Basics
Description
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 lipoproteins
- Chylomicrons
- Very-low-density lipoproteins (VLDL)
- Intermediate-density lipoproteins (IDL)
- Low-density lipoproteins (LDL)
- High-density lipoproteins (HDL)
- Normal serum lipid concentrations
- Total cholesterol: 170 mg/dL (borderline, 170-199 mg/dL)
- LDL cholesterol: <110 mg/dL (borderline, 110-129 mg/dL)
- HDL cholesterol: ≥35 mg/dL
- Total 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 diet
- Maintaining a healthy body weight (BMI <85% for children)
- Recommended lipid levels
- LDL cholesterol <110 mg/dL
- HDL cholesterol >50 mg/dL in women, >40 mg/dL in men
- Triglycerides <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 dyslipidemia
- Almost all cases of primary hyperlipidemia are of dominant inheritance.
- Smoking
- Smoking reduces HDL cholesterol levels and increases the risk of vascular disease.
- Use of oral contraceptives
- Birth 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.
- Diet
- Children with increased intake of fat, carbohydrates, sugar-added drinks, and fast foods are likely to be overweight/obese.
- Obesity
- Obese children are more likely to have abnormal serum lipids.
Physical Exam
- Eye exam
- Arcus corneae: deposits of cholesterol, resulting in a thin, white circular ring located on the outer edge of the iris
- 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.
Diagnostic Tests & Interpretation
Lab
- Starting age 2-8 years
- Screen 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 history
- Obesity (BMI ≥95th percentile) or overweight (BMI ≥85th-<95th percentile)
- Cigarette smoking exposure
- Hypertension
- Diabetes mellitus
- Screen 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 years
- Screen 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
- 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
- Hypertriglyceridemia
- Primary hypertriglyceridemia (see above)
- Acute hepatitis
- Nephrotic syndrome
- Chronic renal failure
- Medications (diuretics, retinoids, oral contraceptives)
- Diabetes mellitus
- Alcohol abuse
- Lipodystrophy
- Myelomatosis
- Glycogen storage disease
- Dietary: 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/dL
- LDL 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 circulation
- Similar safety and efficacy in the treatment of lipid disorders in children as in adults
- Side effects include hepatitis and myositis.
- 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
- 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 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.
- Individual approach
- Focuses on patients who are high risk
- Initial 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 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).
- 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.