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Evaluation of

Dyslipidemia in Children

ardiovascular disease and its link

with blood cholesterol levels and
other risk factors such as smoking, diabetes, hypertension, and obesity
are well documented.1 Much cardiovascular disease can be prevented by good
nutrition, exercise, and avoiding risk factors such as smoking, and controlling the
medical conditions that accelerate its progression.2
The Framingham Study2 and others
identified the risk factors that increase the

incidence of coronary artery disease. These

risk factors include a family history of heart
disease, reduced level of high-density lipoprotein (HDL) cholesterol, elevated serum
cholesterol level, hypertension, cigarette
smoking, impaired carbohydrate tolerance, and lack of physical activity. Male
gender also is a risk factor for premature
coronary artery disease; risk in women is
delayed by about a decade. Cardiovascular
disease remains the most common cause
of death in the United States.

Frances R. Zappalla, DO
808

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Atherosclerosis is a chronic disease

process with origins in childhood. The
rate of disease progression is determined
by the presence of known cardiovascular risk factors (eg, dyslipidemia, hypertension, diabetes mellitus, tobacco
use, physical inactivity). Atherosclerosis begins when there is damage to the
endothelium of the arterial wall.3 The
circulating factors in the blood including platelets and fibrin are deposited in
the area of injury. Over time, fatty particles, in particular cholesterol, are also
deposited causing a fatty streak. This
fatty streak is the earliest precursor to

TYPES OF LIPOPROTEINS
Circulating lipids are present in two
forms in the body: triglyceride and cholesterol.6 These lipids are insoluble in
plasma, but when combined with phos-

atherosclerosis. Eventually, this lesion

becomes permanent. Later, proliferation of cells in the area causes a raised
lesion to be formed. Over years, there is
additional deposition of material such
as fibrin, platelets, and cholesterol that
eventually occludes the vessel, resulting
in a myocardial infarction.
Abnormal lipid levels contribute
significantly to progression of atherosclerosis.4,5 Elevated low-density lipoprotein (LDL) cholesterol, low HDL
cholesterol, and elevated triglycerides
all contribute to atherosclerosis progression. Dyslipidemia may be caused

pholipids and proteins to form lipoproteins, they become soluble and can be
transported in the bloodstream. The
liver and other tissues, including the
gut as part of fat absorption, assemble
lipoproteins. Lipoprotein metabolism is
dynamic, with interactions among the
various types of lipoproteins occurring
throughout the body as part of normal
metabolism.
Lipoprotein levels are genetically
regulated, and significant deviations
from normal usually have genetic
causes. There are five major classes
of lipoproteins. Chylomicrons are

PEDIATRIC ANNALS 35:11 | NOVEMBER 2006

by genetic abnormalities, diet, and, for

the high triglyceride/low HDL cholesterol phenotype overweight and insulin
resistance.2 This article reviews dyslipidemias recognizable in children,
as well as dietary and pharmacologic
approaches to treatment. Recognition
and management will facilitate early
prevention of atherosclerosis.

formed from dietary fat in the gut and

are removed from the blood by the lipoprotein lipase. In otherwise healthy
individuals, the chylomicrons are responsible for the transient rise in triglyceride level after a meal. In individuals with impaired clearance, there is
a marked rise in the triglyceride level.
Very low-density lipoproteins (VLDLs)
are formed by dietary glucose and nonesterified fatty acids in the liver and are
triglyceride rich. They are catabolized
in the blood stream, and LDL and intermediate density lipoproteins are formed
from VLDL remnants. These three lat-

ter lipoproteins are rich in cholesterol

and atherogenic. The liver and small intestine secrete HDL. It is known as the
good cholesterol because it helps remove cholesterol from tissues and carries it to the liver. High levels of HDL
are protective and associated with a decreased risk of cardiovascular disease.
Conversely, low HDL levels increase
the risk of cardiovascular disease.2
LIPID MEASUREMENTS
A lipid profile consists of individually
measured total cholesterol (TC), triglycerides (TG), and HDL. Total cholesterol

