Associations of circulating TNFalpha and IL-18 with myocardial infarction and cardiovascular risk markers: the Glasgow Myocardial Infarction Study.
BACKGROUND
There are a lack of data on the associations of circulating levels of TNFalpha and IL-18 with myocardial infarction (MI), and on the extent of confounding by classical and inflammatory risk markers.


METHODS
We measured TNFalpha and IL-18 in plasma from 446 MI cases and 477 age- and sex-matched controls from North Glasgow.


RESULTS
TNFalpha and IL-18 were elevated in cases compared to controls (TNFalpha medians 0.99 pg/ml [interquartile range 0.65-1.64 pg/ml] versus 0.77 pg/ml [0.52-1.22 pg/ml], p<0.0001; IL-18 medians 287 pg/ml [212-404 pg/ml] versus 271 pg/ml [200-373 pg/ml], p=0.01). IL-18 was moderately associated with HDL cholesterol r=-0.22, triglycerides r=0.16, and BMI r=0.14 (p for all < or =0.003) in the control population, but not among cases. TNFalpha had few associations with classical risk factors among cases or controls. TNFalpha had a significant association with MI: odds ratio (OR) 1.66 (95% confidence interval; 1.10-2.50), comparing extreme thirds after adjusting for classical risk factors, which was reduced on further adjustment for other inflammatory markers (OR 1.47; 0.91-2.37). IL-18 showed no association by thirds after adjustment for classical risk factors (OR 1.07; 0.70-1.62).


CONCLUSIONS
Circulating levels of IL-18 and TNFalpha were elevated in those with previous MI, but only TNFalpha retained an association after adjustment for classical risk factors. Independently elevated TNFalpha among those with previous MI may reflect cardiac expression of TNFalpha in ongoing myocardial remodeling.