title: Prognostic significance of cardiovascular biomarkers and renal dysfunction in outpatients with systolic heart failure: a long term follow-up study.
abstract: OBJECTIVE
  To assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF).
  
  
  BACKGROUND
  It is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF.
  
  
  METHODS
  Clinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5 years (interquartile range: 2-7.7 years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed.
  
  
  RESULTS
  Median age was 73 years (51-83), 29% were female, LVEF was 30% (13-45), 74% were NYHA classes I-II and estimated glomerular filtration rate (eGFR) was 68 ml/min/1.73 m(2) (18-157). A total of 252 patients died. All five biomarkers--log(NT-proBNP) (HR: 2.13, 95% CI: 1.57-2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90-4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01-1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01-1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66-3.38, P<0.001)--were associated with mortality risk, but not affected by RD (P>0.05 for all interactions).
  
  
  CONCLUSIONS
  Established and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.
authors.affiliation: Department of Cardio-, Nephro and Endocrinology, North Zealand University Hospital, Denmark. Electronic address: hbos0002@regionh.dk.
authors.forename: Helle
authors.initials: H
authors.lastname: Bosselmann
authors.forename: Michael
authors.initials: M
authors.lastname: Egstrup
authors.forename: Kasper
authors.initials: K
authors.lastname: Rossing
authors.forename: Ida
authors.initials: I
authors.lastname: Gustafsson
authors.forename: Finn
authors.initials: F
authors.lastname: Gustafsson
authors.forename: Niels
authors.initials: N
authors.lastname: Tonder
authors.forename: Caroline N
authors.initials: CN
authors.lastname: Kistorp
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.forename: Morten
authors.initials: M
authors.lastname: Schou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000097:blood / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009388:Neostigmine; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009388:Neostigmine; D009320:Atrial Natriuretic Factor
keywords: Cardiovascular biomarkers; Mortality risk; Renal function; Systolic heart failure