title: Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction.
abstract: OBJECTIVE
  We aimed to investigate the impact of angiotensin-converting enzyme inhibitors (ACEIs) on hematocrit values in those with heart failure, and the relationship between incident anemia and mortality.
  
  
  BACKGROUND
  Prevalent anemia is an independent risk factor for morbidity and mortality in those with heart failure. Studies in patients with polycythemia have demonstrated that ACEIs are effective in lowering hematocrit values.
  
  
  METHODS
  We used the Studies Of Left Ventricular Dysfunction (SOLVD) database to compare the odds of developing new anemia at one year in patients who were not anemic at entry and who were randomized to enalapril or placebo. Cox proportional hazards models were utilized to determine the impact of incident and prevalent anemia on subsequent mortality.
  
  
  RESULTS
  Enalapril increased the odds of incident anemia (hematocrit < or =39% in men or < or =36% in women) at one year by 48% (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.20 to 1.82) in unadjusted and 56% (OR 1.56, 95% CI 1.26 to 1.93) in adjusted models. With multivariate analysis, prevalent anemia at randomization was associated with a 44% (hazard ratio [HR] 1.44, 95% CI 1.31 to 1.66) increase in all-cause mortality, whereas incident anemia after randomization was associated with a 108% increase (HR 2.08, 95% CI 1.82 to 2.38). After adjusting for incident and prevalent anemia, use of enalapril was associated with a survival benefit.
  
  
  CONCLUSIONS
  Enalapril was associated with increased odds of developing anemia at one year. Those with periods of time with incident anemia had the poorest survival, followed by those with prevalent anemia, then those without anemia. Enalapril was protective of overall mortality after adjusting for incident anemia and in those with prevalent anemia.
authors.affiliation: Section of Nephrology, Department of Medicine, Minneapolis VAMC, One Veterans Drive, Minneapolis, MN 55417, USA. isha0012@umn.edu
authors.forename: Areef
authors.initials: A
authors.lastname: Ishani
authors.forename: Eric
authors.initials: E
authors.lastname: Weinhandl
authors.forename: Zihong
authors.initials: Z
authors.lastname: Zhao
authors.forename: David T
authors.initials: DT
authors.lastname: Gilbertson
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Collins
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004656:Enalapril / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000401:mortality*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril