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To investigate the prognostic value of circulating levels of asymmetric dimethylarginine (ADMA) in patients with acute decompensation of (New York Heart Association (NYHA) class III/IV) chronic heart failure and reduced left ventricular ejection fraction.Single-centre prospective observational study.Tertiary referral centre.A total of 651 consecutive and eligible hospitalised patients were studied. Patients were divided into four groups according to the quartiles of circulating levels of ADMA upon presentation.Incidence of in-hospital (or 7-day in the case of prolonged hospitalisation), 31-day and 1-year cardiac mortality were the pre-specified study end points.Cumulative rates of in-hospital, 31-day and 1-year cardiac mortality were 10.6%, 18.7% and 36.4%, respectively. There was a gradual increased risk of in-hospital (p(for trend)=0.011), 31-day (p(for trend)=0.044) and 1-year (p(for trend)0.001) mortality with increasing ADMA quartiles. After adjustment for possible confounders, patients at the highest ADMA quartile were at significantly higher risk for in-hospital (p=0.042), 31-day (p=0.032) and 1-year (p0.001) mortality than those in the lowest quartile.According to the present results, an elevated circulating level of ADMA is a strong independent predictor of short-term and long-term mortality in patients with acute decompensation of NYHA class III/IV chronic heart failure and reduced left ventricular ejection fraction. ADMA levels upon presentation may confer enhanced risk stratification in this setting.

Objectives: The possible independent effect of mild-to-moderate anemia (hemoglobin value not Methods: A total of 725 consecutive hospitalized patients were studied. All-cause mortalities during hospitalization and by day 31 were the prespecified study end points. Results: A total of 76 (10.5%) and 133 (18.3%) patients died during hospital stay and by day 31 of follow-up, respectively. Patients in the first hemoglobin tertile were at a significantly higher risk of death than those in the second (p = 0.003 and p < 0.001 for unadjusted in-hospital and 31-day mortality, respectively) or third terile (p < 0.001 and p < 0.001, for unadjusted in-hospital and 31-day mortality, respectively). However, after adjustment for concomitant baseline comorbidities and biochemical parameters, there was no significant difference in the risk of death among hemoglobin tertiles. Conclusions: Mild-to-moderate anemia seems not to contribute independently to short-term mortality in patients with decompensation of NYHA class III/IV chronic heart failure. An adverse concomitant baseline risk profile may have a key role in the induction of mild-to-moderate anemia and in the increased risk of death in these patients.

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).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.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 (p0.001). 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 (p0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p0.001) and hs-CRP (p=0.02) were independent predictors of the study end point.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.

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.

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. Intern Med

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).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.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 (p0.001 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).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.

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.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-CT193 seconds and nonresponders as those with a CEPI-CTor = 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.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.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.

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

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.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 ofor = 0.10 mV compared with the reference ECG lasting foror = 1 minute.The incidence of the composite of death, nonfatal myocardial infarction, and recurrent angina by the first year was 28.7%. Patients withor = 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 ofor = 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).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.

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 ≥ 0.10 mV compared with the reference ECG, lasting for ≥l 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

Increased creatine kinase-MB isoenzymes after coronary stenting are common, and many studies have suggested an association of this increase with an adverse long-term prognosis. How such postprocedural creatine kinase-MB release affects long-term prognosis remains unclear. Whether any actual causal relation exists remains unanswered.

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 ≥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 ≥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 ≥60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in 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.

