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Papers In Press, published online ahead of print October 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300309-JLR200
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Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Basel 4031
Corresponding Author: ukeller{at}uhbs.ch
Kinetics of apolipoprotein B (apo B) and apolipoprotein AI (apo AI) in plasma lipoproteins was assessed in 8 male patients with mixed hyperlipidemia at baseline and after 8 weeks of therapy with either atorvastatin 80 mg q.d. or micronised fenofibrate 200 mg q.d. in an open cross-over study. Both increased hepatic production and decreased catabolism of very low density lipoproteins accounted for the elevation of plasma cholesterol and triglycerides at baseline. Atorvastatin significantly decreased plasma triglycerides, total, VLDL and LDL cholesterol and apo B concentrations (-65%, -36%, -57%, -40% and –33%, respectively, p<0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL1 and decreased their production in some patients. Fenofibrate lowered plasma triglycerides and VLDL cholesterol (-57% and –64%, resp., p<0.05) due to both enhanced delipidation of VLDL1 and VLDL2 and an increase in VLDL1 catabolism. LDL cholesterol and apo B concentrations remained unchanged secondary to a decrease in LDL catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, p< 0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, p<0.05). We conclude that in subjects with mixed hyperlipidemia atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity and that fenofibrate but not atorvastatin increases apo AI production and plasma turnover.
Revised on September 17, 2003
Accepted on September 23, 2003
Effects of atorvastatin versus fenofibrate on apolipoprotein B-100 and apolipoprotein A-I kinetics in mixed hyperlipidemia
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