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 Björkelund; Hermann Brenner; Eric Brunner; Robert 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 Engström; 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 Jørgensen; Stefan Kiechl; Akihiko Kitamura; Yutaka Kiyohara; Wolfgang Koenig; Daan Kromhout; Lewis H Kuller; Børge G Nordestgaard; Emerging Risk Factors Collaboration; Anne Tybjærg-Hansen

doi:10.1056/NEJMoa1107477

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 Björkelund, 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 Engström, 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 Jørgensen, Stefan Kiechl, Akihiko Kitamura, Yutaka Kiyohara, Wolfgang Koenig, Daan Kromhout, Lewis H Kuller, Børge G Nordestgaard, Emerging Risk Factors Collaboration, Anne Tybjærg-Hansen

687 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 language	English
Journal	New England Journal of Medicine
Volume	367
Issue number	14
Pages (from-to)	1310-20
Number of pages	11
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa1107477
Publication status	Published - 4 Oct 2012

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10.1056/NEJMoa1107477

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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., Björkelund, C., Brenner, H., ... Tybjærg-Hansen, A. (2012). C-reactive protein, fibrinogen, and cardiovascular disease prediction. New England Journal of Medicine, 367(14), 1310-20. https://doi.org/10.1056/NEJMoa1107477

Kaptoge, S, Di Angelantonio, E, Pennells, L, Wood, AM, White, IR, Gao, P, Walker, M, Thompson, A, Sarwar, N, Caslake, M, Butterworth, AS, Amouyel, P, Assmann, G, Bakker, SJL, Barr, ELM, Barrett-Connor, E, Benjamin, EJ, Björkelund, C, Brenner, H, Brunner, E, Clarke, R, Cooper, JA, Cremer, P, Cushman, M, Dagenais, GR, D'Agostino, RB, Dankner, R, Davey-Smith, G, Deeg, D, Dekker, JM, Engström, G, Folsom, AR, Fowkes, FGR, Gallacher, J, Gaziano, JM, Giampaoli, S, Gillum, RF, Hofman, A, Howard, BV, Ingelsson, E, Iso, H, Jørgensen, T, Kiechl, S, Kitamura, A, Kiyohara, Y, Koenig, W, Kromhout, D, Kuller, LH, Nordestgaard, BG, Emerging Risk Factors Collaboration & Tybjærg-Hansen, A 2012, 'C-reactive protein, fibrinogen, and cardiovascular disease prediction', New England Journal of Medicine, vol. 367, no. 14, pp. 1310-20. https://doi.org/10.1056/NEJMoa1107477

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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.)",

author = "Stephen Kaptoge and {Di Angelantonio}, Emanuele and Lisa Pennells and Wood, {Angela M} and White, {Ian R} and Pei Gao and Matthew Walker and Alexander Thompson and Nadeem Sarwar and Muriel Caslake and Butterworth, {Adam S} and Philippe Amouyel and Gerd Assmann and Bakker, {Stephan J L} and Barr, {Elizabeth L M} and Elizabeth Barrett-Connor and Benjamin, {Emelia J} and Cecilia Bj{\"o}rkelund and Hermann Brenner and Eric Brunner and Robert Clarke and Cooper, {Jackie A} and Peter Cremer and Mary Cushman and Dagenais, {Gilles R} and D'Agostino, {Ralph B} and Rachel Dankner and George Davey-Smith and Dorly Deeg and Dekker, {Jacqueline M} and Gunnar Engstr{\"o}m and Folsom, {Aaron R} and Fowkes, {F Gerry R} and John Gallacher and Gaziano, {J Michael} and Simona Giampaoli and Gillum, {Richard F} and Albert Hofman and Howard, {Barbara V} and Erik Ingelsson and Hiroyasu Iso and Torben J{\o}rgensen and Stefan Kiechl and Akihiko Kitamura and Yutaka Kiyohara and Wolfgang Koenig and Daan Kromhout and Kuller, {Lewis H} and Nordestgaard, {B{\o}rge G} and Anne Tybj{\ae}rg-Hansen and Anne Tybj{\ae}rg-Hansen",

note = "Anne Tybj{\ae}rg-Hansen og Ruth Frikke-Schmidt er i collaboratorgruppen - ikke skrivegruppen",

year = "2012",

month = oct,

day = "4",

doi = "10.1056/NEJMoa1107477",

language = "English",

volume = "367",

pages = "1310--20",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "14",

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TY - JOUR

T1 - C-reactive protein, fibrinogen, and cardiovascular disease prediction

AU - Kaptoge, Stephen

AU - Di Angelantonio, Emanuele

AU - Pennells, Lisa

AU - Wood, Angela M

AU - White, Ian R

AU - Gao, Pei

AU - Walker, Matthew

AU - Thompson, Alexander

AU - Sarwar, Nadeem

AU - Caslake, Muriel

AU - Butterworth, Adam S

AU - Amouyel, Philippe

AU - Assmann, Gerd

AU - Bakker, Stephan J L

AU - Barr, Elizabeth L M

AU - Barrett-Connor, Elizabeth

AU - Benjamin, Emelia J

AU - Björkelund, Cecilia

AU - Brenner, Hermann

AU - Brunner, Eric

AU - Clarke, Robert

AU - Cooper, Jackie A

AU - Cremer, Peter

AU - Cushman, Mary

AU - Dagenais, Gilles R

AU - D'Agostino, Ralph B

AU - Dankner, Rachel

AU - Davey-Smith, George

AU - Deeg, Dorly

AU - Dekker, Jacqueline M

AU - Engström, Gunnar

AU - Folsom, Aaron R

AU - Fowkes, F Gerry R

AU - Gallacher, John

AU - Gaziano, J Michael

AU - Giampaoli, Simona

AU - Gillum, Richard F

AU - Hofman, Albert

AU - Howard, Barbara V

AU - Ingelsson, Erik

AU - Iso, Hiroyasu

AU - Jørgensen, Torben

AU - Kiechl, Stefan

AU - Kitamura, Akihiko

AU - Kiyohara, Yutaka

AU - Koenig, Wolfgang

AU - Kromhout, Daan

AU - Kuller, Lewis H

AU - Nordestgaard, Børge G

AU - Emerging Risk Factors Collaboration

AU - Tybjærg-Hansen, Anne

N1 - Anne Tybjærg-Hansen og Ruth Frikke-Schmidt er i collaboratorgruppen - ikke skrivegruppen

PY - 2012/10/4

Y1 - 2012/10/4

N2 - 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.)

AB - 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.)

U2 - 10.1056/NEJMoa1107477

DO - 10.1056/NEJMoa1107477

M3 - Journal article

C2 - 23034020

SN - 0028-4793

VL - 367

SP - 1310

EP - 1320

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 14

ER -

C-reactive protein, fibrinogen, and cardiovascular disease prediction

Abstract

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