E-Science Station

Coronary revascularization and optimal risk factor management remains central for management of obstructive coronary artery disease. However, identification of patients at risk for adverse events following coronary angiography remains limited despite the development of clinical risk scores. Furthermore, extracellular vesicles (EVs) are pro-thrombotic particles which are elevated in myocardial infarction and may serve as a potential biomarker of major adverse cardiac events (MACE). This study sought to evaluate the utility of plasminogen activatorinhibitor-1 positive platelet-derived extracellular vesicles (PAI-1⁺PEV) as a biomarker for major adverse cardiac events (MACE) followingangiography.

The University of Ottawa Heart Institute is a regional tertiary cardiac care center in the capital region of Canada. The CAPITAL Revascularization Registry is used to capture baseline procedural and patient data. Standardized clinical follow-up is completed at one-year for clinical outcomes. Plasma was collected from patients at the time of catheterization and frozen at -80 degrees Celsius until EV analysis. Platelet PAI-1 EV (Annexin V+/CD41+/PAI-1+EVs on flow cytometry) was isolated from plasma by centrifugation at 20,000 x g, stained, and measured by flow cytometry. A ROC curve was generated in order to evaluate the performance of platelet PAI-1 EVs as a biomarker to identify patients at-risk for MACE.

From August 2016 to August 2019, a total of 1851 patients had completed one-year follow-up with frozen plasma. Of these, 172 (9.3%) patients had their extracellular vesicles measured by flow cytometry. Duringa median follow-up period of 377 days (IQR, 269.5 to 442.5 days), 38 patients(20.9%) experienced MACE. The mean age of our cohort was 67.9 +/- 11.0 years and 69.2% were male. 85 (49.4%) patients were referred for CABG or underwent PCI at the time of coronary angiography. 65 (37.8%) patients had type 2 diabetes, 118 (68.6%) had hypertension and dyslipidemia, 35 (20.3%) were active smokers, and 77 (44.8%) were diagnosed with acute coronary syndrome (ACS) at time of angiography. Lowlog-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=0.0005). Finally, low plasma PAI-1⁺ PEV levels were predictive of MACE in both the discovery and validation cohort.

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 were predictive of MACE in both the discovery and validation cohort.