Associations of circulating TNFα 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 TNFα and IL-18 with myocardial infarction (MI), and on the extent of confounding by classical and inflammatory risk markers. Methods: We measured TNFα and IL-18 in plasma from 446 MI cases and 477 age- and sex-matched controls from North Glasgow. Results: TNFα and IL-18 were elevated in cases compared to controls (TNFα 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 ⩽0.003) in the control population, but not among cases. TNFα had few associations with classical risk factors among cases or controls. TNFα 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 TNFα were elevated in those with previous MI, but only TNFα retained an association after adjustment for classical risk factors. Independently elevated TNFα among those with previous MI may reflect cardiac expression of TNFα in ongoing myocardial remodeling.