Relationship Between Cytochrome P4502C19*2 Allele And Risk Scores With Prognosis For Coronary Stent Placement

Objectives:The aim of this study was to investigate the association between the loss-of-function cytochrome P450 2C19 (CYP2C19)*2 allele, risk scores and major adverse cardiovascular events (MACE) in patients undergoing percutaneous coronary intervention (PCI).Methods:Form January 2009 to December 2010, 355 consencutive hospitalized patients after undergoing elective Percutaneous coronary intervention (PCI) successfully were enrolled in this study(263 male patients, 92 female patients, mean age 64.26±11.16 years). All patients took asprin and clopidogrel conventionally before PCI and then maintained at least 1 year. We recorded the clinical data of these patients, and drawn blood samples to measure platelet count, fibrinogen and the platelet aggregation. PCR-RFLP technology was also used to test CYP2C19 *2 polymorphisms in these patients. All patients were divided into with major adverse cardiac events(MACE) group and without MACE group. We then assessed the patients by review of patients charts on readmission or by telephone. The major adverse cardiovascular events(MACE) was a composite of cardiac death, acute coronary syndrome(ACS), ischemic stroke or target vessel revascularization(TVR) after a follow-up for one year in the 355 patients undergoing PCI.Results:1. Patients identified with the incidence of cardiovascular outcomes in the MACE group were significantly older ( 69.06±9.40 vs. 63.20±10.25 years, P=0.028), higher CYP2C19*2 gene mutation (75.0% vs. 36.43%, P<0.001), increased residual platelet activity (34.45±15.58 vs. 25.76±12.69, P<0.001), more frequently had ACS (P=0.038), diabetes (P=0.001) and renal failure (P=0.010), showed a poorer left ventricular function (P=0.005) compared with patients measured in the non-MACE group. However, the drug-drug interactions, the incidence of hypertension, hyperlipidemia and multi-vessel disease did not show statistically different between the two groups.2. In bivariate correlation analyses, CYP2C19*2 genotype (GA+AA) showed a statistically positive correlation with residual platelet activity, indicating the RPA were influenced strongly by CYP2C19 *2 polymorphisms(r=0.437, P<0.001).3. The logistic regression analysis indicated that an age > 65 years, CYP2C19*2 carrier, diabetes, renal failure with a serum creatinine >1.5 mg/dl, reduced left ventricular function with EF<50%, and diabetes mellitus are independent risk factors of the recurrence of adverse cardiovascular events after PCI. After adjusting for common risk factors of CHD after PCI,logistic regression analysis indicated that the odds ratios(OR) of GA+AA(vs. GG) genotype was 4.037 (95%Cl: 2.205-9.379, P<0.001).4.In the factor-weighed model, Patients with higher score levels had a higher ratio of recurrence MACE than those with lower score levels (score 1-3, HR 1.753, 95% CI 0.342-7.452, P=0.491; score 4-7, HR 3.063, 95%CI 1.934-11.163, P=0.023; score 8-11, HR 5.135, 95% CI 2.3174-15.123, P=0.002).Conclusions:1.Old age, CYP2C19*2 carrier, diabetes, renal failure, and reduced left ventricular function are independent risk factors of the recurrence of adverse cardiovascular events.2.The risk scores could provide a good tool to evaluate the incidence of MACE. However, Loss-of-function CYP2C19*2 allele regarded as a convenient indicator not only evaluated the risk for the incidence of MACE, bur also showed a statistically positive correlation with platelet aggregation.