Review
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Fernanda Luisa
Ceragioli Oliveira†,
Rose Vega Patin and
Maria Arlete Meil
Schimith Escrivão
†
Author for correspondence
Division of Nutrology,
Departament of Pediatrics,
Universidade Federal de
São Paulo, Rua Loefgreen 1647,
Vila Clementino,
CEP 04037-020 São Paulo,
São Paulo, Brazil
Tel.: +1 5511 5084 4538
Fax: +1 5511 5084 4538
fernandalco.dped@epm.br
www.expert-reviews.com
Atherosclerosis prevention
and treatment in children
and adolescents
Expert Rev. Cardiovasc. Ther. 8(4), 513–528 (2010)
The atherosclerotic process starts in childhood and studies show its development in fetuses.
Clinical manifestation often occurs only in the sixth decade of life. Adolescence is a critical period
in the development of atherosclerosis, because fatty streaks may change to transition plaque
owing to genetic and environment factors. Healthcare by professionals plays a crucial role in
the prevention and treatment of atherosclerosis, identifying poor lifestyle, positive family history
of early cardiovascular disease, or other diseases such as dyslipidemia, obesity, arterial
hypertension and diabetes. Dyslipidemia in childhood and adolescence should be treating by
dietary therapy and change in lifestyle. Children with high-risk lipid abnormalities should be
considered for drug treatment.
Keywords : adolescents • atherosclerosis • children • diet • drug • dyslipidemia • prevention • risk factors • therapy
Based on literature from the last decade, the The Bogalusa Study [1,12] and the Pathobio­
atherosclerotic process begins early in life and logical Determinants of Atherosclerosis in Youth
its progression depends on genetic factors that (PDAY) [13,14] study showed that the atheroscle-
may be influenced by environmental factors [1–3] . rosis process starts in childhood. These autopsy
The earliest pathological finding in athero- studies demonstrated that the extent to which
sclerosis is the presence of fatty streaks in arterial the intimal surface was covered with atheroscle-
intima, which has been identified as the accu- rosis was significantly associated with an abnor-
mulation of lipid-filled macrophages and a pro- mal lipid profile and the presence of risk factors,
liferation of vascular smooth muscle cells. The such as arterial hypertension and obesity [12] . In
pathogenesis of atherosclerotic disease involves the the Bogalusa Study, fatty streaks were presented
inflammatory and immune systems. These cells in 50% of the children, increasing with age, and
migrate into the arterial intima and form a fibrous were seen in 85% of adults. The prevalence of
plaque that is responsible for clinical outcomes fibrous plaque also increased with age, being
such as ischemic and thrombotic events in adult found in 8% of children and 69% of adults.
age [3] . Fatty streaks in arterial intima were found In PDAY, for every 5‑year increase in age, the
in the fetus of hypercholesterolemic mothers [4] . place of damage is the same, but the grade of
Early cholesterol intake may have an influence atherosclerosis increased from grades  I–II to
on cholesterol metabolism later in life, so sev- grades IV–V [14] .
eral surveys have tried to identify the association The Muscatine study used ultrasonography to
between infant nutrition, adult lipid profile and evaluate intima media thickness (IMT) of the
cardiovascular risk [5,6–10] . Dremmers et al. exam- carotid arteries as a non-invasive indicator of the
ined for the first time the endogenous cholesterol atherosclerosis process [2] . It demonstrated that
fractional synthesis rate (FSR) among human the increased carotid IMT in adults was associ-
infants, and found that early intake of choles- ated with an altered lipid profile and other CVD
terol affects the FSR and the plasma lipid levels risk factors in childhood. The adolescents with
at 4 months, but the differences observed did not dyslipidemia have an increased risk of developing
persist at 18 months [11] . This study showed that high carotid IMT in adulthood (1,6–2,5), and
there is no imprinting of cholesterol biosynthe- if overweight or obese, they have higher carotid
sis at early life-cycle stages with ­different dietary intima thickness in adulthood compared with
levels of cholesterol in infancy. those who did not have both risk factors [15] .
10.1586/ERC.09.170 © 2010 Expert Reviews Ltd ISSN 1477-9072 513
 Review Oliveira, Patin & Escrivão

