Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease

Abstract

The pivotal role of hypoactive endogenous fibrinolysis in the occurrence of thrombotic cardiovascular events is now well-recognized. To evaluate the diagnostic and prognostic role of impaired fibrinolysis, plasma fibrinolysis markers have been investigated in large prospective studies in both healthy individuals and patients with established coronary disease. Antigen and activity levels of components of the fibrinolytic system were measured by immunoassays, which replaced earlier global fibrinolysis tests. This review covers 45 studies in nearly 50,000 subjects, examining the association between plasma markers of fibrinolysis and coronary artery disease, to establish the usefulness of these markers in predicting future cardiovascular events. The predictive value of plasma levels of tissue-type plasminogen activator, platelet activator inhibitor-1, plasmin-antiplasmin complex, D-dimer, thrombin activatable fibrinolysis inhibitor, and lipoprotein(a) for major adverse cardiac events is highly variable and conflicting, especially after adjusting for conventional risk factors, judging from the published data in the last decade. The value of fibrinolysis activity markers is very limited in aiding diagnosis and risk stratification in the individual patient, on the basis of the weak prognostic values obtained in some studies and the lack of power in others. The physiological limitations of such markers in reflecting endogenous fibrinolysis is discussed. The emerging novel global assays of fibrinolysis will require large-scale clinical trials before their prognostic power or superiority to multiple biomarker measurements can be evaluated.