title: Comparative assessment of short-term adverse events in acute heart failure with cystatin C and other estimates of renal function: results from the ASCEND-HF trial.
abstract: OBJECTIVE
  The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C (CysC) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure (ADHF).
  
  
  BACKGROUND
  Newer renal biomarkers or their derived estimates of renal function have demonstrated long-term prognostic value in chronic heart failure.
  
  
  METHODS
  CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) biomarker sub-study (randomized to nesiritide therapy vs. placebo), and followed for all-cause death (180 days) and recurrent hospital stay (30 days).
  
  
  RESULTS
  Median CysC levels were 1.49 (interquartile range [IQR]: 1.20 to 1.96) mg/l at baseline, 1.56 (IQR: 1.28 to 2.13) mg/l at 48 to 72 h, and 1.58 (IQR: 1.24 to 2.11) mg/l at 30 days. Higher baseline (but not follow-up) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as well as 180-day mortality, although not incremental to blood urea nitrogen. Worsening renal function (defined as a 0.3 mg/l increase in CysC) occurred in 161 of 701 (23%) patients, but it was not predictive of adverse events. Changes in CysC levels were similar between the nesiritide and placebo groups.
  
  
  CONCLUSIONS
  Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF. However, worsening renal function based on CysC rise was not predictive of adverse events. Nesiritide did not worsen renal function compared with placebo.
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WHW
authors.lastname: Tang
authors.affiliation: Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dupont
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Cardiovascular Division, Stony Brook University, Stony Brook, New York.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Department of Cardiology, University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Department of Cardiology, University of Otago, Christchurch, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.affiliation: Department of Cardiology, University of Maryland, Baltimore, Maryland.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.affiliation: Department of Cardiology, University of Glasgow, Glasgow, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: McMurray
authors.affiliation: Department of Cardiology, University of Alberta, Edmonton, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: San Francisco Veterans Affairs Medical Center, University of California-San Francisco, San Francisco, California.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Massie
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
mesh_terms: D000208:Acute Disease; D000368:Aged; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D055316:Cystatin C; D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain
keywords: acute heart failure; cystatin C; nesiritide; renal insufficiency