Circulating TNFα levels in older men and women do not show independent prospective relations with MI or stroke
Received 1 October 2008; received in revised form 20 November 2008; accepted 1 December 2008. published online 12 January 2009.
Abstract
Background
Tumour necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in atherosclerotic plaque formation. We investigated whether circulating TNFα 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 TNFα 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
TNFα levels were 11.4% (95% CI 9.5, 13.3%) higher among MI cases than controls; geometric mean 1.84pg/mL compared to 1.63pg/mL, p (difference)<0.001. Participants in the top third of baseline TNFα 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 TNFα and stroke was observed.
Conclusions
This study suggests that TNFα is not a strong independent risk marker for MI, and is not associated with risk of stroke.
aUCL Department Primary Care & Population Health, Royal Free & University College Medical School, London, UK
bDivision of Community Health Sciences, St George's, University of London, UK
cDivision of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK
dNon-Communicable Diseases Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
Corresponding author at: British Regional Heart Study, UCL Department Primary Care & Population Health, Royal Free & University College Medical School, Rowland Hill Street, London NW3 2PF, UK. Tel.: +44 207 830 2230; fax: +44 20 7794 1224.