title: Determinants of tPA antigen and associations with coronary artery disease and acute cerebrovascular disease.
abstract: The aim of this study was to determine the association of tPA antigen levels with CAD and ischaemic stroke and whether associations are independent of levels of PAI-1 antigen. In subjects with CAD (n = 247) tPA was associated with the number of coronary arteries with > or = 50% stenosis, but this association was lost after adjustment for PAI-1, which was found to be the largest determinant of tPA levels in linear regression models and accounted for as much as 38% of the variation in levels. Levels of tPA were significantly higher in patients with a history of MI compared with those without, even after adjustment 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 comparing patients with MI to patients without MI, the odds ratio for tPA levels 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) were 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 suggest that the associations of tPA with acute thrombosis are independent of levels of PAI-1 but the mechanisms whereby enhanced fibrinolysis may predispose to thrombosis remain unclear.
authors.affiliation: Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, UK. medamc@medphysics.leeds.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Carter
authors.forename: A J
authors.initials: AJ
authors.lastname: Catto
authors.forename: P J
authors.initials: PJ
authors.lastname: Grant
mesh_terms: D015415:Biomarkers; D002561:Cerebrovascular Disorders / Q000097:blood / Q000276:immunology*; D003327:Coronary Disease / Q000097:blood / Q000276:immunology*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D019396:Tissue Polypeptide Antigen / Q000097:blood*
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D019396:Tissue Polypeptide Antigen