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Hyperlipidemia, Pediatric

Basics

Description

- Skin exam - Tendon xanthomas: thickened tissue surrounding the Achilles and extensor tendons - Xanthelasma: yellowish deposits of cholesterol surrounding the eye - Palmar xanthomas: pale lines in palmar creases - Eruptive xanthomas: characteristic of hypertriglyceridemia; papular yellowish lesions with a red base that occur on the buttocks, elbows, and knees - Enlarged tender liver may present in association with fatty liver.

- Hypercholesterolemia - Primary hypercholesterolemia (see above) - Hypothyroidism - Nephrotic syndrome - Liver disease (cholestatic) - Renal failure - Anorexia nervosa - Acute porphyria - Medications (antihypertensives, estrogens, steroids, microsomal enzyme inducers, cyclosporine, diuretics) - Pregnancy - Dietary: excessive dietary intake of fat, cholesterol, and/or calories

- Bile acid-binding resins - Bind cholesterol in bile acids in intestine and prevent reuptake into enterohepatic circulation - Associated with GI discomfort - Very poor compliance in children

- Niacin - Lowers LDL and triglycerides while increasing HDL - Poorly tolerated in children due to side effects in >50%, including flushing, itching, and elevated hepatic transaminases

- Outpatient management unless secondary hyperlipidemia caused by liver or renal failure, which would necessitate inpatient management of primary illness. Note: The cause of secondary hyperlipidemia should be treated with disease-specific therapy to reduce elevated lipid levels. - Risk assessment and treatment - Population approach - General emphasis on healthy lifestyle to prevent development of dyslipidemias - Recommendations include increasing intake of fruits, vegetables, fish, whole grains, and low-fat dairy products; reducing intake of fruit juice, sugar-sweetened beverages and food.

- Familial hypercholesterolemia - Homozygotes: coronary artery disease in 1st or 2nd decade of life - Heterozygotes: 50% of males develop premature heart disease by age 50 years (females, age 60 years).

Hyperlipidemia is an elevation of serum lipids. These lipids include cholesterol, cholesterol esters (compounds), phospholipids, and triglycerides. Lipids are transported as part of large molecules called lipoproteins.

  • 5 major families of lipoproteinsChylomicronsVery-low-density lipoproteins (VLDL)Intermediate-density lipoproteins (IDL)Low-density lipoproteins (LDL)High-density lipoproteins (HDL)
  • Normal serum lipid concentrationsTotal cholesterol: 170 mg/dL (borderline, 170-199 mg/dL)LDL cholesterol: <110 mg/dL (borderline, 110-129 mg/dL)HDL cholesterol: ≥35 mg/dLTotal triglycerides: 100 mg/dL (borderline, 100-140 mg/dL)More detailed age- and gender-specific values are available (refer to Table 2 of 2008 Clinical report: lipid screening and cardiovascular health in childhood).
  • Primary hypercholesterolemia or hypertriglyceridemia: elevation in serum cholesterol or triglyceride as a result of an inherited disorder of lipid metabolism (i.e., familial hypercholesterolemia)
  • Secondary hypercholesterolemia or hypertriglyceridemia: elevation in serum cholesterol or triglyceride as a result of another disease process (e.g., diabetes mellitus)

Epidemiology

  • The prevalence of homozygous familial hypercholesterolemia (FH) is 1 in 1,000,000; the incidence of the heterozygous state is 1 in 500.
  • Unknown causes result in hypercholesterolemia and/or hypertriglyceridemia, occurring in 2% of the population.
  • National Health and Nutrition Examination Surveys (NHANES I-III) provides information about pediatric serum cholesterol concentrations.For all children 4-17 years, the 95th percentile for serum total cholesterol is 216 mg/dL and the 75th percentile is 181 mg/dL.Before puberty, average total and LDL cholesterol levels are significantly higher in girls than boys.The mean total cholesterol level for all children from 4 to 11 years old peaks at age 9-11 years and then gradually decreases until mid to late adolescence.