Atherosclerosis prevention effect of diet on coronary disease etiology. The study observed
The prevention of atherosclerosis should begin in childhood with that the Crete population presented a smaller incidence of coro-
modifications to lifestyle and the control of present risk factors. nary disease among the countries studied, despite a high total fat
Changing behavior by motivational strategies should be incor- intake (33–40% total energy). The result was attributed to the
porated into educational programs to be use in the daily clinical high consumption of olive oil, which is rich in monounsaturated
practice (Box 1) [16] . (16–29% total energy) and a low saturated fat intake (7–8% total
energy) [28] .
Lifestyle prevention Phytosterols are also effective in the reduction of total cho-
Epidemiologic studies have documented modifications in behav- lesterol (TC) and LDL-C in children and adolescents when
iors, therefore making it possible to note several risk factors that present in their diet and associated with other nutraceutical or
induce precocious CVD in children and adolescents [17,18] , owing medication  [36–38] . They perform functions that are analogous
to an increase in the intake of foods rich in saturated/trans fatty to cholesterol, because it is believed that there is a competition
acids, cholesterol, salt and sugar (Box 2) [19–23] . against choles­terol at the intestinal absorption moment [38,39] .
A study evaluating saturated fatty acids points out that lauric Phytosterols reduce the cholesterol absorption derived from diet
acids and stearic acids were more closely related to the reduction and biliary acids [38,40] . The exact mechanism by which is reduces
of HDL cholesterol (HDL-C) levels [24] . Nevertheless, cardio- cholesterol absorption is yet to elucidated; however, it appears
vascular risk is more closely associated with the presence of trans to decrease solubility of cholesterol micelles, hence the choles-
fatty acids when compared with saturated fat, in which higher terol availability for absorption is decreased. Studies carried out
levels of LDL cholesterol (LDL-C), apolipoprotein A (apo A) and using food enriched with phytosterols (margarines, milk, yogurt,
lower levels of HDL-C are observed [18,20,25–27] . Comparing three bread and cereals) promoted a reduction in serum TC and LDL-C
kinds of diets, including either margarine rich in hydrogenated (5–15%) levels [41,42] . The recommended dose of phytosterols
fat, soybean oil or butter, showed that excessive consumption of for the treatment of dyslipidemia is 2 g/day [18] . It is must be
trans fatty acids in margarines contributed to an increase in IL-6 highlighted that the intake of more than 6 g/day might reduce
and TNF-a levels. bioavailability of the fat-soluble vitamins [43] .
Changes in the types of fats consumed is fundamental to the Intake of dietary fiber and antioxidants, present in fruits, veg-
prevention of atherosclerosis [19,20,22] . Protective effects are asso- etables and wholegrains, also helps to control the lipid profile,
ciated with the intake of diets rich in unsaturated fatty acids, reducing lipid peroxidation and cardiovascular risk [28,23,44,45] .
showing a reduced risk of developing CVD [28–32] . The inclusion of functional fiber in a diet promotes the reduction
Omega-3 polyunsaturated fatty acids, particularly eicosapen- in biliary acid reabsorption, and as a consequence, helps to reduce
taenoic (EPA) and docosahexaenoic acid (DHA), found in oily cholesterol. An increase in the hepatic conversion of cholesterol
fish promote the reduction of the levels of triglycerides (TG) in to biliary acids contributes to lower serum LDL-C levels [46,47] .
the blood [22] . Several mechanisms explain this reduction, and the Positive results are observed with the inclusion of b-glucan (oat-
best one accepted is related to the reduction of hepatic lipogenesis, meal) during meals [46–48] . b-glucan used alone (3/5 g) or com-
or more specifically, smaller production and secretion of very low bined with phytosterols (5/1.5 g) promotes a LDL-C reduction
density lipoproteins (VLDLs) and triglycerides [33] . In order to of 3.7% to 5% and 9.6%, respectively [49] .
obtain the desired effects, it is imperative not to exceed a dose of b-glucan might have more modest effects than medication,
1 g/day of fish oil (EPA/DHA), otherwise an intake higher than but is enough to reduce cardiovascular risks [46] . b-glucan can
3 g/day might increase the risk of CVD, due to platelet aggre- also enhance serum cholesterol reduction, due to short-cycle fatty
gation and inflammation [30] . The American Heart Association acid formation. It is believed that acetate, butyric and propionate
(AHA) recommended eating oily fish twice a week, or any other produced by intestinal fermentation, act at a hepatic level, inhibit-
food rich in a-linolenic acid, such as flaxseed, nuts and canola, ing cholesterol and fatty acid synthesis, thus reducing biliary acid
and soybean oils [18] . absorption and LDL-C levels [46] .
Monounsaturated fatty acids are found in olive and canola oils, Antioxidant nutrients, such as some groups of polyphenols,
avocado and oils in general [25,34] . When compared with satu- vitamins and minerals, act as anti-atherogenic agents, inhibiting
rated fatty acids, they reduce the levels of LDL-C and increase lipid peroxidation [18,50] . Among the several classes of polyphe-
the levels of HDL-C [35] . The Seven Countries Study followed nols, lignans and flavonoids must be highlighted (i.e., isoflavone,
adult men for a period of 25 years with the aim of analyzing the flavone, flavonol, anthocyanidin, catechins, quercetins).
Several types of lignans can be found
Box 1. Atherosclerosis prevention strategy levels. in small quantities in vegetable oils, who-
legrains, vegetables and fruits, nonetheless,
• Children and adolescents: genetic, learning capacity and flavor experience greater concentrations are found in flax-
• Family environment: lifestyle (diet and physical activity), education and culture seed. Lignans are bioactive material found
• Micro-environment: local community school and other activities in water-insoluble dietary fiber, and metab-
• Macro-environment: media, laws, industry products and government policies olized in enterolignans (enterodiol, entero-
Data adapted from [16]. lactone) by intestinal fermentation  [51] .

514 Expert Rev. Cardiovasc. Ther. 8(4), (2010)

 Atherosclerosis prevention & treatment in children & adolescents Review

They belongs to the class of polyphenols

Box 2. Nutritional advice to prevent the development
and have a similar action to isoflavones in
of atherosclerosis.
estrogenic metabolism. Another effect is
related to their antioxidant action, which • Increase the intake of vegetables, fruits and legumes (beans)
reduces oxidative stress and inhibits oxi- • Introduce high-fiber foods, wholegrains and cereals
dation by LDL-C, therefore it is possible • Include fish in your meal (at least twice a week)
to keep lower levels of this lipoprotein, • Bake or grill meat, poultry and fish
reducing cardiovascular risk [52] . Some • Prepare foods with little or no salt and sugar
studies suggest that when lignans are used • Reduce total sugar and salt intake, including from industrialized products (juices, soft
as medications, they do not have the same drinks, breakfast cereals, cookies and soups), processed foods and condiments (soy
biological activity as the seeds and/or meals sauce and ketchup)
enriched with flaxseed [53,54] . In a meta- • Use vegetable oils and soft margarines
ana­lysis, it was observed that the dietary • Use lean cuts of meat and remove the skin from poultry before eating
intake of flaxseed and lignans promoted • Choose, prepare and eat smaller portions
a reduction in the levels of LDL-C, espe- Data adapted from [16,18].
cially in postmenopausal women; positive
effects in serum TG and HDL-C levels were not observed. In subjects who underwent hemodialisis and also in healthy ones,
order to support its indication, further studies must be developed higher serum HDL-C and apo A-I levels, and smaller LDL-C and
to evaluate the benefits in other cardiometabolic risk factors, and apo B levels were noted following a polyphenol ­consumption of
in different age groups [54] . 644 mg for 14 days (100 ml grape juice/day) [64] .
Beneficial effects associated with the presence of flavonoids There are associations between the intake of diets rich in ascor-
and cardiovascular risks are related to actions that inhibit platelet bic acid, folates, a-tocopherol, lycopene, b-carotene and selenium
aggregation and enhance endothelial function, thus regulating and a smaller cardiovascular risk [65–67] . It is believed that antioxi-
vascular homeostasis. Flavonoids are present in several foods, such dant substances found in a varied diet with fruits and vegetables
as soybeans, tea, cocoa, chocolate, red fruit, purple grapes, apples, could work together, increasing the antioxidant capacity and pro-
onions and broccoli [50,55] . tecting individuals from lipid peroxidation [23,50,66,67] . On the
In recent decades, epidemiologic, clinical and experimental other hand, there is no evidence to indicate that supplementation
studies have shown an association between soybean consumption with antioxidants is beneficial, and it is not possible to attribute
and reduced risk of chronic diseases, particularly CVD. Several the protective effect to a single food or nutrient [18,50,67] . Studies
investigations and meta-ana­lyses analyzed soybean and its bio­ with children should be developed to determine safe dietary
active components (isoflavones). The hypothesis that phytoes- intake recommendations that may help to prevent diseases [23,50] .
trogens are involved in inhibiting platelet aggregation or arterial Cross-sectional studies that assess the impact of physical exer-
vasoconstriction [56] has not been confirmed due to conflicting cise programs on lipid profiles generally show positive effects with
results [57] . Studies in humans were not satisfactory and they did 5–30% variation in lipoproteins [68–70] . Muscatine Study data
not have the same effects as found in animals experiments. Soy have shown that 11% of changes in relation to TC/HDL-C and
protein intake might not be viable, because it would demand the 3% in LDL-C were due to aerobic physical activity [71] . Although
consumption of enormous servings [57,58] . There are suggestions further long-term studies are necessary in children and adoles-
that the greater benefit with soybean consumption is related to cents in order to clearly identify the role of the physical activity
the substitution of animal fat/protein by the vegetal one, which on lipid profile changes; the beneficial effects of physical activity
would contribute to a higher consumption of polyunsaturated for the control of body weight in obesity has been well established.
fatty acids, vitamins, dietary fibers and, consequently, to a lower Increased physical activity allied to dietary changes contributes to
saturated fat and cholesterol intake [18,57,58] . the reduction of body weight, improving the metabolic effects of
Studies evaluating other polyphenols present in green tea (cat- obesity, such as insulin resistance and hypertension, thus reduc-
echins), in red fruit (anthocyanins, procyanidins and flavonoids) ing cardiovascular risk factors. The AHA recommends the daily
and in bitter chocolate (flavonoids and procyanidins), showed bet- practice of moderate-to-vigorous physical activity for a minimum
ter results with the latter, such as the enhancement of HDL-C, of 60 min for children and adolescents for cardiovascular health
and a reduction in serum LDL-C levels and platelet aggregation promotion [72] . The physical activity should be fun for children.
markers. Red fruit promoted a blood pressure reduction and an For adolescents there is also a recommendation for resistance exer-
increase in polyphenols, vitamin C and HDL-C levels [59–61] . An cises (10–15 repetitions) of moderate intensity combined with
experimental study showed a synergy between quercetins and cat- aerobic activity. Time spent doing sedentary activities (e.g., watch-
echins in inhibiting platelet aggregation, due to the production ing television, using computers, playing video games and using
of peroxide hydrogen, as an answer to the activation of phospho­ the telephone) should be limited to 2 h/day.
lipase C [62] . The reduction in platelet aggregation, smaller super- The following aspects should be investigated when guiding
oxide hydrogen production and increase of nitric oxide platelet physical activity programs for children and adolescents: physical
production was associated with grape juice intake [63] . In individual activity performed by them within the school environment and

