Influence of apolipoprotein E polymorphism on the effect of atorvastatin and bezafibrate in patients with mixed dyslipidemia, atomix study

Influence of apolipoprotein E polymorphism on the effect of atorvastatin and bezafibrate in patients with mixed dyslipidemia, atomix study

71st EAS Meeting Abstracts accepted for presentation in the abstract book COMBINED PRAVASTATIN - FENOFIBRATE THERAPY IN SECONDARY PREVENTION OF CORONA...

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71st EAS Meeting Abstracts accepted for presentation in the abstract book COMBINED PRAVASTATIN - FENOFIBRATE THERAPY IN SECONDARY PREVENTION OF CORONARY ARTERY DISEASE D. Pella, R. Rybfir, D. Trejbal. 2nd Internal Clinic Faculty Hospital Kogice,

Slouakia Secondary prevention target levels 2.5 mmol/I may be achieved with monotherapy in only fraction of cases. Others may require the concomitant administration of other cholesterol lowering drugs. The authors submit experiences with the treatment of 20 patients suffering from coronary artery disease and combined hyperlipidaemia types D or E - EAS classification. They started therapy with the morning dose of 200 mg of micronised fenofibrate combined with the evening dose of 20 mg of pravastatin. They determined levels of serum lipids and fibrinogen before and after 3 months of this therapy. Laboratory results in mmol.q (selected): befo~ therapy

after therapy

tots] cholesterol

7.52:1:0.81

4.98±O53"

triglyccrides

4, ! 0~: 1.92

2.2 ! ± 0 . 9 2 °

fibrinogen (g/I)

4.60±0,45

2.83=1=0.41 *

" p < 0.01

Combined treatment with pravastatin and fenofibrate was well tolerated by all patients. No adverse events were observed during therapy period. In conclusion LDL target levels were achieved in 16 patients (80%), significant decrease of serum fibrinogen levels were observed. INFLUENCE OF APOLIPOPROTEIN E POLYMORPHISM ON THE EFFECT OF ATORVASTATIN AND BEZAFIBRATE IN PATIENTS WITH MIXED DYSLIPIDEMIA. ATOMIX STUDY L. Garcia-Otin 2, R. Aristegui 1, C. Diaz 1, J.M a. Sol t , G. Herufindez1, M. Pocovi2. For the ATOMIX study group. I R&D Department. Parke-Davis.

Spain. 2Department of Biochemistry, Molecular and Cellular Biology. UniuersiO, of Zaragoza. Spain Objectives: Apolipoprotein E (apo E) is a polymorphic protein controlled by 3 alleles (E2, E3, and E4), resulting in 6 different phenotypes. This polymorphism influences cholesterol metabolism and could also modify the effect of lipid-regulating drugs. ATOMIX is a I-year, double-blind, multicenter study that evaluates the efficacy and safety o f atorvastatin compared with bezafibrate in patients with mixed dyslipidemia. The objective of this substudy is to evaluate the influence of ApoE polymorphism on the lipid response to these two pharmacological treatments. M e t h o d o l o g y : ApoE genotype was determined in 80 patients by apoE restriction isotyping of amplified DNA. Results: Enrollment was completed in January 1998 and the results o f the study will be available in April 1999. Baseline analysis showed that the most frequent genotypes were E3/E3 (68%), and E3/E4 (24%). The were no statistically significant differences between apoE subgroups regarding demographic and baseline lipid data with the exception of the presence of HTA, more frequent in group E3/E3 (64%) vs. the E3/E4 (27%), (p<0.05). Conclusions: The results of the study will be presented and will demonstrate whether ApoE polymorphism influences the efficacy of lipid-lowering therapy in mixed dyslipidemia.

WHAT'S THE REASON FOR THE DIFFERENCE OF CAD MORTALITY RATE DURING VARIOUS SEASONS IN ISFAHAN _M. Rafiei, M. Boshtam, N. Sarrafzadegan, Gh. Naderi, A. Asgary, S. Zarfeshani. Isfahan Cardiovascular Research Center, [sfahan. lran Coronary artery disease (CAD) is one o f the prevalent disease in the world. In Isfahan, a big city of iran, CAD is the first killer in people over 25 years. Some studies have showed that the occurence of this disease is more in cool seasons than the warm ones. In a 16-year study done in Isfahan we observed that the mortality rate from CAD is more (about 27%) in spring than other seasons, during 1980-1995. In another study in Isfahan population we found that the amount of urinary excretion sodium chloride is more in spring than others (n = 1800). The results of a 24-hr recall study in 1994 on dietary habits and nutrients intake in this population showed that there is the most intake of protein (70 ~ 49 gr/day), fat (90 ~ 41 gr/day) and carbohydrate (450 ~ 167 gr/day) in spring than other 3 seasons (n = 3200). The mean of salt consume is more in spring season than the others (for

