Monday 6 October 1997: Posters Hypolipidemic treatments 59

beta-oxidation correlated to the CPT-II and not the CPT-I activity. Our data suggest that WI-11 has a more important role than WI-1 concerning the stimulated beta-oxidation after thia fatty acid administration.

Several lines of evidence have implicated that ape C-III in plasma triglyc- eride metabolism. For example, apo C-III impairs the uptake of triglyceride rich lipoproteins by the liver. The 3-thia fatty acid, TTA lowered rat liver apo C-III mRNA levels. An unchanged apo E may lead to a decreased apo C-III/ape E ratio of triglyceride-rich particles, which then could be more efficiently cleared from plasma. Therefore, the decrease in apo C-III gene expression by ‘ITA provides an additional potential mechanism by which this drug induce a less atherogenic plasma lipoprotein profile.

[ 1 .P.ZOO ] Marked reduction of LDL-apheresis by treatment with LDL-apheresis and atorvastati in a case of homozygous familial hypercholesterolemia (FH)

Y. Mikami’, Y. Hommaz, K. Tagata:‘. ‘Department of Cardiology, Shizuoka Red Cross Hospital, 8-2, Otemachi, Shizuoka; “Division of Medical Electronics, Shizuoka Red Cross Hospital, 8-2, Otemachi, Shizuoka; 2Tokai University Oiso Hospital, Japan

Normalization of plasma LDL-C levels was attempt by treatment with LDL apheresis and potent hypochoresterolemic drugs in a case of FH. A case of homozygous FH was treated by LDL-apheresis using dextran sulfate cellulose columns every 2 weeks and drugs. 6L of plasma were treated at each LDL-apheresis. The effect of regimen A [probucol (1000 mg/day) + pravastatin (20 mg/day) + cholestyramin (12 g/day)] and regimen B [probucol (1000 mg/day) + atorvastatin (10 mg/day)] were compared at 2 weeks after LDL-apheresis. Plasma LDL-C levels was 337 mg/dl on regimen A before LDL-apheresis treatment. Plasma LDL-C levels were 236 f 22 mg/dl2 weeks after LDL-apheresis on regimen A. Those were 180 f 5 mg/dl 2 weeks after LDL-apheresis and regimen B. Thus the combination treatment with LDL-apheresis and potent hypocholesterolemic drugs is expected to normalize plasma LDL-C levels in this homozygous FH treatment.

( 1 .P.201 1 Anti-atherogenic effect of calcium antagonist plus statin cotreatment realises at lipoprotein level

A.N. Orekhov, V.V. Tertov, LA. Sobenin, E.M. Pivovarova. Institute of Experimental Cardiology, Cardiology Research Centre, Institute for Atherosclerosis Research, Ltd., Moscow, Russia

Recently, the Regression Growth Evaluation Statin Study (REGRESS) re- vealed synergistic anti-atherogenic effect of lipid lowering therapy with pravastatin in combination with calcium antagonists. In our study, we tried to elucidate the mechanism of more pronounced effect of statin-calcium antago- nist cotreatment. Smooth muscle cells cultured from subendothelial intima of human aorta were incubated with whole blood serum or low density lipopro- tein (LDL) taken from patients cotreated with lovastatin and amlodipine. As a result of the cotreatment, serum added to cells cultured from atheroscle- rotic lesion reduced cell cholesterol. Such an anti-atherosclerotic effect of the cotreatment has been revealed earlier and was more pronounced compared with the effect of the treatment with amlodipine or lovastatin alone. LDL isolated from atherogenic plasma stimulated cell cholesterol accumulation. Treatment with amlodipine alone and amlodipine-lovastatin combination lowered this atherogenic effect of LDL but combination demonstrated considerably higher anti-atherogenic effect at the lipoprotein level. Amlodipine-lovastatin cotreat- ment increased sialic acid and decreased LDL susceptibility to oxidation more effectively than amlodipine alone. In addition, the cotreatment reduced LDL negative charge while amlodipine alone was impotent. These findings may serve as an explanation of more pronounced anti-atherogenic effect at the lipoprotein level of amlodipine-lovastatin cotreatment compared with amlodipine alone.

