Abstract 138: Plasma Soluble ST2 Concentration Predicts Functional Outcome and Hemorrhagic Transformation After Acute Ischemic Stroke

Abstract

Introduction: Soluble ST2 (sST2) is a member of the interleukin-1 receptor family that predicts mortality and outcome in cardiovascular disease. We aimed to determine whether baseline sST2 predicts functional outcome after stroke and examined its potential role in hemorrhagic transformation (HT). Methods: We measured plasma sST2 and matrix metalloproteinase-9 (MMP-9) in 646 patients who presented with acute ischemic stroke and were enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. Soluble ST2 and total MMP-9 were measured by ELISA. Functional outcome was assessed at 3 months with the modified Rankin Scale (mRS), with good outcome defined as mRS 0-2, and poor outcome defined as mRS 3-6. HT was classified in 246 patients with available CT scans, using the ECASS III criteria. The relationships between sST2, outcome, and HT were evaluated using multivariate logistic regression. Results: Median admission sST2 level was 35.0 ng/mL [IQR 25.7—49.8] in 646 patients (mean age 69 years; 44% women). The plasma concentration of sST2 was independently associated with poor outcome (OR 3.06, 95% CI 1.15-8.31, P =0.02) and mortality (OR 8.94, 95% CI 2.13-39.55, P =0.003) after adjustment for age, sex, NIHSS, admission glucose, cardioembolic stroke subtype, and tPA treatment. Of the 246 patients with imaging data available, HT occurred in 37 (15%) patients: 18 (48%) with hemorrhagic infarction type 1 (HI1), 11 (30%) with hemorrhagic infarction type 2 (HI2), 4 (11%) with parenchymal hemorrhage type 1 (PH1) and 4 (11%) with parenchymal hemorrhage type 2 (PH2). Admission sST2 level was associated with the subsequent development of any HT ( P =0.03) and with hemorrhagic infarction type 2 or greater (HI2, PH1, or PH2; P =0.008). Elevated sST2 independently predicted HI2 or greater after adjustment for age, MMP-9, blood glucose level, and tPA treatment (OR 9.27, 95% CI, 1.05-86.76, P =0.045). Conclusion: Plasma sST2 levels predicted mortality, functional outcome, and risk of HT after ischemic stroke. Further study of the potential link between sST2 and the brain injury response after stroke is warranted.