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Lymphocyte count and prognosis in patients with heart failure

Article  in  International Journal of Cardiology · April 2015

DOI: 10.1016/j.ijcard.2015.04.043 · Source: PubMed

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 International Journal of Cardiology 188 (2015) 60–62
Contents lists available at ScienceDirect
International Journal of Cardiology
journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Lymphocyte count and prognosis in patients with heart failure☆
Magaly Marçula a, Marcelo Felipe de Souza Buto a, Bruna Affonso Madaloso a,⁎, Rafael Amorim Belo Nunes a,
Marco Antonio Romeo Cuoco a, Rogério Silva de Paula a, Alice Tatsuko Yamada a, Monica Carneiro Sandoval b,
Denise Aparecida Botter b, Alfredo J. Mansur a
a
Heart Institute (InCor), Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil
b
Center of Applied Statistics, Institute of Mathematics and Statistics, São Paulo, Brazil
a r t i c l e i n f o
Article history:
Received 2 April 2015
Accepted 3 April 2015
Available online 7 April 2015
Keywords:
Heart failure
Lymphocyte count
Outpatients
Heart failure begets neurohumoral activation [1], release of
catecolamines, other inflammatory mediators and an increase in
serum cortisol [2] causing a decrease in lymphocyte count [3,4]. Studies
in patients with decompensated heart failure [3] or evaluated for heart
transplantation [4] demonstrated that a decrease in lymphocyte count
was associated with prognosis [3,4]. We evaluated leukocyte, monocyte
and lymphocyte counts relative to prognosis in outpatients with stable
heart failure.
We studied 3139 outpatients with heart failure, mean age 58 ±
13.8 years, (1972) 63% men and (1167) 37% women with the diagnosis
of heart failure between July 2003 and December 2005. Patients were
identified retrospectively in a routine hospital database and data re-
trieved from hospital charts. Etiologies of heart failure were: hyperten-
sive in 572 (35%) patients, ischemic in 300 (19%), Chagas' heart disease
in 208 (13%), and alcoholic in 61 (4%). In 394 (25%) patients, etiology
was not identified (idiopathic dilated cardiomyopathy).
Pharmacological therapy was administered according to patients'
needs at physician discretion and included beta blockers (carvedil-
ol), angiotensin-converting enzyme inhibitors (enalapril, captopril),
angiotensin receptor blockers (losartan) and diuretics (furosemide,
spironolactone). Therapy was administered by the physician in
☆ The authors take responsibility for all aspects of the reliability and freedom from bias
of the data presented and their discussed interpretation.
⁎ Corresponding author at: Heart Institute (InCor), Hospital das Clinicas, São Paulo
University Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo 05403-900,
Brazil.
E-mail address: brunamadaloso@uol.com.br (B.A. Madaloso).
http://dx.doi.org/10.1016/j.ijcard.2015.04.043
0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
charge of the patient and titrated according to patients' needs and
tolerance.
Studied variables were age, sex, duration of symptoms, smoking, al-
cohol consumption, etiology of heart failure, NYHA functional class,
body weight, height, body mass index, heart rate, systolic arterial pres-
sure, diastolic arterial pressure, cardiac rhythm and heart rate on 12-
lead electrocardiogram, left atrium diameter, diastolic diameter of left
ventricle, systolic diameter of left ventricle, left ventricle ejection frac-
tion, ventricular septum thickness and left ventricle posterior wall
thickness on echocardiography, blood hemoglobin, leukocyte count,
lymphocyte count, fasting glucose, creatinine, serum sodium, serum po-
tassium, LDL-cholesterol, HDL-cholesterol, triglycerides, and thyroid stim-
ulating hormone. We adopted the reference values of our routine clinical
laboratory. Lymphocyte count was categorized in low (b900/mm3), nor-
mal range — between 900/mm3 and 3400/mm3, and high (N 3400/mm3).
End point was defined as death of any cause. Mortality data were obtain-
ed from hospital records, from database of Sao Paulo City Authority Pro-
gram for the Study of Mortality and from SEADE Foundation (State
Authority Statistical System for Data Analysis).
Survival rate relative to lymphocyte count was evaluated with
Kaplan–Meier method [5]. Cox proportional hazards models [6] were
adjusted to evaluate the risk of death in two steps: first, models were
adjusted for age and sex and each one of 27 clinical and laboratory var-
iables studied; in the second step, a model was adjusted for age, sex and
all statistically significant variables (p b 0.05) that were selected in the
previous step; variables for the final model were selected by backward
testing. Continuous variables were categorized and missing variables
were considered as one category. The study was approved by the Com-
mittee of Ethics on Human Research of the Hospital.
The probability of survival relative to lymphocyte count (low, refer-
ence range, higher) is presented in Fig. 1; 1386 patients died in the
follow-up. The number of patients (53) with lymphocyte count N 3400
was small; therefore low lymphocyte count for further analysis was cat-
egorized below and above 900/mm3.
In the first exploratory step of Cox proportional hazards modeling,
eight out of 27 variables were excluded from analysis for lack of statis-
tical significance: etiology of heart failure, diabetes, smoking, heart
rate, ventricular septum thickness, left ventricle posterior wall thick-
ness, serum glucose and potassium. In the remaining 19 variables, miss-
ing values were set in a specific category that was later excluded in the
final model.
 M. Marçula et al. / International Journal of Cardiology 188 (2015) 60–62 61