www.expert-reviews.com 515
 Review Oliveira, Patin & Escrivão
out of it; family attitude towards participation in physical exer-
cise programs and games; the child or adolescent’s access to own
sites to practice physical exercises; and time spent by the child or
adolescent in sedentary activities.
The use of tobacco and secondary exposure to its products
increase the risk for CVDs. Smoking should be investigated in
children from 10 years of age and also their families [73] . Parents
should be discouraged from smoking due to the double impact
that such a behavior causes, so as to eliminate passive smoking, and
to prevent their children from taking up smoking. Young smokers
should be treated within therapeutic groups with cognitive behav-
ioral therapy. The content and approach of counseling sessions
should be tailored to youngsters, using appropriate dynamics,
language and didactic materials aimed at a younger audience.
Obesity & the metabolic syndrome
The metabolic syndrome in adults is known as an important
risk factor for the development of Type 2 diabetes and CVD.
Obesity has a central role in establishing the adverse effects that
constitute the metabolic syndrome. One study that analyzed the
contribution of generalized adiposity, assessed by BMI, to carotid
atherosclerosis in individuals with and without metabolic syn-
drome showed that obesity promotes cardiovascular risk factor
clusters [74] .
In children and adolescents, the components of the metabolic
syndrome such as obesity (particularly central adiposity), hyper-
insulinemia, insulin resistance, blood pressure and abnormalities
in lipoprotein profile, may also override and increase the risk of
CVD. A study with 262 obese children observed that 83.4%
presented at least one cardiovascular risk factor, and most of these
factors were significantly associated with increased waist circum-
ference that reflects central adiposity [75] . Obese children and
those with high waist circumference values have a higher risk
of developing the metabolic syndrome when adults, as demon-
strated in a sample ana­lysis of individuals who participated in the
Fels Longitudinal Study [76] . In 2008, Morrison et al. used data
from the Princeton Prevalence Study (1973–1976) and from the
Princeton Follow-up Study (2000–2004), and found strong asso-
ciations between metabolic syndrome in childhood and metabolic
syndrome in adulthood [77] . Other studies have also found strong
associations between obesity in childhood, and the development
of insulin resistance and increased cardiovascular risk [78–80] . A
study in Chinese children has observed that obesity was associated
with an increase in cardiovascular risk (high levels of triglycerides,
LDL-C and apo B, and reduced levels of HDL-C and apo A) [81] .
Obesity increases the risk of Type 2 diabetes that, in turn, is
associated with an accelerated development of vascular disease. The
physiopathology of Type 2 diabetes is complex and multifactorial.
Obesity, particularly abdominal with visceral fat stores, leads to
insulin resistance and hyperinsulinemia and, when glycemic control
is reduced, Type 2 diabetes and glucose intolerance occur. Obese
individuals develop different degrees of insulin resistance and not
all of them present glucose intolerance. Some studies have found an
association between insulin and blood pressure in children and ado-
lescents. The Bogalusa Heart Study has found a positive correlation
516
between high blood pressure and hyperinsulinemia in children, even
after adjustments for BMI [82] . In adolescents, insulin resistance has
been associated with sodium retention, which is reversible with
weight loss [83,84] . Increases in vascular resistance is also reversible
with weight loss and has been observed in obese adolescents with
insulin resistance [85] . Based on studies from diverse populations,
a meta-ana­lysis reinforces the concept that blood pressure tracks
from childhood to adulthood and that an elevated blood pressure
in childhood is likely to help predict adult hypertension [86] .
Insulin resistance has an important role in lipoprotein altera-
tions, such as increased triglyceride and cholesterol levels, and
reduced HDL-C levels. The Bogalusa Heart Study data shows
that obese children, when compared with lean children, had an
increased chance of presenting with high levels of TC, LDL-C,
and triglycerides and hyperinsulinemia [78] .
Bodyweight control in children and adolescents with changes
in eating habits and lifestyle has a positive impact on all meta-
bolic effects derived from obesity, thus reducing the risk of
developing CVD.
Overweight and obese children or adolescents should initiate
programs for weight management in order to regulate energy
balance by dietary and physical activity changes with family
participation [87] .
­
Blood pressure levels (systolic and diastolic) are considered nor-
mal when below the 90th percentile for age, sex and height [88] .
Children and adolescents with hypertension, in addition to gen-
eral dietetic guidance for weight control, should also be guided to
reduce sodium intake. When blood pressure levels remain elevated
despite changes in diet and lifestyle, and there are lesions in target
organs, pharmacologic treatment should be considered.
Dyslipidemia
Dyslipidemia refers to lipoprotein disorders detected by laboratory
tests, and usually occur without signs or symptoms during child-
hood and young adult age. Proper recognition and management
of lipoprotein disorders can reduce cardiovascular morbidity and
mortality [89] .
Dyslipidemia can be conceptually considered primary when
it includes genetic lipoprotein disorders that provide defects in
the metabolic pathways and secondary as to lifestyle and envi-
ronment, medication, metabolic or endocrine disorders, or con-
comitant diseases [90] . Familial hypercholesterolemia is the most
common primary dyslipidemia in childhood and adolescence,
characterized by autonomic dominant disease with a prevalence
of 1 in 250–500 in the general population for heterozygous geno-
type. This involves a functional alteration where there is a defect
in either the LDL receptor, or the LDL receptor’s ability to iden-
tify apo B, and is associated with an increased risk of premature
CVD. This lipid disorder causes a significant increase in TC and
LDL-C levels [89] . Children with lipid abnormalities such as a
