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

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.