Evaluation of plasminogen activator inhibitor-1 as a biomarker of unplanned revascularization and major adverse cardiac events in coronary angiography and percutaneous coronary intervention

Richard G Jung; Trevor Simard; Pietro Di Santo; Shan Dhaliwal; Caleb Sypkes; Anne-Claire Duchez; Robert Moreland; Katlyn Taylor; Simon Parlow; Sarah Visintini; Alisha Labinaz; Jeffrey Marbach; Kiran Sarathy; Jordan Bernick; Joanne Joseph; Paul Boland; Omar Abdel-Razek; David T Harnett; F Daniel Ramirez; Benjamin Hibbert

doi:10.1016/j.thromres.2020.04.025

Evaluation of plasminogen activator inhibitor-1 as a biomarker of unplanned revascularization and major adverse cardiac events in coronary angiography and percutaneous coronary intervention

Thromb Res. 2020 Jul:191:125-133. doi: 10.1016/j.thromres.2020.04.025. Epub 2020 Apr 24.

Authors

Richard G Jung¹, Trevor Simard², Pietro Di Santo³, Shan Dhaliwal⁴, Caleb Sypkes⁵, Anne-Claire Duchez⁵, Robert Moreland⁶, Katlyn Taylor⁷, Simon Parlow⁸, Sarah Visintini⁹, Alisha Labinaz¹⁰, Jeffrey Marbach¹¹, Kiran Sarathy¹², Jordan Bernick¹³, Joanne Joseph¹⁴, Paul Boland¹⁵, Omar Abdel-Razek¹¹, David T Harnett¹⁵, F Daniel Ramirez¹⁶, Benjamin Hibbert¹⁷

Affiliations

¹ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
² CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
³ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
⁴ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁶ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada.
⁸ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Internal Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
⁹ Berkman Library, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹⁰ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹¹ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹² CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹³ Ottawa Cardiovascular Research Methods Center, Ottawa, Ontario, Canada.
¹⁴ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Internal Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
¹⁵ Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
¹⁶ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Hôpital Cardiologique du Haut-Lévêque, CHU Bordeaux, Bordeaux-Pessac, France; L'Institut de Rythmologie et Modélisation Cardiaque (LIRYC), University of Bordeaux, France.
¹⁷ CAPITAL Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Vascular Biology and Experimental Medicine Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. Electronic address: bhibbert@ottawaheart.ca.

PMID: 32447094
DOI: 10.1016/j.thromres.2020.04.025

Abstract

Background: The stented coronary artery remains at high-risk of complications, particularly in the form of stent thrombosis and in-stent restenosis. Improving our ability to identify patients at high-risk for these complications may provide opportunities for intervention. PAI-1 has been implicated in the pathophysiology of stent complications in preclinical studies, suggesting it may be a clinically valuable biomarker to predict adverse events following percutaneous coronary intervention.

Methods: Plasma PAI-1 levels were measured in 910 subjects immediately after coronary angiography between 2015 and 2019. The primary outcome was the incidence of unplanned revascularization (UR) at 12 months. The secondary outcome was the incidence of major adverse cardiac events (MACE).

Results: UR and MACE occurred in 49 and 103 patients in 12 months. Reduced plasma PAI-1 levels were associated with UR (4386.1 pg/mL [IQR, 2778.7-6664.6], n = 49, vs. 5247.6 pg/mL [IQR, 3414.1-7836.1], n = 861; p = 0.04). Tertile PAI-1 levels were predictive of UR after adjustment for known clinical risk factors associated with adverse outcomes. In post-hoc landmark analysis, UR was enhanced with low plasma PAI-1 levels for late complications (beyond 30 days). Finally, an updated systematic review and meta-analysis did not reveal an association between plasma PAI-1 and MACE.

Conclusion: PAI-1 levels are not independently associated with UR nor MACE in patients undergoing angiography but associated with UR following adjustment with known clinical factors. In our landmark analysis, low PAI-1 levels were associated with UR for late stent complications. As such, future studies should focus on the mediatory role of PAI-1 in the pathogenesis of stent complications.

Keywords: Biomarkers; Coronary artery disease; Percutaneous coronary intervention; Plasminogen activator inhibitor-1.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Biomarkers
Coronary Angiography*
Coronary Artery Disease* / diagnosis
Coronary Artery Disease* / surgery
Humans
Percutaneous Coronary Intervention* / adverse effects
Plasminogen Activator Inhibitor 1*
Risk Factors
Stents
Treatment Outcome

Substances

Biomarkers
Plasminogen Activator Inhibitor 1