title: Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality.
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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Noemi
authors.initials: N
authors.lastname: Pavo
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Raderer
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Hülsmann
authors.affiliation: Division of Cardio-Thoracic-Vascular Anesthesia and Intensive Care Medicine, Department of Anesthesia, Medical University of Vienna, Vienna, Austria.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Neuhold
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.affiliation: Complexity Research, Vienna, Austria.
authors.forename: Guido
authors.initials: G
authors.lastname: Strunk
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Goliasch
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Günther G
authors.initials: GG
authors.lastname: Steger
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köstler
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Zöchbauer-Müller
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kornek
authors.affiliation: Department of Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Leo
authors.initials: L
authors.lastname: Auerbach
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: Sven
authors.initials: S
authors.lastname: Schneider
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Parschalk
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Scheithauer
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Pirker
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.affiliation: Division of Oncology and Hematology, Department of Internal Medicine I, Medical University of Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.affiliation: Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D000368:Aged; D058070:Asymptomatic Diseases; D009320:Atrial Natriuretic Factor / Q000097:blood; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000401:mortality / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D006020:Glycopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D020107:Troponin T; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein