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Hemostasis
Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study
Ferrata Storti Foundation
Haematologica 2020 Volume 105(9):2327-2334
Pauline C.S. van Paridon,1,2* Marina Panova-Noeva,2* Rene van Oerle,1 Andreas Schulz,3 Iris M. Hermanns,3,4 Jürgen H. Prochaska,2,3,5 Natalie Arnold,3 Harald Binder,6,7 Irene Schmidtmann,7 Manfred E. Beutel,8 Norbert Pfeiffer,9 Thomas Münzel,5,10 Karl J. Lackner,10,11 Hugo ten Cate,1,2 Philipp S. Wild2,3,10# and Henri M.H. Spronk1#
1Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands; 2Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany; 3Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; 4University of Applied Sciences, Hochschule Fresenius, Idstein, Germany; 5Cardiology I, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; 6Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; 7Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg- University Mainz, Germany; 8Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; 9Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; 10DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany and 11Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Germany
*PCSvP and MP-N contributed equally as co-first authors. #PSW and HMHS contributed equally as co-senior authors.
ABSTRACT
Thrombin generation may be a potential tool to improve risk strat- ification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovas- cular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endoge- nous thrombin potential, and peak height were derived from the throm- bin generation curve. Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Cox regression models adjusted for age, sex, cardiovascular risk factors and vitamin K antagonists investigated the association between throm- bin generation parameters and total mortality. Lag time was positively associated with obesity and dyslipidaemia for both sexes (P<0.0001). Obesity was also positively associated with endogenous thrombin potential in both sexes (P<0.0001) and peak height in males (1 pM tissue factor, P=0.0048) and females (P<0.0001). Cox regression models showed an increased mortality in individuals with lag time (1 pM tissue factor, hazard ratio=1.46, 95% confidence interval: 1.07-2.00; P=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio=1.50, 95% confidence interval: 1.06-2.13; P=0.023) above the 95th percentile of the reference group, independently of the cardiovascular risk profile.
Correspondence:
HENRI M.H. SPRONK
henri.spronk@maastrichtuniversity.nl
Received: March 13, 2019. Accepted: December 3, 2019. Pre-published: December 5, 2019.
doi:10.3324/haematol.2019.221655 ©2020 Ferrata Storti Foundation
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haematologica | 2020; 105(9)
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