Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

Abstract

To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as Δ visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects ( p < 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia ( r = 0.47, p < 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that Δ visual uptake score was significantly higher in multivessel disease ( p < 0.01). Multivessel disease had significantly high PAI activity both in the basal condition ( p < 0.05) and at peak exercise ( p < 0.05) because of significantly high free PAI-1 ( p < 0.05, respectively) in addition to a significant reduction in tissue plasminogen activator release ( p < 0.01) compared to single-vessel disease. These results suggest that PAI activity may be an important index for assessing the severity of CAD and the extent of ischemia, and they also suggest that impaired fibrinolysis in CAD may be caused by the vascular endothelial damage resulting from ischemia and atherosclerosis.