Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis

Abstract

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.