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. Knuiman; U. 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; D. G. Blazer; K. T. Khaw; H. Brenner; E. Raum; H. Müller; D. Rothenbacher; J. H. Jansson; P. Wennberg; A. Nissinen; C. Donfrancesco; 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; 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; S. Shea; A. Döring; W. Koenig; C. Meisinger; H. B. Bueno-De-Mesquita; L. H. Kuller; G. Grandits; R. Selmer; A. Tverdal; W. Nystad; R. F. Gillum; M. Mussolino; S. Hankinson; J. E. Manson; C. Knottenbelt; K. A. Bauer; K. Davidson; S. Kirkland; J. Shaffer; M. R. Korin; Y. Naito; I. Holme; 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; B. V. Howard; Y. Zhang; L. Best; J. Umans; Y. Ben-Shlomo; G. Davey-Smith; A. Onat; 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; H. Ulmer; G. Diem; H. Concin; A. Tosetto; F. Rodeghiero; S. Wassertheil-Smoller; M. Marmot; R. Clarke; A. Fletcher; E. Brunner; M. Shipley; J. Buring; J. Shepherd; S. Cobbe; I. Ford; M. Robertson; Y. He; A. Marin Ibañez; E. J.M. Feskens; M. Walker; S. Watson; S. Erqou; S. Lewington; L. Pennells; P. L. Perry; K. K. Ray; N. Sarwar; M. Alexander; A. Thompson; I. R. White; A. M. Wood

doi:10.1016/S0140-6736(09)61717-7

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, D. G. Blazer, K. T. Khaw, H. Brenner, E. Raum, H. Müller, D. Rothenbacher, J. H. Jansson, P. Wennberg, A. Nissinen, C. Donfrancesco, 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, 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, S. Shea, A. Döring, W. Koenig, C. Meisinger, H. B. Bueno-De-Mesquita, L. H. Kuller, G. Grandits, R. Selmer, A. Tverdal, W. Nystad, R. F. Gillum, M. Mussolino, S. Hankinson, J. E. Manson, C. Knottenbelt, K. A. Bauer, K. Davidson, S. Kirkland, J. Shaffer, M. R. Korin, Y. Naito, I. Holme, 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, B. V. Howard, Y. Zhang, L. Best, J. Umans, Y. Ben-Shlomo, G. Davey-Smith, A. Onat, 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, H. Ulmer, G. Diem, H. Concin, A. Tosetto, F. Rodeghiero, S. Wassertheil-Smoller, M. Marmot, R. Clarke, A. Fletcher, E. Brunner, M. Shipley, J. Buring, J. Shepherd, S. Cobbe, I. Ford, M. Robertson, Y. He, A. Marin Ibañez, E. J.M. Feskens, M. Walker, S. Watson, S. Erqou, S. Lewington, L. Pennells, P. L. Perry, K. K. Ray, N. Sarwar, M. Alexander, A. Thompson, I. R. White, A. M. Wood

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2023 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	132-140
Número de páginas	9
Publicación	The Lancet
Volumen	375
N.º	9709
DOI	https://doi.org/10.1016/S0140-6736(09)61717-7
Estado	Published - 2010

Nota bibliográfica

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.

Funding Information:
JD has received research funding from the British Heart Foundation, BUPA Foundation, diaDexus, European Union, Evelyn Trust, Fogarty International Centre, GlaxoSmithKline, MRC, Merck, National Heart Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Roche, and the Wellcome Trust. RC is paid by the British Heart Foundation, National Health Service, and UK Biobank, and has received research funding and reimbursement of costs for attending scientific meetings (but no honoraria or consultancy payments) from AstraZeneca, Bayer, Bristol-Myers Squibb, British Heart Foundation, Cancer Research UK, European Union, Kadoorie Trust, MRC, Merck, Roche, Sanofi, Schering, Solvay, and UK Biobank. SGT has received research funding from MRC, National Institute for Health Research, BUPA, British Heart Foundation, and European Union. The other authors declare that they have no conflicts of interest.

