Open Journal of Internal Medicine, 2012, 2, 7-10 OJIM
http://dx.doi.org/10.4236/ojim.2012.21002 Published Online March 2012 (http://www.SciRP.org/journal/ojim/)
Red cell distribution width in patients with HIV infection
María L. Gallego, Isabel A. Pérez-Hernández, Rosario Palacios*, Josefa Ruiz-Morales,
Enrique Nuño, Manuel Márquez, Jesús Santos
Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Universitario Virgen de la Victoria, Málaga, Spain
Email: *med006809@saludalia.com
Received 24 January 2012; revised 3 February 2012; accepted 14 February 2012
ABSTRACT
Objective: To examine the association between ele-
vated levels of red cell distribution width (RDW) and
cardiovascular risk factors (CVRF) and metabolic
syndrome (MS) in HIV-patients. Methods: Cross-sec-
tional study including all asymptomatic HIV-outpa-
tients under follow-up during 2007. Patients com-
pleted a questionnaire about CVRF, underwent a
physical examination, and an 8-hour fasting blood
analysis. Elevated RDW was defined as 75th percen-
tile. Patients with and without an elevated RDW were
compared. Results: 666 patients (79.3% men) were
included: mean age 44.7 years, mean CD4 506/mm3
and 87.5% on antiretroviral therapy (85.3% with
undetectable viral load). Mean RDW was 13.7%
(range: 7.7% - 33.6%; 75th percentile, 14.1%). The
prevalence per quartile of MS was 15.7%, 9.3%,
18.8% and 16.6% and of patients with CVRF > 20%
was 8.4%, 4.0%, 4.4%, and 6.4%, respectively (p >
0.05); 23.4% of the patients had an elevated RDW
(>14.1%). The top percentile of RDW was associated
with AIDS (OR 1.6; 95% CI, 1.0 - 2.4; p = 0.02), de-
tectable viral load (OR 1.5; 95% CI, 1.01 - 2.4; p =
0.04) and hypertension (OR 2.3; 95% CI, 1.4 - 4.0; p
= 0.001). Conclusions: In HIV-outpatients, higher
RDW is related with detectable viral load and with
AIDS. Although it was associated with hypertension,
we found no relation with MS nor with higher car-
diovascular risk.
Keywords: HIV; Red Cell Distribution Width;
Cardiovascular Risk; Metabolic Syndrome
1. INTRODUCTION
Red cell distribution width (RDW), which indicates the
degree of anisocytosis, is currently considered a new
marker of inflammatory activity [1]. A rise in this pa-
rameter has been related with cardiovascular disease, the
metabolic syndrome (MS) and increased morbidity and
mortality in persons with prior cardiovascular disease as
well as in the general population [2-8]. In patients in-
fected with the human immunodeficiency virus (HIV)
the prevalence of cardiovascular risk factors (CVRF) is
greater than in the general population, with the resulting
increase in the incidence of cardiovascular events [9,10].
Both the HIV infection itself and the antiretroviral treat-
ment taken play a role in the development of cardiovas-
cular events in this population [11-13]. In addition, these
patients also have a higher prevalence of the MS [14,15].
The aim of this study was to examine the possible asso-
ciation between elevated levels of RDW and CVRF and
MS in patients with HIV infection.
2. PATIENTS AND METHODS
We undertook an observational, cross-sectional study
including all patients with HIV infection under follow-up
at the Infectious Diseases Unit of Virgen de la Victoria
Hospital, Malaga, during 2007. The patients, who were
all asymptomatic, completed a questionnaire about CVRF
and underwent a physical examination with measure-
ments of anthropometric data, blood pressure and an
8-hour fasting blood analysis that included the lipid and
glucose profile. The 10-year cardiovascular risk was de-
termined form the Framingham equation and the diagno-
sis of MS was based on the criteria of the National Cho-
lesterol Education Program [16]. The RDW was consi-
dered to be elevated when it was 75th percentile. The
continuous variables were expressed as the mean (range
and interquartile range) and the categorical variables as
an absolute number (%). The characteristics of the pa-
tients with an elevated RDW were compared to those of
the patients without an elevated RDW. Comparison of
the continuous variables was done with the Student t test
or the Mann-Whitney U test if they did not follow a
normal distribution. The degree of association of cate-
gorical variables was measured by the χ2 test with Yates
correction or Fisher’s exact test. The statistical analyses
were done using SPSS 17.0 (Chicago, IL).
3. RESULTS
The study included 666 patients (79.3% men), and the
*Corresponding author.
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M. L. Gallego et al. / Open Journal of Internal Medicine 2 (2012) 7-10
8
mean age was 44.7 years. The mean CD4 lymphocyte
count was 506 mm3 and 87.5% were on antiretroviral
therapy, 290 (43.5%) with non-nucleoside reverse tran-
scriptase inhibitors and 258 (38.7%) with protease in-
hibitors. The use of nucleoside reverse transcriptase in-
hibitors were as follows: lamivudine 289 (43.3%), aba-
cavir 279 (41.8%), tenofovir 250 (37.5%), emtricitabine
181 (27.1%), didanosine 120 (18.0%), zidovudine 64
(9.6%), and stavudine 27 (4.0%). 85.3% of patients on
antiretroviral therapy had an undetectable viral load. The
mean RDW was 13.7% (range: 7.7% - 33.6%; 75th per-
centile, 14.1%). The prevalence per quartile of MS was
15.7%, 9.3%, 18.8% and 16.6% and the prevalence of
patients with CVRF > 20% was 8.4%, 4.0%, 4.4%, and
6.4%, respectively (p > 0.05); 23.4% of the patients had
a RCDW above the 75th percentile (>14.1%). Table 1
shows the comparison between the patients with and
without an elevated RDW. In the multivariate analysis,
the top percentile of RDW was associated with a diagno-
sis of AIDS (OR 1.6; 95% CI, 1.0 - 2.4; p = 0.02), having
a detectable HIV viral load (OR 1.5; 95% CI, 1.01 - 2.4;
p = 0.04) and hypertension (OR 2.3; 95% CI, 1.4 - 4.0; p
= 0.001).
