AIM: Interleukin-18 (IL-18) is a pro-inflammatory cytokine with a central role in the inflammatory cascade. In the present study, we investigated whether patients with precocious myocardial infarction have higher plasma IL-18 concentrations than matched controls. Furthermore, the relationships between plasma IL-18 concentrations and coronary atherosclerosis, C-reactive protein (CRP), interleukin-6 (IL-6) and traditional cardiovascular risk factors were examined. METHODS AND RESULTS: Three hundred eighty-seven unselected survivors of a first myocardial infarction aged less than 60 years and 387 sex and age matched controls were enrolled in the study. A subset of patients (n=236) was evaluated by quantitative coronary angiography. Postinfarction patients had significantly higher mean level of plasma IL-18 than controls (309.6+/-138.6 versus 285.4+/-115.7pg IL-18/mL). Furthermore, plasma IL-18 concentration was significantly associated with coronary plaque area (r=0.17, p=0.009). This relationship remained in a partial correlation analysis adjusting for CRP (r=0.15, p=0.02), for IL-6 (r=0.15, p=0.02) and for both CRP and IL-6 (r=0.15, p=0.02). In addition, IL-18 levels were significantly associated with other cardiovascular risk factors, namely age, low density lipoprotein (LDL) cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, insulin, proinsulin, body mass index (BMI), systolic and diastolic blood pressure. CONCLUSION: The present work provides evidence that plasma IL-18 is increased in postinfarction patients and is associated with coronary atherosclerosis.