High sensitivity C-reactive protein and cardiovascular disease: an association built on unstable foundations?

There is considerable interest in the inflammatory hypothesis of vascular disease. Markers of inflammation predict vascular events, and inflammatory cells and molecules are critical elements within plaques and are especially prominent in unstable lesions. With respect to screening, concentrations of C-reactive protein (CRP), as determined by high-sensitivity assays, have been consistently shown to predict myocardial infarction and other vascular events independently of traditional risk factors. As a result, some authorities proposed potential inclusion of CRP in risk factor stratification. However, more recent evidence in the last two years from larger studies suggests that CRP concentrations are only around as half as predictive for vascular events as suggested in earlier reports. Furthermore, it now appears as if CRP measurements add little additional predictive value to current coronary heart disease risk prediction charts. The short-term variability of CRP is also problematic for risk factor screening. At the same time, other recent evidence questions the proposed causal role of CRP in atherogenesis. Therefore, the current focus in clinical practice should remain on established risk factors (e.g. smoking, lipids and blood pressure), both to determine coronary heart disease risk and to reduce it.