Elucidating the Kidney's Role in Cardiovascular Risk
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DESCRIPTION (provided by applicant): The public health impact of chronic kidney disease is enormous. Over 6 million adults in the United States have chronic renal insufficiency (CRI), with the greatest prevalence among the elderly and African-Americans. Chronic renal insufficiency is associated with an increased risk of morbidity and mortality, particular from cardiovascular disease. Although CRI is associated with a higher risk for myocardial infarction, stroke, heart failure, and cardiovascular mortality, independent of traditional cardiovascular risk factors, such as age, diabetes, hypertension, dyslipidemia, and tobacco use, the mechanisms are poorly defined. The relative contributions of traditional and novel risk factors for predicting cardiovascular events among persons with CRI have not been evaluated. In particular, levels of certain novel cardiovascular risk factors including inflammatory and hemostatic factors, homocysteine, and lipoprotein(a) are elevated in patients with CRI and may mediate the association of CRI with cardiovascular morbidity. Since accelerated atherosclerosis likely begins early in the course of renal disease, one potential barrier to reducing the adverse effects of CRI on cardiovascular disease is the difficulty in measuring renal function accurately, particularly among those with mild CRI. Although current clinical practice and clinical research rely on elevated serum creatinine levels to estimate renal function, creatinine levels are insensitive for identifying CRI, and are influenced by non-renal factors, such as age, sex, race, and muscle mass. Serum cystatin-C is an innovative and promising measure of renal function that is more sensitive than creatinine for detecting CRI and is not affected by age, sex, race, or muscle mass. To that end, we propose to use data from the Cardiovascular Health Study (CHS), an NHLBI-funded longitudinal cohort study to determine which individual cardiovascular risk factors appear most responsible for the association between CRI and cardiovascular events, and to determine the utility of cystatin-C levels as a marker for increased cardiovascular risk in the elderly. The results of this study will lead to a greater understanding of the relationship between CRI and cardiovascular disease in the elderly, and will foster the design of future intervention studies to decrease the burden of cardiovascular disease.
