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

  • van den Berg, Victor J1, 2, 3
  • Bouwens, Elke1
  • Umans, Victor A W M2
  • de Maat, Moniek4
  • Manintveld, Olivier C1
  • Caliskan, Kadir1
  • Constantinescu, Alina A1
  • Mouthaan, Henk5
  • Cornel, Jan-Hein2
  • Baart, Sara1, 3
  • Akkerhuis, K Martijn1
  • Boersma, Eric1
  • Kardys, Isabella1
  • 1 Department of Cardiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. , (Netherlands)
  • 2 Department of Cardiology, Northwest Clinics, Alkmaar, The Netherlands. , (Netherlands)
  • 3 The Netherlands Heart Institute, Utrecht, The Netherlands. , (Netherlands)
  • 4 Department of Hematology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. , (Netherlands)
  • 5 Olink Proteomics AB, Uppsala, Sweden. , (Sweden)
Published Article
Thrombosis and Haemostasis
Georg Thieme Verlag KG
Publication Date
Dec 01, 2019
DOI: 10.1055/s-0039-1696973
PMID: 31659734


This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). 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. 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. 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. Georg Thieme Verlag KG Stuttgart · New York.

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