Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women - Results from the MONICA/KORA Augsburg case-cohort study, 1984-2002

Objectives - We performed a prospective case - cohort study in initially healthy, middle-aged men and women from the MONICA/KORA Augsburg studies conducted between 1984 and 2002 to assess the role of IL-18 in comparison with IL-6 and CRP in the prediction of incident coronary heart disease (CHD). Methods and Results - Concentrations of IL-18 were measured in 382 case subjects with incident CHD and 1980 noncases. Mean follow-up was 11 years. Baseline concentrations of IL-18 were slightly higher in cases than in noncases (172.4 [1.0] versus 161.3 [1.0] pg/mL, respectively; P = 0.114), but were clearly elevated for C-reactive protein (CRP) and IL-6 in cases compared with noncases. In multivariable analyses, accounting for classical cardiovascular risk factors and inflammatory markers, no statistically significant association was seen between increased concentrations of IL-18 and incident CHD both in men (hazard ratio [HR] and 95% confidence intervals [CIs] comparing extreme tertiles, 1.20; 95% CI, 0.85 to 1.69), and in women (HR, 1.25; 95% CI, 0.67 to 2.34). However, in this population increased concentrations of CRP and IL-6 were found to be independent predictors of future CHD events, even after multivariable adjustment. Conclusions - Elevated concentrations of CRP and IL-6, but not IL-18, were independently associated with risk of CHD in subjects from an area with moderate absolute risk.