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

ASJC Scopus Subject Areas

General Medicine

PubMed: MeSH publication types

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

ODS de las Naciones Unidas

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Kaptoge, S., Di Angelantonio, E., Lowe, G., Pepys, M. B., Thompson, S. G., Collins, R., Danesh, J., Tipping, R. W., Ford, C. E., Pressel, S. L., Walldius, G., Jungner, I., Folsom, A. R., Chambless, L., Ballantyne, C. M., Panagiotakos, D., Pitsavos, C., Chrysohoou, C., Stefanadis, C., ... Wood, A. M. (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis. The Lancet, 375(9709), 132-140. https://doi.org/10.1016/S0140-6736(09)61717-7

Kaptoge, S, Di Angelantonio, E, Lowe, G, Pepys, MB, Thompson, SG, Collins, R, Danesh, J, 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, Tybjærg-Hansen, A, Nordestgaard, BG, Zacho, J, Frikke-Schmidt, R, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Pilotto, L, De La Cámara, AG, Gómez Gerique, JA, Simons, L, McCallum, J, Friedlander, Y, Fowkes, FGR, Lee, A, Taylor, J, Guralnik, JM, Phillips, CL, Wallace, RB, Blazer, DG, Khaw, KT, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, JH, Wennberg, P, Nissinen, A, Donfrancesco, C, 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, CDA, Rimm, E, Pai, JK, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, JT, Nyyssönen, K, Tuomainen, TP, Laukkanen, JA, Deeg, DJH, Bremmer, MA, Meade, TW, Cooper, JA, Hedblad, B, Berglund, G, Engström, G, Verschuren, WMM, Blokstra, A, Shea, S, Döring, A, Koenig, W, Meisinger, C, Bueno-De-Mesquita, HB, Kuller, LH, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, RF, Mussolino, M, Hankinson, S, Manson, JE, Knottenbelt, C, Bauer, KA, Davidson, K, Kirkland, S, Shaffer, J, Korin, MR, Naito, Y, Holme, I, 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, MMB, Hofman, A, Tunstall-Pedoe, H, Tavendale, R, Howard, BV, Zhang, Y, Best, L, Umans, J, Ben-Shlomo, Y, Davey-Smith, G, Onat, A, Njølstad, I, Mathiesen, EB, Løchen, ML, Wilsgaard, T, Ingelsson, E, Basu, S, Cederholm, T, Byberg, L, Gaziano, JM, Stampfer, M, Ridker, PM, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Wassertheil-Smoller, S, Marmot, M, Clarke, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Shepherd, J, Cobbe, S, Ford, I, Robertson, M, He, Y, Marin Ibañez, A, Feskens, EJM, Walker, M, Watson, S, Erqou, S, Lewington, S, Pennells, L, Perry, PL, Ray, KK, Sarwar, N, Alexander, M, Thompson, A, White, IR & Wood, AM 2010, 'C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis', The Lancet, vol. 375, n.º 9709, pp. 132-140. https://doi.org/10.1016/S0140-6736(09)61717-7

@article{eece5e0147544ff3ae2f4b0ff5fb62c5,

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

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 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.",

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

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. Funding Information: JD has received research funding from the British Heart Foundation, BUPA Foundation, diaDexus, European Union, Evelyn Trust, Fogarty International Centre, GlaxoSmithKline, MRC, Merck, National Heart Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Roche, and the Wellcome Trust. RC is paid by the British Heart Foundation, National Health Service, and UK Biobank, and has received research funding and reimbursement of costs for attending scientific meetings (but no honoraria or consultancy payments) from AstraZeneca, Bayer, Bristol-Myers Squibb, British Heart Foundation, Cancer Research UK, European Union, Kadoorie Trust, MRC, Merck, Roche, Sanofi, Schering, Solvay, and UK Biobank. SGT has received research funding from MRC, National Institute for Health Research, BUPA, British Heart Foundation, and European Union. The other authors declare that they have no conflicts of interest. Publisher Copyright: {\textcopyright} 2010, Lancet Publishing Group. All rights reserved.",

year = "2010",

doi = "10.1016/S0140-6736(09)61717-7",

language = "English",

volume = "375",

pages = "132--140",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9709",

}

TY - JOUR

T1 - C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality

T2 - An individual participant meta-analysis

AU - Kaptoge, Stephen

AU - Di Angelantonio, Emanuele

AU - Lowe, Gordon

AU - Pepys, Mark B.

