Abstract 13552: Clinical Relevance of Endogenous Tissue-plasminogen Activator in Patients With Aortic Valve Sclerosis

Abstract

Introduction: Impaired fibrinolysis featuring elevated tissue plasminogen activator (t-PA) induces cardiovascular outcomes. Aortic valve sclerosis (AVSc) shares similar aspects of pathophysiology with atherosclerosis and correlates with adverse cardiovascular events. Hypothesis: We investigated whether endogenous t-PA is associated with AVSc and clinical outcomes of these patients. Methods: Plasma levels of t-PA were measured in 155 AVSc patients and 140 non-AVSc counterparts. The composite major adverse cardio-cerebral events (MACCE), including cardiovascular death, nonfatal myocardium infarction, stroke, and re-hospitalization because of heart failure or unplanned revascularization were recorded during follow-up in 143 patients with AVSc (median, 6.5 years). Expression of t-PA was detected in human aortic valves with and without sclerosis by immunochemical analysis. Results: Plasma t-PA was higher in patients with AVSc than in those without (median, 2163.10 pg/mL vs 1403.17 pg/mL, p < 0.001). After adjusting for confounding variables, t-PA level remained an independent risk factor for AVSc (OR=1.66, 95%CI: 1.18-2.34, P=0.004). Based on the optimal cut-off of 1787.8 pg/mL determined by X-tile program, AVSc patients with low t-PA displayed better survival free from MACCE than those with high t-PA (p=0.0018). After full adjustment, t-PA was independently associated with composite MACCE (HR=1.33, 95% CI: 1.07-1.66, p=0.009). The area under the curve of plasma t-PA for predicting composite MACCE within three years was 0.71(95%CI: 0.63-0.80). The expression of t-PA was three times higher in sclerotic compared to non-sclerotic aortic valves. Conclusions: Elevated endogenous t-PA in plasma may serve as an indicator of AVSc and is associated with poor clinical outcomes in patients with AVSc.