ARTICLE IN PRESS

Characteristics, Management, and Short-Term

Outcomes of Adults ≥65 Years Hospitalized With Acute
Myocardial Infarction With Prior Anemia and Heart
Failure
Mayra Tisminetzky, MD, PhDa,b,c,*, Jerry H. Gurwitz, MDa,b,c, Ruben Miozzo, MD, PhDd,
Joel M. Gore, MDc, Darleen Lessard, MSc, Jorge Yarzebski, MD, MPHc, and Robert J. Goldberg, PhDa,c

Our study objectives were to examine the impact of anemia and heart failure (HF) on in-
hospital complications, and postdischarge outcomes (7 and 30-day rehospitalizations and
mortality) in adults ≥65 years hospitalized with acute myocardial infarction (AMI). We
used multivariable-adjusted logistic regression models to examine the association between
the presence of anemia and/or HF, and the examined outcomes. The study population con-
sisted of 3,863 patients ≥65 years hospitalized with AMI at the 3 major medical centers in
Worcester, MA, during 6 annual periods between 2001 and 2011. Individuals were catego-
rized into 4 groups based on the presence of previously diagnosed anemia (hemoglobin
≤10 mg/dl) and/or HF: Those without these conditions (n = 2,300), those with anemia only
(n = 382), those with HF only (n = 837), and those with both conditions (n = 344). The
median age of the study population was 79 years and 49% were men. Individuals who had
been previously diagnosed with anemia and HF had the highest proportion of older adults
(≥85 years) and the lowest proportion of those who had received any cardiac interven-
tional procedure during hospitalization. After multivariable adjustment, individuals who
presented with both previously diagnosed conditions were at the greatest risk for
experiencing adverse events. Patients who presented with HF only were at higher risk for
developing several clinical complications during hospitalization, whereas those with ane-
mia only were at slightly higher risk of being rehospitalized within 7-days of their index
hospitalization. In conclusion, anemia and HF are prevalent chronic conditions that
increased the risk of adverse events in older adults hospitalized with AMI. Published by
Elsevier Inc. (Am J Cardiol 2019;00:1−6)

Anemia and heart failure (HF) are recognized as important are at greater risk for subsequent morbidity and mortality
independent risk factors for morbidity and mortality in older when hospitalized for an AMI in comparison with those who
adults hospitalized with an acute myocardial infarction do not have this clinical syndrome.6,7 Although a number of
(AMI).1−4 Anemia is a prevalent condition in older adults studies have examined the natural history of patients who
with an AMI, with a frequency ranging from 6% to 45%, and present with either anemia or HF at the time of hospitalization
this condition has been associated with a greater risk of dying for AMI,1−7, there are extremely limited data available
at the time of hospitalization for AMI as compared with those describing the characteristics, management, and frequency of
without anemia.1−4 The magnitude of HF increases with adverse outcomes in adults ≥65 years who present with either
advancing age,5 and patients with previously diagnosed HF or both of these 2 prevalent conditions at the time of hospitali-
zation for AMI. The objectives of this observational study
were to describe the overall differences in the characteristics,
a
Meyers Primary Care Institute, University of Massachusetts Medical in-hospital management, clinical complications, in-hospital
School, Worcester, Massachusetts; bDivision of Geriatric Medicine, Uni- death rates, and 30-day outcomes in patients with pre-existing
versity of Massachusetts Medical School, Worcester, Massachusetts; cDe- anemia and/or HF, as compared with those without these con-
partment of Population and Quantitative Health Sciences, University of ditions, who were diagnosed with AMI at the 3 major medical
Massachusetts Medical School, Worcester, Massachusetts; and dJohns centers in central Massachusetts on a biennial basis between
Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Manu-
2001 and 2011.8−10
script received May 29, 2019; revised manuscript received and accepted July
25, 2019.
Funding: This work was supported by the National Heart, Lung, and
Blood Institute (Grants numbers: RO1 HL35434 and 1 R01 HL135219-02). Methods
Drs J.G, R.J.G, and J.Y.’s effort was supported in part by funding from the
National Heart, Lung, and Blood Institute (Grant number: U01HL105268).
The Worcester Heart Attack Study is an ongoing popula-
Drs. M.T and J.H.G were supported by grants from the National Institute on tion-based investigation that is examining long-term trends
Aging (Grant numbers: R24AG045050 and R33AG057806). in the clinical epidemiology of AMI among residents of the
See page 5 for disclosure information. Worcester, Massachusetts (MA), metropolitan area hospi-
*Corresponding author: Tel: (508) 856-3586. talized at all medical centers in central MA on an approxi-
E-mail address: [email protected] (M. Tisminetzky). mate biennial basis.8−12

