Kwiterovich P O
Johns Hopkins University Lipid Clinic, and Department of Pediatrics, Johns Hopkins University Medical School, Baltimore, Maryland, USA.
Am J Cardiol. 1998 Nov 5;82(9A):13Q-21Q. doi: 10.1016/s0002-9149(98)00808-x.
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.
过去5年中具有里程碑意义的临床研究表明，降低低密度脂蛋白（LDL）胆固醇后死亡率和首次冠心病事件减少，这在医学界引起了相当大的关注。然而，将循环胆固醇转运至肝脏进行清除的高密度脂蛋白（HDL）胆固醇显然也具有抗动脉粥样硬化作用。弗明汉心脏研究得出了令人信服的流行病学证据，表明HDL胆固醇水平低是冠状动脉疾病（CAD）的独立预测因素。新出现的实验和临床研究结果共同为这种关系提供了坚实的科学基础。首先，对逆向胆固醇转运途径——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）、胆固醇酯转运蛋白以及肝脏从HDL摄取胆固醇酯的作用——有了更好的理解。例如，肝脏HDL受体SR-BI的发现提示了一种将胆固醇酯输送到肝脏的机制，这与受体介导的LDL摄取不同。其次，HDL的主要蛋白质成分载脂蛋白A-I以及HDL上的两种酶——对氧磷酶和血小板活化因子乙酰水解酶——似乎能减少高度致动脉粥样硬化的氧化LDL的形成。第三，HDL胆固醇水平较低与血管造影记录的动脉粥样硬化冠状动脉的严重程度和数量呈剂量反应关系。第四，HDL胆固醇水平低可预测CAD患者的总死亡率以及总胆固醇水平理想（<200mg/dL）的患者的总死亡率。第五，HDL胆固醇浓度低似乎与经皮腔内冠状动脉成形术后再狭窄率增加有关。就提高HDL胆固醇而言，戒烟、减至理想体重和定期进行有氧运动似乎都很重要。大多数用于治疗血脂异常的药物会适度提高HDL胆固醇水平；然而，烟酸似乎在这方面潜力最大，可使HDL胆固醇升高多达30%。认识到这些数据后，国家胆固醇教育计划的最新报告将HDL胆固醇水平低确定为CAD的一个危险因素，并建议对所有健康成年人进行总胆固醇和HDL胆固醇水平筛查。
