Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD).

BACKGROUND: The BRCA proteins play a key role in the homologous recombination (HR) pathway. Beyond BRCA1/2, other genes are involved in the HR repair (HRR). Due to the prominent role in the cellular repair process, pathogenic or likely pathogenic variants (PV/LPVs) in HRR genes may cause inadequate DNA damage repair in cardiomyocytes. PATIENTS AND METHODS: This was a multicenter, hospital-based, retrospective cohort study to investigate the heart toxicity from anthracycline-containing regimens (ACRs) in the adjuvant setting of breast cancer (BC) patients carrying germline BRCA PV/LPVs and no-BRCA HRR pathway genes. The left ventricular ejection fraction (LVEF) was assessed using cardiac ultrasound before starting ACR therapy and at subsequent time points according to clinical indications. RESULTS: Five hundred and three BC patients were included in the study. We predefined three groups: (i) BRCA cohort; (ii) no-BRCA cohort; (iii) variant of uncertain significance (VUS)/wild-type (WT) cohort. When baseline (T0) and post-ACR (T1) LVEFs between the three cohorts were compared, pre-treatment LVEF values were not different (BRCA1/2 versus HRR-no-BRCA versus VUS/WT cohort). Notably, during monitoring (T1, median 3.4 months), patients carrying BRCA or HRR no-BRCA germline pathogenic or likely pathogenic variants showed a statistically significant reduction of LVEF compared to baseline (T0). To assess the relevance of HRR on the results, we included the analysis of the subgroup of 20 BC patients carrying PV/LPVs in other genes not involved in HRR, such as mismatch repair genes (MUTYH, PMS2, MSH6). Unlike HRR genes, no significant differences in T0-T1 were found in this subgroup of patients. CONCLUSION: Our data suggest that deleterious variants in HRR genes, leading to impaired HR, could increase the sensitivity of cardiomyocytes to ACR in early BC patients. In this subgroup of patients, other measurements, such as the global longitudinal strain, and a more in-depth assessment of risk factors may be proposed in the future to optimize cardiovascular risk management and improve long-term survival.

Chronic inflammation: A key role in degeneration of bicuspid aortic valve.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect resulting from abnormal aortic cusp formation during heart development, where two of the three normal and equal sized cusps fuse into a single large cusp resulting in a two cusps aortic valve. Over the past years, much interest has been given in understanding the pathogenesis of BAV and its complications. In this review, we focused on the role of inflammation, involved in the degeneration of BAV and the development of its complications. ROLE OF INFLAMMATION: From a pathophysiological point of view, BAV may rapidly progress into aortic stenosis (AS) and is related to aortopathy. Several histopathologic studies have demonstrated that the development and progression of alterations in bicuspid aortic valve are related to an active process that includes: oxidative stress, shear stress, endothelial dysfunction, disorganized tissue architecture, inflammatory cells and cytokines. These factors are closely related one to each other, constituting the basis of the structural and functional alterations of the BAV. CONCLUSION: Chronic inflammation plays a key role in the degeneration of BAV. Severe aortic stenosis in bicuspid aortic valves is associated with a more aggressive inflammatory process, increased inflammatory cells infiltration and neovascularization when compared to tricuspid AS. These findings might help to explain the more frequent onset and rapid progression of AS and the heavy aortic valve calcification seen in patients with BAV.

Quantitative criteria for the diagnosis of the congenital absence of pericardium by cardiac magnetic resonance.

