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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2793.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Haemostatic Factors and the Risk of Cardiovascular Death in Patients With Coronary Artery Disease

The AtheroGene Study

P.E. Morange; C. Bickel; V. Nicaud; R. Schnabel; H.J. Rupprecht; D. Peetz; K.J. Lackner; F. Cambien; S. Blankenberg; L. Tiret for the AtheroGene Investigators

From INSERM UMR S 525 and Université Pierre et Marie Curie-Paris 6 (P.E.M., V.N., F.C., L.T.), Paris, France; INSERM UMR626 (P.E.M.), Marseille, France; Innere Abteilung (C.B.), Bundeswehrzentralkrankenhaus Koblenz, Germany; the Department of Medicine II (R.S., H.J.R., S.B.), Johannes Gutenberg-University Mainz, Germany; and Clinical Chemistry and Laboratory Medicine (D.P., K.J.L.), Johannes Gutenberg-University Mainz, Germany.

Correspondence to P.E. Morange, Lab. Hematology, CHU Timone. 264, Rue Saint-Pierre 13385 Marseille Cedex 05, France. E-mail pmorange{at}ap-hm.fr

Objective— To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients.

Methods and Results— The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively.

Conclusions— In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

We examined the association between 5 hemostatic markers and the incidence of fatal cardiovascular events in the prospective Atherogene cohort, including 1057 individuals with coronary artery disease at baseline. Fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Key Words: coagulation • hemostasis • coronary disease • atherosclerosis • arterial thrombosis