Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure

Objectives: This study sought to investigate the clinical correlates and prognostic roles of urokinase-type plasminogen activator receptor (uPAR) on circulating monocytes in patients with coronary artery disease (CAD). Methods: 263 angina patients were included in this study. The percentage of uPAR expressing monocytes (PUEM) and the mean fluorescence intensity (MFI) index of uPAR were measured using flow cytometry. Patient follow-up was on average 604 days. Major adverse cardiac events (MACE) were defined as a composite of cardiac death, reinfarction, acute heart failure and hospitalization for revascularization. Results: The PUEM and MFI index levels were significantly more elevated in acute coronary syndrome patients than in stable ones. uPAR expressions on circulating monocytes at admission were correlated to inflammatory biomarkers and myocardial necrosis. Logistic regression analysis revealed that PUEM ≥15% (OR 21.96, 95% CI 7.31-65.98, p < 0.001) and uPAR MFI index ≥3.00 (OR 3.54, 95% CI 1.18-10.59, p = 0.024) were independent determinants of clinical instability in patients with CAD. When followed up, a high PUEM level at admission was an independent prognostic parameter for long-term MACE (HR 3.99, 95% CI 1.31-12.11, p = 0.015). Conclusions: uPAR expression on circulating monocytes is associated with clinical instability and myocardial necrosis and independently predicts the risk of MACE in patients with CAD.

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Longitudinally Measured Fibrinolysis Factors are Strong Predictors of Clinical Outcome in Patients with Chronic Heart Failure: The Bio-SHiFT Study

Thrombosis and Haemostasis ◽

10.1055/s-0039-1696973 ◽

2019 ◽

Vol 119 (12) ◽

pp. 1947-1955

Author(s):

Victor J. van den Berg ◽

Elke Bouwens ◽

Victor A. W. M. Umans ◽

Moniek de Maat ◽

Olivier C. Manintveld ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Plasminogen Activator ◽

Left Ventricular ◽

Tissue Type ◽

Cardiac Events ◽

Type Plasminogen Activator ◽

Adverse Cardiac Events ◽

Pai 1

Abstract Objective This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). Methods A median of 9 (interquartile range [IQR] 5–10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4–2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. Results Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28–3.45) for PAI-1, 1.91 (1.18–3.24) for uPA, and 3.96 (2.48–6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. Conclusion Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.

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Soluble urokinase-type plasminogen activator receptor strongly predicts global mortality in acute heart failure patients: insight from the STADE-HF registry

Future Science OA ◽

10.2144/fsoa-2020-0197 ◽

2021 ◽

pp. FSO697

Author(s):

Fabien Huet ◽

Anne-Marie Dupuy ◽

Claire Duflos ◽

Cintia Azara Reis ◽

Nils Kuster ◽

...

Keyword(s):

Heart Failure ◽

Plasminogen Activator ◽

Acute Heart Failure ◽

Prognostic Indicator ◽

Supar Level ◽

Risk Of Mortality ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Significant Difference ◽

Plasminogen Activator Receptor

Background: Whether soluble urokinase-type plasminogen activator receptor (suPAR) could be a valuable prognostic indicator remains uncertain. Materials & methods: Patients from STADE-HF (Soluble Suppression of Tumorigenesis-2 as a Help for Management of Diagnosis, Evaluation and Management of Heart Failure) were included for analysis. Results: 95 patients were included. The suPAR level of expression was significantly higher in the group of patients who died at one month (7.90 ± 4.35 ng/ml vs 11.94 ± 6.86 ng/ml; p < 0.05) or 1 year (7.28 ± 4.27 ng/ml vs 11.81 ± 4.88 ng/ml; p < 0.01), but there was no significant difference according to the readmission. Conclusion: High suPAR levels during hospitalization for acute heart failure were highly predictive for the risk of mortality, but not the risk of readmission.

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