Jia-Hui Zhang

Association of PEAR1 genetic variants with platelet reactivity in response to dual antiplatelet therapy with aspirin and clopidogrel in the Chinese patient population after percutaneous coronary intervention

INTRODUCTION Platelet Endothelial Aggregation Receptor-1 (PEAR1) is a recently reported platelet transmembrane protein which plays an important role in platelet aggregation. The aim of this study was to investigate whether PEAR1 genetic variations were associated with platelet reactivity as assessed by adenosine diphosphate(ADP)-induced platelet aggregation in Chinese patients treated with aspirin and clopidogrel. METHODS Patients with coronary heart disease (CHD) who underwent percutaneous coronary intervention (PCI) were enrolled in the study. All patients were on dual antiplatelet therapy with aspirin and clopidogrel. ADP-induced platelet aggregation was measured by thromboelastography and defined as percent inhibition of platelet aggregation (IPA). Patients (n=204) with IPA <30% were identified as high on-treatment platelet reactivity (HPR). Patients (n=201) with IPA >70% were identified as low on-treatment platelet reactivity (LPR). Sixteen single nucleotide polymorphisms (SNPs) of PEAR1 were determined by a method of improved multiple ligase detection reaction. RESULTS Among the 16 SNPs examined by univariate analysis, 5 SNPs were significantly associated with ADP-induced platelet aggregation. Minor allele C at rs11264580 (p=0.033), minor allele G at rs2644592 (p=0.048), minor allele T at rs3737224 (p=0.033) and minor allele T at rs41273215 (p=0.025) were strongly associated with HPR, whereas homozygous TT genotype at rs57731889 (p=0.009) was associated with LPR. Multivariate logistic regression analysis further revealed that the minor allele T at rs41273215 (p=0.038) was an independent predictor of HPR and the homozygous TT genotype at rs57731889 (p=0.003) was an independent predictor of LPR. CONCLUSIONS PEAR1 genetic variations were strongly associated with ADP-induced platelet aggregation in Chinese patients with CHD treated with aspirin and clopidogrel. These genetic variations may contribute to the variability in platelet function. The utility of PEAR1 genetic variants in the assessment and prediction of cardiovascular risk warrants further investigation.

Relationship Between ABCB1 Polymorphisms, Thromboelastography and Risk of Bleeding Events in Clopidogrel-Treated Patients With ST-Elevation Myocardial Infarction

INTRODUCTION This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI). METHODS 467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19*2, *3, *17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12months. RESULTS By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) ≥ 3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p=0.009; cut-off value > 93.4%). ADP inhibition can also predict BARC ≥ 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value > 92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19*17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition > 92.5% (OR 2.247, 95%CI 1.082-4.665, P=0.03), carriage of rs1045642 (OR 2.943, 95%CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95%CI 0.219-0.936, P = 0.032) were independent predictors of BARC ≥ 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients. CONCLUSIONS In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.

Effect of platelet receptor gene polymorphisms on outcomes in ST-elevation myocardial infarction patients after percutaneous coronary intervention

Abstract Polymorphisms in platelet receptor genes may influence platelet function. This study aimed to assess the impact of five polymorphisms of genes encoding platelet receptors on the risk of ischemic and bleeding events in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). 503 consecutive Chinese patients with STEMI after an uneventful PCI and exposed to standard dual antiplatelet therapy for 12 months were enrolled. Polymorphisms of platelet receptors, GPIa (ITGA2, 807C > T, rs1126643), GPVI (GP6, 13254T > C, rs1613662), PAR-1 (F2R, IVS-14A > T, rs168753) and P2Y12 (P2RY12, 34C > T, rs6785930 and H1/H2 haplotype, 52G > T, rs6809699) were detected by the ligase detection reaction. The follow-up period was 12 months. Overall, 34 (6.8%) ischemic events occurred and 46 (9.1%) major bleedings occurred. Multivariate Cox regression analysis showed the carriage of F2R rs168753 minor allele was an independent predictor of the composite ischemic events (HR 0.387, 95% CI 0.193–0.778, p = 0.008) after adjusted for established risk factors. Multivariate logistic regression model identified that carriage of P2RY12 rs6809699 minor allele (OR 2.71, 95% CI 1.298–5.659, p = 0.008) was an independent predictor of major bleedings. The associations were then validated in a second cohort of 483 STEMI patients. In STEMI patients after PCI, F2R rs168753 minor allele could significantly contribute to the risk of ischemic events, and P2RY12 rs6809699 minor allele could predict bleedings. The genetic testing of platelet receptors can be valuable in predicting adverse events in STEMI patients after PCI.

CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention

INTRODUCTION Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible. METHODS Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis. RESULTS AND CONCLUSIONS Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.

Comparing of Light Transmittance Aggregometry and Modified Thrombelastograph in Predicting Clinical Outcomes in Chinese Patients Undergoing Coronary Stenting with Clopidogrel

Background:Several platelet function tests are currently used to measure responsiveness to antiplatelet therapy. This study was to compare two tests, light transmittance aggregometry (LTA) and modified thrombelastography (mTEG), for predicting clinical outcomes in Chinese patients after percutaneous coronary intervention (PCI). Methods:Prospective, observational, single-center study of 789 Chinese patients undergoing PCI was enrolled. This study was investigated the correlations between the two tests and performed receiver operating characteristic curve (ROC) analysis for major adverse cardiovascular events (MACEs) at 1-year follow-up. Results:MACEs occurred in 32 patients (4.1%). Correlations were well between the two tests in the adenosine diphosphate induced platelet reactivity (Spearman r = 0.733, P < 0.001). ROC-curve analysis demonstrated that LTA (area under the curve [AUC]: 0.677; 95% confidence interval [CI]: 0.643–0.710; P = 0.0009), and mTEG (AUC: 0.684; 95% CI: 0.650–0.716; P = 0.0001) had moderate ability to discriminate between patients with and without MACE. MACE occurred more frequently in patients with high on-treatment platelet reactivity (HPR) when assessed by LTA (7.4% vs. 2.7%; P < 0.001), and by TEG (6.7% vs. 2.6%; P < 0.001). Kaplan–Meier analysis demonstrated that HPR based on the LTA and mTEG was associated with almost 3-fold increased risk of MACE at 1-year follow-up. Conclusions:The correlation between LTA and mTEG is relatively high in Chinese patients. HPR measured by LTA and mTEG were significantly associated with MACE in Chinese patients undergoing PCI.

Long-term Outcomes of Primary Percutaneous Coronary Intervention with Second-generation Drug-eluting Stents in ST-elevation Myocardial Infarction Patients Caused by Very Late Stent Thrombosis

Background: The ST-segment elevation myocardial infarction (STEMI) patients due to stent thrombosis (ST) remain a therapeutic challenge for a clinician. Till date, very few researches have been conducted regarding the safety and effectiveness of primary percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) for STEMI caused by very late ST (VLST). This retrospective study evaluated the safety, efficacy, and outcomes of primary PCI with second-generation DES for STEMI due to VLST compared with primary PCI for STEMI due to de novo lesion. Methods: Between January 2007 and December 2013, STEMI patients with primary PCI in Fuwai Hospital had only second-generation DES implanted for de novo lesion (558 patients) and VLST (50 patients) were included in this retrospective study. The primary end points included cardiac death and reinfarction. The secondary end points included cardiac death, reinfarction, and target lesion revascularization. Continuous variables were expressed as mean (standard deviation) or median (interquartile range) and compared by Students t-test or Mann-Whitney U-test as appropriate. Categorical variables were expressed as counts and percentages, and comparison of these variables was performed with Chi-square or Fishers exact test. A two-tailed value of P < 0.05 was considered statistically significant for all comparisons. Statistical analyses were performed by SAS software (version 9.4, SAS Institute Inc., Cary, USA) for Windows. Results: In-hospital primary end point and the secondary end point were no significant differences between two groups (P = 1.000 and P = 1.000, respectively). No significant differences between two groups were observed according to the long-term primary end point and the secondary end point. Kaplan-Meier survival curves showed no significant difference between the two groups in the primary end point and the secondary end point at 2 years (P = 0.340 and P = 0.243, respectively). According to Cox analysis, female, intra-aortic balloon pump support, and postprocedural thrombolysis in myocardial infarction flow 3 were found to be independent predictors for long-term follow-up. Conclusion: Primary PCI with second-generation DES is a reasonable choice for STEMI patients caused by VLST.

