Novel Cardiovascular Risk Factors in Renal Insufficiency

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DESCRIPTION (provided by applicant): The incidence of cardiovascular disease (CVD) is 10-20 fold greater in end-stage renal patients compared to the general population even after adjusting for age, diabetes, gender and race. The National Kidney Foundation Task Force on Cardiovascular Disease concluded that emphasis should be placed on risk factors related to uremia such as proteinuria, elevated Lp(a) and homocysteine whose adverse profile worsens as the chronic kidney disease (CKD) progresses. Because half of all cardiovascular events occur in patients without any known traditional risk factors, it is important to screen for subclinical CVD in an effort to identify high-risk individuals. The optimal evaluation for the presence of cardiovascular disease in particular coronary artery disease in patients with CKD is unknown. Carotid intima-media thickness (IMT) measured by ultrasound has been shown to assess the extent and severity of atherosclerosis. The proposed study will examine prospectively 100 asymptomatic patients with CKD and without diabetes and determine if nontraditional risk factors such as homocysteine, lipoprotein (a) and C-reactive protein are independent risk factor for presence and progression of subclinical cardiovascular disease as measured by repeated noninvasive carotid US measures of IMT adjusting for known cardiovascular risk factors over a 24-month interval. We propose to utilize this promising new non-invasive technique for the quantitative assessment of subclinical CVD. We are responding to program announcement PA-01-127 which includes the objective of use of epidemiological and biochemical approaches to identifying new, non-traditional risk factors for cardiovascular disease in patients with CKD. For the determination of baseline carotid IMT, the tool of analysis will be multiple linear regression. A change will be measured by the difference in IMT measurements. Models using standard mixed effects growth curves will be used to allow both the estimation of individual subjects' slopes and intercepts and for the comparison of groups defined by baseline or time varying covariates. Elucidation of these relationships is an essential component of identifying modifiable risk factors for the progression of cardiovascular disease and may lead to targeted medical interventions to easily identifiable high-risk groups to decrease disease progression.