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低密度脂蛋白分离术:重度高胆固醇血症治疗的临床经验与适应证

LDL-apheresis: clinical experience and indications in the treatment of severe hypercholesterolemia.

作者信息

Thiery J, Seidel D

机构信息

Institute of Clinical Chemistry, Ludwig-Maximilians-University, Hospital Grobetahadern, Munich, Germany.

出版信息

Transfus Sci. 1993 Jul;14(3):249-59. doi: 10.1016/0955-3886(93)90005-F.

Abstract

LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that plasma LDL-cholesterol below 100 mg/dL decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dL LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.--LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with 1 week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by +12%. Fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P. treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.--apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.

摘要

低密度脂蛋白胆固醇是影响已有冠心病患者临床预后的主要危险因素。临床试验表明,血浆低密度脂蛋白胆固醇低于100mg/dL可降低心肌梗死复发率,并可使冠心病患者病情出现逆转。然而,在大多数严重高胆固醇血症病例中,血浆低密度脂蛋白胆固醇浓度高于220mg/dL,仅靠最大程度的饮食和药物治疗无法充分降低低密度脂蛋白水平。如今,对于这组高危冠心病患者,可采用体外程序从血浆循环中清除低密度脂蛋白,即血脂分离治疗法(H.E.L.P.--LDL-apheresis)。这种从血浆中选择性去除低密度脂蛋白、脂蛋白(a)和纤维蛋白原的方法,已被证明是治疗纯合子家族性高胆固醇血症患者或严重高胆固醇血症冠心病患者的一种临床安全且非常有效的方法。每隔1周进行一次血脂分离治疗法(H.E.L.P.),结果显示低密度脂蛋白平均降低51%,脂蛋白(a)降低45%,载脂蛋白B降低46%,而高密度脂蛋白升高12%。纤维蛋白原降低46%。除了显著降低低密度脂蛋白和纤维蛋白原血浆浓度外,血脂分离治疗法(H.E.L.P.)还能显著改善血液流变学参数,并提高组织中的氧张力。我们还研究了联合治疗的效果,即使用HMG-CoA还原酶抑制剂与血脂分离治疗法(H.E.L.P.--apheresis)联合使用。在这种联合治疗下,低密度脂蛋白胆固醇水平的间隔降低了70 - 80%,而脂蛋白(a)和纤维蛋白原未受到进一步影响。我们现在报告我们在使用血脂分离治疗法(H.E.L.P.)系统治疗不同脂蛋白异常患者方面的长期临床经验:(1)家族性高胆固醇血症的纯合子形式;(2)患有家族性和非家族性高胆固醇血症的冠心病患者;(3)脂蛋白(a)浓度极高的冠心病患者;(4)心脏移植后的高胆固醇血症患者。基于目前的经验,讨论了冠心病二级预防指南中血脂分离治疗法(H.E.L.P.--LDL-apheresis)治疗的适应证。

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