BACKGROUND: Congenital absence of the left ventricular pericardium (LCAP) is a rare and poorly known cardiac malformation. Cardiac Magnetic Resonance (CMR) is generally used for the diagnosis of LCAP because of its high soft tissue contrast, multiplanarity and cine capability, but the diagnosis is usually made by only qualitative criteria. The aim of the present study was to establish quantitative criteria for the accurate diagnosis of LCAP on CMR. METHODS: We enrolled nine consecutive patients affected by LCAP (mean age 26±8years, 7 males), 13 healthy controls, 13 patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and 13 patients with right ventricular overload (RVO). All patients underwent CMR. The whole-heart volume was measured in end-systole and end-diastole. Whole-heart volume change (WHVC), was the systo-diastolic change of volume, expressed percentage of the end-diastolic volume. The angle of clockwise-rotation of the heart was also measured in the end-diastolic phase of the axial cine stack. RESULTS: The WHVC was significantly higher in LCAP (21.9±5.4), compared to healthy subjects (8.6±2.4, p<0.001), DCM (7.1±1.8, p<0.001), HCM (9.3±2.4, p<0.001) and RVO (8±2.4, p<0.001). The clockwise-rotation was significantly higher in LCAP (76±14°) than healthy controls (40±11°, p<0.001), DCM (41±5°, p<0.001), HCM (30±6°, p<0.001) and RVO (49±8°, p<0.001). WHVC had the highest sensitivity (100%) and specificity (100%) for diagnosing LCAP, using a threshold of >13%. CONCLUSIONS: In LCAP the systo-diastolic WHVC was significantly higher than controls, DCM, HCM and RVO patients and resulted an optimal quantitative criteria for the diagnosis of LCAP.

Selective pacing sites.

he right ventricular apex (RVA) has always been the most used pacing site, because it is easily accessible and provides a stable lead position with a low dislodgment rate. However, it is well-known that long-term right ventricular apical pacing may have deleterious effects on left ventricular function by inducing a iatrogenic left bundle branch block, which can have strong influences on the left ventricle hemodynamic performances. More specifically, RVA pacing causes abnormal contraction patterns and the consequent dyssynchrony may cause myocardial perfusion defects, histopathological alterations, left ventricular dilation and both systolic and diastolic left ventricular dysfunction. All these long-term changes could account for the higher morbidity and mortality rates observe in patients with chronic RVA pacing compared with atrial pacing. This observation led to the reassessment of traditional approaches and to the research of alternative pacing sites, in order to get to more physiological pattern of ventricular activation and to avoid deleterious effects. Then, attempts were made with: right ventricular outflow tract (RVOT) pacing, direct His bundle pacing (DHBP), parahisian pacing (PHP) and bifocal (RVA + RVOT) pacing. For example, RVOT pacing, especially in its septal portion, is superior to the RVA pacing and it would determine a contraction pattern very similar to the spontaneous one, not only because the septal portions are the first parts to became depolarized, but also for the proximity to the normal conduction system. RVOT is preferable in terms of safety too. DHBP is an attractive alternative to RVA pacing because it leads to a synchronous depolarization of myocardial cells and, therefore, to an efficient ventricular contraction. So it would be the best technique, however the procedure requires longer average implant times and dedicated instruments and it cannot be carried out in patients affected by His bundle pathologies; furthermore, due to the His bundle fibrous area, higher pacing thresholds are required, causing accelerated battery depletion. For all these reasons, PHP could be considered an important alternative to DHBP, to be used on a large scale. Finally, bifocal pacing in CRT candidates, provides better acute hemodynamic performance than RVA pacing, derived from a minor intra- and interventricular dyssynchrony, expressed also by the QRS shortening. Then, bifocal pacing could be taken into account when RVA pacing is likely to be the origin of serious mechanical and electrical dyssynchrony or when CRT is contraindicated or technically impossible. So, whatever chosen as selective pacing site, you must look also at safety, effectiveness and necessary equipment for an optimal pacing site.

Medical management of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence- based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤7%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.

Left ventricular non compaction: epidemiology, clinical findings, diagnosis and therapy.

Left ventricular non compaction (LVNC) is a cardiomyopathy due to an arrest of the normal development of myocardium which determines the persistence of fetal myocardium in postnatal life in at least 2/3 of the wall (criterion known as non compacted/ compacted ratio greater than 2). Although in absence of a confirmed prevalence of LVNC, reviewing literature shows an increasing number of reports over the years, though diagnosed cases represent just the tip of a realistically far wider phenomenon. Clinical manifestations are variable, ranging from the absence of any symptom to congestive heart failure, arrhythmias and systemic thromboembolism. Echocardiography is the gold standard for the diagnosis. Tissue Doppler and three-dimensional echocardiography may give further information in the evaluation of patients affected by LVNC. Magnetic resonance could refine diagnosis particularly in those patients with not conclusive echocardiogram: it may help in differential diagnosis and give prognostic information. There is no specific therapy for patients with LVNC but the treatment is aimed at treating heart failure, or other complications such as arrhythmias and thromboembolic events.

