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N Engl J Med. 2012 Oct 4;367(14):1310-20. doi: 10.1056/NEJMoa1107477.

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

Collaborators (310)

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 SJ, Barr EL, Barrett-Connor E, Benjamin EJ, Björkelund C, Brenner H, Brunner E, Clarke R, Cooper JA, Cremer P, Cushman M, Dagenais GR, D'Agostino RB Sr, Dankner R, Davey-Smith G, Deeg D, Dekker JM, Engström G, Folsom AR, Fowkes FG, 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, Lawlor DA, Meade TW, Nissinen A, Nordestgaard BG, Onat A, Panagiotakos DB, Psaty BM, Rodriguez B, Rosengren A, Salomaa V, Kauhanen J, Salonen JT, Shaffer JA, Shea S, Ford I, Stehouwer CD, Strandberg TE, Tipping RW, Tosetto A, Wassertheil-Smoller S, Wennberg P, Westendorp RG, Whincup PH, Wilhelmsen L, Woodward M, Lowe GD, Wareham NJ, Khaw KT, Sattar N, Packard CJ, Gudnason V, Ridker PM, Pepys MB, Thompson SG, Danesh J, Tipping RW, Folsom AR, Chambless LE, Ballantyne CM, Astor BC, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C, Atkins R, Barr EL, Shaw JE, Zimmet PZ, Whincup PH, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Mayr A, Schett G, Ebrahim S, Lawlor DA, Yarnell JW, Gallacher J, Cushman M, Psaty BM, Tracy R, Tybjærg-Hansen A, Frikke-Schmidt R, Benn M, Nordestgaard BG, Giampaoli S, Palmieri L, Panico S, Vanuzzo D, Pilotto L, Fowkes FG, Lee AJ, Khaw KT, Wareham NJ, Brenner H, Schöttker B, Müller H, Rothenbacher D, Jansson JH, Wennberg P, Nissinen A, Donfrancesco C, Giampaoli S, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Woodward M, D'Agostino RB Sr, Wolf PA, Benjamin EJ, Pencina MJ, D'Agostino RB Sr, Wolf PA, Vasan RS, Benjamin EJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, Wilhelmsen L, Eriksson H, Svärdsudd K, Welin L, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Björkelund C, Lissner L, Bengtsson C, Cremer P, Nagel D, Tilvis RS, Strandberg TE, Kiyohara Y, Arima H, Doi Y, Ninomiya T, Rodriguez B, Dekker JM, Nijpels G, Stehouwer CD, Iso H, Kitamura A, Yamagishi K, Noda H, Kauhanen J, Salonen JT, Deeg D, Bremmer MA, Meade TW, Cooper JA, Hedblad B, Nilsson P, Engström G, Cushman M, Folsom AR, Psaty BM, Shea S, Döring A, Koenig W, Meisinger C, Wilhelmsen L, Rosengren A, Lappas G, Kuller LH, Grandits G, Gillum RF, Mussolino M, Meade TW, Cooper JA, Knottenbelt C, Cooper JA, Bauer KA, Davidson KW, Kirkland S, Shaffer JA, Shimbo D, Kitamura A, Iso H, Sato S, Bakker SJ, Gansevoort RT, Hillege HL, Amouyel P, Arveiler D, Evans A, Ferrières J, Schulte H, Assmann G, Packard CJ, Sattar N, Westendorp RG, Buckley BM, Cantin B, Lamarche B, Després JP, Dagenais GR, Barrett-Connor E, Wingard DL, Bettencourt R, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Eiriksdottir G, Witteman J, Kardys I, Dehghan A, Hofman A, Tunstall-Pedoe H, Tavendale R, Lowe GD, Woodward M, Howard BV, Zhang Y, Best L, Umans J, Ben-Shlomo Y, Davey-Smith G, Onat A, Can G, Meade TW, Ingelsson E, Basu S, Cederholm T, Byberg L, Gaziano JM, Stampfer M, Ridker PM, Gaziano JM, Ridker PM, Tosetto A, Rodeghiero F, Wassertheil-Smoller S, Kaplan R, Kooperberg C, Marmot M, Clarke R, Collins R, Fletcher A, Brunner E, Shipley M, Kivimäki M, Ridker PM, Buring J, Cook N, Ford I, Shepherd J, Cobbe SM, Robertson M, Feskens EJ, Kromhout D, Walker M, Watson S, Alexander M, Butterworth AS, Di Angelantonio E, Franco OH, Gao P, Gobin R, Haycock P, Kaptoge S, Kondapally Seshasai SR, Lewington S, Pennells L, Rapsomaniki E, Sarwar N, Thompson A, Thompson SG, Walker M, Watson S, White IR, Wood AM, Wormser D, Zhao X, Danesh J.

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.).

PMID:
23034020
PMCID:
PMC3714101
DOI:
10.1056/NEJMoa1107477
[Indexed for MEDLINE]
Free PMC Article

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