Review Article

Prevention and Management of Cardiovascular Disease Risk

Factors during Childhood
Elhadi H. Aburawi
Department of Pediatric, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE

Abstract
Coronary artery disease (CAD) or alternatively called atherosclerosis is the leading cause of death worldwide. There are multiple cardiovascular
disease risk factors (CVDRFs), which are the precursors for CAD. A chronic inflammation prompted by cholesterol‑rich lipoproteins and
other noxious CVDRF is central in the pathogenesis of CAD. Endothelial dysfunction is the first step in the development of CAD. There are
many theories in the development of the atherosclerotic process such as the hygiene theory, genetic susceptibility, and the endothelial injury.
For the modification and management of CVDRF, the disturbances in lipid and glucose metabolism, hypertension, obesity, and smoking are
the most important targets. The main aim of both primordial and primary preventions is to prevent the first cardiovascular event rather than
preventing the further myocardial infarction. The prevention should be considered and started early in childhood and not after the first cardiac
event. The primary healthcare physicians, obstetricians, neonatologists, and pediatricians need to work together on prevention of CAD early
in life and as early as in fetal life.

Keywords: Cardiovascular disease risk factor, coronary artery disease, endothelial cell dysfunction, infection, inflammation

Cardiovascular Disease Risk Factors
There are multiple cardiovascular disease risk factors (CVDRFs)
that have been reported as precursors for atherosclerosis
or coronary artery disease (CAD), which then progresses
gradually throughout life. These include a family history of
premature CAD, hyperlipidemia, diabetes mellitus, obesity,
cigarette smoking, sedentary lifestyle, and hypertension.
Other noxious CVDRFs are recurrent attacks of infection
and inflammation, hyperhomocysteinemia, and stress.[1]
Atherosclerosis is considered as a chronic inflammatory
disease with an autoimmune element. These independent
risk factors hasten or adjust recurrent infections or chronic
inflammatory vascular courses that finally present as
atherosclerotic plaque.[2‑4]
There are many theories behind the development of CAD such
as the hygiene theory, genetic susceptibility, and the endothelial
injury following infection and inflammation. The endothelial
injury and consequently dysfunction could be the result of
CVDRF. The endothelial dysfunction is considered the first
step for the atherosclerosis development. However, probably
the most putative theory is the endothelial injury and the body’s
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endeavor to heal, leading to loss of the coronary artery vascular
tone and formation of atherosclerotic plaque. Eventually, the
fibrous cap is formed, which is composed of extracellular lipid
core and layers of smooth muscle and connective tissue matrix.
Plaque rupture leads to dissemination of thrombogenic core
of lipid and necrotic material to the circulation. This in turn
will lead to platelet adherence, aggregation, and progressive
narrowing of the lumen of the coronary artery, which can
quickly progress to atherosclerosis.
A chronic inflammation triggered by cholesterol‑rich
lipoproteins and other noxious factors is central in the
pathogenesis of CAD. [2‑4] The biochemical markers for
CVDRF, for example, increased high sensitive or ultrasensitive
C‑reactive protein in the absence of acute infection or
inflammation, are considered to indicate a high risk of and
probably rapidly advancing CAD, where there is a real
Address for correspondence: Prof. Elhadi H. Aburawi,
Department of Pediatric, College of Medicine and Health Sciences, United
Arab Emirates University, P. O. Box 17666, Al Ain, Abu Dhabi, UAE.
E‑mail: e.aburawi@uaeu.ac.ae
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DOI: How to cite this article: Aburawi EH. Prevention and management of
10.4103/ijmbs.ijmbs_40_17 cardiovascular disease risk factors during childhood. Ibnosina J Med Biomed
Sci 2017;9:150-3.

