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

Stephen Kaptoge, Emanuele Di Angelantonio, Gordon Lowe, Mark B. Pepys, Simon G. Thompson, Rory Collins, John Danesh, R. W. Tipping, C. E. Ford, S. L. Pressel, G. Walldius, I. Jungner, A. R. Folsom, L. Chambless, C. M. Ballantyne, D. Panagiotakos, C. Pitsavos, C. Chrysohoou, C. Stefanadis, M. W. KnuimanU. Goldbourt, M. Benderly, D. Tanne, P. Whincup, S. G. Wannamethee, R. W. Morris, S. Kiechl, J. Willeit, A. Mayr, G. Schett, N. Wald, S. Ebrahim, D. Lawlor, J. Yarnell, J. Gallacher, E. Casiglia, V. Tikhonoff, P. J. Nietert, S. E. Sutherland, D. L. Bachman, J. E. Keil, M. Cushman, B. M. Psaty, R. Tracy, A. Tybjærg-Hansen, B. G. Nordestgaard, J. Zacho, R. Frikke-Schmidt, S. Giampaoli, L. Palmieri, S. Panico, D. Vanuzzo, L. Pilotto, A. Gómez De La Cámara, J. A. Gómez Gerique, L. Simons, J. McCallum, Y. Friedlander, F. G R Fowkes, A. Lee, J. Taylor, J. M. Guralnik, C. L. Phillips, R. B. Wallace, J. M. Guralnik, C. L. Phillips, D. G. Blazer, J. M. Guralnik, C. L. Phillips, C. L. Phillips, J. M. Guralnik, K. T. Khaw, H. Brenner, E. Raum, H. Müller, D. Rothenbacher, J. H. Jansson, P. Wennberg, A. Nissinen, C. Donfrancesco, S. Giampaoli, V. Salomaa, K. Harald, P. Jousilahti, E. Vartiainen, M. Woodward, R. B. D’Agostino, P. A. Wolf, R. S. Vasan, E. J. Benjamin, E. M. Bladbjerg, T. Jørgensen, L. Møller, J. Jespersen, R. Dankner, A. Chetrit, F. Lubin, A. Rosengren, L. Wilhelmsen, G. Lappas, H. Eriksson, C. Björkelund, L. Lissner, C. Bengtsson, P. Cremer, D. Nagel, R. S. Tilvis, T. E. Strandberg, Y. Kiyohara, H. Arima, Y. Doi, T. Ninomiya, B. Rodriguez, J. Dekker, G. Nijpels, C. D A Stehouwer, E. Rimm, J. K. Pai, S. Sato, H. Iso, A. Kitamura, H. Noda, U. Goldbourt, J. T. Salonen, K. Nyyssönen, T. P. Tuomainen, J. A. Laukkanen, D. J H Deeg, M. A. Bremmer, T. W. Meade, J. A. Cooper, B. Hedblad, G. Berglund, G. Engström, W. M M Verschuren, A. Blokstra, M. Cushman, A. R. Folsom, B. M. Psaty, S. Shea, A. Döring, W. Koenig, C. Meisinger, W. M M Verschuren, A. Blokstra, H. B. Bueno-De-Mesquita, L. Wilhelmsen, A. Rosengren, G. Lappas, L. H. Kuller, G. Grandits, R. Selmer, A. Tverdal, W. Nystad, R. F. Gillum, M. Mussolino, E. Rimm, S. Hankinson, J. E. Manson, J. K. Pai, V. Salomaa, K. Harald, P. Jousilahti, E. Vartiainen, T. W. Meade, J. A. Cooper, C. Knottenbelt, J. A. Cooper, K. A. Bauer, K. Davidson, S. Kirkland, J. Shaffer, M. R. Korin, S. Sato, A. Kitamura, Y. Naito, H. Iso, I. Holme, R. Selmer, A. Tverdal, W. Nystad, H. Nakagawa, K. Miura, P. Ducimetiere, X. Jouven, G. Luc, C. J. Crespo, M. R. Garcia-Palmieri, P. Amouyel, D. Arveiler, A. Evans, J. Ferrieres, H. Schulte, G. Assmann, C. J. Packard, N. Sattar, R. G. Westendorp, B. M. Buckley, B. Cantin, B. Lamarche, J. P. Després, G. R. Dagenais, E. Barrett-Connor, D. L. Wingard, R. R. Bettencourt, V. Gudnason, T. Aspelund, G. Sigurdsson, B. Thorsson, M. Trevisan, J. Witteman, I. Kardys, M. M B Breteler, A. Hofman, H. Tunstall-Pedoe, R. Tavendale, G. Lowe, M. Woodward, B. V. Howard, Y. Zhang, L. Best, J. Umans, Y. Ben-Shlomo, G. Davey-Smith, A. Onat, T. W. Meade, I. Njølstad, E. B. Mathiesen, M. L. Løchen, T. Wilsgaard, E. Ingelsson, S. Basu, T. Cederholm, L. Byberg, J. M. Gaziano, M. Stampfer, P. M. Ridker, J. M. Gaziano, P. M. Ridker, H. Ulmer, G. Diem, H. Concin, A. Tosetto, F. Rodeghiero, S. Wassertheil-Smoller, J. E. Manson, M. Marmot, R. Clarke, R. Collins, A. Fletcher, E. Brunner, M. Shipley, P. M. Ridker, J. Buring, J. Shepherd, S. Cobbe, I. Ford, M. Robertson, Y. He, A. Marin Ibañez, E. J M Feskens, M. Walker, S. Watson, R. Collins, E. Di Angelantonio, S. Erqou, S. Kaptoge, S. Lewington, L. Pennells, P. L. Perry, K. K. Ray, N. Sarwar, M. Alexander, A. Thompson, S. G. Thompson, M. Walker, S. Watson, I. R. White, A. M. Wood, J. Danesh

Research output: Contribution to journalArticlepeer-review

1690 Scopus citations


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 Loge 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 loge 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.

Original languageEnglish (US)
Pages (from-to)132-140
Number of pages9
JournalThe Lancet
Issue number9709
StatePublished - 2010

Bibliographical note

Funding Information:
The ERFC Coordinating Centre is underpinned by a programme grant from the British Heart Foundation and supported by specific grants from the UK Medical Research Council and the BUPA Foundation, and an unrestricted educational grant from GlaxoSmithKline. A variety of sources have supported recruitment, follow-up, and laboratory measurements in the 116 cohorts contributing to the ERFC. Investigators of several of these studies have contributed to a list of some of these funding sources . We thank Juan-Pablo Casas, Aroon Hingorani, and Liam Smeeth for helpful comments. The writing committee accepts full responsibility for the content of this report.

Publisher Copyright:
© 2010, Lancet Publishing Group. All rights reserved.


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