2018CCCP&SCC:常敏之教授畅谈家族性高胆固醇血症的治疗进展

2018-04-07 国际循环编辑部 国际循环

编者按:2018年4月6日,2018中国医师协会心血管内科医师年会和2018中国南方国际心血管病学术会议“心血管病临床国际论坛Session 2”专场上,来自中国台北荣民总医院的常敏之教授就家族性高胆固醇血症(FH)的治疗进展作了专题解析,让参会者对FH的治疗新药有了更多了解。

编者按:2018年4月6日,2018中国医师协会心血管内科医师年会和2018中国南方国际心血管病学术会议心血管临床国际论坛Session 2”专场上,来自中国台北荣民总医院的常敏之教授就家族性高胆固醇血症(FH)的治疗进展作了专题解析,让参会者对FH的治疗新药有了更多了解。

FH概览

FH是常染色体不完全线性遗传病,是低密度脂蛋白受体(LDLR)基因突变引起细胞膜上的LDLR结构及功能异常而导致脂质代谢紊乱而产生的一组临床综合征。1938年,Müller C率先描述了FH的临床表现。1974年,Goldstein和Brown发现了成纤维细胞表面的LDLR进而阐明了FH的发病机制即LDLR基因突变。HF的主要临床表征包括血清胆固醇水平尤其是低密度脂蛋白胆固醇明显升高、皮肤及跟腱黄色脂肪瘤、早发动脉粥样硬化等,以高胆固醇、脂肪瘤及早发心肌梗死为突出特点。临床实践中,FH可分为杂合子型和纯合子型(图1),以前者发生率更高;患者临床可表现为脂肪瘤、早发性心肌梗死及主动脉瓣重度狭窄等。



图1. FH的分型及各自特征

FH的治疗

FH治疗可供选择的措施包括最大剂量强效他汀类药物、依折麦布或胆汁酸结合树脂、LDL-C机采分离治疗及肝移植等。需强调的是鉴于传统药物治疗效果(尤其是对纯合子型HF治疗效果不佳),近年来不少新药(APOB反义寡核苷酸Mipomersen、MTP抑制剂Lomitapide及PSCK9抑制剂等)经研发和临床试验验证后获批上市。上述新药与传统药物可分别作用于不同靶点,通过具体机制抑制VLDL的分泌进而达到降低LDL-C的效果(图2)。展望未来,CETP抑制剂及基因治疗也有望成为FH治疗的新希望(图3)。



图2. 不同FH治疗药物的作用机制



图3. 纯合子FH治疗流程

中国台湾FH情况

常敏之教授开展的中国台湾地区纯合子型FH患者相关研究共计发现23例纯合子型FH患者,其中接受最大剂量他汀+依折麦布治疗者11例,脂蛋白机采分离治疗者3例(死亡1例),接受肝移植治疗者2例,接受新型药物Mipomersen、Lomitapide及PCSK9抑制剂治疗者分别有4例(最初4例,但后来都停用)、5例和2例。就治疗目标而言,目前中国台湾2017高风险患者血脂异常临床治疗指南推荐将成人、儿童及有心血管疾病FH患者的LDL-C分别降至小于100 mg/dl、135 mg/dl和70 mg/dl。

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    2018-12-15 柳叶一刀
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    2018-04-09 wetgdt
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    2018-04-08 1ddf0692m34(暂无匿称)

    学习了.长知识

    0

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    2018-04-08 易水河

    学习学习.知之为知之

    0

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    2018-04-07 chenfeixian

    谢谢分享

    0

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    2018-04-07 清风拂面

    谢谢分享学习

    0

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