LDL-C concentration above 240 mg/dl and HDL-C level below
40 mg/dl, showed a 1.7- and 1.8-times higher risk than those
whose parents had premature CVD, respectively [91] . Plasma lipid
profiles of children with and without primary dyslipidemia were
shown in Cortner et al.’s study [92] .
Expert Rev. Cardiovasc. Ther. 8(4), (2010)
 Atherosclerosis prevention & treatment in children & adolescents
Frequently, the diagnosis of genetic lipid abnormalities occurs
after ruling out the most common causes of secondary dyslipid-
emia due to the high cost of tests and difficulties in analyzing
lipid profile by advanced technology in order to identify metabolic
pathway defects.
The secondary causes of dyslipidemia in children and adoles-
cents are described in Box 3 [90] . The most prevalent secondary
cause of dyslipidemia in childhood is obesity, which is character-
ized by an elevation of triglycerides levels, low HDL-C concentra-
tion and abnormalities in the structure of LDL-C, which becomes
a smaller, denser and more atherogenic particle  [93,94] . The
metabolic syndrome lipid profile alterations include: increased
plasma VLDL-1 and remnant particles, elevated non-HDL-C,
high serum levels of triglycerides, a preponderance of small dense
LDL-C and HDL-C, elevated apoprotein B100 and CIII, reduced
concentration of HDL-C and apoprotein AI, raised plasma free
fatty acid levels and postprandial lipidemia [95] . The metabolic
syndrome definition for adolescents (aged 12–17 years) was pub-
lished by Cook et al. [96] , which recognizes three or more of the
following factors:
• Triglycerides ≥100 mg/dl
• HDL-C ≤40 mg/dl
• Waist circumference ≥90th percentile or BMI >95th percentile
• Fasting glucose ≥110 mg/dl
• Systolic blood pressure ≥90th percentile for age, sex and height
The Bogalusa Study data indicated that either BMI or waist
circumference values, when categorized by a threshold approach,
independently predicted CVD risk factor [97] .
Children and adolescents with HIV infection also need atten-
tion [98–100] . The HIV protease inhibitor effect and the chronicle
viral infection inflammatory status increased atherosclerosis risk.
A study of HIV-infected children and adolescents showed increase
carotid intima arterial thickness when compared with a control
group [101] .
In developed countries, adequate lipid profile was defined
according to population reference values regarding sex and age,
ranging between -2 and +2 standard deviations or higher than
the 5th and less than the 95th percentile [90] . These curves did
not consider ethnicity nor adolescent sexual maturation, which is
known to cause major differences in lipoprotein and triglyceride
values due to sexual hormone effects. Dyslipidemia is diagnosed
when one or more of the lipoproteins is higher or equal to the 95th
percentile for TC, LDL-C, triglycerides and apo B, and lower
than the 5th percentile for HDL-C and apo AI [90] .
The first pediatric joint statement was published by the National
Cholesterol Education Program (NCEP), and points out two ways
of detecting dyslipidemia in children and adolescents [102] . One of
them mentions that children with a family history of early CVD
should have their TC serum levels measured. Family history is
defined as parents or grandparents aged 55 years or younger with
evidence of atherosclerosis, peripheral vascular disease, cerebro-
vascular disease, or who have undergone coronary artery surgical
www.expert-reviews.com
Review
procedure, or suffered acute myocardial infarction or sudden
cardiac death. The other mentions that children with parental
history of hypercholesterolemia (TC level ≥240 mg/dl) should
have their TC level measured. If cholesterol level is borderline
(170–200 mg/dl), measurement should be repeated. If two TC
measurements are 170 mg/dl or higher, or the first measurement
is greater than 200 mg/dl, children should have their serum cho-
lesterol fractions measured. Serum cholesterol measurements and
fractions should be assessed twice in the same clinical laboratory
to confirm diagnosis of dyslipidemia, always following a 12-h
overnight fast.
In Brazil, cut-off points for lipid profiles of children aged 2 years
or older are described in Table 1, and ana­lysis of lipid profile is
recommended for those [73] :
• Whose parents or grandparents have a history of ­atherosclerosis
at age 55 years or younger
• Whose parents have TC over 240 mg/dl
• Who present additional risk factors such as hypertension,
­obesity, smoking, or consumption of saturated and/or trans
fat-rich foods
• Who use corticosteroids or have diseases that develop along
with dyslipidemia (AIDS, hyperthyroidism, lupus, chronic
renal disease and anorexia nervosa)
• Who show clinical manifestations of dyslipidemia (xan-
thoma, xanthelasma, corneal arcus, recurrent abdominal pain
and ­pancreatitis)
This guideline recommends lipid profile (triglycerides, TC,
LDL-C, VLDL-C and HDL-C) for all children with the afore-
mentioned characteristics. The Committee on Nutrition of the
American Academy of Pediatrics showed the lipid and lipoprotein
percentiles distribution in subjects aged 5–19 years, and the values
did not differ from the cut-off points adopted and neither did the
criteria to indicate lipid ana­lysis [17] .
Kwiterovich et al. included non-HDL-C in the lipid profile
of children and adolescents (Table 2), and this measurement, as
well as TC, can be determined with a nonfasting test [103] . It is
defined by HDL-C subtraction from TC, which includes ath-
erogenic apoB-containing lipoproteins (VLDL, IDL, LDL and
Lipoprotein [a]). This has proven to be a better independent
predictor of CVD than LDL-C [103] . In children, non-HDL-C
has being indicated as good a CVD risk predictor, as is LDL-C
of adulthood dyslipidemia [104,105] . Recommended cut-off points
for apo B and apo AI from the National Health and Nutrition
Education Survey (NHANES) [106] ; and for non-HDL-C from
Bogalusa Heart Study [107] . The universal screening of TC for
children and adolescents has not been accepted by many inves-
tigators. The lipid profile ana­lysis recommendation based on
positive family history of CVD has also been found in the lit-
erature. Studies have suggested that pediatric screening based on
family history is ineffective [108,109] . There were 75% of children
with abnormalities in lipid profile that were not screened due
517
 Review Oliveira, Patin & Escrivão

