[The effects of cytochrome P450 2C19 genetic polymorphism on clopidogrel resistance and recent prognosis of patients with acute coronary syndrome].

OBJECTIVE: To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and clopidogrel resistance(CR) in patients with acute coronary syndrome(ACS), and to assess the effects of genetic polymorphism at CYP2C19 (681G>A) on the prognosis of ACS patients. METHODS: A total of 462 patients with ACS were enrolled and received loading dose clopidogrel(600 mg). The blood samples of patients were collected before and 24 hours after taking loading dose clopidogrel, then 5 µmol/L ADP-induced platelet aggregation ratio (PAR) was examined. Difference of two PAR ≤ 10% was defined as CR. Genomic DNA of patients were extracted from whole blood samples according to standard protocols and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the single nucleotide polymorphism of the CYP2C19 681G>A. According to whether the gene CYP2C19 681A was carried, patients were divided into two groups: wild type group and non-wild type group. After PCI treatment, patients were followed up for 6 months and major cardiac adverse events (MACE) happened during follow-up periods were recorded. RESULTS: Totally 127 enrolled cases were finally defined as CR (27.5%) , the frequency of CYP2C19 681A in patients with CR was higher than that in patients without CR (46.9% vs 28.1%, P < 0.01) . The ratio of CR in wild type group were lower than non-wide type group (17.4% vs 36.1%, P < 0.01) . Binary logistic regression analysis indicated that gene CYP2C19 681A was a strong independent predictor for CR in patients with ACS (OR 3.642, P < 0.05). After 6 months of follow-up, Kaplan-Meier survival analysis showed patients of wild type group and non-wild type group had significantly different cumulative non-events survival rates (94.8% vs 89.6%, Log rank = 4.296, P = 0.038) . CONCLUSIONS: The genetic polymorphism of CYP2C19 was associated with CR in patients with ACS. The mutation of CYP2C19 gene increased the risk of MACE in ACS patients undergoing PCI treatments and affected the patients' prognosis.

[The association of insulin resistance, blood pressure variability and severity of acute coronary syndrome].

OBJECTIVE: To investigate the association of insulin resistance (IR), blood pressure variability (BPV) and the severity of acute coronary syndrome (ACS), and assess the effect of percutaneous coronary intervention (PCI) on recent prognosis. METHODS: A total of 260 patients diagnosed as ACS and hospitalized in our department of cardiology from December 2009 to December 2010 were enrolled in the study. There were 93 cases of unstable angina pectoris(UAP), 84 of non ST segment elevation myocardial infarction and 83 of unstable angina pectoris. The subjects were divided into two groups according to 24 hour systolic blood pressure coefficient of variability (24 h SBP-CV) levels: high-CV group (24 h SBP-CV > 11.5, n = 130) and low-CV group(24 h SBP-CV < 11.5, n = 130). The differences in HOMA-IR and the severity of coronary artery diseases between the two groups were compared. The association of major adverse cardiac events within 6 months after PCI treatment, and IR as well as BPV was analyzed. RESULTS: Compared with the low-CV group, ACS patients in the high-CV group had obviously higher HOMA-IR levels (5.7 ± 1.2 vs 4.0 ± 1.4, P < 0.01), more multivessel diseases (49.2% vs 33.3%, P < 0.05) and B2/C type coronary diseases (48.5% vs 27.7%, P < 0.01), and higher coronary Gensini scores (59.7 ± 17.5 vs 43.8 ± 18.6, P < 0.01). Multi-factors logistic regression analysis indicated that both 24 h BPV-CV and IR were independent predictors for MACE incidence within 6 months after undergone PCI (P < 0.05 or P < 0.01). CONCLUSIONS: IR and BPV were obviously associated with the severity of coronary artery diseases in ACS patients. IR and 24 h BPV-CV were valuable in predicting recent prognosis of ACS patients.

Altered serum creatine kinase level and cardiac function in ischemia-reperfusion injury during percutaneous coronary intervention.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) resulting from primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is considered harmful to the patient, but its clinical significance remains unclear. This study explored the relationship of cardiac function examined by echocardiography and serum creatine kinase (CK) and CK-MB levels with MIRI in a cohort of Chinese AMI patients. MATERIAL/METHODS: We retrospectively analysed the clinical and angiographic data in 228 AMI patients in whom the infarct-related artery (IRA) was successfully recanalized by primary PCI. Cardiac function was evaluated by use of echocardiography before discharge from hospital. RESULTS: The in-hospital mortality rate in the MIRI group was 13.4% (16/119), which was significantly higher than the 4.6% (5/109) mortality rate in the non-MIRI group (P=0.021). The median of peak serum CK level was remarkably lower in the suppression-type MIRI group than in the non-MIRI group. There were no significant differences in the peak serum CK or CK-MB levels between the irritation-type MIRI group and the non-MIRI group. The peak CK and CK-MB levels were significantly higher in the no-reflow-type MIRI group than in the non-MIRI group. Left ventricular ejection fraction in the no-reflow-type MIRI group was significantly lower than in the non-MIRI group; left ventricular end-diastolic volume was significantly higher than in the irritation-type MIRI subgroup; and left ventricular end-systolic volume was greater than that in non-MIRI group and suppression-type MIRI group. CONCLUSIONS: MIRI (especially the no-reflow type) may lead to acute hemodynamic disorders and increase the mortality rate. However, suppression- and irritation-type MIRI may imply the existence of surviving myocardium.

Determinants and prognostic implications of reperfusion injury during primary percutaneous coronary intervention in Chinese patients with acute myocardial infarction.

