Lin Yun, Mousa Shaymaa S, Elshourbagy Nabil, Mousa Shaker A
The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12144, USA.
Vasc Health Risk Manag. 2010 Mar 3;6:73-85. doi: 10.2147/vhrm.s8725.
Current lipid management guidelines are focused on decreasing low-density lipoprotein (LDL-C) levels as the primary target for reducing coronary heart disease (CHD) risk. Yet, many recent studies suggest that low levels of high-density lipoprotein (HDL-C) are a major independent risk factor for cardiovascular diseases. According to several clinical trials, a 1% increase in HDL-C is associated with a 0.7%-3% decrease in CHD events. The direct link between high levels of triglycerides (TG) and CHD, on the other hand, is less well defined. A large reduction in TG is needed to show a difference in CHD events, especially in men. Evidence for a shift in lipid management toward targeting both LDL-C and HDL-C as primary targets for therapy is presented. Currently, the 3-hydroxy-3-methylgutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors) have proven to significantly decrease LDL-C levels, reduce CHD morbidity/mortality and improve overall survival. However, improvement of survival with statins may be due to other pleiotropic effects beyond LDL-C lowering. Fibric acid derivatives and niacin are primarily used to increase HDL-C levels, although with side effects. Future therapies targeting HDL-C may have profound results on reducing CHD morbidity and mortality. This article highlights existing and future targets in lipid management and is based on available clinical data. There is an urgent need for new treatments using a combination of drugs targeting both LDL-C and HDL-C. Such treatments are expected to have a superior outcome for dyslipidemia therapy, along with TG management.
当前的血脂管理指南将降低低密度脂蛋白(LDL-C)水平作为降低冠心病(CHD)风险的主要目标。然而,最近的许多研究表明,高密度脂蛋白(HDL-C)水平低是心血管疾病的主要独立危险因素。根据多项临床试验,HDL-C每增加1%,冠心病事件就会减少0.7%-3%。另一方面,高甘油三酯(TG)水平与冠心病之间的直接联系尚不明确。需要大幅降低TG才能在冠心病事件中显示出差异,尤其是在男性中。本文提出了将血脂管理转向以LDL-C和HDL-C作为主要治疗靶点的证据。目前,3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂(HMG-CoA还原酶抑制剂)已被证明能显著降低LDL-C水平,降低冠心病发病率/死亡率并提高总体生存率。然而,他汀类药物改善生存率可能是由于除降低LDL-C之外的其他多效性作用。纤维酸衍生物和烟酸主要用于提高HDL-C水平,尽管有副作用。未来针对HDL-C的治疗可能会对降低冠心病发病率和死亡率产生深远影响。本文基于现有临床数据,重点介绍了血脂管理的现有和未来靶点。迫切需要使用同时针对LDL-C和HDL-C的联合药物进行新的治疗。这种治疗有望在血脂异常治疗以及TG管理方面取得更好的效果。