Related Experiment Videos
End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link?
1Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom.
Insights
In uremic patients, cardiovascular disease risk is high. Elevated C-reactive protein (CRP) may drive accelerated atherosclerosis in these individuals, contributing to increased mortality.
Area of Science:
- Nephrology
- Cardiology
- Immunology
Background:
- Cardiovascular disease (CVD) morbidity and mortality are significantly elevated in uremic patients compared to the general population.
- Metabolic alterations in uremia have been linked to accelerated atherogenesis.
- Inflammation is increasingly recognized as a central factor in atherosclerotic vascular disease pathogenesis.
Purpose of the Study:
- To review the evidence linking C-reactive protein (CRP) with atherosclerosis in uremic patients.
- To propose a role for elevated CRP in the initiation and progression of accelerated atherosclerosis in uremia.
Main Methods:
- Review of epidemiological data and scientific literature.
- Examination of CRP's functions, including lipoprotein binding and complement activation.
- Analysis of CRP's localization in atherosclerotic vessels.
Main Results:
- C-reactive protein (CRP) is associated with cardiovascular disease in the general population.
- The uremic state involves altered immune responses and elevated proinflammatory cytokines.
- Elevated CRP concentrations are observed in end-stage renal disease patients and linked to mortality.
Conclusions:
- CRP's functions suggest a potential role in the atherosclerotic process.
- Elevated CRP may contribute to the accelerated atherosclerosis seen in uremia.
- Further investigation into CRP's role in uremic cardiovascular complications is warranted.
Abstract:
In uremic patients, the morbidity and mortality of cardiovascular disease are 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 with uremia. Advancement in the understanding of the pathogenesis of atherosclerotic vascular disease now suggests a central contribution of inflammation to atherogenesis, with involvement of a number of key mediators and markers 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 associated with an altered immune response, which is associated with elevated proinflammatory cytokine levels. CRP concentrations are increased in a significant proportion of end-stage renal disease patients and have been associated with certain clinical outcome measures, including all-cause and cardiovascular mortality. This review outlines the evidence linking CRP with atherosclerosis and proposes that elevated CRP concentrations may be involved in the initiation and progression of accelerated atherosclerosis in uremia.