Endothelial fibrinolytic capacity predicts future adverse cardiovascular events in patients with coronary heart disease.
OBJECTIVE
The endothelium-derived fibrinolytic factor tissue plasminogen activator (t-PA) is a major determinant of vessel patency after coronary plaque rupture and thrombosis. We assessed whether endothelial fibrinolytic capacity predicts atherothrombotic events in patients with coronary heart disease.


RESULTS
Plasma t-PA and plasminogen activator inhibitor (PAI)-1 concentrations were measured during intrabrachial substance P infusion in 98 patients with angiographically proven stable coronary heart disease. Forearm blood flow was measured during infusion of substance P and sodium nitroprusside. Cardiovascular events (cardiovascular death, myocardial infarction [MI], ischemic stroke [CVA], and emergency hospitalization for unstable angina) were determined during 42 months of follow-up. Patients experiencing a cardiovascular event (n=19) had similar baseline characteristics to those free of events. Substance P caused a dose-dependent increase in plasma t-PA concentrations (P<0.001). However, net t-PA release was 72% lower in the patients who experienced death, MI, or CVA, and 48% lower in those who suffered death, MI, CVA or hospitalization for unstable angina (P<0.05). Major adverse cardiovascular events were most frequent in those with the lowest fibrinolytic capacity (P=0.03 for trend); patients with the lowest quartile of t-PA release had the highest rate of adverse events (P=0.01).


CONCLUSIONS
Endothelial fibrinolytic capacity, as measured by stimulated t-PA release, predicts the future risk of adverse cardiovascular events in patients with coronary heart disease. We suggest that endothelial fibrinolytic capacity is a powerful novel determinant of cardiovascular risk.
Robinson
Simon D
SD
Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh, Scotland, EH16 4SB, UK. simon.robinson@ed.ac.uk
Ludlam
Christopher A
CA
Boon
Nicholas A
NA
Newby
David E
DE
D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism*; D011237:Predictive Value of Tests; D011336:Probability; D011446:Prospective Studies; D012720:Severity of Illness Index; D013373:Substance P / Q000008:administration & dosage*; D016019:Survival Analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000378:metabolism*; D016896:Treatment Outcome
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D013373:Substance P; D010959:Tissue Plasminogen Activator