Head to Head Comparison of Two Point-of-care Platelet Function Tests Used for Assessment of On-clopidogrel Platelet Reactivity in Chinese Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

Background: Platelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy. In China, the thromboelastography (TEG) test has been well accepted in clinics, whereas VerifyNow, mainly used for scientific research, has not been used in routine clinical practice. The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention (PCI). Methods: A total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study. On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist. Based on the previous reports, an inhibition of platelet aggregation (IPA) <30% for TEG or a P2Y12 reaction unit (PRU) >230 for VerifyNow was defined as high on-clopidogrel platelet reactivity (HPR). An IPA >70% or a PRU <178 was defined as low on-clopidogrel platelet reactivity (LPR). Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient (r) and kappa value (&kgr;), respectively. Results: Our results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity (r = −0.511). A significant although poor agreement (&kgr; = 0.225) in identifying HPR and a significantly moderate agreement in identifying LPR (&kgr; = 0.412) were observed between TEG and VerifyNow. By using TEG as the reference for comparison, the cutoff values of VerifyNow for the Chinese patients in this study were identified as PRU >205 for HPR and PRU <169 for LPR. Conclusions: By comparing VerifyNow to TEG which has been widely used in clinics, VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients.

Effect of sex difference in clinical presentation (stable coronary artery disease vs unstable angina pectoris or non-ST-elevation myocardial infarction vs ST-elevation myocardial infarction) on 2-year outcomes in patients undergoing percutaneous coronary intervention

OBJECTIVE To determine whether there is a difference in 2-year prognosis among patients across the spectrum of coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS We analyzed all consecutive patients undergoing PCI at a single center from 1/1-12/31/2013. Clinical presentations were compared between sexes according to baseline clinical, angiographic, and procedural characteristics and 2-year (mean 730 ± 30-day) outcomes. RESULTS We grouped 10 724 consecutive patients based on sex and clinical presentation. Among patients with ST-elevation myocardial infarction (STEMI), rates of all-cause death (6.7% vs 1.4%) and cardiac death (3.8% vs 1.1%) were significantly higher in women than in men (P < 0.05), but these rates did not differ between men and women with stable coronary artery disease (SCAD) and non-ST-elevation acute coronary syndrome ((NSTE-ACS). Incidence of major bleeding was greater than in men only in those women presenting with ACS. After multivariable adjustment, female sex was not an independent predictor of outcomes in STEMI (hazard ratio [HR] for all-cause death: 1.33, 95% confidence interval [CI]:0.52-3.38; P = 0.55; HR for cardiac death: 0.69, 95%CI: 0.23-2.09, P = 0.51], but was still an independent predictor of bleeding in STEMI (HR: 3.53, 95%CI: 1.26-9.91, P = 0.017). CONCLUSION Among STEMI patients, women had worse 2-year mortality after PCI therapy, but female sex was not an independent predictor of mortality after adjustment for baseline characteristics. In STEMI patients, women were at higher bleeding risk than men after PCI, even after multivariable adjustment.

TCT-155 Prognostic Impact of the Residual SYNTAX Score on 2-years Outcomes in Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

Imcomplete revascularization(IR) after PCI is common and most studies have suggested that IR is associated with a worse prognosis compared with complete revascularization(CR).The aim of this study was to evaluate the use of the residual SYNTAX score (rSS) following a complete vs. incomplete

TCT-346 Impact of anemia after coronary stenting on long-term outcomes of patients with coronary disease.

Anemia is an important co-morbidity in patients undergoing percutaneous coronary intervention(PCI). The effect of hemoglobin decrease and anemia after PCI on long-term outcomes of patients with coronary disease have not been defined. We used the registry database which prospectively collected data