Administration of eicosapentaenoic acid may alter high-density lipoprotein heterogeneity in statin-treated patients with stable coronary artery disease: A 6-month randomized trial.

Abstract

BACKGROUND

Combined statin plus eicosapentaenoic acid (EPA) therapy might be a potentially effective treatment option to prevent coronary artery disease (CAD). The serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for CAD. Few data exist whether administration of epa could affect high-density lipoprotein (HDL) particle size. We hypothesized that the addition of epa to ongoing statin therapy may result in altered HDL heterogeneity.

METHODS

We conducted this 6-month, single-center, prospective, randomized open-label clinical trial to investigate the effect of the additional administration of epa on the HDL heterogeneity (HDL(2), HDL(3,) and HDL(2)/HDL(3) ratio) in stable CAD patients receiving treatment with statins. We assigned stable CAD patients already receiving statin therapy to the epa group (1800mg/day: n=50) or the control group (n=50).

RESULTS

A significant decrease in the serum HDL(3) level (-4.7% vs. -0.5%, p=0.037), but not of the serum HDL(2) level, and a significant increase in the HDL(2)/HDL(3) ratio (5.5% vs. -5.1%, p=0.032) were observed in the epa group as compared to the control group. Multiple regression analysis with adjustments for coronary risk factors identified the achieved EPA/ AA ratio as an independent and significant predictor of an increase of the HDL(2)/HDL(3) ratio (β=0.295, p=0.001). Furthermore, the change in the serum cholesterol ester transfer protein mass was positively correlated with the change in the EPA/AA ratio in the epa group (r=0.286, p=0.044), but not in the control group (r=0.121, p=0.401).

CONCLUSION

Administration of epa might decrease the serum HDL(3) level, resulting in an increase in the HDL(2)/HDL(3) ratio. Furthermore, increased EPA/AA ratio by the addition of epa to ongoing statin therapy might be an indicator of an increase in the HDL(2)/HDL(3) ratio, thereby regulating HDL particle size.

CLINICAL TRIAL REGISTRATION

UMIN (http://www.umin.ac.jp/)

Study ID

UMIN000010452.