Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism

Background Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of fibrinolysis, is frequently elevated in obesity and could potentially mediate the risk of venous thromboembolism (VTE) in obese subjects. However, whether PAI-1 is associated with VTE remains uncertain. Objective To investig...

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Bibliographic Details
Published in:Journal of Thrombosis and Haemostasis
Main Authors: Frischmuth, Tobias, Hindberg, Kristian, Aukrust, Pål, Ueland, Thor, Brækkan, Sigrid Kufaas, Hansen, John Bjarne, Morelli, Vania Maris
Format: Article in Journal/Newspaper
Language:English
Published: 2022
Subjects:
Tromsø
Online Access:http://hdl.handle.net/10852/96661
https://doi.org/10.1111/jth.15701
Description
Summary:Background Plasminogen activator inhibitor-1 (PAI-1), the main inhibitor of fibrinolysis, is frequently elevated in obesity and could potentially mediate the risk of venous thromboembolism (VTE) in obese subjects. However, whether PAI-1 is associated with VTE remains uncertain. Objective To investigate the association between plasma PAI-1 levels and risk of future incident VTE and whether PAI-1 could mediate the VTE risk in obesity. Methods A population-based nested case-control study, comprising 383 VTE cases and 782 age- and sex-matched controls, was derived from the Tromsø Study cohort. PAI-1 antigen levels were measured in samples collected at cohort inclusion. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE across PAI-1 tertiles. Results The VTE risk increased dose-dependently across PAI-1 tertiles (P for trend <.001) in the age- and sex-adjusted model. The OR of VTE for the highest versus lowest tertile was 1.73 (95% CI 1.27–2.35), and risk estimates were only slightly attenuated with additional stepwise adjustment for body mass index (BMI; OR 1.59, 95% CI 1.16–2.17) and C-reactive protein (CRP; OR 1.54, 95% CI 1.13–2.11). Similar results were obtained for provoked/unprovoked events, deep vein thrombosis, and pulmonary embolism. In obese subjects (BMI of ≥30 kg/m2 vs. <25 kg/m2), PAI-1 mediated 14.9% (95% CI 4.1%-49.4%) of the VTE risk in analysis adjusted for age, sex, and CRP. Conclusion Our findings indicate that plasma PAI-1 is associated with increased risk of future incident VTE and has the potential to partially mediate the VTE risk in obesity.

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