Calabresi L, Donati D, Pazzucconi F, Sirtori C R, Franceschini G
Center E. Grossi Paoletti, Institute of Pharmacological Sciences, University of Milano, via Balzaretti 9, 20133, Milan, Italy.
Atherosclerosis. 2000 Feb;148(2):387-96. doi: 10.1016/s0021-9150(99)00267-1.
Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9+/-0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27+/-0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40+/-0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0+/-0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients.
在家族性混合型高脂血症（FCHL）患者中，血浆胆固醇和/或甘油三酯水平升高，以及小而密的低密度脂蛋白（LDL）颗粒的患病率显著增加冠状动脉风险。共研究了14例FCHL患者，以调查含n-3脂肪酸二十碳五烯酸和二十二碳六烯酸（EPA和DHA）的药物Omacor对血浆脂质/脂蛋白水平和LDL颗粒分布进行有利校正的能力。在一项随机、双盲、交叉研究中，患者每天服用四粒Omacor胶囊（每天提供3.4克EPA+DHA）或安慰剂，持续8周。Omacor显著降低血浆甘油三酯和极低密度脂蛋白胆固醇（VLDL-胆固醇）水平，分别降低了27%和18%。总胆固醇没有变化，但低密度脂蛋白胆固醇和载脂蛋白B（apoB）浓度分别增加了21%和6%。正如预期的那样，在选定的受试者中，LDL颗粒较小（直径=24.9±0.3纳米）且富含apoB（LDL-胆固醇/apoB比率=1.27±0.26）。Omacor治疗后，LDL富含胆固醇（LDL-胆固醇/apoB比率=1.40±0.17），主要是胆固醇酯，表明血浆中更具浮力且富含核心的LDL颗粒积累。实际上，通过速率区带超速离心法分离LDL亚类显示，服用Omacor后，中间密度脂蛋白（IDL）以及更具浮力、快速漂浮的LDL-1和LDL-2亚类的血浆浓度增加，而密度更大、缓慢漂浮的LDL-3亚类的浓度则相应降低。然而，服用Omacor后LDL的平均大小没有变化（25.0±0.3纳米）。小LDL模式对药物诱导修饰的抗性意味着必须实现最大降脂效果才能降低FCHL患者的冠状动脉风险。
