The impact of treatment with omeprazole on the effectiveness of clopidogrel drug therapy during the first year after successful coronary stenting.

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.

The impact of right ventricular involvement on the postdischarge long-term mortality in patients with acute inferior ST-segment elevation myocardial infarction.

OBJECTIVES: To investigate the long-term impact of right ventricular myocardial involvement (RVI) after acute inferior ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 1208 consecutive patients, who survived to discharge after hospitalization for acute inferior STEMI, were studied. Patients were divided into those with (n = 459) or without (n = 749) of RVI involvement, defined as ST-segment elevation > or =1 mm in V4R. Cardiac death by 3 years was the primary study end point. RESULTS: By the end of follow-up, 207 (17.1%) patients had died. Patients with RVI were at similar risk for death at 3 years than those without (17.6% vs 16.8%, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P = .79). By multivariate Cox analysis, several variables, but not RVI, were associated with the incidence of 3 years cardiac death. CONCLUSIONS: Right ventricular myocardial involvement does not portend any increased risk for long-term mortality, in patients who survived to discharge after hospitalization for acute inferior STEMI.

Multimarker strategy for the prediction of 31 days cardiac death in patients with acutely decompensated chronic heart failure.

BACKGROUND: To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF). METHODS: A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point. RESULTS: A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p<0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point. CONCLUSIONS: In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

The impact of aspirin resistance on the long-term cardiovascular mortality in patients with non-ST segment elevation acute coronary syndromes.

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

Comparison of simvastatin and nicotinic acid administration in alcohol-treated Wistar rats.

INTRODUCTION: Previous studies of ours have shown that simvastatin (S) and nicotinic acid (NA) lower the alcohol (Alc)-induced increase of triglycerides. The aim of this study was to evaluate which drug is more effective and safe in decreasing Alc-induced hypertriglyceridaemia in Wistar rats. METHODS: Male Wistar rats were randomised into 6 groups, which were fed with: (1) olive oil (Oil group, n=10); (2) Oil + Alc, (Alc group, n=10); (3) S solution in Oil (65 microg/100g body weight), (S group, n=10); (4) NA solution in Oil (8.5 mg/100g body weight), (NA group, n=8); (5) S solution in Oil + AIc (S+Alc group, n=10); and (6) NA solution in Oil + Alc (NA+Alc group, n=9). Another 13 male Wistar rats were fed only a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers were removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed. RESULTS: Liver histopathology was similar in all groups and within the normal range. The TG plasma concentration in the Alc group was higher than in the control rats (p < 0.001) or any other groups (Oil, p < 0.001, or S, p < 0.001, or NA, p = 0.003). The Oil, S+Alc, NA+Alc and control groups had similar TG levels, but these were significantly lower compared to the Alc group (p < 0.001). AST plasma concentration was higher in the Alc group compared to controls (p < 0.001), Oil (p < 0.001), S (p < 0.001) and NA (p < 0.001) groups, while the AST concentration in the S+Alc and Na+Alc groups was lower than in the Alc group (p = 0.042, p < 0.001, respectively). CONCLUSIONS: NA and S, two drugs of different classes, seem to decrease Alc-induced secondary hypertriglyceridaemia to the same extent. Moreover, NA displays a better alleviation of Alc-induced AST raises compared to S, although it enhances small increases in AP and ALT levels.

The impact of circulating total homocysteine levels on long-term cardiovascular mortality in patients with acute coronary syndromes.

