Exploration Of Clinical Predictive Model Of HTPR To Clopidogrel And The Relationship With PDI、T2DM

Purpose High on-treatment platelet reactivity(HTPR)and Type 2 diabetes mellitus(T2DM)have been shown to increase the rate of major cardiovascular events and cerebrovascular diseases,while protein disulfide isomerase(PDI)plays an important role in platelet activation and fibrin formation.The aim of this study was to investigate the clinical model and prognosis of HTPR to clopidogrel in different populations,and the relationship among PDI,HTPR and T2 DM.Methods A total of 2708 patients with acute ischemic vascular disease were retrospectively analyzed,and of 441 patients were followed up.Logistic regression analysis was used to determine the relationship between HTPR and candidate risk factors.Discrimination and calibration of HTPR predictive model were assessed by the receiver operating characteristic(ROC)curve and HosmerLemeshow goodness-of-fit test.Survival curves were constructed with Kaplan-Meier.To 50 patients with ischemic cerebrovascular diseases,flow cytometry was used to prospectively explore the relationship among PDI on the surface of resting and activated platelet,HTPR and T2 DM,as well as the changes of PDI under insulin intervention.Results 388(14.3%)patients were HTPR.By Logistic regression analysis,HTPR prediction model for non-diabetic patients(area under Curve(AUC)of ROC :0.700,p <0.001;HosmerLemeshow test,p =0.190)included advanced age(p =0.002),female(p <0.001),LDL(p= 0.004),PDW(p <0.001),PCT(p <0.001),and CYP2C19*2(p=0.046)or CYP2C19*3(p= 0.001),and for patients with DM(AUC: 0.709,p <0.001,Hosmer-Lemeshow test,p =0.788),included advanced age(p=0.004),female(p<0.001),DAPT Regimen(p=0.014),PLT(p=0.028),PCT(p=0.025).Kaplan-Meier analysis showed that patients with HTPR had a higher incidence of MACE(21.1% vs.9.9%,p= 0.010).Multiple linear regression analysis showed that PDI on the surface of resting platelet were affected only by Hb A1c(p:0.014).After platelet activated,PDI on platelet surface increased(p= 0.006),and there were significant differences between different concentrations insulin groups(p = 0.024).Conclusion Our results suggest that HTPR to clopidogrel is associated with numerous biomarkers.Predictive models of HTPR have useful discrimination and good calibration,which may predict long-term MACE.Hb A1 c affected the expression of PDI on platelet surface,but nothing to do with the HTPR defined by TEG or VerifyNow.Exogenous insulin inhibited the expression of PDI on platelet surface but had no significant effect on T2 DM patients.This may be important for future tailored antiplatelet strategies in patients with ischemic vascular events.