Association between endothelial activation and stress index and all-cause mortality risk in cerebral infarction patients

Abstract Background Acute cerebral infarction (ACI) is a major cause of global morbidity and mortality, with endothelial dysfunction being a key factor in its pathophysiology. The Endothelial Activation and Stress Index (EASIX) is a novel biomarker reflecting endothelial injury and systemic stress; however, its prognostic role in mortality remains unclear. Methods This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care-IV database to investigate the association between EASIX and mortality in patients with ACI. A total of 1647 patients aged 18 years or older with a diagnosis of ACI at the time of intensive care unit admission were included. EASIX was calculated as lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelet count (10⁹/L) and categorized into tertiles. The primary outcomes were 28-day, 90-day, and 365-day all-cause mortality. Data were analyzed using Cox proportional hazards regression models, adjusting for age, gender, race, comorbidities, and illness severity scores (Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation III). Kaplan-Meier curves were plotted to visualize survival differences across EASIX tertiles, and subgroup analyses were performed to assess the robustness of the findings. Results Higher EASIX scores were significantly associated with increased mortality across all time points ( P < 0.001 for all comparisons). The hazard ratios for the highest EASIX tertile were 1.99 (95% confidence interval [CI] 1.49–2.67) for 28-day mortality, 1.66 (95% [CI] 1.31–2.11) for 90-day mortality, and 1.80 (95% [CI] 1.45–2.23) for 365-day mortality. Kaplan-Meier curves demonstrated a clear trend of decreasing survival with increasing EASIX tertiles. Additionally, a non-linear relationship with mortality was identified, with threshold effects observed at EASIX values of 4.584, 4.54, and 4.43 for 28-day, 90-day, and 365-day mortality, respectively. Conclusion EASIX is independently associated with mortality in patients with ACI, demonstrating a non-linear relationship with a threshold effect. This suggests that EASIX may serve as a clinically relevant biomarker for risk stratification in ACI, although further external validation is required. Future studies should investigate the dynamic changes in EASIX and its potential therapeutic implications.