Highlights
1. Elevated baseline growth differentiation factor-15 (GDF-15) is associated with increased risk of venous thromboembolism (VTE) in cancer patients.
2. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) are linked to higher bleeding risk.
3. Increasing high-sensitivity troponin T (hs-TnT) from baseline to 1 month correlates with higher VTE risk.
4. Nomograms developed in the study can help estimate VTE and bleeding risks in clinical practice.
Background
Cancer patients face a dual challenge: an elevated risk of venous thromboembolism (VTE) and bleeding complications. These events significantly impact morbidity and mortality, yet predicting them remains a clinical challenge. Inflammatory and cardiac biomarkers have emerged as potential predictors, but their precise roles are not well understood. This study aimed to clarify these associations using data from the AVERT trial, which evaluated apixaban for VTE prevention in ambulatory cancer patients.
Study Design
The study conducted a post hoc analysis of the AVERT trial, focusing on cancer patients with a Khorana score of ≥2. Biomarkers including CRP, GDF-15, NT-proBNP, and hs-TnT were measured at baseline, 1 month, and (for CRP) 3 months. The analysis used Fine and Gray regression models to account for the competing risk of death, adjusting for age and advanced cancer. Subdistribution hazard ratios (SHRs) were calculated to estimate risks for VTE and clinically relevant bleeding.
Key Findings
VTE Risk
Elevated baseline GDF-15 levels were associated with a 36% increase in VTE risk (SHR 1.36, 95% CI 1.01-1.84). Additionally, an increase in hs-TnT from baseline to 1 month was linked to an 89% higher VTE risk (SHR 1.89, 95% CI 1.14-3.16).
Bleeding Risk
Higher baseline levels of NT-proBNP (SHR 1.44, 95% CI 1.08-1.92) and CRP (SHR 1.38, 95% CI 1.07-1.76) were associated with increased bleeding risk.
Nomograms
The study developed nomograms to estimate VTE and bleeding risks, providing a practical tool for clinicians to assess individual patient risks.
Expert Commentary
The findings highlight the potential of biomarkers in risk stratification for cancer-associated thrombosis and bleeding. However, the study has limitations, including its post hoc design and the lack of external validation. Prospective studies are needed to confirm these associations and refine the predictive models. Mechanistically, the link between inflammation, cardiac stress, and thrombosis underscores the complex interplay of these pathways in cancer patients.
Conclusion
Inflammatory and cardiac biomarkers offer valuable insights into VTE and bleeding risks in cancer patients. The developed nomograms present a step forward in personalized risk assessment. Future research should focus on prospective validation and exploring the underlying biological mechanisms.
Funding and ClinicalTrials.gov
The study was part of the AVERT trial. For detailed funding information and trial registration, refer to the original citation.
References
Roy DC, Wang TF, Mallick R, Burger D, Carrier M, Wells P, Hawken S. Venous thromboembolism and bleeding in cancer patients: role of inflammatory and cardiac biomarkers. European heart journal. 2026-Apr-22;47(16):1933-1945. PMID: 41384379.
