Modified Endothelial Activation and Stress Index (mEASIX) Predicts Long-Term Mortality in Patients with Acute Coronary Syndromes

Endothelial dysfunction, inflammation, and microvascular injury are key mechanisms involved in the development and progression of acute coronary syndrome (ACS). The Endothelial Activation and Stress Index (EASIX) and its derivatives have emerged as readily available biomarkers of endothelial stress; however, the prognostic value of modified EASIX (m-EASIX), which incorporates C-reactive protein, remains uncertain. This study evaluated the prognostic performance of EASIX-derived indices and investigated whether high admission m-EASIX was independently associated with long-term post-discharge all-cause mortality in patients with ACS. Adult patients admitted with ACS between January 2019 and February 2020 who survived the index hospitalization and were discharged alive were retrospectively identified from a tertiary referral center. EASIX, simplified EASIX (s-EASIX), and m-EASIX were calculated from admission laboratory measurements, and their prognostic performance was evaluated using receiver operating characteristic analysis, Kaplan–Meier survival curves, and multivariable Cox proportional hazards models. Among 102 patients who survived the index ACS hospitalization, 29 (28.4%) died during a mean post-discharge follow-up of 68.2 ± 28.0 months. m-EASIX showed the numerically highest AUC for post-discharge all-cause mortality (AUC 0.730, 95% CI 0.617–0.843; p<0.001), followed by EASIX (AUC 0.715) and s-EASIX (AUC 0.629). However, paired DeLong comparisons showed no significant difference between m-EASIX and EASIX (p=0.809) or between m-EASIX and s-EASIX (p=0.158). Patients with m-EASIX ≥1.21 had significantly higher mortality than those with lower values (53.7% vs. 11.5%; p<0.001). After adjustment for age, hemoglobin concentration, and left ventricular ejection fraction, high m-EASIX remained independently associated with post-discharge all-cause mortality (HR 2.759, 95% CI 1.109–6.865; p=0.029). Among the evaluated indices, m-EASIX showed the numerically highest AUC, although its discriminatory performance was not statistically superior to that of EASIX or s-EASIX. Further prospective validation is required before clinical implementation.