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C-reactive protein, fibrinogen, and cardiovascular disease prediction

Kaptoge, Stephen, Di Angelantonio, Emanuele, Pennells, Lisa, Wood, Angela M., White, Ian R., Gao, Pei, Walker, Matthew, Thompson, Alexander, Sarwar, Nadeem, Caslake, Muriel, Butterworth, Adam S., Amouyel, Philippe, Assmann, Gerd, Bakker, Stephan J. L., Barr, Elizabeth L. M., Barrett-Connor, Elizabeth, Benjamin, Emilia J., Björkelund, Cecilia and Brenner, Hermann (2012). C-reactive protein, fibrinogen, and cardiovascular disease prediction. New England Journal of Medicine,367(14):1310-1320.

Document type: Journal Article

IRMA ID 84473306xPUB12
Title C-reactive protein, fibrinogen, and cardiovascular disease prediction
Author Kaptoge, Stephen
Di Angelantonio, Emanuele
Pennells, Lisa
Wood, Angela M.
White, Ian R.
Gao, Pei
Walker, Matthew
Thompson, Alexander
Sarwar, Nadeem
Caslake, Muriel
Butterworth, Adam S.
Amouyel, Philippe
Assmann, Gerd
Bakker, Stephan J. L.
Barr, Elizabeth L. M.
Barrett-Connor, Elizabeth
Benjamin, Emilia J.
Björkelund, Cecilia
Brenner, Hermann
Journal Name New England Journal of Medicine
Publication Date 2012
Volume Number 367
Issue Number 14
ISSN 0028-4793   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84867164377
Start Page 1310
End Page 1320
Total Pages 10
Publisher Massachusetts Medical Society
HERDC Category C1 - Journal Article (DIISR)
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.

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.


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.

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.)
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