Exercise training enhances endogenous fibrinolysis in peripheral arterial disease

Purpose: Acute clinical events resulting from atherosclerosis (myocardial infarction, stroke) are associated with impaired endogenous fibrinolysis, the system by which the body lyses inappropriately formed thrombus. Endurance exercise training improves fibrinolysis in normal subjects and those with coronary artery disease. The hypothesis of this study was that exercise training would improve fibrinolysis in subjects with peripheral arterial disease (PAD). Methods and results: Twenty-one men with intermittent claudication (IC-EX) underwent treadmill exercise training for 6 months. Twenty age-matched male subjects with IC were followed for the same period (IC-NONEX). Fibrinolytic activity was measured prior to entry into exercise or "usual care," and at the completion of the study period. Fibrinolysis was quantified by measurement of the activity levels of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1), using an amidolytic method. Fibrinolysis, quantified as increased PAI-1 activity, was reduced in both claudicant groups relative to healthy controls at baseline.After 6 months of exercise, subjects in the IC-EX group experienced significant improvements in fibrinolytic activity, manifested as a 23% decrease in PAI-1 activity and a 28% increase in tPA activity. No changes occurred in the IC-NONEX group. In the IC-EX group, subjects with the highest initial PAI-1 values experienced the greatest decreases in PAI-1 activity and thus the greatest benefit from exercise. Conclusions: Patients with PAD have impaired fibrinolytic activity, manifested primarily as increases in the inhibitor of fibrinolysis, PAI-1. Six months of exercise training reduced these impairments, and may serve as an intervention to reduce cardiovascular mortality and morbidity in these patients.