Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079512.66448.1D
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© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
C-Reactive Protein, Interleukin-6, and Fibrinogen as Predictors of Coronary Heart Disease
The PRIME Study
From the Department of Atherosclerosis (G.L., J.-C.F.), SERLIA-INSERM UR545, Institut Pasteur de Lille and University Lille II, France; U.F.R. of Pharmacy (J.-M.B.), INSERM UR539, Nantes, France; Department of Hematology (I.J.-V.), Hôpital de la Timone, Marseille, France; Toulouse MONICA Project (J.F.), INSERM U588, Department of Epidemiology, Paul Sabatier-Toulouse Purpan University, Toulouse, France; Department of Epidemiology and Public Health (A.E.), Queen’s University Belfast, Northern Ireland; Lille Monica Project (P.A.), INSERM U508, Pasteur Institute of Lille, France; Strasbourg MONICA Project (D.A.), Department of Epidemiology and Public Health, Faculty of Medicine, Strasbourg, France; and Coordinating Center (P.D.), INSERM U258, Hôpital Paul Brousse, Villejuif, France.
Correspondence to Gérald Luc, Department of Atherosclerosis, SERLIA-INSERM UR545, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, 59019 Lille Cedex, France. E-mail Gerald.Luc{at}pasteur-lille.fr
Objective— This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein (CRP), interleukin-6, and fibrinogen with the incidence of coronary heart disease within the prospective cohort study on myocardial infarction (PRIME study).
Methods and Results— Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease (CHD) on entry. Nested case-control comparisons were carried out on 317 participants who suffered myocardial infarction (MI)-coronary death (n=163) or angina (n=158) as an initial CHD event during a follow-up for 5 years. After adjustment for traditional risk factors, incident MI-coronary death, but not angina, was significantly associated with CRP, interleukin-6, and fibrinogen, but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model. The different interleukin-6 levels in Northern Ireland and France partly explained the difference in risk between these countries. Interleukin-6 appeared as a risk marker of MI-coronary death, and it improved the definition of CHD risk beyond LDL cholesterol.
Conclusions— This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression.
Key Words: coronary heart disease • C-reactive protein • interleukin-6 • fibrinogen
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