Mora Samia, Ridker Paul M
Center for Cardiovascular Disease Prevention and Division of Cardiovascular Disease, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Am J Cardiol. 2006 Jan 16;97(2A):33A-41A. doi: 10.1016/j.amjcard.2005.11.014. Epub 2005 Dec 1.
The most important action of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is their ability to lower levels of low-density lipoprotein (LDL) cholesterol. Statins have proved highly effective in reducing the risk of cardiovascular events in both primary and secondary prevention studies. However, the magnitude of risk reduction associated with statins is greater than that predicted on the basis of LDL cholesterol lowering alone. A likely explanation for this effect is the anti-inflammatory action of statins. Following the observation that high-sensitivity C-reactive protein (hs-CRP) is a powerful predictor of cardiovascular events, investigators in the Cholesterol and Recurrent Events (CARE) and Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trials demonstrated that the magnitude of risk reduction associated with statin therapy was higher among those with elevated hs-CRP levels. In addition, there is accumulating evidence that statins lower plasma levels of hs-CRP in a manner largely independent of LDL cholesterol lowering. In contrast, little benefit has been demonstrated for statin therapy in the absence of both hyperlipidemia and inflammation. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a large multinational, long-term, double-blind, placebo-controlled, randomized clinical trial designed to assess directly whether statin therapy (rosuvastatin 20 mg/day) should be given to apparently healthy individuals with low LDL cholesterol levels but elevated hs-CRP levels--a critical issue for the prevention of cardiovascular disease. Support for the concept behind the JUPITER trial is also now available from several recent trials comparing different intensities of statin therapy on disease progression as well as clinical end points. These studies indicate that the hs-CRP level achieved after initiation of statin therapy may be as important as the LDL cholesterol level achieved. All of these data raise the possibility that hs-CRP could be used to target high-risk patients who may benefit from early statin use. Ongoing work will determine whether hs-CRP reduction, independent of LDL cholesterol reduction, results in a net clinical benefit.
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）最重要的作用是降低低密度脂蛋白（LDL）胆固醇水平。在一级和二级预防研究中，他汀类药物已被证明在降低心血管事件风险方面非常有效。然而，与他汀类药物相关的风险降低幅度大于仅基于降低LDL胆固醇所预测的幅度。对此效应的一个可能解释是他汀类药物的抗炎作用。在观察到高敏C反应蛋白（hs-CRP）是心血管事件的有力预测指标后，胆固醇与再发事件（CARE）试验以及空军/德克萨斯冠状动脉粥样硬化预防研究（AFCAPS/TexCAPS）的研究人员表明，在hs-CRP水平升高的人群中，与他汀类药物治疗相关的风险降低幅度更高。此外，越来越多的证据表明，他汀类药物降低hs-CRP血浆水平的方式在很大程度上独立于降低LDL胆固醇。相比之下，在既无高脂血症又无炎症的情况下，他汀类药物治疗几乎没有显示出益处。《他汀类药物在一级预防中的应用：评估瑞舒伐他汀的干预试验》（JUPITER）是一项大型跨国、长期、双盲、安慰剂对照、随机临床试验，旨在直接评估对于LDL胆固醇水平低但hs-CRP水平升高的看似健康的个体，是否应给予他汀类药物治疗（瑞舒伐他汀20毫克/天）——这是预防心血管疾病的一个关键问题。最近几项比较不同强度他汀类药物治疗对疾病进展以及临床终点影响的试验，也为JUPITER试验背后的概念提供了支持。这些研究表明，开始他汀类药物治疗后达到的hs-CRP水平可能与达到的LDL胆固醇水平同样重要。所有这些数据都增加了hs-CRP可用于确定可能从早期使用他汀类药物中获益的高危患者的可能性。正在进行的研究将确定独立于降低LDL胆固醇的情况下降低hs-CRP是否会带来净临床益处。
