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
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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
This article has been cited by other articles:
 |
|
 |
|
  K. Thomas, S. Rafiq, T. M. Frayling, S. Ebrahim, M. Kumari, J. Gallacher, L. Ferrucci, S. Bandinelli, R. B. Wallace, D. Melzer, et al. Interleukin-18 Polymorphism and Physical Functioning in Older People: A Replication Study and Meta-Analysis J Gerontol A Biol Sci Med Sci, November 1, 2009; 64A(11): 1177 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Woodward, P. Welsh, A. Rumley, H. Tunstall-Pedoe, and G. D.O. Lowe Do inflammatory biomarkers add to the discrimination of cardiovascular disease after allowing for social deprivation? Results from a 10 year cohort study in Glasgow, Scotland Eur. Heart J., April 10, 2009; (2009) ehp115v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Wenwei Liu, Qizhu Tang, Hua Jiang, Xiangwu Ding, Yongsheng Liu, Rui Zhu, Yongqian Tang, Bin Li, and Min Wei Promoter Polymorphism of Interleukin-18 in Angiographically Proven Coronary Artery Disease Angiology, April 1, 2009; 60(2): 180 - 185. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Troseid, I. Seljeflot, E. M. Hjerkinn, and H. Arnesen Interleukin-18 Is a Strong Predictor of Cardiovascular Events in Elderly Men With the Metabolic Syndrome: Synergistic effect of inflammation and hyperglycemia Diabetes Care, March 1, 2009; 32(3): 486 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Porazko, J. Kuzniar, M. Kusztal, T. J. Kuzniar, W. Weyde, M. Kuriata-Kordek, and M. Klinger IL-18 is involved in vascular injury in end-stage renal disease patients Nephrol. Dial. Transplant., February 1, 2009; 24(2): 589 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J Stott, P. Welsh, A. Rumley, M. Robertson, I. Ford, N. Sattar, R. G J Westendorp, J W. Jukema, S. M Cobbe, and G. D O Lowe Adipocytokines and risk of stroke in older people: a nested case-control study Int. J. Epidemiol., February 1, 2009; 38(1): 253 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B Schnabel and S. Blankenberg Commentary: Circulating cytokines and risk stratification of stroke incidence--will we do better in future? Int. J. Epidemiol., February 1, 2009; 38(1): 261 - 262. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Welsh, G. D.O. Lowe, J. Chalmers, D. J. Campbell, A. Rumley, B. C. Neal, S. W. MacMahon, and M. Woodward Associations of Proinflammatory Cytokines With the Risk of Recurrent Stroke Stroke, August 1, 2008; 39(8): 2226 - 2230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Platis, Q Yu, D Moore, E. Khojeini, P Tsau, and D. Larson The effect of daily administration of IL-18 on cardiac structure and function Perfusion, July 1, 2008; 23(4): 237 - 242. [Abstract] [PDF]
|
|
|
|
 |
|
 R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Thompson, D. Novick, C. J. Stock, J. Sanders, D. Brull, J. Cooper, P. Woo, G. Miller, M. Rubinstein, and S. E. Humphries Free Interleukin (IL)-18 Levels, and the Impact of IL18 and IL18BP Genetic Variation, in CHD Patients and Healthy Men Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2743 - 2749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Thompson, P. A. McCaskie, J. P. Beilby, J. Hung, M. Jennens, C. Chapman, P. Thompson, and S. E. Humphries IL18 Haplotypes Are Associated with Serum IL-18 Concentrations in a Population-Based Study and a Cohort of Individuals with Premature Coronary Heart Disease Clin. Chem., December 1, 2007; 53(12): 2078 - 2085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, I. Graham, D. Atar, K. Borch-Johnsen, G. Boysen, G. Burell, R. Cifkova, J. Dallongeville, G. De Backer, S. Ebrahim, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts) Eur. Heart J., October 1, 2007; 28(19): 2375 - 2414. [Full Text] [PDF]
|
|
|
|
|
|
A. Zirlik, S. M. Abdullah, N. Gerdes, L. MacFarlane, U. Schonbeck, A. Khera, D. K. McGuire, G. L. Vega, S. Grundy, P. Libby, et al. Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis: Results From the Dallas Heart Study Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2043 - 2049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orozco, E. Gemmell, M. Bickel, and G.J. Seymour Interleukin 18 and Periodontal Disease Journal of Dental Research, July 1, 2007; 86(7): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Musaad and E. N. Haynes Biomarkers of Obesity and Subsequent Cardiovascular Events Epidemiol. Rev., May 10, 2007; (2007) mxm005v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P. Kadoglou, D. Perrea, F. Iliadis, N. Angelopoulou, C. Liapis, and M. Alevizos Exercise Reduces Resistin and Inflammatory Cytokines in Patients With Type 2 Diabetes Diabetes Care, March 1, 2007; 30(3): 719 - 721. [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Frayling, S. Rafiq, A. Murray, A. J. Hurst, M. N. Weedon, W. Henley, S. Bandinelli, A.