Eicosapentaenoic Acid-Enriched High-Density Lipoproteins Exhibit Anti-Atherogenic Properties

Tanaka, Nobuaki; Irino, Yasuhiro; Shinohara, Masakazu; Tsuda, S.; Mori, Takeki; Nagao, Manabu; Oshita, Toshihiko; Mori, Kensaku; Hara, Tetsuya; Toh, Ryuji; Ishida, Tatsuro; Hirata, Ken‐ichi

doi:10.1253/circj.cj-17-0294

Cited by 44 publications

(35 citation statements)

References 30 publications

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“…This decrease is comparable to that seen in the entire ANCHOR population 20 and in the MARINE trial of icosapent ethyl in patients with very high TG at baseline. 23 The decrease in HDL-C with DHA-free icosapent ethyl could be considered adverse, but might not be so in light of reports that the addition of EPA to reconstituted HDL in vitro 33 and icosapent ethyl treatment in vivo 34 may both enhance antioxidant and anti-inflammatory HDL function. Further research is needed to explore the net clinical effects, if any, of the above changes in LDL-C and HDL-C concentration, particles, and function with EPA-only therapy.…”

Section: Discussionmentioning

confidence: 99%

Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis

Brinton

Ballantyne

Guyton

et al. 2018

Journal of Women's Health

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Background: High triglycerides (TG) and diabetes mellitus type 2 (DM2) are stronger predictors of cardiovascular disease (CVD) in women than in men, but few randomized, controlled clinical trials have investigated lipid-lowering interventions in women and none have reported results specifically in women with high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG ≥500 mg/dL.Methods: The 12-week ANCHOR trial randomized 702 statin-treated patients (73% with DM; 39% women) at increased CVD risk with TG 200–499 mg/dL despite controlled low-density lipoprotein cholesterol (LDL-C; 40–99 mg/dL) to receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis included 146 women with DM2 (97% white, mean age 62 years) randomized to icosapent ethyl 4 g/day (n = 74) or placebo (n = 72).Results: Icosapent ethyl significantly reduced TG (−21.5%; p < 0.0001) without increasing LDL-C and lowered other potentially atherogenic lipid/lipoprotein, apolipoprotein, and inflammatory parameters versus placebo. Icosapent ethyl increased EPA levels in plasma (+639%; p < 0.0001; n = 49) and red blood cells (+599%; p < 0.0001; n = 47) versus placebo. Safety and tolerability of icosapent ethyl were generally similar to placebo.Conclusion: In women with DM2 at high CVD risk with persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially atherogenic parameters with safety and tolerability comparable to placebo. Potential CVD benefits of icosapent ethyl are being tested in ∼8000 men and women at high CVD risk with high TG on statins in the ongoing Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) cardiovascular (CV) outcome trial.

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Section: Discussionmentioning

confidence: 99%

Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis

Brinton

Ballantyne

Guyton

et al. 2018

Journal of Women's Health

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“…A number of specific salutary actions have been reported relating to endothelial function, oxidative stress, foam‐cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture (Figure ) . EPA‐enriched high‐density lipoprotein (HDL) particles, from patients with dyslipidemia treated with 1.8 g of EPA and in reconstituted HDL particles, have been shown to increase cholesterol efflux from macrophages and markedly inhibit cytokine‐induced expression of adhesion molecules in human umbilical‐vein endothelial cells . EPA also improves atherogenic dyslipidemia by reducing triglyceride (TG) levels and remnant cholesterol without raising low‐density lipoprotein cholesterol (LDL‐C) levels in patients with very high TG levels and in statin‐treated patients with high TG levels and high residual CV risk .…”

Section: Introductionmentioning

confidence: 99%

Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200–499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study

Budoff

Muhlestein

et al. 2018

Clinical Cardiology

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Despite reducing progression and promoting regression of coronary atherosclerosis, statin therapy does not fully address residual cardiovascular (CV) risk. High‐purity eicosapentaenoic acid (EPA) added to a statin has been shown to reduce CV events and induce regression of coronary atherosclerosis in imaging studies; however, data are from Japanese populations without high triglyceride (TG) levels and baseline EPA serum levels greater than those in North American populations. Icosapent ethyl is a high‐purity prescription EPA ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults with TG levels >499 mg/dL. The objective of the randomized, double‐blind, placebo‐controlled EVAPORATE study is to evaluate the effects of icosapent ethyl 4 g/d on atherosclerotic plaque in a North American population of statin‐treated patients with coronary atherosclerosis, TG levels of 200 to 499 mg/dL, and low‐density lipoprotein cholesterol levels of 40 to 115 mg/dL. The primary endpoint is change in low‐attenuation plaque volume measured by multidetector computed tomography angiography. Secondary endpoints include incident plaque rates; quantitative changes in different plaque types and morphology; changes in markers of inflammation, lipids, and lipoproteins; and the relationship between these changes and plaque burden and/or plaque vulnerability. Approximately 80 patients will be followed for 9 to 18 months. The clinical implications of icosapent ethyl 4 g/d treatment added to statin therapy on CV endpoints are being evaluated in the large CV outcomes study REDUCE‐IT. EVAPORATE will provide important imaging‐derived data that may add relevance to the clinically derived outcomes from REDUCE‐IT.

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“…Interestingly, induction of apoA-I expression by n -3 PUFAs (EPA) may also critically influence the anti-oxidative effects of HDLs [ 33 , 34 ]. ApoA-I is known to stabilize the enzymatic activity of paraoxonase-1 (PON1) [ 35 , 36 ] which associates with HDL particles.…”

Section: Introductionmentioning

confidence: 99%

The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review

et al. 2017

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The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8. Based on current knowledge, we conclude that n-3 PUFAs may beneficially affect RCT, mainly by influencing high-density lipoprotein (HDL) remodeling and by promoting hepatobiliary sterol excretion.

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Eicosapentaenoic Acid-Enriched High-Density Lipoproteins Exhibit Anti-Atherogenic Properties

Cited by 44 publications

References 30 publications

Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis

Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis

Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200–499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study

The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review

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