Potential benefits of eicosapentaenoic acid on atherosclerotic plaques

Abstract

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy.

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

“…These macrophages take up oxidized apolipoprotein B–containing LDL particles, a process leading to foam cell and fatty streak formation, the precursor of advanced atherosclerotic lesions. Potential beneficial effects of EPA on atherosclerotic plaque include anti‐inflammatory and antioxidant effects, decreased adhesion of monocytes to the endothelium, decreased macrophage and foam cell accumulation in fatty streaks, and increased thickness of the fibrous cap overlying lipid‐rich plaque28, 29, 30 (reviewed in Nelson et al) 31. EPA and DHA are also converted to specialized proresolving lipid mediators, with EPA and DHA being the respective precursors of the E‐series and D‐series resolvins 32.…”

“…Potential beneficial effects of EPA on atherosclerotic plaque include anti-inflammatory and antioxidant effects, decreased adhesion of monocytes to the endothelium, decreased macrophage and foam cell accumulation in fatty streaks, and increased thickness of the fibrous cap overlying lipid-rich plaque [28][29][30] (reviewed in Nelson et al). 31 EPA and DHA are also converted to specialized proresolving lipid mediators, with EPA and DHA being the respective precursors of the E-series and D-series resolvins. 32 The resolvins have been shown to stimulate the resolution of acute inflammation by stopping further neutrophil recruitment to inflamed tissues and stimulating nonphlogistic infiltration of monocytes, which differentiate into resolution macrophages.…”

Different monocyte phenotypes result in proresolving macrophages in conjugated linoleic acid‐induced attenuated progression and regression of atherosclerosis

“…Lymphoid cells including DCs were also altered in HFHCD+CLA-treated mice. Many studies have investigated attenuation of disease progression using lipid mediators such as v-3 fatty acids (39,40), eicosapentaenoic acid (41), and lipid mediators maresin-1 and resolvin D2 (41). N-3 fatty acids had no effect on slowing progression of atherosclerosis in carotid arteries of patients (39) or in ApoE 2/2 mice, but they did attenuate lesion progression and reduce plasma cholesterol in LDL receptor knockout mice (40).…”

“…Eicosapentaenoic acid showed beneficial effects on plaque characteristics and lower plasma triglyceride levels without raising LDL cholesterol. Eicosapentaenoic acid in combination with a statin reduced 19% of major coronary artery events (41). Limited studies have used in vivo murine models, with only 1 study reporting successful prevention of disease progression in ApoE 2/2 mice using resolvin D2 and maresin-1 (42).…”

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

“…The effects of EPA on atherosclerotic plaque have been investigated in animal and clinical studies [32]. Preclinical data from animal models support beneficial effects of EPA on atherosclerotic lesions including stable morphology, reduction of established plaques, and decreased inflammation [33][34][35].…”