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Thromb Haemost 2022; 122(07): 1169-1176
DOI: 10.1055/a-1792-7720
Stroke, Systemic or Venous Thromboembolism

Growth Differentiation Factor-15, High-Sensitivity Cardiac Troponin T, and N-Terminal pro-B-type Natriuretic Peptide for Predicting Risk of Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy

Danielle Carole Roy 
1   School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
,
Tzu-Fei Wang
2   Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Ranjeeta Mallick
1   School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2   Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Marc Carrier
2   Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Eisi Mollanji
3   Cardiac Function Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
,
Peter Liu
3   Cardiac Function Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
,
Liyong Zhang
3   Cardiac Function Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
,
Steven Hawken
1   School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2   Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Philip Wells
2   Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
› Author Affiliations Funding This study was supported by funding from Canadian Institute of Health Research (CIHR) and Bristol Myers Squibb/Pfizer (to P.W.).
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Abstract

Growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased risk of venous thromboembolism (VTE) in noncancer patients. However, the performance of these biomarkers in cancer patients is unknown. Our objective was to assess performance of these biomarkers in predicting VTE in cancer patients at intermediate to high risk for VTE (Khorana Score ≥ 2). We used 1-month plasma samples from AVERT trial patients to determine if GDF-15, NT-proBNP, and hs-TnT levels are associated with VTE incidence between 1 and 7 months from the start of chemotherapy. The minimal Euclidean distance of the receiver operating characteristic curve was used to derive optimal cut-offs for GDF-15 and NT-proBNP given there was no evidence of a commonly used cut-off. Logistic and Fine and Gray competing risk regression analyses were used to calculate odds ratios (ORs) and subdistribution hazard ratios, respectively, while adjusting for age, sex, anticoagulation, and antiplatelet therapy. We tested in two groups: all patients (n = 476, Model 1) and all patients with nonprimary brain cancers (n = 454, Model 2). In models 1 and 2, GDF-15 ≥2,290.9 pg/mL had adjusted ORs for VTE of 1.65 (95% confidence interval [CI]: 0.89–3.08), and 2.28 (95% CI: 1.28–4.09), respectively. hs-TnT ≥14.0 pg/mL was associated with higher odds of VTE in models 1 and 2 (adjusted ORs: 2.26 [95% CI: 1.40–3.65] and 2.03 [95% CI: 1.07–3.84], respectively). For NT-proBNP, levels ≥183.5 pg/mL were not associated with VTE. Similar results were observed in the Fine and Gray analysis. Our results indicate that increased GDF-15 and hs-TnT levels predicted increased VTE risk.

Keywords

venous thromboembolism - cancer - prediction - biomarkers

Ethical Approval

No ethics approval was sought for this study. The AVERT trial did receive ethical approval for plasma and DNA blood banking for future thrombosis research, on the condition of patient consent.


Author Contributions

D.C.R. designed the research, performed statistical analysis, analyzed results, made the tables, and wrote the manuscript. L.Z. and P.L. designed the research, contributed laboratory tools, performed experiments, and proofread the manuscript. T-.F.W., M.C., and P.W. designed the research, collected the data, interpreted the data, and proofread the manuscript. R.M. designed the research, assisted with performing the statistical analysis, analyzing the results, and proofreading the manuscript. E.M. analyzed and interpreted the data and proofread the manuscript. S.H. aided with statistical analysis, analyzed results, and proofread the manuscript.




Publication History

Received: 03 November 2021

Accepted: 07 March 2022

Accepted Manuscript online:
09 March 2022

Article published online:
31 May 2022

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Comment to this article:

Growth Differentiation Factor-15: A Novel Biomarker for Predicting Risk of Venous Thromboembolism and Bleeding in Patients with CancerThromb Haemost 2022; 122(07): 1075-1075
DOI: 10.1055/a-1827-7328