High thrombin activatable fibrinolysis inhibitor levels are associated with an increased risk of premature peripheral arterial disease.
PURPOSE Acute complications of atherosclerosis such as stroke and myocardial infarction are caused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). METHODS The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance > or = 200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean +/- SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls. RESULTS Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC (p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication (p = 0.001). CONCLUSIONS All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis.