Cardiovascular disease is common in chronic kidney disease (CKD) patients. CKD patients are more likely to have a cardiovascular event (myocardial infarction, stroke, heart failure and sudden death) than to progress to end-stage renal disease requiring dialysis or transplantation. Traditional risk factors, such as dyslipidemia, diabetes, smoking and hypertension, are very prevalent in this population, and contribute to the progression of CKD, but are limited predictors of cardiovascular events in these patients. Use of traditional risk factors in risk prediction scores such as the Framingham risk score results in underestimation of cardiovascular disease (CVD) risk. Recent studies have shown that novel cardiovascular risk factors such as oxidative stress and chronic inflammation are independent risk factors for cardiovascular disease in CKD patients on dialysis. We are responding to program announcement PAR-07-024, titled "Ancillary Studies to Major Ongoing NIDDK and NHLBI Clinical Research Studies". The NIDDK Chronic Renal Insufficiency Cohort (CRIC) study was initiated in 2003 to identify risk factors for CVD and progression of renal disease in adults with mild to severe CKD;follow-up visits will extend through June 2013. This cohort provides an unprecedented opportunity to investigate the role of oxidative stress and chronic inflammation in the presence and progression of CVD as measured by carotid intima-media thickness (IMT). Carotid IMT measured by ultrasound assesses the extent and severity of atherosclerosis. Preliminary data in 425 CRIC subjects demonstrate an association of IMT with traditional and non-traditional cardiovascular risk factors. The proposed prospective study will add IMT measurements in an additional 400 subjects at 2 different CRIC sites, allow for evaluation of progression of IMT in the above 425 subjects and determine if carotid IMT predicts cardiovascular events in CKD patients. Assays for oxidative stress and inflammatory markers will be measured at the same time points as the carotid IMT evaluation.
The aims of the study are: to determine the prevalence and risk factors for increased carotid IMT in mild to severe CKD, to determine risk factors for progression of carotid IMT in mild to severe CKD and to determine if IMT is a predictor for cardiovascular events in CKD patients. Novel cardiovascular risk factors likely contribute to the substantial burden of cardiovascular complications in patients with CKD. Elucidation of the relationship between CVD and novel risk factors is an essential component for the prediction of cardiovascular risk and to identify modifiable risk factors for the progression of CVD that could aid in the development of anticipated randomized clinical trials to decrease disease progression. PROJECT NARRATIVE Cardiovascular disease is 5-10 times more likely in patients with chronic kidney disease compared to people of their same age group. It is important to identify individuals at high risk for events using non- invasive measures. We propose to utilize a measure of the carotid vessels by ultrasound to determine if we can identify patients at risk for cardiovascular disease. This will aid in future clinical trials to slow disease progression.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-N (M3))
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Kusek, John W
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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