Dietary therapy
Table 1. Lipid profile for children and adolescents aged over 2 years
The strategies in nutritional intervention
according to the Guidelines on the Prevention of Atherosclerosis in
in dyslipidemia stimulate the adoption of
Childhood and Adolescence.
healthy food habits, promoting an energetic
Lipoproteins Acceptable (mg/dl) Borderline (mg/dl) Elevated (mg/dl) balance in order to keep appropriate weight,
TC <150 150–169 ≥170 without modifications to growth rhythm
and sexual maturation [16,113] . Therefore,
LDL-C <100 100–129 ≥130
besides the orientation already in use to
HDL-C <45 prevent CVD (Box 2) , recommendations are
TG <100 100–129 ≥130 described for lipid ­abnormalities in Box 4 [113] .
C: Cholesterol; TC: Total cholesterol; TG: Triglyceride. For children aged under 2  years, it is
Data from [73].
agreed that breastfeeding should be main-
tained up until 6 months of age, and then
to having a negative family history of dyslipidemia  [108–110] . A there should be an introduction of complementary feeding, which
study with school children found 64.4% of positive family his- should match age and physical activity, without any restrictions
tory, but there was no correlation between family history and on fat intake [16,18,113] . For children older than 2 years of age, it
serum lipids [111] . is recommended that cholesterol intake is restricted to less than
Otherwise, studies had showed that the universal screening of 300 mg/day and fats at 20–35% of total energy intake (saturated:
TC might be performed to detect those who present undiagnosed <10%; trans: <1%). Dietary fiber intake should be calculated
heterozygous familial hypercholesterolemia, who will need more considering the age of the child plus 5 g/day, up to the maximum
attention during treatment, including drug therapy. The use of of 20 g/day [17] . With regards to the anti­oxidant micronutrients,
TC measurement alone has being identified in 88–96% of cases the same recommendations are indicated for children without
of familial hypercholesterolemia, with less than 1% false-positive abnormalities in the lipid profile, because there is no consensus yet
rates found in a meta-ana­lysis study [44] . Some investigators pro- as to the benefits of the use of supplements [18] . The consumption
posed that 10 years of age has been considered a good age to of sodium should not be over 2.3 g/day [18] .
screen, due to the potential future effect of sexual hormones that More restrictive diets are recommended after 3  months of
will decrease the LDL-C levels, and will be closer to an age when dietetic intervention with no normalization of the LDL-C levels
drug therapy may be allowed [44,73,102,112] . [113] . In this case, dietary cholesterol should be kept at approxi-
mately 200 mg/day and saturated fats at approximately 7% of total
Dyslipidemia treatment energy intake [17,113] . Despite quantitative restrictions, the total fat
Lifestyle modifications are recommended in the treatment of dys- intake should follow the recommendation for a given age [18,113] .
lipidemia to reduce coronary heart disease risk. Diet change, daily Another positive measure is the inclusion of soluble dietary fibers
exercise and smoking cessation are the main points to modify lipid and foods rich in phytosterols to control the lipid profile [18,113] .
profile [17,89,90,102,103,112,113] . In case of hypertriglyceridemia, it is also recommended the con-
trol of simple carbohydrate intake, and a diet
Box 3. The causes of secondary dyslipidemia in children rich in omega-3 fatty acids consumption,
and adolescents. by the intake of fish rich in DHA and EPA,
• Lifestyle conditions: 2–3-times a week is also recommended [113] .
–– Diet, physical inactivity, smoking, obesity or starvation
Physical activity
• Use of regular medication:
Physical activity recommendation for dyslip-
–– Corticosteroids, retinoic acid, exogenous estrogens, immunosuppressive medications
idemia is the same for atherosclerosis preven-
–– Cyclosporine, antiviral-HIV protease inhibitors, b-blockers, testosterone,
oral contraceptives or anabolic steroids
tion cited earlier. Physical activity seems to
• Disease:
modify the lipid profile in children and ado-
lescents, and also brings additional benefits
–– Metabolic disease: diabetes mellitus Types 1 and 2 or lipodystrophy
such as BMI [114] and blood pressure reduc-
–– Hormonal disorders: hypothyroidism or Cushing syndrome
tion [115] , which contributes to the decrease in
–– Storage disease: Gaucher, Juvenile Tay–Sachs, Niemann–Pick
cardiovascular risk. Aerobic activity reduces
–– Renal disease: chronic renal failure, glomerulonephritis or nephrotic syndrome
TC, LDL-C and triglyceride levels, and also
–– Kawasaki disease
increases HDL-C concentration [115–120] .
–– Neoplasic treatment
–– Chronic inflammatory: systemic lupus or rheumatoid arthritis Drug therapy
–– Congenital heart: aorta coartation The NCEP recommendeds drug treatment
–– Hepatic disease: cirrhosis or congenital biliary atresia for children aged over 10 years with LDL-C
Adapted from [90,103,113]. over 190  mg/dl, whose cholesterol levels