809

and HDL do not need to be measured

in the fasting state. LDL is a calculated
measurement based using the Friedewald
equation (LDL = TC [HDL + TG/5]).2
This equation can only be used if the triglyceride level is below 400 mg/dL. If
the triglyceride level is above 400 mg/dL,
significant chylomicronemia is present.
An overnight fast of least 8 hours,
preferably 12 to 14 hours, is required
for an accurate triglyceride measurement. Triglyceride levels are dependent
on the diet of the individual and can vary
daily; multiple fasting serum levels may
be needed to determine accurate lipid
classification.7 Severe illness can cause
transient lipid abnormalities; therefore,
lipid levels should be delayed at least 4
to 6 weeks after an acute illness to get an
accurate measurement. The exception is
when hypertriglyceridemia is believed to
be the underlying cause of the disease,
such as in acute pancreatitis.
TYPES OF HYPERLIPIDEMIA
There are several types of hereditary
hyperlipidemias. A family history and
parental lipid panels are helpful to distinguish genetic from acquired types.6
In homozygous familial lipoprotein
lipase (LPL) deficiency, the triglyceride

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EDUCATIONAL OBJECTIVES

1. Discuss the rationale for cholesterol screening in children.

2. Identify children with abnormal
lipid profiles.
3. Implement dietary and pharmacologic management of abnormal
lipid profiles.
Dr. Zappalla is attending cardiologist, Nemours Cardiac Center, Wilmington, DE.
Address reprint requests to: Frances
R. Zappalla, DO, Nemours Cardiac Center, 1600 Rockland Rd., Wilmington, DE
19899; or e-mail fzappall@nemours.org.
Dr. Zappalla disclosed no relevant financial relationships.

810

SIDEBAR.

Risk Factors for Dyslipidemia in Children

Parents, grandparents, or a sibling of one parent experience heart disease by age 55,
including coronary angiography with evidence of coronary atherosclerosis, as well as
coronary artery bypass, balloon angioplasty, or stent placement.
Parents, grandparents, or a sibling of one parent had a documented myocardial infarction,
angina pectoris, peripheral vascular disease, cerebrovascular disease, or sudden cardiac
death by age 55.
Parent with elevated cholesterol level of 240 mg/dL or higher.
Parental history unknown.
Other risk factors for coronary heart disease, such as cigarette smoking, obesity with
a body mass index at or above the 95th percentile for age and height, hypertension,
diabetes, or physical inactivity.

levels are dramatically elevated. It is a

relatively rare disorder seen in children
and associated with pancreatitis and abdominal pain. The activity of LPL is diminished or absent causing the hydrolysis and removal of the chylomicrons from
the blood to be impaired. Decreased LPL
activity may also occur secondarily in
systemic lupus, pancreatitis, or immunologic disorders. The risk for atherosclerotic heart disease is debated. Many genetic traits including heterozygosity for
this disorder can cause the high triglyceride/low HDL cholesterol phenotype.
Familial hypercholesterolemia is the
lipoprotein disorder for which children
are screened. It is characterized by elevated LDL and usually normal triglycerides and is due to lack of functional LDL
receptors on the liver cell membrane or
abnormalities of apoplipoprotein B configuration. The homozygous form can
present in the first year of life with serum cholesterol levels higher than 500
mg/dL. The LDL level in the homozygous form is about twice as high as the
level in a heterozygous family member.
Xanthomas can appear before age 10,
and vascular disease can present before
age 20. It is a rare disorder, occurring
once per million population. These children may need LDL apheresis as part of
their treatment. Other disorders causing
secondary hyperlipidemia must also be
excluded to make the diagnosis. The het-

erozygote condition (1:500 population)

usually has no xanthomas, and LDL
cholesterol levels are usually above 160
mg/dL.
Familial combined hyperlipidemia
presents with elevated triglycerides,
elevated serum cholesterol levels (increased LDL and VLDL), or both. The
parents may have different types of familial hyperlipidemia resulting in varying levels of triglyceride or serum cholesterol elevation.
Hypertriglyceridemia is associated
with lack of exercise, stress, nonfasting
blood sample, or diabetes; these must be
ruled out before a genetic dyslipidemia
is considered. High carbohydrate (sugar)
intake worsens the high triglyceride/low
HDL phenotype, whereas mono-and
polyunsaturated fats lower triglycerides and raise HDL cholesterol levels.
In general, TG levels under 100 mg/dL
are normal. Levels over 200 mg/dL are
abnormal and suggest the possibility of
heterozygosity for a disorder of lipid
metabolism, especially if one of the parents has a similar dyslipidemia. Levels
between 100 and 200 mg/dL are usually
secondary to overweight, insulin resistance, high carbohydrate intake, lack of
fasting prior to the test, or heterozygosity for a disorder of lipid metabolism.
Hypolipidemia, or low HDL level,
is also associated with increased risk of
cardiovascular disease. An HDL level

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less than 40 mg/dL for men and less than

50 mg/dL in women is associated with
increasing risk. An HDL level in excess of 60 mg/dL has a protective effect
against future cardiovascular disease
and longevity is often present in families
with HDL levels over 70 to 80 mg/dL.
HDL levels less than 25 to 30 mg/dL reflect a genetic abnormality and may be
associated with significant risk of acceleration of atherosclerosis and future cardiovascular disease. Acute inflammation
can also lowers HDL levels.
PRIMORDIAL PREVENTION
Prevention of dyslipidemia in childhood is based on good nutrition and
maintenance of normal weight for
height. The American Heart Association, with endorsement of the American
Academy of Pediatrics, released its consensus statement for dietary recommendations for Children and Adolescents in
September 2005.8 These stated that children should eat nutrient-dense foods and
beverages in age-appropriate amounts.
Foods that are calorie-dense with minimal nutritional value (junk foods) need
to be limited and given only as discretionary treats.
A healthy diet consists primarily of
fruit, vegetables, whole grains, low-fat
and nonfat dairy, lean meat and fish,
nuts, and legumes. Daily physical activity is also an integral part of this healthy
lifestyle. Foods with added sugar, salt,
and saturated and trans fats should be
limited. These foods typically are processed foods, fast foods, snacks, and
sweetened drinks.
Not all fats are created equal and
some can be beneficial. Healthful oils
include olive, canola, and safflower. Saturated fat, cholesterol, and trans fatty acids should be limited. A healthy total fat
intake is about 20% to 35% of daily calories. Saturated fat, such as that found in
whole milk, butter, cream, or fatty cuts
of meat, should be limited to less than
10% of calories. Cholesterol should be

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Not all fats are created equal

and some can be beneficial.
limited to 300 mg per day, or the amount
found in one egg yolk. Trans fats or partially hydrogenated oils should be kept
to a minimum because these increase
LDL (or bad cholesterol).
The Web site http://www.mypyramid.
org contains useful tools for both the practitioner and the Web-savvy parent to help
achieve dietary goals. Included in the site
is a food intake calorie chart that assigns
the appropriate calorie intake based on
age, sex, and activity level beginning for
the 2-year-old. There are also downloads
available for each daily calorie requirement breaking down the daily requirement of grains, dairy, fruits, vegetables,
protein, and oils. For example, the average 2-year-old requires 1,000 to 1,400
calories a day, which should include 1
ounces of grains, 1 cup of fruits, 1 cup of
vegetables, 2 cups of milk or its equivalent, and 2 ounces of protein. Using this
as a guideline, a typical breakfast for a
2-year-old could be a quarter-slice of
toast, 1 tablespoon of applesauce, cup
of milk, and of a scrambled egg. Parents need to be taught appropriate portion
sizes for toddlers and young children.
Once children reach age 2, they can
be switched to low-fat (1%) milk and
nonfat dairy products. These products