BACKGROUND: The poor clinical outcome in acute myocardial infarction (AMI) patients undergoing primary percutaneous coronary intervention (PCI) has been attributed to myocardial ischemia-reperfusion injury (MIRI). OBJECTIVE: This study aimed to identify the predictive factors of MIRI during PCI in Chinese AMI patients with or without ST-segment elevation. METHODS: Clinical and angiographic data of 228 patients in whom the infarct-related artery (IRA) was successfully recanalized by primary PCI were retrospectively analyzed. Multiple logistic regressions were used. RESULTS: Compared with non-MIRI group (n=109), patients with MIRI (n=119) were characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more lesion vessels, more often thrombolysis in myocardial infarction (TIMI) 0 flow in IRA prior to PCI, less preinfarction angina, and more renal insufficiency. Ischemic time

[Reperfusion arrhythmias in acute myocardial infarction do not enhance myocardial injury].

OBJECTIVE: To investigate the clinical implications of reperfusion arrhythmias during primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI). METHODS: Data from 228 AMI patients in whom the infarct-related artery (IRA) were successfully recanalized by primary PCI were retrospectively analyzed. The 228 patients were divided into 2 groups: myocardial ischemia-reperfusion injury (MIRI) group (n=119) in whom MIRI events occurred within minutes after successful recanalization of IRA, and non-MIRI group (n=109). The 119 patients in MIRI group were further divided into 3 subgroups: severe bradycardia with hypotension (brady-arrhythmia subgroup), lethal ventricular arrhythmias requiring electrical cardioversion (tachy-arrhythmia subgroup), and IRA antegrade flow less than or equal to TIMI 2 grade without angiographic evidence of abrupt closure (no-reflow subgroup). RESULTS: (1) Clinical and angiographic data: Compared with non-MIRI group, MIRI group was characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more diseased vessels, more often TIMI 0 grade of initial antegrade flow in IRA, less pre-infarction angina, more renal insufficiency, and higher in-hospital mortality (13.4% vs. 4.6%, P=0.021). (2) The peak CK level was remarkably lower in brady-arrhythmia subgroup than that in non-MIRI group (2010 IU/L vs. 2521 IU/L, P=0.039). The peak CK or CK-MB level was notably higher in no-reflow subgroup than in non-MIRI group (4573 IU/L, 338 IU/L, respectively, P=0.000). (3) Left ventricular ejection fraction in no-reflow subgroup was significantly lower than in non-MIRI group (38.7% +/- 8.3% vs. 51.2% +/- 8.1%, P=0.000), left ventricular end-diastolic volume in no-reflow subgroup was greater than that in tachy-arrhythmia subgroup [(135 +/- 32) ml vs. (105 +/- 19) ml, P=0.029]. CONCLUSION: Reperfusion arrhythmias may imply the existence of much survived myocardium and do not enhance myocardial damage, while no-reflow increases myocardial injury and induces permanent impairment of cardiac function.

[Analysis on correlative factors for occurrence of myocardial ischemia-reperfusion injury during primary percutaneous coronary intervention for acute myocardial infarction].

OBJECTIVE: To explore the risk and protective factors for the occurrence of myocardial ischemia-reperfusion injury (MIRI) during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). METHODS: Clinical and angiographic data of 228 AMI patients in whom the infarct-related arteries (IRA) were successfully revascularized by primary PCI were analyzed retrospectively. MIRI was defined if the following conditions existed after PCI: severe bradycardia with hypotension, or lethal ventricular arrhythmias requiring electrical cardioversion, or IRA antegrade flow < or = TIMI 2 grade flow without angiographic evidence of thrombus, emboli, dissection or spasm. Multivariate logistic regression was used to identify independent relative factors among 18 clinical and angiographic factors for occurrence of MIRI. RESULTS: Multivariate logistic regression analysis showed that independent risk factors for MIRI were the time intervals from AMI onset to IRA reflow < or = 6 h (P = 0.014), inferior infarction localization (P = 0.006), IRA antegrade flow prior to PCI < or = TIMI 1 grade (P = 0.028), multivessel lesions (P = 0.063) and renal insufficiency (P = 0.067). Pre-infarction angina was found to be an independent protective factor (P = 0.005). CONCLUSIONS: Short time intervals from AMI onset to IRA revascularization, inferior wall infarction location, low IRA antegrade flow prior to PCI, multivessel lesions and renal insufficiency may promote the occurrence of MIRI during primary PCI, whereas pre-infarction angina may be a cardioprotective factor attenuating MIRI.

[Effect of percutaneous coronary intervention on QT dispersion and its clinical implication in patients with acute myocardial infarction].

OBJECTIVE: To observe the effects of percutaneous coronary intervention (PCI) on QT dispersion (QTd) and explore its clinical significance in patients with acute myocardial infarction (AMI). METHODS: The electrocardiograms recorded before and one day after PCI were analyzed in 138 patients with AMI. The duration from the onset of AMI to PCI operation was less than 6 h in 72 patients and 6 to 12 h in the other patients. All the patients underwent emergency percutaneous transluminal coronary angioplasty and subsequent coronary stenting. QT intervals, QTd, and heart rate-corrected QT intervals (QTc) and QTd (QTcd) were measured and calculated. RESULTS: In both patient groups receiving PCI with delay shorter and longer than 6 h after AMI, QT and QTc after PCI were not significantly different from that before PCI, but the QTd and QTcd were remarkably decreased after PCI (all the P <0.01). Moreover, the QTd and QTcd in the patients with delay of PCI less than 6 h were significantly shorter than those in patients the with greater-than-6-hour delay (P<0.05), and the inhospital mortality was 4.2% and 7.6% in the two groups, respectively (P=0.394). CONCLUSION: Successful PCI may notably reduce QTd in the patients with AMI, whose earlier performance usually produces better effects.