Risk Factors

Genetics

  • FH: dominantly inherited defect of LDL receptor
  • Familial combined hyperlipidemia (FCHL): dominantly inherited lipid disorder, polygenic
  • Familial hypertriglyceridemia (FHTG): autosomal recessive disorder due to defects in lipoprotein lipase

General Prevention

  • Fat intake is generally unrestricted prior to 2 years of age. After 2 years of age, two complementary approaches are recommended.
  • Diet and lifestyle guidelines are to promote:Consuming an overall healthy dietMaintaining a healthy body weight (BMI <85% for children)
  • Recommended lipid levelsLDL cholesterol <110 mg/dLHDL cholesterol >50 mg/dL in women, >40 mg/dL in menTriglycerides <150 mg/dL
  • Normal, age-appropriate BP
  • Normal blood glucose level (fasting blood glucose ≤100 mg/dL)
  • Remaining physically active
  • Avoiding use of and exposure to tobacco products

Diagnosis

History

  • Family history of premature heart disease or dyslipidemiaAlmost all cases of primary hyperlipidemia are of dominant inheritance.
  • SmokingSmoking reduces HDL cholesterol levels and increases the risk of vascular disease.
  • Use of oral contraceptivesBirth control pills have been shown to cause elevations in lipoprotein levels and, when coupled with already elevated lipid levels, can increase the risk of atherosclerosis.
  • DietChildren with increased intake of fat, carbohydrates, sugar-added drinks, and fast foods are likely to be overweight/obese.
  • ObesityObese children are more likely to have abnormal serum lipids.

Physical Exam

  • Eye examArcus corneae: deposits of cholesterol, resulting in a thin, white circular ring located on the outer edge of the iris
  • Skin examTendon xanthomas: thickened tissue surrounding the Achilles and extensor tendonsXanthelasma: yellowish deposits of cholesterol surrounding the eyePalmar xanthomas: pale lines in palmar creasesEruptive xanthomas: characteristic of hypertriglyceridemia; papular yellowish lesions with a red base that occur on the buttocks, elbows, and kneesEnlarged tender liver may present in association with fatty liver.

Diagnostic Tests & Interpretation

Lab

  • Starting age 2-8 yearsScreen children and adolescents who have:Positive family history of dyslipidemia or premature cardiovascular disease (CVD) (≤55 years old for men, ≤65 years old for women), such as coronary atherosclerosis, documented myocardial infarction (MI)Unknown family historyObesity (BMI ≥95th percentile) or overweight (BMI ≥85th-<95th percentile)Cigarette smoking exposureHypertensionDiabetes mellitusScreen using a fasting lipid profile (FLP): total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides.If FLP is within normal range, repeat test in 3-5 years.
  • Age 9-11 years: NHLBI-AAP recommend universal screening.Screen using either an FLP or nonfasting lipid profile (LP): if done nonfasting and non-HDL >145 mg/dL, then repeat as FLP.Non-HDL = total cholesterol-HDL
  • Age 12-16 yearsScreen children and adolescents with risk factors as with 2-8 years group.

Consider other testing:

  • Chemistry panel (glucose, ALT, AST, bilirubin, BUN, creatinine, urinalysis)Screening test for diabetes, liver, and kidney disease
  • Thyroid evaluation (thyroxine [total T4], thyroid stimulating hormone [TSH])Determines the presence of hypothyroidism

Alert

  • Serum total cholesterol is inaccurate when serum triglycerides are >400 mg/dL.
  • Hypertriglyceridemia is associated with falsely lowered serum Na.

Differential Diagnosis

  • HypercholesterolemiaPrimary hypercholesterolemia (see above)HypothyroidismNephrotic syndromeLiver disease (cholestatic)Renal failureAnorexia nervosaAcute porphyriaMedications (antihypertensives, estrogens, steroids, microsomal enzyme inducers, cyclosporine, diuretics)PregnancyDietary: excessive dietary intake of fat, cholesterol, and/or calories
  • HypertriglyceridemiaPrimary hypertriglyceridemia (see above)Acute hepatitisNephrotic syndromeChronic renal failureMedications (diuretics, retinoids, oral contraceptives)Diabetes mellitusAlcohol abuseLipodystrophyMyelomatosisGlycogen storage diseaseDietary: excessive dietary intake of fat and/or calories

Treatment

Medication

  • Drug therapy should be considered only for children ≥8 years of age after an adequate trial of diet therapy (for 6-12 months) and if they have one of the following:LDL cholesterol level remains >190 mg/dLLDL cholesterol level remains >160 mg/dL, and there is a family history of premature CVD (≤55 years of age for men, ≤65 for women) or ≥2 other risk factors are present (obesity, hypertension, cigarette smoking).LDL ≥130 mg/dL and have diabetes mellitus
  • Physicians caring for overweight and obese children who have lipid disorders should emphasize the importance of diet and exercise rather than drug therapy for most of their patients.
  • Statins (first-line drug therapy)Decrease endogenous cholesterol synthesis and increase clearance of LDL from circulationSimilar safety and efficacy in the treatment of lipid disorders in children as in adultsSide effects include hepatitis and myositis.
  • Bile acid-binding resinsBind cholesterol in bile acids in intestine and prevent reuptake into enterohepatic circulationAssociated with GI discomfortVery poor compliance in children
  • NiacinLowers LDL and triglycerides while increasing HDLPoorly tolerated in children due to side effects in >50%, including flushing, itching, and elevated hepatic transaminases
  • Drugs needing further pediatric studies: cholesterol absorption inhibitors and fibrates

