Prognostic role of tissue plasminogen activator in coronary artery disease with or without aortic valve sclerosis

AIMS: We sought to investigate the relationship between circulating tissue plasminogen activator (t‐PA) level and long‐term outcomes in stable coronary artery disease patients with or without aortic valve sclerosis (AVSc). METHODS AND RESULTS: Serum levels of t‐PA were determined in 347 consecutive stable angina patients with (n = 183) or without (n = 164) AVSc. Outcomes were prospectively recorded as planned clinic evaluations every 6 months up to 7 years. The primary endpoint was a composite of cardiovascular death and rehospitalization due to heart failure. The secondary endpoint included all‐cause mortality, cardiovascular death, and rehospitalization due to heart failure. Serum t‐PA was significantly higher in AVSc than in non‐AVSc patients (2131.22 pg/mL vs. 1495.85 pg/mL, P < 0.001). For patients with AVSc, those with t‐PA level above the median (>1840.68 pg/mL) were more likely to meet the primary and secondary endpoints (all P < 0.001). After adjusting for potential confounding factors, serum t‐PA level remained significantly predictive for each endpoint in the Cox proportional hazard models. The prognostic value of t‐PA was good, with an AUC‐ROC of 0.753 (P < 0.001). The combination of t‐PA with traditional risk factors improved the risk reclassification of AVSc patients, with a net reclassification index of 0.857 and an integrated discrimination improvement of 0.217 (all P < 0.001). However, for patients without AVSc, both primary and secondary endpoints were similar, irrespective of t‐PA levels. CONCLUSIONS: Elevated circulating t‐PA confers an increased risk for poor long‐term clinical outcomes in stable coronary artery disease patients with AVSc.