Medical School, University of Western Australia.
Nantes Université, CNRS, INSERM, l'institut du thorax.
J Atheroscler Thromb. 2023 Mar 1;30(3):274-286. doi: 10.5551/jat.63587. Epub 2022 Jun 8.
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.
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.
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).
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.
脂蛋白（a）（Lp(a)）是一种富含载脂蛋白（a）（apo(a)）的低密度脂蛋白样颗粒，可增加家族性高胆固醇血症（FH）患者发生动脉粥样硬化性心血管疾病（ASCVD）的风险。apo(a)蛋白从 Lp(a)到富含甘油三酯的脂蛋白（TRL）的餐后再分布也可能增加 TRL 颗粒的致动脉粥样性。ω-3 脂肪酸（ω3FA）补充剂可改善 FH 患者的餐后 TRL 代谢。然而，其对餐后 apo(a)代谢的影响尚未得到研究。
我们进行了一项 8 周的开放标签、随机、交叉试验，以测试 ω3FA 补充剂（4 g/天）对 FH 患者口服脂肪负荷后餐后 apo(a)反应的影响。通过液相色谱-串联质谱法测量餐后血浆总 TRL-apo(a)浓度，并使用梯形规则确定相应的曲线下面积（AUC）（0-10 小时）。
与无 ω3FA 治疗相比，ω3FA 补充剂可显著降低餐后 TRL-apo(a)在 0.5（-17.9%）、1（-18.7%）、2（-32.6%）和 3 小时（-19.2%）的浓度（均 P＜0.05）。ω3FA 可使餐后 TRL-apo(a) AUC 降低 14.8%（P＜0.05）。相比之下，ω3FA 对 apo(a)、apoC-III 和 apoE 的总 AUC 没有显著影响（均 P＞0.05）。餐后 TRL-apo(a) AUC 的降低与甘油三酯（r=0.600；P＜0.01）和 apoB-48（r=0.616；P＜0.01）的 AUC 变化显著相关。
ω3FA 补充剂可降低 FH 患者餐后 TRL-apo(a)对脂肪餐的反应；ω3FA 的这种新的代谢作用可能降低 FH 患者发生 ASCVD 的风险，特别是在那些血浆甘油三酯和 Lp(a)浓度升高的患者中。然而，这些代谢发现的临床意义需要在结局或替代终点试验中进一步评估。
