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Transforming growth factor (TGF)-β levels and unprovoked recurrent venous thromboembolism

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Abstract

Prediction of recurrence in patients with unprovoked venous thromboembolism (VTE) remains a challenge. Studies of atherosclerosis suggest a protective role of transforming growth factor (TGF)-β. However, the role of TGF-β has not been studied in VTE. The aim of this study was to investigate TGF-β as a predictive marker of recurrent VTE in patients with a first episode of unprovoked VTE. Patients in the Malmö Thrombophilia Study (MATS) were followed after the discontinuation of anticoagulant treatment until the diagnosis of recurrent VTE or the end of the study in December 2008 (mean ± SD 38.5 months ± 27). Among patients with a first episode of unprovoked VTE, we identified 42 patients with recurrent VTE during the follow-up period. Two age- and sex-matched control subjects without recurrent VTE were selected for each patient (n = 84). Plasma levels of the three isoforms of TGF-β (TGF-β1, TGF-β2 and TGF-β3) were quantified simultaneously by TGF-β 3-plex immunoassay. Compared to controls, plasma levels of TGF-β1 and TGF-β2 were significantly lower in patients with recurrent VTE (p < 0.05), whereas no difference was found for TGF-β3. In a multivariate Cox regression analyses, adjusted for inherited thrombophilia, age, sex and BMI, low levels of TGF-β1 [hazard ratio (HR) = 2.2, 95 % confidence interval (CI) 1.1–4.3; p = 0.02] and TGF-β2 (HR = 2.4, 95 % CI 1.2–4.7; p = 0.01) were independently associated with a higher risk of recurrent VTE. We propose TGF-β1 and TGF-β2 as potential predictive markers for recurrence in patients with unprovoked VTE.

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Acknowledgments

We would like to thank Anna Hedelius for excellent technical support, Sven-Arnne Olsson for his help in collecting clinical data and science editor Stephen Gilliver for critical reading of the manuscript. This work was supported by grants awarded to Dr Bengt Zöller by the Swedish Heart–Lung Foundation and Region Skåne (REGSKANE-124611); ALF funding awarded to Drs Bengt Zöller, Kristina Sundquist, and Jan Sundquist by Region Skåne; grants awarded to Drs Kristina and Jan Sundquist by the Swedish Research Council (K2009-70X-15428-05-3 and K2012-70X-15428-08-3); and Grants awarded to Dr Jan Sundquist by the Swedish Council for Working Life and Social Research (2007-1754), King Gustaf V and Queen Victoria’s Foundation of Freemasons and FORTE, Swedish Reserch Council for health, Working life and welfare.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Medicine, Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden

    Ashfaque A. Memon, Kristina Sundquist, Xiao Wang, Jan Sundquist & Bengt Zöller

  2. Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA

    Kristina Sundquist & Jan Sundquist

  3. Department of Coagulation Disorders, Skåne University Hospital, Malmö, Sweden

    Peter J. Svensson

  4. Wallenberg Laboratory, 6th Floor, Skåne University Hospital, Inga Marie Nilssons gata 53, 205 02, Malmö, Sweden

    Ashfaque A. Memon

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  1. Ashfaque A. Memon
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  2. Kristina Sundquist
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  4. Peter J. Svensson
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Correspondence to Ashfaque A. Memon.

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Memon, A.A., Sundquist, K., Wang, X. et al. Transforming growth factor (TGF)-β levels and unprovoked recurrent venous thromboembolism. J Thromb Thrombolysis 38, 348–354 (2014). https://doi.org/10.1007/s11239-013-1047-0

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  • DOI: https://doi.org/10.1007/s11239-013-1047-0

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