Corsini Alberto, Ferri Nicola, Cortellaro Michele
Department of Pharmacological Sciences, Luigi Sacco University of Milan, Milano, Italy.
Vasc Health Risk Manag. 2007;3(5):611-3.
The clinical benefits of statins are strongly related to their low density lipoprotein-cholesterol (LDL-C) lowering properties. However, because mevalonic acid (MVA), the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA) reductase reaction, is the precursor not only of cholesterol but also of nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result in pleiotropic effects, independent of their hypocholesterolemic properties. The discrimination between the pleiotropic from LDL-C lowering effects may potentially be more evident during the early phase of treatment since plasma MVA levels drop up to 70% within 1-2 hours while a reduction of LDL-C, detectable after 24 hours, became significant after 6-7 days. Therefore, the deprivation of circulating MVA-derived isoprenoids in the early phase of treatment could be the main mechanism responsible for the atheroprotective effect of statins. This early window of protection in the absence of LDL-C lowering suggests that the anti-inflammatory and the pleiotropic properties of statins may have clinical importance. Therefore, acute coronary syndromes could represent a clinical condition for addressing the early benefits of statins therapy, ie, within 24 h of the event, independent of LDL-C lowering.
他汀类药物的临床益处与其降低低密度脂蛋白胆固醇（LDL-C）的特性密切相关。然而，由于3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶反应的产物甲羟戊酸（MVA）不仅是胆固醇的前体，也是非甾体类异戊二烯化合物的前体，抑制HMG-CoA还原酶可能会产生多效性作用，与其降胆固醇特性无关。在治疗早期，多效性作用与降低LDL-C作用之间的区别可能更为明显，因为血浆MVA水平在1-2小时内可下降高达70%，而LDL-C的降低在24小时后才可检测到，在6-7天后才变得显著。因此，在治疗早期循环中MVA衍生的异戊二烯类物质的缺乏可能是他汀类药物动脉粥样硬化保护作用的主要机制。在没有降低LDL-C的情况下这种早期保护窗口表明他汀类药物的抗炎和多效性特性可能具有临床重要性。因此，急性冠状动脉综合征可能代表一种临床情况，可用于探讨他汀类药物治疗的早期益处，即在事件发生后24小时内，与降低LDL-C无关。
