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

Pauline C. S. van Paridon; Marina Panova-Noeva; Rene van Oerle; Andreas Schulz; Jürgen H. Prochaska; Natalie Arnold; Irene Schmidtmann; Manfred Beutel; Norbert Pfeiffer; Thomas Münzel; Karl J. Lackner; Tilman M. Hackeng; Hugo ten Cate; Philipp S. Wild; Henri M. H. Spronk

doi:10.1055/s-0040-1715897

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2021; 121(02): 174-181
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‡^*

¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

²Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Marina Panova-Noeva‡^*

²Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

⁴German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

,

Rene van Oerle

¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

,

Andreas Schulz

³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Jürgen H. Prochaska

²Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

⁴German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

,

Natalie Arnold

³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Irene Schmidtmann

⁵Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Manfred Beutel

⁶Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Norbert Pfeiffer

⁷Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Thomas Münzel

⁴German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

⁸Center for Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Karl J. Lackner

⁴German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

⁹Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Tilman M. Hackeng

¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

,

Hugo ten Cate

¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

²Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

,

Philipp S. Wild‡^*

²Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

⁴German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany

,

Henri M. H. Spronk^*

¹Department of Internal Medicine, Laboratory for Clinical Thrombosis and Hemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands

› Author Affiliations

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.

Keywords

total TFPI activity - population - epidemiology - mortality - cardiovascular risk factors

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References

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