Uric acid: a cardiovascular risk factor in patients with recent myocardial infarction.

BACKGROUND: To date uric acid (UA) is not considered a cardiovascular risk factor, although evidence about a relationship between UA and cardiovascular diseases has been reported. METHODS: Information from 10,840 patients enrolled in the GISSI-Prevenzione trial was used to evaluate the relationship between UA and risk for total mortality and cardiovascular events (CVE). UA levels were categorized in quintiles, as ≤ 4.5 (Q1), 4.6 to 5.3 (Q2), 5.4 to 6.0 (Q3), 6.1 to 6.8 (Q4) and >6.8 (Q5) mg/dL. Multivariable analysis was used to estimate the relative risks (HR) of outcome measures across categories of UA. The analysis of the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) tests were used to evaluate the incremental prognostic information of UA. RESULTS: During 36,802 person-years of follow-up, 974 deaths and 1120 cardiovascular events occurred. We found a statistically significant association between high UA and total mortality [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.13, 0.267]; Q3 [1.06, 0.619]; Q4 [1.23, 0.063]; Q5 [1.63, <0.0001], test for trend P<0.0001. Similar results were obtained for cardiovascular events [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.12, 0.271]; Q3 [1.19, 0.094]; Q4 [1.25, 0.031]; Q5 [1.38, 0.002], test for trend P=0.0009. The prognostic accuracy of prediction models for CVE was significantly increased by adding UA to classical cardiovascular risk factors (AUC P=0.0041; NRI P=0.0004; IDI P<0.0001). CONCLUSION: High UA may be considered a risk factor for death and CVE.

Wine consumption and risk of cardiovascular events after myocardial infarction: results from the GISSI-Prevenzione trial.

BACKGROUND: To evaluate the association of wine intake with incident cardiovascular events (CVE) and total mortality after myocardial infarction (MI). METHODS: We used prospectively ascertained information among 11,248 Italian patients with recent MI enrolled in the GISSI-Prevenzione Trial. Usual wine consumption has been categorised as never/almost never, up to 0.5L/day, and >0.5L/day. Multiple imputation was used for missing values at baseline and during follow-up. We assessed adjudicated cumulative incidence of major CVE during 3.5years of follow-up and total mortality at long-term follow-up (7.3years), respectively. Multivariate Cox proportional hazards models were fitted to estimate hazard ratios (HR) first using data at baseline and then updated using time-varying covariates. RESULTS: During 37,021 person-years of follow-up, 1168 CVE occurred. Moderate wine intake at baseline was associated with significantly reduced risk of CVE (adjusted HR 0.87; 95% CI 0.76-0.99) as compared with non-drinkers. In time-updated analyses, results were virtually the same, though they were barely statistically not significant (adjusted HR 0.88; 95% CI 0.77-1.00). Wine intake was associated with lower risk of total mortality. In time-updated adjusted analyses, patients with wine consumption up to 0.5L/day (HR 0.83; 95% CI 0.74-0.92) and >0.5L/day (HR 0.77; 95% CI 0.63-0.94) had lower mortality compared with non-drinkers (P for trend=0.0003). CONCLUSIONS: Among patients with established heart disease, moderate consumption of wine seems to be associated with lower incidence of CVE and total mortality as compared with non drinkers.

Global secondary prevention strategies to limit event recurrence after myocardial infarction: results of the GOSPEL study, a multicenter, randomized controlled trial from the Italian Cardiac Rehabilitation Network.

