Targeting hypertriglyceridemia to mitigate cardiovascular risk: A review

Fig. 1. Hazard Ratios of Clinical Endpoints for the Japan EPA Lipid Intervention Study (JELIS). Superscript 1 and 2 indicate primary and secondary prevention endpoints, respectively [60]. ∗P ​< ​0.05. Reprinted from The Lancet, 369, Yokoyama M, Origasa H, Matsuzaki M et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis, 1090–1098. Copyright 2007, with permission from Elsevier.

Fig. 2. Absolute Risk Reduction (ARR) in REDUCE-IT Endpoints. Percentages were calculated by taking absolute differences in endpoint rates between icosapent ethyl and control groups [ARR = (n/N)placebo – (n/N)icosapent ethyl]. Primary composite endpoint events: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. Key secondary composite endpoint events: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke [14]. ∗P ​< 0.05; ∗∗P ​≤ ​0.01; ∗∗∗P ​< 0.001 [14].

Fig. 3. Cellular and Molecular Mechanisms of Atherosclerosis and Role of EPA. Mechanisms are depicted in the illustration; effects of EPA are listed to the right indicating increases (↑) or decreases (↓). LDL is subject to oxidative modification, progressing from mm-LDL to ox-LDL. Monocytes attach to endothelial cells, migrate into the subendothelial space, and differentiate into macrophages. Ox-LDL cholesterol uptake leads to foam cell formation. Interactions between macrophage foam cells, Th1 cells, and Th2 cells establish a chronic inflammatory process. Cytokines secreted by lymphocytes and macrophages exert both pro- and anti-atherogenic effects on each of the cellular elements of the vessel wall. SMCs migrate from the medial portion of the arterial wall, proliferate, and secrete extracellular matrix proteins that form a fibrous plaque [75,76]. ACAT, acyl CoA:cholesterol acyltransferase; Apo E, apolipoprotein E; CCR, C–C chemokine receptor; CD, clusters of differentiation; CS, connecting segment; EPA, eicosapentaenoic acid; EPA/AA, eicosapentaenoic acid/arachidonic acid ratio; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; ICAM, intercellular adhesion…

Fig. 4. Biosynthetic Cascades and Actions of Selected Lipid Mediators Derived From Arachidonic Acid (AA), Eicosapentaenoic Acid (EPA), and Docosahexaenoic Acid (DHA). COX, cyclooxygenase; HDHA, hydroxy-docosahexaenoic acid; HETE, hydroxyeicosatetraenoic acid; LO, lipoxygenase; LT, leukotriene; LX, lipoxin; MaR, maresin; PD, protectin; PG, prostaglandin; Reproduced with permission from Serhan CN, Petasis NA. Resolvins and protectins in inflammation resolution. Chem Rev. 2011; 111(10):5922–5943, copyright 2011 American Chemical Society [78].