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Background: Because clopidogrel is converted to its active metabolite by P450 isoenzymes, which are also involved in the metabolism of omeprazole, there is concern regarding whether the action of clopidogrel would be reduced in patients also taking omeprazole., Objective: To evaluate the impact of omeprazole administration on the effectiveness of clopidogrel drug therapy during the first year following successful coronary stenting (CS)., Methods: A total of 588 consecutive patients who underwent successful CS for stable or unstable coronary artery disease were studied. Patients were classified into those who were treated (group A, n=340) or not treated (group B, n=248) with omeprazole for seven or more consecutive days during the entire observation period. The composite of cardiac death or rehospitalization for nonfatal myocardial infarction during the first year was the prespecified primary study end point., Results: Baseline characteristics, and dual clopidogrel and acetylsalicylic acid drug therapy were well balanced between the study groups. By one year, the primary end point was reached by 58 (9.9%) patients, including 20 (3.4%) who died due to cardiac reasons and 38 (6.5%) who were rehospitalized because of a nonfatal myocardial infarction. Patients in groups A and B, respectively, were at similar risk of the primary composite end point (10% versus 9.7%, hazard ratio 1.1 [95% CI 0.6 to 1.8]; P=0.89)., Conclusions: According to the results of the present study, treatment with omeprazole had no impact on the clinical efficacy of clopidogrel drug therapy during the first year after successful CS.

Background: Aspirin resistance has been associated with an adverse long-term outcome in patients with atherosclerotic coronary artery disease, but more studies are needed., Hypothesis: The aim of this study was to investigate the impact of aspirin resistance, assessed by the Platelet Function Analyzer-100 (PFA-100) (Dade Behring Inc., Deerfield, Ill., USA) on the long-term prognosis in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS)., Methods: A total of 496 consecutive patients were studied. The 1-y incidence of cardiovascular death was the prespecified study endpoint. The patients were divided, according to the values of PFA-100 collagen epinephrine closure time (CEPI-CT) upon presentation, into aspirin sensitives (those with a PFA-100 CEPI-CT>193 sec) and aspirin resistants (those with a PFA-100 CEPI-CT

Objective: The value of the recently introduced definitions of metabolic syndrome (MetS) in the identification of high cardiovascular risk subjects remains questionable. We examined the association among different definitions of MetS, and the occurrence of a first-ever acute coronary syndrome (ACS)., Methods: We studied 211 patients with a first-ever ACS and 210 control subjects. We recorded cardiovascular risk factors and the presence of MetS using 3 different definitions, according to the National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III, National Heart, Lung and Blood Institute/American Heart Association (NHLBI/AHA), and International Diabetes Federation (IDF), respectively. The association of MetS with ACS was assessed using univariate and multivariate logistic regression models after adjusting for potential confounding factors, such as gender, age, body mass index, hypertension, diabetes mellitus, and lipids., Results: ACS cases had a prevalence of metabolic syndrome according to NCEP-ATP III, NHLBI/AHA, and IDF criteria of 72.5%, 81.2%, and 79.1%, respectively. The unadjusted odds ratio (OR) for a first-ever ACS were 2.32 (95% CI: 1.53-3.52, p=0.001), 2.82 (95% CI: 1.79-4.43, p=0.001), and 3.26 (95% CI: 2.12-5.00, p=0.001) for NCEP-ATP III, NHLBI/AHA, and IDF MetS definitions, respectively. Multivariate analyses revealed that only IDF-defined MetS was significantly associated with ACS (OR: 2.23 95% CI: 1.30-3.82, p=0.003), while of the MetS components only waist circumference remained independently associated with ACS (O.R: 1.045 95% CI: 1.014-1.078, p=0.005)., Conclusion: The definition of MetS according to the IDF criteria appears to be a better predictor of ACS than NCEP-ATP III and NHLBI/AHA.

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI., Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population., Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77-1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63-2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29-4.04, P = 0.908)., Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AMI.

The choice of optimal revascularization strategy in patients with coronary artery disease (CAD) is becoming more challenging lately, due to recent advances in percutaneous coronary intervention (PCI) and coronary artery bypass grafting surgery (CABG). On one hand, drug-eluting stents (DES) have emerged as a solution to the problem of restenosis after balloon angioplasty or bare-metal stent implantation, which was responsible for a higher rate of events (mainly repeat revascularization) in relation to CABG. On the other hand, off-pump bypass techniques and minimally invasive grafting of the left anterior descending artery appear to be safe and efficacious alternatives to traditional, on-pump CABG. Available literature includes studies outdated by current technologies, leaving the dilemma of best revascularization strategy unanswered in the general CAD population, but also in high-risk groups, such as diabetics and patients with chronic kidney disease. A number of ongoing trials, especially designed for this purpose, are set to end the debate, providing headto- head comparisons between DES-assisted PCI and contemporary bypass surgery.