518 Expert Rev. Cardiovasc. Ther. 8(4), (2010)

 Atherosclerosis prevention & treatment in children & adolescents Review

remained elevated despite dietary treat-

Table 2. Lipid profile for children and adolescents aged over 2 years,
ment for 6–12 months. The NCEP also
according to Kwiterovich.
considered treatment for those children
with LDL-C greater than 160 mg/dl with Lipoproteins Acceptable (mg/dl) Borderline (mg/dl) Alterated (mg/dl)
two or more risk factors for CVD or with TC †
<170 170–199 >200
family history of early CVD. Bile resins
Non-HDL <123 123–143 >144
were considered first-line drugs because cholesterol‡
they were not systemically absorbed [88]
LDL cholesterol† <110 110–129 >130
and there is a substantial clinical ­experience
with them [121] . HDL cholesterol †
>45 35–45 <35
McCrindle et al. recently established new Triglycerides : †

recommendations to start high-risk dyslip- 0–9 years of age <75 75–99 >100

idemic children on drug treatment  [119] . 10–19 years of age <90 90–129 >130
The criteria for drug treatment remain the Apolipoprotein B §
<90 90–109 >110
same as those from the 1992 statement, Apolipoprotein AI § >120 110–120 <110
after 6–12  months with a fat-restricted †
Data from NCEP [102]; ‡Bogalusa (2002) [107]; § NHANES III (1997) [106].
diet, Tanner’s II stage or higher, and after TC: Total cholesterol.
menstruation in girls (Figure 1) . Statins are Data from [101,103].
recommended as first-line drugs. In some
cases, treatment can be considered before the age of 10 years: LDL-C of 190 mg/dl or higher, including children with the
those with lipid profile abnormalities combined with additional metabolic syndrome. A total of 60% achieved LDL-C levels less
risk factors can present a reduced cut-off point for serum LDL-C than 130 mg/dl among the atorvastatin group, whereas none of
levels to start drug therapy [17,73,89,90,103,113,118] . Risk factors are as the patients in the control group achieved this target LDL-C
follows: positive family history of early CVD or event; an associa- level after a 6‑month follow-up [124] . Metformin has been used
tion of low HDL-C level with increased levels of triglycerides and to treat hyperinsulinemic adolescents with the metabolic syn-
small-sized LDL-C particles; an association between overweight drome, which may enhance insulin sensitivity, as well as reduce
or obesity and metabolic syndrome signs; the presence of other fasting blood glucose, insulin levels, plasma lipids free fatty
medical conditions associated with an increased risk of athero- acid and leptin [130,131] . In adults, when pharmacologic therapy
sclerosis, such as diabetes, AIDS, systemic lupus erythematosus, becomes necessary, fibrates and 3-hydroxy-3-methylglutaryl
organ transplant or cancer; the presence of arterial hypertension; coenzyme A reductase inhibitors (statins) are the most effective
smoking and second-hand smoking; and the presence of other drugs in controlling metabolic syndrome hyper­lipidemia, and
markers such as increase in homocysteine and C-reactive protein. are thus the drugs of choice [131] . Fibrates are effective in lower-
Some studies have established the effectiveness and safety of med- ing triglycerides and increasing HDL-C levels, the two most
ication in prepubertal children (aged 8–10 years) [121] , but in those frequent abnormalities associated with the metabolic syndrome,
younger than 8 years there should be pharmacologic intervention and statins are effective in lowering LDL-C levels, although
only in the event of dramatic elevation of LDL-C (>500 mg/dl), hypercholesterolemia occurs less frequently. In addition, the
such as in those homozygous for LDL recep-
tor deficiency [122] . Interventional stud- Box 4. Dyslipidemia dietary therapy.
ies in children with primary dyslipidemia • Elevated LDL-cholesterol:
were important to demonstrate drug safety, –– Reduce food consumption with high saturated fat (meats, poultry and organ meats)
with no interference in children’s growth or –– Limit fried foods and products with hydrogenated fat consumption
development, and, importantly, the reversal –– Limit egg yolk intake (2–3/week)
of functional vascular abnormalities by drug –– Use vegetable oils (soybean, canola and olive oil) and soft margarines
treatment [121,123–129] . –– Eat more vegetables, fruits and legumes
In cases of secondary dyslipidemia in chil-
–– Increase intake of high-fiber foods, whole-grains and cereals
dren and adolescents, such as the metabolic
–– Use low-fat or skim milk, and dairy products
syndrome, diabetes, renal disease, congeni-
–– Include fish at least twice a week
tal heart disease, collagen vascular disease,
• High triglycerides and low HDL-cholesterol:
oncologic therapy and AIDS, more aggres-
–– Limit refined carbohydrates, including from industrialized products (juice and soft drink)
sive treatment is indicated to lower CVD
risk [113,122] . –– Eat more vegetables, fruits and legumes
Drug treatment studies in children –– Increase intake of high-fiber foods, wholegrain and cereals
with the metabolic syndrome are rare in –– Use vegetable oils (soybean, canola and olive oil)
the literature. Atorvastatin therapy was –– Eat fish 2–3/week
used in children aged 10–17 years with Adapted from [16,113].

www.expert-reviews.com 519
 Review Oliveira, Patin & Escrivão

Adolescence

Positive CVD family history 12 h fasting to measure TC, TG, LDL-C and HDL-C

Parental dyslipidemia Repeat and average

Secondary dyslipidemia:
Clinical conditions
Lifestyle conditions (e.g., obesity)
Regular use of medication
Metabolic, renal or hepatic disease LDL-C <110 mg/dl:
Hormonal disorders Repeat lipid profile after 1 year
Provide education program
Lifestyle and risk factor advice

LDL-C 110–130 mg/dl

Re-evaluate lifestyle every 3 months
Repeat lipid profile after 1 year
Risk factor advice
Treatment: diet/physical activity

LDL-C >130 mg/dl

Re-evaluate lifestyle monthly
Repeat lipid profile after 3 months
Evaluate for primary or secondary causes
Screen all family members
Intensive clinician intervention: dietary therapy and physical intervention
Goal: minimal LDL-C <130 mg/dl
ideal LDL-C <110 mg/dl

Drug medication + diet therapy + physical activity

LDL-C ≥190 mg/dl
LDL-C ≥160 mg/dl is associated with the following risk factors:
– Positive family history
– Premature CVD
– Metabolic syndrome
– Tobacco use
LDL-C ≥130 mg/dl: diabetes mellitus
TG >400 mg/dl: high risk of the development of pancreatitis

Figure 1. Screening and management algorithm: outpatient of dyslipidemia. Nutrology Division, Pediatric Department,
Universidade Federal de São Paulo – UNIFESP.
CVD: Cardiovascular disease; TC: Total cholesterol; TG: Triglyceride.
Adapted from [102,103,113] .

combination of fibrates and statins is highly effective in con-
trolling abnormalities of the lipid profile in patients with the
metabolic syndrome [132] .
There are no consensus recommendations for drug therapy
for elevated triglyceride levels. However, in patients at risk of
pancreatitis, such as those with lipoprotein lipase deficiency
(homozygote), HIV with protease inhibitors, or children with
multiple cardiovascular risk factors, the use of medication to
control ­triglyceride levels was allowed [37,73,89,90,103,112,113,119] .
The evidence-based pharmacologic intervention for dyslipid-
emia in children is limited and the recommendations are based
largely on expert consensus and short- to medium-term random-
ized trials conducted for statins [113] . There are limited data for
the use of medications other than bile resin and statins [103,113] .

