Improved arterial inflammation with high dose omega-3 fatty acids in patients with elevated lipoprotein(a): Selective effect of eicosapentaenoic acid?

Elevated lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease. However, there are no approved and effective treatments for lowering Lp(a) and the associated cardiovascular risks. Omega-3 fatty acids (ω-3FAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have both triglyceride-lowering and anti-inflammatory properties. This pilot study investigated the effect of high dose ω-3FAs (3.6 g/day) on arterial inflammation in 12 patients with elevated Lp(a) (> 0.5 g/L) and stable coronary artery disease (CAD) receiving cholesterol-lowering treatment. Arterial inflammation was determined using 18F-fluorodexoyglucose positron emission tomography/computed tomography before and after 12-weeks intervention. ω-3FAs significantly lowered plasma concentrations of triglycerides (-17%, p < 0.01), Lp(a) (-5%, p < 0.01) as well as aortic maximum standardized uptake value (SUVmax) (-4%, p < 0.05). The reduction in SUVmax was significantly inversely associated with average on-treatment EPA (r = -0.750, p < 0.01), but not DHA and triglyceride, concentrations. In conclusion, high dose ω-3FAs decrease arterial inflammation in patients with elevated Lp(a) and stable CAD, which may involve a direct arterial effect of EPA.

Effect of Omega-3 Fatty Acid Supplementation on the Postprandial Metabolism of Apolipoprotein(a) in Familial Hypercholesterolemia.

AIM: Lipoprotein(a) (Lp(a)) is a low-density lipoprotein-like particle containing apolipoprotein(a) (apo(a)) that increases the risk of atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH). Postprandial redistribution of apo(a) protein from Lp(a) to triglyceride-rich lipoproteins (TRLs) may also increase the atherogenicity of TRL particles. Omega-3 fatty acid (ω3FA) supplementation improves postprandial TRL metabolism in FH subjects. However, its effect on postprandial apo(a) metabolism has yet to be investigated. METHODS: We carried out an 8-week open-label, randomized, crossover trial to test the effect of ω3FA supplementation (4 g/day) on postprandial apo(a) responses in FH patients following ingestion of an oral fat load. Postprandial plasma total and TRL-apo(a) concentrations were measured by liquid chromatography with tandem mass spectrometry, and the corresponding areas under the curve (AUCs) (0-10h) were determined using the trapezium rule. RESULTS: Compared with no ω3FA treatment, ω3FA supplementation significantly lowered the concentrations of postprandial TRL-apo(a) at 0.5 (-17.9%), 1 (-18.7%), 2 (-32.6%), and 3 h (-19.2%) (P＜0.05 for all). Postprandial TRL-apo(a) AUC was significantly reduced with ω3FA by 14.8% (P＜0.05). By contrast, ω3FA had no significant effect on the total AUCs of apo(a), apoC-III, and apoE (P＞0.05 for all). The decrease in postprandial TRL-apo(a) AUC was significantly associated with changes in the AUC of triglycerides (r=0.600; P＜0.01) and apoB-48 (r=0.616; P＜0.01). CONCLUSIONS: Supplementation with ω3FA reduces postprandial TRL-apo(a) response to a fat meal in FH patients; this novel metabolic effect of ω3FA may have implications on decreasing the risk of ASCVD in patients with FH, especially in those with elevated plasma triglyceride and Lp(a) concentrations. However, the clinical implications of these metabolic findings require further evaluation in outcome or surrogate endpoint trials.