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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 1, January/February 2016
AFRICA
17
Methods
This was a cross-sectional, case–control study of the cohort
of children with sickle cell anaemia attending the paediatric
haematology clinic of Wesley Guild Hospital, Ilesa Unit,
Obafemi Awolowo University Teaching Hospital, Ile-Ife. Cases
were consecutive children with SCA (confirmed by haemoglobin
electrophoresis) aged two to 15 years in steady state. The age
limits were set at 15 and two years, as the older children are
managed in our hospital in the adult haematology clinic, and
those younger than two would not be old enough to cooperate
during electrocardiography.
Steady state was defined as a period without any acute
event such as pain, fever, infection or severe anaemia, and no
transfusion in the four weeks preceding recruitment.
10
Controls
were age- and gender-matched apparently healthy haemoglobin
AA children who attended the children’s welfare clinic of the
hospital for pre-school-entry medical tests. Children with SCA
on hydroxyurea, or those with known congenital or acquired
heart disease, as well as controls with any acute illness in the
previous two weeks were not incuded in the study. Also, none
of the subjects were on medications known to prolong QT
C
interval, such as halofantrine and anti-histamine. Parents of all
participants agreed to and signed written, informed consents
before commencing the study.
Data on sociodemographic characteristics (age, gender, socio-
economic class) and age at diagnosis were obtained by structured
questionnaires. Socio-economic class was determined using the
occupation of the father and the highest academic qualification
of the mother, as described by Olusanya
et al
.
11
Severity of SCD
was assessed using frequency of significant painful episodes,
blood transfusions and SCD-related hospitalisation in the
previous 12 months, and history of complications.
The children’s weights (kg) were measured using the SECA
®
electronic scale with an accuracy of 0.1 kg, with subjects standing
upright, barefoot and wearing only light clothing. Heights (cm)
were measured with a fixed stadiometer, Spirit Height
®
, with the
children standing erect and barefoot. From the measured values
of weight and height, the body mass index (BMI) was calculated
(kg/m
2
).
12
Liver and splenic enlargement were assessed clinically and
documented as size (cm), palpable from the corresponding
costal margins, vertically along the mid-clavicular line, using an
inelastic tape measure.
13
Blood pressures (BP) were taken supine
using the Accuson
®
mercurial sphygmomanometer. The average
of two readings was documented in mmHg. The systolic BP
corresponded to the first Korotkoff sound while the diastolic BP
corresponded to the fifth Korotkoff sound.
14
The lipid profiles were determined using CardioMetabolic
®
Profile 1 test kits to obtain total cholesterol (TC), HDL-C and
triglyceride (TG) levels. Low-density lipoprotein cholesterol
(LDL-C) levels were calculated using the Friedwald equation.
15
Haematocrit, platelet and total leucocyte counts, serum bilirubin,
creatinine levels, total protein, albumin, aspartate transferase
(AST), alanine transferase (ALT) and alkaline phosphatase
assays were done for the cases using standard methods.
All the participants were evaluated with 12-lead
electrocardiography, which was performed using the Biocare
®
IE-12A model digital electrocardiography machine at a paper
speed of 25 mm/s and standardised at 0.1 mV/mm. One of the
authors (JAOO) performed and analysed all electrocardiograms.
Measurements of the heart rate, cardiac axis, PR interval, QRS
duration and QT
C
interval were done in the standard fashion, as
previously described.
16,17
Electrocardiographic reference values
for Nigerian children were used as cut-off values for the duration
of electrocardiographic deflections and intervals.
17
Sokolow and
Lyon voltage criteria was used to determine LVH on ECG.
18
Statistical analysis
The clinical, laboratory and ECG profiles of cases and controls
were summarised and presented as proportions and percentages
for categorical data and means
±
standard deviation (SD), and
median and range for continuous data. Categorical variables
were compared using the chi-squared or Fisher’s exact tests,
while metric data were compared with the independent samples
t
-test, analysis of variance (ANOVA) or Pearson/Spearman
correlation test as indicated;
p
-values
<
0.05 were taken as
statistically significant.
Results
A total of 102 children, comprising 62 homozygous SS cases
and 40 age- and gender-matched haemoglobin AA controls, were
recruited for this study. The overall male:female ratio was 1.4:1.
Their ages ranged from two to 15 years, with a mean
±
SD of
7.76
±
3.66 years.
The sociodemographic characteristics and anthropometric
measurements of the cases and controls were similar (Table 1).
However, the cases had lower mean diastolic blood pressure and
mean arterial pressure than the controls (
p
<
0.05) (Table 2).
While the mean total cholesterol and LDL-C levels were
significantly lower among the cases than the controls, the mean
triglyceride level was significantly higher among the cases (
p
<
0.001). The mean HDL-C value was however comparable
between the two groups (
p
=
0.858). Total cholesterol:HDL-C
ratio was also lower among the cases (
p
=
0.029) (Table 1).
Table 2 shows the comparison of age-dependent ECG indices
between the cases and controls. The mean ECG-generated heart
rate (HR), PR interval, QRS duration and corrected QT interval
were higher among children with SCA than the controls (
p
<
0.05). The average RV5 voltage and combined RV5 and SV1
voltages were also higher among the cases (
p
<
0.05), however,
the mean QRS axis was lower, while the mean QT intervals were
comparable between the two groups.
ECG abnormalities: left ventricular hypertrophy (71.0 vs
27.5%), first-degree atrio-ventricular block (19.4 vs 0%) and
T-wave abnormalities consistent with lateral ischaemia (12.9 vs
0%) were significantly more prevalent among cases than controls
(
p
=
0.000, 0.008 and 0.021, respectively). Also, children with
SCA were about six times more likely to have LVH than age-
and gender-matched haemoglobin AA children (OR
=
6.4, 95%
CI
=
2.7–15.6). None of the study participants had left atrial
enlargement or T-wave inversion.
There was no statistical difference in the frequency of
occurrence of tall T-wave abnormalities, sinus rhythm with
ventricular premature complex, right atrial enlargement, right
or biventricular hypertrophy, ST depression and conduction
anormalies, such as right ventricular conduction delay and
non-specific intraventricular conduction block between the
two groups. On the other hand, abnormal left-axis deviation