title: 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 (HDL2) and 3 (HDL3) 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 HDL3 and HDL2 subfractions.
  
  
  OBJECTIVE
  This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-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, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 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, HDL2-C, and HDL3-C (all P<0.01), K2 (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 HDL2-C and HDL3-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL3-C by promoting TG-rich lipoprotein catabolism and may increase HDL2-C by promoting the conversion of HDL3 to HDL2.
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Nagahiko
authors.initials: N
authors.lastname: Sakuma
authors.affiliation: Takikawa Ikiiki Clinic, Nagoya, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikeuchi
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hibino
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mukai
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Akita
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yajima
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Miyabe
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Takada
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohte
authors.affiliation: Department of Biochemistry, Nagoya Women's University, Nagoya, Japan.
authors.forename: Mitoshi
authors.initials: M
authors.lastname: Kunimatu
authors.affiliation: Department of Internal Medicine and Pathophysiology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Genjiro
authors.initials: G
authors.lastname: Kimura
keywords: bezafibrate; hepatic triglyceride lipase; high-density lipoprotein 2; high-density lipoprotein 3; lipoprotein lipase; serum triglyceride clearance