Update of HDL in atherosclerotic cardiovascular disease

Leonie Schoch , Sebastián Alcover , Teresa Padró , Soumaya Ben-Aicha , Guiomar Mendieta , Lina Badimon , Gemma Vilahur
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Abstract

Epidemiologic evidence supported an inverse association between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major cardiovascular risk factor and postulating diverse HDL vascular- and cardioprotective functions beyond their ability to drive reverse cholesterol transport. However, the failure of several clinical trials aimed at increasing HDL-C in patients with overt cardiovascular disease brought into question whether increasing the cholesterol cargo of HDL was an effective strategy to enhance their protective properties. In parallel, substantial evidence supports that HDLs are complex and heterogeneous particles whose composition is essential for maintaining their protective functions, subsequently strengthening the “HDL quality over quantity” hypothesis.

The following state-of-the-art review covers the latest understanding as per the roles of HDL in ASCVD, delves into recent advances in understanding the complexity of HDL particle composition, including proteins, lipids and other HDL-transported components and discusses on the clinical outcomes after the administration of HDL-C raising drugs with particular attention to CETP (cholesteryl ester transfer protein) inhibitors.

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动脉粥样硬化性心血管疾病中HDL的最新进展
流行病学证据支持HDL(高密度脂蛋白)胆固醇(HDL- c)水平与动脉粥样硬化性心血管疾病(ASCVD)之间的负相关,确定HDL- c是主要的心血管危险因素,并假设多种HDL血管和心脏保护功能超出其驱动逆向胆固醇运输的能力。然而,几项旨在增加明显心血管疾病患者HDL- c的临床试验的失败,使人们质疑增加HDL的胆固醇载货量是否是增强其保护特性的有效策略。同时,大量证据支持HDL是复杂的非均质颗粒,其组成对维持其保护功能至关重要,从而加强了“HDL质量大于数量”的假设。下面的综述涵盖了对HDL在ASCVD中的作用的最新理解,深入了解HDL颗粒组成的复杂性的最新进展,包括蛋白质、脂质和其他HDL转运成分,并讨论了使用HDL- c升高药物(特别是CETP(胆固醇酯转移蛋白)抑制剂)后的临床结果。
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