PROGRESSIVE INTERMITTENT CLAUDICATION IS ASSOCIATED WITH IMPAIRED FIBRINOLYSIS

Purpose: Acute complications of atherosclerosis such as stroke and myo cardial infarction are caused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to de termine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tiss ue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). Methods: The stud y group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walkin g distance greater than or equal to 200 meters) and 51 patients with s evere 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 immunoadsorb ent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean +/- SEM levels of the enzyme levels in patien ts with progressively more severe PAD were compared with normal contro ls. Results: Serum PAI-1 activity levels were significantly elevated i n both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity revels in groups wit h worsening degrees of PAD. There was a significant decrease in tPA ac tivity 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 be tween tPA antigen levels and pain-free walking time in patients with c laudication (p = 0.001). Conclusions: All patients with PAD in this st udy had significant reductions in endogenous fibrinolytic activity. Pa tients 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 fibri nolysis.