The evidence base for the association of hs-CRP and other inflammatory markers with cardiovascular disease endpoints has continued to expand, including the interpretation and application of the evidence for use in clinical and public health practice. The evidence for or against hs-CRP as a useful marker for clinical practice continues to create controversy (1). In March, 2002, a joint CDC/American Heart Association Task Force was convened to review the growing body of research on inflammatory markers in cardiovascular disease, and to make recommendations on which tests should be used, which results constituted high risk, which patients should be tested, etc. (2). However, of equal importance were development of 14 recommendations for laboratory, clinical and population sciences in order to fill gaps in our understanding of pathophysiology, predication, and practical utilization of these markers. This summary will contrast the recommendations made in 2002 with current research findings as a means to summarize progress made and gaps remaining.
For the basic/laboratory sciences, the role of CRP as a risk factor causative of atherothrombosis versus a risk marker produced by an active disease process continues to be debated. Use of animal models and genetic variants in CRP are useful, but clinical trials of agents altering levels in human research subjects are likely need to enlighten this controversy. The optimal measurement of inflammation for the purpose of prediction of CV disease needs to be clarified, adding the possible uses of new markers, combinations of hs-CRP and other inflationary markers, or the combination of hs-CRP with other risk assessment strategies such as noninvasive testing/imaging.
Clinical studies have yet to define the full impact of risk categorization using hs-CRP in clinical practice. Randomized trials of screening strategies still need to define the effect on patient and provider behavior. Secondly, the clinical significance of a reduction (or lack of reduction) of hs-CRP level after a lifestyle or drug intervention remains poorly defined, despite apparent widespread use of testing for this purpose. The potential role of the CRP testing to motivate patients to adhere to lifestyle or drug interventions is also poorly defined. Finally, the cost effectiveness of hs-CRP testing has not been addressed as a means to support or refute its reimbursement.
Finally, population studies have been able to show similar distributions for hs-CRP levels in diverse populations. Less is known about the risk of categories of hs-CRP levels across race and ethnic groups, in children and young adults, and in genetic subgroups. The evidence for utility of hs-CRP in identifying high risk subjects in general populations is also lacking and enters the debate on predication versus association as the best evidence for hs-CRP as a disease marker.
Therefore, considerable progress has been made over the past four years, yet key questions remain unanswered. Further progress addressing these issues will likely not only clarify the use of hs-CRP in clinical practice, but also add understanding of the critically important role of inflammation in atherothrombotic disease.
- Mosca L. C-reactive protein: to screen or not to screen? New England Journal of Medicine 2002; 347:1615-1617.
- Pearson TA, Mensah GA, Alexander RW, et al. Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice. Circulation 2003; 107: 499-511.