The presence of leukoaraiosis enhances the association between sTWEAK and hemorrhagic transformation.

Objective To investigate whether elevated serum levels of sTWEAK (soluble tumor necrosis factor-like inducer of apoptosis) might be involved in a higher frequency of symptomatic hemorrhagic transformation (HT) through the presence of leukoaraiosis (LA) in patients with acute ischemic stroke (IS) undergoing reperfusion therapies. Methods This is a retrospective observational study. The primary endpoint was to study the sTWEAK-LA-HT relationship by comparing results with biomarkers associated to HT and evaluating functional outcome at 3-months. Clinical factors, neuroimaging variables and biomarkers associated to inflammation, endothelial/atrial dysfunction or blood-brain barrier damage were also investigated. Results We enrolled 875 patients (mean age 72.3 ± 12.2 years; 46.0% women); 710 individuals underwent intravenous thrombolysis, 87 endovascular therapy and 78 both. HT incidence was 32%; LA presence was 75.4%. Patients with poor functional outcome at 3-months showed higher sTWEAK levels at admission (9844.2 [7460.4-12,542.0] vs. 2717.3 [1489.7-5852.3] pg/mL, P Conclusions Higher sTWEAK levels are independently associated with HT and poor functional outcome in patients with IS undergoing reperfusion therapies through the presence of LA. sTWEAK could become a therapeutic target to reduce HT incidence in patients with IS.