Differential effects of fenofibrate and extended-release niacin on high-density lipoprotein particle size distribution and cholesterol efflux capacity in dyslipidemic patients

J Clin Lipidol. 2013 Sep-Oct;7(5):414-22. doi: 10.1016/j.jacl.2013.06.007. Epub 2013 Jun 27.

Abstract

Background: The effectiveness of therapies that raise high-density lipoprotein cholesterol (HDL-C) to lower cardiovascular disease risk is currently under debate, and further research into the relationship between HDL-C and function is required.

Objective: o investigate whether 2 established HDL-C-raising therapies had differential effects on parameters of high-density lipoprotein (HDL) quality and function, such as HDL particle profile and cholesterol efflux capacity (CEC), in patients with dyslipidemia.

Methods and results: Sixty-six patients with dyslipidemia, 24 with low HDL-C levels (<40 mg/dL) and 42 with normal HDL-C levels (40-59 mg/dL), were treated for 6 weeks with fenofibrate (160 mg/d) or extended-release (ER) niacin (0.5 g/d for 3 weeks, then 1 g/d) with 4 weeks of washout between treatments. Lipoprotein particle size distribution was determined using nuclear magnetic resonance, and pathway-specific serum CECs were assessed in J774 macrophages, hepatoma, and Chinese hamster ovary-human adenosine triphosphate-binding cassette transporter G1 cells. Comparable increases in HDL-C and apolipoprotein A-I levels were seen with fenofibrate and ER niacin. There was a shift toward larger HDL, predominantly to medium-size HDL particles for fenofibrate (+209%) and to large HDL particles for ER niacin (+221%). Minor changes in serum CECs were observed with fenofibrate and ER niacin for all the efflux pathways measured. Small increases in plasma cholesteryl ester transfer protein and lecithin: cholesterol acyltransferase concentrations, and decreases in cholesteryl ester transfer protein activity were seen with both drugs.

Conclusions: Fenofibrate and ER niacin increased plasma HDL-C level similarly, but modulated HDL particle size distribution differently; however, these changes did not result in differential effects on serum CECs.

Keywords: Cholesterol efflux capacity; Cholesteryl ester transfer protein; Fenofibrate; High-density lipoprotein cholesterol; Niacin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Biological Transport / drug effects
  • CHO Cells
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / chemistry*
  • Cholesterol, HDL / metabolism*
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / chemistry
  • Cholesterol, LDL / metabolism
  • Cricetinae
  • Cricetulus
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / enzymology
  • Dyslipidemias / metabolism*
  • Female
  • Fenofibrate / adverse effects
  • Fenofibrate / pharmacology*
  • Fenofibrate / therapeutic use
  • Humans
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Niacin / administration & dosage*
  • Niacin / adverse effects
  • Niacin / pharmacology*
  • Niacin / therapeutic use
  • Particle Size*
  • Phosphatidylcholine-Sterol O-Acyltransferase / blood
  • Safety
  • Triglycerides / blood
  • Young Adult

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Triglycerides
  • Niacin
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Fenofibrate