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Neurology:“坏胆固醇LDL-C越低越好”受质疑,挑战PCSK9抑制剂安全性:Neurology杂志研究称,<70mg/dl脑出血风险增倍

2019-04-21 朱柳媛 中国循环杂志

作为人体内的“坏胆固醇”,低密度脂蛋白胆固醇(LDL-C)与心脑血管病的发生、发展非常密切,因此降LDL-C是预防心脑血管病的重要措施之一。

作为人体内的“坏胆固醇”,低密度脂蛋白胆固醇(LDL-C)与心脑血管病的发生、发展非常密切,因此降LDL-C是预防心脑血管病的重要措施之一。

而且,近年来不少研究提示,LDL-C可能降得越低越好。在业界热议的FOURIER研究中,心血管高危患者的LDL-C水平最低降至19 mg/dl都未出现明显的不良事件,这比新生儿的平均LDL-C水平(35 mg/dl左右)都要低。

然而,对于普通人群来说,LDL-C也是越低越好吗?

发表在Neurology杂志上的一项基于美国女性健康研究的最新分析结果表明,LDL-C水平<70 mg/dl的女士发生脑出血的风险是LDL-C水平为100~130 mg/dl的女士的2倍以上。

类似地,甘油三酯水平处于极低水平的女士也更容易发生脑出血。

校正年龄、吸烟状态、绝经状态、绝经后激素状态、体重指数、饮酒量、糖尿病高血压病史、体力活动、降胆固醇药物等潜在混淆因素后,研究者发现,LDL-C水平与脑出血风险之间的关系为U型曲线关系。

LDL-C水平处于100~129.9 mg/dl之间时脑出血风险最低,LDL-C水平<70 mg/dl时脑出血风险增加1.17倍。LDL-C水平≥160 mg/dl时,脑出血风险也呈升高趋势,但并无统计学意义。

将脑出血按颅内出血和蛛网膜下腔出血细分分析后,得出的结果均与上述结果一致。

进一步校正甘油三酯水平后,LDL-C水平<70 mg/dl和≥160 mg/dl的女士发生脑出血的风险分别是LDL-C水平为100~129.9 mg/dl者的2.04倍和1.75倍。

研究者集中在基线没有应用降胆固醇药物的2.7万名人中进行分析时,得出的结果也与主分析结果类似,但LDL-C水平<70 mg/dl者脑出血风险的增加不再有统计学意义。

另外,甘油三酯水平处于最低四分位(空腹≤74 mg/dl,非空腹≤85 mg/dl)的女士发生脑出血的风险也较甘油三酯水平处于最高四分位者增倍,主要是蛛网膜下腔出血风险增加。

进一步校正LDL-C水平后,甘油三酯水平处于最低四分位的女士发生脑出血的风险仍较甘油三酯水平处于最高四分位者增加1.14倍。

研究者发现,高密度脂蛋白胆固醇和总胆固醇水平与脑出血风险之间无关。

研究者表示,具体机制尚不清楚,可能与LDL-C水平较低的人血管壁完整性较差有关。但值得注意的是,该研究中受试者是在上世纪90年代初期接受血液检查,彼时他汀类降脂药物还未普遍应用。

有专家指出,该研究结果并不会改变目前的临床实践。该研究所要传达的关键点在于,LDL-C水平极低的人可能相对不那么健康,从而更易于发生脑出血。

需要指出的是,在该研究中,LDL-C水平<70 mg/dl相对更年轻,且有高血压病史或应用降胆固醇药物者较少,体重正常、积极运动者多,但更喜欢喝酒。

但也有专家表示,该研究随访时间较长,对积极深度降低LDL-C(例如应用PCSK9抑制剂)的长期安全性提出了疑问。

研究人员对女性健康研究中大约2.8万名女性受试者20年随访数据进行了分析。LDL-C水平<70 mg/dl者占3.8%。随访期间发生137例脑出血事件,LDL-C水平<70 mg/dl者脑出血发生率为0.8%,其余受试者中发生率为0.4%。

原始出处:
Rist PM1, Buring JE2, Ridker PM2, et al.Lipid levels and the risk of hemorrhagic stroke among women.Neurology. 2019 Apr . pii: 10.1212/WNL.0000000000007454. doi: 10.1212/WNL.0000000000007454. [Epub ahead of print]

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    2019-08-31 yinhl1978
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    2020-02-02 Tamikia
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    2019-11-24 saikp
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    2019-06-04 FukaiBao
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    2019-09-25 jklm09
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    2019-04-23 zhwj

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