Association of the paraoxonase-1 Q192R polymorphism with coronary artery disease in AMI patients, non AMI CAD patients and healthy controls

Association of the paraoxonase-1 Q192R polymorphism with coronary artery disease in AMI patients, non AMI CAD patients and healthy controls

313 II XVIII S.I.S.A. National Congress [ I [ SECONDARY HYPERLIPEMIA WITH BILIOUS OBSTRUCTION. M. Pasquale . S. Asciutto , V. Bruzzese*, F. Nasso ...

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313 II

XVIII S.I.S.A. National Congress [

I

[

SECONDARY HYPERLIPEMIA WITH BILIOUS OBSTRUCTION. M. Pasquale . S. Asciutto , V. Bruzzese*, F. Nasso , R. Prete , E. Stellitano.

Impaired Endothelium-Dependent Brachial Arterial Reactivity in Patients with Familial Combined Hypedipidemia M. De Michele, A. Salvato, M. de Divitiis, P. Pauciullo, G. Marotta, S. Pan±co, A. lannuzzi, P. Rubba.

U.O. Medic±ha - U.O. Emodialisi* -P.O. Taurianova - A S 10 Palm± CLINICAL CASE: Patient woman, 73 aa., BMI 27,7, diabetic, hypertensive, with nodular goitre. Her didn't present familiarity for dyslipidemia and once the profil of lipids was always been normal. During an antecedent hospital±tat±on,we have diagnosed that she had a hepatic disease HCV correlated; the ultrasounds and the TAC of abdomen underlined a suspicious hepatic tumour that then was diagnosed as "hepatocarcinoma moderately differentiated". After about one year, blood tests showed increase of T-chol (457 mg/dl) and of bilirubin. For this reason she goes at new hospital±tat±on. Her exams showed: HDLchol: 6 mg/dl; T-bil: 7 mg/dl; D-bil: 5.23 mg/dl; GOT: 226 UI, Fibrinogen: 648 UI; gGT: 301 UI; T-chol (457 mg/dl). ApoA was of 0,26 g/I and ApoB was of 2.5 g/I. The measuring out of thyroid hormones noticed a decrease of TSH (0,226 UI) with FT3 and FT4 on the norm. The proteinuria was absent. The remarked hypercolesterolemia of our patient is a classical example of hyperlipemia secondary at biliary obstruction and is caused by a hydrate density such as LDL. In these cases, in fact, there are a lot of anomalous lipoproteins, defined LpX; the normal LDL, nevertheless, although are present, are in a reduced concentration and the ApoB serum is at lower levels than it could be anticipated by the concentration of the serum chol. The LpX consituted by 25% of chol, completely in free form, by more than 60% of phospholipids, by 6% of proteins, and for more of the half by Albumin. ApoB and ApoE are absent, ApoC and ApoD are on the surface. The increase of T-Chol follows the biliary stasis and the same cholesterolemia is the mirror of evolution of biliary obstruction as in this case.

Impaired brachial artery reactivity in offspring of type 2 diabetics Tesauro M, lantorno M, Rizza S, Cardellini M, Mar±n± MA, Sesti G, Federici M, Lauro D, A, Bellia Lauro R. Internal Medicine Department, Tor Vergata University-Rome Backgraound: Individuals with a parent with type 2 diabetes (DM) have an increased risk of diabetes, a major risk factor for cardiovascular disease. Endothelial dysfunction plays a central role in the development of atherosclerosis. The aim of this study was to determine whether differences exist in the endothelium-dependent and independent dilation of the conductance vessels beteween young first-degree relatives (FDRs) of subjects with DM and young control subjects (NS). Methods: Endothelium-dependent (posthyperemia flow-mediated dilation) and indipendent (nitroglycerin) dilation of the brachial artery was measured in two age, sex and BMI comparable groups: 40 FDRs (23 men, 17 women; mean age 32 years) and 23 NS with negative family history of diabetes (11 men, 12 women; 31 years), both normoglycemic normotensive nonsmoker and normocholesterelemic. Results: Baseline diameter was similar in FDRs and in NS (3,5+0,7 vs. 3,2+0,5 mm). Mean reactive hyperemia after cuff deflation was similar in the two groups (920+704 % in FDRs and 791+580% in NS; p=0,4). Flow-mediated dilation was significantly lower in FDRs compared with NS (9,6+6,2 vs. 13,8+8,2%; p=0,04). Nitroglycerin-mediated dilation was also significantly lower in FDRs compared with NS (13,8±8,0vs. 21,0+8,0%; p=0,001). Conclusions: FDRs of individuals with DM show reduced responsiveness of conductance arteries to both endogenous and exogenous NO compared with subjects with negative family history of diabetes. These findings suggest that abnormalities in vascular reactivity are present eady in individuals at risk of developing type 2 diabetes, even at a stage of normal fasting plasma glucose.

