de Graaf J, Demacker P N, Stalenhoef A F
Department of General Internal Medicine, University Hospital, Nijmegen, Netherlands.
Neth J Med. 1993 Dec;43(5-6):254-61.
The effect of simvastatin treatment on the low-density lipoprotein (LDL) subfraction profile was studied in 26 patients with familial hypercholesterolaemia. Before treatment LDL consisted of three LDL subfractions, using density-gradient ultracentrifugation (LDL1, LDL2 and LDL3) present in a relatively narrow density range (d = 1.030-1.045 g/ml). Simvastatin did not influence this profile with respect to the number and density range of the LDL subfractions. However, the composition of the isolated LDL subfractions changed after treatment, as evidenced by the reversal towards normal of the increased cholesterol/protein ratio (mean 1.51 before vs. 1.38 after therapy, p < 0.01; mean 1.36 in normolipidaemic subjects). When the subjects were stratified by their plasma triglyceride levels or the change in plasma triglycerides during simvastatin therapy, a strong dependence of the LDL subfraction profile and its composition on plasma triglyceride levels was observed; increasing plasma triglyceride levels were associated with a more dense LDL subfraction profile, characterized by a high relative contribution of dense LDL3 to total LDL and changes in LDL composition, reflected by a relatively low cholesterol/protein ratio. Our results indicate that in patients with familial hypercholesterolaemia: (1) plasma triglyceride levels have an important role in determining the properties of LDL and (2) simvastatin treatment results in changes in composition of LDL, which may affect the intrinsic metabolic characteristics and thus the atherogenic potential of LDL.
在26例家族性高胆固醇血症患者中研究了辛伐他汀治疗对低密度脂蛋白（LDL）亚组分谱的影响。治疗前，采用密度梯度超速离心法，LDL由三个LDL亚组分组成（LDL1、LDL2和LDL3），存在于相对较窄的密度范围内（d = 1.030 - 1.045 g/ml）。辛伐他汀对LDL亚组分的数量和密度范围未产生影响。然而，治疗后分离出的LDL亚组分的组成发生了变化，胆固醇/蛋白质比值升高趋势逆转至正常即为明证（治疗前平均为1.51，治疗后为1.38，p < 0.01；正常血脂受试者平均为1.36）。当根据受试者的血浆甘油三酯水平或辛伐他汀治疗期间血浆甘油三酯的变化进行分层时，观察到LDL亚组分谱及其组成强烈依赖于血浆甘油三酯水平；血浆甘油三酯水平升高与更致密的LDL亚组分谱相关，其特征为致密的LDL3对总LDL的相对贡献较高以及LDL组成的变化，表现为胆固醇/蛋白质比值相对较低。我们的结果表明，在家族性高胆固醇血症患者中：（1）血浆甘油三酯水平在决定LDL的性质方面起重要作用；（2）辛伐他汀治疗导致LDL组成发生变化，这可能会影响LDL的内在代谢特征，进而影响其致动脉粥样硬化潜力。
