Prevention of Cardiovascular Events with Omega-3 Polyunsaturated Fatty Acids and the Mechanism Involved - PubMed (original) (raw)

Review

. 2020 Mar 1;27(3):183-198.

doi: 10.5551/jat.50658. Epub 2019 Oct 3.

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Review

Prevention of Cardiovascular Events with Omega-3 Polyunsaturated Fatty Acids and the Mechanism Involved

Yasuhiro Watanabe et al. J Atheroscler Thromb. 2020.

Abstract

An epidemiological study of Greenlandic Inuit suggested that fish oil, or omega-3 polyunsaturated fatty acids (PUFA), was important in preventing atherosclerotic disease. After this landmark study, many large-scale epidemiological studies and meta-analyses have examined the health benefits of omega-3 PUFA as part of a fatty acid-rich diet to demonstrate its beneficial roles in the prevention of cardiovascular diseases. Recent research has also focused attention on the anti-inflammatory effects of omega-3 PUFA and on specialized pro-resolving mediators. Findings of these studies have led to the development of omega-3 PUFA preparations for the treatment of dyslipidemia, including a highly purified eicosapentaenoic acid (EPA)-ethyl ester product (Epadel®) in Japan and an EPA/docosahexaenoic acid (DHA) preparation (Lotriga®) in the United States and Europe. Although various large-scale clinical trials on the cardiovascular preventive effect of omega-3 PUFA were conducted and reported, the results were not always consistent. The issues of not targeting subjects with hypertriglyceridemia and using low dose of omega-3 PUFA have been suggested to contribute to the failure of demonstrating the preventive effect of omega-3 PUFA in these clinical trials. Taking into account the above issues, the REDUCE-IT trial evaluated a highly purified EPA preparation at a high dose of 4 g/day in patients with hypertriglyceridemia and high cardiovascular risk, and demonstrated an extraordinary outcome of 25% relative reduction in cardiovascular events. This article reviews studies on omega-3 fatty acids during the last 50 years, including the progress in elucidating molecular mechanisms and recent large-scale clinical studies.

Keywords: Cardiovascular disease; Fatty acid metabolism; Large-scale clinical trial; Omega-3 polyunsaturated fatty acids.

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Figures

Fig. 1.

Fig. 1.

Saturated and unsaturated polyunsaturated fatty acids

Fig. 2.

Fig. 2.

Effect of omega-3-deficient diet in the body This figure was drawn based on Su _et al._19).

Fig. 3.

Fig. 3.

Proposed mechanism of statin-induced increment of Fads1, Fads2, and Elovl5 gene expression via geranylgeranyl pyrophosphate-dependent Rho kinase pathway This figure was drawn based on Tanaka _et al._66).

Fig. 4.

Fig. 4.

Anti-inflammatory lipid mediators (specialized pro-resolving mediators) derived from EPA and DHA

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