Schaefer Ernst J, Asztalos Bela F
Cardiovascular Research Laboratory, Tufts University School of Medicine, Boston, MA 02111, USA.
Curr Atheroscler Rep. 2006 Jan;8(1):41-9. doi: 10.1007/s11883-006-0063-3.
Statins inhibit cholesterol synthesis and are effective in lowering total cholesterol levels in plasma or serum due to reductions in low-density lipoprotein and very low-density lipoproteins, as well as reducing progression of coronary atherosclerosis, coronary heart disease, and stroke morbidity and mortality. These agents also modestly raise levels of high-density lipoprotein (HDL) cholesterol and its major protein, apolipoprotein (apo) A-I. The more effective statins can also raise the levels of large alpha-1 HDL particles as assessed by two-dimensional gel electrophoresis. High levels of these particles promote reverse cholesterol transport and protect against coronary heart disease and progression of coronary atherosclerosis. The mechanism whereby statins alter HDL and its subspecies appears to be due to reduction of triglyceride-rich lipoproteins, with a secondary decrease in cholesteryl ester transfer protein activity, and less transfer of HDL cholesterol to triglyceride-rich lipoprotein acceptor particles. Increasingly, statins will be combined with other agents such as ezetimibe, fibrates, niacin, and cholesteryl ester transfer protein inhibitors to optimize the entire lipoprotein profile to alter not only low-density lipoprotein, but also HDL, triglycerides, lipoprotein(a), and C-reactive protein, and also to reduce cardiovascular morbidity and mortality.
他汀类药物可抑制胆固醇合成，通过降低低密度脂蛋白和极低密度脂蛋白水平，有效降低血浆或血清中的总胆固醇水平，还能减少冠状动脉粥样硬化、冠心病以及中风的发病率和死亡率。这些药物还能适度提高高密度脂蛋白（HDL）胆固醇及其主要蛋白质载脂蛋白（apo）A-I的水平。通过二维凝胶电泳评估，更有效的他汀类药物还能提高大α-1 HDL颗粒的水平。这些颗粒水平较高可促进胆固醇逆向转运，并预防冠心病和冠状动脉粥样硬化的进展。他汀类药物改变HDL及其亚类的机制似乎是由于富含甘油三酯的脂蛋白减少，导致胆固醇酯转运蛋白活性继发性降低，以及HDL胆固醇向富含甘油三酯的脂蛋白受体颗粒的转移减少。越来越多的他汀类药物将与其他药物如依泽替米贝、贝特类药物、烟酸和胆固醇酯转运蛋白抑制剂联合使用，以优化整个脂蛋白谱，不仅改变低密度脂蛋白，还改变HDL、甘油三酯、脂蛋白(a)和C反应蛋白，并降低心血管疾病的发病率和死亡率。
