Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

Abstract

Objective ST2 is a member of the toll‐like receptor superfamily that can alter inflammatory signaling of helper T‐cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.MethodsWe measured sST2 in patients enrolled in the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) network biomarker study. 646 patients had plasma samples collected at the time of hospital admission and 210 patients had a second sample collected 48 h after stroke onset. Functional outcome was assessed using the modified Rankin Scale (mRS), with good and poor outcomes defined as mRS 0‐2 and 3‐6, respectively. HT was classified using ECASS criteria. The relationships between sST2, outcome, and HT were evaluated using multivariable logistic regression, Kaplan–Meier survival analysis and receiver operating characteristic curves.Results646 patients were included in the analysis (mean age 69 years; 44% women), with a median NIHSS of 5 [IQR: 2–12]. The median sST2 level on hospital admission was 35.0 ng/mL [IQR: 25.7–49.8 ng/mL] and at 48 h it was 37.4 ng/mL [IQR 27.9–55.6 ng/mL]. sST2 was independently associated with poor outcome (OR: 2.77, 95% CI: 1.54–5.06; P = 0.003) and mortality (OR: 3.56, 95% CI: 1.58–8.38, P = 0.001) after multivariable adjustment. Plasma sST2 was also associated with hemorrhagic transformation after adjustment for traditional risk factors (OR: 5.58, 95% CI: 1.40–37.44, P = 0.039).InterpretationSoluble ST2 may serve as a prognostic biomarker for outcome and hemorrhagic transformation in patients with acute stroke. ST2 may link neuroinflammation and secondary injury after stroke.

Serum Soluble ST2 as a Novel Inflammatory Marker in Acute Ischemic Stroke

“…Recently, the high level of serum sST2 has been found to be associated with incident stroke/transient ischemic attack (TIA) [16]. The elevated sST2 has also been shown to be related to worse outcome and higher mortality after AIS [17]. However, the conclusions from another study in a large cohort of AIS patients revealed that serum sST2 may not be a strong and independent prognostic marker for AIS mortality [18].…”

Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage

“…17 sST2 acts as a decoy receptor, reducing the interaction of IL-33 with transmembrane ST2 and therefore shifting toward a proinflammatory response. 25,26 We recently identified sST2 as a marker of secondary brain injury and functional neurologic outcome after ischemic stroke, 27 suggesting it may also play a role in the immune response to neurovascular injury. 25,26 We recently identified sST2 as a marker of secondary brain injury and functional neurologic outcome after ischemic stroke, 27 suggesting it may also play a role in the immune response to neurovascular injury.…”

Serum soluble ST2 is a predictor for poor long-term prognosis after transient ischemic attack and ischemic stroke: a cohort study

“…In cerebrovascular disease, prior work found that sST2 is an independent predictor for poor functional outcomes (mRS>2) 3 months after AIS [8,9]. Additionally, sST2 levels were found to independently correlate with 90-day mortality and hemorrhagic transformation after AIS [9]. However, the predictive value of sST2 for all-cause mortality 90 days after ischemic stroke showed no statistical significance after multivariate adjustment [10].…”

“…sST2 is a prognostic marker in patients with heart failure and myocardial infarction [24,25] and significantly associated with incident stroke/TIA in previously stroke-free individuals [7]. In cerebrovascular disease, prior work found that sST2 is an independent predictor for poor functional outcomes (mRS>2) 3 months after AIS [8,9]. Additionally, sST2 levels were found to independently correlate with 90-day mortality and hemorrhagic transformation after AIS [9].…”

“…Studies have found that higher sST2 levels increase risk for incident stroke/TIA in the Framingham Offspring cohort [7]. Elevated sST2 is also associated with increased risk of hemorrhagic transformation, 90-day poor functional outcomes, and higher mortality after acute ischemic stroke (AIS) [8,9]. However, results have been mixed, with another study reporting that sST2 offered no prognostic value for 90-day all-cause mortality after AIS in multivariate analysis [10].…”