BACKGROUND: Secondary prevention is not adequately implemented after myocardial infarction (MI). We assessed the effect on quality of care and prognosis of a long-term, relatively intensive rehabilitation strategy after MI. METHODS: We conducted a multicenter, randomized controlled trial in patients following standard post-MI cardiac rehabilitation, comparing a long-term, reinforced, multifactorial educational and behavioral intervention with usual care. A total of 3241 patients with recent MI were randomized to a 3-year multifactorial continued educational and behavioral program (intervention group; n = 1620) or usual care (control group; n = 1621). The combination of cardiovascular (CV) mortality, nonfatal MI, nonfatal stroke, and hospitalization for angina pectoris, heart failure, or urgent revascularization procedure was the primary end point. Other end points were major CV events, major cardiac and cerebrovascular events, lifestyle habits, and drug prescriptions. RESULTS: End point events occurred in 556 patients (17.2%). Compared with usual care, the intensive intervention did not decrease the primary end point significantly (16.1% vs 18.2%; hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.74-1.04). However, the intensive intervention decreased several secondary end points: CV mortality plus nonfatal MI and stroke (3.2% vs 4.8%; HR, 0.67; 95% CI, 0.47-0.95), cardiac death plus nonfatal myocardial infarction (2.5% vs 4.0%; HR, 0.64; 95% CI, 0.43-0.94), and nonfatal MI (1.4% vs 2.7%; HR, 0.52; 95% CI, 0.31-0.86). A marked improvement in lifestyle habits (ie, exercise, diet, psychosocial stress, less deterioration of body weight control) and in prescription of drugs for secondary prevention was seen in the intervention group. CONCLUSION: The GOSPEL Study is the first trial to our knowledge to demonstrate that a multifactorial, continued reinforced intervention up to 3 years after rehabilitation following MI is effective in decreasing the risk of several important CV outcomes, particularly nonfatal MI, although the overall effect is small. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00421876.

[Metabolic syndrome: a true syndrome or only a cluster of risk factors?]. / Sindrome metabolica o solo un "cluster" di fattori di rischio?

Although the classical cardiovascular risk factors (such as smoking, hypertension and hypercholesterolemia) are becoming gradually more effectively controlled, a continuous increase of the so-called "cardiometabolic risk" linked to obesity and impaired glycemic control is observed. Starting from the beginning of this century, the definition of the "metabolic syndrome" has become very popular to identify a combination of different factors concurring to increase cardiovascular risk. In the medical literature a controversy does exist concerning this question: is the metabolic syndrome a real syndrome or should it be considered a simple cluster of risk factors? In this synthetic review the analysis of the most recent studies suggests that a) the metabolic syndrome causes an increased cardiovascular risk; b) this risk varies in accordance with the number and characteristics of the diagnostic criteria used; and c) the adjustment for the traditional risk factors lowers but does not eliminate entirely the incremental relative risk attributable to the metabolic syndrome. Whether the risk of metabolic syndrome is greater than the risk attributable to the sum of each component remains to be elucidated. However, the most reliable evidence supports the opinion that the risk prediction associated with this syndrome is not greater than the sum of its parts.

Exploring the gap between National Cholesterol Education Program guidelines and clinical practice in secondary care: results of a cross-sectional study involving over 10 000 patients followed in different specialty settings across Italy.

OBJECTIVES: To evaluate implementation of low-density lipoprotein cholesterol (LDL-C) control recommendations in secondary care and explore key points in the decisional workup. METHODS AND RESULTS: In a nationwide survey of secondary-care outpatients (n=11,124), we studied prevalence/predictors of (1) LDL-C value availability; (2) ongoing treatment with statins; (3) achievement of US National Cholesterol Education Program III target LDL-C values. Agreement between US National Cholesterol Education Program III risk category and physicians' personal risk assessments was also studied. LDL-C values were available for 78% evaluable patients; 71% of the patients with dyslipidema were undergoing treatment with statins; 34% patients undergoing treatment had target LDL-C values. At regression analysis, non-availability of LDL-C values was predicted by absence of diabetes, presence of normotension, and advancing age; lack of statins treatment by female sex, diabetes, overweight and northern location (southern location predicted treatment); non-achievement of target LDL-C values by age, diabetes, attending a diabetic clinic, cigarette smoking, history of cardiovascular disease, and taking less than six pills per day. Physicians provided underestimates of patients' risk (39% high-risk patients were rated as intermediate-risk patients and a further 10% as low-risk patients). CONCLUSION: Suboptimal prevention practice seems to be associated with various factors acting at different levels within the complex process running from individual risk-level ascertainment to LDL-C target achievement. Multicomponent interventions that target the different key steps need to be considered.