520 Expert Rev. Cardiovasc. Ther. 8(4), (2010)

 Atherosclerosis prevention & treatment in children & adolescents
It is important to note any side effects of the drug therapy and
to ask the opinion of parents and family when deciding on the
medication for dyslipidemia treatment [112] .
On the other hand, advanced grades of atherosclerosis may be
detected by the third decade in patients who have multiple risk
factors or who present with high lipid concentrations; so, it seems
logical to begin the dyslipidemia drug treatment in adolescence
in case of severe lipid abnormalities based on the risk stratifica-
tion [133] . Several classes of drugs are available for the management
of dyslipidemia.
Bile resins
Bile resins reduce bile acid absorption from the intestine and
increase hepatic LDL-C receptor expression, lowering serum
cholesterol and increasing LDL-C clearance [113] . They might
increase triglyceride levels, interfere in the absorption of fat-
soluble vitamins, and often cause gastrointestinal side effects
(constipation, bloating and flatulence) [37,103,113,119] . Reduction
in serum LDL-C levels varies from 13 to 20%, and doses
usually start at 4–5 g/day and may be increased up to 20 g/
day  [17,37,103,119] . Although bile resins are a first-line treatment
for dyslipidemia, according to the NCEP [102] , in practice,
bile resins are not well tolerated and some patients complain
of the bad taste, thus contributing to their low effectiveness.
There are two forms of cholestyramine, powder or tablets, and
patients preferred tablet form for daily intake. Colesevelam is a
new bile resin medication with more potent binding and fewer
adverse effects including no effect on triglyceride levels and
vitamin/drug absorption [134] . No pediatric studies have been
developed with this medication yet.
Statins
Statins (3-hydroxy-3-methylglutaryl coenzyme reductase inhibi-
tors) reduce cholesterol synthesis by inhibiting the enzyme HGM-
CoA reductase, thus controlling a step of cholesterol synthesis
[119,135] . This decrease in intracellular sterol causes the LDL-C
receptor gene to increase the number of LDL-C receptors and,
consequently, to reduce circulation of this lipoprotein. Their
effectiveness and safety in children and adolescents is similar to
that found in adults, and reduction in LDL-C levels varies from
21 to 41% [118] .
Statins may be useful in adolescents with primary and second-
ary dyslipidemia, such as those with familial combined hyper-
lipidemia and metabolic syndrome when LDL-C is higher than
160 mg/dl after diet and weight control, including CVD multiple
risk factors [103] . If LDL-C is less than 160 mg/dl after lifestyle
measures, metformin should be used by obese adolescents with
metabolic syndrome [131,135] .
Side effects of statins include hepatotoxicity with increases in
transaminases (usually transitory), myotoxicity with myalgia
and/or rarely with rhabdomyolysis, and teratogenicity  [37,119] .
Female adolescents on statin therapy should be guided with
regards to contraceptive methods owing to potential risk to
a developing fetus. Other drug interactions may occur with
increased risk of toxicity (macrolides, antifungals, protease
www.expert-reviews.com
Review
inhibitors, calcium channel blockers, cyclosporine, amiodarone),
and decrease in serum statin levels (rifampicin, barbiturates, car-
bamazepine) [135] . Simvastatin and lovastatin should be avoided
for severe drug interaction with antiretroviral therapy  [136] .
Patients who developed muscle cramps should be advised to dis-
continue the medication [89] .
There are four statins currently approved by the US FDA for
clinical use: simvastatin, lovastatin, atorvastatin and pravas-
tatin. A daily dose of statin is recommended at bedtime:
simvastatin/lovastatin 10–40 mg; atorvastatin 10–20 mg; pravas-
tatin 20 mg for children aged 8–13 years and 40 mg from 14 years
and over; rosuvastatin 5–40 mg [135] . Rosuvastatin, a new statin,
has proven to be effective and safe in the treatment of hyperlip-
idemia in adults with primary dyslipidemia, although studies in
children are currently lacking [137–139] .
Statins are the first option to treat hyperlipidemia but some
monitoring has to be done (Box 5) [119] . In addition, patients should
be monitored regarding growth (height, weight and BMI), sexual
maturation and development (Tanner stage of pubertal develop-
ment). Biochemical laboratory measurements (creatine kinase,
alanine aminotransferase and aspartate aminotransferase) should
be performed every 3 or 6 months.
Nicotinic acid
Nicotinic acid is a soluble vitamin and its action remains under
study. It lowers triglycerides, LDL-C and Lipoprotein (a) ­levels,
and raises HDL-C, apo AI and LDL-C particle size levels [37,90,113] .
Nicotinic acid also reduces plasma fibrinogen, and increases serum
homocysteine and uric acid levels by blocking the breakdown of
adipose tissue, decreasing the concentration of free fatty acid in
blood and the secretion VLDL-C by the liver, resulting in less
metabolite LDL-C due to a reduction in apoprotein B production
[89,90] . Therapeutic dose is 2–6 g/day, beginning with small doses
[89] . It is rarely used for treatment in the pediatric population
owing to the high incidence of adverse effects, such as diarrheic
disease and other more severe side effects such as glucose intoler-
ance, myopathy, hot flashes, pruridus, gastrointestinal symptoms,
hyperuricemia and hepatototoxity [89,90,140] .
Fibrates
Fibrates are fibric acid derivatives with a complex mechanism
of action, which decrease LDL-C and triglyceride levels and
increased HDL-C levels [90] . Fibrates are structurally and phar-
macologically related to the antidiabetic drugs, thiazolidinediones
[90] . They regulate the transcription of lipoprotein lipase, apo CII
and apo AI by the activation on proliferator-activated receptor‑a,
which has action on lipid metabolism [90] . This process results in
an increase in triglyceride-rich particle catabolism, reduction of
the secretion of VLDL-C and modification in HDL apoprotein
expression [90] . Bezafibrate dose varies from 10–20 mg/day and
its side effects include cutaneous manifestations, gastrointesti-
nal symptoms (abdominal discomfort and increase in bile litho-
genicity), interaction with anticoagulants, elevated transaminases,
creatinekinase enzymes, and plasma homocysteine, myo­pathy and
rhabdomyolysis, particularly when in combination with statins
521
 Review Oliveira, Patin & Escrivão

Box 5. Treatment with statins for dyslipidemia in childhood and adolescence: specific monitoring.
• Statins are first-line drugs in the treatment of dyslipidemia. Decision on which statin to be used is based on the experience and/or
preference of the professional;
• Start with the lowest daily dose before going to bed. Always perform serum creatine kinase, ALT and AST measurements;
• Guide patients on adverse affects, especially myopathies. If myopathy occurs, evaluate its relationship with physical activity; withdraw
medication and perform serum creatine kinase measurement. Wait until symptoms and laboratory changes disappear;
• Alert female adolescents to the use of contraceptive methods;
• Take care about drug interactions: cyclosporine, fibrates, niacin, erythromycin, azole antifungals, nephazodone, and protease inhibitors;
• After 4 weeks, monitor serum creatine kinase, AST and ALT measurements, and compare them to baseline levels. Serum creatine kinase
levels ten-times higher than the upper limit should be investigated (take into account the impact of physical activity), as well as ALT and
AST three-times higher than the upper limit. The minimum acceptable LDL-C concentration should be less than 130 mg/dl, and the
ideal concentration should be less than or equal to 110 mg/dl;
• If the desirable LDL-C concentration is achieved and no laboratory changes are observed, continue treatment and monitor biochemical
examinations every 8 weeks and, subsequently, every 3 months;
• If laboratory abnormalities or symptoms are observed, withdraw medication temporarily and repeat examinations in 2 weeks. If
biochemical parameters return to normal values, statin therapy can be resumed along with monitoring;
• If LDL-C concentration does not meet the goal, double the dose used and repeat laboratory examinations in 4 weeks. Increase the dose
continuously up to the maximum dose recommended until LDL-C achieves the desirable levels, and, mainly, if no clinical or laboratory
evidence of toxicity is observed.
ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; C: Cholesterol; HDL: High-density lipoprotein; LDL: Low-density lipoprotein.
Adapted from [112,119].

