Background:
A few cross-sectional studies have reported associations between hemostatic factors and peripheral arterial disease (PAD), but prospective data are largely lacking.
Hypothesis:
Plasma hemostatic factors are associated with incident PAD, independently of traditional atherosclerotic risk factors.
Methods:
In 14,071 men and women (age 45-64 years and 25.4% blacks) at visit 1 (1987-1989) of the ARIC Study, we investigated the associations of fibrinogen, Von Willebrand factor (VWF), factor VIII, factor VII, Antithrombin III (ATIII) with incidence of PAD (defined as hospitalizations with PAD diagnosis [ICD-9: 440.2x, 440.3, and 440.4] or leg revascularization [38.18, 39.25, 39.29 and 39.50]). We also explored associations of d-dimer measured at visit 3 (1993-1995) in 11,619 participants.
Results:
We identified 540 incident PAD during a median follow-up of 24.4 years. Fibrinogen, VWF, factor VIII, and d-dimer demonstrated positive dose-response relationships to incident PAD, independent of other risk factors (Table). In comparison with respective referent categories, significantly higher PAD risk was observed in the top two quintiles of fibrinogen, VWF, and d-dimer and the highest quintile of factor VIII. When fibrinogen, VWF, and factor VIII were modeled simultaneously (d-dimer was measured at a different visit), only fibrinogen and VWF remained significantly associated with PAD.
Conclusion:
Hemostatic factors, particularly fibrinogen and VWF (as well as d-dimer), were independently associated with future risk of PAD. Our findings suggest the pathophysiological involvement of hemostasis in the development of PAD and potential usefulness of those factors for classifying long-term risk of PAD.
