Association of Interleukin-18 Levels With Global Arterial Function and Early Structural Changes in Men Without Cardiovascular Disease

BACKGROUND Increased levels of interleukin-18 (IL-18) have been related to plaque progression and vulnerability and cardiovascular outcomes. Arterial functional and structural characteristics and endothelial/inflammatory activation are important determinants of cardiovascular performance and predictors of risk. We whether IL-18 is a determinant of global arterial function and early structural changes in men. METHODS We evaluated arterial structural and functional characteristics (carotid-femoral pulse wave velocity (PWV), central aortic pressures, wave reflection indexes, flow-mediatedd dilation of the brachial and common carotid intima-media thickness (IMT) and we systemic inflammatory markers in 97 men (mean age 57.8 +/- 8.6 years) without manifest cardiovascular/atherosclerotic disease. RESULTS Multivariable analysis adjusting for age, mean pressure, other risk factors, high-sensitivity C-reactive protein (hsCRP), and treatment showed independent associations between IL-18 level and carotid-femoral PWV (P < 0.01) and IMT (P = 0.03). On the other hand, no relationship between IL-18 and flow-mediated dilation, central pressures or augmentation index (Alx) was found. The combination of higher IL-18 level with higher carotid-femoral PWV and carotid IMT values showed greater effect on 10-year risk of a cardiovascular event. CONCLUSIONS IL-18 level is independently associated with aortic stiffening and carotid early atherosclerosis. This finding underlines the important role of IL-18 as a marker of arterial damage, and implies a contribution of this compound to the pathophysiology of cardiovascular disease.