Comparison of coronary artery flow impairment in diabetic and hypertensive patients with stable microvascular angina.

OBJECTIVE: Stable microvascular angina (SMVA) describes patients with angina, findings compatible with myocardial ischemia and normal coronary angiograms. The aim of this study was to evaluate the impact of diabetes on the coronary microcirculation troughs angiography indexes (TIMI Frame Count, Myocardial Blush Grade, Total Myocardial Blush Score) and a new index: Total TIMI Frame Count (TTFC). PATIENTS AND METHODS: The study population included 310 patients with SMVA that we split into two populations: diabetic-non hypertensive (164 patients) and non-diabetic-hypertensive (146 patients). We calculated, on angiographic images of each patient, TIMI Frame Count (TFC), Myocardial Blush Grade (MBG) and Total Myocardial Blush Score (TMBS) using the protocol described by Gibson and Yusuf. On the basis of Yusuf's experience we imagined a new index: TTFC like sum of the three coronary TFC. RESULTS: We found a worse coronary microcirculation in diabetic-non hypertensive patients with lower values of TFC, MBG and TMBS (p = 0.02), compared with non-diabetic hypertensive. New index TTFC is usually higher in diabetics-non hypertensive than non-diabetic hypertensive patients. Patients with positive scintigraphy had a worse TMBS than patients with a negative one, with a high statistical significance (p = 0.003). CONCLUSIONS: Analysis of diabetic non hypertensive and non-diabetic and hypertensive patients with cardiac syndrome X has led to asses that the diabetic population has a greater involvement of microcirculation. Also the new index, TTFC, proved to be a good marker, in agreement with results of other indexes.

Is local stiffness, as measured by radio frequency, more sensitive than intima-media thickness?

AIM: The aim of our study was to explore the changes in common carotid arterial intima-media thickness (CCA IMT) and local arterial stiffness to evaluate, non-invasively, early vascular disease in patients with cardiovascular (CV) risk factors and "normal" carotid IMT (<0.9 mm). METHODS: We studied 50 patients (mean age 42 years±14), with no history of cardio-cerebrovascular events and "normal" IMT. We assessed the traditional cardiovascular risk factors, the CCA IMT, and the local stiffness with Quality Arterial Stiffness technology, based on Radio frequency signal (RFQAS-ESAOTE, Italy). CCA distensibility coefficient (DC), compliance coefficient (CC), pulse wave velocity (PWV) and ß parameter were measured in patients, with and without traditional cardiovascular risk factors. 25 subjects with risk factors (mean age 49±13) were compared with 25 controls (mean age 36±12). RESULTS: We did not find any significant differences in the IMT measurement between subjects with CV risk factors compared to controls (0.530±0.99 mm vs. 0.626±0.127 mm; P=5.68). The mean DC (0.030±0.014 1/kPa vs. 0.0221±0.016 1/kPa; P<0.05) and CC (1.087±0.47 mm²/kPA vs. 0.864±0.41 mm²/kPA; P<0.05), were significantly lower, while PWV (6.21±1.74 m/s vs. 7.68±2.07 m/s; P<0.05) and ß (7.67±4.09 m/s vs. 10.45±5.58 m/s; P<0.05) were significantly higher in subjects with CV risk factors. ROC curves showed that PWV>6.05 m/s better identified, among patients with IMT <0.9 mm, those with cardiovascular risk factors (sensitivity 82.0% specificity 62.0%; AUC 0.73). CONCLUSION: Increased stiffness is a result of change both in quantity and quality of the arterial wall. Arterial functional changes and distention alterations may herald the onset of vascular disease before manifestation of symptoms or detection of preclinical atherosclerotic lesions.

Carotid intima-media thickness measurement through semi-automated detection software and analysis of vascular walls.

