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dc.contributor.authorKaptoge, Stephenen
dc.contributor.authorSeshasai, Sreenivasa Rao Kondapallyen
dc.contributor.authorGao, Peien
dc.contributor.authorFreitag, Danielen
dc.contributor.authorButterworth, Adamen
dc.contributor.authorBorglykke, Andersen
dc.contributor.authorDi, Angelantonio Emanueleen
dc.contributor.authorGudnason, Vilmunduren
dc.contributor.authorRumley, Annen
dc.contributor.authorLowe, Gordon DOen
dc.contributor.authorJørgensen, Torbenen
dc.contributor.authorDanesh, Johnen
dc.date.accessioned2014-11-12T12:24:24Z
dc.date.available2014-11-12T12:24:24Z
dc.date.issued2013-09-11en
dc.identifier.citationEuropean Heart Journal 35.9, p578-589. DOI: 10.1093/eurheartj/eht367en
dc.identifier.issn0195-668X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246352
dc.description.abstractAims Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta-analysis of prospective studies. Methods and Results Interleukin-6 (IL-6), interleukin-18 (IL-18), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor–alpha (TNF-α) were measured at baseline in a case-cohort study of 1514 participants and 833 incident CHD events within population-based prospective cohorts at the Danish Research Centre for Prevention and Health. Age- and sex-adjusted hazard ratios (HR) for CHD per 1-SD higher log-transformed baseline levels were: 1.37 (95% CI, 1.21-1.54) for IL-6, 1.26 (1.11-1.44) for IL-18, 1.30 (1.16-1.46) for MMP-9, 1.01 (0.89-1.15) for sCD40L, and 1.13 (1.01-1.27) for TNF-α. Multivariable adjustment for conventional vascular risk factors attenuated the HRs to: 1.26 (1.08-1.46) for IL-6, 1.12 (0.95-1.31) for IL-18, 1.21 (1.05-1.39) for MMP-9, 0.93 (0.78-1.11) for sCD40L, and 1.14 (1.00-1.31) for TNF-α. In meta-analysis of up to 29 population-based prospective studies, adjusted relative risks for non-fatal MI or CHD death per 1-SD higher levels were: 1.25 (1.19-1.32) for IL-6; 1.13 (1.05-1.20) for IL-18; 1.07 (0.97-1.19) for MMP- 9; 1.07 (0.95-1.21) for sCD40L and 1.17 (1.09-1.25) for TNF-α. Conclusions Several different pro-inflammatory cytokines are each associated with CHD risk independent of conventional risk factors and in an approximately log-linear manner. The findings lend support to the inflammation hypothesis in vascular disease, but further studies are needed to assess causality.
dc.description.sponsorshipThis work was supported by a grant from the British Heart Foundation (RG/08/014), the U.K. Medical Research Council, and the U.K. National Institute of Health Research Cambridge Biomedical Research Centre.
dc.languageEnglishen
dc.language.isoenen
dc.publisherOxford Journals
dc.subjectInflammationen
dc.subjectCHDen
dc.subjectCytokinesen
dc.subjectRisk factorsen
dc.subjectMeta-analysisen
dc.titleInflammatory Cytokines and Risk of Coronary Heart Disease: New Prospective Study and Updated Meta-Analysisen
dc.typeArticle
dc.description.versionThis is the accepted manuscript. The final version is available from OUP at http://eurheartj.oxfordjournals.org/content/35/9/578.en
prism.endingPage589
prism.publicationDate2013en
prism.publicationNameEuropean Heart Journalen
prism.startingPage578
prism.volume35en
dc.rioxxterms.funderBHF
dc.rioxxterms.funderMRC
dc.rioxxterms.funderNIHR
dc.rioxxterms.projectidRG/08/014
rioxxterms.versionofrecord10.1093/eurheartj/eht367en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2013-09-11en
dc.contributor.orcidKaptoge, Stephen [0000-0002-1155-4872]
dc.contributor.orcidButterworth, Adam [0000-0002-6915-9015]
dc.contributor.orcidDanesh, John [0000-0003-1158-6791]
dc.identifier.eissn1522-9645
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (RG/08/014/24067)


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