The Implications of the American Academy of Pediatrics Policy
Statement on Cholesterol in Childhood
Disclosure
• Disclosure of Affiliations and Significant
Relationships:
Dr. Smith has received honoraria related to speakers'
bureau activities from Abbott, Merck, Merck ScheringPlough, Schering-Plough, and AstraZeneca.
• Disclosure of Unlabeled Use and Investigational
Product Discussions:
Dr. Smith has indicated that his presentation will not
include the discussion of unlabeled uses of commercial
products or products that have not yet been approved by
the FDA for use in the United States for any purpose.
RF 6 year old boy.
Mother now 44: CABG, age 20, multiple ongoing PCI’s with latest to
left main and SVG; bilateral carotid endarterectomies, age 31;
on Crestor 40, Niaspan 2000, Zetia 10 and biweekly LDL apheresis.
Baseline TC 682, TG 94, HDLC 47, LDLC 623, T/HDL 13.2,
Lp(a) 47 (nl < 30).
Father: nl lipids
HT: 3’ 11” (35% ile, was 10th)
WT: 46lbs. (25% ile, was 5th)
BP: 90/60
No xanthomas.
Lp(a) = 98 (< 75nmol/L)
usCRP = 0.1
TC
TG
HDLC
LDLC
T/HDL
Metamucil
425
94
44
362
9.7
316
82
54
241
5.8
202
70
58
130
3.5
Benecol
BID
Crestor 5
qd
Zetia 10
DZ 17 yr old young lady
Hypertriglyceridemia on diet very low in saturated fat
On Estrostep(Estradiol 20-35mcg, norethindrone 1mg) for irregular
menses
Father 55 has  TC, TG, no CHD.
Mother 52 healthy but maternal grandmother MI –age 52.
Sister age 22 with similar lipids.
PE: 5’ 4”
WT: 118lbs (IW=128bs)
BP: 110/64
Lp(a) = 105nmol/L (nl < 75nmol/L
us CRP = 2.3mg/dl
TC TG HDLC
LDLC
T/HDL Non
Glucose
HDL
242 288
44
140
5.5
198
86
167 103
44
102
3.8
123
86
218 315
36
119
6.1
182
79
196 249
39
107
5.0
157
73
Stop juices,
decrease sugar
levels
Soluble fiber
The Implications of the American Academy of Pediatrics Policy
Statement on Cholesterol in Childhood
Mary P. McGowan, MD
Director: Cholesterol Treatment Center
Concord Hospital
Assistant Professor of Medicine
University of Massachusetts Medical Center
Disclosure
• Disclosure of Affiliations and Significant
•
Relationships:
Dr. McGowan has received honoraria related to speakers'
bureau activities from Merck and Co. She has also
received honoraria related to consulting and speaking
activities from Schering-Plough.
Disclosure of Unlabeled Use and Investigational
Product Discussions:
Dr. McGowan has indicated that her presentation will not
include the discussion of unlabeled uses of commercial
products or products that have not yet been approved by
the FDA for use in the United States for any purpose.
Rationale for Retiring 1998 AAP Policy
Statement “Cholesterol in Childhood”
• The current epidemic of childhood obesity has
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resulted in an increase in type 2 diabetes, HTN
and lipid disorders
Studies have clearly demonstrated that the
atherosclerotic process begins in childhood
New data has established the effectiveness and
safety of some of the available lipid lowering
agents in children as young as 8 years of age.
Pediatrics 1998;101(1pt1):141-147
Pediatrics 2008;122:198-208
Evidence for Atherosclerosis Beginning in
Childhood
• Fatty streak formation occurs in human fetal aortas and
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is enhanced by maternal hypercholesterolemia
(JCI 1997;100:2680-2690)
Bogalusa Heart Study: Fatty streaks at age 3. More
frequent in adolescence (NEJM 1986;314:138-144)
Pathobiological Determinants of Atherosclerosis in Youth
(PDAY) (N=2876, ages 15-34) Found that the extent of
fatty streaks and fibrous plaques in the Ao and Cor
arteries is strongly correlated with elevated cholesterol
(ATVB 1997;17(1):95-106)
Evidence for Atherosclerosis Beginning in
Childhood
• Bogalusa Heart Study: Fatty Streaks were present in
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about 50% of individuals during childhood and in 85% of
young adults.
By young adulthood, fibrous plaques were present in
69% of individuals studied.
The extent of atherosclerotic lesions correlated positively
with total cholesterol, LDL cholesterol, triglycerides,
blood pressure and with body mass index.