Objectives: To evaluate, using continuous 12-lead ECG ST-segment monitoring, the role of circulating levels of both cardiac troponin I (cTnI) and high-sensitivity C reactive protein (hs-CRP), on presentation, in the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction (STEMI)., Design and Setting: Prospective observational study in a tertiary referral centre., Patients: 786 consecutive patients with STEMI, who received intravenous thrombolysis in the first 6 h from index pain., Main Outcome Measures: The incidence of failed thrombolysis and of cardiac death by 30 days. Failed thrombolysis was defined as the absence of abrupt and sustained > or =50% ST-segment recovery in the first 90 min after the initiation of intravenous thrombolysis., Results: The incidence of failed thrombolysis and 30-day cardiac death was 57.4% and 11.8%, respectively. By multivariate logistic regression analysis according to tertiles of both cTnI (RR, 1.5; 95% CI 1.1 to 1.8, p = 0.004 for highest vs middle third; 2.2, 1.9 to 3.5, p<0.001 for highest vs lowest third; 1.5, 1.2 to 1.8, p = 0.001 for middle vs lowest third) and hs-CRP (RR, 2.0, 95% CI, 1.6 to 2.2; p<0.001 for highest vs middle third; 2.6, 2.1 to 3.5, p<0.001 for highest vs lowest third; 1.3, 1.2 to 1.7, p = 0.02 for middle vs lowest third), were independently associated with failed thrombolysis. Moreover, by multivariate Cox regression analysis according to tertiles of both cTnI (HR 1.2, 95% CI 1.1 to 1.8, p = 0.03 for highest vs middle third; 1.5, 1.2 to 2.2, p = 0.004 for highest vs lowest third; 1.1, 0.6 to 1.4, p = 0.6 for middle vs lowest third) and hs-CRP (HR1.2, 95% CI 1.1 to 1.6, p = 0.04 for highest vs middle third; 1.7, 1.3 to 2.6, p = 0.001 for highest vs lowest third; 1.1, 0.9 to 2.1, p = 0.1 for middle vs lowest third), were independently related with an increased risk of 30-day cardiac death., Conclusions: High circulating levels of both cTnI and hs-CRP are related with an independent increased risk of intravenous thrombolysis failure and 30-day cardiac death in patients who received intravenous thrombolysis in the first 6 h of STEMI.

Background: Continuous 12-lead electrocardiographic (ECG) ST monitoring and the Thrombolysis In Myocardial Infarction Risk Score (TIMI-RS), both have been shown to be useful for early risk stratification in patients with non-ST elevation acute coronary syndromes (NSTACS)., Hypothesis: Transient ST ischemic events, detected by continuous 12-lead ECG ST monitoring, early in the course of NSTACS, may add prognostic information to the TIMI-RS., Methods: In all, 567 consecutive patients with a NSTACS underwent 24-h continuous 12-lead ECG ST monitoring. An ST ischemic event was defined as a transient ST shift in any lead of > or = 0.10 mV compared with the reference ECG, lasting for > or = 1 min., Results: The incidence of the composite of death, nonfatal myocardial infarction (or reinfarction) and recurrent ischemia by Day 14 was 22.2%. By Day 30, the incidence of the composite of death and nonfatal myocardial infarction (or reinfarction) was 14.7%. There was a significantly increased risk of 14-day (p value for trend < 0.001) or 30-day (p value for trend <0.001) composite endpoint with increasing of TIMI-RS. Moreover, the occurrence of > or = 1 ST shifts during ST monitoring was associated with a significantly increased risk of 14- (p value < 0.001) or 30-day (p value < 0.001) composite endpoint, and this was true throughout the groups of TIMI-RS., Conclusions: The present study suggests that continuous 12-lead ECG ST monitoring, early in the course of NSTACS, may serve as an affordable tool to add prognostic information to the TIMI-RS.