0002-9149/Published by Elsevier Inc. www.ajconline.org

https://doi.org/10.1016/j.amjcard.2019.07.057
 ARTICLE IN PRESS
2 The American Journal of Cardiology (www.ajconline.org)

Computerized printouts of residents of central MA Results

admitted to the 3 largest hospitals in Worcester, MA with
A total of 3,863 residents of central MA 65 years and
possible AMI (International Classification of Disease [ICD]
older were hospitalized with AMI at the 3 largest teaching
9 codes 410-414, and 786.5) on a biennial basis between
and community medical centers in Worcester, MA, between
2001 and 2011 were identified. Cases of possible AMI were
2001 and 2011. The median age of this patient population
independently validated using predefined criteria for AMI,
was 79 years and 48.9% were men.
including diagnoses of ST segment elevation myocardial
Patients without anemia or HF were the youngest and
infarction (STEMI) and non-ST segment elevation myocar-
were more likely to be male as compared with those in the
dial infarction (NSTEMI).13,14 This study was approved by
other 3 groups (Table 1). Individuals who presented with
the Institutional Review Board at the University of Massa-
HF, with or without anemia, had the highest proportion of
chusetts Medical School.
individuals diagnosed with an acute NSTEMI (Table 1).
Trained nurses and physicians abstracted information on
Relatively similar trends were observed with regards to the
patient’s demographic and clinical characteristics, hospital
frequency distribution of other previously diagnosed
treatment practices, and short-term outcomes through the
chronic conditions in the 4 comparison groups. Hyperten-
review of hospital medical records. These characteristics
sion, hyperlipidemia, diabetes, and a previous AMI were
included the patient’s age, sex, race/ethnicity, hospital
the most common chronic conditions diagnosed in our
length of stay, and previously diagnosed chronic conditions.
study population.
The presence of anemia was defined based on the review of
The 2 more common complications during the hospital
hospital medical records as well as hospital lab values
stay in our 4 comparison groups were AF and HF. Approxi-
(hemoglobin levels ≤10 mg/dl)15 at the time of the index
mately 1 in every 3 patients with HF with or without anemia
admission for AMI. The presence of HF was defined based
developed AF and 3 in every 4 patients with HF with or
on the review of information contained in-hospital medical
without anemia developed HF (Table 1). Individiduals who
records as was information on the development of impor-
presented with both anemia and HF were at the greatest risk
tant in-hospital complications including atrial fibrillation,16
for dying during their hospitalization for AMI.
cardiogenic shock,17 heart failure,18 stroke,19 and death. Data
Patients who presented with HF with or without anemia
on the receipt of 3 coronary diagnostic and interventional pro-
had the lowest proportion of individuals who were treated
cedures (cardiac catheterization, percutaneous coronary inter-
in the hospital with beta-blockers and lipid lowering medi-
vention [PCI], and coronary artery bypass grafting [CABG])
cations (Table 2). The proportion of patients with HF with
during hospitalization, and evidence-based pharmacothera-
or without anemia that received any cardiac diagnostic/
pies during hospitalization, namely, angiotensin converting
interventional procedure was significantly lower as com-
inhibitors (ACE-I)/angiotensin receptor blockers (ARBs),
pared with the other 2 groups (Table 2).
aspirin, beta blockers, and lipid lowering agents were also
Figure 1 summarizes the frequency of adverse outcomes
collected.
according to the presence of anemia and/or HF. Similar
A rehospitalization was defined as the patient’s first
trends were found in the frequency of in-hospital death or
admission to a study hospital for any reason within 7 or
in-hospital complications and 30-day rehospitalization in
30 days of discharge after their index hospitalization for
patients with HF with and without anemia (Figure 1).
AMI during the years under the study.
After controlling for several factors of prognostic impor-
We stratified our study population into 4 groups according
tance, we found an increased risk of dying during hospitali-
to the presence of previously diagnosed anemia and/or HF:
zation in patients who presented with HF and anemia as
those without anemia or HF, those with anemia only, those
compared with those without these conditions (Table 3). The
with HF only, and patients who presented with both condi-
risk of developing any clinically significant in-hospital com-
tions. We compared differences in the baseline demographic
plication, namely HF, stroke, cardiogenic shock, or AF was
and clinical characteristics, hospital management practices,
increased across all comparison groups, with the highest risk
and the development of in-hospital complications and postdi-
observed for patients with HF, with or without anemia, as
scharge hospital readmissions and mortality between each of
compared with those without these chronic conditions.
these 4 groups using chi-square tests for categorical variables
The risk of being readmitted to the hospital within 7 days
and the ANOVA test for continuous variables.
after the index hospitalization for AMI was significantly
For purposes of more systematically examining the asso-
higher among patients with previously diagnosed anemia
ciation between the presence of previously diagnosed ane-
only, and among those with both anemia and HF, as com-
mia and/or HF with the risk of dying during the patient’s
pared with those without these conditions. Slightly different
index hospitalization, developing clinically significant in-
trends were found in the risk of readmission within 30 days,
hospital complications, or having a rehospitalization or
with the highest risk noted among patients with HF and ane-
dying within 7 or 30 days after being discharged form the
mia (Table 3). Similar results were observed with regards to
hospital, we used logistic regression modeling, adjusting
the risk of dying at 30 days with the highest estimates noted
for several potentially confounding demographic and clini-
in those who presented with both chronic conditions.
cal factors of prognostic importance in these models. The
variables, we controlled for included age, sex, type of AMI
(STEMI vs NSTEMI), the presence of other chronic condi-
Discussion
tions, hospital length of stay, and the hospital receipt of 5
evidence-based cardiac medications and 3 coronary diag- In this investigation of more than 3,800 patients
nostic and interventional procedures. ≥65 years hospitalized with a confirmed AMI at the 3
 ARTICLE IN PRESS
Coronary Artery Disease/Outcomes in Patients With Heart Failure and Anemia 3

