Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19
Background Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive...
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.025198 |
| _version_ | 1797857393248305152 |
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| author | Shengyuan Luo Alexi Vasbinder Jeanne M. Du‐Fay‐de‐Lavallaz Joanne Michelle D. Gomez Tisha Suboc Elizabeth Anderson Annika Tekumulla Husam Shadid Hanna Berlin Michael Pan Tariq U. Azam Ibrahim Khaleel Kishan Padalia Chelsea Meloche Patrick O'Hayer Tonimarie Catalan Pennelope Blakely Christopher Launius Kingsley‐Michael Amadi Rodica Pop‐Busui Sven H. Loosen Athanasios Chalkias Frank Tacke Evangelos J. Giamarellos‐Bourboulis Izzet Altintas Jesper Eugen‐Olsen Kim A. Williams Annabelle Santos Volgman Jochen Reiser Salim S. Hayek |
| author_facet | Shengyuan Luo Alexi Vasbinder Jeanne M. Du‐Fay‐de‐Lavallaz Joanne Michelle D. Gomez Tisha Suboc Elizabeth Anderson Annika Tekumulla Husam Shadid Hanna Berlin Michael Pan Tariq U. Azam Ibrahim Khaleel Kishan Padalia Chelsea Meloche Patrick O'Hayer Tonimarie Catalan Pennelope Blakely Christopher Launius Kingsley‐Michael Amadi Rodica Pop‐Busui Sven H. Loosen Athanasios Chalkias Frank Tacke Evangelos J. Giamarellos‐Bourboulis Izzet Altintas Jesper Eugen‐Olsen Kim A. Williams Annabelle Santos Volgman Jochen Reiser Salim S. Hayek |
| author_sort | Shengyuan Luo |
| collection | DOAJ |
| description | Background Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID‐19. Whether suPAR levels identify patients with COVID‐19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID‐19 with suPAR and D‐dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine‐Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D‐dimer levels. There was a positive association between suPAR and D‐dimer (β=7.34; P=0.002). Adjusted for clinical covariables, including D‐dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51–4.75]; P<0.001). Findings were consistent when stratified by D‐dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D‐dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D‐dimer in patients hospitalized for COVID‐19. Combining suPAR and D‐dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866. |
| first_indexed | 2024-04-09T20:57:03Z |
| format | Article |
| id | doaj.art-fced70faf2de433098fd1689f287ccf8 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-09T20:57:03Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-fced70faf2de433098fd1689f287ccf82023-03-29T18:38:57ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-09-01111810.1161/JAHA.122.025198Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19Shengyuan Luo0Alexi Vasbinder1Jeanne M. Du‐Fay‐de‐Lavallaz2Joanne Michelle D. Gomez3Tisha Suboc4Elizabeth Anderson5Annika Tekumulla6Husam Shadid7Hanna Berlin8Michael Pan9Tariq U. Azam10Ibrahim Khaleel11Kishan Padalia12Chelsea Meloche13Patrick O'Hayer14Tonimarie Catalan15Pennelope Blakely16Christopher Launius17Kingsley‐Michael Amadi18Rodica Pop‐Busui19Sven H. Loosen20Athanasios Chalkias21Frank Tacke22Evangelos J. Giamarellos‐Bourboulis23Izzet Altintas24Jesper Eugen‐Olsen25Kim A. Williams26Annabelle Santos Volgman27Jochen Reiser28Salim S. Hayek29Department of Medicine Rush University Medical Center Chicago ILDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDepartment of Medicine University Hospital Basel Basel SwitzerlandDivision of Cardiology Smidt Heart Institute, Cedars Sinai Medical Center Los Angeles CADepartment of Medicine Rush University Medical Center Chicago ILDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDepartment of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine University of Michigan Ann Arbor MIClinic for Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty University Hospital Düsseldorf Düsseldorf GermanyDepartment of Anesthesiology, Faculty of Medicine University of Thessaly Larisa GreeceDepartment of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow‐Klinikum Charité University Medicine Berlin Berlin Germany4th Department of Internal Medicine National and Kapodistrian University of Athens Athens GreeceDepartment of Clinical Research Copenhagen University Hospital Hvidovre Hvidovre DenmarkDepartment of Clinical Research Copenhagen University Hospital Hvidovre Hvidovre DenmarkDepartment of Internal Medicine University of Louisville School of Medicine Louisville KYDepartment of Medicine Rush University Medical Center Chicago ILDepartment of Medicine Rush University Medical Center Chicago ILDivision of Cardiology, Department of Internal Medicine University of Michigan Ann Arbor MIBackground Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID‐19. Whether suPAR levels identify patients with COVID‐19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID‐19 with suPAR and D‐dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine‐Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D‐dimer levels. There was a positive association between suPAR and D‐dimer (β=7.34; P=0.002). Adjusted for clinical covariables, including D‐dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51–4.75]; P<0.001). Findings were consistent when stratified by D‐dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D‐dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D‐dimer in patients hospitalized for COVID‐19. Combining suPAR and D‐dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.https://www.ahajournals.org/doi/10.1161/JAHA.122.025198COVID‐19soluble urokinase plasminogen activator receptorthromboembolism |
| spellingShingle | Shengyuan Luo Alexi Vasbinder Jeanne M. Du‐Fay‐de‐Lavallaz Joanne Michelle D. Gomez Tisha Suboc Elizabeth Anderson Annika Tekumulla Husam Shadid Hanna Berlin Michael Pan Tariq U. Azam Ibrahim Khaleel Kishan Padalia Chelsea Meloche Patrick O'Hayer Tonimarie Catalan Pennelope Blakely Christopher Launius Kingsley‐Michael Amadi Rodica Pop‐Busui Sven H. Loosen Athanasios Chalkias Frank Tacke Evangelos J. Giamarellos‐Bourboulis Izzet Altintas Jesper Eugen‐Olsen Kim A. Williams Annabelle Santos Volgman Jochen Reiser Salim S. Hayek Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease COVID‐19 soluble urokinase plasminogen activator receptor thromboembolism |
| title | Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 |
| title_full | Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 |
| title_fullStr | Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 |
| title_full_unstemmed | Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 |
| title_short | Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19 |
| title_sort | soluble urokinase plasminogen activator receptor and venous thromboembolism in covid 19 |
| topic | COVID‐19 soluble urokinase plasminogen activator receptor thromboembolism |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.025198 |
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