M.Remo

6/29/2010

Lipid Management in Pediatrics

Research in children and adolescents show that risk factors for adult cardiovascular disease (CVD) may be present at a young age. These factors include high concentration of low-density lipoprotein (LDL), low concentration of high-density lipoprotein (HDL), elevated blood pressure, type 1 or 2 diabetes mellitus, cigarette smoking, obesity and the metabolic/insulin-resistance syndrome, and decreased level of physical activity and fitness. The epidemic of childhood obesity in the United States is also important to consider. During the past 25 years, prevalence of pediatric obesity has tripled and recent research suggests that increasing body weight in childhood is strongly associated with the risk of cardiovascular disease in adulthood. Identification of children who are at-risk for atherosclerosis may allow intervention that can prevent or delay adult CVD.

The National Cholesterol Education Program (NCEP) has created recommendations to identify children and adolescents (age 2-18) with abnormal lipid and lipoprotein concentrations.

NCEP: Cut Points for Total Cholesterol and LDL Concentrations in Children/Adolescents

Category	Percentile	Total Cholesterol (mg/dL)	LDL (mg/dL)
Acceptable	<75^th	<170	<110
Borderline	75^th-95^th	170-199	110-129
Elevated	>95^th	>200	>130

The clinical approach for treatment of abnormalities in lipid and lipoprotein concentrations can be approached by preventative measures as well as examining the individual for associated risk factors and need for pharmacologic therapy.

· A healthy lifestyle for all children is recommended for the prevention of development of dyslipidemia. A low saturated fat, low cholesterol diet with balanced caloric intake is recommended, accompanied with sufficient physical activity and the consumption of fruits, vegetables, fish, whole grains, and low-fat dairy products. Intake of fruit juice, sugar-sweetened beverages and foods, and salt should be reduced. Trans fatty acids should be limited to <1% of total calories. Dietary changes are not recommended for children younger than 2 years, because younger children require fat to support appropriate growth and development. But if children between 12 months and 2 years have a positive family history of obesity, dyslipidemia, or CVD and there is concern for overweight or obesity, caregivers may use reduced-fat milk.

· Individual assessment focuses on children at high-risk, including a positive family history of CVD or a personal history of high cholesterol and LDL. Initially, at least a six month trial of lifestyle changes can be used with recommended changes in diet, nutritional counseling, and increased physical activity. But these children may eventually be candidates for pharmacologic intervention. The concentrations of LDL at which pharmacologic intervention is recommended for children age 8 or older and adolescents are below. The initial goal is to at least lower the LDL concentration <160mg/dL, but a lower goal is desirable if there is a presence of associated risk factors.

Recommendations for Pharmacologic Intervention for Dyslipidemia in Children/Adolescents (age 8-18)

Patient Characteristics	Recommended Cut Points
No other risk factors for CVD	LDL persistently >190mg/dL despite diet therapy
Other risk factors present, including obesity, HTN, cigarette smoking, +family history of premature CVD	LDL persistently >160mg/dL despite diet therapy
Children with diabetes mellitus	Consider when LDL is >130mg/dL

In children younger than eight years of age, pharmacological therapy should only be considered if the LDL concentration >500mg/dL (ie. in cases of familial hypercholesterolemia).

Medications Available for Dyslipidemia:

· 3-Hydroxy-3-methyl-glutaryl Coenzyme A reductase Inhibitors (Statins):

Statins inhibit the rate-limiting enzyme needed for cholesterol synthesis. Statins are generally well-tolerated. Adverse effects include increased hepatic transaminase levels, elevated creatine kinase (associated with rare rhabdomyolysis), and potential teratogenicity -- these effects should be monitored. Studies have shown statins to be safe and effective in lowering cholesterol concentrations in children.

· Bile Acid Binding Resins:

These medications bind cholesterol in bile acids in the intestinal lumen, preventing reuptake in the enterohepatic circulation. Adverse effects is limited to GI discomfort, with no systemic effects but compliance of these resins in children have shown to be poor.

· Niacin:

Niacin decreases hepatic production of very low-density lipoprotein (VLDL) and is effective in lowering LDL and triglyceride concentrations and increasing HDL concentration. Adverse effects including flushing, hepatic failure, myopathy, glucose intolerance, and hyperuricemia – making niacin an unattractive medication in pediatrics.

· Cholesterol-Absorption Inhibitors/Fibrates: These have not been extensively studied in children.

In summary, below are the final 2008 AAP Recommendations on Hypercholesterolemia in Children/Adolescents.

2008 AAP Recommendations on Hypercholesterolemia

Recommendation
Screening	Assess fasting lipid profile Recommended with family history of high cholesterol or early atherosclerosis Recommended with unknown family history Recommended given personal risk factors Screen every 3-5yr beginning at 2yr of age Use age and sex specific cholesterol norms (>95^th percentile considered abnormal)
Diet and Exercise	Begin nutritional therapy with reduced-fat milk at 1yr for children at risk owing to obesity or family history Follow Dietary Guidelines for Americans, with saturated fat <7%, trans fat <1%, dietary cholesterol <200mg/day, and suggested fiber intake equal to child’s age plus 5g/day up to 20g/day at 15 years of age Encourage physical activity for weight management and for treatment of high triglyceride levels and low HDL cholesterol levels
Pharmacology*	Include statins among potential first-line agents 8yr minimum age for pharmacotherapy Use new LDL cholesterol treatment cutoff point of >130mg/dl if diabetes mellitus is present

*Former 1998 AAP guidelines for pharmacology: use bile acid-binding agents as first-line agent, statins is not recommended; 10 yr minimum age for pharmacotherapy initiate pharmacotherapy for LDL cholesterol level of >190mg/dL or >160mg/dL with positive family history or two additional risk factors

References:

Daniels S, Greer F, and the Committee on Nutrition. “American Academy of Pediatrics: Lipid Screening and Cardiovascular Health in Childhood.” (2008). Pediatrics; 122:198-208

Ferranti S, Ludwig D. “Storms over statins – the controversy surrounding pharmacologic treatment of children.” (2008). NEJM 359 (13): 1309-1312.

EKRs used: UptoDate