34 / 80
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017
168
AFRICA
in particular).
18
Several studies have demonstrated that there is
a relationship between increased mortality rates and
β
2
-agonists
in patients with BA. Moreover, there have been cases of sudden
cardiac death
19,20
and congestive heart failure
21
related to
β
2
-agonists.
However, in the present study, we administered the
β
2
-agonist,
salbutamol, for only seven days to ease the symptoms, and
thereafter we excluded the patients who required additional
β
2
-agonist therapy. We administered only one month of
montelukast. After the first month, patients received only ICS
therapy for five months. Therefore our study is also important
in terms of assessing the effects of inhaled corticosteroids
(ICS) on aortic stiffness. The cardiac risk that develops after
corticosteroid administration is related to the dosage. ICSs are
commonly used in BA. Although ICSs are considered to have far
less systemic absorption and possible systemic side effects, there
are still some concerns. Therefore, they are recommended to be
used in the lowest possible therapeutic doses.
22
Lorenzo
et al
. noted that the risk of acute myocardial
infarction (MI) increases in patients using oral corticosteroids;
however, there is no such risk increase in patients using ICS.
23
Conversely, acute MI risk in patients with BA decreased with
the use of ICS therapy in another study.
10
In general, this finding
supports the studies demonstrating the role of inflammation
in the aetiology of atherosclerosis, as well as the results of
our study.
7
This might be explained by the fact that the dose
that enters into the systemic circulation upon ICS therapy is
low enough to be below the level to exacerbate cardiovascular
risk, but still at a level to have the potential to repress the
inflammation associated with atherosclerosis.
In line with these studies, an animal study demonstrated that
the circulating levels of cholesterol and triglycerides did not
increase upon administration of corticosteroids, whereas plaque
formation and progression decreased.
24
In another study, a
decreased cardiovascular mortality rate was demonstrated upon
ICS administration in patients with asthma.
25
Corticosteroids
show cardiovascular effects through direct inhibition of
expression of the vascular adhesion molecules, in addition
to non-transcriptional activation of endothelial nitric oxide
synthase.
26
As is already known, nitric oxide (NO) released
from the endothelium contributes to arterial compliance and
distensibility.
6
Chronic inflammation and oxidative stress are
known to co-exist in BA.
27
The levels of reactive oxygen species
such as hydroxyl radicals, superoxides, and peroxides are elevated
in BA patients who have inflammation.
28
Chronic inflammation
is associated with endothelial dysfunction, atherosclerosis
and arterial stiffness, all of which are risk factors for future
cardiovascular events.
29
In paediatric BA patients who do not use ICS therapy,
carotid intima–media thickness (CIMT) was increased compared
to the control group and a positive correlation was noted
between CIMT and total oxidant status.
28
In another study, BA
patients treated with ICSs had decreased carotid atherosclerosis
compared to the control group.
30
The results of the present
study are not surprising, considering previous studies and
keeping in mind that atherosclerosis starts during childhood.
However, considering the age group examined in this study,
it does not seem right to attribute the improvement in aortic
stiffness after ICS therapy only to the role of inflammation in
the aetiopathogenesis of atherosclerosis. The suppression of the
negative cardiac effects of inflammatory steroids by ICS therapy
may be the dominant mechanism leading to healing, since
studies have demonstrated that steroids improve aortic stiffness
through a similar mechanism.
31
Some studies have established that assessment of aortic
stiffness can be used for early detection of atherosclerosis.
Moreover, aortic stiffness has been shown to increase with
advanced age, and in the presence of various conditions such as
hypertension, atherosclerosis,
β
-thalassaemia, smoking, obesity,
Marfan syndrome and Kawasaki disease.
32-34
Finally, in the present study the significant improvement in
TAPSE and haemodynamic recovery can be explained by the
anti-inflammatory effects of medications especially steroids,
in addition to being a direct outcome of the decrease in
the frequency of acute BA exacerbations; in other words, a
decrease in the duration of exposure to hypoxia. Hence, it can
be speculated that in addition to improving aortic stiffness, BA
medication may also improve right ventricular systolic function.
Previous studies have demonstrated that the presence of BA
in paediatric populations can result in subclinical ventricular
dysfunction as detected by tissue Doppler imaging.
35
The limitations of this study include the small number of
patients, the treatment regimen including both
β
2
mimetics,
montelukast and steroids, the short duration of treatment and
absence of a control group. The number of patients was 60
at the beginning of study; however, 15 patients who required
re-initiation of
β
2
mimetics apart from the standard therapy
were excluded. Patients were administered
β
2
mimetics and
montelukast only at the beginning of therapy, and thereafter
they were monitored on steroids alone. Therefore, therapies
other than steroids can be considered not to have affected aortic
stiffness during this period. A control group was not deemed
necessary, since the purpose of the study was to assess the effects
of ICS therapy on aortic stiffness in BA patients.
Conclusion
Contrary to the usual concerns about cardiac effects, medications
to treat asthma can be used safely in childhood BA and may
improve aortic stiffness through their anti-inflammatory effects,
and additionally by decreasing exposure to hypoxia. Moreover,
early diagnosis of BA and the initiation of therapy may
contribute to a decrease in cardiac mortality and morbidity rates;
however, additional long-term studies are required to develop
accurate conclusion on this subject.
This study was presented at 64th International Congress of the European
Society for Cardiovascular and Endovascular Surgery on 26–29 March 2015.
References
1.
Expert Panel Report 3 (EPR-3). Guidelines for the diagnosis and
management of asthma: Summary Report 2007.
J Allergy Clin Immunol
2007;
120
: 94–138.
2.
Wood LG, Baines KJ, Fu J, Scott HA, Scott HA, Gibson PG.
The neutrophilic inflammatory phenotype is associated with systemic
inflammation in asthma.
Chest
2012;
142
: 86–93.
3.
Deraz TE, Kamel TB, El-Kerdany TA, El-Ghazoly HM. High-sensitivity
C-reactive protein as a biomarker for grading of childhood asthma in
relation to clinical classification. induced sputum cellularity. and spirom-
etry.
Pediatr Pulmonol
2012;
47
: 220–225.