Coffee consumption and risk of cardiovascular events after acute myocardial infarction: results from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevenzione trial.

BACKGROUND: The relation between coffee consumption and cardiovascular disease has been studied extensively, but results are still debated. In addition, little evidence is available on patients with established coronary heart disease. METHODS AND RESULTS: Prospectively ascertained information among 11,231 Italian patients (9584 males and 1647 females) with recent (< or = 3 months) myocardial infarction enrolled in the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevenzione trial was used. Usual dietary habits were assessed at baseline and updated at 0.5 and 1.5 years. Coffee consumption was categorized as never/almost never, < 2 cups per day, 2 to 4 cups per day, and > 4 cups per day. Medication use and fasting glucose were assessed at 0.5, 1, 1.5, 2.5, and 3.5 years. Risk was evaluated with Cox proportional hazards with time-varying covariates. The main outcome measure was the cumulative incidence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke). A total of 1167 cardiovascular events occurred during 36,961 person-years of follow-up. After multivariable adjustment for potential confounders in the time-dependent analysis, the relative risk of cardiovascular events across categories of coffee consumption was 1.02 (95% CI 0.87 to 1.20) for < 2 cups per day, 0.91 (95% CI 0.75 to 1.09) for 2 to 4 cups per day, and 0.88 (95% CI 0.64 to 1.20) for > 4 cups per day compared with abstainers (P for trend=0.18). Ultimately, coffee consumption did not change the risk of coronary heart disease events, stroke, and sudden death. CONCLUSIONS: No association between moderate coffee intake and cardiovascular events was observed in post-myocardial infarction patients.

Efficacy of n-3 polyunsaturated fatty acids according to clinical characteristics of patients with recent myocardial infarction: insights from the GISSI-Prevenzione trial.

The GISSI-Prevenzione trial established the efficacy of n-3 polyunsaturated fatty acids (PUFAs) for reducing mortality in patients after recent myocardial infarction. The generalisability of such results to clinical practice could vary according to other individual patient characteristics. We analysed the GISSI-Prevenzione database to assess whether other major risk factors, comorbidities, dietary habits, or medications could interact with the efficacy of n-3 PUFA treatment to reduce total mortality. We found no evidence that concomitant disease states, habits, or interventions altered the therapeutic benefit of n-3 PUFA consumption in survivors of recent myocardial infarction.

High pulse pressure and low mean arterial pressure: two predictors of death after a myocardial infarction.

OBJECTIVES: Although the negative prognostic implication of a clinical history of arterial hypertension in myocardial infarction (MI) survivors is well known, the predictive role of the blood pressure (BP) regimen after MI is not well defined. The aim of this study was to investigate the prognostic significance of different BP indices in post-MI. METHODS AND RESULTS: We evaluated the relationship between baseline systolic, diastolic, pulse and mean arterial pressure (MAP), measured by sphygmomanometry at discharge from hospital or within 3 months of an MI, and total and cardiovascular mortality in 11 116 patients enrolled in the GISSI-Prevenzione trial. Over 3.5 years of follow-up, 999 patients died, 657 of them from cardiovascular causes. Low mean and high pulse pressure were significantly associated with total and cardiovascular mortality after controlling for potential confounders in the multivariate analysis. As compared with patients with less extreme BP values, patients with MAP of 80 mmHg or less (n = 1241; 11.2%) had a 48% higher risk of cardiovascular death [95% confidenceinterval (CI) 1.16-1.87; P = 0.001] and those with pulse pressure greater than 60 mmHg (n = 958; 8.6%) had a 35% higher risk (95% CI 1.09-1.69; P = 0.007); only four subjects (0.04%) had both a high pulse pressure and a low MAP (relative risk of cardiovascular death 3.48; 95% CI 0.48-25.88; P = 0.218). CONCLUSIONS: Our results show for the first time an additional prognostic importance of two easily measurable components of BP, definitely high pulse pressure (> 60 mmHg) and low MAP (< or = 80 mmHg), in a large sample of non-selected patients surviving MI who entered a modern programme of cardiovascular prevention.

