title: Interleukin 18 and coronary heart disease: prospective study and systematic review.
abstract: OBJECTIVE
  Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis.
  
  
  METHODS
  We measured baseline IL-18 levels in stored serum samples of subjects from a case-control study nested within a prospective study of 5661 men aged 40-59 years recruited from general practices in 18 British towns in 1978-1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls).
  
  
  RESULTS
  IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.64 [corrected] (95% CI 1.48, 1.83) [corrected] after age adjustment, 1.39 (95% CI 1.25, [corrected] 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.53) [corrected] after additional adjustment for inflammatory markers.
  
  
  CONCLUSIONS
  Circulating IL-18 is prospectively and independently associated with CVD risk.
authors.affiliation: Department of Primary Care and Population Health, University College London, London NW3 2PF, UK. B.jefferis@ucl.ac.uk
authors.forename: Barbara J M H
authors.initials: BJ
authors.lastname: Jefferis
authors.forename: Olia
authors.initials: O
authors.lastname: Papacosta
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Owen
authors.forename: S Goya
authors.initials: SG
authors.lastname: Wannamethee
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Lucy T
authors.initials: LT
authors.lastname: Lennon
authors.forename: Andrew
authors.initials: A
authors.lastname: Thomson
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics* / Q000503:physiopathology; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007249:Inflammation; D020382:Interleukin-18 / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D006113:United Kingdom
chemical_list: D020382:Interleukin-18