Long-term efficacy of bezafibrate in reduction of small, dense low-density lipoprotein by hypotriglyceridemic action

Abstract

Objective We examined both the effects of long-term bezafibrate treatment on low-density lipoprotein (LDL) particle size in hyperlipidemic patients and the relationship between changes in plasma lipids and LDL particle size. Background It is well recognized that small, dense LDL is a highly atherogenic lipoprotein and is strongly associated with coronary artery disease. Mechanisms for generating small, dense LDL are multifactorial; however, plasma triglyceride concentration is a powerful determinant of LDL size. Methods We observed changes in LDL particle diameter in 17 hyperlipidemic patients before and during 3 years of bezafibrate treatment (200-mg tablet BID) and examined the relationship between changes in LDL size and plasma lipid levels. Results Bezafibrate reduced plasma triglyceride concentration by 37% and LDL-C concentration by 13% and increased high-density lipoprotein cholesterol (HDL-C) concentration by 44%. Mean LDL particle diameter determined by 2% to 16% gradient polyacrylamide gel electrophoresis was increased by bezafibrate treatment from 25.2 ± 1.4 nm to 26.4 ± 0.5 nm ( P < 0.0001); thus the prevalence of small, dense LDL (diameter ≤25.5 nm, pattern B) was markedly reduced from 59% to 12%. The favorable lipoprotein profiles and enlargement of LDL size persisted throughout the study. A significant inverse correlation was observed between LDL size and plasma triglyceride concentration before bezafibrate treatment ( r = −.694, P < 0.002), and increased LDL sizes were substantially associated with decreased plasma triglyceride levels after 3 years of bezafibrate treatment ( r = −.839, P < 0.0001). In contrast, HDL-C plasma concentration was not associated with LDL size at baseline, and changes in LDL size were not associated with changes in HDL-C concentration during the treatment. Conclusions Results of this study suggest that the increased LDL size that occurs with bezafibrate treatment is strongly attributed to its hypotriglyceridemic action but not to increased concentrations of HDL-C. Long-term treatment with bezafibrate may have favorable effects on preventing coronary artery disease through the reduction of a potent atherogenic lipoprotein, small, dense LDL.