GlObal Secondary Prevention strategiEs to Limit event recurrence after myocardial infarction: the GOSPEL study. A trial from the Italian Cardiac Rehabilitation Network: rationale and design.

BACKGROUND: Cardiac rehabilitation programmes are a proven treatment for individuals with recent myocardial infarction, resulting in reduced morbidity and mortality compared to usual care. Unfortunately, following completion of a cardiac rehabilitation programme, risk factors and lifestyle behaviours may deteriorate. The GlObal Secondary Prevention strategiEs to Limit event recurrence after myocardial infarction (GOSPEL) study investigates the benefits of a programme of continued educational and behavioural interventions to achieve optimal long-term secondary prevention goals. DESIGN: This will be a multicentre, randomized, controlled study carried out in 78 Italian cardiac rehabilitation centres. METHODS: After completion of an initial cardiac rehabilitation programme, patients with recent (<3 months) myocardial infarction were randomized to either a long-lasting (over 3 years) multifactorial continued educational and behavioural programme (intensive approach) or usual care (control) group. Intensive approach patients participated in extensive cardiac rehabilitation sessions, monthly from months 1 to 6, then every 6 months for 3 years. Each session consisted of aerobic exercise, comprehensive lifestyle and risk factor counselling, and clinical assessment. Usual care patients returned to their family physicians' care, and attended the reference centre only for the 6-month and then annual scheduled assessment. The efficacy of the two different strategies will be evaluated in terms of morbidity and mortality as primary endpoint. RESULTS: From January 2001 through December 2002, 3241 patients were enrolled. Results will be available in mid 2006. CONCLUSIONS: The GOSPEL trial, the rationale and design of which we present here, was designed to test a new strategy of secondary prevention delivery and to raise standards of long-term secondary prevention in Italy. With a cohort of over 3200 patients, GOSPEL is the largest randomized, multifactorial lifestyle and risk factor intervention trial after myocardial infarction conducted so far.

[Determinants of late-onset heart failure in myocardial infarction survivors: GISSI Prevenzione trial results]. / Determinantes de insuficiencia cardíaca tardía postinfarto de miocardio: resultados del estudio GISSI Prevenzione.

INTRODUCTION AND OBJECTIVES: Improvement in the early phase of myocardial infarction (MI) is associated with a higher rate of late complications, including late-onset heart failure (LHF). The factors predicting LHF are not well understood. Our aims were to identify the factors predicting LHF and to determine the survival rate in these patients. PATIENTS AND METHOD: The GISSI-Prevenzione trial involved 11,323 low-risk patients (NYHA class < or = II) who had had a recent MI (< 3 months). It was a multicenter, open-label, clinical trial of the efficacy of treatment with polyunsaturated fatty acids, vitamin E, both, or neither. Patients with heart failure at baseline and those whose ejection fraction was unknown (n = 2908) were excluded from the present analysis. Late-onset heart failure was defined prospectively as hospital admission due to heart failure. A Cox regression model adjusted for major covariates was used for risk analysis. RESULTS: The study included 8415 patients. During 3.5 years of follow-up, 192 (2.3%) developed LHF. The risk of LHF could be predicted from readily available parameters: age (per year; RR=1.07; 95% CI, 1.05-1.09), ejection fraction (per 1% increment; RR=0.96; 95% CI, 0.94-0.97), heart rate (> or = 74 beats/min; RR=1.62; 95% CI, 1.21-2.16), white blood cell count (> or = 8900 per ml; RR=1.42; 95% CI, 1.05-1.94), diabetes (RR=1.62; 95% CI, 1.17-2.24), hypertension (RR=1.76; 95% CI, 1.33-2.34), peripheral artery disease (RR=2.11; 95% CI, 1.32-3.37), and reinfarction (RR=2.09; 95% CI, 1.28-3.39). LHF was associated with poor survival: (RR=2.34; 95% CI, 1.63-3.36). CONCLUSIONS: The risk of LHF in post-MI patients can be predicted from readily available parameters. LHF was associated with a poor prognosis.