are a major source of saturated fat and

cholesterol in this age group. Sweetened
drinks and foods are also a problem in
this age group. These foods should not
be forbidden but should be discretionary.
A concept that incorporates parental role
modeling is for parents to understand
they are responsible for what and where
the child eats, but the child can choose if
and how much to consume. The childs
satiety clues need to be recognized, and
children should not be forced to eat.
Dietary recommendations stress not
only the quality of the food but also the
quantity. An important aspect is learning to read food labels. After age 6 or 7,
children can be taught how to read food
labels and make good choices. Daily energy (caloric) input should be equal to
energy expenditure to maintain a healthy
weight. In order to lose weight, the scale
must be tipped so that energy expenditure exceeds input.
SCREENING
The American Academy of Pediatrics
Committee on Nutrition, along with the
National Cholesterol Education Program
of the American Heart Associations
Council on Cardiovascular Disease in the
Young, has released recommendations
for acceptable lipid levels in children
and screening guidelines.9 There are two
approaches to improving childrens cholesterol levels. The population approach
targets all children older than 2. The em-

811

phasis is on meeting nutritional goals of a

low-fat diet rich in fruits, vegetables, lean
meat, low-fat dairy, and whole grains.
Education of parents, caregivers including school and daycare staff, and primary
caregivers is essential for this approach.
The second approach is to identify high-risk children and adolescents
with elevated cholesterol levels through
screening.10 Risk factors for dyslipidemia
in children are listed in the Sidebar (see
page 810). A problem with the high-risk
selective screening approach is that some
children at risk can be missed. About
25% of children need to be screened to
identify about half of those with elevated
LDL cholesterol.11 High-risk parents who
are too young to demonstrate risks factors
or who have not sought medical attention
for a variety of reasons can be missed.
An acceptable total cholesterol level
is less than 170 mg/dL, with LDL of 100
mg/dL or less. A borderline measurement is total cholesterol of 170 to 199
mg/dL with LDL of 100 to 129 mg/dL.
High cholesterol is a total level over 200
mg/dL with LDL 130 mg/dL or higher.
Puberty plays a factor in variability
of cholesterol levels, which rise during
prepuberty and then falling to the lowest
levels of childhood as puberty advances
(about age 12 for girls and age 14 to 16
for boys). An increase in cholesterol level
from previously established values at age
9 to 12 may not reflect worsening dyslip-

812

Sweetened drinks and foods are

also a problemthese foods
should not be forbidden but
should be discretionary.
idemia but normal pubertal variability.12
Children with normal cholesterol levels should be provided with education on
nutrition, healthy eating pattern recommendations, and counseling on the other
risk factors that can lead to cardiovascular
disease. The fasting lipid panel should be
repeated in 5 years. Children with borderline cholesterol levels and their families
also should be provided with advice on
reduction of risk factors and nutritional
counseling as outlined above. Studies can
be repeated in 1 year.
Children with high cholesterol levels
should be examined for secondary causes
of hyperlipidemia (eg, thyroid, liver, or
renal disorders). All family members,
including parents and siblings, should
have a fasting lipid panel. Dietary management should be initiated for the entire
family. If the child has elevated cholesterol, it is likely that the parents and siblings
are also affected, and they can all benefit
from a diet change. It is also easier for
the child to adhere to his diet if the whole
family is eating the same way. These children should be re-evaluated in 3 months.

