Interleukin-18 and the Risk of Coronary Heart Disease in European Men: The Prospective Epidemiological Study of Myocardial Infarction (PRIME).
Blankenberg, Stefan MD; Luc, Gerald MD, PhD; Ducimetiere, Pierre PhD; Arveiler, Dominique MD; Ferrieres, Jean MD, MSc; Amouyel, Philippe MD, PhD; Evans, Alun MD, FRCP; Cambien, Francois MD; Tiret, Laurence PhD; on behalf of the PRIME Study Group
108(20):2453-2459, November 18, 2003.
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Background-: Interleukin (IL)-18 promotes atherosclerotic plaque growth and vulnerability. It is unknown, however, whether elevations of circulating IL-18 precede the onset of coronary events in apparently healthy individuals.
Methods and Results-: We evaluated the relationship between baseline plasma levels of IL-18 and the subsequent incidence of coronary events over a 5-year follow-up in the Prospective Epidemiological Study of Myocardial Infarction (PRIME),which included 10 600 healthy European men aged 50 to 59 years at baseline. Analysis was performed in a nested case-control manner comparing 335 cases with a coronary event to 670 age-matched controls. Baseline levels of IL-18 were significantly higher in men who developed a coronary event than in controls (225.1 versus 203.9 pg/mL, P =0.005). After adjustment for most potential confounders, including C-reactive protein, IL-6, and fibrinogen, the relative risk of future coronary events associated with increasing tertiles of IL-18 was 1.65 (95% CI 1.14 to 2.40, P =0.008) in Northern Ireland, 1.29 (95% CI 0.96 to 1.73, P =0.09) in France, and 1.42 (95% CI 1.13 to 1.79, P =0.003) in both populations combined (P =0.31 for the test of homogeneity between populations). In all models, IL-18 made an independent contribution to the prediction of risk over lipids or other inflammatory markers such as C-reactive protein, IL-6, or fibrinogen.
Conclusions-: Plasma IL-18 level was identified as an independent predictor of coronary events in healthy, middle-aged European men. Determination of circulating IL-18 might improve the prediction of coronary events.
(C) 2003 American Heart Association, Inc.