Introduction: Soluble ST2 (sST2) is a member of the interleukin-1 receptor family known to predict outcome and mortality in cardiovascular disease and ischemic stroke. We sought to determine whether plasma sST2 concentration is associated with functional outcome after intraparenchymal hemorrhage.
Methods: Concentration of sST2 was measured on plasma samples from a prospectively collected cohort of 75 patients who presented with spontaneous intraparenchymal hemorrhage. Blood samples were drawn between 24 and 72 hours after symptom onset. Soluble ST2 was measured using a commercially-available ELISA (Critical Diagnostics, San Diego, CA). Injury severity was determined using the admission Glasgow Coma Scale (GCS), with GCS ≤ 8 defined as severe injury. Outcome was assessed by modified Rankin Scale (mRS) at 90 days, with poor outcome defined as mRS 4-6. The association between sST2 and outcome, adjusted for clinical variables, was determined using ordinal logistic regression and receiver operating curve (ROC) analysis.
Results: Median sST2 concentration was 54.6ng/mL [IQR 25.7-156.5] in the entire cohort. Patients with a more severe presentation (GCS ≤ 8) had a higher sST2 concentration (165.1ng/ml [IQR 91.2-238.3] vs. 36.8ng/ml [IQR 23.0-62.6], p<0.0001). ROC analysis demonstrated that sST2 concentration >114.0ng/mL predicted poor outcome with a sensitivity of 63.3%, specificity of 82.2%, and an area under the curve of 0.766. Plasma sST2 concentration was also associated with ordinal mRS at 90 days (OR 2.99, 95% CI 1.84-4.88, p < 0.0001). Other univariate predictors of ordinal mRS included admission GCS, admission NIHSS, hematoma volume, and ICH score. Plasma sST2 remained an independent predictor of mRS after adjustment for ICH score (adjusted OR 1.97, 95% CI 1.09-3.53, p = 0.024). Similarly, adjustment for admission NIHSS, admission GCS or hematoma volume demonstrated that sST2 remained an independent predictor of outcome.
Conclusion: Plasma sST2 is independently associated with functional outcome after intraparenchymal hemorrhage. These results support the role of sST2 as a candidate biomarker for both ischemic and hemorrhagic stroke, and argue for further investigation of the ST2 pathway in the pathogenesis of neurologic injury.