1 1 .P.202 ] Verapamil plus garlic: A development of non-lipid-lowering anti-atherogenic therapy

A.N. Grekhov, E.M. Pivovarova, IV. Shutikhma, G.I. Kuntsevich. Institute for Atherosclerosis Research, Ltd., Russian Cardiology Research Centre, A. V -Vishnevsky Surgery Institute, Moscow, Russia -’

A culture of human aortic smooth muscle cells was used as a model for the development of a direct antiatherogenic drug therapy. Blood serum obtained from patients with carotid atherosclerosis induces cholesterol accumulation in cultured cells. Serum taken after administration of a single dose of calcium

antagonist, verapamil, or garlic powder tablet causes significantly less intra- cellular cholesterol accumulation. Long-term treatment with garlic powder tablets eliminated serum atherogenicity completely or dramatically reduced it. The combination of garlic powder tablet plus verapamil possessed higher antiatherogenic efficacy. Neither the combination nor verapamil or garlic tablet alone affectecl blood lipids significantly. To reveal a relationship between the reduction of c,erum atherogenicity and the development of carotid atheroscle- rosis, a pilot study was performed. The development of atherosclerosis was monitored by B-mode ultrasonography every 3 month during a two-year period. The trial included men without diseases requiring continuous therapy. Atherosclerotic lesions in their carotid arteries did not require surgery. Plaque monitoring was accompanied with the determination of serum atherogenic potential in cell culture. The preliminary data of l-year observation show that cotreatment with verapamil and garlic powder tablets reduces intima plus media thickness by 0.05 mm (p < 0.006).

1 P.203 I p&king physician in Korea

Quality assessment on management of hyperlipidemia in

H.S. Park, H. Cho. Department of Family Medicine, Asan Medical Center, College of Medicine, Ulsan University, 388-l Poongnapdong Sopagu, Seoul, Korea

Hyperlipidemia is a well-known risk factor of coronary heart disease (CHD). Comprehensive care for the prevention of CHD have been reinforced recently according to the increment of mortality by CHD in Korea. The guideline of management for hyperlipidemia was established in Korea as well as in many countries. This study was designed to investigate how the hyperlipidemia was managed by primary care physician in community. We surveyed the status of management for hyperlipidemia about screening, diagnosis, risk factor analysis, nonpharmacological patient education, and drug treatment by questionnaire using mailing to 3,385 primary physicians in our coun- try. The response rate was 12.8%. The subjects were composed by family physicians 38.8% and internist 60.5%. The frequency of carrying out screen- ing test was 65.4%. The frequency of screening test in terms of 5 years was only 1.4%, and of testing TC and HDL-C as screening test was only 0.3%. Risk factor analysis and nonpharmacological patient education were carried out well relatively. The barrier to carrying out screening test and risk factor analysis was noticed to curtailment by medical insurance. After serum lipid profiles were normalized, 43.6% of physicians stopped medica- tion, 36.1% reduced dose of medication, and 17.2% continued medication. Carrying out about screening test was far from recommend guidelines, and screening test and LDL-cholesterol assessment were affected by insurance system and reimbursement. Modification of payment system and education about guidelines are needed for the quality improvement of management for hyperlipidemia.

m. 1. P 204 Hi density lipoproteins functional properties in patients treated with fluvastatin

N. Perova, G. Kolpakova, I. Ozerova, D. Aronov, V. Metelskaya. National Research Centre for Preventive Medicine, Moscow, Russia

In multicenler fluvastatin (Sandoz Pharma) drug trial conducted in Moscow it was detected that HDL cholesterol (HDL-C)-elevating effect of fluvastatin appeared significantly later than its hypolipidemic effect (8 weeks vs 4 weeks of treatment). This study addressed the issue whether the modulation of HDL-C level by fluvastatin was associated with modification of HDL particles themselves as well as HDL components determining their choles- terol accepting function. To meet this aim we studied the ability of total HDL (d = 1.065-1.21 g/ml) to promote the efflux of t3H]-C from cultured human fibroblasts preliminary loaded with cholesterol. Cholesterol efflux was evaluated as a per cent of radioactive label found in medium after 6-hours incubation Iof cells with HDL (40 wg of protein/ml) from total radioactivity in cells and medium. Experiments were carried out using HDL isolated from blood of CHD patients treated with fluvastatin during 4 and 8 weeks: phospholipid composition of HDL from the same patients was analyzed by thin layer chromatography. In all cases after 4-weeks of fluvastatin treatment HDL had increased efflux ability, 9% in average. After 8 weeks there was no significant difference in mean HDL ability to promote cholesterol efflux. It is noteworthy that the most prominent HDL phospholipid composition changes were detected also after first 4 weeks of treatment: significantly increased portion of phosphatidylcholine from 69.8% to 71.6%, sphingomyelin from 10.5% to 1:!.6%, phosphatidylethanolamine from 3.0% to 4.3%, and decreased portion of lysophosphatidylcholine from 15.8% to 9.5%.

Ilth International Symposium on Atherosclerosis, Paris, October 1997