title: Clinical risk stratification optimizes value of biomarkers to predict new-onset heart failure in a community-based cohort.
abstract: BACKGROUND
  We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction.
  
  
  RESULTS
  Thirteen biomarkers reflecting diverse pathophysiologic domains were examined in 8569 HF-free participants in Prevention of Vascular and Renal Endstage Disease (mean age, 49 years; 50% men). Subjects were categorized in 2 risk groups based on cardiovascular history. Incremental value per biomarker was assessed using Harrell C-indices. One hundred sixty-eight subjects (2.4%) were diagnosed with new-onset HF in the low-risk group (n=6915; Framingham Risk Score, 5.9%) and 206 (12.2%) subjects in the high-risk group (n=1654; Framingham Risk Score, 18.6%). The association of natriuretic peptides, adrenomedullin, endothelin, and galectin-3 with new-onset HF was stronger in the high-risk group (all P<0.05). Troponin-T, high-sensitive C-reactive protein, urinary albumin excretion, and cystatin-C had similar risk for new-onset HF between both risk groups. The best model for new-onset HF included the combination of N-terminal pro-B-type natriuretic peptide, troponin-T, and urinary albumin excretion, increasing model accuracy to 0.81 (9.5%, P<0.001) in the high-risk group. Except for a modest effect of cystatin-C, no biomarker was associated with increased risk for HF with preserved ejection fraction.
  
  
  CONCLUSIONS
  Risk stratification increases the incremental value per biomarker to predict new-onset HF, especially HF with reduced ejection fraction. We suggest that routine biomarker testing should be limited to the use of natriuretic peptides and troponin-T in patients with increased cardiovascular risk.
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. f.p.j.brouwers@umcg.nl.
authors: Frank P
authors: FP
authors: Brouwers
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Wiek H
authors: WH
authors: van Gilst
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Kevin
authors: K
authors: Damman
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Maarten P
authors: MP
authors: van den Berg
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Ron T
authors: RT
authors: Gansevoort
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Stephan J L
authors: SJ
authors: Bakker
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Hans L
authors: HL
authors: Hillege
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Dirk J
authors: DJ
authors: van Veldhuisen
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Pim
authors: P
authors: van der Harst
authors: From the Department of Cardiology (F.P.B., W.H.v.G., K.D., M.P.v.d.B., H.L.H., D.J.v.V., P.v.d.H., R.A.d.B.) and Division of Nephrology, Department of Internal Medicine (R.T.G., S.J.L.B.), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Rudolf A
authors: RA
authors: de Boer
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: biomarkers; epidemiology; heart failure, diastolic; heart failure, systolic