Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

The clinical efficacy of fish oil and high-purity eicosapentaenoic acid ethyl ester (hp-EPA-E) for treating cardiovascular disease (CVD) has been reported. Fish oil contains saturated and monounsaturated fatty acids that have pharmacological effects opposite to those of omega 3 fatty acids (omega 3). Moreover, omega 3, such as EPA and docosahexaenoic acid (DHA), do not necessarily have the same metabolic and biological actions. This has obscured the clinical efficacy of omega 3. Recently, the Japan EPA Lipid Intervention Study (JELIS) of hp-EPA-E established the clinical efficacy of EPA for CVD, and higher levels of blood EPA, not DHA, were found to be associated with a lower incidence of major coronary events. A significant reduction in the risk of coronary events was observed when the ratio of EPA to arachidonic acid (AA) (EPA/AA) was > 0.75. Furthermore, the ratio of prostaglandin (PG) I-3 and PGI(2) to thromboxane A(2) (TXA(2)) ([PGI(2)+ PGI(3)]/TXA(2)) was determined to have a linear relationship with the EPA/AA ratio as follows: (PGI(2)+ PGI(3))/TXA(2) = lambda + pi* (EPA/AA). Like PGI(2), PGI(3) not only inhibits platelet aggregation and vasoconstriction, but also is assumed to reduce cardiac ischemic injury and arteriosclerosis and promote angiogenesis. Thus, the effects of EPA in reducing the risk of CVD could be mediated by biological action of PGI(3) in addition to hypotriglyceridemic action of EPA. Compared with DHA, EPA administration increases the EPA/AA ratio and the (PGI(2) + PGI(3))/TXA(2) balance to a state that inhibits the onset and/or progression of CVD.