Effects of niacin and omega-3 fatty acids on HDL-apolipoprotein A-I exchange in subjects with metabolic syndrome

Abstract

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers.

Fig 1. Change in apoA-I levels following 16 weeks of therapy with placebo (Pb), ERN, P-OM3, or combination (Combo).

Statistical significance was determined using ANOVA adjusted for baseline (P = 0.04). The group differences were evident by post-hoc testing. Combined, ERN treatment (ERN and Combo: A) had increased apoA-I by 12 mg/mL (3, 20) P = 0.009) compared to groups with no niacin (B).

Fig 2. Effect of ERN, P-OM3, or combination therapy on HAE.

A, the increase in %HAE relative to placebo adjusted for baseline %HAE, age, BMI, and sex. All treatments significantly increased %HAE (Dunnett test). B, the individual changes in HAE by treatment group.

Fig 3. Effect ERN, P-OM3, and combination therapies on apoA-I specific exchange activity.

ApoA-I specific exchange activity is calculated as %HAE / mg/dL apoA-I and shown as fold change from placebo. ERN therapy was 20% higher after treatment (P = 0.02), while P-OM3 exhibited a 28% increase in apoA-I specific activity (P = 0.0006). Combination therapy increased non-significantly (10%).