title: Determinants of plasminogen activator inhibitor-1 activity in survivors of myocardial infarction.
abstract: A significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immunoenzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs = 0.43; p < 0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p < 0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p < 0.0001) and des-31,32-proinsulin (rs = 0.54; p < 0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.
authors.affiliation: Department of Medicine, University College London Medical School, UK.
authors.forename: R P
authors.initials: RP
authors.lastname: Gray
authors.forename: V
authors.initials: V
authors.lastname: Mohamed-Ali
authors.forename: D L
authors.initials: DL
authors.lastname: Patterson
authors.forename: J S
authors.initials: JS
authors.lastname: Yudkin
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D017741:Survivors
chemical_list: D017395:Plasminogen Activator Inhibitor 1