4. DISCUSSION
In this cohort of patients with HIV infection and a good
clinical and immune-virological status, an elevated RDW
was associated with having AIDS, a detectable HIV viral
load and hypertension. No association was found with a
higher prevalence of CVRF or the presence of MS.
Although the exact pathophysiological mechanism
Table 1. Characteristics of the 666 study patients and comparison between those with the highest quartile of elevated red cell distri-
bution width (RCDW) (>14.1%) and those below this quartile.
Variables RCDW > 14.1% (n = 156) RCDW < 14.1% (n = 510) p
Male sex 109 (69.8) 419 (82.1) 0.001
Age (years) 44.6 (38.6 - 49.0) 44.7 (38.6 - 49.1) 0.8
BMI (kg/m2) 24.3 (21.6 - 26.5) 24.3 (21.9 - 26.3) 0.9
Smoker 99 (63.4) 339 (66.4) 0.3
HIV sexual risk 105 (67.3) 354 (69.4) 0.5
Months with HIV 122.5 (62.5 - 174.5) 120.6 (59.9 - 170.2) 0.7
AIDS 70 (44.8) 129 (25.2) 0.03
ART 132 (84.6) 443 (86.8) 0.3
CD4 (cells/mL) 483 (218 - 687) 513 (332 - 654) 0.2
CD4 < 350 cells/mL 56 (35.8) 136 (26.6) 0.03
CD4 nadir (cells/mL) 205 (43 - 272) 210 (70 - 313) 0.7
HIV viral load
<50 cop/mL* 103 (66.0) 388 (76.0) 0.01
Mean RCDW (%) 15.5 (14.4 - 15.8) 12.3 (11.6 - 13.2) 0.001
Diabetes 18 (11.5) 73 (14.3) 0.4
Hypertension 30 (19.2) 54 (10.5) 0.006
Hypertriglyceridemia 57 (36.5) 199 (39.0) 0.6
Low HDL cholesterol 82 (52.5) 214 (41.9) 0.02
Central obesity 23 (14.7) 54 (10.5) 0.1
MS 26 (16.6) 74 (14.5) 0.5
CVR at 10 years (%) 6.17 (1 - 8) 6.88 (1 - 11) 0.2
CVR > 10% 33 (21.1) 144 (28.2) 0.09
RCDW: red cell distribution width. BMI: body mass index. ART: antiretroviral therapy. MS: metabolic syndrome. CVR: cardiovascular risk. *Patients on ART.
he quantitative variables are expressed as the mean (IQR) and the qualitative variables as n (%). T
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M. L. Gallego et al. / Open Journal of Internal Medicine 2 (2012) 7-10 9
concerning the association between RDW, cardiovascular
disease and morbidity and mortality is unknown, any
systemic factor that alters red cell homeostasis, such as
inflammation or oxidative stress, may play a role [7].
The relation found in this study between an elevated
RDW, the presence of AIDS and, particularly, a detect-
able viral load, could be explained by the inflammatory
state induced by HIV replication, as well as by the dis-
ease itself. This inflammatory state prevents red cell
maturation, producing anisocytosis, as has been sug-
gested in other studies in the non-HIV population, inde-
pendently of the existence or otherwise of anemia [2,6].
The relation between an elevated RDW and hypertension
has been reported in patients with coronary disease [2],
as well as in a recent study in hypertensive persons. An
association has also been found between an elevated
RDW and carotid artery atherosclerosis [17]. Unlike the
findings of Sánchez-Chaparro et al. [3] in the general
population, an elevated RCDW in our series of HIV pa-
tients was not associated with the presence of MS. Fi-
nally, it has been reported that RDW may be modified
after starting treatment with thymidin nucleoside reverse
transcriptase inhibitors [18], which are the type of these
drugs less used in our series.
Nevertheless, the data from the various studies are not
all in agreement, possibly due in part to the different
methods used and the different characteristics of the
study patients. For instance, the mean age in our series
was lower than that of most earlier studies.
The cross-sectional design of our study, with its possi-
ble residual confounding factors, is a limitation. In addi-
tion, no measurements were made of vitamin B12, iron
or folic acid, which can normally modify the RDW,
though the data were adjusted for the hemoglobin and the
mean corpuscular volume, which are surrogate markers
of these parameters.
This study provides the first data concerning the pos-
sible importance of the RDW in patients with HIV infec-
tion, highlighting its relation with a poor control of the
disease, though we found no association with CVRF.
In summary, the RDW, which is usually determined
with the blood cell count and involves no extra cost, can
be considered an inflammatory marker which might help
improve the risk stratification in HIV-infected patients.
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