Omega-3 polyunsaturated fatty acids focusing on eicosapentaenoic acid and docosahexaenoic acid in the prevention of cardiovascular diseases: a review of the state-of-the-art

ABSTRACT

Introduction

: An epidemiological study of Greenlandic Inuit suggested the importance of omega-3 polyunsaturated fatty acids (PUFAs) in preventing ischemic heart disease. After this landmark study, large-scale epidemiological studies have examined the benefits of omega-3 PUFAs in the prevention of cardiovascular diseases.

Areas covered

: This article reviews studies on omega-3 PUFAs, and identifies issues relevant to cardiovascular risk.

Expert opinion

: Recent studies have focused on the anti-inflammatory effects of omega-3 PUFAs and specialized pro-resolving mediators. High-purity eicosapentaenoic acid (EPA) ethyl ester and EPA/docosahexaenoic acid (DHA) preparations have been developed primarily for the treatment of hypertriglyceridemia. Various trials on the cardiovascular protective effects of omega-3 PUFAs have been reported, but the results have not been consistent. Some issues of the trials have been suggested, such as using low-dose omega-3 PUFAs and not including hypertriglyceridemia in subject selection criteria. REDUCE-IT study that used a high dose of high-purity EPA preparation showed a relative reduction in cardiovascular events, but, the STRENGTH study that used a high dose of EPA/DHA preparation did not support this benefit. This article reviews the roles of omega-3 PUFAs in cardiovascular diseases, including progress in understanding the molecular mechanisms and recent large-scale clinical trials.

KEYWORDS:

• Cardiovascular disease
• fatty acid metabolism
• omega-3 polyunsaturated fatty acids
• reduce-IT
• strength

Article highlights

• The role of omega-3 polyunsaturated fatty acids (PUFAs) in the prevention of atherosclerosis has been established by large-scale epidemiological studies, clinical outcome trials, and meta-analyses.

• Potent anti-inflammatory lipid mediators such as resolvins, protectins, and maresins are produced from omega-3 PUFAs at the end of the inflammatory process. Research on the roles of anti-inflammatory mediators is necessary not only for arteriosclerotic diseases but also other inflammatory diseases.

• In patients treated with statins, increase in plasma arachidonic acid (AA) and decrease in plasma omega-3 PUFAs concentration and/or plasma omega-3/AA ratio may be associated with residual cardiovascular risk.

• Although recent secondary prevention trials have not consistently showed the effectiveness of omega-3 PUFAs in patients with multiple cardiovascular (CV) risk factors, REDUCE-IT evaluated a high dose (4 g/day) of high-purity EPA preparation in patients with hypertriglyceridemia and high CV risk, and demonstrated an extraordinary outcome of 25% relative reduction in CV events.

• Unlike REDUCT-IT, STRENGTH, that evaluated a high dose of EPA and DHA preparation failed to demonstrate a benefit in reducing CV events, raising questions about the usefulness of omega-3 PUFAs in patients with high CV risk.

Declaration of interest

I. Tatsuno has received lecture fees from Takeda Pharmaceutical Co., Ltd and Novartis Pharma K.K., and received research grants from Takeda Pharmaceutical Co., Ltd and Sunny Health Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.