Department of Medicine, University of Florida College of Medicine, 655 West 11th Street, Jacksonville, FL, 32209, USA,
Drugs. 2015 May;75(7):713-22. doi: 10.1007/s40265-015-0390-1.
Although cardiovascular mortality has been decreasing in industrialized countries, there continues to be a substantial residual risk; thus, novel therapeutic agents and new targets of therapy have been sought. One highly plausible therapeutic target is high-density lipoprotein (HDL). HDL is a key player in reverse cholesterol transport and possesses a slew of other cardioprotective properties; however, recent trials with agents known to increase HDL levels have generally not shown any reduction in cardiovascular events. Further analysis of these trials suggest that fibrates have consistently reduced some cardiovascular outcomes, at least in the subgroup of patients with high serum triglycerides and low HDL cholesterol (HDLc) levels. Since fibrates, unlike niacin or cholesterol ester transfer protein inhibitors, increase HDLc level mostly through the stimulation of apolipoprotein A-I production, it is suggested that the quality and functionality of HDL are enhanced when de novo synthesis rather than inhibition of turnover is the mechanism of increasing HDL level. In this communication, the evidence for and against the cardioprotective properties of HDL is reviewed and the contemporary clinical trials are discussed.
尽管心血管疾病死亡率在工业化国家已经下降，但仍存在大量的剩余风险；因此，人们一直在寻找新的治疗药物和治疗靶点。高密度脂蛋白（HDL）是一个非常有前途的治疗靶点。HDL 是胆固醇逆向转运的关键因子，具有许多其他的心脏保护特性；然而，最近使用已知能增加 HDL 水平的药物进行的临床试验并未显示出任何心血管事件的减少。对这些试验的进一步分析表明，贝特类药物一直降低了某些心血管结局，至少在血清甘油三酯高和 HDL 胆固醇（HDLc）水平低的患者亚组中如此。由于贝特类药物与烟酸或胆固醇酯转移蛋白抑制剂不同，主要通过刺激载脂蛋白 A-I 的产生来增加 HDLc 水平，因此，当增加 HDL 水平的机制是从头合成而不是抑制周转率时，HDL 的质量和功能得到增强。在本通讯中，回顾了 HDL 的心脏保护特性的证据，并讨论了当代的临床试验。
