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

Abstract 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 < 0.0001). By means of logistic regression models, PDGF‐CC and sTWEAK were associated with mechanisms linked simultaneously to HT and LA. Serum sTWEAK levels at admission ≥6700 pg/mL were associated with an odds ratio of 13 for poor outcome at 3‐months (OR: 13.6; CI 95%: 8.2–22.6, P < 0.0001). 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.