Determinantes de insuficiencia cardíaca tardía postinfarto de miocardio: resultados del estudio GISSI Prevenzione / Determinants of late-onset heart failure in myocardial infarction survivors: GISSI prevenzione trial results

Introducción y objetivos. La mejoría pronóstica de la etapa inicial del infarto conlleva un mayor número de complicaciones a largo plazo. Entre éstas destaca la insuficiencia cardíaca tardía (ICT). Los factores relacionados con la ICT no son del todo conocidos. El objetivo es determinar qué factores pronósticos se relacionan con la ICT y cuál es la supervivencia de estos pacientes. Pacientes y método. El estudio GISSI Prevenzione fue multicéntrico, abierto, aleatorizado y se estudió a 11.323 pacientes postinfarto reciente (< 3 meses) de bajo riesgo (NYHA ≤ II) para evaluar la eficacia del tratamiento con ácidos grasos poliinsaturados, vitamina E, ambos o ninguno. Para este análisis se excluyó a los pacientes con insuficiencia cardíaca durante el ingreso y a aquellos sin determinación de la fracción de eyección (FE) (n = 2.908). La ICT se definió previamente como la necesidad de hospitalización por insuficiencia cardíaca. La predicción de riesgo se realizó con el modelo de Cox ajustado por diversas covariables. Resultados. Se incluyó a 8.415 pacientes. Durante 3,5 años de seguimiento, 192 pacientes (2,3%) desarrollaron ICT. Variables fácilmente asequibles permiten predecir el riesgo de ICT: edad (por año), riesgo relativo [RR] = 1,07; intervalo de confianza [IC] del 95%, 1,05-1,09), FE (por cada 1% de incremento, RR = 0,96; IC del 95%, 0,94-0,97), frecuencia cardíaca ≥ 74 lat/min (RR = 1,62; IC del 95%, 1,21-2,16), recuento de leucocitos ≥ 8.900/ml (RR = 1,42; IC del 95%, 1,05-1,94), diabetes (RR = 1,62; IC del 95%, 1,17-2,24), hipertensión (RR = 1,76; IC del 95%, 1,33-2,34), vasculopatía periférica (RR = 2,11; IC del 95%, 1,32-3,37) e infarto recurrente (RR = 2,09; IC del 95; 1,28-3,39). La ICT presentó mayor mortalidad alejada (RR = 2,34; IC del 95%, 1,63-3,36). Conclusiones. Elementos fácilmente asequibles en la consulta permiten predecir el riesgo de ICT en pacientes postinfarto. La ICT se asocia con un mal pronóstico