AIM: The aim of the present study was to compare the semi-automatic measurement of carotid intima thickness (RFQIMT - Esaote, Italy), with the conventional method. METHODS: We enrolle 81 patients, mean age 46 years ±15, with no history of cardio-cerebrovascular events and we assessed the traditional cardiovascular risk factors. We examined the IMT of the common carotid artery with manual and RFQIMT method (based on the "Radio Frequency" signal), according to the ASE protocol. RESULTS: Semi-automatic measurement was on average lower than manual measurement (617 µm ±191 vs. 676 µm ± 222) with a statistically significant difference (P<0.01). In agreement with manual measurements, the values of RFQIMT increased with increasing age and presence of cardiovascular risk factors. CONCLUSION: The RFQIMT measurement was, on average, lower than manual measurement, this means that probably, age- and gender-related reference values of RFQIMT need to be revised.

Rare cardiomyopathies: diagnostic features.

Cardiomyopathies (CM) are an important and heterogeneous group of diseases affecting the myocardium. They can induce mechanical and/or electrical disorders and are due to a variety of causes, they frequently are genetic. However, since their high number and their clinical complexity, the identification is still a challenge. Echocardiography is a very useful tool in the assessment of CM. In this review we aim to define the typical clinical features and to discuss the main diagnostic tool, above all echocardiography that can help physicians in the correct assessment of CM.

Prevalence of metabolic syndrome: a comparative analysis in an unselected sample of mediterranean subjects.

AIM: The metabolic syndrome (MS) is associated with increased cardiovascular and cerebrovascular risk. This study aimed to compare the difference of the three established diagnostic criteria of MS, developed by Adult Treatment Panel III (ATP III), American Heart Association (AHA) and National Heart Lung and Blood Institute (NHLBI), and International Diabetes Federation (IDF), with regard to the prevalence of the syndrome and the ability to correctly identify individuals with cardiovascular or cerebrovascular disease or subclinical atherosclerosis. METHODS: We studied 947 consecutive patients underwent clinical evaluation between the 1997-2002. The project design included a medical assessment, biochemical analyses and the ecocolordoppler examination of carotid arteries. RESULTS: The MS prevalence was 37% in ATPIII subjects, 36% in AHA/NHLBI subjects and 43% in IDF subjects. Excluding patients with diabetes (N.=259), the MS prevalence ranged from 32% (ATPIII and AHA/NHLBI subjects) and 40% (IDF subjects). By most criteria, MS-positive subjects had significant incidence of carotid atherosclerosis (P<0.05) and cardiovascular events (P<0.05) than MS-negative subjects, but not cerebrovascular events. Finally, patients with MS had higher serum levels of fibrinogen (P<0.04). CONCLUSION: Subclinical atherosclerosis and cardiovascular events were increased in presence of the MS, irrespective of the several definitions.

Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study.

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, considered as emerging and promoting atherosclerosis. This study aimed at the evaluation of the influence of MetS on the prediction of cerebro and cardiovascular events during a 20 years follow-up period in an asymptomatic population of middle-aged subjects. METHODS: We evaluated 529 asymptomatic persons through a prospective study. Study population was divided into two subgroups: patients with and without MetS. Echo-color-Doppler was used in order to assess the presence of subclinical atherosclerosis. A 20 years follow-up study was carried out in order to estimate the incidence of cerebro and cardiovascular, fatal and non fatal, events (AMI, stroke, abdominal aortic aneurysm, TIA, angina pectoris). RESULTS: 242 cerebro and cardiovascular events were registered, 43 fatal (24 in MetS and 19 in controls) and 199 non fatal (120 with MetS and 79 without it, p < 0.0001). Free-events survival was lower in patients suffering from MetS (p < 0.0012; HR 0.6847; C.I.95%: 0.5274-0.8889). Ultrasound showed a higher prevalence of subclinical atherosclerosis in patients with MetS than in the unaffected ones (68.12% vs. 57.5% p < 0.01; OR = 1.58 with C.I.95% = 1.10-2.28, p < 0.01). CONCLUSIONS: Patients with MetS have a higher cardiovascular risk that can be explained by atherosclerotic changes: the components of MetS interact to affect vascular thickness synergistically and promote the development of subclinical atherosclerosis. So we recommend to prevent the development of MetS abnormalities and to investigate the presence of subclinical atherosclerosis by echo-color-Doppler in order to stratify more accurately the global CV risk.

