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Thromb Haemost 2017; 117(03): 471-478
DOI: 10.1160/TH16-08-0600
Coagulation and Fibrinolysis
Schattauer GmbH

Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction

Max-Paul Winter   *
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Marcus E. Kleber   *
2   Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
5   Mannheim Institute for Public Health, Social- and Preventive Medicine, Mannheim, Germany
,
Lorenz Koller
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Patrick Sulzgruber
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Hubert Scharnagl
6   Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
,
Graciela Delgado
2   Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
,
Georg Goliasch
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
,
Winfried März
2   Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
7   Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz Medical University, Graz, Austria
8   Synlab Academy, Synlab Services LLC, Mannheim, Germany
,
Alexander Niessner
1   Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
› Institutsangaben Financial support: The study was supported and received funding for materials by the ‘Association for the Promotion of Research in Atherosclerosis, Thrombosis and Vascular Biology’ (ATVB). (Vienna, Austria).
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Publikationsverlauf

Received: 06. August 2016

Accepted after major revision: 16. November 2016

Publikationsdatum:
28. November 2017 (online)

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Summary

Heart failure with preserved ejection fraction (HFpEF) represents a major epidemic, clinical and public health problem with rising patient numbers every year. Traditional markers for heart failure have been shown to be of limited sensitivity in patients with HFpEF, as those do not reflect pathophysiology of the disease properly. Dysregulation of haemostasis is thought to be central for the initiation and progression of HFpEF. For this reason, we aimed to assess markers of fibrinolytic activity as potential biomarkers for risk assessment in patients with HFpEF. We evaluated blood coagulation parameters in 370 patients with HFpEF included in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. Within an observation period of 9.7 years, 40 percent of these patients died from any cause. tPA/PAI-1 complex significantly predicted all-cause mortality with a hazard ratio (HR) of 1.24 (95 % confidence interval [CI] 1.04–1.47) per increase of 1 SD and cardiovascular mortality with a HR 1.26 (95 % CI 1.02–1.56) per increase of 1 SD. Both associations remained significant after adjustment for cardiovascular risk factors, N-terminal pro–B-type natriuretic peptide (NT-proBNP) and frequent HFpEF- related comorbidities. Importantly, tPA/PAI-1 complex had additional prognostic value above and beyond NT-proBNP as indicated by integrated discrimination improvement (0.0157, p=0.017). In conclusion, the concentration of tPA/ PAI-1 complex is an independent predictor of mortality from all causes and from cardiovascular causes in patients with HFpEF. The concomitant measurement of tPA/PAI-1 complex might be useful in clinical practice to add prognostic value to traditional markers of heart failure.

Keywords

Heart failure and preserved ejection fraction (HFpEF) - tissue plasminogen activator (tPA) - plasminogen activator inhibitor 1(PAI-1)

Notes

* These authors contributed equally