Renal dysfunction and abnormalities of the cardiovascular system often occur simultaneously and may share common pathophysiology. Factors influencing progression of one disease state are thought to influence progression of the other. The Strong Heart Study (SHS) provides a unique opportunity to study changes in renal function, CVD risk factors, subclinical CVD as well as clinical events in American Indians (AI). AI are a health disparity population due to their extremely high rates of diabetes and diabetic complications. I propose to (1) perform secondary data analyses to examine the co-progression of renal and cardiovascular disease in AI in the SHS and (2) conduct a pilot study involving measurement of oxidative stress markers in relation to progression of renal and cardiovascular disease in AI. Specifically, I propose to conduct a series of cross-sectional, survival and repeated measures analyses involving glomerular filtration rate and measures of clinical (Ml, CHD) and subclinical (carotid atherosclerosis, echocardiography) cardiovascular disease to better define the co-progression of renal and CVD in AI. Further, I propose to conduct a pilot study of CVD cases and controls in which I will use stored specimens from the SHS to examine levels of F2-isoprostane and 8- hydroxyguanine, two markers of oxidative stress. Achievement of these aims, along with the other training activities described in this application, and the structured mentoring offered by Drs. Resnick and Umans will provide me with the skills, knowledge and direction that will help me begin developing a research program focused in health disparities in renal disease. My long term professional objective is to develop a funded research program dealing with renal disease in minority populations. ? ? ? ?