Acute myocardial infarction (AMI) in young adult presents a typical pattern of risk factors, clinical, angiographic and prognostic characteristics.In the last years we demonstrated that hemorheological profile is altered in these patients in a persistent way and independently of the number of risk factors and of the extent of coronary lesions. Thus, the hyperviscosity syndrome following AMI could be considered an intrinsic characteristic of these patients. Consequently it is possible to hypothesise the presence of a genetic background at the origin of this predisposition. If this background is able to influence the risk of ischemic heart disease, this should be particularly evident in young subjects.Since inflammatory mechanisms play a central role in mediating all phases of atherosclerosis, genes encoding for inflammatory or anti-inflammatory molecules are candidates for the risk of developing atherosclerosis.As atherosclerosis is the first cause of mortality in Western countries and if pro-inflammatory genotypes contribute to risk of coronary heart disease, alleles associated to disease susceptibility should not be included in the genetic background favouring longevity: People genetically predisposed to a weak inflammatory activity have fewer chances to develop cardiovascular disease and, therefore, have better chance for a long-life. According to this hypothesis, we studied in our population of young patients with AMI, the distribution of some polymorphisms influencing a inflammation and found an higher prevalence of pro-inflammatory polymorphisms (SNP A2080G of pyrin gene, SNP Gly670Arg of PECAM gene, C1019T of Cx 37 gene, SNP G1059C of PCR gene) and a lower prevalence of anti-inflammatory polymorphisms (Asp299Gly of TLR4 gene, SNP -1082 G/A of IL10 gene, CCR5 Delta 32).Results of these studies show that early myocardial infarction could be associated with a genetic predisposition to an intense inflammatory response, associated also to an hyperviscosity syndrome.

AIM:The aim of the study was to evaluate the prevalence of carotid atherosclerosis and endothelial dysfunction in 45 young patients (38 mens and 7 females) with myocardial infarction (MI), age 29-45, mean age 42+/-3 years, to verify its possible role as a marker of coronary atherosclerosis.METHODS:Vascular echography was performed to verify the presence of carotid atherosclerosis and/or endothelial dysfunction in 45 young patients with MI and in 45 healthy control subjects well matched for age and sex.RESULTS:We observed a normal intima media thickness (IMT) only in 30% of patients with juvenile myocardial infarction (JMI) compared with 66% in the control group (P<0.0001) and 34% of patients showed an increased IMT compared with 24% of healthy subjects (P<0.0001). Compared with control subjects, patients with JMI had lower flow-mediated reactivity of the brachial arteries (P<0.05). There was a negative linear relationship between flow-mediated dilation and IMT (P<0.001). The severity of coronary artery disease (CAD) was correlated with increased IMT and with a lower flow-mediated dilation. Finally, multiple regression analysis, demonstrated that both brachial-artery reactivity and carotid IMT were significantly and independently correlated with severity of CAD.CONCLUSIONS:Structural (carotid atherosclerosis) and functional changes (endothelial dysfunction) were present at an early age in the arteries of persons with history of JMI.

AIM:Impaired endothelial function and increased carotid intima-media thickness are key events in the atherosclerotic process and predict future cardiovascular events in subjects with and without coronary artery disease. The purpose of this study was to investigate whether the vasodilator response to increased flow in the brachial artery and the presence of carotid lesions may have a prognostic significance for in-stent restenosis in patients undergoing coronary angioplasty.METHODS:The study population included 58 patients undergoing percutaneous coronary intervention (PCI) with stenting and at least 10 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI. Flow mediated dilatation (FMD) was investigated after 5 minutes of occlusion of the artery and nitroglycerin mediated dilation (NMD) was investigated after administration of sublingual nitrates. Vascular echography was performed to measure intima media thickness (IMT) of carotid arteries. At baseline we evaluated all the established traditional cardiovascular risk factors. We also subdivided our study cohort according to values of FMD in patients with FMD above and patients below the median value.RESULTS:Patients with FMD above the median value showed higher prevalence of hypertension (P=0.002), diabetes (P=0.02) and carotid IMT (P=0.006) than those below the median. Brachial FMD was inversely correlated (P=0.001) to carotid IMT. At the end of follow-up clinical events occurred in nine patients. In a multivariate analysis, including all the variables evaluated at baseline, carotid IMT (P=0.02), level of glycemia (P=0.001), a lower FMD (P=0.005) and presence of carotid plaque remained the only variables predictive of restenosis.CONCLUSIONS:Evaluation of FMD and carotid IMT may provide important prognostic information in patients undergoing PCI.

