Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia

Abstract

Kinetics of apo B and apo AI were assessed in 8 patients with mixed hyperlipidemia at baseline and after 8 weeks of atorvastatin 80 mg q.d. and micronised fenofibrate 200 mg q.d. in a cross-over study. Both increased hepatic production and decreased catabolism of VLDL accounted for elevated cholesterol and triglyceride concentrations at baseline. Atorvastatin significantly decreased triglyceride, total, VLDL and LDL cholesterol and apo B concentrations ( ؊ 65%, ؊ 36%, ؊ 57%, ؊ 40% and ؊ 33%, respectively, P Ͻ 0.05). Kinetic analysis revealed that atorvastatin stimulated the catabolism of apo B containing lipoproteins, enhanced the delipidation of VLDL 1 and decreased VLDL 1 production. Fenofibrate lowered triglycerides and VLDL cholesterol ( ؊ 57% and ؊ 64%, respectively, P Ͻ 0.05) due to enhanced delipidation of VLDL 1 and VLDL 2 and increased VLDL 1 catabolism. Changes of HDL particle composition accounted for the increase of HDL cholesterol during atorvastatin and fenofibrate (18% and 23%, P Ͻ 0.01). Only fenofibrate increased apo AI concentrations through enhanced apo AI synthesis (45%, P Ͻ 0.05). We conclude that atorvastatin exerts additional beneficial effects on the metabolism of apo B containing lipoproteins unrelated to an increase in LDL receptor activity. Fenofibrate but not atorvastatin increases apo AI production and plasma turnover.

Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism

“…In our study, no significant effect of atorvastatin on apoA-I PR or FCR was observed. These results are in agreement with previously published studies indicating no effect of atorvastatin on the kinetics of apoA-I (6,(40)(41)(42)(43). The change in HDL-C with atorvastatin was independent of apoA-I kinetics.…”

Fenofibrate Effectively Reduces Remnants, and Small Dense LDL, and Increases HDL Particle Number in Hypertriglyceridemic Men — A Nuclear Magnetic Resonance Study

“…The latter observation was further supported by the significant reduction of RLP-C, a clinical parameter of remnants. The underlying metabolic mechanisms for these reductions are likely due to the increased catabolic rate, as consistently demonstrated by two recent kinetics studies (31,32). Although TG-rich lipoproteins are heterogeneous in size and composition, whereby in association with atherosclerosis, large VLDL, which possesses the highest capacity for inducing macrophage lipid loading, is preferentially reduced by fenofibrate (34).…”

“…Several studies have focused on the effects of fenofibrate on li-indicate that increased HDL-C by fenofibrate is likely due to an increased production of apoA-I (31,32), together with decreased cholesteryl ester transfer protein activity (19) and increased ABCA1 (33). Overall, its observed alteration of HDL makes fenofibrate an ideal agent for strengthening the anti-atherogenic properties of HDL, when used in hypertriglyceridemic patients.…”

Molecular Mechanisms of HDL-Cholesterol Elevation by Statins and Its Effects on HDL Functions

“…8). Clinical results demonstrated that atorvastatin did not change the production rate (PR) or fractional catabolic rate (FCR) of ApoA-I 113) . Administration of atorvastatin to mice did not significantly change ApoA-I expression in the liver and reduced ABCA1 and CETP expressions in the liver, indicating that the HDL-elevating effect of atorvastatin may be mediated mainly by CETP inhibition 59) .…”