Effects of risk factor control on atherosclerosis, vasoreactivity and cardiac ischemia in patients on dialysis

终末期肾衰竭是最常见的严重慢性疾病之一；在澳大利亚，超过1万名患者正在接受透析治疗或进行功能移植。这组患者中最常见的死亡原因是冠状动脉疾病，通常会尝试识别有这个问题的患者，目的是通过血管成形术或搭桥手术来控制这种风险。不幸的是，这些手术可能不如通常有效，因为肾脏疾病患者的动脉狭窄过程更具侵袭性。此外，这一过程可能导致在某一时间点冠状动脉疾病检测呈阴性的患者在随访中出现冠状动脉问题。在这项研究中，我们建议使用标准的压力测试方案来对一组透析高危患者的冠状动脉事件风险进行分层。风险最高的患者将接受搭桥手术，而中低风险的患者将随机接受常规治疗，或通过降低胆固醇、补充叶酸（旨在使同型半胱氨酸正常化）、控制血压和血糖来积极治疗动脉粥样硬化。这种方法的效果将随后检查动脉粥样硬化的生化标志物，动脉厚度和反应性成像（反映血管结构和功能的测试）。我们还将评估异常心脏应激反应的进展或减少，以及随访中事件的发生。最后，利用随访数据比较两种压力测试方案的预测值。本研究的结果将增强我们对肾脏患者动脉粥样硬化过程的重要性的理解，并将对肾功能衰竭的冠状动脉疾病的管理方法转向主动控制危险因素和远离血运重建术。

End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing is more aggressive in patients with renal disease. Moreover, this process may cause patients with negative testing for coronary disease at one point in time to develop coronary problems over follow-up. In this study, we propose to use a standard stress testing protocol to stratify the risk of coronary events in a group of at risk patients on dialysis. Those at highest risk will undergo bypass surgery, while those at intermediate and low risk will be randomized to usual care, or an aggressive treatment of atheroma with cholesterol reduction, folic acid supplementation (aiming to normalize homocysteine), blood pressure and blood sugar control. The effects of this approach will be followed by examination of biochemical markers of atherosclerosis, and imaging of arterial thickness and reactivity (reflecting tests of structure and function of the vasculature). We will also assess of the progression or reduction of abnormal cardiac stress responses, and the occurence of events at follow-up. Finally, follow-up data will be used to compare the predictive value of the 2 stress testing protocols. The results of this study will enhance our understanding of the importance of the atherosclerotic process in renal patients, and move the management approach for coronary disease in renal failure toward active risk factor control and away from revascularization.