Monday 6 October 1997: Posters Clinical trials (prevention, regression) 45

I 1 P. 134 LDL Y&e” and Lp(a) isoforms in polygenic hypercholesterolemia

D. Sieoi, S. Pagliaricci, R. Paltriccia. A.R. Roscini, G. Lupattelli, C. Parisi, S. Marchesi, M.T. Mrmzi, E. M annatino. Internal Medicine, Angiology and Atherosclemsis Unit, Policlinico Monteluce, University of Perugia 06122, Italy

Elevated LDL cholesterol levels, pattern “B” LDL and high lipoprotein (a) levels are important risk factors for atherotbrombosis. Lp(a) have different apoprotein isoforms: F, B, Sl, S2, S3, S4 and low molecular weight isoforms are associated with high Lp(a) concentration.

Ibis study investigated LDL pattern (using electrophoresis on polyacty- lamide gel) and isoforms (by immuno-blotting after electrophoresis on agarose gel) in 26 patients (16 males, 10 females, age range 45-65 years) with poly- genie hypercholesterolemia (PH.) and in 25 normolipemic controls (12 males, 13 females, age range 42-68 years). No significant differences emerged in LDL size in the group with PH. (x = 26.65 & 1.5 mn) compared with normal controls (x = 26.12 ZIZ 1.6 nm). In patients with polygenic hyper- cholesterolemia Lp(a) levels were higher than in controls (median 21.40 mg/dl, range 12.10-194.0 mg/dl vs median 14.85, range 12.10-11.0 mg/dl p < .OOOl) and the apo (a) isoforms were single band in 76% patients with P.H. and in 77% controls, double band in 24% compared with 19% controls. No band (null allele) was present in only 4% of the controls. These results seem to indicate the high risk of atherosclerosis in patients with polygenic hypercholesterolemia may be increased.

I 1 .P 135 Reduced HDL levels aIp a major feature of the dyslipidemia charncteristic of juvenile chronic arthritis

A.D. Tseleois’, S. Besis’, M. Eli&, S.-A.P. Karabma’, P.D. Lapatsanis2, M.J. Chanman4, A. Siamopoulou 2 ‘Department of Chemistry; 2Department . of Pediatrics; 3Department of Internal Medicine, Medical School, University of Ioannina, Greece; ‘INSERM V321 Hopital de la Pitie, 75651, Paris Cedex 13, France

One of the features of juvenile chronic arthritis (JCA) is dyslipidemia, charac- terized by low total plasma cholesterol (C) and high triglyceride (TG) levels. In the present study we ipirestigated the plasma lipoprotein subfraction profile and composition in JCA patients.

Methods: Twenty six JCA patients (12 boys and 14 girls; mean age 11 f 3 years) and 22 age and sex matched healthy volunteers (controls) were included in the study. Fifteen had polyarticular, 8 oligoarticular and 3 systemic JCA, whereas 14 had active and 12 inactive disease. Plasma lipoproteins were fractionated by isopycnic gradient ultracentrifugation into 9 subfractions, VLDL+IDL, LDLt-s, HDLz, HDLs and VHDL. The plasma C, TG levels as well as the C, TG, phospholipid and protein content of each subfraction were determined.

Resultsz Children with active JCA had lower levels of plasma C (122 f 17 vs 146 & 19 mg/dl, P c: 0.05) and HDL-C (27 & 6 vs 39 & 9 mgldl, P < 0.05), and higher plasma TG levels (59 -+ 14 vs 43 f 9 mg/dl, P e 0.003) compared to controls. The lower plasma C levels were mainly due to the decrease in the C content of VLDL+IDL and HDLz whereas the higher plasma TG levels were mainly due to the increase in the TG content of VLDL+IDL and LDL1-t. The lipoprotein mass of HDLz and HDLs was significantly lower compared to controls (114 f 47 vs 156 f 34 mg/dl, P < 0.009 and 156 i 25 vs 182 f 33 mg/dl, P < 0.03, respectively). No difference was observed in the pattern of subfraction profile of either LDL or HDL. Additionally, no differences were found in all the above parameters between controls and children with inactive JCA.

Conclusion: Children with JCA exhibit a dyslipoproteinemia which de- pends on the disease activity and concerns mainly the HDL levels (especially the HDL:! and HDLs subfractions) and the TG levels of the subfractions VLDL+IDL and LDL,4.

