Circulation. 2003;108:2453-2459
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000099509.76044.A2
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000099509.76044.A2
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(Circulation. 2003;108:2453.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Interleukin-18 and the Risk of Coronary Heart Disease in European Men
The Prospective Epidemiological Study of Myocardial Infarction (PRIME)
From INSERM U525 (S.B., F.C., L.T.), Faculté de Médecine Pitié-Salpétrière, Paris, France; Department of Medicine II (S.B.), Johannes Gutenberg-University Mainz, Germany; INSERM U545 (G.L.), Department of Atherosclerosis, Pasteur Institute, Lille, France; INSERM U258 (P.D.), Villejuif, France; Department of Epidemiology and Public Health (D.A.), Faculty of Medicine, Strasbourg, France; INSERM U558 (J.F.), Department of Epidemiology, Toulouse, France; INSERM U508 (P.A.), Pasteur Institute, Lille, France; and Department of Epidemiology and Public Health (A.E.), Queen’s University Belfast, Belfast, Northern Ireland.
Correspondence to Dr Stefan Blankenberg, Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany. E-mail stefan.blankenberg{at}uni-mainz.de
Received June 9, 2003; de novo received August 8, 2003; revision received September 16, 2003; accepted September 18, 2003.
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.
Key Words: inflammation • cardiovascular diseases • myocardial infarction • prognosis • interleukins
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