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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2745.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Wolfgang Koenig; Natalie Khuseyinova; Jens Baumert; Barbara Thorand; Hannelore Loewel; Lloyd Chambless; Christa Meisinger; Andrea Schneider; Stephan Martin; Hubert Kolb; Christian Herder

From Department of Internal Medicine II-Cardiology (W.K., N.K.), University of Ulm Medical Center, Ulm, Germany; GSF National Research Centre for Environment and Health (J.B., B.T., H.L., C.M., A.S.), Institute of Epidemiology, Neuherberg, Germany; University of North Carolina at Chapel Hill (L.C.), Chapel Hill, NC; German Diabetes Clinic (S.M., H.K., C.H.), German Diabetes Centre, Leibniz Centre at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

Correspondence to Dr Barbara Thorand, MPH; GSF National Research Center for Environment and Health, Institute of Epidemiology, Postfach 1129, 85758 Neuherberg, Germany. E-mail thorand{at}gsf.de

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.

Within the MONICA/KORA Augsburg case–cohort study, concentrations of IL-18 were measured in 382 cases with incident coronary heart disease (CHD) and 1980 noncases. We found no statistically significant association between increased IL-18 concentrations and incident CHD, whereas CRP and IL-6 were independent predictors of future cardiovascular risk in this population.

Key Words: case–cohort study • coronary heart disease • IL-18 • inflammation • risk factors

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