Introduction and objectives. Improvement in the early phase of myocardial infarction (MI) is associated with a higher rate of late complications, including late-onset heart failure (LHF). The factors predicting LHF are not well understood. Our aims were to identify the factors predicting LHF and to determine the survival rate in these patients. Patients and method. The GISSI-Prevenzione trial involved 11 323 low-risk patients (NYHA class ≤ II) who had had a recent MI (< 3 months). It was a multicenter, open-label, clinical trial of the efficacy of treatment with polyunsaturated fatty acids, vitamin E, both, or neither. Patients with heart failure at baseline and those whose ejection fraction was unknown (n = 2908) were excluded from the present analysis. Late-onset heart failure was defined prospectively as hospital admission due to heart failure. A Cox regression model adjusted for major covariates was used for risk analysis. Results. The study included 8415 patients. During 3.5 years of follow-up, 192 (2.3%) developed LHF. The risk of LHF could be predicted from readily available parameters: age (per year; RR=1.07; 95% CI, 1.05-1.09), ejection fraction (per 1% increment; RR=0.96; 95% CI, 0.94-0.97), heart rate (≥74 beats/min; RR=1.62; 95% CI, 1.21-2.16), white blood cell count (≥8900 per ml; RR=1.42; 95% CI, 1.05-1.94), diabetes (RR=1.62; 95% CI, 1.17-2.24), hypertension (RR=1.76; 95% CI, 1.33-2.34), peripheral artery disease (RR=2.11; 95% CI, 1.32-3.37), and reinfarction (RR=2.09; 95% CI, 1.28-3.39). LHF was associated with poor survival: (RR=2.34; 95% CI, 1.63-3.36). Conclusions. The risk of LHF in post-MI patients can be predicted from readily available parameters. LHF was associated with a poor prognosisIntroduction and objectives. Improvement in the early phase of myocardial infarction (MI) is associated with a higher rate of late complications, including late-onset heart failure (LHF). The factors predicting LHF are not well understood. Our aims were to identify the factors predicting LHF and to determine the survival rate in these patients. Patients and method. The GISSI-Prevenzione trial involved 11 323 low-risk patients (NYHA class ≤ II) who had had a recent MI (< 3 months). It was a multicenter, open-label, clinical trial of the efficacy of treatment with polyunsaturated fatty acids, vitamin E, both, or neither. Patients with heart failure at baseline and those whose ejection fraction was unknown (n = 2908) were excluded from the present analysis. Late-onset heart failure was defined prospectively as hospital admission due to heart failure. A Cox regression model adjusted for major covariates was used for risk analysis. Results. The study included 8415 patients. During 3.5 years of follow-up, 192 (2.3%) developed LHF. The risk of LHF could be predicted from readily available parameters: age (per year; RR=1.07; 95% CI, 1.05-1.09), ejection fraction (per 1% increment; RR=0.96; 95% CI, 0.94-0.97), heart rate (≥74 beats/min; RR=1.62; 95% CI, 1.21-2.16), white blood cell count (≥8900 per ml; RR=1.42; 95% CI, 1.05-1.94), diabetes (RR=1.62; 95% CI, 1.17-2.24), hypertension (RR=1.76; 95% CI, 1.33-2.34), peripheral artery disease (RR=2.11; 95% CI, 1.32-3.37), and reinfarction (RR=2.09; 95% CI, 1.28-3.39). LHF was associated with poor survival: (RR=2.34; 95% CI, 1.63-3.36). Conclusions. The risk of LHF in post-MI patients can be predicted from readily available parameters. LHF was associated with a poor prognosis

Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids.

BACKGROUND: Sudden death (SD) has a major impact on mortality (M) in patients with left ventricular systolic dysfunction (SyD). In GISSI-Prevenzione, treatment with n-3 polyunsaturated fatty acids (PUFA) reduced M and SD in post-MI patients, but their effect in patients with SyD is unknown. METHODS: 11,323 patients with prior MI and NYHA class < or = II were recruited. After excluding patients with no ejection fraction (EF) measurement (1684), and those with missing data (n=9), 9630 patients were available for analysis. Multivariate Cox regression adjusted models were fitted. RESULTS: Compared to patients with EF > 50%, SyD patients had higher M (12.3% vs. 6.0%) and SD (3.4% vs. 1.4%) rates. PUFA reduced M similarly in patients with (RR 0.76 (0.60-0.96) P=0.02) and without SyD (RR 0.81 (0.59-1.10) P=0.17) (heterogeneity tests P=0.55). In contrast, the effect on SD was markedly asymmetrical: PUFA produced a marked reduction (RR 0.42 (0.26-0.67) P=0.0003) of risk in SyD patients whereas the effect was less evident (RR 0.89 (0.41-1.69) P=0.71) in patients with EF > 50% (heterogeneity tests P=0.07). There was a significant increase in SD with worsening EF (P test for trend=0.02), the benefit on SD in patients with EF < or = 40% being 4-fold higher than in those with EF > 50%. CONCLUSIONS: Increasing SyD is associated with elevated risk of SD and with increasing benefit from PUFA. The effect of PUFA on SD reduction was greater in patients with SyD. Prospective trials testing the effect of PUFA in populations with SyD are required.

