CONCENTRATION OF ENDOGENOUS TPA ANTIGEN IN CORONARY-ARTERY DISEASE - RELATION TO THROMBOTIC EVENTS, ASPIRIN TREATMENT, HYPERLIPIDEMIA, AND MULTIVESSEL DISEASE

Tissue plasminogen activator (tPA) is the major plasminogen activator responsible for dissolving blood clots found in blood vessels. However , elevated concentrations of tPA antigen were found to be related to a dverse events in patients with coronary artery disease (CAD). Consider able controversy about the significance of these results exists. The g oal of this cross-sectional study was to identify independent determin ants for tPA antigen concentrations in patients with CAD, to possibly clarify the above paradoxical relationship. The baseline tPA antigen c oncentrations of 366 patients with angiographic evidence of coronary s clerosis were determined. Univariate analysis showed that age (P = 0.0 13), angiographic extent of disease (P < 0.001), presence of angina at rest (P < 0.001), diabetes mellitus (P = 0.004), hypercholesterolemia (P = 0.045), hypertriglyceridemia (P = 0.015), and chronic intake of nitrates (P < 0.001) were significantly and positively related to tPA antigen concentration, while the chronic intake of aspirin was inverse ly related to tPA antigen (P < 0.001). Ln addition, plasminogen activa tor inhibitor type 1 (PAI-I) activity was found to be significantly an d positively associated with tPA antigen concentration (P < 0.001). A multivariate analysis identified chronic low-dose aspirin therapy (P < 0.001), PAI-1 activity (P < 0.001), hypertriglyceridemia (P = 0.005), the type of angina (P = 0.026), multivessel disease (P = 0.041), and hypercholesterolemia (P = 0.043) as significant and independent determ inants of tPA antigen. While hypertriglyceridemia and hypercholesterol emia both are related to the underlying disease, the type of angina an d the number of involved vessels are linked to the severity and extent of disease, and all of them are indicators of a prothrombotic state f ound during the progression of CAD. In contrary, low-dose aspirin rath er would decrease the likelihood of thrombotic events. The relation of tPA antigen to PAI-1 activity furthermore underlines the relation bet ween tPA antigen concentration and a prothrombotic state. Therefore, t he positive or-in case of aspirin therapy-negative correlation of thes e parameters with tPA antigen concentration would indicate that thromb us formation and simultaneous endothelial cell activation might be maj or determinants for tPA antigen concentration in CAD.