Considerations for routinely testing for high lipoprotein(a).

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in lipidology Pub Date : 2023-08-01 Epub Date: 2022-10-18 DOI:10.1097/MOL.0000000000000838

Nick S Nurmohamed, Patrick M Moriarty, Erik Sg Stroes

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Abstract

Purpose of review: Lipoprotein (a) [Lp(a)] is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a). This review focuses on the clinical importance and therapeutic consequences of Lp(a) measurement.

Recent findings: Development of RNA-based Lp(a) lowering therapeutics has positioned Lp(a) as one of the principal residual risk factors to target in the battle against lipid-driven ASCVD risk. Pelacarsen, which is a liver-specific antisense oligonucleotide, has shown Lp(a) reductions up to 90% and its phase 3 trial is currently underway. Olpasiran is a small interfering RNA targeting LPA messenger RNA, which is being investigated in phase 2 and has already shown dose-dependent Lp(a) reductions up to 90%.

Summary: Lp(a) should be measured in every patient at least once to identify patients with very high Lp(a) levels. These patients could benefit from Lp(a) lowering therapies when approved. In the meantime, therapy in high Lp(a) patients should focus on further reducing LDL-C and other ASCVD risk factors.

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常规检测高脂蛋白（a）的注意事项。

综述目的：脂蛋白（a）[Lp(a)]可能是动脉粥样硬化性心血管疾病（ASCVD）和主动脉瓣疾病的致病风险因素，这一点已被孟德尔随机法证实。通过可靠的检测方法，已确定脂蛋白（a）与 ASCVD 呈线性相关。目前降低低密度脂蛋白胆固醇（LDL-C）的疗法不能或仅能降低 Lp（a）。本综述将重点讨论脂蛋白（a）测量的临床重要性和治疗效果：基于 RNA 的降 Lp(a) 疗法的开发已将 Lp(a) 定位为对抗脂质驱动的 ASCVD 风险的主要残余风险因素之一。Pelacarsen是一种肝脏特异性反义寡核苷酸，其Lp(a)降低率高达90%，目前正在进行3期试验。Olpasiran是一种靶向LPA信使RNA的小干扰RNA，目前正在进行2期研究，其剂量依赖性Lp(a)降低率已高达90%。一旦降 Lp（a）疗法获得批准，这些患者将从中受益。与此同时，高脂蛋白（a）患者的治疗重点应放在进一步降低低密度脂蛋白胆固醇和其他 ASCVD 危险因素上。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.