Early EASIX and Short-Term Mortality After Acute Myocardial Infarction: A Dual-Cohort Prognostic Study

Background/Objectives: The Endothelial Activation and Stress Index (EASIX) combines lactate dehydrogenase, creatinine, and platelet count in a three-variable laboratory index. We evaluated its association with early mortality after acute myocardial infarction (AMI) and its incremental prognostic information beyond the Global Registry of Acute Coronary Events (GRACE) score. Methods: This retrospective study included a primary hospital cohort of 4167 patients with AMI and an independent MIMIC-IV cohort of 3183 patients with AMI requiring intensive care. EASIX was calculated from the first component measurements within 24 h after admission and log₂-transformed. Cox models assessed 30-day mortality and changes in the association over time. Incremental performance beyond GRACE and sex was examined in the primary cohort. Results: Thirty-day mortality was 3.3% in the primary cohort and 22.9% in MIMIC-IV. Each doubling of EASIX was associated with higher 30-day mortality after adjustment for GRACE and sex in the primary cohort (hazard ratio [HR], 1.25; 95% CI, 1.13-1.38) and after clinical adjustment in MIMIC-IV (average HR, 1.40; 95% CI, 1.36-1.45). The association was strongest near admission and remained consistent across 6, 12, and 24 h exposure windows. Adding EASIX to GRACE modestly improved discrimination, whereas calibration and decision-curve net benefit changed little. Conclusions: Early EASIX was independently associated with short-term mortality across two clinically distinct AMI cohorts and provided complementary prognostic information beyond GRACE. Its three laboratory components offer a low-burden summary of early systemic physiological stress.