Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?
Abstract
Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk.
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The omega-3 fatty acids EPA and DHA may have a preventive role in the development and progression of atherosclerotic cardiovascular disease.
“The omega-3 (OM-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have a preventive role in the development and progression of atherosclerotic cardiovascular disease (ASCVD) [1–4].”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [2]
Differences in omega-3 fatty acid composition may have contributed to disparate cardiovascular outcomes trial findings.
“Differences in OM-3 fatty acid composition may also have contributed to disparate CVOT findings.”
From Critical Differences Between Dietary Supplement and Prescription Omega-3 Fatty Acids: A Narrative Review (2020) · cites this paper as [2]
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- Authors
- Nelson, J. R., True, W. S., Le, V., & Mason, R. P.
- Affiliations
- California Cardiovascular Institute, Fresno, CA, USA
- Sharp Rees-Stealy Medical Group (US)
- Intermountain Medical Center (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Nelson, John R.
- Venue
- Postgraduate Medicine
- Publisher
- Informa UK Limited
- Published
- 2017-10-09
- Volume
- 129
- Issue
- 8
- Pages
- 822-827
- ISSN
- 0032-5481 (ISSN-L)
- 1941-9260
- OpenAlex
- W2762372979
- Cited by
- 27
- References
- 51
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 12 · 2019: 3 · 2018: 1
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Postgraduate Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amarin Pharma Inc.
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- eicosapentaenoic acid, icosapent ethyl, residual cardiovascular risk, statin-treated patients, hypertriglyceridemia, omega-3 fatty acids, atherosclerotic plaque, plaque vulnerability, inflammation, lipid oxidation, phospholipid membranes, LDL cholesterol, triglycerides, REDUCE-IT trial
- MeSH terms
- Cardiovascular Diseases, Humans, Risk Factors, Triglycerides, Eicosapentaenoic Acid, Hypertriglyceridemia, Atherosclerosis, Plaque, Atherosclerotic
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