Lipoprotein(a): from Causality to Treatment.

IF 5.7 2区医学 Q1 PERIPHERAL VASCULAR DISEASE

Current Atherosclerosis Reports Pub Date : 2024-03-01 Epub Date: 2024-01-22 DOI:10.1007/s11883-024-01187-6

Florian Kronenberg

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Abstract

Purpose of review: This paper reviews the evidence why lipoprotein(a) (Lp(a)) is a causal risk factor for cardiovascular disease and how high Lp(a) concentrations should be managed now and with an outlook to the future.

Review findings: No optimal and widely available animal models exist to study the causality of the association between Lp(a) and cardiovascular disease. This has been a major handicap for the entire field. However, genetic studies turned the page. Already in the early 1990s, the principle of Mendelian randomization studies was applied for the first time ever (even if they were not named so at that time). Genetic variants of the LPA gene such as the apolipoprotein(a) isoform size, the number and sum of kringle IV repeats and later single nucleotide polymorphisms are strongly associated with life-long exposure to high Lp(a) concentrations as well as cardiovascular outcomes. This evidence provided a basis for the development of specific Lp(a)-lowering drugs that are currently in clinical testing phase. Lp(a) is one of the most important genetically determined risk factors for cardiovascular disease. With the specific Lp(a)-lowering therapies, we might get tools to fight this common risk factor in case the outcome trials will be positive.

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脂蛋白（a）：从成因到治疗。

综述目的：本文回顾了脂蛋白（a）（Lp(a)）是心血管疾病因果风险因素的证据，以及现在和未来应如何管理高浓度脂蛋白（a）：综述结果：目前还没有最佳的、可广泛使用的动物模型来研究脂蛋白（a）与心血管疾病之间的因果关系。这一直是整个研究领域的一大障碍。然而，基因研究翻开了新的一页。早在 20 世纪 90 年代初，孟德尔随机化研究的原则就首次得到应用（尽管当时并没有将其命名为随机化研究）。LPA 基因的遗传变异，如载脂蛋白（a）异构体的大小、Kringle IV 重复序列的数量和总和，以及后来的单核苷酸多态性，都与终生暴露于高浓度脂蛋白（a）以及心血管疾病的结局密切相关。这些证据为开发特定的降低脂蛋白（a）药物提供了依据，目前这些药物正处于临床试验阶段。脂蛋白（a）是由基因决定的心血管疾病最重要的风险因素之一。有了降低脂蛋白（a）的特异性疗法，如果试验结果呈阳性，我们就有可能获得对抗这一常见风险因素的工具。

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 Atherosclerosis Reports 医学-

CiteScore

9.00

自引率

3.40%

发文量

审稿时长

6-12 weeks

期刊介绍： The aim of this journal is to systematically provide expert views on current basic science and clinical advances in the field of atherosclerosis and highlight the most important developments likely to transform the field of cardiovascular prevention, diagnosis, and treatment. We accomplish this aim by appointing major authorities to serve as Section Editors who select leading experts from around the world to provide definitive reviews on key topics and papers published in the past year. We also provide supplementary reviews and commentaries from well-known figures in the field. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.