Abstract 15603: Discovery of Plasminogen Activator Inhibitor-1 Platelet-derived Extracellular Vesicles to Predict Major Adverse Cardiac Events

Abstract

Objective: To evaluate the utility of plasminogen activator inhibitor-1 positive platelet-derived extracellular vesicles (PAI-1 + PEV) as a biomarker for major adverse cardiac events (MACE) following angiography. Background: The stented coronary artery is at high-risk for complications, predominantly in the form of stent thrombosis and in-stent restenosis. Clinical risk scores have been attempted but no current models nor biomarkers yet accurately identifies the high-risk cohort following revascularization. Methods: PAI-1 + PEV was measured by flow cytometry in 172 patients undergoing coronary angiography. Biological characteristics and utility of PAI-1 + PEV as a biomarker were evaluated. The primary outcome was the incidence of MACE (composite of death, myocardial infarction, cerebrovascular accident, and unplanned revascularization) at 12 months. Results: During a median follow-up period of 377 days (IQR, 269.5 to 442.5 days), 38 patients (20.9%) experienced MACE. In this study, the existence of PAI-1 + PEV complex was validated by flow cytometry (Figure 1A). Furthermore, low log-transformed PAI-1 + PEV levels were associated with MACE (4.17 0.40 vs. 4.33 0.59 logPAI-1 + PEV, p=0.02). After adjustment for known clinical risk factors, low PAI-1 + PEV levels were independently associated with MACE with a hazard ratio of 7.79 (95% CI, 1.87 to 32.4, p=0.005). Finally, low plasma PAI-1 + PEV levels was predictive of MACE in both the discovery and validation cohort (Figure 1B-C). Conclusion: Our results demonstrate the existence of a PAI-1 + PEV and its potential utility as a biomarker to predict MACE. Low plasma PAI-1 + PEV levels was predictive of MACE in both the discovery and validation cohort.