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与高脂蛋白血症(a)相关的心血管风险增加以及当前和未来治疗可能性面临的挑战。

Increased cardiovascular risk associated with hyperlipoproteinemia (a) and the challenges of current and future therapeutic possibilities.

作者信息

Fras Zlatko

机构信息

Division of Medicine, Centre for Preventive Cardiology, University Medical Centre Ljubljana; Medical Faculty, University of Ljubljana; Ljubljana-Slovenia.

出版信息

Anatol J Cardiol. 2020 Jan;23(2):60-69. doi: 10.14744/AnatolJCardiol.2019.56068.


DOI:10.14744/AnatolJCardiol.2019.56068
PMID:32011323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7040869/
Abstract

Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%-35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%-30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).

摘要

人群、遗传和临床研究表明,血浆脂蛋白(a)[Lp(a)]浓度升高与心血管疾病(CVD)的发生发展之间存在因果关系且相互独立,与其他血浆脂蛋白无关,主要与动脉粥样硬化性CVD和钙化性主动脉瓣狭窄有关。目前,对于用于定义高脂蛋白血症(a)的常用单一值,国际上仍未达成强烈共识。根据最常用的阈值水平(>30或>50mg/dL),其在普通人群中的患病率估计在10%-35%范围内。由于Lp(a)升高在一些遗传疾病患者以及其他主要危险因素得到控制的个体中可能具有特殊重要性,因此识别并确立能够降低Lp(a)水平并降低CVD风险的适当治疗干预措施可能非常重要。大多数经典的降脂药物(他汀类药物、依折麦布和贝特类药物)以及营养保健品(辅酶Q10和大蒜)似乎对其血浆水平没有显著影响,而对于已证明具有降低Lp(a)作用的药物(阿司匹林、烟酸和雌激素),它们在降低心血管(CV)事件方面的临床疗效尚未得到明确证实。Lp(a)血浆分离术和前蛋白转化酶枯草杆菌蛋白酶/kexin 9型抑制剂平均可使血浆Lp(a)降低约20%-30%,同时低密度脂蛋白胆固醇降低幅度更大(高达70%),这使我们难以确定降低Lp(a)对降低CV事件的真正贡献。该领域的最新进展是引入了针对载脂蛋白(a)[apo(a)]的新型反义寡核苷酸疗法,该疗法已证明在降低血浆Lp(a)方面非常有效(甚至>90%),但仍需在临床试验中进一步测试。本综述的目的是介绍一些最重要的可获取科学数据,以及与目前和近期可能更广泛应用的高脂蛋白血症(a)治疗选择相关的困境。

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引用本文的文献

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Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

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本文引用的文献

[1]
Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome.

J Am Coll Cardiol. 2020-1-21

[2]
Therapeutic management of hyperlipoproteinemia (a).

Drugs Context. 2019-9-4

[3]
2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.

Eur Heart J. 2020-1-1

[4]
Comparison of lipoprotein (a) serum concentrations measured by six commercially available immunoassays.

Atherosclerosis. 2019-8-27

[5]
Lp(a): Addressing a Target for Cardiovascular Disease Prevention.

Curr Cardiol Rep. 2019-7-31

[6]
Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice.

Curr Atheroscler Rep. 2019-7-27

[7]
Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype.

Atherosclerosis. 2019-7-3

[8]
Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies.

Clin Ther. 2019-7-13

[9]
Lipoprotein(a) reductions from PCSK9 inhibition and major adverse cardiovascular events: Pooled analysis of alirocumab phase 3 trials.

Atherosclerosis. 2019-6-8

[10]
Lipoprotein (a) level is associated with plaque vulnerability in patients with coronary artery disease: An optical coherence tomography study.

Int J Cardiol Heart Vasc. 2019-6-13

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