Additional Therapies

General Measures

  • Outpatient management unless secondary hyperlipidemia caused by liver or renal failure, which would necessitate inpatient management of primary illness. Note: The cause of secondary hyperlipidemia should be treated with disease-specific therapy to reduce elevated lipid levels.
  • Risk assessment and treatmentPopulation approachGeneral emphasis on healthy lifestyle to prevent development of dyslipidemiasRecommendations include increasing intake of fruits, vegetables, fish, whole grains, and low-fat dairy products; reducing intake of fruit juice, sugar-sweetened beverages and food.Individual approachFocuses on patients who are high riskInitial intervention is focused on changing diet, but patients often require pharmacologic intervention.

Additional Therapies

Activity

  • 60 minutes of moderate to vigorous play or physical activity daily
  • Reduce sedentary behaviors (e.g., watching TV, playing videogames, using computers)
  • Participation in organized sports

Ongoing Care

Follow-up Recommendations

Patient Monitoring

  • For patients with primary hyperlipidemia who are off medication, follow-up should be performed every 1-2 years with a lipoprotein profile evaluation. For those patients on medication, follow-up should be conducted every 3-6 months.
  • For all other patients with risk factors and normal lipid profile, a monitored lifestyle and dietary changes should be strongly recommended at every office visit.

Diet

  • Dietary modification is safe in the treatment of hyperlipidemia in children >2 years of age:Restrict saturated fat to <7% daily calories.Restrict dietary cholesterol to 200 mg/day.Limit trans fatty acids to <1% daily calories.Supplemental fiber at goal dose of child's age + 5 g/day (up to 20 g/day)
  • For children between 12 months and 2 years who are overweight, obese, or have a family history of dyslipidemia or CVD, the use of reduced fat milk can be considered.

Prognosis

  • Familial hypercholesterolemiaHomozygotes: coronary artery disease in 1st or 2nd decade of lifeHeterozygotes: 50% of males develop premature heart disease by age 50 years (females, age 60 years).
  • Familial combined hyperlipidemia: occurs in 1-2% of the population and accounts for 10% of all premature heart disease. A reduction of LDL cholesterol by 1% reduces risk by 2%.
  • Children and adolescents with high cholesterol levels are more likely than the general population to have high levels as adults.

Complications

  • Hypercholesterolemia has been linked to premature coronary artery disease and vascular disease.
  • Severe hypertriglyceridemia can cause pancreatitis.

Additional Reading

  • Daniels SR, Greer FR, Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008;122(1):198-208. [View Abstract]
  • Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Instute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(Suppl 5):S213-S256.
  • Gidding SS, Dennison BA, Birch LL, et al. Dietary recommendations for children and adolescents: a guide for practitioners: consensus statement from the American Heart Association. Circulation. 2005;112(13):2061-2075. [View Abstract]
  • Kavey RE, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients. A scientific statement from the American Heart Association. Circulation. 2006;114(24):2710-2738.
  • McCrindle BW, Urbina EM, Dennison BA, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association. Circulation. 2007;115(14):1948-1967. [View Abstract]

Codes

ICD09

  • 272.4 Other and unspecified hyperlipidemia
  • 272.0 Pure hypercholesterolemia
  • 272.1 Pure hyperglyceridemia

ICD10

  • E78.5 Hyperlipidemia, unspecified
  • E78.0 Pure hypercholesterolemia
  • E78.1 Pure hyperglyceridemia
  • E78.4 Other hyperlipidemia

SNOMED

  • 55822004 hyperlipidemia (disorder)
  • 238076009 primary hypercholesterolemia (disorder)
  • 302870006 Hypertriglyceridemia (disorder)
  • 398036000 Familial hypercholesterolemia (disorder)
  • 34528009 Familial hypertriglyceridemia (disorder)

FAQ

  • Q: When should I screen for dyslipidemia, and what test should I use for screening?
  • A: All children between ages 9 and 11 years should be screened for dyslipidemia using a non-FLP. Children between 2-8 years and 12-16 years should be screened using an FLP only if they have risk factors.
  • Q: What should my initial management of a child with dyslipidemia include?
  • A: The management plan of any child with dyslipidemia is dependent on the age of the child and should include dietary recommendations, a focus on all aspects of heart health, and in selected cases, the use of pharmacotherapy.