An effective cholesterol-lowering
diet requires a detailed assessment and
careful planning. Nutritional counseling by a physician, registered nurse, dietitian, or nutritionist is recommended
for the family to help with adherence.
Emphasis is on a low-fat diet with less
than 30% of daily calories from fat, less
than 7% of calories from saturated fat,
less than 10% of calories from polyunsaturated fat, and less than 200 mg of
dietary cholesterol. Dietary management of elevated triglycerides, low HDL
cholesterol, or both emphasizes less the
low total fat portion of the diet and encourages intake of poly- and monounsaturates in lieu of carbohydrates.
PHARMACOLOGIC TREATMENT
The National Cholesterol Education
Program (NCEP) recommends an adequate trial of dietary therapy for at least
6 months to 1 year. Drug therapy is considered in children 10 or older if LDL
remains above 190 mg/dL or if LDL
remains above 160 mg/dL and there are
two additional risk factors for cardiovascular disease or diabetes.10,13 Unless the
LDL cholesterol is extremely elevated
(above 250 mg/dL) or there are other
risk factors, drug therapy can be delayed
until after the adolescent growth spurt is
finished, particularly in girls.
If a child with a high triglyceride/
low HDL phenotype is overweight,
diet and exercise are the primary treatment. Weight loss and dietary changes
can lower the atherogenicity of the lipid
profile effectively, even if total cholesterol is little changed. The effect may
be less dramatic in those children who
have a familial dyslipidemia. Behavioral strategies are critical for the prevention of the acquisition of additional risk
factors to dyslipidemia.
Historically, bile acid binding resins such as cholestyramine and niacin
have been recommended in children.
These medications have low palatability and often are not tolerated for

PEDIATRIC ANNALS 35:11 | NOVEMBER 2006

long periods of time. The usual dose

of cholestyramine (bile acid binding
resin) is 4 to 16 g daily. It is not systemically absorbed, and gastrointestinal side effects are common, including
its unpleasant texture while ingesting,
constipation, flatulence, and bloating.
Niacin inhibits VLDL release from
the liver and is useful in lowering triglycerides and raising HDL cholesterol. However, it too has a high rate
of gastrointestinal side effects, in addition to acute irritating symptoms,
such as flushing and warmth, immediately after taking the medicine. These
symptoms improve with time and can
be limited by gradually increasing the
dose. In adults, the dose is usually 2
to 3 g daily. It is usually started at a
lower dose of 250 mg and built up as
tolerated; changes in the lipid profile
occur at doses above 1 g/day. Aspirin
usually is given with niacin in adults
and has been shown to help limit the
flushing; however, this is controversial in children because of the risk of
Reyes syndrome.
Four statins have been studied in
pediatric randomized safety and efficacy trials of at least 1 year: lovastatin
(Advicor), pravastatin (Pravachol),
simvastatin (Vytorin, Zocor), and atorvastatin (Lipitor). In addition to being
safe and effective, these studies have
shown statin treatment to improve brachial artery reactivity and to slow progression of carotid artery intimal thickening on ultrasound measurement.14,15
Statins reduce the livers production of
cholesterol and increase the ability of
the liver to remove LDL cholesterol
from the blood. They also moderately
reduce triglyceride levels and increase
levels of HDL cholesterol. The treat-

PEDIATRIC ANNALS 35:11 | NOVEMBER 2006

ment goal is LDL cholesterol below

130 mg/dL. The initial dose is 10 mg
daily, increasing to a maximum dose of
40 mg. The exception is atorvastatin,
which is twice as potent as the others
on a milligram for milligram basis.
If triglycerides are consistently
above 500 mg/dL on several determinations, fish oil at a dose of 2 g/day can
be initiated. If this fails, niacin can be
used. Fibrates should be reserved for
those with high risk for pancreatitis.
SUMMARY
Paying attention to cholesterol at
a young age will prevent future atherosclerosis. Clinicians must teach
parents that by making the necessary
nutritional and lifestyle changes, they
can prevent or lower their childs risk
for heart disease, hypertension, and diabetes. Recognition of the occasional
child with a genetic dyslipidemia will
allow more aggressive lipid-lowering
treatment at an age when atherosclerosis is first developing.
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