Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients.

Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia.

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7%) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5% in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): pound2.93 mm (RR = 0.54; 95%CI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm(2) (RR = 0.66; 95%CI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm(3) (RR = 0.74; 95%CI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95%CI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): < or =108.8 mg/dL (RR = 0.53; 95%CI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7 percent) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5 percent in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): £2.93 mm (RR = 0.54; 95 percentCI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm² (RR = 0.66; 95 percentCI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm³ (RR = 0.74; 95 percentCI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95 percentCI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): ≤108.8 mg/dL (RR = 0.53; 95 percentCI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

[Clinical profile, coronary angiography findings and early outcome in young patients with acute myocardial infarction in the thrombolytic era]. / Perfil clínico, cinecoronariográfico e evolutivo precoce de pacientes jovens com infarto agudo do miocárdio na era trombolítica.

PURPOSE: To assess the clinical, angiographic and early follow-up findings of young patients suffering an acute myocardial infarction, in comparison with older patients with infarction, in the thrombolytic era. METHODS: A retrospective analysis of the medical records of 46 patients < 40 years-old (group I) at the time of an acute myocardial infarction was compared with that of 46 older patients, randomly selected, presenting with this syndrome between february, 1991 and february, 1996 (group II). In both groups a comparison was conducted regarding the proportions of gender, risk factors, type of infarction (Q vs non-Q), left ventricular function, coronary anatomy and early mortality (1 month). The medical treatment was comparable for both groups, including the utilization of thrombolytics. RESULTS: The groups were discriminated only by: higher prevalence of smoking, of angiographically normal coronary arteries, and of non-critical (< 75% reduction of luminal diameter) coronary stenosis in group I; in the older group a higher proportion of patients had multivessel disease. Although not reaching statistical significance, a trend was observed to a more benign early course of the infarction in the patients less than < 40 years-old. CONCLUSION: The present findings are similar to those described in the pre-thrombolytic era, for young patients suffering an acute myocardial infarction.

[Risk stratification in acute myocardial infarction survivors. Exercise stress test versus coronary angiography]. / Estratificação prognóstica em sobreviventes ao infarto agudo do miocárdio. Teste ergométrico versus cinecoronariografia.

PURPOSE: To compare the predictive accuracy for future ischemic events of heart rate limited treadmill exercise test (HET) and coronary angiography (CA) applied to survivors of an uncomplicated myocardial infarction. METHODS: 142 consecutive patients (55 +/- 11 years, 80% males), presenting a non complicated acute myocardial infarction (AMI) were included. HET was performed 10 +/- 3 days after AMI, and CA during hospital stay or within 4-6 weeks. HET positivity criteria were: 1) horizontal or down-sloping ST segment displacement > or = 1 mm; 2) angina; 3) arterial pressure drop during exercise; 4) low workload (< 6 METS); 5) complex ventricular arrhythmia. At CA lesions causing > or = 50% of luminal reduction were considered significant. HET and CA results were correlated to ischemic events occurring during the follow-up (unstable angina in 20%, cardiac death 6%, and reinfarction 6%). RESULTS: HET was positive in 69 (49%) patients, exhibiting a positive predictive value for ischemic events (PV+) of 26% and a negative predictive value (PV-) of 77%. The mean event-free time was 43 +/- 3 months for positive HET and 46 +/- 3 months for a negative one (p = 0.48). CA showed 0-1 vessel involvement in 93 (66%) patients and > or = 2 vessels in 49 (34%) patients. The presence of multivascular disease at CA presented a PV+ of 37% and PV- of 82%; the mean event-free time was 37 +/- 4 months for patients with multivascular involvement and 48 +/- 2 months for patients without this pattern (p = 0.007). CONCLUSION: The predictive accuracy of HET for future ischemic events in the thrombolytic era is markedly reduced. This population of AMI survivors presents an overall good prognosis that seems to justify the poor predictive accuracy of this test.