title: Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.
abstract: Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. 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. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk.
authors.affiliation: MediMergent, LLC and The National Medication Safety, Outcomes and Adherence Program, 407 Wyntre Lea Drive, Bryn Mawr, PA 19010, USA. Electronic address: kborow@gmail.com.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Borow
authors.affiliation: UCSF School of Medicine, Fresno-Medicine Residency Program-Volunteer, 7061 N. Whitney Street, Suite 101, Fresno, CA 93720, USA. Electronic address: JR4Nelson@yahoo.com.
authors.forename: John R
authors.initials: JR
authors.lastname: Nelson
authors.affiliation: Harvard Medical School, 100 Cummings Center, Suite 135L, Beverly, MA 01915, USA. Electronic address: rpmason@elucidaresearch.com.
authors.forename: R Preston
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005343:Fibrinolytic Agents; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D008055:Lipids; D015118:Eicosapentaenoic Acid
keywords: Acute coronary syndrome; Atherosclerosis; Atherosclerotic plaque; Eicosapentaenoic acid; Endothelial function; Icosapent ethyl; Inflammation; Thrombosis