Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial

Lipids in Health and Disease

Michael H. Davidson³  Douglas Kling⁶  Judith Johnson⁶  Danielle Curcio⁶  David G. Orloff¹  Eli M. Roth⁷  Kevin C. Maki²  Stephen J. Nicholls⁴  Richard L. Dunbar⁵ 

[1] Medpace, Inc., Cincinnati OH, USA;Midwest Center for Metabolic & Cardiovascular Research, Chicago, IL, USA;AstraZeneca, Wilmington, DE, USA;South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia;Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 8046 Maloney Building, Philadelphia 19104-2699, PA, USA;Omthera Pharmaceuticals, Princeton, NJ, USA;Sterling Research Group, Cincinnati OH, USA

关键词: Docosahexaenoic acid;    Eicosapentaenoic acid;    Lipoprotein subclasses;    Lipoprotein-associated phospholipase A2;    Apolipoprotein CIII;    Low-density lipoprotein cholesterol;    Statin;    Triglycerides;    Omega-3 fatty acids;    Hypertriglyceridemia;   

Others  :  1233278
DOI  :  10.1186/s12944-015-0100-8

 received in 2015-02-20, accepted in 2015-08-20,  发布年份 2015

【 摘 要 】

Background

This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy–assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk.

Methods

After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks.

Results

Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p < 0.01) and 4 g/d (p < 0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p < 0.001 and p < 0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p < 0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A ₂(Lp-PLA ₂ ) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p < 0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses.

Conclusion

OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA ₂ , in patients with hypertriglyceridemia while taking a statin.

Trial registration

ClinicalTrials.gov Identifier NCT01408303.

【 授权许可】

   
2015 Dunbar et al.

【 图 表 】

Fig. 1.

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