Objective: There are conflicting results regarding the impact of type 2 diabetes on intravenous thrombolysis effectiveness during ST elevation myocardial infarction (STEMI). The present study, using a continuous 12-lead electrocardiogram, examined the possible association of type 2 diabetes with both acute intravenous thrombolysis effectiveness and long-term prognosis in this setting., Research Design and Methods: The study included 726 consecutive subjects (214 type 2 diabetic subjects) with STEMI who received intravenous thrombolysis in the first 6 h from index pain and were followed up for 3.5 years., Results: Type 2 diabetic subjects had significantly lower incidence of sustained > or = 50% ST recovery than nondiabetic subjects (P = 0.03). Additionally, the former required a significantly greater time interval through the achievement of this criterion than the latter (P < 0.001). In both type 2 diabetic (P < 0.001) and nondiabetic subjects (P < 0.001), those who had not attained > or = 50% ST recovery were at significantly higher risk of cardiac death than subjects who had reached this criterion. The subjects who attained the above electrocardiographic criterion in > or = 60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in <60 min (P = 0.02). However, this association was true only for type 2 diabetic subjects (P = 0.01) and not for nondiabetic subjects (P = 0.9)., Conclusions: The present study suggests that type 2 diabetes is a strong predictor of acute intravenous thrombolysis failure during STEMI. This finding may significantly contribute to the worse prognosis for type 2 diabetic subjects compared with nondiabetic ones in this setting.

Objectives: To determine the impact of moderate alcohol consumption on long term prognosis after successful coronary stenting, and whether it could be related to preprocedural plasma C reactive protein (CRP)., Design: Part of the prospectively designed GENERATION study which investigated the impact of several biochemical factors, including plasma CRP, on long term prognosis after coronary stenting., Setting: Tertiary referral centre., Patients: 483 consecutive patients with stable or unstable coronary artery disease who underwent successful coronary stenting and were followed for up to four years. Information about alcohol consumption was collected prospectively., Interventions: Successful coronary stenting., Main Outcome Measures: The incidence of the composite end point of readmission to hospital for unstable angina, non-fatal myocardial infarction, or cardiac death, whichever occurred first., Results: By the end of follow up the incidence of the composite end point was 22.8%. Patients with a baseline plasma CRP concentration of < 0.68 mg/dl (defined by ROC analysis) did not show any difference in the composite end point (p = 0.9) or its components, regardless of the amount of alcohol consumed during follow up. However, among patients with plasma CRP concentration of > or = 0.68 mg/dl, those who drank moderately had a lower incidence of the composite end point (p < 0.001) or its components., Conclusions: Moderate alcohol consumption may have a beneficial impact on the long term prognosis following successful coronary stenting. The extent of this effect is positively related to preprocedural inflammatory status. An anti-inflammatory action of moderate alcohol consumption cannot be excluded.

Background: High plasma C-reactive protein (CRP) levels have been associated with an unfavorable outcome in patients with coronary artery disease (CAD), and a direct participation of CRP in the atherosclerotic process has been postulated., Hypothesis: The aim of this study was to evaluate the possible relationship of high plasma CRP levels with the rapid progression of coronary atherosclerosis (RPCAD)., Methods: In all, 194 patients who were readmitted and underwent repeat coronary angiography because of recurrence of symptoms following successful percutaneous coronary intervention were studied. Median angiographic follow-up time was 6 months. Rapid progression CAD was defined as the presence of a new lesion, > 25% in luminal diameter stenosis, in a previously nondiseased vessel, or deterioration of a known, nontreated lesion by at least 25%., Results: By multivariate analysis, patients with high plasma CRP levels upon first admission were at higher risk of RPCAD. In particular, odds ration (OR) = 1.8; 95% confidence interval (CI) = 1.3-3.6; p value = 0.02 in patients with CRP = 0.5-2 mg/dl versus patients with CRP < 0.5 mg/dl, and OR = 7.1; 95% CI = 3.8-9.5; p value < 0.001 in patients with CRP > 2 mg/dl versus patients with CRP < 0.5 mg/dl., Conclusion: Increased plasma CRP levels could possibly identify patients at high risk for the development of RPCAD.

Objectives: The objective of this study was to evaluate the association of high plasma levels of either C-reactive protein (CRP), lipoprotein (a) (Lp[a]) or total homocysteine (tHCY) with the long-term prognosis after successful coronary stenting (CS)., Background: High plasma levels of either CRP, Lp(a) or tHCY may have an impact in coronary artery disease. However, long-term prospective data after coronary stenting (CS) are limited., Methods: Four-hundred and eighty-three consecutive patients with either stable or unstable coronary syndromes were followed for up to three years after successful CS. The composite of cardiac death, myocardial infarction or rehospitalization for rest unstable angina, whichever occurred first, was the prespecified primary end point. Moreover, the one-year incidence of clinical recurrence of symptoms, in-stent restenosis (ISR) and progression of atherosclerosis to a significant lesion (PTSL) were additionally evaluated. PTSL was defined as an increase by at least 25% in the luminal diameter stenosis of a known nonsignificant lesion (or=70% luminal diameter stenosis)., Results: By the end of the follow-up, high plasma levels of either CRP or Lp(a) but not tHCY were independently associated with the primary end point. In particular, CRP >or=0.68 mg/dl (p < 0.001) or Lp(a) >or=25 mg/dl (p = 0.003) conferred a significantly increased risk. By 1 year, a CRP >or=0.68 mg/dl conferred a significantly increased risk for clinical recurrence of symptoms (p < 0.001) or PTSL (p < 0.001). None of the studied biochemical markers was related to ISR., Conclusions: High plasma levels of either CRP or Lp(a) but not tHCY may be associated with a higher incidence of late adverse events after successful CS. PTSL in vessels not previously intervened upon may play a significant role in the underlying pathophysiology as opposed to ISR.

