de Faire U, Ericsson C G, Grip L, Nilsson J, Svane B, Hamsten A
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Cardiovasc Drugs Ther. 1997 May;11 Suppl 1:257-63. doi: 10.1023/a:1007787713191.
A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.
大量的一级和二级预防试验表明,治疗血浆脂质升高可能会降低冠心病(CHD)事件的发生频率。荟萃分析表明,胆固醇每降低10%,冠心病死亡率降低13%,全因死亡率降低10%。多项血管造影试验的经验还表明,降低低密度脂蛋白(LDL)胆固醇和/或升高高密度脂蛋白(HDL)胆固醇可延缓冠状动脉粥样硬化,在某些情况下还可诱导有限的病变消退。冠状动脉造影研究表明,尽管对致动脉粥样硬化病变的延缓/消退作用较小,管腔直径变化约为0.10 mm,但对临床事件的影响更为显著,降低幅度约为50%。也有证据表明,就临床冠状动脉事件的发生而言,轻度和中度病变尤其值得关注。动脉粥样硬化的进展和冠状动脉事件的发生可能并非完全取决于LDL胆固醇浓度的降低。来自动脉粥样硬化监测回归研究(MARS)、降胆固醇动脉粥样硬化研究(CLAS)以及高脂血症手术控制项目(POSCH)的分析表明,富含甘油三酯的脂蛋白对于接受降胆固醇治疗方案的受试者中轻度/中度病变的进展可能也很重要。最近,5年的苯扎贝特冠状动脉粥样硬化干预试验(BECAIT)结果表明,通过最小管腔直径的变化评估,苯扎贝特可显著延缓心肌梗死年轻男性幸存者的冠状动脉粥样硬化进展和冠状动脉事件。这一积极结果很可能归因于对血清甘油三酯水平(-31%)、血浆纤维蛋白原水平(-12%)和HDL胆固醇水平(+9%)的有益治疗效果。尽管脂质和代谢作用不同,但BECAIT关于冠状动脉粥样硬化进展的结果与最近两项使用HMG-CoA还原酶抑制剂的血管造影试验,即多中心抗动脉粥样硬化研究(MAAS)和他汀类药物回归生长评估研究(REGRESS)的结果相当。BECAIT是第一项表明贝特类药物可显著延缓冠状动脉粥样硬化进展的对照血管造影研究。其确切发生机制仍有待阐明。然而,BECAIT的结果说明了除LDL胆固醇外的其他因素在冠状动脉粥样硬化进展中的重要性。