S26 Nutrition, Metabolism & Cardiovascular Diseases (2009) S1âS32 development of atherosclerosis. Recently, we demonstrated the presence of HCVRNA sequences within carotid plaques of HCV seropositive (HCV+) patients and showed evidences of a local pro-atherogenetic action of the virus inside the plaque and that HCV infection facilitates the occurrence of carotid atherosclerotic lesions. In order to evaluate whether peculiar molecular mechanisms might support a different pathogenesis of carotid artery disease in HCV+ patients with respect to HCV seronegative (HCV ) patients, we performed the gene expression proï¬le by Affymetrix GeneChip technology (Human Genome U133 Plus 2.0 Array, 47,000 transcripts) of carotid biopsies of 6 HCV+ and 6 age and gender comparable HCV patients who underwent carotid revascularization. The status of carotid arteries, studied as intima-media thickness (IMT) in carotid bifurcation and prevalence and severity of plaques in internal carotid artery, was investigated by high-resolution B-mode ultrasonography. The atherosclerotic risk proï¬le, inï¬ammation markers and main liver function tests were also studied in all patients. HCVRNA sequences were investigated by highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) in plaque tissues and serum of HCV+ patients. Two hundreds and seventy eight genes resulted differentially expressed in HCV+ with respect to HCV patients (53 genes expressed at lower levels and 225 at higher levels in HCV+ than in HCV ). After the application of an unsupervised hierarchical clustering with complete method using euclidean distance as similarity measure to both sample and all the differentially expressed genes, HCV and HCV+ cases resulted co-clustered, and we were able to separate by the gene expression proï¬le HCV+ and HCV patients. Interestingly, among genes with increased expression in HCV+ patients we found: ITIH4, an anti-inï¬ammatory protein associated with diagnosis and prognosis of acute ischemic stroke; BAT4, thought to be involved in some aspects of immunity; thioredoxin, a gene involved in oxidative stress and associated with intraplaque hemorrhage of coronary culprit lesions or atherosclerotic plaques; IRAK3, HLAB and C2, involved in the establishment of an immune response; ADAM23, a member of the âa disintegrin and metalloprotease domainâ family; WNK1, showed to play a role in angiogenesis and heart development in mice; ARF6 and FMN1 associated with actin cytoskeleton rearrangements during virus internalization. In conclusion, our data identiï¬ed differential gene expression proï¬les in HCV+ and HCV patients affected by carotid artery disease suggesting the presence of peculiar mechanisms of disease in the two groups of patients. 105 EZETIMIBE/SIMVASTATIN COMPARED WITH DOUBLING THE DOSE OF SIMVASTATIN IN PATIENTS WITH CORONARY HEART DISEASE (CHD), WITH AND WITHOUT DIABETES (T2DM), NOT AT LDL-C TARGET WITH SIMVASTATIN ALONE: A POOLED ANALYSIS OF TWO DOUBLE-BLIND, RANDOMIZED ITALIAN STUDIES C.M. Rotella1 , A. Zaninelli3 , C. Le Grazie2 , G.F. Gensini3 . 1 Sezione di Endocrinologia, Dip. Fisiopatologia Clinica, Universit` di Firenze; 2 Direzione a Medica Schering-Plough SpA, Italy; 3 Dip. di Area Critica Medico-chirurgica, AO Careggi, Firenze, Italy E-mail: cristina.le.grazie@spcorp.com Introduction: Two multicenter, randomized, double-blind, studies comparing two different switch strategies (ezetimibe/simvastatin versus doubling the simvastatin dose for 6 weeks) have been carried out in Italian populations of high CV risk patients with CHD alone (DIALOGUE study) or CHD and T2DM (LEAD study) not at the recommended target of LDL-C after at least 6 weeks of simvastatin 20 mg/day. Ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg/day proved to be superior to simvastatin (SIMVA) 40 mg/day in reducing LDL-C and in getting patients to the LDL-C target <100 mg/dl (2.8 mmol/L) after 6 weeks of treatment in both studies. Objectives and methods: To identify with adequate statistical power the factors signiï¬cantly correlated with the probability to reach the LDL-C target <100 mg/dl in a population of high CV risk subjects not at the LDL-C target with SIMVA 20 mg/day who are switched either to EZE/SIMVA 10/20 or to a double dose of SIMVA (40 mg/day). A stepwise logistic regression analysis was carried out pooling the data of the LEAD and DIALOGUE studies. The dependent variable was LDL-C <100 mg/dl at endpoint, independent variables were: T2DM (yes/no), treatment (EZE/SIMVA, SIMVA), gender, age ( 65 years/ <65 years), LDL-C at randomization. Participants: Data from 87 subjects in the LEAD study and 112 in the DIALOGUE study were pooled. In both studies adult subjects on a stable daily dose of SIMVA 20 mg for at least 6 weeks prior to randomization, with LDL-C concentration 2.6 mmol/L (100 mg/dL) and 4.1 mmol/L (160 mg/dL) and triglycerides (TG) concentration <3.99 mmol/L (350 mg/dL) were randomized to EZE/SIMVA 10/20 mg or SIMVA 40 mg/day for 6 weeks. The study design, objectives, treatment duration, type and times of evaluations were the same in both studies. Results: A total of 93 subjects treated with EZE/SIMVA 10/20 and 106 with SIMVA 40 were included in the analysis. Basal values of LDL-C did not differ signiï¬cantly in the 2 groups nor between diabetics and non diabetics. Among the independent variables T2DM (p = 0.003, OR = 2.9, CI95%: 1.4 5.9), EZE/SIMVA treatment (p < 0.001, OR = 6.1, CI95%: 2.9 12.4) and LDL-C at randomization (p = 0.001, OR = 0.9, CI95%: 0.93 0.97) were signiï¬cantly correlated with the probability to reach the LDL-C target. When T2DM was removed from the model as potential confounding factor, EZE/SIMVA treatment and LDL-C at randomization maintained statistical signiï¬cance with Conclusions: High serum concentrations of ADMA were associated with early carotid atherosclerotic lesions as measured by CIMT and represent a new marker of asymptomatic carotid atherosclerosis. 