I 1 P 136 Premature wwneal arcus in familial hypercholesterolaemia is characteristic but not a marker of hulividnal coronary risk

A.F. Winder, L.B. Day, P.F. Butowski. Royal Free Hospital & School of Medicine, London, UK

The mean extent and rate of progression of comeal arcus with age was determined on a graded scale of O-4 from observations on 84 male 76 female total 160 definite heterozygotes for familial hypercholesterolaemia assessed before any lipid treatment [new HFH]. Scatter round this average was then determined for the 20 male and 11 female HFH patients within the group with

clinical coronary disease [CHD] plus 5 males, 3 females with confirmed silent CHD, and for 91 further HFH cases assessed after commencement of lipid treatment [old HFH]: 20 males and 11 females had clinical or silent CHD [8 cases]. Arctu progression with age was not relatively more advanced, faster tbsn average, in male or female new or old cases with clinical or silent CHD. Arcus is a qualitative marker of hypercholestemlaemia with progression with age in HFH some 10 years ahead of the general population, but within the HFH group the extent of progression is not a marker of individual risk of premature CHD. However the relationship for treated old HFH patients showed a trend with age below the mean relationship for the new FH group, consistent with some effects of treatment on the lipid-related processes underpinning arcus progression. FH is a good model for arcus as lipids are consistent until first treatment and these observations may apply beyond W.

We thank Foumier Pharmaceuticals UKfor supportfor LED

I 1 P.137 Dyslipidemias have a detrimental effect on left ventricular systolic function in patients with acute myocardial infarction

C.-C. Wu, T-D. Wang, W.-K. Tseng, W.-J. Chen, C.-M. Lee, M.-F Chen, C.-S. Liau, Y.-T. Lee. Department of Internal Medicine (Cardiology), National Taiwan University Hospital, Taipei, Taiwan

To examine the hypothesis that dyslipidemias can aggravate myocardial vulnerability following MI and that this deleterious effect is not entirely asso- ciated with the severity of coronary athemsclerosis, we assessed serum lipid profiles, other coronary risk factors, as well as tbe clinical, hemodynamic, and angiographic characteristics following MI in 165 consecutive patients presenting to our hospital with clinical and ECG evidence of acute myocardial infarction (AMI).

The patients were divided into three groups according to their total serum cholesterol level measured 3 months after MI. Group 1 consisted of 60 men and 6 women with a total serum cholesterol of ~200 mg/dl. Group 2 consisted of 5 1 men .md 8 women with a cholesterol level between 200 and 240 mg!dl. Group 3 consisted of 37 men and 3 women with a cholesterol level of >2Ao mg/dl. Age, gender distribution, body mass index, risk factors for comnary artery disease, and the prevalence of Q wave MI, anterior wall involvement, use of thrombolytic therapy, and Killip class III or IV were comparable in the 3 groups. Patients in group 3 tended to have more severe coronary atherosclerosis, as manifested by a higher Gemini score in group 3 (47 f 30) than in group 1 (36 f 24) and group 2 (37 i 27), though statistical significance was not reached (p = 0.13). The mean left ventricular ejection fraction was highest in group 1 (53 f 13%). middle in group 2 (43 f 14%), and lowest in group 3 (35 & 11%) (p < 0.0001). A significant correlation was found between the radionuclide left ventricular ejection fraction and 3-month total cholesterol (r = -0.48; p SC 0.0001) and LDL cholesterol (r = -0.55; p i O.OOOl), respectively. Stepwise multiple regression analysis revealed a significant correlation between post-MI left ventricular systolic function and LDL cholesterol (p = O.OOOOO3) and HDL cholesterol (p = 0.017) measured 3 months after MI; peak CK level (p = 0.026) and product of peak CK and time to CK peak (p = 0.011); and patency of infarct-related artery (p = 0.002), respectively.

In conclusion, dyslipidemias per se have a detrimental effect on left ven- tricular systolic function in patients with MI independent of their atherogenic properties.

CLINICAL TRIALS (PRJWENTION, REGRESSION)

I 1 P.138 Cerivastatin - M&ice&e, double-bUnd wmpwison with placebo and shnvastath~ in prhnary bedesterolaemia

D.J. Betteridge. The International Cerivastatin Study Group; University College Iondon Medical School, The Middlesex Hospital, London, UK

HMG-CoA reductase inhibitors have shown considerable benefit in the treat- ment of coronary heart disease and hypercholesterolaemia. Cerivastatin (CER) - a new, completely synthetic and highly selective HMG-CoA reductase inhibitor - effectively reduces LDL-C, total cholesterol and triglycerides at extremely low doses. In a double-blind, multicentre study (63 centres; 12 countries) patients were randomised to receive CER (0.025,0.05,0.1 and 0.2 mg/day), simvastatin (SIM, 20 mg/day) or placebo for 12 weeks following an optional 4-week dietary period and a 6-week single-blind placebo phase. A total Iof 894 patients (609 patients on CER) were evaluable for efficacy at the end of 12 weeks. CER at all doses significantly reduced LDL-C (up to

11th International Symposium on Atherosclerosis, Paris, October 1997