Cholesteryl ester transfer in hypercholesterolaemia: fasting and postprandial studies with and without pravastatin

Subjects with hypercholesterolaemia (HC) have increased fasting cholesteryl ester transfer protein (CETP) activity and accelerated cholesteryl ester t ransfer (CET) from HDL to apo B-containing lipoproteins. The aim of this st udy was to examine the effects of postprandial lipaemia and pravastatin tre atment on plasma triglycerides (TG) and CETP activity and on CET and LDL St okes' diameter in primary HC (n = 19, total cholesterol greater than or equ al to 6.5, LDL-cholesterol greater than or equal to 4.5, TG < 4.0 mmol/l). Samples were collected fasting and 6 h after an oral fat load (0.88 g/kg bo dy weight) after 6 weeks therapy with placebo or pravastatin 40 mg nocte ac cording to a double-blind randomized cross-over study. Apart from significa nt reductions in plasma total cholesterol: LDL-cholesterol apo B and TG, pr avastatin significantly reduced CETP activity in both the fasting (mean +/- SD, 37.9 +/- 12.2 to 32.0 +/- 10.3 nmol/ml plasma per h) and postprandial state (35.5 +/- 11.3 to 31.3 +/- 9.5 nmol/ml plasma per h) compared to equi valent placebo phases. CETP activity did not change during postprandial lip aemia despite a significant 45-55% increase in CET to triglyceride-rich lip oproteins (TRL) of d < 1.006 g/ml. LDL Stokes' diameter was unchanged postp randially or by pravastatin. The mass of TRL was the strongest contributor to variation in CET in both fasting and postprandial plasma, accounting for at least 77% of the variance of GET. Postprandial TRL-TG was the strongest contributor to variation in fasting LDL Stokes' diameter in untreated HC ( 54%) whilst HDL-cholesterol was the strongest fasting contributor to variat ion (45%) for placebo- and pravastatin-treated HC. We conclude that pravast atin may reduce the atherogenicity of the lipoprotein profile in HC by redu cing CETP activity. Furthermore, CET is strongly influenced by postprandial lipaemia which may have a cumulative effect on LDL size. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.