Table 1
Patient characteristics according to the presence of previously diagnosed anemia and/or heart failure
Anemia/heart failure 0/0 +/0 0/+ +/+
variable (n = 2,300) (n = 382) (n = 837) (n = 344)
Age (years) (median) 77.0% 81.0% 81.0% 81.0%
65-74 35.7% 23.6% 24.0% 21.5%*
75-84 40.1% 39.0% 39.6% 40.1%**
≥85 24.2% 37.4% 36.4% 38.4%*
Men 51.2% 41.1% 47.1% 46.5%*
White 91.5% 93.3% 92.2% 91.1%
NSTEMI 68.5% 78.5% 83.0% 86.6%**
Length of stay (days, median) 4.0% 5.0% 5.0% 5.0%*
Acute myocardial infarction 30.3% 36.9% 58.3% 60.8%**
Atrial fibrillation 13.4% 16.2% 32.5% 34.6%**
Chronic kidney disease 13.3% 40.8% 34.7% 58.7%**
Chronic obstructive pulmonary disease 17.0% 20.7% 27.2% 30.8%**
Depression 13.4% 23.6% 18.6% 22.4%**
Diabetes mellitus 30.2% 41.6% 49.7% 54.7%**
Hyperlipidemia + 56.5% 57.9% 59.1% 62.5%
Hypertension ++ 77.1% 84.8% 85.1% 86.6%**
Peripheral vascular disease 16.4% 26.2% 29.2% 37.5%**
Stroke 12.3% 15.7% 17.3% 22.1%**
Hemoglobin (g/dL) 13.5% 10.7% 13.0% 10.6%
Glucose (mg/dL) median 145% 151% 169% 162%
Glomerular filtration rate (mL/min per 1.73 m2) median 57.2% 45.5% 43.0% 34.1%
Complications during hospitalization
Atrial fibrillation 24.6% 25.1% 31.5% 28.5%**
Cardiogenic shock 6.4% 3.1% 6.3% 5.5%
Heart failure 43.0% 54.7% 75.2% 77.3%**
Stroke 2.6% 1.3% 2.0*% 1.2%
Death 10.7% 10.7% 13.9% 18.0%**
NSTEMI = Non-ST-elevation myocardial infarction.
Significant *p<.01; **p<.001.
Hyperlipidemia + defined as total serum cholesterol level >200 mg/dL.
Hypertension ++ defined as systolic ≥140/>diastolic 90 mm Hg.

