Addition of marine omega-3 fatty acids to statins in familial hypercholesterolemia does not affect in vivo or in vitro endothelial function

Abstract

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.

Diet and Cardiovascular Disease Risk Among Individuals with Familial Hypercholesterolemia: Systematic Review and Meta-Analysis

“…The majority of the included studies was double-blind, placebo-controlled and randomized with a cross-over design. [9][10][11][12][13][14][15] Their duration ranged from 3 to 13 weeks and their samples from 10 to 62 subjects. Seven trials enrolled children fulfilling the criteria of FH.…”

“…[9,11,14,[16][17][18][19] Among the rest studies including adults with FH, in 8 RCTs the subjects were also treated with lipid-lowering drugs. [10,13,15,[20][21][22][23][24] Randomized, cross-over (4-5w) 10 adults with familial hypercholesterolemia (2 of those had possibly FCH) (aged 50 ± 5 yrs old) Low-fat/low-cholesterol/high-protein (23%) diet vs low-fat/low-cholesterol/low-protein (11%) diet d, day; FCH, familial combined hyperlipidemia; FH, familial hypercholesterolemia; m, months; w, weeks; yrs, years.…”

“…[21] • Three trials compared the effect of treatment with omega-3 fatty acids in comparison with placebo. [10,13,20] The daily supplementation of omega-3 fatty acids was 5.1 g with a ratio of eicosapentaenoic acid/ docosahexaenoic acid (EPA/DHA) of 1:1 in the oldest trial [10], whereas the treatment arm in the rest RCTs comprised of 4 gr/d of EPA/DHA (46% EPA and 38% DHA). [13,20].…”

“…[10,13,20] The daily supplementation of omega-3 fatty acids was 5.1 g with a ratio of eicosapentaenoic acid/ docosahexaenoic acid (EPA/DHA) of 1:1 in the oldest trial [10], whereas the treatment arm in the rest RCTs comprised of 4 gr/d of EPA/DHA (46% EPA and 38% DHA). [13,20]. All of these trials included adults taking lipid-lowering therapy [10,13,20] and only one reported that its subjects adhered to cholesterol-lowering diet.…”

“…[13,20]. All of these trials included adults taking lipid-lowering therapy [10,13,20] and only one reported that its subjects adhered to cholesterol-lowering diet. [10] • Two trials evaluated the impact of modified fat on FH patients.…”