Association Between Endothelial Activation and Stress Index and Risk of Neurologic Deterioration and Mortality in Patients With Acute Ischemic Stroke: A Retrospective Cohort Study

In‐hospital neurologic deterioration (ND) in patients with acute ischemic stroke (AIS) is associated with worse prognosis, and endothelial dysfunction may be involved in this process. This study is aimed at evaluating the association between the endothelial activation and stress index (EASIX) and the risk of ND and short‐term mortality in patients with AIS. This retrospective cohort study included patients with AIS from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database from 2008 to 2022. EASIX was calculated as (serum lactate dehydrogenase level [U/L] × creatinine level [mg/dL])/platelet count (10 9 /L). Multivariable logistic regression and Cox regression analyses were utilized to examine the associations of log‐transformed EASIX (Ln (EASIX)) and ND and 28‐day mortality, respectively. Propensity‐score matching (PSM) and overlap weighting (OW) were performed to assess the robustness of the findings. A total of 1157 AIS patients were enrolled; 305 (26.36%) died within 28 days, and 673 (58.17%) experienced ND. Patients with Ln (EASIX) ≥ 0.40 had a higher risk of ND (OR = 1.56, 95% CI: 1.17–2.07) and 28‐day mortality (HR = 1.47, 95% CI: 1.12–1.94) compared with those with Ln (EASIX) < 0.40. These associations remained significant after PSM and OW (all p < 0.05). Mediation analysis suggested that ND partially mediated the relationship between Ln (EASIX) and 28‐day mortality risk, with a mediation proportion of 89.34% ( β = 0.35, 95% CI: 0.11–0.63). Elevated EASIX was associated with an increased risk of ND and 28‐day mortality in patients with AIS. ND may partially explain the EASIX‐mortality association, but these hypothesis‐generating findings warrant validation in future prospective studies.