Department of Clinical and Experimental Medicine, Federico II University, Naples-Italy Background. Familial combined hyperlipidemia (FCHLP) is associated with a markedly increased dsk of premature coronary artery disease. The present study was designed to evaluate whether preclinical atherosclerotic functional abnormalities are detectable in the systemic arteries of FCHLP patients. Methods. Sixty subjects were recruited for the study: 30 individuals with FCHLP (mean age, 48 +/- 9 years), defined by fasting total plasma cholesterol and/or triglyceride concentrations > 250 mg/dL and by the occurrence of multiple lipoprotein phenotypes within a family, and 30 age- and sex-matched healthy controls. All subjects underwent high resolution B-mode ultrasound examination and the brachial arterial reactivity, a marker of endothelial function, was measured by using a sere±automated computerized program. Lipid profile, insulin, C-reactive protein, resting blood pressure, body mass index, and smoking status were also determined. Results. Compared with controls, FCHLP subjects had significantly higher body mass index, diastolic blood pressure, fasting total cholesterol, triglycerides, apoB and insulin concentrations. There was no difference in baseline vessel diameter between the two groups (3.4 +/- 0.5 mm for FCHLP vs 3.6 +/- 0.6 mm for controls, p = 0.17). In response to flow increase, the arteries of the control subjects dilated 8.9 +/- 4.9 % (range 2.3 to 20.8 %), whereas in the FCHLP subjects, brachial arterial reactivity was significantly impaired (5.5 +/- 2.5 %, range 0 to 10.1%, p = 0.002). In multivariate analysis, diastolic blood pressure values were independent determinants of attenuated brachial artery response to reactive hyperemia. Conclusions. The present findings suggest that vascular reactivity is impaired in the systemic arteries of FCHLP patients.

Association of the Paraoxonase-1 Q192R Polymorphism with Coronary Artery Disease in AMI patients, non AMI CAD patients and healthy controls. Min~ M, Onorato K, Fayer F, Caldarella R,G Novo, Valenti V, Barraco G, Davi' V, Cefalu' AB, Buglino C, Noto D, Notarbartolo A e Averna MR. Department of internal Medicine and Geriatrics - University of Palermo. Paraoxonase 1 (PON1) gene has been linked to atherosclerosis. PON's are HDL associated enzymes able to clear metabolites of lipid oxidation from circulation, reducing the generation of oxidated LDLs. The PON-I Q192R polymorphism is the only one linked to reduced enzyme activity. The association studies of this polymorphism gave contrasting result. In our study PON-1 Q192R was assessed in 702 AMI patients, in 613 healthy subjects of comparable age, gender and diabetes prevalence and in 163 non AMI, CAD patients ascertained by coronarography. AMI patients showed lower levels of total, LDL and HDL cholesterol, higher prevalence of diabetes meflitud, hypertension and family history of CAD. PON-1 polymorphism showed an increased prevalence of the rare allele only in women ( IMA 28%, CHD 28%, controls 22%) but not in men ( IMA 25%, CHD 25%, controls 24%). The same allele was not associated with the extension of the coronary disease by coronarography ( 0,1,2 or more vessels respectively 21%, 20%, 20%). The polymorphism was not associated in patients with higher risk such as diabetic or smokers, in our sample classic risk factors as diabetes mellitus, smoke, hypertension low HDL cholesterol are associated with the cardiovascular disease.