Abstract 192: Correlates of the Apolipoprotein C-III Response to the Addition of Prescription Omega-3 in Adults with Hypertriglyceridemia Despite Stable Statin Therapy
Objectives: An elevated apolipoprotein (apo) C-III level has been shown to be an independent predictor of cardiovascular risk.1 Apo C-III inhibits activation of lipoprotein lipase, and higher levels of apo C-III are associated with prolonged circulatory residence of triglyceride (TG)-rich lipoproteins. LDL particle size is inversely associated with plasma TG concentration. The present study evaluated the effect of prescription omega-3-acid ethyl esters (P-OM3) on apo C-III and lipoprotein subfraction levels in adults with high TG levels (200 – 499 mg/dL) in subjects treated with stable statin therapy.
Methods: Multicenter, randomized, double-blind, placebo-controlled trial. After 8 weeks on simvastatin 40 mg/d, 256 subjects were randomly assigned to 4 g/d of P-OM3 (Omacor®*) or placebo for an additional 8 weeks (COMBOS trial).
Results: In the P-OM3 +simvastatin group, apo C-III was significantly reduced vs placebo (−7.1% vs +3.8%, P<0.001) and TGs were also significantly reduced (−29.5% vs −6.3% in the placebo group, P<0.0001). Reductions in apo C-III were significantly correlated (all P<0.01) with reductions in very-low-density lipoprotein cholesterol (VLDL-C) (r =0.56), TG (r =0.51), and remnant lipoprotein particle cholesterol (r =0.43), LDL-C (r =0.27), and increases in LDL particle size (r =−0.23). In addition, lowering of apo C-III was associated with a reduction in the concentration of small LDL particles (r =0.32) and an increase in the concentration of large high-density-lipoprotein (HDL) particles (r =−0.24). Apo C-III response was unrelated to the changes in HDL-C (r =0.03).
Conclusions: Results are consistent with the hypothesis that P-OM3-induced reductions in apo C-III may contribute to enhanced conversion of VLDL to LDL, as well as to increased lipolysis and reduced circulatory residence for TG-rich lipoproteins. The resulting reduction of serum TGs may produce a beneficial shift in particle size, yielding larger and less atherogenic LDL particles. The combined effect of P-OM3 + simvastatin’s ability to lower apo C-III and serum TGs, together with inducing a LDL particle size shift, may contribute to cardiovascular risk reduction and warrants future study.
Funding: Reliant Pharmaceuticals, Inc.