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Effects of Omega‐3‐acid Ethyl Esters on LDL Particle Size in Subjects with Hypertriglyceridemia Despite Statin Therapy

Small, dense LDL are more atherogenic than larger LDL particles. It has been hypothesized that individuals shift from a predominance of larger (pattern A) to smaller LDL particles (pattern B) when the fasting triglyceride (TG) concentration exceeds a threshold, typically in the range of 100–250 mg/dL. The present investigation assessed the influence of TG‐lowering with prescription omega‐3‐acid ethyl esters on LDL size in men and women with TG 200 to 499 mg/dL while on statin therapy. After 8 weeks on simvastatin 40 mg/d, 254 subjects were randomly assigned to 4 g/d of Omacor® (3.4 g/d EPA + DHA) or placebo for an additional 8 weeks. Median LDL particle size increased in the omega‐3 treated group (19.90 to 20.20 nm, p=0.007 vs. placebo). Median changes from baseline were 0.60, 0.40, 0.15 and −0.20 nm, when the on‐treatment TG concentrations were <150, 150–199, 200–249 and ≥250 mg/dL, respectively (p<0.001). In these on‐treatment TG subsets, pattern B was present in 36, 50, 82 and 84% of subjects (p<0.001), compared to 68, 79, 93, and 73%, respectively, at baseline. The association of on‐treatment TG category with the change in LDL particle size remained highly significant (p<0.001) after adjusting for the degree of TG‐lowering. These results support the concept of a TG threshold for conversion from LDL subclass pattern B to A.