Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor?
OBJECTIVE
To compare the activity of plasminogen activator inhibitor (PAI-1) in diabetic and non-diabetic patients admitted with acute myocardial infarction and to determine whether PAI-1 activity influences reperfusion after thrombolytic therapy.


METHODS
Prospective study of patients admitted with acute myocardial infarction.


METHODS
District general hospital.


METHODS
Reperfusion assessed by time to peak release of creatine kinase-MB isoenzyme.


RESULTS
Baseline PAI-1 activity and antigen concentrations were significantly higher in diabetic patients (n = 45) than in non-diabetic patients (n = 110) (24.6 (6.9) v 18.6 (7.9) AU/ml (AU = arbitrary units) (p = 0.0001) and 58.8 (13.1-328.8) v 41.0 (10.9-125.4) ng/ml (p = 0.004). Time to peak release of creatine kinase-MB was calculated in 123 (80%) patients. In 98 who received thrombolytic therapy the median time to peak enzyme release was 15.5 h (7.5-24 h) in diabetic patients (n = 26) and 12 h (5-26 h) in non-diabetic patients (n = 72) (p = 0.005). In those with a time to peak release of < or = 12 h, indicating likely successful reperfusion, PAI-1 activity was 17.5 (7.8) AU/ml compared with 22.8 (7.7) AU/ml in those with a time to peak release of > 12 h (p = 0.001). In multiple regression analysis both diabetes (p = 0.0001) and PAI-1 activity at admission (p = 0.029) were independently related to successful reperfusion. In 13 patients with evidence of reinfarction in hospital PAI-1 activity on day 3 was 26.7 (6.4) AU/ml compared with 21.7 (6.3) AU/ml in those without evidence of reinfarction (p = 0.032).


CONCLUSIONS
Both raised PAI-1 activity on admission and diabetes were associated with a reduced likelihood of enzymatic evidence of reperfusion after thrombolytic therapy. Increased PAI-1 activity on day 3 was associated with an increased risk of reinfarction. Diabetic patients had higher PAI-1 activity on admission. This may partly explain their reduced likelihood of reperfusion.
Gray
R P
RP
Department of Medicine, University College London Medical School, Whittington Hospital.
Yudkin
J S
JS
Patterson
D L
DL
D001324:Autoantigens / Q000032:analysis; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D009206:Myocardium / Q000201:enzymology*; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology; D013300:Streptokinase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D017211:Treatment Failure
D001324:Autoantigens; D017395:Plasminogen Activator Inhibitor 1; D013300:Streptokinase