funded by the Italian MOH(GR-2011-02352816). <h3>REFERENCES:</h3> [1] Rajai N., et al. Prognostic value of peripheral endothelial function on major adverse cardiovascular events above traditional risk factors, European Journal of Preventive Cardiology. 2023; 30:1781–1788. <h3>Acknowledgements:</h3> The present work has been submitted on behalf of the EDRA study group. We thank all the EDRA study collaborators: Cadoni ML, Sassari; Cangemi I, Cagliari; Castagna F, Sassari; Cauli A, Cagliari; Congiu F, Cagliari; Dessì M, Cagliari; Fedele AL, Roma†; Ferraccioli G, Roma; Longu MG, Sassari; Mathieu A, Cagliari; Mundula N, Sassari; Mura S, Sassari; Murgia D, Sassari; Passiu G, Oristano; Piras A, Sassari; Piras M, Sassari; Saba PS, Sassari; Taras L, Sassari. <h3>Disclosure of Interests:</h3> <b>None declared.</b>