or when a patient has renal insufficiency [37,89] . These drugs may
be used preferentially in children with severe increases in tri­
glycerides and at high risk of developing ­pancreatitis (­triglycerides
>400 mg/dl) [17,89,90,102,112,113,119,132,141] .
Inhibitors of cholesterol absorption
Selective inhibitors of cholesterol absorption are new agents that
lower lipid levels. Although they are thought to act mainly on
intestinal absorption, unlike resins, these drugs are absorbed, enter
the enterohepatic circulation and may have systemic effects [17] .
Ezetimibe seems to limit the uptake of cholesterol and other sterols
by intestinal epithelial cells by interfering with the Niemann-Pick-
C1-like-protein 1 [90,142] . It also reduces LDL-C levels in 20%
and triglycerides in 5%; causing a slight increase (1%) in HDL-C
levels [90,113,122] . The adverse effect is limited to gastrointestinal
discomfort. It is used preferentially in combination with statins in
children with severe hyperlipidemia who do not respond to statin
monotherapy. The use in children aged over 10 years has already
been approved for patients with severe hypercholesterolemia at
doses of 10 mg/day [143] .
Expert commentary
Studies indicate strong evidence that atherosclerosis development
begins at an early age, so healthcare professionals play a crucial role
in the prevention and treatment of atherosclerosis. Keeping a healthy
lifestyle should be encouraged throughout childhood and adoles-
cence, especially in those who face high risk of CVD. Children
and adolescents should be advised of additional risk factors such as
weight gain, smoking and sedentary lifestyle. Risk factors such as
family history of premature CVD or dyslipidemia, obesity, arterial
hypertension and diabetes should be identified early in life. The
genetic component of primary dyslipidemia often produces sus-
ceptibility to environmental factors that increase the risk of CVD.
Secondary dyslipidemias such as inadequate lifestyle, the use of regu-
lar medication or disease should be detected owing to their capacity
to accelerate the development of atherosclerosis. Obesity prevalence
was increased concomitantly with comorbidities such as hyperten-
sion, dyslipidemia and diabetes. The metabolic syndrome is con-
sidered a cluster of risk factors for CVD, so should be identified in
childhood and adolescence. Diet should be monitored, emphasizing
low lipid content and highlighting the importance of a healthy diet
to the success of the treatment. Dietary recommendations include
a reduction of total fat, saturated fat, cholesterol and simple-sugar
intake. Sedentary lifestyle and smoking should be strongly discour-
aged. Children and adolescents have been encouraged to increase
their regular intake of fruit, vegetables, fiber-rich foods, complex
carbohydrates and fish. The lipid profile must be measured in
­children and adolescents who had one or more than one risk factor.
Drug treatment should be used only in children with high-risk lipid
abnormalities or other associated high-risk conditions that do not
respond to lifestyle changes, and should not be the first option of
treatment. Evidence from studies on the drug treatment of children
with primary dyslipid­emia shows safety and effectiveness similar to
that found in the treatment of adults. Studies have demonstrated
safety and effectiveness of statin treatment in children; however, due
to the lack of long-term studies, these ­recommendations should be
carefully used and with adequate criteria.
Five-year view
The literature highlights the need for CVD morbidity and mortal-
ity reduction in adults. Epidemiologic studies feature the presence
of both genetic and environmental risk factors, which combined,
result in the development of atherosclerosis.
Studies have shown that the atherosclerotic process can origi-
nate in childhood and might be detected even during intra-
uterine life depending on maternal health. Therefore, specialist

522 Expert Rev. Cardiovasc. Ther. 8(4), (2010)

 Atherosclerosis prevention & treatment in children & adolescents Review

guidelines recommend the identification of risk factors for CVD,
which involves positive family history, and the presence of dys-
lipidemia in parents, children or adolescents. Other diseases such
as arterial hypertension, diabetes and obesity must be prevented,
diagnosed and treated. Lipid abnormalities are considered a
coronary disease predictor factor.
Dyslipidemia prevention, diagnosis and treatment must be
considered strategies of utmost importance for the reduction of
atherogenic risk. In children, as well as in adolescents, treatment
must focus on changing lifestyle and feeding habits, avoiding
tobacco, and stimulating regular physical activity.
It is important to stress that drug treatment should be used
only in patients with severe lipid abnormalities, in patients
with high-risk conditions who did not meet their lipid-lowering
goals through diet and lifestyle approaches, or whenever these
changes are associated with the regular use of medications
or disease.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this
manuscript.

Key issues
• Cardiovascular disease (CVD) is an important cause of mortality in adult age.
• The atherosclerotic process starts in childhood, and studies show its development in the intrauterine period.
• Healthcare professionals should identify and modify risk factors, including inadequate lifestyle (e.g., diet high in calories, high fat, high
sugar and salty foods, sedentary lifestyle, and tobacco use), and also diagnose and treat diseases such as obesity, dyslipidemia, arterial
hypertension and diabetes.
• Dyslipidemia should be investigated in children and adolescents who have a positive familial history of premature CVD, familial
dyslipidemia, use of regular medication (corticosteroids, protease inhibitors or immunosuppressants) and disease (obesity, systemic
Lupus, rheumatoid arthritis or neoplasic treatment) that might lead to secondary dyslipidemia.
• Diet therapy and physical activities must be the first option to treat dyslipidemia in childhood and adolescence. Some clinical patients
suffering from primary dyslipidemia with severe lipid abnormalities and high-risk factors may need drug therapy.
• Drug therapy in childhood should only be used in patients with severe lipid abnormalities (LDL >190 mg/dl or LDL >160 mg/dl who
present the risk factors mentioned above) that are at least 10 years of age, after a 6–12‑month fat-restricted diet, Tanner’s II stage or
higher, and after menstruation in girls.
• Some studies have demonstrated the safety and effectiveness of statin therapy in children; however, due to the lack of long-term
studies, these recommendations should be carefully used and with adequate criteria.

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