maintaining near-normal glycemia. 5 Group B patients were treated using the usual protocols, with oral hy- poglycemic drugs or 2 daily doses of intermediate- acting insulin. Supplementary small doses of short- acting insulin were administered subcutaneously only if glucose levels were 250 mg/dl. Mean daily plasma glucose levels were assessed in each patient in both groups by employing all the measured glucose values obtained during the study. The mean glucose level in the conservative treatment group was assessed by the 3 standard preprandial glucose values (at 7 A.M., 1 P.M., 6 P.M.), 1 measurement at 12 A.M. hours and any additional measurements that were performed accord- ing to the discretion of the attending physician. All patients were treated with an optimal antianginal reg- imen. Complete 2-dimensional, spectral, and color-fl ow Doppler echocardiographic examinations were per- formed by 2 examiners not involved in the fi nal anal- ysis of data, with a Hewlett-Packard Sonos 1000 Ul- trasound Machine (Andover, Massachusetts) with a 2.5-MHz transducer, while the patients were asymp- tomatic. Images were obtained within 3 hours from ad- mission and 72 hours later and stored on high-quality videotapes for later blinded analysis. A DI designed to determine the combined systolic and diastolic myocar- dial performance, and defi ned as the sum of isovolumet- ric contraction time plus isovolumetric relaxation time divided by ejection time, was estimated from LV outfl ow and mitral infl ow velocity patterns ((IVCT IVRT)/ ET).6 Videotape recordings were analyzed by 1 investi

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 (≤50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (≥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 ≥0.68 mg/dl (p 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.

Angiographic studies support an association between troponin elevation, intracoronary thrombus, and presumed embolization, but previous studies have indicated that only 20% to 25% of patients with positive troponin levels had angiographic evidence of intracoronary thrombus compared with 5% of patients who were troponin negative. 1–3 Although there already exists an association, 75% to 80% of patients with increased troponin levels had no evidence of intracoronary thrombus. It has been previously shown that the angiographic morphology of the culprit lesion in unstable angina pectoris (UAP) or non–Q-wave acute myocardial infarction (AMI) is characteristic, with 50% to 70% of patients having an acute coronary or complex lesion, which is the angiographic correlate of a disrupted or fi ssured atherosclerotic plaque and/or the presence or intracoronary thrombus. 4,5 This lesion is uncommon in culprit lesions from patients presenting with symptoms of stable angina. Therefore, it was hypothesized that this lesion classifi cation system might represent a more sensitive method for examining the association between elevated troponin and the presence of intracoronary thrombus.

BACKGROUND: Many clinical and laboratory observations give support to the hypothesis that strict metabolic control by insulin infusion during acute coronary events may improve the ischemic damage and prognosis. HYPOTHESIS: We investigated the impact of intensive insulin treatment on fibrinolytic parameters during an acute ischemic myocardial event (unstable angina or acute myocardial infarction) in patients with type 2 diabetes mellitus. METHODS: The study group consisted of 48 type 2 diabetic patients, of whom 24 were randomized to conventional therapy plus intensive insulin treatment (Group 1) and 24 to conventional therapy only (Group 2). The two groups were comparable according to gender, age, body mass index, waist:hip ratio, duration of diabetes, previous antidiabetic treatment, type of ischemic events, concomitant therapy, and the classic risk factors for coronary disease. Insulin-treated patients were excluded from the study. Plasma levels of fibrinogen, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) were measured on admission and discharge. Fibrinogen (fibr) was measured using the photometric method. PAI-1 and t-PA were measured by enzyme-linked immunosorbent assays. RESULTS: T-PA increased in both groups during hospitalization (t-PA(admission) vs. t-PA(discharge): Group 1: 15.42 +/- 4.4 ng x ml(-1) vs. 21.2 +/- 5.74 ng x ml(-1), p = 0.000037; Group 2: 14.47 +/- 6.31 ng x ml(-1) vs. 19.18 +/- 6.88 ng x ml(-1), p = 0.001). On the other hand, fibr and PAI-1 levels increased remarkably in controls (Group 2, fibr(admission) vs. fibr(discharge): 2.98 +/- 1.04 g x l(-1) vs. 3.59 +/- 1.01 g x l(-1), p = 0.002, and PAI-1admission vs. PAI-1 discharge: 30.6 +/- 17.34 ng x ml(-1) vs. 40.62 +/- 23.48 ng x ml(-1), p = 0.003). This finding was not observed in the intensive insulin treatment group (Group 1, fibr(admission) vs. fibr(discharge): 2.87 +/- 0.73 g x l(-1) vs. 2.67 +/- 0.72 g x l(-1), p = 0.101, and PAI-1 admission vs. PAI-1 discharge: 30.75 +/- 15.81 ng x ml(-1) vs. 27.75 +/- 6.43 ng x ml(-1), p = 0.484). CONCLUSION: Intensive insulin treatment during an acute coronary event improves fibrinolytic profile in patients with diabetes mellitus. This is a possible mechanism for the reduced short- and long-term mortality in diabetic patients treated with intensive insulin treatment protocol.

