Lancet. 2010 Jan 9;375(9709):132-40. Epub 2009 Dec 22.
C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.
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.
Source
Emerging 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.
- PMID:
- 20031199
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3162187
Free PMC ArticleFigure 2
Cross-sectional associations between geometric mean C-reactive protein (CRP) concentration and some conventional risk factors and other characteristics
Mean CRP concentration was adjusted to age 50 years. Error bars represent the 95% CIs. BP=blood pressure. r=Pearson's correlation coefficient (95% CI) for association between the risk marker and loge CRP concentration in men and women combined.
Lancet. Lancet;375(9709):132-140.
Figure 4
Age-adjusted and sex-adjusted risk ratios for mortality from vascular and non-vascular diseases per three-fold higher usual C-reactive protein (CRP) concentration
Data are numbers, unless otherwise indicated. Risk ratios (boxes) were adjusted only for age, and stratified (when appropriate), by sex and trial group. Studies with fewer than ten cases of any outcome were excluded from the analysis of that outcome. The risk ratios are presented per 1·11 higher loge CRP (ie, 1-SD), corresponding to a three-fold higher CRP concentration. Horizontal lines represent the 95% CIs. The sizes of the boxes are proportional to the inverse of the variance of the risk ratios.
Lancet. Lancet;375(9709):132-140.
Figure 1
Geometric mean C-reactive protein (CRP) concentration in men and women according to cohort and assay source (A) and within 5-year bands adjusted for cohort (B)
Data from the third National Health and Nutrition Examination Survey (NHANESIII) and Population Study of Women in Göteborg (GOTOW) are not represented in the graph because they did not use high sensitivity CRP assays. 19 NS=not stated. Error bars represent the 95% CIs.
Lancet. Lancet;375(9709):132-140.
Figure 3
Risk ratios for major vascular and non-vascular outcomes by quantiles of C-reactive protein (CRP) concentration, with different degree of adjustment for potential confounders
Adjusted study-specific loge risk ratios were combined by use of multivariate random-effects meta-analysis. The adjustments were age, sex, and study only (A); age, sex, study, systolic blood pressure, smoking, history of diabetes, body-mass index, concentrations of loge triglycerides, non-HDL cholesterol, and HDL cholesterol, and alcohol consumption (B); and (A) plus (B) plus fibrinogen (C). Studies with fewer than ten cases of any outcome were excluded from the analysis of that outcome. Error bars represent the 95% CIs, calculated using floating absolute risk technique. The sizes of the boxes are proportional to the inverse of the variance of the risk ratios.
Lancet. Lancet;375(9709):132-140.
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