SHARP

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。心脏和肾脏保护研究(SHARP)将评估辛伐他汀和胆固醇吸收抑制剂依折麦布的联合作用。9,000名慢性肾脏疾病(CKD)患者-其中约6,000人将在透析前，3,000人将随机接受透析。首先，对透析患者的观察研究报告了血液总胆固醇与死亡率之间的负相关。其次，在这类患者中，只有大约四分之一的心脏死亡似乎明确可归因于急性心肌梗死，并有可能通过降低胆固醇来避免，而其他常见原因(如心脏骤停、心律失常和心力衰竭)可能不那么依赖于胆固醇水平。最后，慢性肾脏病患者降低胆固醇的长期安全性尚不清楚。SHARP的主要目的是评估联合使用辛伐他汀20毫克和依泽米特10毫克降低低密度脂蛋白胆固醇与安慰剂相比对首次发生重大血管事件(定义为非致命性心肌梗死或心脏死亡、非致命性或致命性中风或血管再通)的时间的影响。这项研究的次要目标包括评估依折麦布/辛伐他汀在以下方面的效果：进展为终末期肾脏疾病(在透析前患者中)；各种死亡原因；重大心脏事件(定义为非致命性心肌梗死或心源性死亡)；中风和因心绞痛住院。50名受试者将进入梅哈里的这项研究，包括透析前和透析患者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Study of Heart and Renal Protection (SHARP) will assess the effects of a combination of simvastatin and the cholesterol-absorption inhibitor ezetimibe among approx. 9,000 patients with chronic kidney disease (CKD) -around 6,000 of who will be pre-dialysis and 3,000 on dialysis at randomization. First, observational studies among dialysis patients have reported a negative association between blood total cholesterol and mortality. Secondly, only about one quarter of cardiac mortality in such patients appears to be definitely attributable to acute myocardial infarction, and potentially avoidable with cholesterol-lowering, while the other common causes (e.g. cardiac arrest, arrhythmia, and heart failure) may not be as dependent on cholesterol levels. Finally, the long-term safety of cholesterol reduction among patients with CKD remains unclear. The primary aim of SHARP is to assess the effects of lowering LDL cholesterol with combined simvastatin 20 mg and ezetimide 10 mg versus placebo on the time to a first major vascular event (defined as non-fatal myocardial infarction or cardiac death, non-fatal or fatal stroke, or revascularisation). Secondary aims of the study include an assessment of the effects of ezetimibe/simvastatin on: progression to end-stage renal disease (among pre-dialysis patients); various causes of death; major cardiac events (defined as non-fatal MI or cardiac death); stroke and hospitalization for angina. Fifty subjects will be entered into this study at Meharry, including pre-dialysis and dialysis patients.