End-stage renal disease, atherosclerosis, and cardiovascular mortality: IsC-reactive protein the missing link?

In uremic patients, the morbidity and mortality of cardiovascular disease a re substantially higher than in the general population. This has led to the formulation of an 'accelerated atherogenesis hypothesis in uremic patients and has been commonly linked with the metabolic alterations associated wit h uremia. Advancement in the understanding of the pathogenesis of atheroscl erotic vascular disease now suggests a central contribution of inflammation to atherogenesis, with involvement of a number of key mediators and marker s of the inflammatory process. Recent epidemiological data have documented associations between C-reactive protein (CRP), the prototypical acute phase response protein, and cardiovascular disease in general population. Given the lipoprotein binding and complement activation functions of CRP and its localization in atherosclerotic vessels, there is a strong likelihood that CRP may be involved in the atherosclerotic process. The uremic state is ass ociated with an altered immune response, which is associated with elevated proinflammatory cytokine levels. CRP concentrations are increased in a sign ificant proportion of endstage renal disease patients and have been associa ted with certain clinical outcome measures, including all-cause and cardiov ascular mortality. This review outlines the evidence linking CRP with ather osclerosis and proposes that elevated CRP concentrations may be involved in the initiation and progression of accelerated atherosclerosis in uremia.