102 OCCULT IMPAIRED GLUCOSE REGULATION IN PATIENTS WITH ATHEROSCLEROSIS IS ASSOCIATED TO THE NUMBER OF AFFECTED VASCULAR DISTRICTS AND INFLAMMATION S. Rizza, M. Cardellini, E. Martelli, O. Porzio, A. Nicolucci, N. Marx, N. Senese, D. Lauro, R. Lauro, M. Federici. Department of Internal Medicine and Department of Vascular Surgery, University of Rome Tor Vergata, Italy E-mail: rizza@med.uniroma2.it Objectives: The purpose of this study was to test the hypothesis that in subjects with atherosclerotic vascular disease and no previous medical record of DM2, the diagnosis of occult impaired glucose regulation (IGR) is related to the severity of atherosclerosis, measured as the single or combined presence of an history of Coronary Artery Disease (CAD), Carotid Atherosclerosis (CarATS) and Peripheral Artery Disease (PAD). Background: The role of inï¬ammatory adipokines has clear mechanistic effects in the promotion of both Type 2 diabetes mellitus (DM2) and cardiovascular diseases (CVD), but it is unknown at what extent atherosclerosis-related inï¬ammation might promote defects of glucose metabolism. Methods: In a population of 551 subjects (440 men and 111 women) with a previous history of atherosclerosis, we investigated the presence of IGR (including both impaired glucose tolerance and DM2). To test the correlations between conventional and not conventional risk factors for cardiovascular disease and diabetes we used logistic and regression analysisâs models. Results: IGR was more prevalent in patients with a documented vascular disease in 2 or 3 vessel districts compared with patients with only 1 symptomatic district (p = 0.010). Among classic risk factors we found that waist circumference was correlated neither to IGR nor to symptomatic vascular disease extension. By contrast, adiponectin level was independently associated to vascular and glucose regulation status (p = 0.012 and p < 0.001, respectively). Conclusion: In subjects affected by atherosclerotic vascular diseases, the presence of impaired glucose regulation is associated to the number of vascular districts affected and to a reduced adiponectin level. 103 SWEET EATERS: LESS OBESITY BUT MORE CARDIOMETABOLIC RISK G. Rossi, A.R. Tusino, M. Rossetti, G. Tanzi, T. Lorusso, E. Altomare. University of Foggia, Internal Medicine II, Department of Internal Medicine, Italy E-mail: grossi23@alice.it The objective of our study is to explore the main features of the sweet eating patients. Methods: The subjects were recruited in our out-patients departement in the ï¬rst 3 months of 2009. Data were collected on 198 subjects (160 females and 38 males). In each patients were performed a questionnaire reported eventually sweet foods and drinks recruitment and craving behaviours. Results: In 51 patients (44 females and 7 males) were found craving and high intake of sweet foods and drinks (sweet eaters, S). They submitted average values of age, total cholesterol, triglycerides lower than non sweet (NS), the 39.21% fulï¬lled the criteria ATP III for metabolic syndrome against the 24.48% of NS. Reported family history for obesity (41.1% vs 34%), hypertension (35.2% vs 33.3%), diabetes mellitus (33.3% vs 31.9%), dyslipidemia (37.2% vs 21.7%) more frequently in group S, for cardiovascular diseases (20.40% vs 36.7%) in NS. The population S showed more emotional eating (26.4% vs 14.9%), grazing (11.7% vs 9.5%), depression (11.7% vs 6.1%), more cases of obesity ï¬rst class (39.2% vs 29.9%) and overweight (21.5% vs 20.4%). Conclusions: The sweet eaters, while presenting a lighter degree of obesity (prevalence of overweight and obesity class I), mean values of triglycerides and total cholesterol lower, have a greater waist circumference ( 88 cm in 63.60% women vs. 56.90 % of NS; 102 cm in 71.40% males vs 54.80% of NS), a mean blood glucose and basal metabolic rate higher than the NS and the metabolic syndrome include the 39.21% vs 24.48% of NS. Moreover, family members positive for DM2, obesity, hypertension and dyslipidemias more frequently than NS. Therefore, sweet eaters appears to present a cluster of characteristics shifted towards more cardiometabolic risk (despite a degree of obesity lighter) than the NS population, with more suffering and psychiatric co-morbidity. 104 DIFFERENTIAL GENE EXPRESSION PROFILES OF CAROTID ARTERY STENOSIS BIOPSIES OF HCV+ AND HCV PATIENTS SUGGEST PECULIAR MOLECULAR MECHANISMS IN THE PATHOGENESIS OF THE DISEASE L. Rossi1 , I. Lapini1 , A. Magi1 , M. Boddi1 , A.L. Zignego2 , G. Pratesi3 , R. Pulli4 , C. Pratesi4 , R. Abbate1 , B. Giusti1 . 1 Department of Medical and Surgical Critical Care and DENOTHE Center, University of Florence, Italy; 2 Department of Internal Medicine, University of Florence, Italy; 3 Vascular Surgery Unit, Department of Surgery, University of Rome âTor Vergataâ, Rome, Italy; 4 Department of Vascular Surgery, University of Florence, Italy E-mail: betti.giusti@uniï¬.it Clinical and experimental evidence suggests that hepatitis C virus (HCV) infection shows peculiar characteristics that strongly support a role in the
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