title: Prospective study of IL-18 and risk of MI and stroke in men and women aged 60-79 years: a nested case-control study.
abstract: OBJECTIVE
  IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD. We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population.
  
  
  METHODS
  A case-control study was nested within a prospective cohort of men and women aged 60-79 years recruited from general practices in 25 British towns in 1998-2000 and followed-up for 7.5 years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI (n=364) or stroke (n=300) and two controls per case.
  
  
  RESULTS
  Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84 pg/mL (IQR 316.25, 537.44) compared to 386.90 pg/mL (IQR 296.54, 482.33), p(difference)=0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44). Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age.
  
  
  CONCLUSIONS
  Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.
authors.affiliation: British Regional Heart Study, UCL Department of Primary Care & Population Health, UCL, London NW3 2PF, UK. b.jefferis@ucl.ac.uk
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Jefferis
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: S Goya
authors.initials: SG
authors.lastname: Wannamethee
authors.forename: Ann
authors.initials: A
authors.lastname: Rumley
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications; D016017:Odds Ratio; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000150:complications
chemical_list: D020382:Interleukin-18