-M. Corsi, L. Ferrucci, J. M. Guralnik, et al. An Interleukin-18 Polymorphism Is Associated With Reduced Serum Concentrations and Better Physical Functioning in Older People J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2007; 62(1): 73 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Koenig and N. Khuseyinova Biomarkers of Atherosclerotic Plaque Instability and Rupture Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Koenig, N. Khuseyinova, J. Baumert, B. Thorand, H. Loewel, L. Chambless, C. Meisinger, A. Schneider, S. Martin, H. Kolb, et al. Increased Concentrations of C-Reactive Protein and IL-6 but not IL-18 Are Independently Associated With Incident Coronary Events in Middle-Aged Men and Women: Results From the MONICA/KORA Augsburg Case-Cohort Study, 1984-2002 Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2745 - 2751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vlachopoulos, K. Aznaouridis, N. Ioakeimidis, K. Rokkas, C. Vasiliadou, N. Alexopoulos, E. Stefanadi, A. Askitis, and C. Stefanadis Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease Eur. Heart J., November 2, 2006; 27(22): 2640 - 2648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Blankenberg and S. Yusuf The Inflammatory Hypothesis: Any Progress in Risk Stratification and Therapeutic Targets? Circulation, October 10, 2006; 114(15): 1557 - 1560. [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Tso, W.-N. Huang, H.-Y. Huang, and C.-K. Chang Relationship of plasma interleukin-18 concentrations to traditional and non-traditional cardiovascular risk factors in patients with systemic lupus erythematosus Rheumatology, September 1, 2006; 45(9): 1148 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Blankenberg, M. J. McQueen, M. Smieja, J. Pogue, C. Balion, E. Lonn, H. J. Rupprecht, C. Bickel, L. Tiret, F. Cambien, et al. Comparative Impact of Multiple Biomarkers and N-Terminal Pro-Brain Natriuretic Peptide in the Context of Conventional Risk Factors for the Prediction of Recurrent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study Circulation, July 18, 2006; 114(3): 201 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Blankenberg, T. Godefroy, O. Poirier, H. J. Rupprecht, S. Barbaux, C. Bickel, V. Nicaud, R. Schnabel, F. Kee, C. Morrison, et al. Haplotypes of the Caspase-1 Gene, Plasma Caspase-1 Levels, and Cardiovascular Risk Circ. Res., July 7, 2006; 99(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Circulation, June 20, 2006; 113(24): e873 - e923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Stroke, June 1, 2006; 37(6): 1583 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]
|
|
|
|
 |
|
 S G Baidya and Q-T Zeng Helper T cells and atherosclerosis: the cytokine web Postgrad. Med. J., December 1, 2005; 81(962): 746 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Van Guilder, G. L. Hoetzer, D. T. Smith, H. M. Irmiger, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E807 - E813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mallat, Ph. G. Steg, J. Benessiano, M.-L. Tanguy, K. A. Fox, J.-P. Collet, O. H. Dabbous, P. Henry, K. F. Carruthers, A. Dauphin, et al. Circulating Secretory Phospholipase A2 Activity Predicts Recurrent Events in Patients With Severe Acute Coronary Syndromes J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thorand, H. Kolb, J. Baumert, W. Koenig, L. Chambless, C. Meisinger, T. Illig, S. Martin, and C. Herder Elevated Levels of Interleukin-18 Predict the Development of Type 2 Diabetes: Results From the MONICA/KORA Augsburg Study, 1984-2002 Diabetes, October 1, 2005; 54(10): 2932 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tiret, T. Godefroy, E. Lubos, V. Nicaud, D.-A. Tregouet, S. Barbaux, R. Schnabel, C. Bickel, C. Espinola-Klein, O. Poirier, et al. Genetic Analysis of the Interleukin-18 System Highlights the Role of the Interleukin-18 Gene in Cardiovascular Disease Circulation, August 2, 2005; 112(5): 643 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamagami, K. Kitagawa, T. Hoshi, S. Furukado, H. Hougaku, Y. Nagai, and M. Hori Associations of Serum IL-18 Levels With Carotid Intima-Media Thickness Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1458 - 1462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hung, B. M. McQuillan, C. M. L. Chapman, P. L. Thompson, and J. P. Beilby Elevated Interleukin-18 Levels Are Associated With the Metabolic Syndrome Independent of Obesity and Insulin Resistance Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1268 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Kritchevsky, M. Cesari, and M. Pahor Inflammatory markers and cardiovascular health in older adults Cardiovasc Res, May 1, 2005; 66(2): 265 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cushman Leukocyte Count in Vascular Risk Prediction Arch Intern Med, March 14, 2005; 165(5): 487 - 488. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tripepi, F. Mallamaci, and C. Zoccali Inflammation Markers, Adhesion Molecules, and All-Cause and Cardiovascular Mortality in Patients with ESRD: Searching for the Best Risk Marker by Multivariate Modeling J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S83 - S88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schnabel, H. J. Rupprecht, K. J. Lackner, E. Lubos, C. Bickel, J. Meyer, T. Munzel, F. Cambien, L. Tiret, S. Blankenberg, et al. Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study Eur. Heart J., February 1, 2005; 26(3): 241 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. de Nooijer, J.H. von der Thusen, C.J.N. Verkleij, J. Kuiper, J.W. Jukema, E.E. van der Wall, Th.J.C. van Berkel, and E.A.L. Biessen Overexpression of IL-18 Decreases Intimal Collagen Content and Promotes a Vulnerable Plaque Phenotype in Apolipoprotein-E-Deficient Mice Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2313 - 2319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mills and D. L. Bhatt The yin and yang of arterial inflammation J. Am. Coll. Cardiol., July 7, 2004; 44(1): 50 - 52. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kemp, J. Donovan, H. Higham, and J. Hooper Biochemical markers of myocardial injury Br. J. Anaesth., July 1, 2004; 93(1): 63 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
|
|