A 58-year-old man with no history of cardiac diseases or cardiovascular risk factors was stung by honeybees. Soon after, he gradually developed signs of an allergic reaction followed by severe retrosternal pain. Electrocardiographic, echocardiographic evidence and positive biochemical markers were consistent with an acute anterolateral myocardial infarction. Coronary arteriography showed a left anterior descending artery thrombotic lesion. This is a case of Kounis syndrome, which is the concurrence of acute coronary syndromes with conditions associated with mast cell activation including allergic or hypersensitivity reactions as well as anaphylactic or anaphylactoid insults. The clinical implications and pathophysiology of this dangerous association are discussed.

It has been reported that increased levels of C-reactive protein are related to adverse long-term prognosis in the setting of ST-segment elevation acute myocardial infarction (MI). In previous studies, the timing of C-reactive protein determination has varied widely. In the present study, serial high-sensitivity C-reactive protein (hsCRP) measurements were performed to investigate if any of the measurements is superior regarding long-term prognosis. A total of 861 consecutive patients admitted for ST-segment elevation MI and treated with intravenous thrombolysis within the first 6 hours from the index pain were included. HsCRP levels were determined at presentation and at 24, 48, and 72 hours. The median follow-up time was 3.5 years. New nonfatal MI and cardiac death were the study end points. By the end of follow-up, cardiac death was observed in 22.4% and nonfatal MI in 16.1% of the patients. HsCRP levels were found to be increasing during the first 72 hours. Multivariate Cox regression analysis demonstrated that hsCRP levels at presentation were an independent predictor of the 2 end points (relative risk [RR] 2.8, p = 0.002, and RR 2.1, p = 0.03, for MI and cardiac death, respectively), while hsCRP levels at 24 hours did not yield statistically significant results (RR 1.4, p = 0.40, and RR 1.1, p = 0.80, for MI and cardiac death, respectively). The corresponding RRs at 48 hours were 1.2 (p = 0.5) for MI and 3.2 (p = 0.007) for cardiac death and at 72 hours were 1.6 (p = 0.30) for MI and 3.9 (p

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 ≥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.

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 ≤ 193 sec). Results Aspirin resistants were younger (p-value = 0.04), and less frequently hypertensives (p-value = 0.05) or diabetics (p-value = 0.04) than aspirin sensitives. By 1 y, the incidence of cardiovascular deaths in the entire cohort was 12.9% (64/496), and aspirin resistants were at significantly higher risk of cardiovascular death (23.1% versus 9.6%; hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.6–4.3; p-value < 0.001), than aspirin sensitives. By multivariate Cox regression analysis, aspirin resistance (a PFA-100 CEPI-CT ≤ 193 sec) was among the most potent predictors of the 1-y incidence of cardiovascular death (HR = 2.8; 95% CI = 1.7–4.6; p-value < 0.001). Conclusion According to the present data, aspirin resistance, assessed by the PFA-100, is an independent predictor of long-term cardiovascular mortality in patients with NSTE-ACS. Copyright © 2009 Wiley Periodicals, Inc.

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).Prospective observational study in a tertiary referral centre.786 consecutive patients with STEMI, who received intravenous thrombolysis in the first 6 h from index pain.The incidence of failed thrombolysis and of cardiac death by 30 days. Failed thrombolysis was defined as the absence of abrupt and sustainedor =50% ST-segment recovery in the first 90 min after the initiation of intravenous thrombolysis.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, p0.001 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; p0.001 for highest vs middle third; 2.6, 2.1 to 3.5, p0.001 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.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.

