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

Abstract

Hypertriglyceridemia is often associated with small dense low density lipoprotein (LDL), elevated remnants, and decreased high density lipoprotein (HDL)-cholesterol (C), which comprise the dyslipidemic triad. The objective of this study was to investigate the effect of fenofibrate on the lipoprotein subfraction profile and inflammation markers in hypertriglyceridemic men. Twenty hypertriglyceridemic men were administered fenofibrate, 200 mg daily, for 8 weeks. Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy. Inflammation markers including C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were also determined. Fenofibrate lowered triglyceride (TG) by 58% and increased HDL-C by 18%. NMR analysis revealed that very low density lipoprotein (VLDL), particularly large VLDL, intermediate density lipoprotein (IDL), and small LDL, were significantly decreased, and LDL distribution shifted towards the larger particles. HDL distribution was altered; there was an increase in small HDL and a decrease in large HDL, resulting in a significant decrease in HDL particle size, from 9.1 to 8.9 nm, as well as a 27% increase in HDL particle number. Among inflammation markers, CRP was significantly decreased by 42%. In conclusion, fenofibrate effectively improves atherogenic dyslipidemia by reducing remnants and small LDL, as well as by increasing HDL particles. These effects, together with the favorable effect on inflammation, might provide a clinical benefit in hypertriglyceridemic subjects. J Atheroscler Thromb, 2004; 11: 278-285.

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

“…Our findings on NMR-measured lipoprotein subclasses are consistent with an earlier open-label report of fenofibrate (200 mg daily) therapy (27). Among 20 patients with severe hypertriglyceridemia (mean triglyceride levels 5.08 Ϯ 2.84 mmol/l), fasting chylomicron and large VLDL triglyceride levels were reduced (Ϫ84.0 and Ϫ65.5%, respectively), as was small LDL cholesterol (Ϫ42.0%).…”

Effects of fenofibrate on atherogenic dyslipidemia in hypertriglyceridemic subjects

“…Several previous studies have shown that fibrate therapy increases LDL particle size. [10][11][12] In the Diabetes Atherosclerosis Intervention Study (DAIS), fenofibrate reduced the rate of coronary artery disease progression in subjects with type 2 diabetes mellitus. 13 Multivariate regression demonstrated that LDL particle size was an independent predictor of the degree of disease progression in models containing LDL-C or Apo B.…”

Interaction of Fenofibrate and Fish Oil in Relation to Lipid Metabolism in Mice

“…PPAR are ligand-activated transcriptional factors and members of the nuclear hormone receptor superfamily 20,28) . Fibrates 29) and n-3 PUFA 30) are ligands of the PPAR .…”

“…A number of reports have shown that fenofibrate decreases fatty acid synthesis and increases hepatic fatty acid oxidation, thus reducing the amount of fatty acid available to triglyceride synthesis 16,17) . Fenofibrate lowers plasma triglycerides and LDL-cholesterol and raises HDLcholesterol [18][19][20] . Previous studies have reported that the lipid-lowering effects of EPA and DHA are different.…”