School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Thromb Haemost. 2022 Jul;122(7):1169-1176. doi: 10.1055/a-1792-7720. Epub 2022 Mar 9.
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 ( = 476, Model 1) and all patients with nonprimary brain cancers ( = 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.
生长分化因子 15(GDF-15)、高敏心肌肌钙蛋白 T(hs-TnT)和 N 末端 pro-B 型利钠肽(NT-proBNP)与非癌症患者静脉血栓栓塞(VTE)风险增加相关。然而,这些生物标志物在癌症患者中的表现尚不清楚。我们的目的是评估这些生物标志物在预测 Khorana 评分≥2 的中高危 VTE(癌症患者)发生 VTE 方面的性能。我们使用 AVERT 试验患者的 1 个月血浆样本,以确定 GDF-15、NT-proBNP 和 hs-TnT 水平是否与化疗开始后 1 至 7 个月内 VTE 的发生率相关。使用接收器操作特征曲线的最小欧几里得距离来推导出 GDF-15 和 NT-proBNP 的最佳截断值,因为没有证据表明存在常用的截断值。使用逻辑和 Fine 和 Gray 竞争风险回归分析分别计算优势比(OR)和亚分布风险比,同时调整年龄、性别、抗凝和抗血小板治疗。我们在两组中进行了测试:所有患者( = 476,模型 1)和所有非原发性脑癌患者( = 454,模型 2)。在模型 1 和 2 中,GDF-15≥2290.9 pg/mL 的 VTE 校正 OR 分别为 1.65(95%置信区间[CI]:0.89-3.08)和 2.28(95% CI:1.28-4.09)。hs-TnT≥14.0 pg/mL 与模型 1 和 2 中 VTE 的高几率相关(校正 OR:2.26 [95% CI:1.40-3.65]和 2.03 [95% CI:1.07-3.84])。对于 NT-proBNP,水平≥183.5 pg/mL 与 VTE 无关。Fine 和 Gray 分析也得到了类似的结果。我们的结果表明,升高的 GDF-15 和 hs-TnT 水平预示着 VTE 风险增加。