doi: 10.1161/01.CIR.0000149807.32506.F4
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;110:e532.)
© 2004 American Heart Association, Inc.
Correspondence |
Letter Regarding Article by Ridker et al, "Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk?"
Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill
To the Editor:
In calling for the addition of C-reactive protein (CRP) to global cardiovascular disease (CVD) risk prediction, Ridker et al1 have not considered standard tenets of evaluating screening tests. When making decisions about the predictive utility of new tests, the focus is not on relative risks. Rather, the best measure of the additional utility of a new test is to be found in comparing the areas under receiver operating characteristic curves (AUC) for risk scores calculated without and with the novel risk factor.2 Although risk prediction with standard CVD risk factors remains imperfect, it has proved extremely difficult to improve on its risk prediction/discrimination capability, even when adding fairly strong new measures such as the coronary calcium score.3
In light of the authors’ call for the addition of CRP to global risk estimation scores, and hence for universal CRP screening, the appropriate question is: Does CRP testing add to traditional risk factors and risk scores in discriminating the portion of the population who will experience CVD events from those who will not? Several studies cited by Ridker et al as showing a positive association for CRP independent of traditional risk factors also showed small increments of at most 1% to 2% in the AUC.4,5 Furthermore, the authors did not cite Rotterdam Study data6 that showed no significant association for CRP and no increase in the AUC. In addition, the Framingham group has presented data indicating little incremental value for CRP over and above traditional risk factors.7
In an article examining CRP for risk prediction, Ridker and colleagues calculated an AUC of 0.81 for a multivariable (Framingham-like) model without CRP (but with LDL cholesterol) and an apparently identical AUC of 0.81 for a model containing CRP (without LDL cholesterol).8 Although it was noted that these 2 AUCs were statistically different (in light of the sample size of nearly 30 000), for clinical purposes, whatever difference was present was clearly trivial in that it represents no meaningful improvement in clinical risk discrimination.
The data from population studies at best indicate that CRP may be used appropriately as a niche test in making treatment decisions for patients predicted to be at intermediate risk by the Framingham equations, as recommended by the Centers for Disease Control and Prevention–American Heart Association task force9 and reinforced by recent data published in Circulation.4 Unfortunately, there is no advantage to adding CRP to the standard risk prediction model for all patients at this time.
References
1. Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation. 2004; 109: 2818–2825.
2. Pepe MS, Janes H, Longton G, Leisenring W, Newcomb P. Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol. 2004; 159: 882–890.
3. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA. 2004; 291: 210–215.
4. Koenig W, Lowel H, Baumert J, Meisinger C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation. 2004; 109: 1349–1353.
5. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GDO, Pepys MB, Gudnason V. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004; 350: 1387–1397.
6. van der Meer IM, de Maat MPM, Kiliaan AJ, van der Kuip DAM, Hofman A, Witteman JCM. The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study. Arch Intern Med. 2003; 163: 1323–1328.
7. Wilson PW, D’Agostino RB, Nam BH, Benjamin EJ, O’Donnell CJ. C-reactive protein and CVD risk in Framingham. Circulation. 2003; 108: IV-748–IV-749.
8. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002; 347: 1557–1565.
9. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003; 107: 499–511.
Related Article:
Circulation 2004 110: 3617.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||