title: NT-proBNP is increased in differentiated thyroid carcinoma patients and may predict cardiovascular risk.
abstract: BACKGROUND
  Chronic suppression of TSH in patients treated for differentiated thyroid carcinoma (DTC) may induce cardiac damage and increase risk for cardiovascular events and premature mortality. We aimed to compare circulating concentrations of N-terminal pro Brain Natriuretic Peptide (NT-proBNP) of DTC patients with controls, and to investigate whether higher NT-proBNP is associated with an increased risk for cardiovascular events and all-cause mortality in DTC patients.
  
  
  METHODS
  Serum NT-proBNP levels were determined in 266 DTC patients, median 10.4 [IQR 4.1-18.5] years after DTC diagnosis, and compared to 798 age- and sex-matched controls. Using multivariable Cox regression analyses, the association of NT-proBNP with cardiovascular events and all-cause mortality was determined. Hazard ratios (HR) and 95% confidence intervals (CIs) were expressed per SD increase of log-transformed NT-proBNP.
  
  
  RESULTS
  Mean age±SD of DTC patients and controls was 54.8±14.5 and 54.8±12.8years, respectively; 74% were women. Median NT-proBNP level was 70 [40-119] ng/L for DTC patients vs. 49 [25-89] ng/L for controls (p<0.001). During median follow-up of 8.6 [6.6-9.0] years, 30 DTC patients (11.4%) had a cardiovascular event and 38 (14.4%) died. Higher NT-proBNP was associated with an increased risk for cardiovascular events and all-cause mortality, age- and sex-adjusted HRs (95% CIs) 3.22 (2.17-4.79) and 1.61 (1.17-2.23), respectively. In further models with adjustment for cardiovascular risk factors, NT-proBNP remained independently associated with outcome.
  
  
  CONCLUSIONS
  NT-proBNP levels are elevated in patients with DTC, and are associated with an increased risk for cardiovascular events and all-cause mortality. Determination of NT-proBNP may identify DTC patients at increased cardiovascular risk, who could benefit from more stringent cardiovascular risk surveillance.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Vascular Medicine, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands.
authors.forename: Esther N
authors.initials: EN
authors.lastname: Klein Hesselink
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands.
authors.forename: Anouk N A
authors.initials: ANA
authors.lastname: van der Horst-Schrivers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
authors.forename: Iwan C C
authors.initials: ICC
authors.lastname: van der Horst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJL
authors.lastname: Bakker
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen, The Netherlands.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Muller Kobold
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands.
authors.forename: Adrienne H
authors.initials: AH
authors.lastname: Brouwers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands.
authors.forename: Jourik A
authors.initials: JA
authors.lastname: Gietema
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RPF
authors.lastname: Dullaart
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands. Electronic address: t.p.links@umcg.nl.
authors.forename: Thera P
authors.initials: TP
authors.lastname: Links
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Vascular Medicine, Groningen, The Netherlands.
authors.forename: Joop D
authors.initials: JD
authors.lastname: Lefrandt
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000601:surgery; D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000097:blood* / Q000150:complications / Q000401:mortality / Q000601:surgery; D013965:Thyroidectomy; D013972:Thyrotropin
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013972:Thyrotropin
keywords: Cardiovascular risk; Differentiated thyroid cancer; NT-proBNP