Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: A randomized, controlled, double-blind trial

Richard L. Dunbar, Stephen J. Nicholls, Kevin C. Maki, Eli M. Roth, David G. Orloff, Danielle Curcio, Judith Johnson, Douglas Kling, Michael H. Davidson

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35 Citations (Scopus)


Background: This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy-assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk. Methods: After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks. Results: Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p∈<∈0.01) and 4 g/d (p∈<∈0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p∈<∈0.001 and p∈<∈0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p∈<∈0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p∈<∈0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p∈<∈0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p∈<∈0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses. Conclusion: OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA2, in patients with hypertriglyceridemia while taking a statin. Trial registration: ClinicalTrials.gov Identifier NCT01408303.

Original languageEnglish
Article number98
JournalLipids in health and disease
Issue number1
Publication statusPublished or Issued - 2 Sep 2015


  • Apolipoprotein CIII
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • Hypertriglyceridemia
  • Lipoprotein subclasses
  • Lipoprotein-associated phospholipase A<inf>2</inf>
  • Low-density lipoprotein cholesterol
  • Omega-3 fatty acids
  • Statin
  • Triglycerides

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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