title: Circulating TNFalpha levels in older men and women do not show independent prospective relations with MI or stroke.
abstract: BACKGROUND
  Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFalpha is prospectively associated with myocardial infarction (MI) or stroke in the older general population, independently of established cardiovascular risk factors and other inflammatory markers related to CHD risk.
  
  
  METHODS
  We measured baseline TNFalpha concentrations in stored serum samples of 362 incident MI and 299 incident stroke cases and controls (2 per case, frequency matched by age, gender and town) who were 'nested' in parallel prospective studies of 4252 men and 4286 women aged 60-79 years assessed in general practices in 24 British towns in 1998-2000 and followed up for an average 7 years for fatal and non-fatal MI and stroke.
  
  
  RESULTS
  TNFalpha levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84 pg/mL compared to 1.63 pg/mL, p (difference)<0.001. Participants in the top third of baseline TNFalpha levels had an age-adjusted odds ratio (OR) for MI of 1.75 (95%CI 1.22, 2.49) compared with those in the bottom third, which was reduced to 1.47 (95%CI 1.01, 2.14) after adjustment for established cardiovascular risk factors. However, further adjustment for C-reactive protein and interleukin-6 abolished the association OR 1.33 (95% CI 0.91, 1.66) and the linear trend. Excluding subjects with pre-existing CVD did not materially affect results. No significant association between TNFalpha and stroke was observed.
  
  
  CONCLUSIONS
  This study suggests that TNFalpha is not a strong independent risk marker for MI, and is not associated with risk of stroke.
authors.affiliation: UCL Department Primary Care & Population Health, Royal Free & University College Medical School, London, UK. b.jefferis@pcps.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: Lucy T
authors.initials: LT
authors.lastname: Lennon
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Thomson
authors.forename: Claire
authors.initials: C
authors.lastname: Carson
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Gordon D O
authors.initials: GD
authors.lastname: Lowe
mesh_terms: D000368:Aged; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha