C-Reactive Protein and Cardiovascular Disease Risk: Still an Unknown Quantity?

The role of C-reactive protein (CRP) in cardiovascular disease risk remains controversial, and several interrelated questions are unresolved. Although it is clear that higher circulating CRP levels are associated with coronary heart disease (CHD) incidence and mortality rates in prospective studies, the magnitude of this association has been downgraded in recent years (1). It is also clear that CRP levels are strongly related to many potential confounding factors that influence CHD incidence and mortality rates. In predictive models that appropriately account for these confounders, the magnitude of the association between CRP levels and CHD outcomes is considerably attenuated toward the null (2). Whether CRP is a marker of cardiovascular disease risk or is causally related to cardiovascular disease is uncertain. Nonetheless, some authors have recently claimed that CRP itself is indeed a promoter of atherosclerosis and increased CHD risk (3, 4). If this is true, CRP would become a clear and explicit target for therapeutic intervention.

In this issue, 2 articles (5, 6) express widely divergent views regarding the role of CRP in cardiovascular disease risk stratification. Because individuals at greatest risk for disease have the most to gain from medical interventions (7), correctly specifying level of risk is an important clinical task. Both Cook and colleagues (5) and Lloyd-Jones and coworkers (6) investigate whether adding CRP to predictive models could usefully improve the ability of clinicians to target interventions. Lloyd-Jones and coworkers (6), who review the published evidence, show that adding CRP to predictive models containing conventional cardiovascular risk factors leads to minor improvement in measures of discrimination (receiver-operator characteristic curve properties or c-statistics). This finding is in line with the findings of the most recent study on this issue (8). Cook and colleagues (5) argue that these measures of discrimination are not …