BACKGROUND: To evaluate the possible independent impact of circulating total homocysteine (tHcy) levels on long-term cardiovascular mortality, in patients with either ST-segment elevation myocardial infarction (STEMI), or non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: A total of 458 STEMI and 476 NSTE-ACS patients who presented consecutively, within the first 12 and 24 h of index pain respectively were studied. Each cohort was divided according to tertiles of circulating tHcy levels upon presentation. Early (30 days) and late (31 days through 5 years) cardiovascular mortality was the predefined study endpoint. RESULTS: There was no difference in the risk of 30-day cardiovascular death among the tertiles of tHcy in patients with STEMI (7.2%, 8.5% and 12.4% for the first, second and third tertiles respectively; p(trend)=0.3) or NSTE-ACS (3.1%, 3.8% and 5.7% for the first, second and third tertiles respectively; p(trend)=0.5). Patients in the upper tHcy tertile were at significantly higher unadjusted risk of late (from 31 days trough 5 years) cardiovascular death than those in the other two tertiles in STEMI (23.4%, 27.9% and 41.8% for the first, second and third tertiles respectively; p(trend) <0.001), and NSTE-ACS (24.7%, 28.1% and 45.6% for the first, second and third tertiles respectively; p(trend) <0.001) cohorts. However, after adjustment for baseline differences, there was no significant difference in the risk of late cardiovascular death among tHcy tertiles in either cohort. When circulating tHcy levels were treated as a continuous variable, they were significantly associated with late cardiovascular death (p<0.001 for both cohorts) by univariate Cox regression analysis, but not by multivariate Cox regression analysis (p=0.8, and p=1 for STEMI and NSTE-ACS cohorts, respectively). CONCLUSIONS: Based on the present data circulating tHcy levels determined upon admission do not serve as an independent predictor of long-term cardiovascular mortality in patients with either STEMI or NSTE-ACS.

The impact of oral antiplatelet responsiveness on the long-term prognosis after coronary stenting.

BACKGROUND: Decreased responsiveness to oral antiplatelet drug therapy has been associated with an adverse outcome after coronary stenting (CS), but more studies are needed. The purpose of the present study was to prospectively evaluate this issue. METHODS: A total of 612 consecutive patients with stable or unstable coronary artery disease who underwent CS after at least 12 hours of aspirin and clopidogrel loading were studied. The study population was divided into responders and nonresponders to oral antiplatelet therapy, according to the values of preprocedural Platelet Function Analyzer-100 (Dade Behring, Marburg, Germany) collagen epinephrine closure time (CEPI-CT). In particular, responders were considered as patients with a CEPI-CT > 193 seconds and nonresponders as those with a CEPI-CT < or = 193 seconds. The 1-year incidence of the composite of cardiac death and rehospitalization for nonfatal myocardial infarction was the prespecified primary study end point. RESULTS: At 1 year, 9.1% of patients reached the primary end point. Nonresponders to oral antiplatelet therapy were at significantly higher risk for the primary end point (18.7% vs 7.6%) than responders. Nonresponsiveness to oral antiplatelet therapy was a predictor of the primary end point by both univariate (hazard ratio 2.7, 95% CI 1.6-4.5, P < .001) and multivariate (hazard ratio 2.5, 95% CI 1.6-3.8, P < .001) Cox regression analysis. CONCLUSION: Based on the present data, preprocedural responsiveness to oral antiplatelet therapy, assessed by Platelet Function Analyzer-100 CEPI-CT, is an independent predictor of long-term outcome after CS.

The impact of hs C-reactive protein and other inflammatory biomarkers on long-term cardiovascular mortality in patients with acute coronary syndromes.

We evaluated whether high circulating levels of serum amyloid A (SAA), fibrinogen, interleukin-6 (IL-6) or leukocytes count (LC), can provide any additional predictive value over that provided by hs C-reactive protein (hs-CRP) for the incidence of 5-year cardiovascular mortality, in 458 and 476 consecutive patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS), respectively. By 5 years the incidence of cardiovascular mortality was 37.3% and 35.5% in patients with STEMI and NSTE-ACS, respectively. Each of the study inflammatory biomarkers conferred independent to clinical risk predictors (and to cardiac troponin I) long-term prognostic information (all p<0.05), but only LC provided additional predictive value over that provided by hs-CRP, in either cohort (p<0.05). By multivariate Cox regression analysis, hs-CRP (p<0.001 for both cohorts) and LC (p=0.009 and p<0.001 for STEMI and NSTE-ACS, respectively) were the only inflammatory biomarkers independently associated with the incidence of 5-year cardiovascular mortality. According to the present results high circulating levels of LC but not of SAA, fibrinogen or IL-6 can provide additional long-term predictive value over that provided by hs-CRP in patients with acute coronary syndromes.

Continuous 12-lead electrocardiographic ST monitoring and long-term prognosis after successful coronary stenting.

