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, Juergen H. Prochaska, Natalie Arnold, Irene Schmidtmann, Manfred Beutel, Norbert Pfeiffer, Thomas Muenzel, Karl J. Lackner, Tilman M. Hackeng, Hugo ten Cate, Philipp S. Wild, Henri M. H. Spronk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


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 (beta 0.095 [0.054-0.136]) as a positive determinant for total TFPI activity, while diabetes (beta-0.072 [-0.134 to -0.009]), obesity (beta-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 (beta 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.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalThrombosis and Haemostasis
Issue number02
Early online date2 Sep 2020
Publication statusPublished - Feb 2021


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

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