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脂蛋白(a):心血管疾病、主动脉瓣狭窄和新的治疗选择。

Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option.

机构信息

Cardiology 4, Cardio Center A. De Gasperis, ASST GOM Niguarda, 20162 Milan, Italy.

School of Medicine and Surgery, Milano-Bicocca University, 20126 Milan, Italy.

出版信息

Int J Mol Sci. 2022 Dec 22;24(1):170. doi: 10.3390/ijms24010170.


DOI:10.3390/ijms24010170
PMID:36613613
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9820656/
Abstract

Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)-Lp(a)-lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.

摘要

动脉粥样硬化是一种慢性进行性炎症过程,早在生命早期就开始,并在晚期出现临床症状。这种缓慢的病理趋势强调了早期识别高危患者的重要性,并需要强化治疗危险因素,以预防动脉粥样硬化病变的发生和/或进展。除了常见的心血管(CV)危险因素外,还发现了一些新的标志物能够增加患 CV 疾病的风险。其中,脂蛋白(a)[Lp(a)]水平升高与未来 CV 疾病的极高风险相关;这一关系已在流行病学、孟德尔随机化和全基因组关联研究以及荟萃分析中得到了很好的证明。最近,又发现了一些新的方面,如它与主动脉瓣狭窄的关联。尽管在最近几年,它被认为是一种不可改变的危险因素,但已经开发出了一些具有降低 Lp(a)循环水平的强效药物,其降低随后 CV 事件的能力正在正在进行的试验中进行测试。本文将综述所有这些方面:从 Lp(a)的合成、清除和检测,到其与 CV 疾病和主动脉瓣狭窄的关联的研究结果,再到未来几年将出现的新治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b4/9820656/0881c8de5bd5/ijms-24-00170-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b4/9820656/2b649ecd1acb/ijms-24-00170-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b4/9820656/0881c8de5bd5/ijms-24-00170-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b4/9820656/2b649ecd1acb/ijms-24-00170-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b4/9820656/0881c8de5bd5/ijms-24-00170-g002.jpg

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[3]
The Role of Lipoprotein(a) in Peripheral Artery Disease.

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[4]
Amyloid and collagen templates in aortic valve calcification.

Trends Mol Med. 2024-11

[5]
Impact of Lipoprotein(a) Levels on Cardiovascular Risk Estimation.

High Blood Press Cardiovasc Prev. 2024-7

[6]
Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Arch Med Sci. 2024-1-31

[7]
Current RNA strategies in treating cardiovascular diseases.

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[8]
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[9]
Lipoprotein(a)-60 Years Later-What Do We Know?

Cells. 2023-10-17

[10]
Current Management and Future Perspectives in the Treatment of Lp(a) with a Focus on the Prevention of Cardiovascular Diseases.

Pharmaceuticals (Basel). 2023-6-23

本文引用的文献

[1]
Low lipoprotein(a) concentration is associated with atrial fibrillation: a large retrospective cohort study.

Lipids Health Dis. 2022-11-14

[2]
Lipoprotein(a) is a Promising Residual Risk Factor for Long-Term Clinical Prognosis in Peripheral Arterial Disease.

Ann Vasc Dis. 2022-9-25

[3]
Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement.

Eur Heart J. 2022-10-14

[4]
Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification.

Eur Heart J. 2022-10-14

[5]
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Am Heart J. 2022-9

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Eur Heart J. 2022-5-14

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J Am Coll Cardiol. 2022-4-26

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Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels.

JAMA. 2022-5-3

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Managing Atherosclerotic Cardiovascular Risk in Young Adults: JACC State-of-the-Art Review.

J Am Coll Cardiol. 2022-3-1

[10]
Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a).

Nat Med. 2022-1

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