Metabolic syndrome and risk of cardiovascular events after myocardial infarction.

OBJECTIVES: We aimed to assess the prevalence and prognostic role of metabolic syndrome (METS) and diabetes in post-myocardial infarction (MI) patients. BACKGROUND: Diabetes is a well known risk factor for patients with previous MI, but glycemic dysmetabolism develops over a protracted period of time. Scanty data are available on the role of METS in patients with previous MI. METHODS: Adjusted Cox's regression models, having diabetes, death, major cardiovascular events (CVE), and hospitalization for congestive heart failure (CHF) during follow-up as outcome events, were fitted on 11,323 patients with prior MI enrolled in the GISSI-Prevenzione Trial. RESULTS: At baseline, 21% and 29% of patients had diabetes mellitus and METS, respectively. The METS patients had a significant (93%) increased risk of diabetes during follow-up. As compared with control subjects, the probability of death and CVE were higher in both METS (+29%, p = 0.002; +23%, p = 0.005) and diabetic patients (+68%, p <0.0001; +47%, p <0.0001), although diabetic but not METS patients were more likely to be hospitalized for CHF (+89%, p <0.0003 and +24%, p = 0.241). Moderate (-6% to -10%) and substantial (>-10%) weight reduction were associated with a significant (18% and 41%, respectively) decreased risk of diabetes. Weight gain was significantly associated with increased risk of diabetes. The risk conferred by METS and diabetes tended to be higher among women. CONCLUSIONS: In patients with MI, METS and diabetes were highly prevalent and are associated with increased risk of death and CVE. Diabetes is also associated with increased risk of hospitalization for CHF. Weight reduction significantly decreased the risk of becoming diabetic in patients with METS.

Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction.

BACKGROUND: Inflammation has a pathogenetic role in acute myocardial infarction (MI). Pentraxin-3 (PTX3), a long pentraxin produced in response to inflammatory stimuli and highly expressed in the heart, was shown to peak in plasma approximately 7 hours after MI. The aim of this study was to assess the prognostic value of PTX3 in MI compared with the best-known and clinically relevant biological markers. METHODS AND RESULTS: In 724 patients with MI and ST elevation, PTX3, C-reactive protein (CRP), creatine kinase (CK), troponin T (TnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assayed at entry, a median of 3 hours, and the following morning, a median of 22 hours from symptom onset. With respect to outcome events occurring over 3 months after the index event, median PTX3 values were 7.08 ng/mL in event-free patients, 16.12 ng/mL in patients who died, 9.12 ng/mL in patients with nonfatal heart failure, and 6.88 ng/mL in patients with nonfatal residual ischemia (overall P<0.0001). Multivariate analysis including CRP, CK, TnT, and NT-proBNP showed that only age > or =70 years (OR, 2.11; 95% CI, 1.04 to 4.31), Killip class >1 at entry (OR, 2.20; 95% CI, 1.14 to 4.25), and PTX3 (>10.73 ng/mL) (OR, 3.55; 95% CI, 1.43 to 8.83) independently predicted 3-month mortality. Biomarkers predicting the combined end point of death and heart failure in survivors were the highest tertile of PTX3 and of NT-proBNP and a CK ratio >6. CONCLUSIONS: In a representative contemporary sample of patients with MI with ST elevation, the acute-phase protein PTX3 but not the liver-derived short pentraxin CRP or other cardiac biomarkers (NT-proBNP, TnT, CK) predicted 3-month mortality after adjustment for major risk factors and other acute-phase prognostic markers.

