Pathological von Willebrand factor fibers resist tissue plasminogen activator and ADAMTS13 while promoting the contact pathway and shear-induced platelet activation

Background Associations of three markers of thrombotic tendency, von Willebrand factor, tissue plasminogen activator antigen and fibrin D-dimer, with coronary heart disease have been reported in meta-analyses. It is not known, however, whether findings are generalizable to older women. Design Prospective cohort of 3582 women aged 60-79 years randomly selected from 23 towns without evidence of cardiovascular disease at entry into the British Women's Heart and Health Study. Methods Women were followed for 4.7 years for incident coronary heart disease. Cox proportional hazard models were used to compare the hazard ratio of coronary heart disease per doubling for each thrombotic factor. Results In models adjusting for age and town only there was no association between von Willebrand factor or D-dimer and incidence of coronary heart disease, but there was a positive association of tissue plasminogen activator: coronary heart disease hazard ratio per doubling was 1.37 (95% confidence interval: 1.08-1.75). Adjustment for potential confounders (socio-economic position, smoking, lung function, physical activity, alcohol consumption, body mass index, waist-to-hip ratio) attenuated association to 1.20 (0.92-1.58). Further adjustment for risk factors that may be part of the same pathophysiological process linking tissue plasminogen activator to coronary heart disease (high density lipoprotein cholesterol, triglycerides, blood pressure, fasting glucose, insulin, C-reactive protein, fibrinogen) attenuated the hazard ratio to 1.05 (0.79-1.40). Conclusion In older women, tissue plasminogen activator was associated with incident coronary heart disease, but does not appear to be an independent risk factor for coronary heart disease as the association was attenuated by adjustment for confounding and other metabolic and vascular risk factors. Eur J Cardiovasc Prev Rehabil 14:638-645 © 2007 The European Society of Cardiology

Download Full-text

von Willebrand Factor, Soluble P-Selectin, Tissue Plasminogen Activator and Plasminogen Activator Inhibitor in Atherosclerosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649788 ◽

1995 ◽

Vol 74 (02) ◽

pp. 626-630 ◽

Cited By ~ 96

Author(s):

A D Blann ◽

M Dobrotova ◽

P Kubisz ◽

C N McCollum

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Von Willebrand Factor ◽

Plasminogen Activator Inhibitor ◽

Tissue Plasminogen ◽

Soluble P ◽

Von Willebrand ◽

Willebrand Factor ◽

Activator Inhibitor ◽

Pai 1

SummaryTissue plasminogen activator antigen (tPA), plasminogen activator inhibitor antigen (PAI-1), soluble P-selectin and von Willebrand factor antigen (vWf) were measured by ELISA in 41 patients with peripheral vascular disease (PVD), 41 with ischaemic heart disease (IHD) and in 46 age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0002) and in patients with PVD (p = 0.0011) relative to the controls but levels did not differ between the two patients groups. Raised tPA found in both PVD (p = 0.0006) and IHD (p = 0.0061) compared to the controls also failed to differentiate the two groups of patients. Soluble P-selectin was also raised in both groups (p = 0.003 in IHD and p = 0.0102 in PVD) with no difference between the groups. There were no differences in levels of PAI-1 between the groups. In the subjects taken as a whole, there were significant Spearman’s correlations between tPA and vWf (r = 0.37, p <0.001), tPA and triglycerides (r = 0.38, p <0.001), tPA and P-selectin (r = 0.19, p = 0.032), vWf and age (r = 0.25, p = 0.005) and inversely between vWf and HDL (r = -0.25, p = 0.006). These data support the concept that increased levels of tPA may be important in atherosclerosis, and indicate that soluble P-selectin may be useful in further analysis of the role of platelets and the endothelial cell in this disease.

Download Full-text