血脂净化治疗家族性高胆固醇血症的单中心研究

Lipoprotein apheresis in patients with familial hypercholesterolemia:a single center research

目的探讨对于接受强化降脂药物治疗后低密度脂蛋白胆固醇(LDL-C)不能达标的家族性高胆固醇血症(FH)患者,采用脂蛋白分离即血脂净化(LA)治疗的有效性与安全性。方法本研究为回顾性、横断面研究。连续选取2015年2月至2019年11月于中国医学科学院阜外医院进行LA治疗的FH患者,所有患者均在强化降脂药物治疗的基础上,采用双重滤过血浆置换(DFPP)法进行LA治疗。收集FH患者的年龄、性别、FH类型等基本临床信息,分析LA治疗前后LDL-C、脂蛋白a[Lp(a)]水平变化及其降幅,同时分析免疫球蛋白(Ig)变化以及LA治疗相关不良反应情况。结果共计纳入115例FH患者,其中杂合型FH患者107例(93.0%)、纯合型8例(7.0%);年龄(43.9±12.2)岁,男性75例(65.2%),合并冠心病108例(93.8%)。LA治疗前LDL-C和Lp(a)水平分别为(5.20±2.94)mmol/L和[428.70(177.00,829.50)]mg/L,LA治疗后即刻LDL-C和Lp(a)水平均显著降低,分别降至(1.83±1.08)mmol/L和148.90(75.90,317.00)mg/L(P均<0.001),降幅分别达64.2%和59.8%。LA治疗后1 d IgG、IgA均可维持于正常水平(降幅分别为15.1%、25.0%,P均<0.001),IgM低于正常水平(降幅58.7%,P<0.001)。6例(5.2%)患者出现LA治疗相关不良反应,包括恶心、低血压、气短、心悸等,程度均轻微,经对症处理后症状缓解。结论对于接受强化降脂药物治疗后LDL-C不达标的FH患者,尤其是伴Lp(a)升高者,DFPP法LA治疗可进一步大幅度降低LDL-C和Lp(a),是一种高效且安全的降脂治疗措施。

Objective We evaluated the safety and efficacy of lipoprotein apheresis(LA)in patients with familial hypercholesterolemia(FH)who can′t reach low-density lipoprotein cholesterol(LDL-C)target goals with the maximal tolerated dose of lipid-lowering agents.Methods This was a retrospective cross-sectional study.Between February 2015 and November 2019,patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled.Based on intensive lipid-lowering agents,these patients received LA by double filtration plasma pheresis(DFPP)method.The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)]were compared before and after LA treatment,and the changes of immunoglobulin(Ig)concentration and LA-related adverse effects were also discussed.Results A total of 115 patients with FH were enrolled in this study,of which 8 cases were homozygous FH and 107 cases were heterozygous FH.The age was(43.9±12.2)years and there were 75(65.2%)males,and 108(93.8%)with coronary artery disease.For pre-and immediately after LA treatment,the LDL-C was(5.20±2.94)mmol/L vs.(1.83±1.08)mmol/L,Lp(a)concentration was 428.70(177.00,829.50)mg/L vs.148.90(75.90,317.00)mg/L(P<0.001),with a decrease of 64.2%and 59.8%respectively.The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value,the reductions of which were 15.1%,25.0%and 58.7%respectively(P<0.001).Six patients had mild symptoms of nausea,hypotension dyspnea and palpitation,the symptoms were relieved by symptomatic treatment.Conclusion For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents,especially those with elevated Lp(a)levels,LA,which can significantly further reduce LDL-C and Lp(a)levels,is an effective and safe option.