The Influence of Eicosapentaenoic Acid to Arachidonic Acid Ratio on Long-term Cardiovascular Events Following Percutaneous Coronary Intervention

Niwa, Kiyoshi; Tanaka, Akihito; Funakubo, Hiroshi; Otsuka, Shuzo; Yoshioka, Naoki; Kudo, Naoko; Sakakibara, Keisuke; Miki, Yusuke; Kataoka, Tetsuro; Fukui, Kenji; Ishii, Hideki; Murohara, Toyoaki

doi:10.2169/internalmedicine.7336-21

Cited by 2 publications

(1 citation statement)

References 35 publications

(50 reference statements)

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“…In a Japanese community, the serum EPA/arachidonic acid (AA) ratio decreased over 10 years 2) . Previous studies showed that a lower serum EPA/AA ratio is predictive of the incidence of cardiovascular events [3][4][5][6] . The JELIS and REDUCE-IT trials verified that highly purified EPA ethyl ester (EPA-E) reduced the risk of cardiovascular events 7,8) .…”

Section: Introductionmentioning

confidence: 99%

Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)

Miyoshi,

Naoe,

Wakabayashi

et al. 2023

JAT

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Aims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived antiinflammatory metabolites following single and multiple administrations of MND-2119.Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated.Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. Conclusions:These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations.

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Section: Introductionmentioning

confidence: 99%

Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)

Miyoshi,

Naoe,

Wakabayashi

et al. 2023

JAT

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Changes in the Eicosapentaenoic Acid to Arachidonic Acid Ratio in Serum over 10 Years in a Japanese Community: The Hisayama Study

Honda

Chen

Hata

et al. 2023

JAT

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Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid found in various foods, including meat, eggs, and fish, and is involved in neurogenesis and, therefore, essential for growth and development 5) . AA has complex biological effects on cardiovascular health, as it is the precursor to various metabolites that promote or suppress inflammation 2) . However, excessive circulating AA can cause atherosclerotic Aim: Circulating omega-3 and omega-6 polyunsaturated fatty acids may to contribute to cardiovascular health at the population level. Over a decade, we investigated changes in the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio, and in serum concentrations of the individual fatty acids, in a Japanese community. Methods: Community surveys took place in 2002-2003 and 2012-2013 in a rural area of Japan. The community surveys included 3,194 and 3,220 community dwellers aged ≥ 40 years who did not take EPA medication in 2002-2003 and 2012-2013, respectively. Fatty acid fractionations in serum were measured using a gas chromatography method. Changes in the serum EPA/AA ratio over time were examined using linear mixed models. Results: Overall, the average serum EPA/AA ratio decreased over the 10 years. A decreasing trend in the serum EPA/AA ratio occurred in all age groups except participants aged ≥ 80 years, with larger decreases in the younger age groups. A similar decline in serum EPA/AA ratio occurred in participants with and those without lipidlowering therapy. Serum EPA concentrations were slightly increased in the whole population but remained stable or even decreased in participants aged 40-69. In contrast, the average serum AA concentrations increased in all age groups. Conclusion: In a Japanese community, the serum EPA/AA ratio decreased over 10 years at the population level, especially in middle-aged participants.

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The Influence of Eicosapentaenoic Acid to Arachidonic Acid Ratio on Long-term Cardiovascular Events Following Percutaneous Coronary Intervention

Cited by 2 publications

References 35 publications

Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)

Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)

Changes in the Eicosapentaenoic Acid to Arachidonic Acid Ratio in Serum over 10 Years in a Japanese Community: The Hisayama Study

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