Background Pre-statin trials reported positive effects of omega-3 fatty acids (n-3 PUFA) in cardiovascular disease (CVD), whereas recent studies and meta-analyses have not reproduced these results. The effect of n-3 PUFA in patients with familial hypercholesterolemia (FH), a group with particularly high risk of CVD, is not well established. Objective We investigated the effect of n-3 PUFA on the early stage of atherosclerosis in FH patients by evaluating in vivo (peripheral arterial tonometry (PAT)) and in vitro (plasma asymmetric dimethylarginine (ADMA) and E-selectin) endothelial function. Methods This was a double blind, placebo-controlled crossover study with 34 FH patients on statin treatment (mean age 46.6 years). In random order, all individuals were treated for three months with high dose n-3 PUFA (2g x2) and three months placebo (olive oil, 2g x2), separated by a three months washout period. Anthropometric data, blood samples and PAT were collected at four time points. Results There were no significant changes in reactive hyperemia index (RHI) measured by PAT after n-3 PUFA compared to placebo, median RHI after n-3 PUFA was 1.98 and after placebo 1.96, p=0.51. No significant changes were detected in the soluble endothelial marker ADMA (in two different assays) when comparing n-3 PUFA and placebo (p=0.92 and 0.14, respectively). Finally, the level of E-selectin did not change significantly during the trial, p=0.26. Conclusion Addition of n-3 PUFA to standard lipid-lowering treatment in genetically verified FH patients did not affect the in vivo endothelial function or soluble endothelial markers.

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