Abstract P249: Hemostatic Factors and Long-Term Risk of Peripheral Arterial Disease: The Atherosclerosis Risk in Communities (ARIC) Study

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.

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A two adenine insertion polymorphism in the 3’ untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis

Thrombosis and Haemostasis ◽

10.1160/th07-02-0103 ◽

2007 ◽

Vol 98 (10) ◽

pp. 733-737 ◽

Cited By ~ 3

Author(s):

Emilie Serve ◽

Jean-Luc Reny ◽

Sepideh Akhavan ◽

Joseph Emmerich ◽

Anne-Marie Fischer ◽

...

Keyword(s):

Risk Factors ◽

Peripheral Arterial Disease ◽

Venous Thrombosis ◽

Untranslated Region ◽

Smoking Status ◽

Arterial Disease ◽

Lower Limbs ◽

Factor Vii ◽

Insertion Polymorphism ◽

Peripheral Arterial

SummaryPolymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3’UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII:Ag) levels were lower in the presence of the 3’UTR 2A insertion (68.4 ± 12.3%, 81.3 ± 14.5% and 89.5 ± 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p<0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06–0.99]. In conclusion, the 2 adenine insertion in the 3’UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.

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Fibrin D-Dimer, Haemostatic Factors and Peripheral Arterial Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649831 ◽

1995 ◽

Vol 74 (03) ◽

pp. 828-832 ◽

Cited By ~ 52

Author(s):

Amanda J Lee ◽

F Gerald R Fowkes ◽

Gordon D O Lowe ◽

Ann Rumley

Keyword(s):

Peripheral Arterial Disease ◽

Arterial Disease ◽

Factor Vii ◽

Predictive Role ◽

Haemostatic Factors ◽

Peripheral Arterial ◽

Von Willebrand ◽

Relationship Of ◽

Willebrand Factor ◽

D Dimer

SummarySeveral haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p ≤0.01) and vWF showed a similar pattern in men only (p ≤0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p ≤0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p ≤0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.

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