203

women = 29.6 ~ 6.0 gr/day, for men 30.1 ~ 6.5 gr/day, total = 29.9 ~ 6.3 gr/day). Also the trend of fat, carbohydrate and protein intake, urinary sodium chlorid excrestion and mortality rate from CAD based on season was the same. Comparing the data from mentioned studies, it is found that in isfahan, nutrition is the most important factor for CAD mortality in various seasons and the role of weather can be rejected. Therefore, to decline CAD motrality rate in Isfahan population, we must focuse on nutrition. =

QUINAPRIL DECREASED I$-LIPOPROTEINS LEVEL WITHOUT SIGNIFICANT CHANGES IN PLASMA CHOLESTEROL CONCENTRATION IN RABBITS FED CHOLESTEROL-RICH DIET M. Stajszczyk 1'2, J. Gminski 1'2, W. Wojakowski 1.2, K. Siemianowicz1, M. Goss I , M. Machalski 2. t Department of Experimental and Clinical

Biochemistry; 2 Clinic of Internal Medicine and Chemiotherapy. Silesian Medical Academy, Poland Activation of renin-angiotensin system seems to play very important role in the pathogenesis of atherosclerosis. In various experimental models of atherosclerosis, including cholesterol-fed animals and WHHL rabbits, ACE inhibitors treatment inhibited the progression of atherosclerotic changes in the arterial wall. In these models ACE inhibitors were found to derease cholesterol accumulation in the vessel wall without significant changes in plasma cholesterol level. The aim the study was to asses the influence o f quinapril, an ACE inhibitor, on plasma lipoproteins level in cholesterol-fed rabbits. Forty male New-Zealend rabbits were devided into four equal groups: I - fed standard diet; II - fed 1% cholesterol diet; Ill and IV - fed I% cholesterol diet + quinapril in oral dose 0.75 and 7.5 mg/kg per day, respectivaly. After six months lipid parameters were assesed: total, LDL, HDL cholesterol and triglycerides were evaluated spectrophotometrically and lipoproteins profile was analysed electrophoretically using Paragon system. At the end of the study total cholesterol, LDL cholesterol and triglycerides concentration and also [~-lipoproteins and pre~-lipoproteins fractions were increased but HDL cholesterol and ct-lipoproteins fraction were decreased in cholesterol-fed rabbits when compared with animals fed a standard diet. Treatment with quinapril in a higher dose significantly decreased triglycerides and increased HDL cholesterol concentration (p < 0.02 and p < 0.05, respectivaly) but had no influence on total and LDL cholesterol level. At the same time it was observed that in quinapril group ~lipoproteins and pre-~8lipoproteins fractions were decreased (p < 0.05 and p < 0.001, respectivaly) and ~-lipoproteins fraction was increased (p < 0.001) in comparison with cholesterol-fed rabbits. In our study we have shown that quinapril, non-sulfhydryl ACE inhibitor, lowered level o f atherogenic ~-lipoproteins without significant changes in plasma cholesterol concentration. Observed effect might be a reason of decreased cholesterol accumulation in arterial wall in cholesterol-fed animals after ACE inhibitor treatment. The precise mechanism ofquinapril action is unknown and may depend on the influence on apo-B-100 synthesis. CORRELATION BETWEEN ISCHEMIC HEART DISEASE AND H. PYLOR1 INFECTION, VITAMIN B I 2 AND FOLIC ACID S. Liberi, E Agelis, N. Sofoulis, B. Armonis, M. Stampori, J. Christakopoulou, K. Karidis. Department of Cardiology Chest Hospital

of Athens. Greece Aim: To investigate the possible importance o f chronic H. Pylori infection as etiologic factor for ischemic Heart Disease due to low serum levels of Vit. BI2 and Folio Acid cansed. Materials and M e t h o d s : We studied two groups: the group o f Coronary Artery Disease - CAD - patients (A) and the group of individuals without CAD (B). Group o f CAD patients (A): It consisted o f 69 ICU patients admitted for an acute coronary episode, 42 (60.9%) were male and 27 (39.1%) were female, mean age was 66.94-9.8 years, H. Pylori seropositive were 52 (75.3%), mean serum Vitamin B12 and Folic Acid serum were 411.8=t:100.9 ng/Ml and 10.2+2.1 ng/mL respectively. Group of individuals without CAD (B): It consisted of 78 individuals with negative history and ECG evidence of CAD, 51 (65.4%) were male and 27 (34.6%) female, mean age was 67=t=9.4 years, mean serum Vitamin BI2 and Folic Acid levels were 456.4+118.1 ng/mL and 114-2.4 ng/mL respectively. - Both groups were comparable in terms of age and sex. We recorded in a special questionnaire their demographic characteristics and cardiocirculatory risk factors.

71st EAS Congress and Satellite Symposia