Table 2
Clinical management during hospitalization for acute myocardial infarction according to the presence of previously diagnosed anemia and/or heart failure
Anemia/heart failure 0/0 +/0 0/+ +/+
diagnostic/interventional procedures (n = 2,300) (n = 382) (n = 837) (n = 344)
Cardiac catheterization 60.0% 38.5% 37.5% 26.5%**
Coronary artery bypass grafting 7.5% 4.7% 4.4% 1.2%**
Percutaneous coronary intervention 40.2% 23.3% 21.4% 16.0%**
Medications
Angiotensin converting enzyme inhibitors /Angiotensin receptor blockers 67.0% 59.7% 69.1% 64.8%*
Aspirin 93.4% 86.9% 89.4% 88.1%**
Beta blockers 90.0% 90.8% 87.0% 87.5%*
Lipid lowering medications 74.7% 73.8% 65.7% 66.9%**
Cumulative number of cardiac medications
Any 2 medications 18.4% 22.3% 22.1% 25.9%*
Any 3 medications 30.6% 30.1% 32.9% 29.4%
All 4 medications 51.0% 47.6% 45.0% 44.8%*
*p <.01; **p <.001.

largest tertiary care and community medical centers in cen- presented with HF and/or anemia.6,20,21 The Controlled
tral MA, patients presented with a considerable burden of Abciximab and Device Investigation to Lower Late Angio-
previously diagnosed anemia and HF. After multivariable plasty Complications trial included over 2,000 patients hos-
adjustment, patients who presented with both chronic con- pitalized with AMI. Researchers reported that those who
ditions had the greatest risk for developing each of the presented with anemia at the time of hospitalization (13%
adverse outcomes examined. of the study sample) had a high prevalence of pre-existing
Our findings are consistent with the results from other diabetes mellitus, hypertension,and peripheral arterial dis-
investigations that have examined the frequency of various ease.20 Among patients enrolled in The Second National
chronic conditions in patients hospitalized with AMI who Registry of AMI (n = »36,000), individuals with previously
 ARTICLE IN PRESS
4 The American Journal of Cardiology (www.ajconline.org)

Figure 1. Frequency of adverse outcomes according to the presence of anemia and/or heart failure.

Table 3
Adverse outcomes according to the presence of previously diagnosed anemia and/or heart failure
Anemia/heart 0/0 +/0 0/+ +/+
failure outcomes (n = 2,300) (n = 382) (n = 837) (n = 344)
In-Hospital death, OR (95% CI)
Unadjusted model, 1.01 (0.71;1.42) 1.34 (1.06;1.70) 1.84 (1.35;2.49)
Adjusted model 0.98 (0.67;1.45) 1.16 (0.88;1.54) 1.66 (1.16;2.36)
Composite endpoint: Atrial fibrillation, heart failure, cardiogenic shock or stroke OR (95% CI)
Unadjusted model 1.37 (1.09;1.71) 3.86 (3.16;4.71) 4.16 (3.08;5.63)
Adjusted model 1.19 (0.93;1.53) 3.13 (2.50;3.90) 3.15 (2.26;4.38)
7-day hospitalization OR (95% CI)
Unadjusted model 1.36 (0.88;2.09) 1.18 (0.85;1.65) 1.58 (1.03;2.43)
Adjusted model 1.61 (1.02;2.56) 1.26 (0.86;1.83) 1.77 (1.08;2.89)
30-day hospitalization OR (95% CI)
Unadjusted model 1.11 (0.83;1.49) 1.37 (1.12;1.68) 2.02 (1.55;2.63)
Adjusted model 1.06 (0.77;1.46) 1.25 (0.99;1.58) 1.89 (1.39;2.57)
30-day mortality OR (95% CI)
Unadjusted model 1.40 (1.11;1.76) 1.25 (1.05;1.49) 1.60 (1.27;2.03)
Adjusted model 1.22 (0.94;1.59) 1.11 (0.91;1.36) 1.45 (1.11;1.91)
Models full adjusted for: age, sex, type of AMI, presence of comorbidities based on medical history, use of in-hospital medications, and receipt of cardiac
and diagnostic interventional procedures.

diagnosed HF had a higher prevalence of previous AMI, dia- and aspirin, whereas older patients who presented with HF,
betes, and hypertension as compared with those without with or without anemia, were less likely to have received
HF.6 These findings suggest that patients with HF and/or beta-blockers and lipid lowering medications during their
anemia carry a significant burden of other chronic conditions hospitalization. Most clinical trials have typically excluded
which may complicate their management and adversely older adults with HF and anemia, which has led to evidence
impact their outcomes during hospitalization for AMI. gaps in how to best treat this medically complex popula-
We observed relatively small differences across the 4 tion.13−14 Another finding of our investigation is that patients
comparison groups in the prescribing of in-hospital cardiac with HF and anemia were less likely to have undergone coro-
medications. Older adults who presented with anemia, how- nary revascularization procedures. Thus, there is a clear need
ever, were less likely to have been prescribed ACEI/ARBs for developing evidence-based data to help clinicians caring
 ARTICLE IN PRESS
Coronary Artery Disease/Outcomes in Patients With Heart Failure and Anemia 5

