Thrombosis Research Center, Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
J Thromb Haemost. 2022 Jul;20(7):1618-1626. doi: 10.1111/jth.15701. Epub 2022 Mar 25.
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.
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.
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.
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.
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.
纤溶酶原激活物抑制剂-1（PAI-1）是纤维蛋白溶解的主要抑制剂，在肥胖症中经常升高，并且可能在肥胖人群中介导静脉血栓栓塞（VTE）的风险。但是，PAI-1 是否与 VTE 相关仍不确定。
研究血浆 PAI-1 水平与未来发生 VTE 的风险之间的关系，以及 PAI-1 是否可以介导肥胖症中的 VTE 风险。
一项基于人群的嵌套病例对照研究，包括 383 例 VTE 病例和 782 例年龄和性别匹配的对照，来源于特罗姆瑟研究队列。在队列纳入时采集的样本中测量了 PAI-1 抗原水平。使用逻辑回归计算 PAI-1 三分位组中 VTE 的比值比（OR）及其 95%置信区间（CI）。
在年龄和性别调整模型中，VTE 风险随 PAI-1 三分位呈剂量依赖性增加（趋势 P<.001）。最高三分位与最低三分位相比，VTE 的 OR 为 1.73（95%CI 1.27-2.35），且随着对体重指数（BMI）和 C 反应蛋白（CRP）的逐步调整，风险估计值仅略有减弱（OR 1.59，95%CI 1.16-2.17；OR 1.54，95%CI 1.13-2.11）。对于诱发/非诱发事件、深静脉血栓形成和肺栓塞，也得到了类似的结果。在肥胖患者（BMI≥30kg/m 2 与 <25kg/m 2 ）中，在调整年龄、性别和 CRP 后，PAI-1 介导了 VTE 风险的 14.9%（95%CI 4.1%-49.4%）。
我们的研究结果表明，血浆 PAI-1 与未来发生 VTE 的风险增加相关，并且可能部分介导肥胖症中的 VTE 风险。
