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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1651.)
© 2007 American Heart Association, Inc.

Thrombosis

Endothelial Fibrinolytic Capacity Predicts Future Adverse Cardiovascular Events in Patients With Coronary Heart Disease

Simon D. Robinson; Christopher A. Ludlam; Nicholas A. Boon; David E. Newby

From the Centre for Cardiovascular Sciences (S.D.R., D.E.N.), University of Edinburgh, the Department of Haematology (C.A.L.), Royal Infirmary of Edinburgh, and the Department of Cardiology (N.A.B., D.E.N.), Royal Infirmary of Edinburgh, UK.

Correspondence to Dr Simon Robinson, Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh, Scotland, EH16 4SB, UK. E-mail simon.robinson{at}ed.ac.uk

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.

Methods and 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).

Conclusion— 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.

We show that endothelial tissue plasminogen activator (t-PA) release is a distinct marker of endothelial function and that in patients with stable coronary heart disease acute t-PA release predicts an increased risk of future adverse cardiovascular events.

Key Words: coronary heart disease • endothelium • fibrinolysis • survival • vasodilation

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