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Lancet. 2010 Jan 9;375(9709):132-40. doi: 10.1016/S0140-6736(09)61717-7. Epub 2009 Dec 22.

C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.

Collaborators (273)

Tipping RW, Ford CE, Pressel SL, Walldius G, Jungner I, Folsom AR, Chambless L, Ballantyne CM, Panagiotakos D, Pitsavos C, Chrysohoou C, Stefanadis C, Knuiman MW, Goldbourt U, Benderly M, Tanne D, Whincup P, Wannamethee SG, Morris RW, Kiechl S, Willeit J, Mayr A, Schett G, Wald N, Ebrahim S, Lawlor D, Yarnell J, Gallacher J, Casiglia E, Tikhonoff V, Nietert PJ, Sutherland SE, Bachman DL, Keil JE, Cushman M, Psaty BM, Tracy R, Tybjaerg-Hansen A, Nordestgaard BG, Zacho J, Frikke-Schmidt R, Giampaoli S, Palmieri L, Panico S, Vanuzzo D, Pilotto L, de la Cámara AG, Gerique JA, Simons L, McCallum J, Friedlander Y, Fowkes FG, Lee A, Taylor J, Guralnik JM, Phillips CL, Wallace RB, Guralnik JM, Phillips CL, Blazer DG, Guralnik JM, Phillips CL, Phillips CL, Guralnik JM, Khaw KT, Brenner H, Raum E, 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, Wolf PA, Vasan RS, Benjamin EJ, Bladbjerg EM, Jørgensen T, Møller L, Jespersen J, Dankner R, Chetrit A, Lubin F, 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 J, Nijpels G, Stehouwer CD, Rimm E, Pai JK, Sato S, Iso H, Kitamura A, Noda H, Goldbourt U, Salonen JT, Nyyssönen K, Tuomainen TP, Laukkanen JA, Deeg DJ, Bremmer MA, Meade TW, Cooper JA, Hedblad B, Berglund G, Engström G, Verschuren WM, Blokstra A, Cushman M, Folsom AR, Psaty BM, Shea S, Döring A, Koenig W, Meisinger C, Verschuren WM, Blokstra A, Bueno-de-Mesquita HB, Wilhelmsen L, Rosengren A, Lappas G, Kuller LH, Grandits G, Selmer R, Tverdal A, Nystad W, Gillum RF, Mussolino M, Rimm E, Hankinson S, Manson JE, Pai JK, Salomaa V, Harald K, Jousilahti P, Vartiainen E, Meade TW, Cooper JA, Knottenbelt C, Cooper JA, Bauer KA, Davidson K, Kirkland S, Shaffer J, Korin MR, Sato S, Kitamura A, Naito Y, Iso H, Holme I, Selmer R, Tverdal A, Nystad W, Nakagawa H, Miura K, Ducimetiere P, Jouven X, Luc G, Crespo CJ, Garcia-Palmieri MR, Amouyel P, Arveiler D, Evans A, Ferrieres 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 RR, Gudnason V, Aspelund T, Sigurdsson G, Thorsson B, Trevisan M, Witteman J, Kardys I, Breteler MM, Hofman A, Tunstall-Pedoe H, Tavendale R, Lowe G, Woodward M, Howard BV, Zhang Y, Best L, Umans J, Ben-Shlomo Y, Davey-Smith G, Onat A, Meade TW, Njølstad I, Mathiesen EB, Løchen ML, Wilsgaard T, Ingelsson E, Basu S, Cederholm T, Byberg L, Gaziano JM, Stampfer M, Ridker PM, Gaziano JM, Ridker PM, Ulmer H, Diem G, Concin H, Tosetto A, Rodeghiero F, Wassertheil-Smoller S, Manson JE, Marmot IM, Clarke R, Collins R, Fletcher A, Brunner E, Shipley M, Ridker PM, Buring J, Shepherd J, Cobbe S, Ford I, Robertson M, He Y, Ibañez AM, Feskens EJ, Walker M, Watson S, Collins R, Di Angelantonio E, Erqou S, Kaptoge S, Lewington S, Pennells L, Perry PL, Ray KK, Sarwar N, Alexander M, Thompson A, Thompson SG, Walker M, Watson S, White IR, Wood AM, Danesh J.

Author information

  • 1Emerging Risk Factors Collaboration Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.

Abstract

BACKGROUND:

Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances.

METHODS:

We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels.

RESULTS:

Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality.

INTERPRETATION:

CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.

FUNDING:

British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

Copyright 2010 Elsevier Ltd. All rights reserved.

Comment in

PMID:
20031199
[PubMed - indexed for MEDLINE]
PMCID:
PMC3162187
Free PMC Article

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