Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial

Gregory C Shearer, James V Pottala, Susan N Hansen, Verdayne Brandenburg, William S Harris, Gregory C Shearer, James V Pottala, Susan N Hansen, Verdayne Brandenburg, William S Harris

Abstract

The metabolic syndrome includes both dyslipidemia and impaired vascular function. Because extended-release niacin (ERN) and prescription omega-3 acid ethyl-esters (P-OM3) independently improve these characteristics, we tested their effects in combination. Sixty metabolic syndrome subjects were randomized to 16 weeks of treatment on dual placebo, P-OM3 (4 g/day), ERN (2 g/day), or combination in a double-blind trial. Lipoprotein subfractions and vascular endpoints were measured and tested using ANCOVA. ERN increased HDL cholesterol by 5.4 mg/dl from baseline (P = 0.04), decreased triglycerides (TG) by 39 mg/dl (-21%, P = 0.003), and decreased the augmentation index, which is a measure of vascular stiffness, by 3.5 units (P = 0.04). P-OM3 reduced TG by 26 mg/dl (-13%, P = 0.04). Combination treatment increased HDL cholesterol by 7.8 mg/dl (P = 002) and decreased TG by 72 mg/dl (-34%) but there was no improvement in vascular stiffness. Detailed analysis of lipoprotein subfractions revealed increased large, bouyant HDL(2) (3.3 mg/dl; P = 0.002) and decreased VLDL(1+2) (-32%; P < 0.0001), among subjects treated with combination therapy, that were not present with either therapy alone. ERN and P-OM3 alone improved characteristics of metabolic syndrome; however, whereas subjects on combination therapy did not have improved vascular stiffness, TG and HDL levels improved as did certain lipoprotein subfractions.

Trial registration: ClinicalTrials.gov NCT00286234.

Figures

Fig. 1.
Fig. 1.
Flow diagram for the study. a safety (elevated CPK), inadequate IV access; b rash, flushing; c inadequate IV access, time constraints, migraine headache; d without index finger, problematic RHI measurement at baseline; e error, subject should have been excluded for high BMI.
Fig. 2.
Fig. 2.
Changes in triglycerides (TG) (including 95% CI bands) as a function of the change in omega-3 index (OMX) levels in the two groups that received P-OM3. For each group, the extent of TG lowering was in proportion to the relative increase in OMX (P = 02). The greater TG lowering with combination therapy is reflected in the step function between treatment groups (P = 0.001). The line at y=1 represents identity, or no change from baseline. The results are shown as the least-squares fit of the semi-log line, note the log-scale of the y -axis. Using the ratios of DHA and of EPA (as final/baseline) gave similar results. N = 30; because there was no change in OMX or TG levels for subjects on placebo P-OM3, they were not included in the analysis.

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