DISCUSSION.
Anemia is an important comorbidity in patients with AHF, however, most
studies on the influence of early and long-term mortality included
patients admitted to different hospitalization
units16,25. The EAHFE registry includes patients with
AHF attended in HEDs, including patients admitted as well as those
discharged after their first episode or managed in alternative
hospitalization units (Observation Units or Short-stay Units), which are
not usually represented in other studies. The ANEM-AHF study was also
aimed at determining the influence of anemia as a prognostic factor of
short- and long-term mortality in patients with AHF attended in HEDs and
to determine the influence in relation to the rest of the variables
which act as confounding factors, an aspect which, up to now, has not
been reported in the literature. On the other hand, it also measured the
potential increase in individual risk at different time points during
follow-up.
The principal findings of the ANEM-AHF were: 1) the frequency of anemia
in patients attended in HEDs is higher than what has been reported in
the literature in hospitalized populations and significantly increases
with age; 2) anemia is a prognostic factor of early (30 days after
inclusion) and long-term (at one year) mortality, and this prognostic
capacity is independent of the differences between the groups with and
without anemia; 3) age, sex and comorbidity are confounding factors
which produce a clinically relavant effect on the relation between
anemia and mortality at 30 days and at one year, and the remaining
parameters (baseline NYHA, previous treatment, clinical and analytical
and electrocardiographic data of the acute episode, emergency treatment
and hospital admission) have a lesser impact; and 4) the effect of
anemia on mortality is much greater in the long term than in
intermediate follow-ups.
The prevalence of anemia in our cohort was 56.9%, being higher than
that of other studies which ranged from 30 to 50%, and increased with
age9. This greater frequency is probably influenced by
age since its coincides with the findings of the study by Formiga26 who analyzed the effect of anemia in 155 patients
with AHF over 90 years of age and found a prevalence of 60%, which is
very similar to that of our patients.
Patients with anemia differ from those without this comorbidity, being a
common aspect in different studies9,16,23: these
patients are older, have more comorbidities, a worse basal status, and
are more often admitted for an acute episode. Anemia was more frequent
among males than controls, contrary to what has been described in the
literature in which women predominate among patients with anemia or
there are no differences between sexes9,16. Taking
into account the data of our large, country-wide study, we consider that
these findings are representative of the real population with anemia and
AHF.
Anemia is correlated with a higher early and long-term mortality. The
relationship between Hb values and mortality was not linear. Patients
with lower Hb values (7 g/dL) presented a lower mortality than those
with intermediate values. This aspect differs from that seen in patients
with chronic heart failure27 and favors the results of
older studies which attempted to demonstrate that the relation between
Hb values and mortality followed a J curve28. This
result may have been due to these patients with such low Hb values
having received treatment for anemia early on, whether by transfusion or
with intravenous iron, conditioning the prognosis, especially in the
short term.
The principal finding of our study is the relationsip between anemia and
both short- (30 days) and long-term mortality (at one year), which
remained independent of all the confounding factors composed of 56
variables including comorbidity, both basal functional status and
dyspnea, chronic treatment of the patient, data of the acute episode,
analytical results, treatment administered in the HED and hospital
admission or stay in an observation unit. After controlling for these
factors, patients with anemia presented an excess of mortality of 30%
at 30 days and 30% at one year. The factors which had the greatest
impact on this relation and produced a significant change in the HRs
were age, sex and comorbidity. Previous studies have analyzed long-term
mortality and other prognostic factors such as readmission within 30
days. Our results of mortality at one year are concordant with previous
studies which have also observed that the presence of low Hb values is
an independent marker of mortality at 3 years, although the survival
curves separate from the beginning and become parallel after one year of
follow-up16. This may have implications in the
follow-up of patients with AHF once the acute phase has been overcome.
On one hand, it would be important to establish the etiological
diagnosis of anemia to administer treatments targeted at reestablishing
Hb values, especially in patients with values for which transfusion is
not indicated. Based on the findings of the Ferinject assessment in
patients with IRon deficiency and chronic Heart Failure (FAIR-HF)
study29,30, the use of is recommended in patients with
iron deficiency who do or do not have anemia. Indeed, the clinical
guidelines of the ESC22 recommend that this
comorbidity should be monitored during the follow-up of these patients.
In the analysis of the impact of anemia on mortality at different one
month time periods between 30 days and one year, we observed that anemia
is independently correlated with early mortality and mortality after 300
days of follow-up, at which time mortality exponentially increases,
making close follow-up of these patients necessary in order to control
the Hb values.
To our knowledge no study has analyzed the effect of anemia on
short-term mortality or has measured the risk of individual mortality at
the different time periods analyzed until the end of follow-up. In the
case of mortality at 30 days, anemia is an independent marker of risk.
This highlights the need for studies on the etiology of anemia at the
time of diagnosis in order to implement the most adequate treatment,
since anemia is a comorbidity, which, on many occasions, in easily
treatable considering that the main causes are usually nutritional
deficits, mainly of iron or situations of chronic inflammation which are
often found in patients with HF.
LIMITATIONS.
This study has several limitations which should not condition the
validity of the results. On one hand, patients with a previous diagnosis
of anemia were not recruited and this was established based on the Hb
value during care in the HED. On the other hand, it is a study on
real-life management of patients with AHF, without intervention and in
which the physicians attending the patients did not receive instructions
regarding their management. Another limitation is that this was not the
principal objective of the study, although it had a multipurpose design.
The last limitation is that patient inclusion was based on clinical
criteria and patients belonging to a single country, although the
participating hospitals were from all around Spain.
Nonetheless, despite these limitations we believe that the results of
the ANEM-AHF study including a large registry of patients with AHF
attended in HEDs are perfectly valid and can be extrapolated to other
similar populations.
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Table 1. Baseline characteristics of the study population and comparison
of the characteristics of the patients based on whether they had anemia
or not.