The extent of atherosclerotic lesions in childhood was
noted to rise exponentially with increasing number of
risk factors. (NEJM 1998;338:1650-1656)
Evidence for Atherosclerosis Beginning in
Childhood
• Bogalusa Heart Study (N=486): Childhood measurement
of LDL-C and BMI predict carotid IMT in young adults
(JAMA.2003;290:2271-2276)
• The Cardiovascular Risk in Young Finns Study (N =
2229): Risk factor profile assessed in 12-18 year olds
predicts adult common carotid IMT independently of
contemporaneous risk factors. Suggesting that exposure
to CVD RF early in life may induce changes in arteries
that contribute to the development of atherosclerosis.
(JAMA.2003;290:2277-2283)
Cholesterol Concentrations in Youth
• Cholesterol levels at birth:
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TC 70 mg/dL, LDL 30 mg/dL, HDL 35 mg/dL
Cholesterol increases rapidly in the first 2 years of life
Mean TC peaks at 171 mg/dL between ages 9-11
Cholesterol levels decrease during puberty and increase
thereafter
HDL falls permanently in young men during puberty
Ethnic differences: Black children--higher HDL/lower TG
than Hispanics or non-Hispanic whites
• J Chronic Dis. 1981;34(1)27-39.
Prev Med.1998;27(6):879-890
Cholesterol Concentrations in Youth
• Elevated concentrations of lipids and lipoproteins are
quite common. In the Child and Adolescent Trial for
Cardiovascular Health (grades 3 – 4) the prevalence of
total cholesterol concentrations > 200 mg/dL was 15.6%
in girls and 11.1% in boys. Am J Epidemiol
1995;141(5):428-439.
• 75% of children in the Muscatine Study and 70% of
children in the Bogalusa Heart Study with elevated lipids
tracked into adulthood. JAMA 1990;264(23):3034-3038
& Am J Epidemiol 1991;133:(9)884-899.
Primary prevention
What does a 20 – 40 mg/dL
lower LDL cholesterol mean
over 4 – 5 decades?
Atherosclerosis Risk in Communities Study
(ARIC)
LDLC and
Proprotein Convertase subtilisin/kexin type 9 (PCSK9)
serine protease gene variants that increase LDL receptors
15 year follow up: MI
fatal CHD
revascularization
in 13,000 Americans in 4 communities age 40 – 55 yrs
Cohen JC et al. NE5M 2006;354:1264.
Atherosclerosis Risk in Communities Study
3363 African Americans vs 85 carriers PCSK9
142X or 679X
LDL-C
138
LDL-C
100
Cohen JC et al. NEJM 2006;354:1264.
HR .12, p 0.03
(90% risk reduction)
NNT 12
Atherosclerosis Risk in Communities Study
9923 Caucasians vs 301 carriers PCSK9 46L
LDL-C
137
LDL-C
116
Cohen JC et al. NEJM 2006;354:1264.
HR 0.50, p 0.003
(50% risk reduction)
NNT = 20
Conclusion: genes that
reduce LDL cholesterol 20 to
40 mg/dL
Can result in 50 to 90%
reductions in ischemic CV events
in Americans in their fifth and
sixth decades
Screening
• Current AAP Clinical Report offers no new guidance on
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whom to screen.
NCEP Guidelines 1992 advocate a targeted approach:
screen children with
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family hx of CVD
elevated chol
family hx unknown
Presence of other CVD RF (obesity, cig smoking, htn, DM)
Targeted Approach to Screening
• Targeted approach results in between 35-46% of
children being screened
• Studies suggest that 30-60% of children and adolescents
with elevated cholesterol are likely to be missed with a
targeted approach - Does this lead to an increase in CVD
in adulthood?
• Pediatrics 1996;98(3 pt 1):383-388
• J pediatr 1995;126(3):345-352
• Pediatrics 1989;84(2):365-373
NCEP Cut Points for TC and LDL in Youth
Pediatrics 1992;89(3 pt 2)525-584
Category
Percentile
TC mg/dL
LDL mg/dL
Acceptable
< 75th
< 170
< 110
Borderline
75-95th
170 -199
110-129
Elevated
> 95th
> 200
> 130
Abnormal Cholesterol Levels
• Current AAP report notes that the NCEP guidelines use the same cut
points for all children ages 2-18
• Sensitivity and specificity of these cut points to predict adult lipid
status may vary according to age and sexual maturation
• One study suggested lowest sensitivity between 14-16 yrs, and
highest sensitivity between 5-10 and 17 – 19 yrs. (pediatrics
2006;118(1)165-172)
• Offers a suggestion that guidelines from LRC pediatric Prevalence
Study might be used – but these guidelines reported in 1981 before
current obesity epidemic and all-white population studied
New AAP Report and
Abnormal Cholesterol Levels
• NCEP guidelines: no pediatric cut points for TG or HDL.
