Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).
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.


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.
INSERM U525, Faculté de Médecine Pitié-Salpétrière, Paris, France. stefan.blankenberg@uni-mainz.de
Stefan
S
Blankenberg
Gérald
G
Luc
Pierre
P
Ducimetière
Dominique
D
Arveiler
Jean
J
Ferrières
Philippe
P
Amouyel
Alun
A
Evans
François
F
Cambien
Laurence
L
Tiret
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology*; D005340:Fibrinogen / Q000032:analysis; D005602:France / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland / Q000453:epidemiology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D020382:Interleukin-18; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein