C-Reactive Protein and Coronary Heart Disease: Predictive Test or Therapeutic Target?

BACKGROUND: The hepatocyte-derived acute-phase reactant C-reactive protein (CRP) has been the subject of intense research over the last 2 decades for its possible role in the pathogenesis of cardiovascular diseases. This research has spawned interest in the use of the blood concentration of CRP for predicting a first coronary heart disease (CHD) event, which has been made possible with the development of high-sensitivity CRP (hsCRP) assays that can measure the typically low concentrations of CRP that circulate in the absence of an overt infective or inflammatory episode, and as a potential causal factor that might be targeted therapeutically. The research has encompassed observational and genetic epidemiology, basic science studies with cells and tissues, experiments with animal models and humans, and randomized trials (although not of specific CRP-lowering therapies as yet). CONTENT: We focus on investigations of the potential role of small differences in basal hsCRP concentration seen in healthy individuals and the relationship of such differences to the long-term risk of a first CHD event, rather than on research devoted to the high acute-phase CRP concentrations, which occur after acute atherothrombotic events and can influence the severity of ischemic tissue damage and the subsequent prognosis. We concentrate mainly on research findings at the translational interface and draw on evidence from human observational and genetic epidemiology, as well as from randomized trials. CONCLUSIONS: As the field matures from one of discovery to an evaluative science, the development of possible clinical applications requires a sharpening of focus on and a critical appraisal of the strengths and deficiencies of the accumulated evidence. Such assessments require attention to both the current state of affairs and the design of future research, so that the existing uncertainties about the utility of CRP in predicting CHD and its role in causing this disease can be resolved.