Prognostic significance of cardiovascular biomarkers and renal dysfunction in outpatients with systolic heart failure: a long term follow-up study

Int J Cardiol. 2013 Dec 10;170(2):202-7. doi: 10.1016/j.ijcard.2013.10.064. Epub 2013 Oct 26.


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).

Conclusion: 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.

Keywords: Cardiovascular biomarkers; Mortality risk; Renal function; Systolic heart failure.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / mortality*
  • Female
  • Follow-Up Studies
  • Heart Failure, Systolic / blood
  • Heart Failure, Systolic / mortality*
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Diseases / blood
  • Kidney Diseases / mortality*
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Neostigmine
  • Peptide Fragments / blood
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Troponin T / blood


  • Biomarkers
  • Peptide Fragments
  • Troponin T
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Neostigmine
  • Atrial Natriuretic Factor