Red cell distribution width in patients with HIV infection

doi:10.4236/ojim.2012.21002

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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: *[email protected]

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.

OPEN ACCESS

M. L. Gallego et al. / Open Journal of Internal Medicine 2 (2012) 7-10

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

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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