Study On The Correlation Between Serum Soluble ST2 Levels And The Prognosis Of Transient Ischemic Attack And Ischemic Stroke

BackgroundIschemic cerebrovascular disease accounts for more than 75% of cerebrovascular disease,which mainly includes transient ischemic attack(TIA)and ischemic stroke(IS).TIA/IS is characterized by high incidence,high recurrence,high disability,and high mortality.Hence it is very important to make an early diagnosis and prognosis evaluation of TIA/IS.Soluble ST2(sST2)functions as a decoy receptor for interleukin-33 and is secreted into the circulation.Recent studies have found that sST2 level elevates in some diseases such as cancer,inflammatory disease,and heart disease.sST2 is also considered as a valuable prognostic biomarker.The elevated sST2 level is associated with adverse outcomes in several diseases such as acute dyspnea,heart failure,and myocardial infarction.In cerebrovascular disease,the higher sST2 level is related to high risk of stroke,the severity of cerebral infarction and poor outcomes.At present,there are few studies on the relationship between sST2 and TIA/IS.These studies lack results in long-term prognosis and recurrence of ischemic stroke.ObjectiveThis study aimed to explore the correlation between serum sST2 levels and the prognosis of TIA/IS.MethodsWe conducted the case control study by continuously enrolling patients with acute ischemic stroke(AIS)and TIA in the third Department of Neurology,the First Affiliated Hospital of Zhengzhou University from October 2015 to June 2018.The first intravenous blood collection for sST2 measurement was completed within 24 hours after symptoms onset.Healthy people without medical history of cerebral and myocardial infarction were recruited as controls from the physical examination center of the First Affiliated Hospital of Zhengzhou University during the same period.Baseline data collection,assessment,intravenous blood collection and ELISA detection of serum sST2 were all completed in patients and controls.The prospective and observational cohort study was conducted by telephone or face-to-face follow-up 6 months after the onset of TIA/IS.The primary outcome was the occurrence of recurrent ischemic stroke.The secondary outcomes were poor functional outcome(mRS>2)and all major events(composite of ischemic or hemorrhage stroke,myocardial infarction and all-cause mortality).The date of outcomes were recorded.Statistical analyses for the study were performed using SPSS 24.0(SPSS Inc.,Chicago,IL,USA).Continuous variables were presented as the mean ± standard deviation for normal distribution or as median with interquartile range for skewed distribution.Student t test or Mann Whitney U test was done to determine difference among continuous variables.Categorical data were expressed as the frequency with the percentage and compared by the Chi-square test.To mitigate differences of baseline characteristics among groups,we conducted propensity score matching.Matched quantitative data were compared using paired sample t test or Wilcoxon test.Receiver operating characteristic(ROC)curve of sST2 was plotted.Some evaluation indexes were calculated as its potential diagnostic value,such as the area under the curve,optimal cut-off value,specificity,sensitivity,positive likelihood ratio,and negative likelihood ratio.Kaplan–Meier survival curves were implemented to investigate the ability of sST2 to predict the occurrence of primary and secondary outcomes,using the log-rank test.The predictive value of sST2 for recurrent ischemic stroke and all major events 6 months after the onset of TIA/IS was assessed by Cox regression analysis with a hazard ratio(HR)and its 95% confidence intervals(CI).The association of sST2 with functional outcome was assessed using logistic regression with a odds ratio(OR)and its 95% CI.Statistical significance was set at P<0.05(two-sided).Results1.A total of 430 patients with TIA/IS and 148 healthy controls were included.Compared to controls,serum sST2 levels in patients were significantly higher [17.72(9.31-28.84)vs.8.29(4.52-15.19)ng/mL,P<0.0001].After using propensity score matching,sST2 levels in patients were still higher(P<0.0001).The area under the ROC curve of sST2 in predicting the onset of TIA/IS was 0.70(95% CI: 0.65-0.75,P<0.001).The optimal cut-off value of sST2 level was 10.40ng/mL,with the sensitivity of 72.79% and the specificity of 61.49%.The positive likelihood ratio was 1.89 and the negative likelihood ratio was 0.44.2.There were 417 patients going into the final analysis,with 13(3.02%)patients lost to the 6-month follow-up.Kaplan-Meier survival curves of 6-month recurrent ischemic stroke and all major events revealed high serum sST2 levels were associated with poor prognosis than low sST2(log-rank test,P=0.025 and 0.001 respectively).In the univariable Cox regression analysis,serum sST2 levels were both associated with recurrent ischemic stroke(P=0.030)and all major events(P=0.002).After adjustment for sex,age,smoking,medical history and NIHSS,serum sST2 levels were found to independently predict recurrent ischemic stroke(HR: 2.83,95% CI: 1.17-6.84,P=0.021)and all major events(HR: 3.50,95% CI: 1.62-7.57,P=0.001)within 6 months.Serum sST2 levels were also related to poor functional outcome in logistic regression analysis.Conclusions1.Serum sST2 levels elevated after the onset of TIA/IS.It had potential diagnostic value for TIA/IS.2.Serum sST2 levels of patients with TIA/IS on admission were an independent predictor for recurrent ischemic stroke,all major events and poor functional outcome.It may be a potential biomarker for prognosis of TIA/IS.