Position paper ANMCO: New perspectives on the role of n-3 polyunsaturated fatty acids in cardiovascular prevention

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most important long-chain polyunsaturated fatty acids of the n-3 series (n-3 PUFA). Recent studies have clarified that EPA and DHA have different tissue distribution and influence target organs in a distinct way. In addition to the main effect of reducing triglycerides (TG), they exert antithrombotic, antiarrhythmic, anti-inflammatory, anti-atherogenic, and hemodynamic effects. The different action of PUFA n-3 depends on the dosage and duration of treatment: the effect on TG requires high doses and a few weeks/months of treatment. Several epidemiological studies have shown a relationship between hypertriglyceridemia and cardiovascular risk, confirmed by post-hoc analysis of statin trials and by recent genetic linkage studies. Moreover in secondary prevention, the evidence of a significant "residual risk", even in the presence of an adequate control of LDL-cholesterol, has led the scientific community to consider further intervention objectives in the context of the individual lipid profile, the most promising of which is certainly hypertriglyceridemia. The recent landmark REDUCE-IT study is the first major lipid intervention study to demonstrate a benefit deriving from an approach not based on the LDL target, focusing on a determinant factor of residual risk such as hypertriglyceridemia and treating it with high doses of n-3 PUFA (4 g/day). Overall, the "lipid residual risk" approach involves two integrated actions: (i) the achievement of the LDL-cholesterol target (<70 mg/dl) by using statins, ezetimibe, PCSK9 inhibitors; (ii) checking TG levels in order to start n-3 PUFA in case of TG values > 150 mg/dl, at an initial dosage of 2-3 g/day (up to 4 g/day after 10-12 weeks).