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; L. Simons; A. Lee; C. L. Phillips; P. A. Wolf; G. Lappas; C. D. A. Stehouwer; Author collaboration

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, L. Simons, A. Lee, C. L. Phillips, P. A. Wolf, G. Lappas, C. D. A. Stehouwer, Author collaboration

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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, 27769 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(c) 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, 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.

Original language	English
Pages (from-to)	132-140
Number of pages	9
Journal	Lancet
Volume	375
Issue number	9709
DOIs	https://doi.org/10.1016/S0140-6736(09)61717-7
Publication status	Published - 9 Jan 2010

Keywords

Low-density-lipoprotein
Cardiovascular-disease
Regression dilution
Plasma-fibrinogen
Nonvascular mortality
Independent predictor
Inflammation
Associations
Markers
Women

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10.1016/S0140-6736(09)61717-7

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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., ... Author collaboration (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet, 375(9709), 132-140. https://doi.org/10.1016/S0140-6736(09)61717-7

@article{3b5e97a1befe40c1bc8fb0e09dc912c1,

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, 27769 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(c) 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, 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.",

keywords = "Low-density-lipoprotein, Cardiovascular-disease, Regression dilution, Plasma-fibrinogen, Nonvascular mortality, Independent predictor, Inflammation, Associations, Markers, Women",

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 L. Simons and A. Lee and Phillips, {C. L.} and Wolf, {P. A.} and G. Lappas and Stehouwer, {C. D. A.} and {Author collaboration}",

year = "2010",

month = jan,

day = "9",

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

language = "English",

volume = "375",

pages = "132--140",

journal = "Lancet",

issn = "0140-6736",

publisher = "Elsevier Science",

number = "9709",

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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, Simons, L, Lee, A, Phillips, CL, Wolf, PA, Lappas, G, Stehouwer, CDA & Author collaboration 2010, 'C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis', Lancet, vol. 375, no. 9709, pp. 132-140. https://doi.org/10.1016/S0140-6736(09)61717-7

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 - Simons, L.

AU - Lee, A.

AU - Phillips, C. L.

AU - Wolf, P. A.

AU - Lappas, G.

AU - Stehouwer, C. D. A.

AU - Author collaboration

PY - 2010/1/9

Y1 - 2010/1/9

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, 27769 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(c) 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, 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.

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, 27769 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(c) 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, 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.

KW - Low-density-lipoprotein

KW - Cardiovascular-disease

KW - Regression dilution

KW - Plasma-fibrinogen

KW - Nonvascular mortality

KW - Independent predictor

KW - Inflammation

KW - Associations

KW - Markers

KW - Women

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

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

M3 - Article

C2 - 20031199

SN - 0140-6736

VL - 375

SP - 132

EP - 140

JO - Lancet

JF - Lancet

IS - 9709

ER -