HDL-C: Role as a risk modifier
HDL-C: Role as a risk modifier
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DOI：
10.1016/s1567-5688(11)70885-6
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发表时间：
2011-11-01
影响因子：
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通讯作者：
Barter, Philip
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文献类型：
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作者：
Barter, Philip
低密度脂蛋白胆固醇（LDL-C）导致心血管疾病（CVD）的证据是压倒性的。毫无疑问，使用他汀类药物降低LDL-C水平也可以降低CV风险。然而，许多人仍然处于高风险状态，即使他们的LDL-C水平已经通过他汀类药物的积极治疗而降低。这种剩余风险的一个原因可能是低水平的高密度脂蛋白胆固醇（HDL-C）。HDL-C浓度是CVD的独立逆预测因子。即使他汀类药物治疗将LDL-C水平降至1.8 mmol/L（70 mg/dL）以下，这种关系也很明显。因此，有人建议，提高HDL-C的水平应被视为一种治疗策略，用于降低残余的CV风险，持续在一些人中，尽管积极的LDL-C降低与他汀类药物。HDL颗粒有几个功能，有可能防止动脉疾病，其中最有名的是涉及到他们的能力，以促进胆固醇流出巨噬细胞在动脉壁。然而，HDL具有几种额外的保护特性，这些特性与其参与胆固醇代谢无关。例如，它们具有减少氧化、血管炎症和血栓形成、改善内皮功能、促进内皮修复、增强胰岛素敏感性和促进胰岛β细胞分泌胰岛素的性质。在动物模型中也有大量令人信服的证据表明，增加HDL水平的干预措施具有深刻的抗动脉粥样硬化作用。低HDL的主要原因是腹部肥胖和2型糖尿病，其全球发病率正以惊人的速度增长。增加高密度脂蛋白浓度的策略应该开始与生活方式的改变，如减轻体重，增加体力活动和戒烟。然而，这些措施的依从性往往很差，可能需要药物干预。目前可用的升高HDL的药物包括贝特类、烟酸和他汀类药物。无可争议的证据表明，使用他汀类药物降低LDL-C水平可大幅降低CV风险。还有越来越多的证据表明，使用他汀类药物提高HDL-C水平有助于进一步降低CV风险。例如，在4S研究中，与辛伐他汀治疗相关的HDL-C水平升高是CV事件减少的重要预测因素。此外，在4项冠状动脉血管内超声成像试验中对1，455例患者进行的荟萃分析显示，通过冠状动脉血管内超声评估，他汀类药物治疗期间达到的LDL-C水平和HDL-C浓度增加均是冠状动脉粥样硬化进展的重要独立预测因素。有证据表明，即使使用他汀类药物将LDL-C降至1.7 mmol/L（70 mg/dL）以下，低水平HDL-C仍与CV风险增加相关。此外，越来越多的证据表明，增加HDL-C水平有能力降低CV风险。因此，有一个令人信服的情况下，针对LDL和HDL组分，以降低血脂异常，高CV风险和低水平HDL-C的人的CV风险。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Evidence that low-density lipoprotein-cholesterol (LDL-C) causes cardiovascular disease (CVD) is overwhelming. It has also been proven beyond all doubt that lowering the level of LDL-C using statins reduces CV risk. However, many people remain at high risk even when their level of LDL-C has been reduced by aggressive treatment with statins. One reason for this residual risk can be a low level of high-density lipoprotein-cholesterol (HDL-C).The concentration of HDL-C is an independent, inverse predictor for CVD. This relationship is apparent even when treatment with statins has reduced the level of LDL-C to below 1.8 mmol/L (70 mg/dL). It has therefore been suggested that raising the level of HDL-C should be considered as a therapeutic strategy for reducing the residual CV risk that persists in some people, despite aggressive LDL-C lowering with statins.HDL particles have several functions with the potential to protect against arterial disease, the best known of which relates to their ability to promote cholesterol efflux from macrophages in the artery wall. However, HDLs have several additional protective properties that are independent of their involvement in cholesterol metabolism. For example, they have properties that reduce oxidation, vascular inflammation and thrombosis, improve endothelial function, promote endothelial repair, enhance insulin sensitivity and promote insulin secretion by pancreatic beta islet cells. There is also a large and compelling body of evidence in animal models showing that interventions that increase HDL levels are profoundly anti-atherogenic.Major causes of low HDL are abdominal obesity and type 2 diabetes, the worldwide incidences of which are increasing at alarming rates. Strategies to increase the concentration of HDL should begin with lifestyle changes such as weight reduction, increased physical activity and smoking cessation. However, compliance with such measures is frequently poor and pharmacological intervention may be required. Currently available HDL-raising medications include fibrates, niacin and statins.There is indisputable evidence that lowering LDL-C levels using statins translates into a large reduction in CV risk. There is also mounting evidence that increasing the level of HDL-C using statins contributes to an additional reduction in CV risk. For example, the increase in HDL-C levels that was associated with simvastatin treatment in the 4S study was a significant predictor for the reduction in CV events. Moreover, a meta-analysis of 1,455 patients in 4 coronary intravascular ultrasound imaging trials showed that both the achieved level of LDL-C and the increase in HDL-C concentration during statin treatment were significant independent predictors for coronary atheroma progression as assessed by coronary intravascular ultrasound.In conclusion, evidence suggests that low levels of HDL-C are associated with an increased CV risk even when LDL-C is reduced to below 1.7 mmol/L (70 mg/dL) with a statin. Moreover, there is mounting evidence that increasing the level of HDL-C has the capacity to reduce CV risk. Thus, there is a compelling case for targeting both the LDL and HDL fractions to reduce CV risk in people with dyslipidemia, high CV risk and low levels of HDL-C. (C) 2011 Elsevier Ireland Ltd. All rights reserved.