on May 29, 2003
Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079512.66448.1D
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Submitted on November 18, 2002
Accepted on May 14, 2003
C-Reactive Protein, Interleukin-6, and Fibrinogen as Predictors of Coronary Heart Disease. The PRIME Study
Gérald Luc *;
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.
* To whom correspondence should be addressed. 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.
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