The Implications of the American Academy of Pediatrics Policy Statement on Cholesterol in Childhood

The Implications of the American Academy of Pediatrics Policy Statement on Cholesterol in Childhood

Disclosure Disclosure

• Disclosure of Affiliations and Significant Relationships:Dr. Smith has received honoraria related to speakers' bureau activities from Abbott, Merck, Merck Schering-Plough, 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.

TC TG HDLC LDLC T/HDL Metamucil Benecol

BID

425 94 44 362 9.7 Crestor 5 qd

316 82 54 241 5.8 Zetia 10

202 70 58 130 3.5

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 Non HDL

Glucose

242

288

44 140 5.5 198 86 Stop juices, decrease sugar levels

167

103

44 102 3.8 123 86

218

315

36 119 6.1 182 79 Soluble fiber

196

249

39 107 5.0 157 73

DZ 17 yr old young ladyHypertriglyceridemia on diet very low in saturated fatOn 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

The Implications of the American Academy of Pediatrics

Policy Statement on Cholesterol in Childhood

Mary P. McGowan, MDDirector: Cholesterol Treatment CenterConcord HospitalAssistant Professor of MedicineUniversity of Massachusetts Medical Center


• 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 Rationale for Retiring 1998 AAP Policy Statement “Cholesterol in Childhood”Statement “Cholesterol in Childhood”

• The current epidemic of childhood obesity has 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 Evidence for Atherosclerosis Beginning in Childhoodin Childhood

• Fatty streak formation occurs in human fetal aortas and 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)


• Bogalusa Heart Study: Fatty Streaks were present in 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)


• 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 YouthCholesterol Concentrations in Youth

• Cholesterol levels at birth: 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 YouthCholesterol 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 preventionPrimary prevention

What does a 20 – 40 mg/dL lower LDL

cholesterol mean over 4 – 5 decades?

Atherosclerosis Risk in Communities Atherosclerosis Risk in Communities Study (ARIC)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 StudyAtherosclerosis Risk in Communities Study3363 3363 African AmericansAfrican Americans vs 85 carriers vs 85 carriers PCSK9 PCSK9 142X or 679X142X or 679X

Cohen JC et al. NEJM 2006;354:1264.

HR .12, p 0.03 (90% risk reduction)

NNT 12

LDL-C 138

LDL-C 100

Atherosclerosis Risk in Communities Atherosclerosis Risk in Communities StudyStudy 9923 9923 CaucasiansCaucasians vs 301 carriers PCSK9 vs 301 carriers PCSK9 46L46L

Cohen JC et al. NEJM 2006;354:1264.HR 0.50, p 0.003 (50% risk reduction) NNT = 20

LDL-C 137

LDL-C 116

Conclusion: genes that Conclusion: genes that reduce LDL cholesterol 20 reduce LDL cholesterol 20

to 40 mg/dLto 40 mg/dL

Can result in 50 to 90% reductions in ischemic CV

events in Americans in their fifth and sixth decades

ScreeningScreening

• Current AAP Clinical Report offers no new guidance on whom to screen.

• NCEP Guidelines 1992 advocate a targeted approach: screen children with – family hx of CVD– elevated chol – family hx unknown – Presence of other CVD RF (obesity, cig smoking, htn,

DM)

Targeted Approach to ScreeningTargeted 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 YouthNCEP Cut Points for TC and LDL in YouthPediatrics 1992;89(3 pt 2)525-584Pediatrics 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 LevelsAbnormal 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 New AAP Report and Abnormal Cholesterol LevelsAbnormal 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 Approach to the treatment of Lipid Abnormalities in YouthAbnormalities in Youth

• Population Approach: Current AAP report concurs with previous guidelines recommending that – 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


• 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


• Individual Approach: High risk children defined as those 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


• Statins first line therapy in appropriate children 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 Summary – New recommendationsrecommendations

• Children between 12 months and 2 years of age 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 Summary – New recommendationsrecommendations

•Children age 8 years and older meeting cut-points for pharmacological treatment –

statins are the drug of first choice

Implications for Practicing Implications for Practicing LipidologistsLipidologists

• 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.


Samuel Gidding, MD Professor

Department of PediatricsJefferson Medical Center

Division HeadNemours Cardiac Center

Haddonfield, NJ


• 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.


Questions ?

Documents

The Implications of the American Academy of Pediatrics Policy Statement on Cholesterol in Childhood