Predictors And Prognostic Models Of Outcomes In Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis

Part one The prognostic accuracy of the THRIVE-c and START models in Chinese stroke patients treated with intravenous thrombolysis: an external validation studyBackground: Current data remain lacking on studies validating stroke prognostic models.THRIVE-c(the Totaled Health Risks in Vascular Events calculation)and START(National Institutes of Health Stroke Scale score,age,pre-stroke modified Rankin score,onset-to-treatment time)are two recently published prognositic models for ischemic stroke patients.We aimed to validate the predictive performance of THRIVE-c and START models for predicting 3-month poor outcome in acute ischemic stroke(AIS)patients treated with intravenous thrombolysis.Methods: AIS patients treated with intravenous tissue-type plasminogen activator(tPA)from April 2015 to June 2019 were retrospectively enrolled from a prospective consecutive database of the China National Comprehensive Stroke Center.The outcome measure was a 3-month unfavorable outcome,defied as modified Rankin Scale 3–6.The two models were evaluated in terms of discrimination and calibration.Discrimination was assessed using the area under the receiver operating characteristic(AUROC),and calibration was evaluated graphically with calibration plots and quantitatively using Brier score.Results: A total of 783 patients(median age 63 years,29.8% women)met our inclusion criteria.The START(AUROC 0.746,95% confidence interval [CI] 0.710~0.782)performed slightly better than THRIVE-c(AUROC 0.743,95% CI 0.707~0.778),although the difference was not statistically significant(P=0.488).Brier scores for THRIVE-c and START were 0.197 and 0.203,respectively.Both models showed weak correlation between predicted and actual outcomes with calibration curves.Conclusions: In this Chinese cohort of AIS patients,the AUROCs of both the THRIVE-c and START models were acceptable for prediction of 3-month poor outcome.However,neither calibrated well in this cohort.External validation in additional cohorts,refinement and updating of the two models,and further impact studies,are needed.Part two Early prediction of the 3-month outcome for individual acute ischemic stroke patients who received intravenous thrombolysis using a nomogram modelBackground: An early and accurate prediction of long-term outcome for stroke patients is of great importance by assisting in the decision-making process.The aim of this study was to establish a nomogram model for individualized early prediction of the 3-month prognosis in patients with AIS who were treated with intravenous tPA thrombolysis.Methods: AIS patients treated with intravenous tPA thrombolysis from January 2016 to June 2019 were retrospectively enrolled in our stroke center.The main outcome measure was a 3-month unfavorable outcome(modified Rankin Scale 3–6).To construct the nomogram model,stepwise logistic regression analysis was applied to select the significant predictors of the outcome.The discriminative performance of the model was assessed by calculating the area under the receiver operating characteristic curve(AUROC).A decision curve analysis was used to evaluate prognostic value of the model.Results: A total of 691 patients were included in this study;564 patients were included in the training cohort,while 127 patients were included in the test cohort.The initial National Institutes of Health Stroke Scale(NIHSS,odds ratio [OR] 1.35,95% CI 1.28~1.44;P<0.001),delta NIHSS(changes in the NIHSS score from baseline to 24 hours,OR 0.75,95% CI 0.70-0.79;P<0.001),hypertension(OR 2.07,95% CI 1.32~3.31;P=0.002),hyperhomocysteinemia(Hhcy,OR 2.18,95% CI 1.20~4.11;P=0.013)and the ratio of high-density lipoprotein cholesterol(HDL-C)to low-density lipoprotein cholesterol(LDL-C)(HDL-C/LDL-C,OR 3.29,95% CI 1.00~10.89;P=0.049)(N2H3)were found to be independent predictors of a 3-month unfavorable outcome from multivariate logistic regression analysis and were incorporated in the N2H3 nomogram model.The AUC-ROC of the training cohort was 0.872(95% CI,0.84~0.902),and the AUC-ROC of the test cohort was 0.900(95% CI,0.848~0.953).Conclusion: The study presented the N2H3 nomogram model,with initial NIHSS score,delta NIHSS,hypertension,Hhcy,and HDL-C/LDL-C as predictors.It therefore provides an individualized early prediction of the 3-month unfavorable outcome in AIS patients treated with intravenous tPA thrombolysis.Part three The impact of lipid levels on ischemic stroke outcomes after thrombolysisBackground: Effects of serum cholesterol levels on stroke outcomes remain controversial,especially in intravenous thrombolysis(IVT)-treated patients.Our previous study in part two showed that the ratio of HDL-C and LDL-C was posivitely related to the unfavorable outcome for patients with AIS who received IVT with tPA.This study explored the association between lipid levels and stroke outcomes in tPA treated AIS patients.Methods: Patients with AIS who received tPA thrombolysis from January 2016 to June 2019 were retrospectively enrolled from a prospective consecutive database of the China National Stroke Center.Fasting lipid profiles,including total cholesterol,triglyceride,LDL-C,HDL-C were collected the morning after admission.Stroke outcomes included hemorrhagic transformation,3-month unfavorable outcome(modified Rankin scale >2),and 3-month mortality.Results: Finally,we enrolled 698 IVT-treated patients with AIS(median age,63 years;449 male).Bivariate comparison of fasting lipid profiles showed that patients with an unfavorable outcome had lower triglyceride(P=0.001)and higher HDL-C(P=0.001)levels.Binary logistic regression analysis showed that a higher HDL-C level was independently associated with a higher risk of a 3-month unfavorable outcome(odds ratio 1.999,95% CI 1.204~3.320,P=0.007).Patients were then divided into high and low HDL-C groups according to a cutoff HDL-C of 1.415 mmol/L.After propensity score matching to adjust for baseline factors,patients in the high HDL-C group were more likely to experience a 3-month unfavorable outcome than those in the low HDL-C group(P=0.041).Conclusions: A higher HDL-C level was independently associated with a 3-month unfavorable outcome in IVT-treated patients with AIS.This observation provides evidence of the lipid paradox in AIS patients and serves as an impetus for further studies of the contributions of lipid profiles on stroke outcomes.