Interleukin 1 gene cluster, myocardial infarction at young age and inflammatory response of human mononuclear cells.

The objective was to investigate whether genotypes, haplotypes and haplotype-pairs of interleukin (IL) gene cluster are associated with risk of Myocardial Infarction (MI) at young age and with the release of IL-1B and expression of tissue factor pro-coagulant activity (TFPCA), after stimulation in vitro with lipopolysaccharide (LPS) of human peripheral blood mononuclear cells (PBMCs). Patients with MI at young age, frequency-matched for age, sex and recruitment centre, with healthy population-based controls and PBMCs from healthy volunteers were studied. Five single nucleotide polymorphisms (SNPs), identifying two haplotype-blocks, in IL-1B gene and one SNP in IL-1A and IL-RA genes were genotyped. In multivariate analyses, haplotype A2 (122) and A4 (112) were associated with decreased risk of MI [OR = 0.62 (95% CI = 0.40-0.95), p = 0.01; OR = 0.69 (95% CI = 0.51-0.92), p = 0.03, respectively]. Haplotype-pair A2/A2 showed significant reduction in the risk of MI [OR = 0.38 (95% CI = 0.18-0.81); p = 0.01]. Haplotype A2 and A4 were associated with lower levels of IL-1B (respectively p = 0.01; p = 0.04, multivariate analysis) and haplotype-pair A2/A4 showed decreased levels of IL-1beta (p = 0.02). No association was found between block "B" IL-1B haplotypes or IL-1A and IL-RA polymorphisms and risk of MI. IL-1B haplotypes influence the inflammatory response of human mononuclear cells to LPS and affect the risk of MI at young age.

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.

Non-pharmacological control of plasma cholesterol levels.

The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Low plasma levels of brain natriuretic peptide in severe acute heart failure: merely a case?

Brain natriuretic peptide (BNP) is commonly used for diagnosis and prognosis of patients with congestive heart failure (HF). High levels of BNP are associated with high probability of cardiogenic dyspnea and higher risk of subsequent cardiovascular events. We describe a case of acute HF (worsening chronic HF) in a 74-year-old male with low plasma BNP levels on admission, in whom a rapid and consistent increase in the marker's concentration occurred after administration of diuretics and vasodilators, despite a prompt clinical and hemodynamic improvement. Reports of cardiogenic dyspnea with moderate increase or normal plasma levels of BNP have been recently published: does this signify a pitfall for BNP as a useful diagnostic and prognostic tool? Clinical implications of our observation are discussed, and we conclude that neurohumoral biomarkers do not obviate the need for a careful physical and instrumental examination of patient.

Interventional strategies in early atherosclerosis.

Atherosclerosis remains clinically mute for a long time and frequently manifests itself with an acute cardiovascular event; therefore, the possibility to detect the disease in a subclinical phase and to reduce or reverse its progression is an issue of relevance. Non-invasive diagnostic procedures such as B-mode ultrasonography of carotid intima-media thickness (CIMT), electron beam computed tomography (EBCT) and magnetic resonance angiography (MRA) allow to identify atherosclerotic disease in its early phases, to evaluate the disease progression and monitor the effects of interventions. In recent years, several therapeutic strategies have been adopted over time to slow early atherosclerosis in asymptomatic individuals at intermediate/high cardiovascular risk. Prospective trials employing multifactorial non-pharmacological interventions (diet, exercise, smoking cessation) have demonstrated a favorable effect on progression of atherosclerosis. Hence lifestyle modification may be an effective therapeutic strategy to be adopted as a first step and a highly cost-effective intervention in a preclinical setting involving a large number of individuals. Drugs should be considered as a second step or should be associated to further reduce the risk in individuals at high probability of future events, who require more intensive interventions. Reducing low-density lipoprotein levels, blood pressure and platelet aggregation seems to be the most effective intervention in these subjects, whereas the treatment of emerging coronary risk factors, e.g. oxidative stress, inflammatory activation and infections has not produced the expected protective effect.

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.

[Recommendations for cardiovascular rehabilitation in diabetes mellitus]. / Raccomandazioni per la riabilitazione cardiovascolare nel paziente con diabete mellito.

Cardiac rehabilitation is accepted as an important component in the management of heart disease. Diabetes Mellitus is a chronic disease frequently associated to ischemic heart disease and both disease require continuing medical care, aggressive treatment of other risk factors, educational programs for self management of disease to prevent acute complication. The scientific community should offer standard of care for management of diabetic patients with coronary artery disease, and should design new strategies to promote prevention in this high risk patients. The need to define characteristics and peculiar problems of diabetics patients with ischemic heart disease encouraged the Board of the Italian Group of Cardiac Rehabilitation and Prevention (GICR) to set up a working group composed of cardiologists and diabetologists chosen on the basis of their proven specific experience. The document is subdivided in six parts. In the first section is described the cardiovascular risks in patients with diabetes and the importance of post-prandial hyperglycemia and glycemic variability. We analyse also the difference in prevalence of ischemic heart disease in Italian diabetic patients compared with other countries. In the second section we described clinical presentation of ischemic heart disease in diabetic patients such as acute myocardial infarction and unstable angina, and the revascularization procedures (balloon angioplasty and coronary bypass surgery). We analysed the differences between the procedures and the evidence-based results. In patients with myocardial infarction we analysed the evidence-based therapy and specific advantages of aspirin, beta-blockers and ace-inhibitor in diabetic patients. In this section we also posed particular attention to the clinical course of patients who underwent bypass grafting and to the impact of diabetes on short and long-term results and on main intervention-related complications including deep infections, mediastinitis, neurological problems, renal failure. In the third section we evaluated the factors responsible of atherosclerosis progression and their treatment, and we underlined that cardiac rehabilitation is less effective for patients with diabetes mellitus. Suggestions proposed in this paper about risk factors are in line with the recommendations of standards guidelines of American Diabetics Association. In patients with concomitant diabetes and ischemic heart disease we suggest blood pressure <130/80, LDL-cholesterol <100 mg/dl, triglycerides <150 mg/dl and daily physical activity. In the fourth section we analysed therapeutic regimens and management of diabetes. We posed particular attention on insulin therapy in acute phase of myocardial infarction and in recent coronary bypass grafting, and chronic use of oral antidiabetic drugs or insulin. In the fifth section we provided some recommendations on the organization of educational programs and physical activity in these patients. In the last section we provided some information on diagnosis of coronary artery disease in diabetes, aim of screening and in which patients is need to perform diagnostic tests. We described the available diagnostic tests with the differences in each method.

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.