Subedi Bishnu H, Joshi Parag H, Jones Steven R, Martin Seth S, Blaha Michael J, Michos Erin D
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA ; Greater Baltimore Medical Center, Baltimore, MD, USA.
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA.
Vasc Health Risk Manag. 2014 Apr 8;10:205-16. doi: 10.2147/VHRM.S45648. eCollection 2014.
Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD) is low high-density lipoprotein cholesterol (HDL-C). Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics.
许多研究表明，动脉粥样硬化性心血管疾病（ASCVD）的一个重要风险因素是高密度脂蛋白胆固醇（HDL-C）水平低。因此，使用治疗药物提高HDL-C水平被认为是一种有吸引力的策略。在他汀类药物出现之前的时代，能使HDL-C适度升高的贝特类药物和烟酸单药治疗可减少ASCVD事件。自引入以来，他汀类药物已成为脂蛋白治疗的基石，其益处主要归因于低密度脂蛋白胆固醇的降低。几项涉及烟酸或胆固醇酯转运蛋白抑制剂的随机试验结果对血浆HDL-C定量升高将一致转化为ASCVD益处这一概念提出了挑战。因此，HDL，或者更准确地说，HDL-C假说变得更具争议性。由于缺乏针对HDL特异性疗法的确切疗效数据，目前尚无针对HDL-C或HDL的明确指南。HDL-C水平只是HDL多种结构或功能特性中的一个指标。目前正在开发和评估新型药物，这些药物紧密模仿天然HDL的结构或复制其各种功能，例如逆向胆固醇转运、血管舒张、抗炎或抑制血小板聚集。诸如HDL输注、去脂HDL、肝脏X受体激动剂、载脂蛋白A-I上调剂、载脂蛋白A模拟物和基因治疗等潜在新方法正处于早期试验阶段。本综述将概述当前疗法并描述HDL治疗的未来方向。
