title: Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction.
abstract: BACKGROUND
  In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.
  
  
  RESULTS
  In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately.
  
  
  CONCLUSIONS
  In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.). gianluigi.savarese@ki.se.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Camilla
authors.initials: C
authors.lastname: Hage
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Nicola
authors.initials: N
authors.lastname: Orsini
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
authors.affiliation: From the Department of Medicine (G.S., C.H., L.H.L.) and Department of Public Health Sciences (N.O.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medical and Health Sciences (U.D.), Linkoping University, Sweden; Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (P.P.-F.); Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK (G.M.C.R.); and IRCCS San Raffaele Pisana, Rome, Italy (G.M.C.R.).
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D013318:Stroke Volume; D013548:Sweden
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: N-terminal pro–B-type natriuretic peptide; heart failure with mid-range ejection fraction; heart failure with preserved ejection fraction; prognosis; registry