Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol

Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1783-9. doi: 10.1161/hq1001.096624.


Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (</=40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7+/-4.0% (P=0.033) and 24.0+/-4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of (125)I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [(3)H]cholesterol ester was approximately 75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.

Publication types

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

MeSH terms

  • Apolipoprotein A-I / biosynthesis*
  • Apolipoprotein A-I / metabolism
  • Apolipoprotein A-II / blood
  • Arteriosclerosis / drug therapy
  • Arteriosclerosis / metabolism*
  • Cholesterol, HDL / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Gemfibrozil / pharmacology*
  • Hepatocytes / metabolism
  • Humans
  • Hypolipidemic Agents / pharmacology*
  • Lipids / blood
  • Lipoproteins, HDL / chemistry*
  • Niacin / pharmacology*
  • Tumor Cells, Cultured


  • Apolipoprotein A-I
  • Apolipoprotein A-II
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Lipids
  • Lipoproteins, HDL
  • Niacin
  • Gemfibrozil