serum hemoglobin (men), HDL-cholesterol and serum creatinine

(Table 1).
In this study sample of outpatients with heart failure, lymphocyte
count b 900 mm3 was associated with less favorable prognosis which
confirms observations made in patients evaluated for heart transplanta-
tion [7], with systolic heart failure or diastolic heart failure [8] and in pa-
tients admitted to the hospital due to decompensated heart failure [3,8–
12]. In 150 patients evaluated for heart transplantation, there was an
association between high jugular venous pressure and low relative lym-
phocyte count [7] and in 211 patients lymphocyte count lower than
20.3% [13] of leukocytes remained an independent variable associated
with prognosis after adjusting for functional class [4].
Interestingly, in decompensated patients lower lymphocyte
count was suggested to be transient and to reverse after clinical com-
pensation up to 100 days [10]; in other cohort of 3717 patients ad-
mitted to the hospital due to decompensated heart failure lower
lymphocyte count (b 15.4% of leukocytes) was associated with mor-
tality, with re-admissions and with unplanned medical visits in the
first 100 days after hospital discharge [12]; our findings demonstrate
that lower lymphocyte count may also be observed in outpatients.
The low lymphocyte count (b 20% of leukocytes) was suggested to
be a consequence of splanchnic congestion and tricuspid valve re-
gurgitation found in biventricular heart failure [10].
We did not detect an association between leukocyte count and
monocyte count with prognosis. We confirm previous observation in
African-American patients admitted to the hospital in that leukocyte
count did not demonstrate a difference with 131 outpatients with com-
pensated heart failure [10].
Fig. 1. Probability of survival relative to lymphocyte count.
Our study has limitations. It was performed in a large outpatient set-
ting under real life conditions and not strict protocol conditions over
In the second step of Cox proportional hazards modeling, lym- years. Pharmacologic treatment followed current guidelines but was
phocytes were significantly associated with mortality, showing not strictly standardized. We had missing values among the studied var-
higher chance of death in patients with less than 900/mm3 (b900 iables. We did not measure serum levels of catecholamines, cortisol and
vs ≥ 900/mm3; RR 1.85, CI 95% 1.25–2.74; p b 0.0001). Other vari- other inflammatory cytokines that may be operative in immune patho-
ables significantly associated with prognosis were age, body mass physiology of low lymphocyte count in this clinical setting.
index, diastolic blood pressure, previous history of arterial hyperten- In conclusion, this study confirms previous observations that low
sion, NYHA functional class, left atrium diameter (men and women), lymphocyte count, part of routine blood testing may be useful to identi-
systolic and diastolic left ventricle diameters, lymphocyte count, fy outpatients with heart failure at higher risk of death providing an ad-
ditional tool for identifying patients in need of close supervision.
Table 1
Variables associated with prognosis in patients with heart failure. Conflict of interest
Variable Risk ratio Confidence P value
interval The authors report no relationships that could be construed as a con-
Age (years) (3050 vs. 1830 and N50) 0.74 0.65–0.86 b0.0001 flict of interest.
Hypertension 1.22 1.02–1.46 0.029
NYHA III and IV vs I and II 1.55 1.33–1.81 b0.0001 References
Body mass index (kg/m2) 0.0008
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