Thromb Haemost
DOI: 10.1055/s-0040-1715897
Coagulation and Fibrinolysis

Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample

Pauline C. S. van Paridon*
1  Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
2  Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Marina Panova-Noeva*
2  Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
3  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
4  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
,
Rene van Oerle
1  Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
,
Andreas Schulz
3  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Jürgen H. Prochaska
2  Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
3  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
4  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
,
Natalie Arnold
3  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Irene Schmidtmann
5  Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Manfred Beutel
6  Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Norbert Pfeiffer
7  Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Thomas Münzel
4  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
8  Center for Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Karl J. Lackner
4  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
9  Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Tilman M. Hackeng
1  Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
,
Hugo ten Cate
1  Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
2  Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
,
Philipp S. Wild*
2  Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
3  Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
4  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany
,
Henri M. H. Spronk*
1  Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands
› Author Affiliations
Funding The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung RheinlandPfalz für Innovation,” contract AZ 961–386261/733), the research programs “Wissenschafft Zukunft” and “Center for Translational Vascular Biology (CTVB)” of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including unrestricted grants for the Gutenberg Health Study. This work was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003) and the Center for Translational Vascular Biology (CTVB) of the University Medical Center Mainz (to P.S.W.). H.t.C. was a Fellow of the Gutenberg Research Foundation.

Abstract

Objective Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality.

Methods Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality.

Results Multivariable linear regression analysis identified smoking (β 0.095 [0.054–0.136]) as a positive determinant for total TFPI activity, while diabetes (β –0.072 [–0.134 to –0.009]), obesity (β –0.063 [–0.101 to –0.024]), and history of coronary artery disease (CAD) were negatively associated with total TFPI activity, independent of age, sex, and the remaining cardiovascular risk factors. After adjustment for lipoprotein levels, the association between total TFPI activity levels and obesity and CAD was lost. The analysis additionally revealed a strong positive association between total TFPI activity levels and low-density lipoprotein (β 0.221 [0.204–0.237]). The Cox regression models revealed that a higher total TFPI activity, above 97.5th percentile of the reference group, was associated with an increased mortality risk (hazard ratio = 2.58 [95% confidence interval: 1.49–4.47]), independent of age, sex, and cardiovascular risk profile.

Conclusion In the Gutenberg Health Study population-based cohort, the highest percentage of total TFPI correlated with an increased mortality risk. While elevated TFPI may reflect endothelial cell activation, the associations between total TFPI activity and obesity and CAD, points to additional mechanistic interactions.

* Equal contribution.




Publication History

Received: 13 May 2020

Accepted: 24 July 2020

Publication Date:
02 September 2020 (online)

Georg Thieme Verlag KG
Stuttgart · New York