Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype

Atheroscler Suppl. 2015 May;18:53-8. doi: 10.1016/j.atherosclerosissup.2015.02.008.

Abstract

Background: Lipoprotein(a) [Lp(a)] is a cardiovascular risk factor; in addition to being a low-density lipoprotein (LDL)-like particle, it contains highly heterogeneous apolipoprotein(a) [apo(a)]. No prior studies have evaluated extended-release (ER) niacin effect on Lp(a) level depending on apo(a) phenotype.

Methods: For this 24-week, prospective, open-label clinical trial we recruited 30 men (mean age 46.2 ± 7.5 years) with Lp(a) levels >20 mg/dL. No participant had previously received lipid lowering therapy, and started ER niacin 500 mg with stepwise dose increasing up to 1.5-2.0 g. Subjects were evaluated for Lp(a), lipids, high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2 (Lp-PLA2), and fibrinolytic markers (plasminogen activator inhibitor-1, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasmin-antiplasmin complex). Patients were divided into two groups with major low- (LMW) or high-molecular weight (HMW) apo(a) isoforms determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of plasma under reducing conditions followed by immunoblotting.

Results: At baseline, groups were comparable in age, lipid, inflammatory and fibrinolytic biomarkers levels. There was a significant difference in baseline Lp(a) concentrations: 92 ± 29 mg/dL versus 54 ± 46 mg/dL in LMW and HMW apo(a) groups, respectively, p < 0.01. During the course of niacin treatment Lp(a) decreased by 28% (p < 0.003), Lp-PLA2 by 22% (p < 0.001), C-reactive protein by 24% (p = 0.07) in LMW apo(a) group, whereas no changes in Lp(a) and biomarkers levels were obtained in HMW apo(a) group.

Conclusion: High-dose ER niacin declines elevated Lp(a) level in male subjects with low- but not high-molecular weight apo(a) phenotype.

Keywords: Apolipoprotein(a) phenotype; Lipoprotein(a); Niacin.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoprotein(a) / blood*
  • Biomarkers / blood
  • Down-Regulation
  • Humans
  • Hyperlipoproteinemias / blood
  • Hyperlipoproteinemias / diagnosis
  • Hyperlipoproteinemias / drug therapy*
  • Hypolipidemic Agents / therapeutic use*
  • Lipoprotein(a) / blood*
  • Male
  • Middle Aged
  • Molecular Weight
  • Niacin / therapeutic use*
  • Patient Selection
  • Phenotype
  • Predictive Value of Tests
  • Prospective Studies
  • Russia
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Hypolipidemic Agents
  • Lipoprotein(a)
  • Niacin
  • Apoprotein(a)