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脂蛋白(a):一种与遗传相关的、因果性的、普遍存在的动脉粥样硬化性心血管疾病风险因素:美国心脏协会的科学声明。

Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association.

出版信息

Arterioscler Thromb Vasc Biol. 2022 Jan;42(1):e48-e60. doi: 10.1161/ATV.0000000000000147. Epub 2021 Oct 14.

Abstract

High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

摘要

脂蛋白(a) [Lp(a)] 水平升高是动脉粥样硬化性心血管疾病的独立和因果危险因素,其作用机制与动脉粥样硬化形成、炎症和血栓形成增加有关。Lp(a) 主要是一种单基因心血管风险决定因素,其水平的个体间差异约为 70%至≥90%由遗传决定。Lp(a) 颗粒的 2 种主要蛋白成分是载脂蛋白 B100 和载脂蛋白(a)。即使在有效降低血浆低密度脂蛋白胆固醇和载脂蛋白 B100 的情况下,Lp(a) 仍然是心血管疾病发展的危险因素。尽管它对动脉粥样硬化性心血管疾病负担有明确的贡献,但我们目前缺乏检测方法的标准化和协调、诊断和提供风险评估的通用指南以及降低 Lp(a) 的靶向治疗。需要了解不同血统人群中 Lp(a) 水平的遗传和生物学基础及其与疾病的关系。本科学声明利用多元化的基础科学和临床工作组的专业知识,重点介绍 Lp(a) 领域的历史、生物学、病理生理学和新出现的临床证据。在此,我们解决了减轻归因于升高的 Lp(a) 水平的动脉粥样硬化性心血管疾病风险所需的关键知识空白和未来方向。

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