Prognostic value of EASIX for short- and long-term mortality in patients with subarachnoid hemorrhage: evidence from a large ICU database

Subarachnoid hemorrhage (SAH) is a devastating subtype of hemorrhagic stroke characterized by high mortality and long-term neurological disability. Endothelial dysfunction is a key pathophysiological process, contributing to cerebral vasospasm, delayed cerebral ischemia (DCI), and unfavorable clinical outcomes. The Endothelial Activation and Stress Index (EASIX)—calculated as lactate dehydrogenase × creatinine/platelet count—has recently been recognized as a surrogate marker of endothelial injury and systemic stress. Nevertheless, its prognostic value in SAH has not been comprehensively investigated. The present study sought to examine the relationship between admission EASIX and all-cause mortality (ACM) in critically ill patients with SAH. This retrospective cohort study included 470 patients with SAH admitted to the intensive care unit (ICU) in the MIMIC-IV database. EASIX was calculated at ICU admission as lactate dehydrogenase × creatinine/platelet count. Participants were stratified either by an optimal cutoff value of 1.19, determined through maximally selected rank statistics, or by tertiles for comparative and trend analyses. The primary endpoints were ACM at ICU discharge, during hospitalization, and at 30-day, 90-day, 180-day, and 1-year follow-up. Survival probabilities were estimated using Kaplan–Meier analysis, and the association between EASIX and mortality was evaluated with Cox proportional hazards models. Potential nonlinear relationships were examined with restricted cubic spline (RCS) functions, and subgroup as well as interaction analyses were performed to assess effect modification. A total of 470 patients with subarachnoid hemorrhage were included, with a median age of 62 years (IQR: 50–72) and 46.2% being male. All-cause mortality was 17.4% in the ICU, 22.3% in-hospital, 23.0% at 30 days, 29.8% at 90 days, 36.6% at 180 days, and 35.3% at 1 year. Elevated EASIX levels were significantly associated with increased mortality across all time points. In fully adjusted Cox models, log₂-EASIX independently predicted ICU (HR 1.68, 95% CI 1.34–2.12), in-hospital (HR 1.52, 95% CI 1.27–1.83), 30-day (HR 1.28, 95% CI 1.09–1.52), 90-day (HR 1.31, 95% CI 1.13–1.52), 180-day (HR 1.27, 95% CI 1.10–1.46), and 1-year mortality (HR 1.25, 95% CI 1.09–1.44), all with p < 0.01. Patients in the highest EASIX tertile exhibited the highest risk of death, with a significant dose–response trend across all endpoints (p for trend < 0.001). Kaplan–Meier analysis confirmed significantly reduced survival in the high EASIX group (log-rank p < 0.0001), while restricted cubic spline models demonstrated nonlinear associations between EASIX and most mortality outcomes. Subgroup analyses showed consistent findings, with limited interaction effects observed for age, gender, and oxygen therapy status. Among critically ill patients with SAH, higher EASIX levels were significantly associated with an increased risk of ACM. Because EASIX is derived from routinely available laboratory parameters and is easy to calculate, it may offer incremental value for early risk assessment. Nonetheless, further prospective investigations and external validation studies are required to verify these findings and to better understand the mechanisms underlying the observed relationship.