SPRINT - Factors Affecting Atherosclerosis Study (FAST)

描述（由申请人提供）：与普通人群相比，慢性肾脏疾病（CKD）人群的心血管事件和心血管死亡发生率明显更高。然而，关于导致CKD人群心血管事件增加的机制仍有几个未解决的问题。目前还不清楚。CKD本身是否会导致动脉粥样硬化加速？传统和非传统危险因素对CKD动脉粥样硬化进展的相对贡献是什么？由于收缩压干预试验（SPRINT）具有独特的设计，招募了大量具有动脉粥样硬化事件高风险的CKD和非CKD参与者，该试验提供了一个很好的机会来检查CKD中动脉粥样硬化的进展是否比非CKD更快，以及导致CKD中动脉粥样硬化患病率更高的因素。因此，在这项SPRINT的辅助研究中，我们建议研究(1)CKD患者动脉粥样硬化的进展速度是否比非CKD人群更快；(2)腹部肥胖和反映骨和矿物质代谢异常的因素(血浆钙、磷、碱性磷酸酶、25和1,25维生素D和成纤维细胞生长因子23水平)在CKD人群动脉粥样硬化的进展或动脉粥样硬化斑块的钙化中起重要作用。SPRINT是一项大型随机试验，约9250名年龄在55岁或以上的心血管高危人群参加，该试验将检验收缩压低目标< 120 mm Hg与标准目标< 140 mm Hg对心血管事件和死亡的主要复合因素的影响。SPRINT预计将于2010年10月开始招募患者。SPRINT将招募45%的CKD研究人群。在这项辅助研究中，将在6个SPRINT站点招募480名SPRINT参与者（240名CKD患者和240名非CKD患者）。这些地点包括犹他大学、斯坦福大学、丹佛科罗拉多大学、凯斯西储大学、克利夫兰诊所和匹兹堡大学。遵循标准化方案，参与者将在基线和30个月时接受颈动脉MRI测量动脉粥样硬化。这些图像将由华盛顿大学颈动脉MRI阅读中心读取。血液和尿液样本将在基线、12个月和30个月时仔细收集、处理和保存。检测将在明尼苏达大学和犹他大学进行。统计分析将在维克森林大学的SPRINT协调中心进行。我们相信该提案的优势（检查大量CKD和非CKD参与者的独特机会，要检查的问题的重要性，调查团队的实力和资源的可用性）将导致辅助研究的成功结论，结果将指导设计未来针对CKD动脉粥样硬化的随机对照试验。

DESCRIPTION (provided by applicant): There is a substantially higher incidence of cardiovascular events and cardiovascular deaths in the chronic kidney disease (CKD) population compared to the general population. However, there are several unresolved questions regarding the mechanisms that lead to increased cardiovascular events in the CKD population. It remains unclear 1. whether CKD by itself leads to accelerated atherosclerosis and 2. What the relative contribution of traditional and non-traditional risk factors to progression of atherosclerosis in CKD are. As the Systolic Pressure Intervention Trial (SPRINT) has a unique design of enrolling a large number of CKD and non-CKD participants at high risk for atherosclerotic events, this trial provides a great opportunity to examine whether atherosclerosis progression is accelerated in CKD compared to non-CKD and the factors that contribute to the greater prevalence of atherosclerosis in CKD. Therefore, in this ancillary study to SPRINT, we propose to examine (1) Whether there is a faster rate of progression of atherosclerosis in CKD compared to the non-CKD population and (2) Whether abdominal obesity and factors reflective of abnormal bone and mineral metabolism (plasma calcium, phosphorus, alkaline phosphatase, 25 and 1,25 vitamin D and fibroblast growth factor 23 levels) play a significant role in progression of atherosclerosis or calcification of atheromatous plaques in the CKD population. SPRINT, a large scale randomized trial of ~ 9250 adults aged 55 years or older with high cardiovascular risk will test the effects of low SBP goal of < 120 mm Hg vs. the standard goal of < 140 mm Hg on the primary composite of cardiovascular events and death. SPRINT is expected to start enrolling patients in Oct, 2010. SPRINT will recruit 45% of the study population with CKD. For this ancillary study, 480 SPRINT participants (240 with CKD and 240 without) will be recruited in 6 SPRINT sites. These sites include the University of Utah, Stanford University, University of Colorado at Denver, Case Western Reserve University, Cleveland Clinic and the University of Pittsburgh. Following standardized protocols, participants will undergo carotid MRI to measure atherosclerosis at baseline and 30 months. These images will be read by the Carotid MRI Reading Center at the University of Washington. Blood and urine samples will be carefully collected, processed and stored at baseline, 12 and 30 months. Assays will be performed at University of Minnesota and the University of Utah. Statistical analyses will be conducted at the SPRINT Coordinating Center at the Wake Forest University. We believe the strengths (the unique opportunity to examine a large number of CKD and non-CKD participants, the importance of the questions to be examined, the strength of the investigative team and the availability of resources) of this proposal will lead to successful conclusion of the ancillary study and the results will guide designing future RCTs targeting atherosclerosis in CKD. PUBLIC HEALTH RELEVANCE: People with chronic kidney disease have a higher risk of cardiovascular events, but the mechanisms are not well understood. The proposed project will address this important issue and provide insights into designing interventional studies to improve the outcomes of chronic kidney disease patients.