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 transfer (CET) from HDL to apo B-containing lipoproteins. The aim of this study was to examine the effects of postprandial lipaemia and pravastatin treatment on plasma triglycerides (TG) and CETP activity and on CET and LDL Stokes' diameter in primary HC (n = 19, total cholesterol > or =6.5, LDL-cholesterol > or =4.5, TG <4.0 mmol/l). Samples were collected fasting and 6 h after an oral fat load (0.88 g/kg body weight) after 6 weeks therapy with placebo or pravastatin 40 mg nocte according to a double-blind randomized cross-over study. Apart from significant reductions in plasma total cholesterol, LDL-cholesterol apo B and TG. pravastatin 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 equivalent placebo phases. CETP activity did not change during postprandial lipaemia despite a significant 45-55% increase in CET to triglyceride-rich lipoproteins (TRL) of d <1.006 g/ml. LDL Stokes' diameter was unchanged postprandially 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 CET. 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 variation (45%) for placebo- and pravastatin-treated HC. We conclude that pravastatin may reduce the atherogenicity of the lipoprotein profile in HC by reducing CETP activity. Furthermore, CET is strongly influenced by postprandial lipaemia which may have a cumulative effect on LDL size.
Contacos
C
C
Department of Clinical Biochemistry, Royal Prince Alfred Hospital, New South Wales, Australia.
Barter
P J
PJ
Vrga
L
L
Sullivan
D R
DR
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D017035:Pravastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D004041:Dietary Fats; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol; D017035:Pravastatin