Richter W O, Donner M G, Höfling B, Schwandt P
Medical Department I, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, Germany.
Metabolism. 1998 Jul;47(7):863-8. doi: 10.1016/s0026-0495(98)90127-5.
Low-density lipoprotein (LDL) apheresis is a potent treatment for patients with coronary heart disease and severe hereditary forms of LDL hypercholesterolemia not adequately responsive to drug treatment. Until now, the beneficial effect of aggressive reduction of LDL cholesterol by LDL apheresis on the course of coronary heart disease has been demonstrated in one 3-year study and several studies lasting 2 years. We now report on the clinical course, lipoprotein concentrations, coronary angiograms, and side effects in patients undergoing LDL apheresis for as long as 8.6 years. Thirty-four patients (21 men and 13 women) with coronary heart disease and heterozygous familial hypercholesterolemia (FH) not adequately responsive to lipid-lowering drugs received weekly (four patients biweekly) LDL apheresis for 4.6 +/- 2.6 years under diet and lipid-lowering drug therapy; after 0.5 to 3 years, simvastatin in the maximal tolerable dose was added. The baseline LDL cholesterol concentration was 6.9 +/- 1.6 mmol/L. Combined treatment in the steady state yielded a pretreatment and posttreatment LDL cholesterol concentration of 4.8 +/- 0.9 and 1.8 +/- 0.4 mmol/L, respectively. The calculated interval mean LDL cholesterol was 3.3 +/- 0.6 mmol/L. Evaluation of the coronary angiographies revealed a definite regression of coronary lesions in four patients (11.8%); in 19 patients, there was a cessation of progression. Two patients developed atheromatous lesions in bypass grafts (L.H., 60% stenosis; S.M., occlusion). Of 23 patients eligible for the scoring of anginal symptoms, five (21.7%) reported a reduction of the frequency and severity of angina pectoris. The mean coronary symptom score in 23 patients changed from 1.65 +/- 0.83 at baseline to 1.39 +/- 0.66 at the end of the study. During the whole observation period, we observed three sudden deaths, one nonfatal myocardial infarction, and five patients requiring hospital admission because of unstable angina pectoris, one of which was followed by a transluminal coronary angioplasty. Aggressive reduction of LDL cholesterol with combined LDL apheresis and drugs induced regression of coronary lesions in four of 34 patients and prevented progression in 29 patients for as long as 8.6 years. The effect on LDL and high-density lipoprotein (HDL) cholesterol and lipoprotein(a) [Lp(a)] was comparable with all three apheresis techniques. Therefore, no obvious difference between the three techniques was found regarding changes in coronary lesions.
低密度脂蛋白（LDL）分离术是治疗冠心病患者以及对药物治疗反应不佳的严重遗传性LDL高胆固醇血症患者的有效方法。到目前为止，在一项为期3年的研究以及几项为期2年的研究中，已证明通过LDL分离术积极降低LDL胆固醇对冠心病病程具有有益作用。我们现在报告接受长达8.6年LDL分离术患者的临床病程、脂蛋白浓度、冠状动脉造影及副作用。34例（21例男性和13例女性）患有冠心病且对降脂药物反应不佳的杂合子家族性高胆固醇血症（FH）患者，在饮食和降脂药物治疗的同时，每周（4例每两周一次）接受LDL分离术治疗4.6±2.6年；0.5至3年后，加用最大耐受剂量的辛伐他汀。基线LDL胆固醇浓度为6.9±1.6 mmol/L。稳态联合治疗产生的治疗前和治疗后LDL胆固醇浓度分别为4.8±0.9和1.8±0.4 mmol/L。计算得出的平均LDL胆固醇间隔值为3.3±0.6 mmol/L。冠状动脉造影评估显示，4例患者（11.8%）冠状动脉病变有明确消退；19例患者病变进展停止。2例患者在搭桥移植物中出现动脉粥样硬化病变（L.H.，狭窄60%；S.M.，闭塞）。在23例符合心绞痛症状评分标准的患者中，5例（21.7%）报告心绞痛发作频率和严重程度降低。23例患者的平均冠状动脉症状评分从基线时的1.65±0.83变为研究结束时的1.39±0.66。在整个观察期内，我们观察到3例猝死、1例非致命性心肌梗死以及5例因不稳定型心绞痛需住院治疗的患者，其中1例随后接受了经皮冠状动脉腔内血管成形术。联合LDL分离术和药物积极降低LDL胆固醇，使34例患者中的4例冠状动脉病变消退，并使29例患者的病变在长达8.6年的时间里停止进展。对LDL、高密度脂蛋白（HDL）胆固醇和脂蛋白(a)[Lp(a)]的影响在所有三种分离术技术中相当。因此，在冠状动脉病变变化方面，三种技术之间未发现明显差异。