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend)0.001 for the 2 groups). A plasma CRP value ofor = 5 andor = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.

We evaluated the possible association of the serum levels of C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, and cardiac troponin I (cTnI) with the presence of complex angiographic characteristics throughout the coronary artery tree in 519 consecutive patients with non-ST-elevation acute myocardial infarction (NSTEMI). Blood samples were obtained in the first 12h of NSTEMI invasion and all patients underwent in-hospital coronary angiography. Coronary lesions were classified as complex lesion (CL) or non-CL according to Ambrose criteria. Serum levels of CRP (p0.001), SAA (p0.001), or fibrinogen (p=0.001), but not of cTnI (p=0.9), were significantly related to the presence of multiple (or =2) CLs. On the contrary, serum levels of cTnI (p0.001), but not of CRP (p=0.5), SAA (p=0.9), or fibrinogen (p=0.9), were significantly associated with the severity of coronary artery disease. The results of the present study suggest that elevated levels of inflammatory biomarkers are associated with a generalized activation of coronary artery tree while elevated cTnI levels are associated with the severity of coronary artery disease in the setting of NSTEMI. It seems that inflammatory biomarkers and cTnI reflect different aspect of the process involved in unstable coronary artery disease.

Diabetes mellitus (DM) is known to cause increased arterial wall stiffness and increased cardiovascular risk, even in the absence of hypertension. This study was designed to investigate whether use of an angiotensin-converting enzyme (ACE) inhibitor may improve arterial stiffness in normotensive diabetics, using pulse wave velocity (PWV) as a surrogate marker.We studied 42 patients (26 with type 2 DM, aged 56.5 +/- 9 years, 16 with type 1 DM, aged 41.5 +/- 11 years) by measuring PWV at baseline (compared to 15 age- and gender-matched normal subjects) and after 6 months of treatment with perindopril (4 mg/d).At baseline, PWV was significantly higher in DM patients versus controls (13.09 +/- 2.59 v 9.5 +/- 1.6 m/sec, respectively, P.001). After 6 months, PWV decreased significantly to 11.68 +/- 3.08 m/sec (P.003) for the whole DM group. However, the results were driven by the change in the younger type 1 DM (from 12.59 +/- 1.59 to 10.35 +/- 2.21 m/sec, P.001), whereas in the type 2 DM it was insignificant (from 13.37 +/- 3.0 to 12.42 +/- 3.28 m/sec). Blood pressure and other hemodynamic and biochemical parameters remained unchanged.The results demonstrate that ACE inhibition can improve arterial elasticity and hence risk of cardiovascular complications even in normotensive diabetics. This short treatment was effective only in younger patients with type 1 diabetes, suggesting that early initiation of therapy before the onset of advanced structural alterations is likely to be more cardioprotective.

Previous studies have shown an incremental role of inflammation in late prognosis following coronary stenting (CS). In particular, high preprocedural levels of plasma C-reactive protein (CRP) have been related to increased hazard of late ischemic complications. Persistent Chlamydia pneumoniae (Cp) infection, detected by positive IgA anti-Cp titers, may be associated with this inflammatory process and portend a high risk of late adverse prognosis after CS.A total of 483 consecutive patients with either stable or unstable coronary syndromes were followed-up for 1 year after successful CS. The composite of cardiac death, myocardial infarction, rehospitalization for rest-unstable angina, and exertional angina, whichever occurred first, was the clinical end point. Additionally, the rate of in-stent restenosis and progression of coronary artery disease during this period were evaluated. Anti-Cp titers and plasma CRP levels were measured before the procedure.Positive immunoglobulin A (IgA), but not positive immunoglobulin G (IgG), titers were significantly associated with high plasma CRP levels in patients with unstable coronary syndromes (P =.005), but not in those with stable angina (P =.7). Moreover, positive IgA titers were significantly related to increased risk of both the composite clinical end point (P =.04) and progression of coronary artery disease (P.001) in patients with unstable coronary syndromes but not in those with stable angina. Neither positive IgA nor positive IgG titers were associated with the rate of in-stent restenosis.Persistent Cp infection may drive an inflammatory response in the coronary vasculature and portends an adverse late outcome after CS in patients with unstable coronary syndromes.

