Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate

Abstract

Background Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL 2) and 3 (HDL 3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL 3 and HDL 2 subfractions. Objective This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K 2) and HDL 2 and HDL 3 cholesterol (HDL 2-C and HDL 3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). Methods Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL 2-C, and HDL 3-C were measured. A fat emulsion tolerance test to assess K 2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. Results Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30–69 years]; mean [SD] body mass index, 23 [2] kg/m 2) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level ( P<0.01). Significant increases were seen in HDL-C, HDL 2-C, and HDL 3-C (all P<0.01), K 2 ( P<0.01), and in plasma LPL mass ( P<0.01) and LPL activity ( P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented. Conclusions In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL 2-C and HDL 3-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL 3-C by promoting TG-rich lipoprotein catabolism and may increase HDL 2-C by promoting the conversion of HDL 3 to HDL 2.