for these patients given their presence of chronic conditions 1. Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA,
and high risk for adverse clinical outcomes. McCabe CH. Association of hemoglobin levels with clinical outcomes
The individual or combined effects of anemia and HF on in acute coronary syndromes. Circulation 2005;111:2042–2049.
2. Lee WC, Fang HY, HC1 Chen, Chen CJ, Yang CH, Hang CL, Wu CJ,
the occurrence of adverse outcomes in older adults hospital- Fang CY. Anemia: a significant cardiovascular mortality risk after ST-
ized with AMI have been infrequently studied.7,22 In a multi- segment elevation myocardial infarction complicated by the comor-
center registry of patients hospitalized with STEMI, patients bidities of hypertension and kidney disease. PLoS One 2017;12:
who presented with previously diagnosed HF were 3 times e0180165.
3. Ariza-Sole A, Formiga F, Salazar-Mendiguchıa J, Garay A, Lorente V,
more likely to have died during hospitalization as compared Sanchez-Salado JC, Sanchez-Elvira G, Gomez-Lara J, Gomez-Hospi-
with those without HF.22 Similar findings were observed in tal JA, Cequier A. Impact of anaemia on mortality and its causes in
more than 45,000 individuals hospitalized with NSTEMI and elderly patients with acute coronary syndromes. Heart Lung Circ
previous HF; these individuals had twice the risk of dying 2015;24:557–565.
during hospitalization as compared with those without HF.7 4. Younge JO, Nauta ST, Akkerhuis KM, Deckers JW, van Domburg RT.
Effect of anemia on short- and long-term outcome in patients hospital-
Our findings suggest that individuals who presented with ized for acute coronary syndromes. Am J Cardiol 2012;109:506–510.
anemia were at higher risk for developing in-hospital com- 5. Roger VL. Epidemiology of heart failure. Circ Res 2013;113:646–659.
plications, being readmitted to the hospital within 7 days, 6. Wu AH, Parsons L, Every NR, Bates ER. Second National Registry of
or dying within 30-days after hospitalization. In a study of Myocardial Infarction Hospital outcomes in patients presenting with
congestive heart failure complicating acute myocardial infarction: a
more than 5,000 patients admitted to the Erasmus Univer- report from the Second National Registry of Myocardial Infarction
sity Medical Center for AMI, patients with anemia had a (NRMI-2). J Am Coll Cardiol 2002;40:1389–1394.
40% increased risk of dying within 30-days after the index 7. Roe MT, Chen AY, Riba AL, Goswami RG, Peacock WF, Pollack CV
hospitalization as compared with those without anemia.4 Jr, Collins SP, Gibler WB, Ohman EM, Peterson ED, CRUSADE
Investigators. Impact of congestive heart failure in patients with non-ST-
The combined effects of anemia and HF on adverse out-
segment elevation acute coronary syndromes. Am J Cardiol 2006;97:
comes in older individuals hospitalized with AMI are less 1707–1712.
well known. We found an increased risk for each of our 8. Goldberg RJ, Gore JM, Alpert JS, Dalen JE. Recent changes in attack
examined outcomes in patients who presented with HF and and survival rates of acute myocardial infarction (1975 through 1981):
anemia as compared with those without these chronic con- the Worcester Heart Attack Study. JAMA 1986;255:2774–2779.
9. Goldberg RJ, Gore JM, Alpert JS, Dalen JE. Incidence and case fatal-
ditions. We were unable to find other studies that examined ity rates of acute myocardial infarction (1975−1984): the Worcester
the combined effects of HF and anemia on adverse out- Heart Attack Study. Am Heart J 1988;115:761–767.
comes in patients hospitalized with AMI. In the Rochester 10. Goldberg RJ, Yarzebski J, Lessard D, Gore JM. A two-decade (1975
(MN) epidemiology project, patients with an incident AMI to 1995) long experience in the incidence, in-hospital and long-term
case-fatality rates of acute myocardial infarction: a community-wide
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lation included only patients who had been hospitalized in 2012 ACCF/AHA focused update of the guideline for the management
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American Heart Association Task Force on Practice Guidelines. J Am
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ing initial acute myocardial infarction: a community-wide perspective.
The authors have no conflicts of interest to disclose. Am Heart J 2002;143:519–527.
 ARTICLE IN PRESS
6 The American Journal of Cardiology (www.ajconline.org)

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