150 © 2017 Ibnosina Journal of Medicine and Biomedical Sciences | Published by Wolters Kluwer - Medknow
 Aburawi: Prevention of CAD risk in children
need for aggressive preventive actions.[5] Commonly, viral
and also bacterial infections in children, especially when
they occur together with abnormal lipid profile, become
proatherosclerotic and are associated with intima‑media
thickness of the coronary arteries of children. [6,7] Minor
induction of inflammatory reaction by influenza vaccination
in children has led to abnormal brachial arterial function and
low‑density lipoprotein (LDL) oxidation, which persisted for
up to at least 2 weeks.[8]
In childhood, the endothelial function gets worse after
respiratory tract viral infections.[9] Furthermore, the endothelial
dysfunction existed for up to 5 years after the onset of Kawasaki
disease.[10] In general, exposure to CVDRF in childhood
may induce preatherocslerotic changes as demonstrated by
increased carotid intima-media thickness (IMT) two decades
later, which also increases with the number of risk factors
involved.[11] Furthermore, endothelial dysfunction in adulthood
at mean ages of 27 and 33 years was associated with early
childhood (<5 years of life) infection‑related hospitalization.[12]
Coronary Artery Disease
CAD is a chronic process, due to the decrease of antegrade
coronary blood flow into the myocardium, which leads to
ischemia. The myocardial ischemia results in an imbalance
between myocardial oxygen supply and demand with
accumulation of the metabolic products. This is caused by
a combination of a narrowing of the lumen and abnormal
vascular tone of the epicardial coronary arteries due to the
endothelial dysfunction and atherosclerotic plaque. This could
be symptomatic or asymptomatic, which may occur with or
without exertion, depending on the severity and speed of its
development. When the myocardial ischemia is severe and
long enough together with the accumulation of metabolic
products, myocardial infarction (MI) or ischemic heart disease
develops. CAD is the most common type of heart disease, and
it is the leading cause of death in the USA in men and women
of all major ethnic group. It was alone estimated to cost over
$100.00 billion/year (in the US for example) in the last few
years.[13]
Early histological features of CAD are fatty streaks and intimal
thickening, which were found in postmortem coronary arteries
of the newborn babies and children.[6,14] Intimal mesenchymal
reaction to injury was reported by Haust and his colleagues.[15]
The first step after the endothelial injury is the development
of fatty streaks, which contain atherogenic lipoproteins and
macrophage foam cells at the intima media, between the
endothelium and internal elastic lamina.
Management and Prevention of Cardiovascular
Disease Risk Factors
The management and preventive measures of CVDRF should
be started in fetal life and continued throughout childhood and
all the way through adulthood. The roots of CAD go back to the
Ibnosina Journal of Medicine and Biomedical Sciences  ¦  Volume 9 ¦ Issue 6 ¦ November-December 2017
intrauterine life, where the risk factors especially the genetic
factors and maternal diet and smoking start to have their effects
on the fetal coronary arteries with fatty streaks formation
and endothelial dysfunction. The prevention of CVDRF
development (primordial prevention) and the prevention
of future CAD by active management of identified risk
factors (primary prevention) are the main target to tackle the
CVD and specially the CAD.[16,17] It is too late to start managing
these risk factors when the patients already have symptoms
and signs or even after the treatment of MI. The prevention
program of CAD may be the best to be done in collaboration
with the obstetricians, neonatologists, pediatricians, and
primary healthcare physicians. The recommendation from the
expert panel documented three impending areas for attention:
maternal obesity, maternal cessation of smoking, and choice
of neonatal feeding method.[16,17]
Dyslipidemia with or without obesity
Dyslipidemia means composite of high levels of "bad" or
LDL cholesterol and low levels of "good" or high‑density
lipoprotein (HDL) cholesterol. It can be acquired genetically, for
example, homozygous hypercholesterolemia and obesity, but
also secondary to specific conditions such as obesity, diabetes
mellitus, chronic renal disease, a history of Kawasaki disease
with current coronary involvement, chronic inflammatory
disease, nephrotic syndrome, postorthotopic heart transplant,
and hypothyroidism. Familial hypercholesterolemia is defined
as raised LDL cholesterol in the child in concurrence with
the positive family history of high LDL cholesterol and/or
CAD.[16,17] Those with a positive family history of premature
MI and sudden cardiac death in relatives <55 years for males
and 65 years for females have a high CVDRF for CAD. The
most common form of dyslipidemia in children is the combined
one, which is seen commonly in obesity. Lipid assessment in
overweight and obese children and especially in those with
morbid obesity detects an important percentage of those with
substantial lipid abnormalities.[16,17]
The indication for pharmacologic treatment of dyslipidemia
is elevated LDL cholesterol level of >250 mg/dL, triglyceride
level of >500 mg/dL, and HDL cholesterol levels <40 mg/dL.
The objective of LDL‑lowering therapy (e.g., statin) in
childhood and adolescence is to decrease the LDL cholesterol
level to the <95th percentile (130 mg/dL). Statins have been
shown to decrease LDL cholesterol in children and adolescents
with markedly high LDL cholesterol. The other indications
for treatment of dyslipidemia in children are in those with
hypertension (blood pressure >99th percentile), current cigarette
smokers and obesity (body mass index >95th percentile), plus
dyslipidemia.[16,17] Furthermore, those who are at high risk
for accelerated atherosclerosis such as those with chronic
kidney disease, Type 1 or Type 2 diabetes mellitus, and
Kawasaki disease with coronary aneurysms and those
