title: Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Interleukin-6 (IL-6), IL-18, matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis factor-α (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 (HRs) 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.
authors.affiliation: Strangeways Research Laboratory, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, CB1 8RN Cambridge, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaptoge
authors.forename: Sreenivasa Rao Kondapally
authors.initials: SR
authors.lastname: Seshasai
authors.forename: Pei
authors.initials: P
authors.lastname: Gao
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Freitag
authors.forename: Adam S
authors.initials: AS
authors.lastname: Butterworth
authors.forename: Anders
authors.initials: A
authors.lastname: Borglykke
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: John
authors.initials: J
authors.lastname: Danesh
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: CHD; Cytokines; Inflammation; Meta-analysis; Risk factors
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