Elevated Plasma Levels of Plasminogen Activator Inhibitor-1 Are Associated with Risk of Future Incident Venous Thromboembolism

Overview

Journal J Thromb Haemost

Publisher Elsevier

Specialty Hematology

Date 2022 Mar 15

PMID 35289062

Authors

Tobias Frischmuth

Kristian Hindberg

Pal Aukrust

Thor Ueland

Sigrid K Braekkan

John-Bjarne Hansen

Vania M Morelli

Affiliations

Soon will be listed here.

Abstract

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/m vs. <25 kg/m ), 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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