BACKGROUND: The possible long-term prognostic value of transient ST ischemic episodes detected by continuous multilead electrocardiographic (ECG) monitoring after successful coronary stenting (CS) has not been thoroughly investigated. METHODS: A total of 739 consecutive patients, who underwent a 24-hour, continuous 12-lead electrocardiographic (ECG) ST monitoring in the first day after successful CS, were studied. An ST ischemic episode was defined as a transient ST shift (depression or elevation) in any lead of > or = 0.10 mV compared with the reference ECG lasting for > or = 1 minute. RESULTS: The incidence of the composite of death, nonfatal myocardial infarction, and recurrent angina by the first year was 28.7%. Patients with > or = 3 (defined by receiver operating characteristics analysis) ST ischemic episodes, detected by continuous 12-lead ECG ST monitoring, were at significantly higher risk for the 1-year composite primary end point than those with either 1 and 2 (52.7% vs 25.7%, hazard ratio [HR] 2.1, 95% CI 1.4-3.7, P < .001) or no (52.7% vs 25%, HR 2.2, 95% CI 1.2-2.9, P < .001) ST ischemic episodes. By multivariate Cox regression analysis, the occurrence of > or = 3 ST ischemic episodes in the first postprocedural day was independently associated with a significant increased risk of the 1-year composite primary end point (HR 1.9, 95% CI 1.4-3.9, P = .002). CONCLUSIONS: The present study suggests that continuous 12-lead ECG ST monitoring in the first day after successful CS may serve as an affordable tool for the identification of patients with an increased risk of fatal or nonfatal ischemic complication during the first year after the procedure.

Continuous 12-lead electrocardiographic ST monitoring adds prognostic information to the thrombolysis in myocardial infarction risk score in patients with non-ST-elevation acute coronary syndromes.

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.

Type 2 diabetes and intravenous thrombolysis outcome in the setting of ST elevation myocardial infarction.

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.

The effect of alcohol and gemfibrozil co-administration in Wistar rats.

INTRODUCTION: The ingestion of alcohol (Alc) as well as gemfibrozil (Gem), a fibrate drug used to treat hypertriglyceridaemia, may occur on a long-term basis in humans. Since both Alc and Gem can disturb liver function, we assessed the effects of administering Alc together with Gem in Wistar rats. MATERIALS AND METHODS: Male Wistar rats were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: i) 2 ml of polyethylene glycol (Peg); group Peg, ii) 2 ml of Peg + 2 ml of 25% v/v pure Alc in water; group Alc + Peg, iii) 2 ml of Gem solution in Peg (3.4 mg/100 g body weight); group Gem +Peg, iv) 2 ml of Gem solution in Peg 2 + 2 ml of Alc; group Gem +Alc +Peg. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks, blood samples were drawn and the livers removed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed. RESULTS: All tube-fed groups had higher body mass index compared to controls (p<0.001). The control group had lower AP compared to Gem+Peg and Gem +Alc+Peg groups (p=0.005 and p=0.018, respectively). The Peg group had lower AP compared to G+Peg (p=0.041). All tube-fed groups had lower ALT compared to controls (p<0.001). The TC levels were lower in tube-fed groups with Gem (Gem +Peg and Gem+Alc +Peg) compared to controls (p=0.002 and p=0.039, respectively). Among the tube-fed groups, the TC level was lower in Gem +Peg compared to Peg and Alc+Peg groups (p=0.047 and p=0.01, respectively). No differences were found among tube-fed groups and control rats in blood AST and TG. Liver histopathology was similar in all groups and within the normal range. CONCLUSION: A moderate amount of Alc daily together with Gem is safe in rats. Peg administration in Wistar rats protects from the Alc-induced TG and AST rises.

Degree of activity at the onset of myocardial infarction and thrombolysis outcome.

