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

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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.