Abstract
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.
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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e025198 |
| Tidsskrift | Journal of the American Heart Association |
| Vol/bind | 11 |
| Udgave nummer | 18 |
| Antal sider | 15 |
| ISSN | 2047-9980 |
| DOI | |
| Status | Udgivet - 2022 |
| Udgivet eksternt | Ja |
Bibliografisk note
Funding Information:Dr Vasbinder is supported by a National Heart, Lung, and Blood Institute– funded postdoctoral fellowship (T32HL007853). Dr Hayek is funded by National Heart, Lung, and Blood Institute 1R01HL153384-01, the National Institute of Diabetes and Digestive and Kidney Diseases 1R01DK12801201A1 and U01-DK119083-03S1, and the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (U-M G024231) award. Dr Giamarellos-Bourboulis is supported by the Hellenic Institute for the Study of Sepsis. Dr Tacke is supported through intramural funds from Charité Universitaetsmedizin Berlin and the Berlin Institute of Health.
Publisher Copyright:
© 2022 The Authors.