Increased levels of tissue plasminogen activator antigen and factor VIII activity in nonvalvular atrial fibrillation: Relation to predictors of thromboembolism

Introduction: Given that nonvalvular atrial fibrillation (AF)-associated st roke can be either cardioembolic or atherothrombotic, we investigated the r elationships between nonvalvular AF and hemostatic factors reflecting intri nsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity ). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiogr aphic predictors of thromboembolism had higher levels of these factors. Methods and Results: Of the 3,212 participants of a Chinese population-base d study, 53 subjects (1.7 %) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and fac tor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, age, s ex, body mass index, systolic blood pressure, total cholesterol, triglyceri des, and left ventricular systolic dysfunction. Features independently asso ciated with factor VIII activity levels included AF, age, and total cholest erol. Levels of both t-PA antigen and factor VIII activity were primarily e levated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemosta tic factors examined were similar to those without AF. Conclusion: We demonstrated that nonvalvular AF was independently associate d with increased peripheral levels of t-PA antigen and factor VIII activity . Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are in dependently predictive of future thromboembolic events in AF patients requi res further investigation.