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Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).
Circulation 2003; 108(20):2453-9Circ

Abstract

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.

Authors+Show Affiliations

INSERM U525, Faculté de Médecine Pitié-Salpétrière, Paris, France. stefan.blankenberg@uni-mainz.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14581397

Citation

Blankenberg, Stefan, et al. "Interleukin-18 and the Risk of Coronary Heart Disease in European Men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME)." Circulation, vol. 108, no. 20, 2003, pp. 2453-9.
Blankenberg S, Luc G, Ducimetière P, et al. Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation. 2003;108(20):2453-9.
Blankenberg, S., Luc, G., Ducimetière, P., Arveiler, D., Ferrières, J., Amouyel, P., ... Tiret, L. (2003). Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation, 108(20), pp. 2453-9.
Blankenberg S, et al. Interleukin-18 and the Risk of Coronary Heart Disease in European Men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation. 2003 Nov 18;108(20):2453-9. PubMed PMID: 14581397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). AU - Blankenberg,Stefan, AU - Luc,Gérald, AU - Ducimetière,Pierre, AU - Arveiler,Dominique, AU - Ferrières,Jean, AU - Amouyel,Philippe, AU - Evans,Alun, AU - Cambien,François, AU - Tiret,Laurence, AU - ,, Y1 - 2003/10/27/ PY - 2003/10/29/pubmed PY - 2003/12/24/medline PY - 2003/10/29/entrez SP - 2453 EP - 9 JF - Circulation JO - Circulation VL - 108 IS - 20 N2 - 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. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/14581397/Interleukin_18_and_the_risk_of_coronary_heart_disease_in_European_men:_the_Prospective_Epidemiological_Study_of_Myocardial_Infarction__PRIME__ L2 - http://www.ahajournals.org/doi/full/10.1161/01.CIR.0000099509.76044.A2?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -