The antiatherogenic role of high-density lipoprotein cholesterol.
The antiatherogenic role of high-density lipoprotein cholesterol.
复制标题
DOI：
10.1016/s0002-9149(98)00808-x
复制
发表时间：
1998-11
期刊：
影响因子：
--
通讯作者：
P. Kwiterovich
中科院分区：
文献类型：
--
作者：
P. Kwiterovich
过去5年的里程碑式临床研究表明，降低低密度脂蛋白（LDL）胆固醇后，死亡率和首次冠状动脉事件减少，引起了医学界的极大兴趣。然而，高密度脂蛋白（HDL）胆固醇，运输循环胆固醇到肝脏清除，显然也发挥抗动脉粥样硬化作用。心脏病研究提供了令人信服的流行病学证据，表明低水平的HDL胆固醇是冠状动脉疾病（CAD）的独立预测因子。新兴的实验和临床发现，集体，现在提供了一个坚实的科学基础，这种关系。首先，逆转胆固醇转运途径-包括新生（前β）HDL，载脂蛋白A-I，卵磷脂胆固醇酰基转移酶（LCAT），胆固醇酯转运蛋白，和肝脏摄取胆固醇酯的作用，从HDL的肝脏-更好地理解。例如，肝HDL受体SR-BI的鉴定表明胆固醇酯向肝的递送机制不同于受体介导的LDL摄取。第二，载脂蛋白A-I，HDL的主要蛋白组分，和HDL上的2种酶，对氧磷酶和血小板活化因子乙酰水解酶，似乎减少了高度致动脉粥样硬化的氧化LDL的形成。第三，低水平的HDL胆固醇与血管造影证实的冠状动脉粥样硬化的严重程度和数量呈剂量反应关系。第四，低HDL胆固醇预测CAD患者的总死亡率和理想的总胆固醇水平（<200 mg/dL）。第五，低HDL胆固醇浓度似乎与经皮腔内冠状动脉成形术后再狭窄率增加有关。在升高高密度脂蛋白胆固醇方面，停止吸烟，减少到理想体重，定期有氧运动都很重要。大多数用于治疗血脂异常的药物都会适度提高高密度脂蛋白胆固醇水平;然而，尼克酸似乎最有可能做到这一点，并且可以使高密度脂蛋白胆固醇增加高达30%。认识到这些数据，国家胆固醇教育计划的最新报告将低HDL胆固醇确定为CAD风险因素，并建议所有健康成年人进行总胆固醇和HDL胆固醇水平筛查。
Landmark clinical studies in the past 5 years that demonstrated diminished mortality and first coronary events following lowering of low-density lipoprotein (LDL) cholesterol stimulated considerable interest in the medical community. Yet, high-density lipoprotein (HDL) cholesterol, which transports circulating cholesterol to the liver for clearance, clearly also exerts antiatherogenic effects. The Framingham Heart Study produced compelling epidemiologic evidence indicating that a low level of HDL cholesterol was an independent predictor of coronary artery disease (CAD). Emerging experimental and clinical findings are, collectively, now furnishing a solid scientific foundation for this relation. First, the reverse cholesterol transport pathway—including the roles of nascent (pre-beta) HDL, apolipoprotein A-I, lecithin–cholesterol acyltransferase (LCAT), cholesteryl ester transport protein, and hepatic uptake of cholesteryl ester from HDL by liver—is better understood. For example, the identification of a hepatic HDL receptor, SR-BI, suggests a mechanism of delivery of cholesteryl ester to liver that differs from the receptor-mediated uptake of LDL. Second, apolipoprotein A-I, the major protein component of HDL, and 2 enzymes on HDL, paraoxonase and platelet-activating factor acetylhydrolase appear to diminish the formation of the highly atherogenic oxidized LDL. Third, lower levels of HDL cholesterol are associated in a dose–response fashion with the severity and number of angiographically documented atherosclerotic coronary arteries. Fourth, low HDL cholesterol predicts total mortality in patients with CAD and desirable total cholesterol levels (<200 mg/dL). Fifth, low HDL cholesterol concentrations appear to be associated with increased rates of restenosis after percutaneous transluminal coronary angioplasty. In terms of elevating HDL cholesterol, cessation of cigarette smoking, reduction to ideal body weight, and regular aerobic exercise all appear important. Most medications used to treat dyslipidemias will raise HDL cholesterol levels modestly; however, niacin appears to have the greatest potential to do so, and can increase HDL cholesterol up to 30%. Recognizing these data, the most recent report of the National Cholesterol Education Program identified low HDL cholesterol as a CAD risk factor and recommended that all healthy adults be screened for both total cholesterol and HDL cholesterol levels.