C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction

Stephen Kaptoge*, Emanuele Di Angelantonio, Lisa Pennells, Angela M. Wood, Ian R. White, Pei Gao, Matthew Walker, Alexander Thompson, Nadeem Sarwar, Muriel Caslake, Adam S. Butterworth, Philippe Amouyel, Gerd Assmann, Stephan J. L. Bakker, Elizabeth L. M. Barr, Elizabeth Barrett-Connor, Emelia J. Benjamin, Cecilia Bjorkelund, Hermann Brenner, Eric BrunnerRobert Clarke, Jackie A. Cooper, Peter Cremer, Mary Cushman, Gilles R. Dagenais, Ralph B. D'Agostino, Rachel Dankner, George Davey Smith, Dorly Deeg, Jacqueline M. Dekker, Gunnar Engstrom, Aaron R. Folsom, F. Gerry R. Fowkes, John Gallacher, J. Michael Gaziano, Simona Giampaoli, Richard F. Gillum, Albert Hofman, Barbara V. Howard, Erik Ingelsson, Hiroyasu Iso, Torben Jorgensen, Stefan Kiechl, Akihiko Kitamura, Yutaka Kiyohara, Wolfgang Koenig, Daan Kromhout, Lewis H. Kuller, Debbie A. Lawlor, Mark Woodward, Emerging Risk Factors Collaboration

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

647 Citations (Scopus)

Abstract

Background

There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events.

Methods

We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen.

Results

The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P <0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), " intermediate" (10% to <20%), and "high" (>= 20%) (P <0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of >= 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years.

Conclusions

In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

Original languageEnglish
Pages (from-to)1310-1320
Number of pages10
JournalNew England Journal of Medicine
Volume367
Issue number14
DOIs
Publication statusPublished - 4 Oct 2012

Keywords

  • CORONARY-HEART-DISEASE
  • NONVASCULAR MORTALITY
  • PRACTICE GUIDELINES
  • PRIMARY PREVENTION
  • COST-EFFECTIVENESS
  • STATIN THERAPY
  • RISK PROFILE
  • ASSOCIATION
  • INFLAMMATION
  • METAANALYSIS

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Cite this

Kaptoge, S., Di Angelantonio, E., Pennells, L., Wood, A. M., White, I. R., Gao, P., Walker, M., Thompson, A., Sarwar, N., Caslake, M., Butterworth, A. S., Amouyel, P., Assmann, G., Bakker, S. J. L., Barr, E. L. M., Barrett-Connor, E., Benjamin, E. J., Bjorkelund, C., Brenner, H., ... Emerging Risk Factors Collaboration (2012). C-Reactive Protein, Fibrinogen, and Cardiovascular Disease Prediction. New England Journal of Medicine, 367(14), 1310-1320. https://doi.org/10.1056/NEJMoa1107477