with a positive family history of MI and sudden cardiac
death should be considered for initiation of medication
therapy. The most important modifiable CVDRFs for the
development of atherosclerosis are disturbances in lipid and
151
 Aburawi: Prevention of CAD risk in children
glucose metabolism, hypertension, obesity, and smoking.
The United States Expert Panel on Integrated Guidelines for
Cardiovascular Health and Risk Reduction in Children and
Adolescents recommends healthy food, adequate physical
exercise, and nonsmoking. Measurement of lipid profile of
all children has raised critique. The recommendation states
that a pathological measurement must be checked with a
repeated test.[16,17]
Inflammation and infection
Validation of reliable and reproducible indices ideally
measured using noninvasive techniques for vascular risk
assessment remains an important task in cardiovascular
research in the young. Inflammation is central in the
pathogenesis of atherosclerosis.[2,3] Even in asymptomatic
individuals, a decrease in coronary microvascular function
is accompanied by a systemic inflammatory response,
independent of CVDRF.[18]
Uses of anti‑inflammatory agents in selected groups of
high‑risk individuals such as those with chronic inflammatory
disease and diabetes should be encouraged. The interleukin‑1
receptor antagonist (Anakinra) was found to be effective and
promotes myocardial deformation recovery in patients with
rheumatoid arthritis.[19]
Furthermore, given the evidence that the most common
etiology of infections is viral in origin, antibiotics use are of
less value in those high CVDRF groups. The use of antibiotics
for the secondary prevention of CAD is not proven.[20]
Lifestyle and dietary intervention
The international data put forward that only 5%–50% of
children and adolescents are meeting the current exercise
guidelines.[21‑25] The main causes of obesity in children and
adolescents are decreased physical activity and reduced
nutrition. According to the exercise guidelines, the energy
intake in obese children is often greater than in healthy
weight children.[26,27] Lifestyle is important to be modified
and to be started early in childhood both at schools and
at home. Physical exertion does decrease overweight and
improve endothelial function due to an increased blood flow
and shear rate during the exercise.[16,17]  In the strip study, the
dietary intervention started in infancy, which was continued
to early adulthood,[28] led to lowered LDL cholesterol and
improved high blood pressure, plus insulin sensitivity, and
diminished clustering of CVDRF. The dietary intervention
was in the form of replacing saturated fat with unsaturated
fat and the increases use of vegetables, fruits, and whole
grain products and a low intake of salt. In another study,
2‑year weight loss diets induced a significant regression of
measurable carotid vessel wall volume.[29] The effect was
similar in low‑fat, Mediterranean, or low‑carbohydrate
strategies and appears to be mediated mainly by the weight
loss–induced decline in blood pressure. [29] Individuals
with a history of   coarctation of aorta (CoA)  demonstrate
excess morbidity and premature mortality associated with
hypertension and CAD.[30] Intrinsic vascular abnormalities
152 Ibnosina Journal of Medicine and Biomedical Sciences   ¦  Volume 9  ¦  Issue 6  ¦  November-December 2017
might contribute to the risk for premature CAD, independent
of hypertension. Elevated blood pressure should be treated
medically.[30]
According to the Expert Panel, the recommendation for routine
blood pressure measurements should be started after 3 years
of the age.[16,17]
Given the multifactorial etiology of the arterial endothelial
dysfunction, and its implications in both atherosclerosis and the
regulation of coronary flow, strategies aimed at decreasing the
burden of CVDRF in childhood should be considered. Factors
to be paid attention to are family history of heart events in
the relatives, overweight, serum lipid concentrations, blood
glucose levels, and blood pressure.
Recommendation
The recommendation is to encourage and pursue screening
programs for more treatable CVDRF including hypertension,
diabetes mellitus, and hyperlipidemia especially familial
hypercholesterolemia, which should be implemented as
early as 3 years of age. Preventive sequence of measures are
immediate termination of smoking and having free smoking
and pollution environment, and lifestyle modifications
including healthy diet and organized physical activity in
schools and at home. Multidisciplinary approach teams and
specialized clinics need to be started for treating CVDRF, for
example, obesity, hypertension, and diabetes mellitus. Early
diagnosis and modification and treatment of the CVDRF over
long term may eradicate or at least delay CAD. These measures
should be implemented in each country at its own national
level according to the resource availability.
Conclusion
CAD is a disease that starts early in childhood and its roots
go back to the intrauterine life. The CVDRF especially the
genetic ones and maternal diet start to have their effects at
the intrauterine life with the formation of fatty streaks and
intimal thickening in the coronary arteries. It is too late to
start managing and preventing these risk factors when the
patients already have symptoms and signs or been diagnosed
and treated for MI. The primordial and primary preventions
should be the main aim to prevent the first cardiovascular
event rather than preventing the recurrent and future MIs.
The obstetricians, neonatologists, and primary healthcare
physicians need to work together on the prevention of CAD
early in life during antenatal care visits, neonatal period, and
as early as 3 years of age.
Disclosures
Single author article.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 Aburawi: Prevention of CAD risk in children
Ethical approval
Not applicable.
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Editors:
Elmahdi Elkhammas (Columbus, Ohio, USA)
Salem A Beshyah, (Abu Dhabi, UAE)
153
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