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

In conclusion, high plasma CRP levels are associated with more myocardial ischemia early in primary UAP. Although the underlying mechanisms are not well understood, these data could have important pathophysiologic and clinical implications. Whether the increased CRP represents a marker either for the extent of atherosclerosis or an inflammatory process in the coronary arteries or directly exerts a pro-inflammatory or prothrombotic effect on the vessel wall leading to the increased ischemia is currently unknown.

OBJECTIVES: This study tested the impact of intensive metabolic treatment with insulin on transient myocardial ischaemia detected with continuous 12-lead ST-segment monitoring during non-ST segment elevation acute coronary syndromes in type 2 diabetic patients. METHODS AND RESULTS: The study included 57 type 2 diabetic patients with non-ST segment elevation acute coronary syndromes.Twenty-eight patients randomized to conventional treatment plus intensive insulin therapy (group A) and twenty-nine to conventional therapy only (group B). Group A patients received insulin by infusion for 48 hours according to a predefined protocol aiming to maintain normoglycaemia. Group B patients received standard coronary care unit treatment. The ST-segment monitoring was performed for 48 hours in the coronary care unit. The two groups were comparable in terms of medical history, clinical and biochemical data. Three patients from both groups were excluded from the analysis because there was objective evidence for evolution in persistent ST-segment elevation acute myocardial infarction. Six patients (24%) from group A vs. twelve from group B (46.2%) had evidence of transient ischaemia (p = 0.098). Group A patients showed significantly lower values in the mean number [group A vs. group B: 0.4 +/- 0.8 vs. 2 +/- 3.1, p < 0.01] and total duration of ST-episodes [group A vs. group B: 2.4 +/- 5.1 vs. 21.2 +/- 31 min, p < 0.01]. Multivariate analysis revealed that the mean plasma glucose during the study period was a powerful predictor of the presence (b:0.377,p < 0.01), the number (b:0.523,p < 0.001) and the total duration (b: 0.686, p < 0.001) of ST-episodes, respectively. CONCLUSIONS; Intensive insulin treatment considerably decreases the number and the total duration of ST-episodes in type 2 diabetic patients suffering from non-ST segment elevation acute coronary syndromes.

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).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.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=50% luminal diameter stenosis) that was located in a nonintervened vessel at restudy, resulting in an angiographically significant lesion (or=70% luminal diameter stenosis).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, CRPor=0.68 mg/dl (p0.001) or Lp(a)or=25 mg/dl (p = 0.003) conferred a significantly increased risk. By 1 year, a CRPor=0.68 mg/dl conferred a significantly increased risk for clinical recurrence of symptoms (p0.001) or PTSL (p0.001). None of the studied biochemical markers was related to ISR.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.

The aim of this study was to investigate the possible association of plasma C-reactive protein (CRP) levels with the presence of angiographically multiple complex lesions (CLs) in patients with primary unstable angina (PUA). For the purpose of this study, 228 consecutive patients with PUA who underwent in-hospital catheterization were evaluated. Plasma CRP levels were measured upon patients’ admission. Coronary plaques were classified as CL or non-CL according to Ambrose's criteria. There were 100 (43.9%) patients with no or one CL (⩽1) and 128 (56.1%) patients with multiple CLs (⩾2). Tertiles of plasma CRP levels upon admission were significantly associated with the number of CLs on angiographic studies. In particular there was a significant gradual increase in either the number of CLs, or the presence of apparently thrombus-containing CLs with increasing of CRP tertiles. By multivariate analysis CRP was independently associated with the presence of either multiple CLs (R.R.=1.8, 95%CI=1.5–2.2, P

We compared the effectiveness of serial snapshot ECGs (S-ECG) and continuous 12-lead ST-segment ECG monitoring (C-ECG) for the prediction of intravenous thrombolysis outcome in 786 patients with ST-segment elevation myocardial infarction. It was found that S-ECG overestimated thrombolysis success over C-ECG by 7.1%. By 1-year patients who were diagnosed as having successful thrombolysis by S-ECG but not by C-ECG were at significantly higher risk of 1-year cardiac death than those who were classified as having successful thrombolysis by both ECG methods, and were at similar risk of 1-year cardiac death than those who were classified as having failed thrombolysis by both ECG methods.

