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(Circulation. 2004;109:1343-1348.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Endothelial Cell Markers and the Risk of Coronary Heart Disease

The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study

P.E. Morange, MD, PhD; C. Simon, MD, PhD; M.C. Alessi, MD, PhD; G. Luc, MD; D. Arveiler, MD; J. Ferrieres, MD, MSc; P. Amouyel, MD, PhD; A. Evans, MD, FRCP; P. Ducimetiere, PhD; I. Juhan-Vague, MD, PhD, on behalf of the PRIME Study Group

From the Department of Hematology, Faculty of Medicine, INSERM U626, Marseilles (P.E.M., M.C.A., I.J.-V.); Nutrition Study Group, Faculty of Medicine (C.S.), and the Strasbourg MONICA Project, Department of Epidemiology and Public Health, Faculty of Medicine (D.A.), Strasbourg; Department of Atherosclerosis, INSERM UR545 (G.L.), and the Lille MONICA Project, INSERM U508 (P.A.), Institut Pasteur de Lille, Lille; the Toulouse MONICA Project, INSERM U558, Department of Epidemiology, Paul Sabatier-Toulouse Purpan University, Toulouse (J.F.); and INSERM U258, Hôpital Paul Brousse, Villejuif (P.D.), France; and the Department of Epidemiology and Public Health, Queen’s University of Belfast, Belfast, Northern Ireland (A.E.).

Correspondence to I. Juhan-Vague, Laboratory of Haematology, CHU Timone, 13385 Marseilles cedex 5, France. E-mail irene.juhan{at}ap-hm.fr

Received July 15, 2003; de novo received September 23, 2003; revision received December 17, 2003; accepted December 30, 2003.

Background— Tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), and thrombomodulin (TM) are 3 major hemostatic regulatory molecules synthesized by endothelium. Data from epidemiological studies aiming to evaluate the relation between plasma levels of these molecules and the development of coronary heart disease (CHD) are sparse or contradictory.

Methods and Results— We examined the association between these endothelial-cell markers and the incidence of fatal or nonfatal myocardial infarction (hard CHD) and stable or unstable angina (angina pectoris) in a prospective cohort (the PRIME Study) of nearly 10 000 healthy men recruited in France and Northern Ireland. We measured baseline plasma concentration of the free form of TFPI (f-TFPI), vWF, and the soluble form of TM (sTM) among 296 participants who subsequently developed CHD over the 5-year follow-up (158 with hard CHD and 142 with angina pectoris) and in 563 control subjects by use of a nested case-control design. Individuals with plasma vWF levels in the highest quartile showed a 3.04-fold increase in the risk of hard CHD compared with those in the lowest quartile (95% CI, 1.59 to 5.80). Individuals with f-TFPI levels below the 10th percentile had a 2.13-fold increased risk of hard CHD compared with those with levels above it (95% CI, 1.08 to 4.18). The risk for both molecules persisted after control for inflammatory parameters. Individuals with vWF levels in the highest quartile and f-TFPI levels below the 10th percentile presented a 6.9-fold increased risk of hard CHD compared with those with vWF levels in the lowest quartile and f-TFPI levels above the 10th percentile (95% CI, 1.3 to 37.8).

Conclusions— vWF and f-TFPI plasma levels were independent risk factors for hard CHD events.

Key Words: endothelium-derived factors • epidemiology • coronary disease • von Willebrand factor

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