AU - Thompson, Simon G.

AU - Collins, Rory

AU - Danesh, John

AU - Tipping, R. W.

AU - Ford, C. E.

AU - Pressel, S. L.

AU - Walldius, G.

AU - Jungner, I.

AU - Folsom, A. R.

AU - Chambless, L.

AU - Ballantyne, C. M.

AU - Panagiotakos, D.

AU - Pitsavos, C.

AU - Chrysohoou, C.

AU - Stefanadis, C.

AU - Knuiman, M. W.

AU - Goldbourt, U.

AU - Benderly, M.

AU - Tanne, D.

AU - Whincup, P.

AU - Wannamethee, S. G.

AU - Morris, R. W.

AU - Kiechl, S.

AU - Willeit, J.

AU - Mayr, A.

AU - Schett, G.

AU - Wald, N.

AU - Ebrahim, S.

AU - Lawlor, D.

AU - Yarnell, J.

AU - Gallacher, J.

AU - Casiglia, E.

AU - Tikhonoff, V.

AU - Nietert, P. J.

AU - Sutherland, S. E.

AU - Bachman, D. L.

AU - Keil, J. E.

AU - Cushman, M.

AU - Psaty, B. M.

AU - Tracy, R.

AU - Tybjærg-Hansen, A.

AU - Nordestgaard, B. G.

AU - Zacho, J.

AU - Frikke-Schmidt, R.

AU - Giampaoli, S.

AU - Palmieri, L.

AU - Panico, S.

AU - Vanuzzo, D.

AU - Pilotto, L.

AU - De La Cámara, A. Gómez

AU - Gómez Gerique, J. A.

AU - Simons, L.

AU - McCallum, J.

AU - Friedlander, Y.

AU - Fowkes, F. G.R.

AU - Lee, A.

AU - Taylor, J.

AU - Guralnik, J. M.

AU - Phillips, C. L.

AU - Wallace, R. B.

AU - Blazer, D. G.

AU - Khaw, K. T.

AU - Brenner, H.

AU - Raum, E.

AU - Müller, H.

AU - Rothenbacher, D.

AU - Jansson, J. H.

AU - Wennberg, P.

AU - Nissinen, A.

AU - Donfrancesco, C.

AU - Harald, K.

AU - Jousilahti, P.

AU - Vartiainen, E.

AU - Woodward, M.

AU - D’Agostino, R. B.

AU - Wolf, P. A.

AU - Vasan, R. S.

AU - Benjamin, E. J.

AU - Bladbjerg, E. M.

AU - Jørgensen, T.

AU - Møller, L.

AU - Jespersen, J.

AU - Dankner, R.

AU - Chetrit, A.

AU - Lubin, F.

AU - Rosengren, A.

AU - Wilhelmsen, L.

AU - Lappas, G.

AU - Eriksson, H.

AU - Björkelund, C.

AU - Lissner, L.

AU - Bengtsson, C.

AU - Cremer, P.

AU - Nagel, D.

AU - Tilvis, R. S.

AU - Strandberg, T. E.

AU - Kiyohara, Y.

AU - Arima, H.

AU - Doi, Y.

AU - Ninomiya, T.

AU - Rodriguez, B.

AU - Dekker, J.

AU - Nijpels, G.

AU - Stehouwer, C. D.A.

AU - Rimm, E.

AU - Pai, J. K.

AU - Sato, S.

AU - Iso, H.

AU - Kitamura, A.

AU - Noda, H.

AU - Salonen, J. T.

AU - Nyyssönen, K.

AU - Tuomainen, T. P.

AU - Laukkanen, J. A.

AU - Deeg, D. J.H.

AU - Bremmer, M. A.

AU - Meade, T. W.

AU - Cooper, J. A.

AU - Hedblad, B.

AU - Berglund, G.

AU - Engström, G.

AU - Verschuren, W. M.M.

AU - Blokstra, A.

AU - Shea, S.

AU - Döring, A.

AU - Koenig, W.

AU - Meisinger, C.

AU - Bueno-De-Mesquita, H. B.

AU - Kuller, L. H.

AU - Grandits, G.

AU - Selmer, R.

AU - Tverdal, A.

AU - Nystad, W.

