The effect of the apolipoprotein E phenotype on cholesteryl ester transferprotein activity, plasma lipids and apolipoprotein A I levels in hypercholesterolaemic patients on colestipol and lovastatin treatment

Background: Apolipoprotein E (apo E) allele E 4 is associated with high ath erogenic lipid levels and coronary heart disease. Cholesteryl ester transfe r protein (CETP) transfers cholesteryl esters from (high density lipoprotei n) HDL to other lipoproteins. CETP gene expression is enhanced in hyperchol esterolaemia and correlates with plasma apo E concentration. Objective: The effect of the apo E phenotype on plasma CETP activity and th e hypolipidaemic efficacy of colestipol and lovastatin was studied in patie nts with type II a or II b hypercholesterolaemia. Results: The baseline mean plasma total, low density lipoprotein (LDL) and HDL cholesterol, triglyceride, apolipoprotein A I (apo A I) concentrations and CETP activity were 8.89 mmol.l(-1), 6.78 mmol.l l(-1) 1.39 mmol.l(-1). 1.59 mmol.l(-1) 1.49 g.l(-1) and 114 nmol.h(-1.)ml(-1) respectively. The co lestipol-induced changes were -26%, -36%, +5%, +12%, -1% and -17%, and the lovastatin-induced changes -34%, -44%, +6%, -18%, +1% and -19%. The lipid a nd apo A I concentrations or the CETP activity did not differ statistically significantly according to the apo E phenotype, although the HDL cholester ol and apo A I levels were lowered in patients with apo E 4/4 but elevated in patients with the other phenotypes. The CETP activity correlated with th e LDL cholesterol concentration (r = 0.52, P = 0.01) and the change in the LDL cholesterol during colestipol (r = 0.51, P = 0.02) and lovastatin(r = 0 .65, P = 0.001) treatment, but only in patients without the apo E 4 allele. Conclusion: Colestipol and lovastatin reduced CETP activity to the same amo unt, regardless of the apo E phenotype. The apo E phenotype seems to modify the interaction between CETP activity and LDL cholesterol in hypercholeste rolaemia and during pharmacological lowering of cholesterol.