Statins but not fibrates improve the atherogenic to anti-atherogenic lipoprotein particle ratio: a randomized crossover study

Sammy Y Chan,Gb John Mancini,Andrew Ignaszewski,Jiri Frohlich

doi:10.1186/1472-6904-8-10

Abstract

BackgroundPrior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis. Knowledge of effects of lipid lowering drugs on lipoprotein subclasses is useful. We treated subjects with hyperlipidemia sequentially with statins and fibrates, the 2 main classes of lipid lowering therapy and studied changes in NMR lipoprotein subclasses.Methods35 subjects (21 males; 60 ± 12 y) were enrolled in a crossover study. Subjects had baseline lipid profile & apoB. Lipoprotein subclasses, particle numbers and diameters were assessed with NMR spectroscopy. Subjects were randomized to simvastatin 20 mg or fenofibrate 200 mg. Repeat testing was done at 12 weeks. After 6 week washout, subjects were started on alternate drug for 12 weeks with pre/post tests.ResultsBoth therapies resulted in expected changes in lipids and apoB. Decreases in total cholesterol, LDL and apoB were greater with simvastatin. Fenofibrate led to small increase in HDL. Both therapies decreased LDLP. Reduction in LDLP was greater with simvastatin (32%, p < .001) compared to fenofibrate (17%; p = .036 vs pre; p = .027 vs simvastatin end). Fenofibrate resulted in 17% rise in large LDLP (p = .06 vs pre) and 32% drop in small LDLP (p = .007 vs pre). Simvastatin led to decrease in both LDLP fractions (19% large LDLP; p = .001 vs fenofibrate end; 34% small LDLP, p = .019 vs pre). With fenofibrate, LDLP size increased from 20.4 nm to 20.8 nm (p = .037). There was no change in LDLP size with simvastatin. There was 18% increase in HDL particle number (HDLP) with fenofibrate (p = .05). There were no changes in HDLP with simvastatin. There were no changes in HDLP size with either drug. Pre- and post-therapy LDLP/HDLP ratio was similar with fenofibrate but was reduced by simvastatin (p = .045).ConclusionSimvastatin reduced LDLP across all subclasses with no effect on size. Simvastatin had no effect on HDLP. Fenofibrate had weak effect on LDLP number but increased LDLP size by raising large LDLP and reducing small LDLP. Fenofibrate had weak effect on HDLP number with no change in size. Importantly, net atherogenic to antiatherogenic lipoprotein ratio (LDLP/HDLP) was reduced by simvastatin but not by fenofibrate.

Highlights

Prior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis
In a detailed analysis of the factors associated with angiographic progression/regression in the Familial Atherosclerosis Treatment Study, Zambon et al showed that LDL buoyancy accounted for 37% of the variance whereas apolipoprotein B only accounted for 12%[5]
Lipid profile At baseline, all subjects had relatively high total cholesterol, LDL-C and apoB. Both fenofibrate and simvastatin therapy resulted in significant changes in all parameters of Glucose Insulin HOMA Creatinine C reactive protein Fibrinogen (g/L) Weight Height Body mass index Lipid profile Total Cholesterol LDL-C high density lipoprotein (HDL)-C Triglycerides ApoB (g/L)

Summary

Introduction

Prior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis. Most of the emphasis has been placed on lowering of low density lipoprotein (LDL) cholesterol. It is usually thought of as a single entity, LDL is comprised of multiple different subclasses that differ in size, density, physicochemical composition, buoyancy and metabolic behaviour. All these factors influence their atherogenicity[3,4]. In a detailed analysis of the factors associated with angiographic progression/regression in the Familial Atherosclerosis Treatment Study, Zambon et al showed that LDL buoyancy accounted for 37% of the variance whereas apolipoprotein B (a measure of number of LDL particles) only accounted for 12%[5]. The same investigators showed that subjects with predominantly large and buoyant LDL require aggressive reduction of LDL cholesterol whereas those with Familial Combined Hypercholesterolemia require LDL cholesterol lowering as well as reduction in the number of small, dense LDL particles[6]

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