Chemotherapy-induced cardiotoxicity: role of the conventional echocardiography and the tissue Doppler.

AIM: The cardiotoxicity of anticancer drugs is an emerging problem and only an identification of the early signs of cardiotoxicity by conventional echocardiography and not (tissue Doppler imaging, TDI), will limit and contain the long-term cardiotoxicity effects. The aim of this study was to identify, through conventional echocardiography and TDI, parameters to use as early "signs" of cardiotoxicity. METHODS: A prospective study was performed using patients with breast cancer (72 women, median age 57 ± 12) treated with anticancer drugs (adjuvant chemotherapy). All patients underwent a careful cardiological evaluation before starting treatment (T0) and during follow-up at 3 months (T1), 6 months (T2) and 1 year (T3). Electrocardiography and echocardiography were performed in all patients in these times. Echocardiography evaluation considered the following parameters: systolic and diastolic diameters and volumes, LVEF, MAPSE, TAPSE, E/A TDI (Em, Am, Sm, IVCT, IVRT, ET, TEI index). On the basis of chemotherapy treatment, patients were divided into 5 groups: A=FEC (fluorouracil, epirubicin, cyclophosphamide), B=FEC+trastuzumab, C=trastuzumab, D=FEC+taxotere, E=FEC+taxolo+trastuzumab. RESULTS: A significant reduction in the echo parameters of TDI was observed. TDI appears to offer important advantages over traditional techniques in revealing the presence of early signs of cardiotoxicity. CONCLUSION: The TDI should be utilized to complement conventional echocardiography in the assessment of cardiotoxicity.

Cardiac risk stratification in elective non-cardiac surgery: role of NT-proBNP.

AIM: The aim of the study was to investigate the utility of NT-proBNP measurement for the stratification of presurgical cardiac risk. METHODS: Cardiac risk before elective non-cardiac surgery was evaluated in 82 consecutive patients. From each patient a venous blood sample was drawn to determinate NT-proBNP levels. Patients were followed up over three months in order to detect the occurrence of cardiac adverse events. RESULTS: NT-proBNP was positively correlated (P<0.0001) with age, days of hospitalization (P=0.001) and ASA class (P=0.001). High surgical risk (P<0.0001), diabetes (P=0.004), dyslipidemia (P=0.006) and elevated levels of NT-proBNP (P<0.0001) were significantly correlated with events. Using a logistic regression analysis we found an independent association between pre-operative elevated NT-proBNP and postoperative cardiac events (OR 1.2, 95% CI 1.0-1.4, P=0.01). CONCLUSION: Measuring NT-proBNP before non cardiac surgery in clinical practice could be useful to better stratify patients' risk.

Modification of the lipidic and coagulative pattern in postmenopause women: effect of hormone replacement therapy.

AIM: We evaluated the changes of lipidic and coagulative pattern during menopause and the influence of hormone replacement therapy (HRT) on these parameters. METHODS: We considered 158 patients divided into 2 groups: Group I consisted of 127 women in physiological/surgical menopause and Group II of 31 women with childbearing potential. Subsequently, we considered a group III formed of 34 patients from menopausal women (group I) who underwent three months of HRT. We evaluated total-cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lpa), fibrinogen, antithrombin III (ATIII), factor VII (FVII) and tissue factor pathway inhibitor (TFPI). RESULTS: We found a worse lipid profile in the post-menopausal group compared to controls (TC 243.8+/-29.7 vs 217.9+/-32.7 mg%, P=0.002; TG 121.5+/-68.4 vs 88.6+/-53.0 mg%, P=0.039; LDL-C 163.0+/-27.9 vs 136.2+/-29.6 mg%, P=0.004; HDL-C 60.9+/-14.9 vs 64.1+/-14.6 mg%, P=ns). With regard to the coagulative pattern, fibrinogen was significantly higher in the post-menopausal group (fibrinogen: 273.3+/-67.4 vs 243.8+/-39.5 mg%, P=0.013; ATIII 112.2+/-11.7 vs 117.5+/-12.7% %, P=0.059; FVII 121.6+/-11.3 vs 117.6+/-10.8 mg%, P=ns; TFPI activity 2.5+/-2.3 vs 2.1+/-1.1 U/mL, P=ns; TFPI antigen 120+/-38 vs 127+/-39 U/mL, P=ns). Comparing the same parameters, before and after three months of HRT, in patients of Group III we observed a significant improvement of TC and TG levels (TC from 232.3+/-42.7 to 215.2+/-37.6 mg%, P=0.0001; TG from 103.7+/-56.8 to 95.0+/-44.3 mg%, P=0.059; HDL-C from 62.3+/-12.9 to 63.6+/-12.6 mg%, P=ns; LDL-C from 149.3+/-38.7 to 132.6+/-34.5 mg%, P=0.0001). The following changes were observed with regard to coagulative parameters: fibrinogen from 270.9+/-69.4 to 253.2+/-56.2 mg%, P=0.07; ATIII from 113.5+/-11.4 to 110.8+/-13.2 mg%, P=0.198; FVII from 108.6+/-18.0 to 104.4+/-17.5 mg%, 0.014. TFPI activity from 2.6+/-2.3 to 2.3+/-1.4 U/ml, P=ns; TFPI antigen from 68+/-13 to 87+/-22 U/mL, P=0.001. CONCLUSION: Our data confirm the presence of an alteration in lipidic and coagulative pattern in post menopausal women and positive changes after HRT.

Insulin resistance and acute coronary syndrome.

BACKGROUND: Insulin resistance (IR), which can be quantified by HOMA index (fasting glucose X fasting insulin/22.5), is considered the "primum movens" for the development of Metabolic Syndrome. Many authors have suggested that insulin resistance could raise both incidence and mortality of coronary heart disease (CHD). IR is also associated with important predictors of cardiovascular disease, as increased concentration of LDL or triglyceride, decreased concentration of HDL, high systolic blood pressure, visceral obesity. There is accumulating evidence that chronic sub-clinical inflammation, as measured by inflammatory markers as C-reactive protein (CRP) and fibrinogen, is related with insulin resistance. AIM OF THE STUDY: To clarify if insulin resistance would predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidemia, by focusing our attention on the relation between Acute Coronary Syndrome (ACS) and high HOMA index. METHODS: We evaluated glucose and insulin levels at baseline and post-prandial phase, in order to estimate HOMA index in both the conditions; we related the data obtained with the incidence of cardiovascular events, also investigating traditional cardiovascular risk factors. The cohort included 118 patients with a clinical diagnosis of ACS and excluded those with type 1 diabetes, acute inflammatory diseases, hepatic or renal failure, disreactive disorders, autoimmunity and cancer. SUBJECTS: Subjects were followed-up for a period of 1 year, being subdivided in three groups: (1) subjects at elevated HOMA (HOMA > or = 6); (2) subjects at intermediate HOMA (HOMA <6 and > or = 2); (3) subjects at low HOMA (HOMA < or = 2). We considered as end points new cardiovascular events, cerebrovascular events (both TIA and stroke), procedures of revascularization with angioplasty or surgery, cardiovascular death, sudden death. RESULTS: Patients with elevated HOMA have a higher incidence of previous cardio- and cerebrovascular events (p=0.03), myocardial infarction without ST elevation (p=0.005), unstable angina (p=0.01), asymptomatic carotid plaques (p=0.05), depressed systolic function (p=0.05); we found, also, a significant statistic correlation between HOMA index and high levels of CRP, fibrinogen, serum creatinine and TnI. Cardiovascular and cerebrovascular events were registered in 61% of patients with elevated HOMA during the follow up, despite of 25% registered in the control group: so we could consider HOMA index as a negative prognostic variable, also in virtue by the statistic correlation with the inflammatory markers, whose power of prediction is already known. CONCLUSIONS: Beyond traditional cardiovascular risk factors, insulin resistance quantified by HOMA index seems to significantly have an important prognostic role, both in primary and secondary prevention in patients with Acute Coronary Syndrome.