AIM:The clinical and prognostic role of cardiac natriuretic peptides (CNP) in patients with heart failure is well known; recently, several studies have evaluated the possibility of using CNP to evaluate their potential prognostic role in patients with acute coronary syndromes (ACS). The aim of this study was to evaluate the short term prognostic value of NT-proBNP in 70 patients admitted for ACS.METHODS:The authors studied 70 patients with ACS, evaluating, at admission, clinical-anamnestic, instrumental and laboratory characteristics including NT-proBNP plasma levels. Patients were monitored in a 6-month-follow-up to record adverse fatal events and their possible correlation with baseline characteristics.RESULTS:The incidence of adverse events during the follow-up period was 28% (10 patients). In patients with adverse events, the authors observed lower left ventricle ejection fraction (P=0.01), higher prevalence of ST elevation myocardial infarction (P=0.03) and higher NT-proBNP levels (P=0.03), compared to those without adverse events. Moreover, the logistic regression analysis underlined how ST elevation myocardial infarction (P=0.05) and higher NT-proBNP levels (P=0.05) were the only predictive variables for adverse events during the follow up period.CONCLUSIONS:This study demonstrates the short term prognostic role of NT-pro BNP in patients admitted for ACS.

AIM:The aim of this paper was to ascertain whether macrophage colony stimulating factor (MCSF) serum levels, measured during the acute phase of coronary syndromes (ACS), are useful to predict short term outcomes.METHODS:Seventy-four consecutive patients (mean age: 66+/-12), admitted to the Intensive Coronary Care Unit of Palermo University Hospital (Italy) affected by ACS were observed; 39 patients showed a non ST elevation (NSTEMI) and 35 showed a ST elevation myocardial infarction (STEMI). During the hospital stay, all patients underwent echocardiography and 84% of patients received coronary angiography. Peripheral venous blood samples were collected for the determination of serum levels of MCSF, C-reactive protein (CRP), fibrinogen, I troponin and complete lipid pattern.RESULTS:There was no significant difference in MCSF concentrations for STEMI versus NSTEMI patients (326.65+/-143.87 vs 297.15+/-110.43 pg/mL, P=NS). Higher levels of MCSF (363.00+/-147.61 vs 251.00+/-186.69, P=0.03) and CRP (1.04+/-0.40 vs 0.97+/-0.50 mg/L, P=0.03) were found in patients with a worst in hospital stay (recurrence of angina, re-infarction, death) and with a more severe coronary artery disease (330.03+/-241.51 vs 223.61+/-128.29 pg/mL, P=0.04 and 1.14+/-0.50 vs 0.60+/-0.22 mg/L, P=0.05).CONCLUSIONS:MCSF levels are useful in the prediction of short term prognosis in ACS patients.

Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory cells. We have tested the hypothesis that anti-inflammatory variants of these genes confer genetic resistance to MI and conversely favour longevity. So, we analyzed MI patients, age-related controls and centenarians. The pro-inflammatory alleles of COX-2 and 5-LO were overrepresented in MI and under-represented in centenarians whereas age-related controls displayed intermediate values. MI is a multifactorial disease, hence MI might be the result of a cumulative effect which contributes with different timing to achieve a threshold where the chance to develop the diseases is very high. In particular, differences in inflammatory status can contribute to the chance of developing a risk phenotype. However, these studies might contribute to the determination of a risk profile which may allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug.

AIM:The aim of the present study was to investigate the prevalence of carotid and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart disease (previous acute myocardial infarction [AMI] or stable angina).METHODS:We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which were investigated for traditional risk factors. Systolic blood pressure, body mass index, lipid profile, fasting glucose and plasma fibrinogen were also measured. We assessed the prevalence of atherosclerotic lesions in carotid and lower limb arteries, by ultrasound duplex scanning (UDS).RESULTS:Angina was present in 33% of the patients, a previous AMI in 67%, a previous transient ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in 13 patients (5%). In lower limb arteries, IMT or plaques were present in 202 patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and lower limb arterial atherosclerosis was detected in 73% of patients with 1 vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD.CONCLUSION:Our study suggests that in patients with CAD, it is useful to screen the peripheral circulation by non-invasive tests, such as UDS. Patients with the diagnosis of ischemic heart disease and combined extracoronary atherosclerosis need a careful follow-up and a more aggressive therapy for secondary prevention.