[Clinical trials with rosuvastatin: efficacy and safety of its use]. / Studi clinici con rosuvastatina: efficacia e sicurezza d'uso.

Cardiovascular diseases remain the leading cause of mortality and morbidity in the western countries. Statins have greatly improved the treatment of dyslipidemias in primary and secondary prevention. Rosuvastatin is a new statin with a high efficacy in reducing LDL cholesterol levels with a good safety profile. At present data about efficacy on mortality and morbidity of this statin are not available; but a very large program of clinical trials, named GALAXY, with over 20,000 subjects in 30 countries, is ongoing. The high capacity of rosuvastatin of lowering LDL cholesterol at usual starting dose of 10 mg is a very interesting characteristic of this molecule, as it helps in reducing the need for dose titration in many patients. Rosuvastatin 10 mg reduces LDL cholesterol levels by 46.7-48.1% vs a reduction of 36.4% with atorvastatin 10 mg, 35.7% with simvastatin 20 mg, and 27.1% with pravastatin 20 mg. Dose-ranging trials have documented that reductions of LDL cholesterol increase with higher doses of rosuvastatin. The STELLAR trial (with rosuvastatin in the range of 10-80 mg vs atorvastatin 10-80 mg, simvastatin 10-80 mg and pravastatin 10-40 mg in 2431 patients) demonstrated that the mean proportional reduction achieved with rosuvastatin at various doses was greater than the one obtained with comparators. Rosuvastatin is also better than other statins in achieving the target level of LDL cholesterol recommended by the recent guidelines. The proportion of patients reaching the goal is 82% with 10 mg and it raises to 89% with 40 mg of rosuvastatin. The proportion of subjects reaching LDL cholesterol levels < 100 mg with different doses of rosuvastatin is significantly higher (p < 0.002) than the one obtained with atorvastatin at the same doses and simvastatin or pravastatin at the same or higher doses. The safety data of rosuvastatin in the dose range of 10-40 mg are similar to the ones achieved by the other statins, therefore, considering the superior efficacy of rosuvastatin in reducing the LDL cholesterol levels, the risk-benefit profile of this new molecule seems very promising.

Variations in lipoprotein levels after myocardial infarction and unstable angina: the LATIN trial.

BACKGROUND: The aim of this study was to prospectively evaluate the magnitude of the variations in lipid levels in a large population of patients admitted for acute myocardial infarction (MI) and unstable angina (UA). Clinical data and blood samples were prospectively collected from consecutive patients with MI and UA. METHODS: The study population consisted of patients with symptoms lasting < or = 12 hours (for MI) or with the last episode of rest pain within 12 hours and associated with ECG changes (for UA). The exclusion criteria were recent hospitalization for any reason or current treatment with lipid-lowering drugs. Blood samples were obtained at admission, the following morning, at discharge and after 3 months. Samples were centrifuged immediately and 4 aliquots of serum were stored at -20 degrees C. The measurements were performed centrally. RESULTS: We enrolled 1864 patients (1275 with MI and 589 with UA). Serum levels of total and LDL-cholesterol decreased significantly after admission, both in MI and UA patients. After 3 months, serum levels of total cholesterol returned to baseline, while those of LDL-cholesterol were still significantly lower. Between admission and the following morning, total and LDL-cholesterol decreased significantly by 7 and 10% respectively for MI and by 5 and 6% for UA. Lipid measurements not performed at admission accounted for a significant decrease in the number of patients identifiable as hyperlipidemic and suitable for lipid-lowering treatment (18% of MI patients and 11% of UA patients). CONCLUSIONS: Serum cholesterol concentrations drop significantly during hospitalization for an acute coronary syndrome after a few hours from admission to the coronary care unit. Lipid profile assessment should be scheduled at admission in order to correctly identify hyperlipidemic patients.

Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.

BACKGROUND: Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction. METHODS AND RESULTS: In this study, 11 323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths. CONCLUSIONS: The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.