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JACC:“好胆固醇”真的能防治心血管疾病吗?

2016-11-09 佚名 药明康德

导语:提高高密度脂蛋白(HDL,也称“好胆固醇”)的水平,多年以来一直被认为能够预防心脏病和中风的发生,但是日前发表的一项新研究对这个观点提出了挑战。这一新发现不但与我们的常识相悖,而且可能帮助解释为什么目前没有药物能通过提高HDL水平来降低因心脏病导致的死亡风险。提高高密度脂蛋白(HDL,也称“好胆固醇”)的水平,多年以来一直被认为能够预防心脏病和中风的发生,但是日前发表的一项新研究对这个观点提

导语:提高高密度脂蛋白(HDL,也称“好胆固醇”)的水平,多年以来一直被认为能够预防心脏病和中风的发生,但是日前发表的一项新研究对这个观点提出了挑战。这一新发现不但与我们的常识相悖,而且可能帮助解释为什么目前没有药物能通过提高HDL水平来降低因心脏病导致的死亡风险。

提高高密度脂蛋白(HDL,也称“好胆固醇”)的水平,多年以来一直被认为能够预防心脏病和中风的发生,但是日前发表的一项新研究对这个观点提出了挑战。这一新发现不但与我们的常识相悖,而且可能帮助解释为什么目前没有药物能通过提高HDL水平来降低因心脏病导致的死亡风险。

HDL被认为能够帮助清理血液中的坏胆固醇并且减少血管内壁的脂肪沉积,所以HDL水平被认为能够预测心脏病和中风的风险。在这项发表在《Journal of American College of Cardiology》的研究中,加拿大临床评价科学研究所的研究人员运用“大数据”的方法,对安大略省超过63万人的HDL水平和因为不同原因导致的死亡数据进行了分析。


▲HDL结构(图片来源:Weebly)

研究结果表明,HDL水平非常低的人群确实更容易死于心血管疾病的并发症。但是,死于心脏病的风险并不是随着HDL水平的升高而持续降低的。随着HDL水平的升高,死于心脏病的风险开始下降,但是很快这一下降就停止了。那些血液中HDL水平为40毫克/分升的人与HDL水平为80毫克/分升的人的风险几乎相同。而且其它原因导致的死亡风险在HDL水平非常高的人群中居然上升了。

更让人困惑的是,HDL水平低的人因为其它原因死亡的风险也升高了。他们大多收入较低,体重较高,并且饮食习惯相对较差。这些都是导致死亡率增加的因素。这个结果表明,“HDL水平可能只是一个反映其它增高死亡风险的健康习惯的指标,它本身并不是一个影响心脏病死亡率的风险因素,”克利夫兰诊所的心脏病专家Steven Nissen博士说。


▲胆固醇在体内的运输(图片来源:Vascular Health and Risk Management)

这也许能解释为何一些能提高HDL水平的新药无法降低患者的心脏病和中风风险。近期,一些药企正在研发一类叫做胆固醇酯转移蛋白(cholesteryl ester transfer protein, CETP)抑制剂的药物,它们能够干扰将HDL转化为LDL的过程。这些药在提高HDL水平方面确实取得了成功,但是好胆固醇和坏胆固醇比例的变化却没有降低患者的死亡率。

那么检查HDL水平还有用么?心脏病专家认为HDL水平仍然是有参考价值的指标,因为它确实与诸如饮食和锻炼习惯这些影响健康水平的其它因素相关。而且HDL是一个包含有不同直径的脂蛋白颗粒的大类别,或许其中的一个亚型与心血管疾病风险有着更紧密的联系。

而CETP 抑制剂可能只对携带特定基因突变的患者有用。例如,一些CETP抑制剂虽然在晚期临床试验中没有抵达目标,但是对试验数据的进一步分析发现这一药物对于携带ADCY9基因变异的患者疗效明显。目前,一家名为DalCor Pharmaceutical的英国初创公司正在试图将它开发为一种靶向疗法。

“我们对HDL的理解已经产生了变化,”曾经主持过多项CETP抑制剂临床试验,纽约长老会医院的心血管疾病专家Bassem Masri博士说:“单单提高HDL水平不足以解决问题。可能只有一部分特殊人群会对HDL水平升高有良好的反应。”

原始出处:

Dennis T. Ko, MD, MSca,b,c; David A. Alter, MD, PhDa,b,d; Helen Guo, MSca; Maria Koh, MSca; Geoffrey Lau, BHSc candidatea; Peter C. Austin, PhDa,c; Gillian L. Booth, MD, MSca,c,e; William Hogg, MD, MCIScf,g; Cynthia A. Jackevicius, PharmD, MSca,c,h,i; Douglas S. Lee, MD, PhDa,c,j; Harindra C. Wijeysundera, MD, PhDa,b,c; John T. Wilkins, MDk; Jack V. Tu, MD, PhDa,b,c.high-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions.jacc.2016.08

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    2017-03-05 hbwxf
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    2016-11-18 ylzr123

    单单提高HDL水平不足以解决问题。可能只有一部分特殊人群会对HDL水平升高有良好的反应。

    0

  4. 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    2016-11-12 L2X496

    不错,学习了

    0

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    2016-11-11 大爰

    学习了增加知识了分享了谢谢

    0

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  8. 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    2016-11-10 inter158

    高密度脂蛋白是不是本身就没有关系只是统计学造成的

    0

  9. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161001/IMG57EE8DCCA0CBC2639.jpg, createdBy=88e51960023, createdName=陈安安, createdTime=Wed Nov 09 12:47:39 CST 2016, time=2016-11-09, status=1, ipAttribution=)]
    2016-11-09 小刘

    学习了,新观点

    0

  10. 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    2016-11-09 陈安安

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