TY - JOUR
T1 - Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample
AU - van Paridon, Pauline C. S.
AU - Panova-Noeva, Marina
AU - van Oerle, Rene
AU - Schulz, Andreas
AU - Prochaska, Juergen H.
AU - Arnold, Natalie
AU - Schmidtmann, Irene
AU - Beutel, Manfred
AU - Pfeiffer, Norbert
AU - Muenzel, Thomas
AU - Lackner, Karl J.
AU - Hackeng, Tilman M.
AU - ten Cate, Hugo
AU - Wild, Philipp S.
AU - Spronk, Henri M. H.
N1 - Funding Information:
The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung RheinlandP-falz 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)
Publisher Copyright:
© 2021 Georg Thieme Verlag. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - total TFPI activity
KW - population
KW - epidemiology
KW - mortality
KW - cardiovascular risk factors
KW - VENOUS THROMBOEMBOLISM
KW - MYOCARDIAL-INFARCTION
KW - FACTOR-V
KW - PLASMA
KW - WOMEN
KW - TFPI
KW - ESTROGEN
U2 - 10.1055/s-0040-1715897
DO - 10.1055/s-0040-1715897
M3 - Article
C2 - 32877953
SN - 0340-6245
VL - 121
SP - 174
EP - 181
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 02
ER -