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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2043.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis

Results From the Dallas Heart Study

Andreas Zirlik; Shuaib M. Abdullah; Norbert Gerdes; Lindsey MacFarlane; Uwe Schönbeck; Amit Khera; Darren K. McGuire; Gloria L. Vega; Scott Grundy; Peter Libby; James A. de Lemos

From the Donald W. Reynolds Centers of the Brigham and Women’s Hospital (A.Z., N.G., L.M., P.L.), Harvard Medical School, Boston, Mass; and the University of Texas Southwestern Medical Center (S.A., A.K., D.K.M., G.L.V., S.G., J.d.L.), Dallas. Current affiliations: Department of Cardiology (A.Z.), University of Freiburg, Germany; Karolinska Institute (N.G.), Stockholm, Sweden; and Cardiovascular Disease (U.S.), Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn.

Correspondence to Andreas Zirlik, MD, University of Freiburg, Department of Cardiology and Angiology, Breisacherstrasse 33, 79106 Freiburg, Germany. E-mail andreas.zirlik{at}uniklinik-freiburg.de

Objective— Although IL-18 promotes atherogenesis in animal studies and predicts cardiovascular risk in humans, it is unknown whether elevated IL-18 levels are associated with coronary atherosclerosis in the general population.

Methods and Results— IL-18 plasma levels were determined by ELISA in 2231 subjects from the Dallas Heart Study. In univariable analysis, IL-18 levels associated with traditional cardiovascular risk factors and particularly with components of the metabolic syndrome (MS, P<0.01 for trend across the number of MS components); IL-18 also associated with coronary artery calcium (CAC) scores measured by electron beam computed tomography and aortic plaque measured by MRI (P<0.01 for each). In multivariable analyses, IL-18 remained associated with multiple components of the MS but not with CAC or aortic plaque.

Conclusions— In a large population-based sample, elevated IL-18 plasma levels associated with risk factors for atherosclerosis and with the metabolic syndrome. The association between IL-18 and atherosclerosis diminished after accounting for traditional cardiovascular risk factors. These data suggest that IL-18 does not add independently to detection of atherosclerotic burden in asymptomatic individuals.

In the Dallas Heart Study, IL-18 levels associated with traditional cardiovascular risk factors, components of the metabolic syndrome, and surrogate markers of subclinical atherosclerosis. The association of IL-18 and atherosclerosis diminished in multivariate analysis suggesting that IL-18 does not predict atherosclerotic burden in this collective.

Key Words: atherosclerosis • imaging • interleukins • risk factors • metabolic syndrome