Introduction: Diastolic function is often studied in the absence of systolic function.There is little information on whether LV filling is related to cause of heart failure when systolic dysfunction is present.Methods: The AREA-IN-CHF (AntiRemodeling Effect of Aldosterone receptors blockade with canrenone IN mild Chronic Heart Failure) is a prospective, randomized, double blind study on antialdosterone treatment in patients with class 2 NYHA chronic heart failure (CHF) and ejection fraction >45%.Among 505 participants who underwent Doppler-echocardiography, we evaluated 351 subjects in sinus rhythm and no history of atrial fibrillation: 154 had coronary heart disease (CHD, 8% women), 116 idiopathic cardiomyopathy (IDCM, 28% women) and 41 load mismatch (LM, 37% women).Results: Age, heart rate and BMI were not statistically different among etiology groups.Blood pressure was expectedly higher in participants with LM than in the other groups (p<0.007).Conclusions: At similar level of systolic dysfunction and abnormal LV geometry, signs and symptoms of low-grade CHF (class 2 NYHA) are associated with different LV diastolic patterns, in relation to the background myocardial alteration leading to CHF.

Introduction: Coronary angiography is actually the gold standard to visualise coronary artery bypass graft patency and to detect bypass stenoses.However, it is an invasive examination that use X ray emission and it may give dangerous effects even if the dose is low.Therefore, it is still needed a noninvasive examination with good diagnostic accuracy for the follow-up of patients with coronary artery bypass grafts.Aim of this study is to evaluate the diagnostic accuracy of a 40 detector row computed tomography scanner for the assessment of bypass versus coronary angiography.Methods: Twenty-seven consecutive patients (20 male, 6 female, mean age 65) and a total number of 68 coronary bypass grafts (25 arterial and 43 venous grafts, 111 anastomoses) were examined by 40-row multi-slice computed tomography.Results: It was possible to analyse coronary artery bypass grafts patency for every patient.In coronary angiography 23 patients showed stenoses or occlusion of bypass.19 of them were correctly diagnosed by computed tomography (sensibility 84%, specificity 100%).In particular computed tomography showed a sensibility of 90% and a specificity of 100% for coronary artery bypass graft, instead, with regard to anastomoses it showed a sensibility of 88% and a specificity of 94%.Conclusions: According to the results of our study, we think that computed tomography is an efficient tool to evaluate coronary artery bypass graft patency.This examination could be included in to the diagnostic pathway of the yearly follow-up of the asymptomatic patient underwent to coronary artery bypass graft.

In acute coronary syndromes, and especially in acute myocardial infarction (AMI), inflammation mechanisms involving platelets and leukocytes play a key role. These cells show a state of activation: Evaluation of proteins released by platelets and leukocytes may provide an index for the estimation of their activation. Two platelet-specific proteins, secreted by αgranules during the release reaction, are used as activation markers: β-thromboglobulin (β-TG) and platelet factor 4 (PF4). Generally these proteins are dosed together in the same sample for a better evidence of in vivo release. In patients with AMI, plasma levels of β-TG are increased (1,2) and inversely correlated with the time elapsed from symptom onset to admission to the hospital (3). In patients with postinfarction angina there is a further increase in β-TG plasma levels (2). Elevated plasma levels of β-TG were found to persist for several weeks after AMI, in spite of the treatment with aspirin (4). Patients with ischemic heart disease show higher basal plasma concentration of PF4 compared with normal controls; in these patients PF4 levels further increase after exercise (5). Thrombolytic treatment induces an increase in β-TG levels, except in patients admitted within 2 hours from the onset of symptoms, in whom platelet activation is near maximal (3). Also coronary artery bypass induces a persistent increase in plasma levels of β-TG, even if revascularization was successful and symptoms were relieved (1). In a Japanese study (6) β-TG and PF4 plasma levels were similar in subjects with AMI or chronic coronary heart disease (CHD) or without coronary lesions. Few are the data concerning these platelet activation markers in young AMI patients. Our group previously examined the behavior of the hemorheological profile (7) and leukocyte rheological pattern (8) in young patients with AMI, and more recently (9) we determined the behavior of β-TG and PF4 (employing enzyme-linked immunosorbent assay methods) in 49 subjects (46 men and 3 women, mean age 38.8 ± 6.8 years; range 19–44 years) with the same clinical condition. The time interval between AMI onset and first examination (T1) was 13.0 ± 7.0 days and the patients were reexamined 3 months after the first evaluation (T2). All the patients were treated with angiotensin-converting enzyme inhibitors, statins, and platelet antiaggregation agents (aspirin or ticlopidine or clopidogrel). Our results showed that β-TG and PF4 were increased in AMI patients, compared with the control group, at T1 as well as at T2. In control subjects and in AMI patients, at either T1 or T2, there was a significant and positive correlation between βTG and PF4 (p < 0.001, for all the three groups) whereas no relationship was found between these platelet activation markers and platelet count. In conclusion, our data showed an increase of β-TG and PF4 at the initial stage of AMI, which was still present after 3 months and emphasized that the antiplatelet aggregation drugs did not modify platelet activation during the observation period. All these findings need further investigation considering that we enrolled young patients

