Non-Linear Temporal Dynamics of Endothelial Progenitor Cells After Stroke: Associations with Perfusion Imaging, ASPECTs and Functional Outcome

Abstract

Endothelial progenitor cells contribute to neurovascular repair after stroke. This study evaluated their temporal dynamics, prognostic value, and association with neuroimaging markers in stroke patients. We conducted a prospective cohort of 114 patients with ischemic strokes admitted to Hospital Universitario de Gran Canaria Doctor Negr & iacute;n (Spain) between September 2023 and June 2024. EPC counts were measured at 48 h, 7 days, and 3 months and correlated with 3-month functional outcome (modified Rankin Scale, mRS). Neuroimaging included non-contrast CT (ASPECTS, established infarction) and, in a subgroup (n = 8), perfusion CT (ischemic core, hypoperfusion, Tmax > 10s, and related indices). The primary objective was to evaluate the association between EPC levels at 7 days and functional outcome at 3 months. Secondary objectives included characterization of EPC temporal dynamics and their association with neuroimaging markers, including non-contrast CT and exploratory CT perfusion parameters. EPC levels exhibited a non-linear temporal trajectory over time (ANOVA quadratic trend, p = 0.011; linear mixed model [LMM], p < 0.001), with LMM showing exploratory stroke subtype-specific dynamics (p = 0.006). Pairwise Wilcoxon analyses showed a significant decrease in EPC counts from 48 h to 7 days (p = 0.018), with no statistically significant differences between 7 days and 3 months or between 48 h and 3 months. EPC levels at 7 days demonstrated a modest but statistically significant discriminative ability for 3-month functional outcome (AUC = 0.623, p = 0.036). EPC counts were not associated with ASPECTS or established infarction. In exploratory perfusion analyses, EPC levels at 7 days were significantly correlated with absolute perfusion volumes, including ischemic core, hypoperfusion volume, and tissue with Tmax > 10 s, whereas relative perfusion indices showed no significant associations. EPC counts display a non-linear temporal evolution after ischemic stroke and show a modest association with functional outcome at 3 months. EPC mobilization appears more closely related to the absolute burden of ischemic injury than to relative perfusion indices. Although limited as standalone biomarkers, EPC measurements may contribute to multimodal prognostic assessment when integrated with clinical and imaging data.