Circulating TNFα levels in older men and women do not show independent prospective relations with MI or stroke

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.

Abbreviations: TNFα, tumour necrosis factor alpha, MI, myocardial infarction, CVD, cardiovascular disease, CHD, coronary heart disease, OR, odds ratio, IQR, inter-quartile range, CI, confidence interval, CRP, C-reactive protein, IL-6, interleukin-6, BMI, body mass index, SBP, systolic blood pressure, DBP, diastolic blood pressure, t-PA, tissue plasminogen activator, LR, likelihood ratio

Keywords: Myocardial infarction, Stroke, Inflammation, Epidemiology, TNFα, Prospective, Cohort