BACKGROUND: The aim of this study was to evaluate the possible relationship between the degree of physical activity at the onset of myocardial infarction and thrombolysis outcome. METHODS: A total of 351 consecutive patients, who underwent thrombolysis due to ST elevation acute myocardial infarction, were prospectively studied. Patients were classified into three groups according to a generally accepted scale: group I patients had experienced symptoms during exertion, group II when sitting and group III during sleep or when reclining. RESULTS: There was a significantly increased chance of either intravenous thrombolysis effectiveness or cardiac survival probability with increasing physical activity at the onset of myocardial infarction. In particular, group I patients had a significantly higher incidence of complete ST-segment resolution (P<0.001 for both II vs. I and III vs. I groups) or TIMI 3 flow in the infarct-related artery (II vs. I: P=0.002, and III vs. I: P<0.001) and less compromised left ventricular function (P<0.001 for both II vs. I and III vs. I) by both univariate and multivariate analysis. Moreover, although the degree of physical activity was associated with lower in-hospital (II vs. I: P=0.048, and III vs. I: P=0.01), and cardiac mortality at 39 months (II vs. I: P=0.002, and III vs. I: P<0.001) by univariate analysis, this did not hold true by multivariate analysis. CONCLUSIONS: In conclusion, the degree of physical activity at the onset of myocardial infarction may be positively associated with acute success of intravenous thrombolysis and this may favorably influence short- and long-term cardiac survival.

Postprandial lipemia in hypertension.

OBJECTIVE: Many studies have shown that patients with coronary artery disease have an exaggerated rise and a delayed fall of plasma triglyceride (TG) concentration postprandially. We examined whether patients with essential hypertension have the same response to a fatty meal. METHODS: A fatty meal (350g per 2 m(2) body surface with 83.5% fat) was given to 25 patients with essential hypertension (H) and to 25 normotensives (N). The two groups were matched for age, body mass index, lipid profile, basal glucose and insulin concentrations, and an index of homeostasis model of insulin resistance (HOMA-IR). A quantitative insulin sensitivity check index (QUICKI) was calculated. Blood samples were taken at 0, 4, 6, and 8 hours after the fatty meal. Lipid variables were measured in all samples. Blood glucose and insulin levels were measured in the fasting state. RESULTS: Total and high density lipoprotein cholesterol, apolipoprotein A1 and B, lipoprotein (a), HOMA-IR and QUICKI did not differ significantly over time between the groups. The plasma TG concentration (mg/dL) increased significantly after fat loading in H (from 118 +/- 31 to 284 +/- 137 at 4 hours, 327 +/- 93 at 6 hours and 285 +/- 71 at 8 hours) compared to N group (from 105 +/- 29 to 150 +/- 38 at 4 hours, 148 +/- 40 at 6 hours and 115 +/- 34 at 8 hours), p = 0.001, p < 0.001 and p < 0.001, respectively. CONCLUSION: This study suggests that patients with hypertension have an exaggerated response and delayed clearance of plasma TG concentration after fat loading.

The effect of co-administration of simvastatin and alcohol in rats.

INTRODUCTION: The effect of chronic co-administration of alcohol (Alc) and lipid-lowering drugs on hepatic function has not been extensively evaluated. We studied the effects of administering Alc together with a 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitor [simvastatin (S)]. MATERIALS AND METHODS: Male Wistar rats (8 weeks old) were randomized and divided into 4 groups of 10 each. They were fed (once a day) via a stomach tube with: 1) 2 ml of olive oil; group Oil, 2) with Oil + 2 ml of 25% v/v pure Alc in water; group Alc + Oil, 3) with Oil + S (65 micrograms/100 g body weight); group S + Oil, 4) with Oil + Alc + S; group S + Alc + Oil. Another 13 male Wistar rats were only fed a standard laboratory diet (control group). After 8 weeks blood samples were drawn and the livers were removed. Blood glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), total protein, albumin, total cholesterol (TC) and triglycerides (TG) were measured. Liver histopathology was also assessed. RESULTS: Differences were found between the control group and tube-fed groups in glucose (p < 0.001). No differences were found among tube-fed groups in blood glucose, ALT, total protein, albumin, AP and TC. AST activity was significantly higher in the Alc + Oil than in the Oil or S + Oil groups (p < 0.001 for both comparisons) demonstrating the effect of Alc on AST. The AST did not differ significantly in the Oil or S + Oil groups indicating a lack of effect of S. Furthermore, S significantly reduced the Alc-induced increase in AST (Alc + Oil vs S + Alc + Oil; p = 0.042). The TG concentration was significantly higher in the Alc + Oil group compared to the Oil, S + Oil and S + Alc + Oil groups (p = 0.02). Therefore, S significantly decreased the alcoholinduced increase in TG. Liver histopathology was similar in all groups and within the normal range. CONCLUSION: A moderate amount of Alc daily together with S is safe in rats. Additionally, S administration in Wistar rats diminishes the Alc-induced TG and AST rises.