Global risk assessment for cardiovascular disease entails examination of all the available risk factors. The Framingham Risk Score, the Munster Heart Study (PROCAM) risk score and the European Society of Cardiology (SCORE Project) risk score are important examples of algorithms used for global risk assessment.

Compared to the Framingham risk score variables of age, total cholesterol, HDL cholesterol, systolic blood pressure and smoking status, the PROCAM algorithm uses 3 additional risk factors: triglycerides, diabetes mellitus and a positive family history of myocardial infarction. The European Society of Cardiology risk score predicts the risk of fatal cardiovascular (CVD) events only.

Algorithms such as these using classical risk factors for coronary heart disease (CHD), can however only predict 50-60% of myocardial infarctions. Therefore a more precise method of risk stratification is required for many patients. In a paper published in JAMA, Greenland et al. have described how the selective use of hypothetical non-invasive testing procedures could improve CHD risk assessment.

Inflammation is an important feature of atherosclerosis, and various acute phase reactants have been linked to future CVD outcomes. Since the late 1990's, high-sensitivity assays for C-reactive protein (CRP) have become available that are reliable, well standardized and available at a low cost. These assays detect CRP levels at low concentrations which is important for the assessment of cardiovascular risk.

Numerous epidemiological studies have shown that high-sensitivity CRP (hs-CRP) levels are predictive of future CVD events. In the Women's Health Study (WHS), it was shown that hs-CRP had an even greater predictive value than LDL cholesterol. The WHS and the MONICA Augsburg study both showed that hs-CRP levels add prognostic information to all categories of the Framingham risk score.

Apart from the prediction of cardiovascular risk, various studies indicate a role of C-reactive protein in atherothrombosis.

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After viewing this presentation the participant will be able to discuss:

- Algorithms for global risk assessment for cardiovascular disease (Framingham, PROCAM and The European Society of Cardiology SCORE Project risk score)
- Epidemiological data and clinical guidelines supporting the use of hs-CRP testing in the global assessment of cardiovascular risk
- Studies indicating a role for C-reactive protein in atherothrombosis

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Guy De Backer et al.European guidelines on cardiovascular disease prevention in clinical practiceEur Heart Journal.2003;24(17):1601-1610.

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Natalie Khuseyinova, Armin Imhof, Gerlinde Trischler, Dietrich Rothenbacher, Winston L. Hutchinson, Mark B. Pepys and Wolfgang Koenig.Determination of C-Reactive Protein: Comparison of Three High-Sensitivity Immunoassays Clinical Chemistry. 2003;49:1691-1695.

Wolfgang Koenig, Malte Sund, Margit Fröhlich, Hannelore Löwel, Winston L. Hutchinson and Mark B. Pepys.Refinement of the Association of Serum C-reactive Protein Concentration and Coronary Heart Disease Risk by Correction for Within-Subject Variation over Time - The MONICA Augsburg Studies, 1984 and 1987 Am J Epidemiol 2003; 158:357-364.

Wolfgang Koenig, MD; Hannelore Löwel, MD; Jens Baumert, MS; Christa Meisinger, MD, MPH.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.

Antoni Paul, PhD; Kerry W.S. Ko, PhD; Lan Li, MD; Vijay Yechoor, MD; Mark A. McCrory, BS; Alexander J. Szalai, PhD; Lawrence Chan, MBBS, DSc.C-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E Deficient Mice Circulation. 2004;109:647-655.

Thomas A. Pearson, MD, PhD (Co-Chair); George A. Mensah, MD (Co-Chair); R. Wayne Alexander, MD, PhD; Jeffrey L. Anderson, MD; Richard O. Cannon, III, MD; Michael Criqui, MD; Yazid Y. Fadl, MD; Stephen P. Fortmann, MD; Yuling Hong, MD, PhD; Gary L. Myers, PhD; Nader Rifai, PhD; Sidney C. Smith, Jr, MD; Kathryn Taubert, PhD; Russell P. Tracy, PhD; Frank Vinicor, MD.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 AssociationCirculation. 2003;107:499.

Paul M. Ridker, M.D., Nader Rifai, Ph.D., Lynda Rose, M.S., Julie E. Buring, Sc.D., and Nancy R. Cook, Sc.D.Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular EventsNEJM 2002.347:1557-1565.

Paul M Ridker, MD.Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention Circulation. 2003;107:363.

Paul M Ridker, MD, MPH; Nancy Cook, ScD.Clinical Usefulness of Very High and Very Low Levels of C-Reactive Protein Across the Full Range of Framingham Risk Scores Circulation. 2004;109:1955-1959.

Paul M Ridker, MD; Peter W.F. Wilson, MD; Scott M. Grundy, MD.Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk?Circulation. 2004;109:2818-2825.

Russell Ross, Ph.D.Atherosclerosis-An Inflammatory DiseaseNEJM.2003;340:115-126

Irene M. van der Meer, MSc; Moniek P. M. de Maat, PhD; Amanda J. Kiliaan, PhD; Deirdre A. M. van der Kuip, MD, PhD; Albert Hofman, MD, PhD; Jacqueline C. M. Witteman, PhD.The Value of C-Reactive Protein in Cardiovascular Risk Prediction Arch Intern Med. 2003;163:1323-1328.

John Danesh, M.B., Ch.B., D.Phil., Jeremy G. Wheeler, M.Sc., Gideon M. Hirschfield, M.R.C.P., Shinichi Eda, Ph.D., Gudny Eiriksdottir, M.Sc., Ann Rumley, Ph.D., Gordon D.O. Lowe, M.D., F.R.C.P., Mark B. Pepys, M.D., Ph.D., and Vilmundur Gudnason, M.D., Ph.D.
C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart NEJM Volume 350:1387-1397

L. Mosca C-Reactive Protein — To Screen or Not to Screen?NEJM Volume 347:1615-1617