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Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality
  1. Noemi Pavo1,
  2. Markus Raderer2,
  3. Martin Hülsmann1,
  4. Stephanie Neuhold3,
  5. Christopher Adlbrecht1,
  6. Guido Strunk4,
  7. Georg Goliasch1,
  8. Heinz Gisslinger2,
  9. Günther G Steger2,
  10. Michael Hejna2,
  11. Wolfgang Köstler2,
  12. Sabine Zöchbauer-Müller2,
  13. Christine Marosi2,
  14. Gabriela Kornek2,
  15. Leo Auerbach5,
  16. Sven Schneider6,
  17. Bernhard Parschalk6,
  18. Werner Scheithauer2,
  19. Robert Pirker2,
  20. Johannes Drach2,
  21. Christoph Zielinski2,
  22. Richard Pacher1
  1. 1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
  2. 2Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria
  3. 3Division of Cardio-Thoracic-Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, Medical University of Vienna, Vienna, Austria
  4. 4Complexity Research, Vienna, Austria
  5. 5Department of Gynecology, Medical University of Vienna, Vienna, Austria
  6. 6Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Austria
  1. Correspondence to Dr Martin Hülsmann, Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria, Währinger Gürtel 18-20, 1090 Vienna, Austria; martin.huelsmann{at}meduniwien.ac.at

Abstract

Objective Patients with cancer may display elevated levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical manifestation of cardiac disease. This study aimed to evaluate circulating cardiovascular hormones and hsTnT and their association with mortality in cancer.

Methods We prospectively enrolled 555 consecutive patients with a primary diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin were measured. All-cause mortality was defined as primary endpoint.

Results During a median follow-up of 25 (IQR 16–31) months, 186 (34%) patients died. All cardiovascular hormones and hsTnT levels rose with tumour stage progression. All markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI 1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR-proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to 1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender, tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR-proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and CRP.

Conclusions Circulating levels of cardiovascular peptides like NT-proBNP, MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected population of patients with cancer prior to induction of any cardiotoxic anticancer therapy. The aforementioned markers and copeptin were strongly related to all-cause mortality, suggesting the presence of subclinical functional and morphological myocardial damage directly linked to disease progression.

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