Stent prosthesis is a high efficacious method with low complication rates. However, the ideal adjunctive therapy following stent implantation remains controversial. The authors compared the effectiveness and complication rates of aspirin-ticlopidine antiplatelet therapy vs anticoagulant therapy with acenocoumarol within 30 days following stent prosthesis. They prospectively studied 404 patients following stent prosthesis while randomly receiving anticoagulant (Group A: 201 patients) vs antiplatelet treatment (Group B: 203 patients). Groups A and B were similar in demographic data (age, gender), stent location, clinical presentation, indication of stenting, and type of implanted stent. Chi-square test, t test, and Wilcoxon test for two samples were used for statistical analysis of the results. Stent implantation was attempted in 434 cases. This was successful in 70/85 (82%) of the bailout, 122/135 (90%) of the suboptimal, and 212/214 (99%) of the elective cases. In 201 patients anticoagulant treatment with acenocoumarol was administered for 4 weeks (group A), while 203 received antiplatelet treatment with ticlo pidine (group B). The need for reintervention was less and total cardiac events were fewer in group B than in group A: three (1.5%) and nine (4.4%) vs 18 (9%) and 29 (14.4%), p < 0.0008 and p < 0.006 respectively. Hemorrhagic complications and total noncardiac events were fewer in group B than in group A: six (3%) and six (3%) vs 18 (9%) and 19 (9.5%), p < 0.01 and p < 0.007 respectively. The length of hospital stay was shorter in group B than in A, p < 0.0001. In conclusion, in this study of intracoronary stenting the authors had a high success rate in 434 attempted cases. Antiplatelet therapy was accompanied by fewer cardiac and noncardiac 1 month events when compared with anticoagulant therapy, supporting its role as the adjunctive treatment of choice post- stenting for the time being.

Early resolution of ST-segment elevation is associated with enhanced clinical outcome following ST elevation myocardial infarction (STEMI). According to previous studies, the incidence of successful reperfusion following STEMI treated with thrombolytic regimen is similar for type 2 diabetic subjects and nondiabetic subjects as assessed by “snapshot” electrocardiographic or angiographic criteria (1). Nevertheless, type 2 diabetic subjects thrombolysed because of STEMI still seem to fare worse, manifesting impaired left ventricular function or long-term prognosis (2). The aim of this prospective study was to test the hypothesis that type 2 diabetic subjects may have a protracted …

Background High plasma levels of C-reactive protein (CRP) are associated with shortor long-term ischemic complications in patients with unstable coronary artery disease. However, a possible direct relationship of plasma CRP with spontaneous myocardial &hernia early I” the course of non ST elevation acute coronary syndromes (NSTACS) was not thoroughly investigated. MethodsTo evaluate this issue 172 consecutive patients with NSTACS with no elevated plasma cardiac troponin T levels upon admission (cTnT-zO.1 yojdl) who underwent a 24 hour continuous IBlead electrocardiographic (ECG) monitoring were studied. The associatlon of plasma CRP levels upon admission with either the incidence or duration of the recorded myocardial ischemla (ST-segment shifts) was evaluated. Patients divided into three groups according to the tertiles of CRP values upon admission. Results During 3,696 hours of contmuous 12.lead ECG monitoring, 169 ST-segment shifts were recorded in 48 patients with a mean number of 3.5k2.0 shifts per patient and a mean duration of 29.6i23.6 min per episode, corresponding to a total duration of 124.4k143.6 mm per patlent. There was a significant gradual increased risk for either the incidence (p