Omega-3 carboxylic acids significantly reduce plasma ApoCIII

EVOLVE analysis demonstrates omega-3 carboxylic acids significantly reduce plasma ApoCIII

News - May 22, 2015

Presented by: Allyson Morton (Boston, USA)

The results of a new analysis of the EVOLVE trial (EpanoVa fOr Lowering Very high triglyceridEs), which demonstrated that omega-3 carboxylic acids significantly reduce plasma apoCIII in addition to lowering serum triglycerides, were presented today in a Clinical Breakthrough Session at the 17th International Symposium on Atherosclerosis, Amsterdam, The Netherlands, which is being held May 23-26, 2015.

Lipoprotein subspecies containing apoCIII have been shown to adversely affect the risk of cardiovascular disease (CVD). Specifically, LDL with apoCIII is a stronger predictor of CVD than LDL without apoCIII, and HDL with apoCIII is also associated with increased CVD risk. Small studies suggest omega-3 fatty acids may reduce total apoCIII in the blood plasma in addition to their triglyceride (TG)-lowering effects.

The EVOLVE trial was a 12-week double-blind study of 399 subjects with fasting TG levels between 500 and 2000 mg/dL randomized to 2,3 or 4 gram/day (g/d) doses of omega-3 carboxylic acids, or an olive oil placebo. Omega-3 carboxylic acids contains EPA (50-60%) and DHA (15-25%) in free fatty acid form. The analysis conducted by the School of Public Health Ph.D. candidate Allyson Morton, Research Scientist Jeremy D. Furtado and Research Associate Jane Lee, examined the baseline and end of treatment plasma samples of 273 subjects randomized to 2 or 4 g/d to determine the effect of omega-3 carboxylic acids on apoCIII concentrations in HDL, LDL and VLDL, as well as on the concentrations of subspecies of HDL, LDL and VLDL that contain or do not contain apoCIII.

The results demonstrated omega-3 carboxylic acids significantly reduced plasma apoCIII as compared to placebo (-4.2 mg/dL, p=0.002 and -4.0 mg/dL, p<0.0001 for 2 and 4g, respectively), as well as apoCIII in HDL (-0.6 mg/DL, p=0.12 and -1.0 mg/dL, p=0.01 for 2 and 4g, respectively) and apoCIII in LDL (-2.9 mg/dL, p<0.0001 and -3.3 mg/dL, p<0.001 for 2 and 4g, respectively).

Omega-3 carboxylic acids selectively increased the concentration of LDL apoB, a subtype that does not contain apoCIII and has a weak correlation to coronary heart disease (5.1 mg/dL, p=0.047 and 7.1 mg/dL, p=0.006 for 2 and 4g, respectively). Treatment did not significantly increase the concentration of LDL with apoCIII (0.15 mg/dL, p=0.7 and 0.2 mg/dL, p=0.6 for 2 and 4g, respectively).

“These results are exciting because they contribute to the growing body of research that support triglyceride lowering as the next target in the treatment of cardiovascular disease. Furthermore, it is becoming evident that simple measurements of HDL-C and LDL-C, without investigating proteins that reside on these particles, do not adequately reflect lipoprotein function in the body and disease risk,” said Allyson Morton, Ph.D. candidate, Harvard T.H. Chan School of Public Health.

These results indicate that omega-3 carboxylic acids at doses of 2 and 4 g/d are effective for lowering total plasma apoCIII and apoCIII in HDL and LDL. Further, the increase in LDL concentration seen with omega-3 carboxylic acids is limited to the less harmful subspecies of LDL without apoCIII. The authors concluded apoCIII may be a mechanism for the TG lowering effects of omega-3 carboxylic acids. Further studies are needed to determine whether omega-3 carboxylic acids reduces cardiovascular risk and whether this is related to apoCIII reduction.


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