CLINICAL RESEARCH Heart Failure
Baseline Anemia Is Not a Predictor
of All-Cause Mortality in Outpatients With
Advanced Heart Failure or Severe Renal Dysfunction
Results From the Norwegian Heart Failure Registry
Bård Waldum, MD,*† Arne S. Westheim, MD, P
H
D,‡ Leiv Sandvik, P
H
D,§ Berit Flønæs, RN,ʈ
Morten Grundtvig, MD,¶ Lars Gullestad, MD, P
H
D,# Torstein Hole, MD, P
H
D,**††
Ingrid Os, MD, P
H
D†
Oslo, Sandvika, Lillehammer, Trondheim, and Ålesund, Norway
Objectives
The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure
attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with se-
vere renal dysfunction or advanced heart failure.
Background
Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality
decreases with increasing creatinine levels.
Methods
Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients
with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as esti-
mated glomerular filtration rate Յ45 ml/min/1.73 m
2
and advanced heart failure as New York Heart Associa-
tion functional classes IIIb and IV.
Results
Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio
[HR]: 1.30, 95% CI: 1.09 to 1.56, p ϭ 0.004). Baseline anemia did not predict mortality in the 752 patients with
severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p ϭ 0.662) and the 528 patients with ad-
vanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p ϭ 0.542). In the 1,743 patients who attended
subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10
to 1.94, p ϭ 0.008), whereas transient and new-onset anemia did not.
Conclusions
According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with
heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimiz-
ing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Associa-
tion functional class. (J Am Coll Cardiol 2012;59:371–8) © 2012 by the American College of Cardiology Foundation
Anemia is prevalent among patients with heart failure
(1). Renal dysfunction, activation of neurohormonal and
inflammatory responses, drug effects, and bone marrow
hyporesponsiveness all seem to contribute to the devel-
opment of anemia in patients with heart failure (2,3).
Estimates of the actual prevalence of anemia among
patients with heart failure vary widely due to differences
in the definition of anemia and in investigated patient
populations. Most studies have identified prevalence of
anemia Ͼ20% (4).
Numerous studies have demonstrated a strong rela-
tionship between anemia and mortality in populations
with heart failure (5,6). It is apparent from a recent
review (5) that most studies were performed in selected
study populations or among hospitalized patients. Epi-
demiological data suggest an inverse relationship between
serum creatinine level and the influence of anemia on
mortality in heart failure patients, because the effect of
anemia on mortality declines with increasing serum
From the *Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo,
Norway; †Department of Nephrology, Oslo University Hospital, Ullevål, Oslo, Norway;
‡Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway; §Depart-
ment of Biostatistics, Oslo University Hospital, Ullevål, Oslo, Norway; ʈDepartment of
Medicine, Vestre Viken Hospital Trust, Division Asker and Bærum Hospital, Sandvika,
Oslo, Norway, ¶Department of Medicine, Innlandet Hospital Trust, Lillehammer, Oslo,
Norway, #Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo,
Norway, **Norwegian University of Science and Technology, Trondheim, Oslo, Norway,
††Department of Medicine, Ålesund Hospital, Sunnmøre Hospital Trust, Ålesund,
Oslo, Norway. All authors have reported that they have no relationships relevant to the
contents of this paper to disclose.
Manuscript received April 29, 2011; revised manuscript received September 5,
2011, accepted October 3, 2011.
Journal of the American College of Cardiology Vol. 59, No. 4, 2012
© 2012 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2011.10.864