AU - Gillum, R. F.

AU - Mussolino, M.

AU - Hankinson, S.

AU - Manson, J. E.

AU - Knottenbelt, C.

AU - Bauer, K. A.

AU - Davidson, K.

AU - Kirkland, S.

AU - Shaffer, J.

AU - Korin, M. R.

AU - Naito, Y.

AU - Holme, I.

AU - Nakagawa, H.

AU - Miura, K.

AU - Ducimetiere, P.

AU - Jouven, X.

AU - Luc, G.

AU - Crespo, C. J.

AU - Garcia-Palmieri, M. R.

AU - Amouyel, P.

AU - Arveiler, D.

AU - Evans, A.

AU - Ferrieres, J.

AU - Schulte, H.

AU - Assmann, G.

AU - Packard, C. J.

AU - Sattar, N.

AU - Westendorp, R. G.

AU - Buckley, B. M.

AU - Cantin, B.

AU - Lamarche, B.

AU - Després, J. P.

AU - Dagenais, G. R.

AU - Barrett-Connor, E.

AU - Wingard, D. L.

AU - Bettencourt, R. R.

AU - Gudnason, V.

AU - Aspelund, T.

AU - Sigurdsson, G.

AU - Thorsson, B.

AU - Trevisan, M.

AU - Witteman, J.

AU - Kardys, I.

AU - Breteler, M. M.B.

AU - Hofman, A.

AU - Tunstall-Pedoe, H.

AU - Tavendale, R.

AU - Howard, B. V.

AU - Zhang, Y.

AU - Best, L.

AU - Umans, J.

AU - Ben-Shlomo, Y.

AU - Davey-Smith, G.

AU - Onat, A.

AU - Njølstad, I.

AU - Mathiesen, E. B.

AU - Løchen, M. L.

AU - Wilsgaard, T.

AU - Ingelsson, E.

AU - Basu, S.

AU - Cederholm, T.

AU - Byberg, L.

AU - Gaziano, J. M.

AU - Stampfer, M.

AU - Ridker, P. M.

AU - Ulmer, H.

AU - Diem, G.

AU - Concin, H.

AU - Tosetto, A.

AU - Rodeghiero, F.

AU - Wassertheil-Smoller, S.

AU - Marmot, M.

AU - Clarke, R.

AU - Fletcher, A.

AU - Brunner, E.

AU - Shipley, M.

AU - Buring, J.

AU - Shepherd, J.

AU - Cobbe, S.

AU - Ford, I.

AU - Robertson, M.

AU - He, Y.

AU - Marin Ibañez, A.

AU - Feskens, E. J.M.

AU - Walker, M.

AU - Watson, S.

AU - Erqou, S.

AU - Lewington, S.

AU - Pennells, L.

AU - Perry, P. L.

AU - Ray, K. K.

AU - Sarwar, N.

AU - Alexander, M.

AU - Thompson, A.

AU - White, I. R.

AU - Wood, A. M.

N1 - 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. Funding Information: JD has received research funding from the British Heart Foundation, BUPA Foundation, diaDexus, European Union, Evelyn Trust, Fogarty International Centre, GlaxoSmithKline, MRC, Merck, National Heart Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Roche, and the Wellcome Trust. RC is paid by the British Heart Foundation, National Health Service, and UK Biobank, and has received research funding and reimbursement of costs for attending scientific meetings (but no honoraria or consultancy payments) from AstraZeneca, Bayer, Bristol-Myers Squibb, British Heart Foundation, Cancer Research UK, European Union, Kadoorie Trust, MRC, Merck, Roche, Sanofi, Schering, Solvay, and UK Biobank. SGT has received research funding from MRC, National Institute for Health Research, BUPA, British Heart Foundation, and European Union. The other authors declare that they have no conflicts of interest. Publisher Copyright: © 2010, Lancet Publishing Group. All rights reserved.

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=73449130797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73449130797&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(09)61717-7

DO - 10.1016/S0140-6736(09)61717-7

M3 - Article

C2 - 20031199

AN - SCOPUS:73449130797

SN - 0140-6736

VL - 375

SP - 132

EP - 140

JO - The Lancet

JF - The Lancet

IS - 9709

ER -

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

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