Herd J A
Atherosclerosis Research Clinic, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Am J Cardiol. 1998 Sep 24;82(6A):22M-25M. doi: 10.1016/s0002-9149(98)00593-1.
Studies of lipid-modifying therapy show that inhibition of cholesterol synthesis is required in at least 2 sites-in hepatic cells and in cells located in the walls of coronary arteries-if the progression of coronary atherosclerosis is to be decreased in patients with relatively normal levels of low-density lipoprotein (LDL) cholesterol. This is clinically important, because the majority of patients with coronary artery disease do not have severely elevated LDL cholesterol levels. Of the 2 angiographic trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ("statins") in patients with coronary artery disease and average cholesterol levels, only the Lipoprotein and Atherosclerosis Study (LCAS) of fluvastatin reported slowed angiographic progression of coronary artery disease in these patients. The change in LDL cholesterol levels during treatment with fluvastatin did not predict the extent of change in coronary atherosclerosis or incidence of clinical cardiac events. Apparently, the metabolic effects of treatment with fluvastatin were more important than the extent to which blood cholesterol levels were lowered. The clinical benefits of treatment with statins should be directly compared in randomized controlled clinical trials among patients with average cholesterol levels.
脂质修饰疗法的研究表明，要降低低密度脂蛋白（LDL）胆固醇水平相对正常的患者冠状动脉粥样硬化的进展，至少需要在两个部位抑制胆固醇合成，即肝细胞和冠状动脉壁中的细胞。这在临床上很重要，因为大多数冠心病患者的LDL胆固醇水平并没有严重升高。在两项针对冠心病且胆固醇水平处于平均水平的患者进行的3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶抑制剂（“他汀类药物”）的血管造影试验中，只有氟伐他汀的脂蛋白与动脉粥样硬化研究（LCAS）报告了这些患者冠状动脉疾病血管造影进展减缓。氟伐他汀治疗期间LDL胆固醇水平的变化并不能预测冠状动脉粥样硬化的变化程度或临床心脏事件的发生率。显然，氟伐他汀治疗的代谢效应比血液胆固醇水平降低的程度更重要。他汀类药物治疗的临床益处应在胆固醇水平处于平均水平的患者中进行随机对照临床试验直接比较。