Objectives: Our aim was to present the immediate and intermediate long-term results of the application of retrograde nontransseptal balloon mitral valvuloplasty (RNBMV) in four cooperating centers from Greece and India., Background: RNBMV is a purely transarterial method of balloon valvuloplasty, developed with the aim to avoid complications associated with transseptal catheterization. Only single-center experience with RNBMV has been previously reported., Methods: The procedure was attempted in 441 patients with symptomatic mitral stenosis (320 women, 121 men, mean age [+/-SD] 44+/-11 years, mean echocardiographic score [+/-SD] 7.7+/-2.0) from 1988 to 1996. Three hundred eighty-five patients with successful immediate outcome were followed clinically for a mean [+/-SD] of 3.5+/-1.9 (range, 0.5-9.1) years., Results: A technically successful procedure was achieved in 388 (88%) cases. The echocardiographic score (p < 0.001), male gender (p=0.005), preprocedural mitral regurgitation (p=0.007) and previous surgical commissurotomy (p=0.029) were unfavorable predictors of immediate outcome. Complications included death (0.2%), severe mitral regurgitation (3.4%) and injury of the femoral artery (1.1%). Event-free (freedom from cardiac death, mitral valve surgery, repeat valvuloplasty and NYHA class > II symptoms) survival rates (+/-SEM) were 100%, 96.9+/-0.9%, 89.8+/-1.9% and 75.5+/-5.5% at 1, 2, 4 and 9 years, respectively. The echocardiographic score (p < 0.001), NYHA class (p=0.008) and postprocedural mitral valve area (p=0.009) were significant independent predictors of intermediate long-term outcome., Conclusions: Multicenter experience indicates that RNBMV is a safe and effective technique for the treatment of symptomatic mitral stenosis. As with the transseptal approach, patients with favorable mitral valve anatomy derive the greatest immediate and intermediate long-term benefit from this procedure.

Objective: To assess the contribution of coronary artery ectasia, either isolated or in association with obstructive coronary artery disease, to morbidity and mortality from ischaemic heart disease., Design: A retrospective study of patients undergoing coronary arteriography at a tertiary cardiac centre., Patients and Methods: The epidemiological, clinical, arteriographic, and follow up characteristics of three groups of patients were examined: group A, 172 patients with coronary artery ectasia and coexisting significant coronary artery disease; group B, 31 patients with coronary artery ectasia only; group C, 165 patients with significant coronary artery disease but without ectasia, matched for sex and age with group A., Results: Group A patients had a similar incidence of a previous myocardial infarction to group C patients (61.6% v 64.2%), exercise performance, severity of obstructive lesions (CASS score 2.19 v 2.14), and similar distribution of diseased vessels. At follow up of approximately two years they experienced a similar incidence of unstable angina (7.5% v 4.4%) and myocardial infarction plus cardiac death (4.9% v 6.1%). They underwent bypass surgery with similar frequency (39% v 42%) but there was a lower frequency of percutaneous transluminal coronary angioplasty (5.8% v 17%, P < 0.01). Patients with pure coronary ectasia (group B) had a lower incidence of a previous myocardial infarction (38.7%, 12/31, P < 0.05) than the two other groups. The infarct in all cases was related to an ectatic artery. Their exercise performance and ejection fraction (9 (SD 3) minutes and 56.5(9)%) were higher (P < 0.01) than group A (5 (2) minutes, 48.3(10)%) and group C (5.3 (2) minutes, 49.3(10)%). Group B had no myocardial infarctions, cardiac death, surgery, or intervention at follow up; 4.4% (5/115) developed unstable angina. The incidence of angina at study entry was similar in all three groups (38.7-49.7%)., Conclusions: Coronary artery ectasia does not confer added risk in patients with coexisting obstructive coronary artery disease. Although there is a measurable incidence of previous myocardial infarction, patients with pure ectasia have a good prognosis. The wisdom of giving oral anticoagulants to such patients is questioned.