Serum angiopoietin-like protein 4 as a predictor of hemorrhagic transformation post-endovascular therapy in acute ischemic stroke: A prospective study

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a major complication after endovascular therapy (EVT) for acute ischemic stroke (AIS), closely associated with blood-brain barrier (BBB) disruption. Angiopoietin-like protein 4 (ANGPTL4) has been implicated in BBB regulation. This study aimed to evaluate ANGPTL4's predictive value in EVT-treated AIS. METHODS: In this prospective study, 122 AIS patients undergoing EVT were enrolled. Serum ANGPTL4 levels were measured before treatment. Patients were categorized into non-HT, hemorrhagic infarction (HI), and parenchymal hematoma (PH) groups based on follow-up CT. Baseline clinical, imaging, and laboratory data were collected. Logistic regression identified independent HT predictors. BBB permeability was estimated using the relative permeability-surface area product (rPS) from CT perfusion. Receiver operating characteristic curves assessed ANGPTL4's predictive value. RESULTS: HT occurred in 48 patients (39.3%), including 33 with HI and 15 with PH. Serum ANGPTL4 levels were higher in HT vs. non-HT patients (median [IQR]: 1315.05 [798.30-1997.85] vs. 826.50 [569.02-1246.35] pg/mL, p < 0.001) and showed a stepwise increase across HT subtypes (p < 0.001). Serum ANGPTL4 levels were independently associated with HT (OR per 100 pg/mL = 1.11, 95% CI: 1.03-1.19, p = 0.005) and positively linearly correlated with rPS (β = 0.02, p < 0.001) in fully adjusted models. ROC analysis showed moderate predictive accuracy for PH (AUC = 0.790). CONCLUSIONS: Elevated serum ANGPTL4 levels were independently associated with HT after EVT in AIS and were correlated with BBB permeability, suggesting a potential link between ANGPTL4 and BBB dysfunction.