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.
Original language | English |
---|---|
Pages (from-to) | 132-140 |
Number of pages | 9 |
Journal | The Lancet |
Volume | 375 |
Issue number | 9709 |
DOIs | |
Publication status | Published - 1 Jan 2010 |
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C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality : An individual participant meta-analysis. / Kaptoge, Stephen; Di Angelantonio, Emanuele; Lowe, Gordon; Pepys, Mark B.; Thompson, Simon G.; Collins, Rory; Danesh, John; 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.; Knuiman, M. W.; Goldbourt, U.; Benderly, M.; Tanne, D.; Whincup, P.; Wannamethee, S. G.; Morris, R. W.; Kiechl, S.; Willeit, J.; Mayr, A.; Schett, G.; Wald, N.; Ebrahim, S.; Lawlor, D.; Yarnell, J.; Gallacher, J.; Casiglia, E.; Tikhonoff, V.; Nietert, P. J.; Sutherland, S. E.; Bachman, D. L.; Keil, J. E.; Cushman, M.; Psaty, B. M.; Tracy, R.; Tybjærg-Hansen, A.; Nordestgaard, B. G.; Zacho, J.; Frikke-Schmidt, R.; Giampaoli, S.; Palmieri, L.; Panico, S.; Vanuzzo, D.; Pilotto, L.; De La Cámara, A. Gómez; Gómez Gerique, J. A.; Simons, L.; McCallum, J.; Friedlander, Y.; Fowkes, F. G.R.; Lee, A.; Taylor, J.; Guralnik, J. M.; Phillips, C. L.; Wallace, R. B.; Blazer, D. G.; Khaw, K. T.; Brenner, H.; Raum, E.; Müller, H.; Rothenbacher, D.; Jansson, J. H.; Wennberg, P.; Nissinen, A.; Donfrancesco, C.; Harald, K.; Jousilahti, P.; Vartiainen, E.; Woodward, M.; D’Agostino, R. B.; Wolf, P. A.; Vasan, R. S.; Rosengren, A.; Bladbjerg, E. M.; 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, R. S.; Strandberg, T. E.; Kiyohara, Y.; Arima, H.; Doi, Y.; Ninomiya, T.; Rodriguez, B.; Dekker, J.; Nijpels, G.; Stehouwer, C. D.A.; Rimm, E.; Pai, J. K.; Sato, S.; Iso, H.; Kitamura, A.; Noda, H.; Salonen, J. T.; Nyyssönen, K.; Tuomainen, T. P.; Laukkanen, J. A.; Deeg, D. J.H.; Bremmer, M. A.; Meade, T. W.; Cooper, J. A.; Hedblad, B.; Berglund, G.; Engström, G.; Verschuren, W. M.M.; Blokstra, A.; Shea, S.; Döring, A.; Koenig, W.; Meisinger, C.; Bueno-De-Mesquita, H. B.; Kuller, L. H.; Grandits, G.; Selmer, R.; Tverdal, A.; Nystad, W.; Gillum, R. F.; Mussolino, M.; Hankinson, S.; Manson, J. E.; Knottenbelt, C.; Bauer, K. A.; Davidson, K.; Kirkland, S.; Shaffer, J.; Korin, M. R.; Naito, Y.; Holme, I.; Nakagawa, H.; Miura, K.; Ducimetiere, P.; Jouven, X.; Luc, G.; Crespo, C. J.; Garcia-Palmieri, M. R.; Amouyel, P.; Arveiler, D.; Evans, A.; Ferrieres, J.; Schulte, H.; Assmann, G.; Packard, C. J.; Sattar, N.; Westendorp, R. G.; Buckley, B. M.; Cantin, B.; Lamarche, B.; Després, J. P.; Dagenais, G. R.; Barrett-Connor, E.; Wingard, D. L.; Bettencourt, R. R.; Gudnason, V.; Aspelund, T.; Sigurdsson, G.; Thorsson, B.; Trevisan, M.; Witteman, J.; Kardys, I.; Breteler, M. M.B.; Hofman, A.; Tunstall-Pedoe, H.; Tavendale, R.; Howard, B. V.; Zhang, Y.; Best, L.; Umans, J.; Ben-Shlomo, Y.; Davey-Smith, G.; Onat, A.; Njølstad, I.; Mathiesen, E. B.; Løchen, M. L.; Wilsgaard, T.; Ingelsson, E.; Basu, S.; Cederholm, T.; Byberg, L.; Gaziano, J. M.; Stampfer, M.; Ridker, P. M.; 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, E. J.M.; Walker, M.; Watson, S.; Erqou, S.; Lewington, S.; Pennells, L.; Perry, P. L.; Ray, K. K.; Sarwar, N.; Alexander, M.; Thompson, A.; White, I. R.; Wood, A. M.
In: The Lancet, Vol. 375, No. 9709, 01.01.2010, p. 132-140.Research output: Contribution to journal › Article › Academic › peer-review
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 - Rosengren, A.
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.
PY - 2010/1/1
Y1 - 2010/1/1
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
U2 - 10.1016/S0140-6736(09)61717-7
DO - 10.1016/S0140-6736(09)61717-7
M3 - Article
C2 - 20031199
AN - SCOPUS:73449130797
VL - 375
SP - 132
EP - 140
JO - Lancet
JF - Lancet
SN - 0140-6736
IS - 9709
ER -