rationale of screening and management

1. Dyslipidemias in Children
Dr. Adhi Arya
Fellow Pediatric Cardiology, FEHI

2. OVERVIEW
• Definition – Basis-Normative data
• Prevalence
• Etiology
• Screening
• Abnormal screen follow up
• Management of dyslipidemia
– Nonpharmacologic
– Pharmacologic –(Monitoring on Statins/ second line
agents)

3. Dyslipidemias are disorders of lipoprotein
metabolism that result in
• High TC/ LDL-C /non-HDL-C/TG)
• Low HDL-C

4. DEFINITION
• Normative values —
• Values vary by age sex , growth, ethnicity
• Relatively stable from 2-18 years
• Puberty-TC and LDL-C levels decrease with
increasing age before rising in the late teenage
years

6. Prevalence
• 20 % (age 6 to 19 years) have adverse levels of
one or more lipid value
• Elevated TG(10.2) >TC (7.1) > LDL-C (6.4)/
Non-HDL-C(6.4)
• Prevalence in normal weight, overweight and
obese were 14, 22, and 43 % respectively
.
Centers for Disease Control and Prevention (CDC). Prevalence of
abnormal lipid levels among youths - United States, 1999-2006

7. Indian data
.
• Grossly lacking in pediatric population
• Studies limited to high risk populations(
Kawasaki / FH
• Very few school based studies
• Ethical issues in conducting these
epidemiological studies for normative data

8. Indian data

9. Indian data

10. Indian data
The study was conducted to assess the incidence and type of lipid disorders in children
whose parents had premature coronary artery disease.
Group A- Lipid profile of 250 children (of parents who had premature coronary artery
disease (age <55 years), was compared with age matched healthy controls (Group B),
whose parents had no evidence of coronary artery disease.
Mean TC, LDL and triglycerides TG were significantly higher in Group A
The absolute values of lipids, TC and LDL in Group A children were within the normal
range for age.
Abnormal high density lipoprotein (HDL) level and elevated triglyceride levels were
present in 25% and 22.5%, respectively in the children of this group.

11. ETIOLOGY
Monogenic conditions ( single gene defect)
• Familial hypercholesterolemia, familial defective
apolipoprotein B or PCSK9, and familial
hypertriglyceridemia , Familial combined
Secondary dyslipidemia
Obesity, NS/ DM 2 / Drugs (eg, alcohol,isotretinoin)
Idiopathic, related to polygenic defects

12. ETIOLOGY

13. SCREENING
Rationale
• Short-term trials in high-risk populations and
studies demonstrating links between pediatric
dyslipidemia and atherosclerosis
• In the high-risk subset of children with severe
dyslipidemia due to FH, treatment reduces the
risk of cardiovascular events.
• Pediatric lipid disorders often track into
adulthood (50%)

14. SCREENING
Why Universal screening ?
Family history is an insensitive predictor
– Identifying and treating the greatest number of
individuals with FH, a group at highest risk
– Selective screening based on family history alone
misses a considerable number (30 to 60 percent)
of children with dyslipidemia
Universal Screening for Familial Hypercholesterolemia in
Children. J Am Coll Cardiol 2015.

15. SCREENING
Universal screening at
– 9-11 years( before puberty )
– 17-21 years ( after puberty)
High risk screening

16. SCREENING

17. SCREENING
Choice of screening test
• Full fasting lipid profile or non-fasting lipid levels
(non-HDL-C is calculated - more practical
screening test for pediatric patients).
• If an initial non-fasting screen is abnormal, a
follow-up fasting lipid profile should be obtained.
• At least two fasting profiles should be used to
guide clinical decision making, including
pharmacologic therapy.
Bogalusa heart study and PDAY
Study

18. SCREENING

19. FOLLOW UP AFTER -SCREENING

20. FOLLOW UP AFTER -SCREENING

21. MANAGEMENT
• Nonpharmacologic
( lifestyle changes -dietary
modification, physical activity, and
weight loss)
• Pharmacologic
Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev 2017.

22. MANAGEMENT

23. MANAGEMENT

24. MANAGEMENT

25. MANAGEMENT

26. MANAGEMENT
Pharmacologic therapy
• Typically with statins
• Generally warranted in children ≥10 years old
who fail to reach the targeted LDL-c goal with
lifestyle counseling by six months.
However, also dependent upon
• The severity of dyslipidemia
• Other comorbid conditions (eg, diabetes CKD);
• Family history of premature CVD

27. MANAGEMENT
Children <10 years old
Pharmacotherapy should not be
used in children <10 years of
age unless one or more of the
following are present:
• High-risk CVD condition
• LDL-C levels >400 mg/dL which
suggest homozygous or severe
heterozygous FH
• TG >500 mg/dL (5.6 mmol/L),
which may suggest primary
genetic hypertriglyceridemia
Children >10 years old
• Pharmacotherapy of older
children with dyslipidemia is
generally initiated when
lifestyle changes fail to
achieve target levels after
six months;

29. • Myopathy, new-onset type 2 DM, hepatic enzyme
elevation.
• More likely at higher doses and in patients taking
other medications (particularly cyclosporine,
azole antifungal, and foods (eg, grapefruit)
• Adolescent females- counseled about the
possibility of drug teratogenicity and appropriate
contraceptive
• Use of statins by breastfeeding mothers is
discouraged
MONITORING ON STATINS

30. MONITORING ON STATINS

31. MONITORING ON STATINS

32. If maximal tolerated dose of Statin is not
successful in achieving the LDL-C goal
• Cholesterol absorption inhibitors -Ezetimibe
• Fibric acid derivatives –, Gemfibrozil,
Fenofibrateare used primarily for treating
severe hypertriglyceridemia
• Bile acid sequestrants – Bile acid sequestrants
are not as effective as statins in lowering LDL-
C and have adverse side effects that result in
poor compliance
SECOND LINE AGENTS

33. PCSK9 inhibitors –Evolocumab and Alirocumab)
-human monoclonal antibodies that bind to
(PCSK9), a protein that plays a key role in
regulating plasma LDL cholesterol levels.
In Europe, evolocumab is approved in
adolescents (≥12 years old) with homozygous
FH
SECOND LINE AGENTS

34. • Mipomersen -inhibits production of
apolipoprotein B. It is used chiefly in patients
with FH- once weekly subcutaneous injection.
• Lomitapide -used chiefly in patients with
homozygous FH or in adults with very severe
heterozygous FH
– orally
SECOND LINE AGENTS

36. KAWASAKI

37. THANK YOU