Growth differentiation factor-15 and prediction of cancer-associated thrombosis and mortality: a prospective cohort study

Stephan Nopp; Florian Moik; Simon Kraler; Cornelia Englisch; Matthias Preusser; Arnold von Eckardstein; Ingrid Pabinger; Thomas F Lüscher; Cihan Ay

doi:10.1016/j.jtha.2023.04.043

Growth differentiation factor-15 and prediction of cancer-associated thrombosis and mortality: a prospective cohort study

J Thromb Haemost. 2023 Sep;21(9):2461-2472. doi: 10.1016/j.jtha.2023.04.043. Epub 2023 May 14.

Authors

Stephan Nopp¹, Florian Moik², Simon Kraler³, Cornelia Englisch¹, Matthias Preusser⁴, Arnold von Eckardstein⁵, Ingrid Pabinger¹, Thomas F Lüscher⁶, Cihan Ay⁷

Affiliations

¹ Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
² Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address: http://www.twitter.com/FlorianMoik.
³ Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland. Electronic address: http://www.twitter.com/KralerSimon.
⁴ Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
⁵ Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Zurich, Switzerland.
⁶ Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland; Royal Brompton and Harefield Hospitals and Imperial College, London, UK; School of Cardiovascular Medicine and Sciences, King's College London, London, UK. Electronic address: http://www.twitter.com/TomLuscher.
⁷ Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. Electronic address: cihan.ay@meduniwien.ac.at.

PMID: 37192696
DOI: 10.1016/j.jtha.2023.04.043

Abstract

Background: Patients with cancer are at increased risk of venous thromboembolism (VTE) and arterial thromboembolic/thrombotic events (ATEs). Growth differentiation factor-15 (GDF-15) improves cardiovascular risk assessment, but its predictive utility in patients with cancer remains undefined.

Objectives: To investigate the association of GDF-15 with the risks of VTE, ATE, and mortality in patients with cancer and its predictive utility alongside established models.

Methods: The Vienna Cancer and Thrombosis Study (CATS)-a prospective, observational cohort study of patients with newly diagnosed or recurrent cancer-which was followed for 2 years, served as the study framework. Serum GDF-15 levels at study inclusion were measured, and any association with VTE, ATE, and death was determined using competing risk (VTE/ATE) or Cox regression (death) modeling. The added value of GDF-15 to established VTE risk prediction models was assessed using the Khorana and Vienna CATScore.

Results: Among 1531 included patients with cancer (median age, 62 years; 53% men), median GDF-15 levels were 1004 ng/L (IQR, 654-1750). Increasing levels of GDF-15 were associated with the increased risks of VTE, ATE, and all-cause death ([subdistribution] hazard ratio per doubling, 1.16 [95% CI, 1.03-1.32], 1.30 [95% CI, 1.11-1.53], and 1.57 [95% CI, 1.46-1.69], respectively). After adjustment for clinically relevant covariates, the association only prevailed for all-cause death (hazard ratio, 1.21; 95% CI, 1.10-1.33) and GDF-15 did not improve the performance of the Khorana or Vienna CATScore.

Conclusion: GDF-15 is strongly associated with survival in patients with cancer, independent of the established risk factors. While an association with ATE and VTE was identified in univariable analysis, GDF-15 was not independently associated with these outcomes and failed to improve established VTE prediction models.

Keywords: biomarkers; cancer; growth differentiation factor 15; neoplasm; thromboembolism; thrombosis.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Growth Differentiation Factor 15
Growth Differentiation Factors
Humans
Neoplasms* / complications
Neoplasms* / diagnosis
Prospective Studies
Risk Factors
Thrombosis* / complications
Thrombosis* / diagnosis
Venous Thromboembolism*

Substances

Growth Differentiation Factors
Growth Differentiation Factor 15