Omega‐3 fatty acids, cardiovascular risk, and the resolution of inflammation

Although a high marine food intake is considered cardioprotective, randomized trials of ω‐3 fatty acids initially generated conflicting results in terms of the role of ω‐3 supplementation in cardiovascular prevention. This work demonstrates the results of the 3 most recent clinical trials with ω‐3 fatty acids are put into the context of possible mechanisms mediating their beneficial cardiovascular effects. In particular, the randomized Reduction of Cardiovascular Events with EPA Intervention Trial (REDUCE‐IT) showed that icosapent ethyl, which is the ethyl ester form of the ω‐3 fatty acid eicosapentaenoic acid (EPA), induced a significant reduction of cardiovascular events. Importantly, EPA serves as a substrate for the formation of the specialized proresolving mediator resolvin E1 (RvE1), which stimulates the resolution of inflammation. RvE1 reduces atherosclerosis and intimai hyperplasia by means of its specific receptor ERV1/ChemR23. The decreased levels of proinflammatory and proatherosclerotic leukotrienes by ω‐3 fatty acids may further contribute to a beneficial inflammatory balance. Consequently, the Rv/leukotriene ratio is emerging as a marker of nonresolving vascular inflammation. Recent experimental studies have shown that anti‐inflammatory and proresolving effects of lipid mediators derived from ω‐3 fatty acids inhibit atherosclerosis independently of cholesterol and triglyceride levels. The results of the 3 most recent clinical trials of ω‐3 fatty acid supplementation indicate an importance of the type and dose of ω‐3 supplementation and highlight the need for risk stratification in the patient selection for ω‐3 supplementation for either primary or secondary prevention of cardiovascular disease.—Bäck, M., Hansson, G. K. Omega‐3 fatty acids, cardiovascular risk, and the resolution of inflammation. FASEB J. 33, 1536–1539 (2019). www.fasebj.org