血脂代谢紊乱及治疗.ppt

* 以LDL-C为核心的动脉粥样硬化模型 首先是内皮功能受损，为LDL-C进入血管壁创造了条件。 LDL-C进入血管壁后，首先被氧化形成氧化LDL-C，由于氧化LDL可释放趋化因子，吸引血液中的单核细胞向血管壁移行，单核细胞进入血管壁形成巨噬细胞，巨噬细胞吞噬氧化的LDL形成泡沫细胞，泡沫细胞死亡破裂后，释放大量游离LDL，在内皮下形成“脂质核心”，也就是动脉粥瘤。激活的巨噬细胞、淋巴细胞、内皮细胞可以通过表达各种细胞因子和生长因子，使血管平滑肌移行、增生，形成纤维帽，纤维帽下覆盖着脂质斑块。 当LDL不断被氧化，进入内皮下，被巨噬细胞吞噬，炎症细胞很多时，会使胶原合成减少，纤维帽变薄；同时，炎症细胞释放的多种蛋白水解酶，能加速纤维帽降解，使斑块变得不稳定，容易破裂。 * 纵观整个动脉粥样硬化的进展过程，LDL在起始、进展、并发症等阶段均起重要作用。在起始阶段，LDL进入动脉壁后被氧化，形成氧化LDL，穿过血管内皮进入血管壁，释放趋化因子，吸引单核细胞进入动脉壁，引发炎症，使内皮功能降低；在进展阶段，LDL持续进入动脉壁，巨噬细胞吞噬氧化LDL形成泡沫细胞，泡沫细胞死亡后释放大量游离的LDL，形成脂质核心，平滑肌细胞移行、增生形成纤维帽。随着炎症加剧，脂质核心增大，平滑肌细胞和纤维组织减少，斑块变为易损斑块，易损斑块破裂，形成急性血栓，引发各种事件。 * * One reason why many patients fail to reach the LDL-C goal is the relatively small additional therapeutic response to a statin when titration extends beyond the starting dose. The response to any statin corresponds to the “rule of 6,”1,2 that is, each doubling of a statin dose further lowers LDL-C by an average 6%. In view of the need for better lipid-lowering therapy to achieve the lower goals now recommended, it has been suggested that combination therapy with agents such as ezetimibe plus a statin is an effective approach to reach goals.3 Ezetimibe coadministered with a statin provides innovative dual inhibition of cholesterol absorption from the intestine (ezetimibe) and cholesterol synthesis in the liver (statin).4 The result is greater lipid lowering versus the statin alone.4 References Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999;341:498–509. Stein E. Managing dyslipidemia in the high-risk patient. Am J Cardial 2002;89(suppl):50C–57C. O’Keefe JH, Cordain L, Harris W et al. Optimal low-density lipoprotein is 50 to 70 mg/dl. Lower is better and physiologically normal. J Am Coll Cardiol 2004;43:2142–2146. Summary of Product Characteristics, Ezetimibe, MSP. * In the HPS, similar reductions in absolute risk of major vascular events with simvastatin extended over a range of baseline cholesterol levels. At a baseline LDL-C 100 mg/dl, the optimal target set by t