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As in many other fields of human activity, medicine is subject to fashion, and in recent years much attention has been given to C-reactive protein (CRP). Numerous studies have described CRP as a risk marker for coronary artery disease (CAD) in the general population, with some even suggesting that CRP could be a true risk factor for CAD, while other studies have described CRP as a major prognostic stratification tool in patients with known CAD. In short, CRP tends to be presented as the α and ω of CAD.
CRP: a risk marker rather than a risk factor
This picture, however, may be too good to be true. In 2008, a remarkable study carried out in over 10 000 Danish people definitively (if anything can be considered definitive in medicine) discarded the theory of causality between CRP and atherogenesis.1 In this large observational cohort, a modest, but significant correlation was found between elevated (>3 mg/l) CRP levels and the risk of ischaemic heart disease (hazards ratio (HR)=2.2; adjusted HR=1.6) and that of ischaemic cerebrovascular disease (HR=1.6; adjusted HR=1.3). Combinations of four genetic polymorphisms were found to be associated with markedly increased levels of CRP, but were not associated with an increased risk of either ischaemic heart or cerebrovascular disease. In other words, genetically determined CRP elevations were not associated with an increased risk of ischaemic vascular disease, whereas non-genetically determined elevated levels were. In contrast, in the same population, apolipoprotein E genotypes were associated with both raised cholesterol levels and an increased risk of vascular events. These findings illustrate the difference between a causal factor (lipid disorders) and a risk marker without causal relationship with vascular disease (CRP).
The limited added value of CRP for prognostic stratification
Likewise, the meta-analysis by He et al2 published in this issue of Heart presents a somewhat sobering view of the information that CRP measurement might add to the clinicians' …