AIM:The aim of our study was to determine if patients with multifocal atherosclerosis have a worse prognosis than patients with atherosclerosis only in the coronary bed.METHODS:We studied 45 subjects admitted to intensive coronary care unit of the Division of Cardiology with the diagnosis of acute myocardial infarction (AMI). Traditional cardiovascular risk factors were investigated and laboratory analysis included measurement of plasma lipids, glycemia, fibrinogen and high-sensitivity-C-reactive protein (hs-CRP). Each patient underwent coronary-angiography as well as carotid and peripheral arterial ultrasound examination. A follow-up of 13+/-2 months was performed.RESULTS:We found that the severity of coronary atherosclerosis is significantly associated with the presence of carotid (P<0.05) and peripheral atherosclerosis (P<0.005). Markers of inflammation, hs-CRP (P<0.005) and fibrinogen (P<0.05), were significantly associated with multifocal atherosclerosis. We have shown that an increased number of coronary vessels with atherosclerotic stenosis is associated with a higher value of carotid (P<0.0001) and peripheral intima media thickness (P<0.0001). During 13 months of follow-up the incidence of fatal or non fatal events was 18%. The multivariate analysis showed that the variables independently associated with fatal and non fatal events were: male sex (P<0.001), family history of cardiovascular disease (P<0.005), hypertension (P<0.01), diabetes mellitus (P<0.05), higher levels of total cholesterol (P<0.05), smoking habit (P<0.05), and multifocal atherosclerosis (P<0.05).CONCLUSIONS:The ultrasound examination of carotid and peripheral atherosclerotic lesions may be useful in placing patients with AMI in a category of higher risk of cerebrovascular and cardiovascular events. Moreover, the precocious identification of patients at risk can suggest a more aggressive pharmacological treatment and a more accurate follow-up in order to avoid future events.

Our goal was to evaluate some plasma markers of platelet and polymorphonuclear leukocyte (PMN) activation in a group of young adults with acute myocardial infarction (AMI) at the initial stage and after three months. We enrolled 49 AMI subjects aged<45 years and examined plasmatic levels of platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), elastase and myeloperoxidase (MPO) using ELISA methods. PF4 and beta-TG were increased, compared to control subjects, both at the initial stage and after 3 months. In control subjects and in AMI patients, at both times of observation, there was a significant and positive correlation between the two platelet parameters, while no correlation was present between each parameter and platelet count. In AMI patients there was an increase in elastase levels in comparison with the control group; this increase was evident at the initial stage and after 3 months. There was no difference in MPO levels between control subjects and AMI patients. In control subjects and in AMI patients there was a significant and positive correlation between elastase and MPO level, whereas no relationship was found between each marker and PMN count. Our data show that in young AMI patients the discharge treatment including antiplatelet drugs did not modify platelet activation and suggest the association of molecules able to inhibit PMN activation to the conventional therapy of these AMI patients.

Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular diseases. In this case-control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in -174 promoter region of the IL-6 gene. Plasma concentrations of IL-6 and C-reactive protein (CRP) in a group of patients and controls were measured. The -174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801-4.624, P = 0.0001) in older patients, while no association was found in younger ones. The IL-6 plasma levels were higher in patients with MI carrying the CC genotype than in GG patients (CC carriers, IL-6 = 2.97 pg mL(-1) vs. GG carriers = 1.81 pg mL(-1), P = 0.016). A positive correlation of IL-6 levels with those of CRP in serum from patients with MI was also found. Data from this study suggest that the C allele of the promoter polymorphism in the IL-6 gene is a risk factor for MI in the elderly, and the production of the IL-6 is differentially affected by different genotypes of the IL-6 -174 promoter polymorphism.