DETERMINANTS OF TPA ANTIGEN AND ASSOCIATIONS WITH CORONARY-ARTERY DISEASE AND ACUTE CEREBROVASCULAR-DISEASE

The aim of this study was to determine the association of tPA antigen levels with CAD and ischaemic stroke and whether associations are inde pendent of levels of PAI-1 antigen. In subjects with CAD (n = 247) tPA was associated with the number of coronary arteries with greater than or equal to 50% stenosis, but this association was lost after adjustm ent for PAI-1, which was found to be the largest determinant of tPA le vels in linear regression models and accounted for as much as 38% of t he variation in levels. Levels of tPA were significantly higher in pat ients with a history of MI compared with those without. even after adj ustment for covariates and PAI-1 (MI: 10.0 [9.4-10.6] ng/ml, no MI: 8. 9 [8.5-9.4] ng/ml, p = 0.004). In a logistic regression model comparin g patients with MI to patients without MI, the odds ratio for tPA leve ls in the upper quartile compared with the lowest quartile was 2.03 (1 .33-3.10). Levels of tPA in subjects with ischaemic stroke (n = 338) w ere significantly higher than age matched healthy control subjects (n = 366) and again this difference remained after adjustment (patients: 10.4 [9.9-10.9] ng/ml; controls: 9.0 [8.7-9.3] ng/ml, p <0.0001). In a logistic regression model comparing patients with ischaemic stroke to healthy control subjects the odds ratio for tPA in the upper quartile compared with the lowest quartile was 4.23 (3.02-5.92), These data su ggest that the associations of tPA with acute thrombosis are independe nt of levels of PAI-1 but the mechanisms whereby enhanced fibrinolysis may predispose to thrombosis remain unclear.