Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia

BackgroundPrescription omega-3-acid ethyl esters (P-OM3) often are used for hypertriglyceridemic patients receiving statin therapy who have residual increases in atherogenic lipoprotein lipid levels. To date, limited information has been published regarding the effects of omega-3 fatty acid consumption on lipoprotein particle concentrations.ObjectiveWe evaluated the effects of adding P-OM3 4 g/d to an ongoing regimen of simvastatin 40 mg/d on lipoprotein particles (P) in subjects with hypertriglyceridemia.MethodsData were analyzed from the multicenter, randomized, double-blind, placebo-controlled Combination of Prescription Omega-3s with Simvastatin (COMBOS) study. After an 8-week simvastatin lead-in, 254 subjects received P-OM3 (n = 122) or placebo (n = 132) for an additional 8 weeks. Nuclear magnetic resonance spectroscopy was used to assess lipoprotein concentrations and sizes. Remnant-like particle cholesterol, apolipoprotein (Apo) CIII, Apo AI, and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels also were measured.ResultsCompared with placebo, P-OM3 reduced mean very-low-density lipoprotein (VLDL-P) size and increased low-density lipoprotein particle (LDL-P) size (P < .006 for both) without altering high-density lipoprotein particle (HDL-P) size. P-OM3 did not significantly change total VLDL-P or LDL-P concentrations relative to placebo, but large VLDL-P and intermediate-density lipoprotein particle (IDL-P) concentrations were lowered (P < .01 for both), and the large LDL-P concentration was increased (P < .0001). HDL-P concentration was reduced (P < .0001) as the result of a decrease in medium HDL-P. Remnant-like particle cholesterol, Apo CIII, and Lp-PLA2 concentrations were reduced compared with placebo (all P < .003).ConclusionsP-OM3 induces changes in sizes, concentrations, and compositions of lipoproteins that may have relevance for the atherothrombotic process.