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. 2022 Jul;20(7):1618-1626.
doi: 10.1111/jth.15701. Epub 2022 Mar 25.

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

Tobias Frischmuth  1   2 , Kristian Hindberg  1 , Pål Aukrust  1   3   4   5 , Thor Ueland  1   3   4 , Sigrid K Braekkan  1   2 , John-Bjarne Hansen  1   2 , Vânia M Morelli  1   2
Affiliations

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

Tobias Frischmuth et al. J Thromb Haemost. 2022 Jul.

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/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.

Keywords: deep vein thrombosis; fibrinolysis; obesity; plasminogen activator inhibitor 1; pulmonary embolism; venous thromboembolism.

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Conflict of interest statement

There are no conflicts of interest reported by any of the authors.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study population. The flowchart illustrates the nested case‐control study derived from the fourth survey of the Tromsø study (1994–1995). VTE, venous thromboembolism
FIGURE 2
FIGURE 2
Plot of estimated odds ratios (ORs) for overall venous thromboembolism (VTE) as a function of time from blood sampling in Tromsø 4 (1994–1995) to VTE events. Participants with plasma levels of plasminogen activator inhibitor 1 (PAI‐1) in the highest tertile (T3) were compared to those with levels in the lowest tertile (T1, reference category). Circles indicate ORs adjusted for age, sex, body mass index, and C‐reactive protein. Solid blue circles indicate ORs with P values <.05. The number of VTE events are described above the plot
See this image and copyright information in PMC

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