With the epidemic of pediatric obesity these lipoprotein
parameters have become important.
• Cites AHA recommendation
(J Pediatr2003;142:368-372)
– Triglyceride concentrations of > 150 mg/dL*
– HDL concentration < 35 mg/dL** as abnormal
– Single cut point for TG or HDL may be of limited use given age,
sexual and ethnic differences in these lipoproteins offers LRC
Pediatric Prevalence Study for consideration
* > 95th percentile for any age or sex
** < 5th percentile for any age or sex
Approach to the treatment of Lipid
Abnormalities in Youth
• Population Approach: Current AAP report concurs with
previous guidelines recommending that
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children / adolescents have a balanced caloric intake
sufficient physical activity to achieve appropriate weight
more fruits, vegetables, fish, whole grains low fat dairy products
reduced fruit juice, sugar-sweetened beverages/foods, salt
Trans fats < 1% of calories
• New in these recommendations:
– Children between 12 months and 2 years for whom overweight
or obesity is a concern or who have a family hx. of obesity,
dyslipidemia or CVD
• reduced fat milk would be appropriate
Approach to the treatment of Lipid
Abnormalities in Youth
• Individual Approach: Focus on children and adolescents
– with a family hx of CVD or hyperlipidemia or
– who themselves have elevated cholesterol
The diet restricts saturated fat to 7% of calories and
dietary cholesterol to < 200 mg/day
Involve the entire family and a dietitian
• Other approaches in this population:
– Fiber (age + 5 g up to 20 grams)
– Plant stanols or sterols and
– Increased physical activity
Approach to the treatment of Lipid
Abnormalities in Youth
• Individual Approach: High risk children defined as those
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•
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having an LDL > 190 mg/dL despite dietary therapy, or
LDL > 160 mg/dL with other risk factors or > 130 mg/dL
with diabetes are candidates for pharmacologic
intervention. This is not a new recommendation
1992 NCEP recommended these cut points (with
exception of the third – did not single out diabetes as a
special circ) but did not suggest statins as first line drugs
Circulation 2007;115(14)1948-1967: Statins as first line
beginning at age 10 – also added other high risk children
including (DM, transplantation, HIV, SLE, nephrotic
syndrome)
New in this report: Initiate drug therapy between 8-10
Approach to the treatment of Lipid
Abnormalities in Youth
• Statins first line therapy in appropriate children
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statins approved for use in children include:
lovastatin, pravastatin, simvastatin, and atorvastatin
Bile Acid – Binding Resins: poor compliance
Niacin: LFT abnormalities reported in up to 26% of
children. Pediatrics 1993;92(1)78-82
Cholesterol-absorption Inhibitors: attractive,
not extensively studied
Fibrates: not extensively studied
Summary – New recommendations
• Children between 12 months and 2 years of age
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overweight or obese, or
family hx. of obesity, dyslipidemia or CVD
reduced fat milk is appropriate
Overweight triggers a full lipid profile
First lipid screening -- after age 2 and before age 10
Should be done fasting and if normal re-checked every
3-5 years
Overweight/obese children with high TG or low HDL
weight management treatment of choice
Summary – New recommendations
• Children age 8 years and older meeting
cut-points for pharmacological treatment –
statins are the drug of first choice
Implications for Practicing
Lipidologists
• If you do not see children in your practice
recommend screening the children of your
adult patients.
• Our EMR generates a letter sent to
pediatricians / family practitioners who
care for children of our adult patients
• We have two pediatricians on staff in our
practice.
The Implications of the American Academy of Pediatrics Policy
Statement on Cholesterol in Childhood
Samuel Gidding, MD
Professor
Department of Pediatrics
Jefferson Medical Center
Division Head
Nemours Cardiac Center
Haddonfield, NJ
Disclosure
• Disclosure of Affiliations and Significant
•
Relationships:
Dr. Gidding has disclosed that he has no significant
relationships with the grantors or any other commercial
company whose products and services are discussed in
his presentation.
Disclosure of Unlabeled Use and Investigational
Product Discussions:
Dr. Gidding has indicated that his presentation will not
include the discussion of unlabeled uses of commercial
products or products that have not yet been approved by
the FDA for use in the United States for any purpose.
The Implications of the American Academy of Pediatrics Policy
Statement on Cholesterol in Childhood
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