Hyperlipidemia The 5 Minute Pediatric Consult


	Hyperlipidemia

Chris A. Liacouras

Database
Differential Diagnosis
Data Gathering
Physical Examination
Laboratory Aids
Therapy
Follow-Up
Bibliography

DATABASE

DEFINITION

Hyperlipidemia refers to serum elevations of cholesterol, triglycerides, and lipoprotein. Total cholesterol consists of very low density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).

Normal serum concentrations:
- Total cholesterol: 170 mg/dL (borderline, 170–199 mg/dL)
- LDL cholesterol: 110 mg/dL (borderline, 110–129 mg/dL)
- Total triglycerides: 100 mg/dL (borderline, 100–140 mg/dL)

Primary hypercholesterolemia or hypertriglyceridemia (hyperlipidemia): elevation in serum cholesterol as a result of an inherited disorder of lipid metabolism (i.e., familial hypercholesterolemia)

Secondary hypercholesterolemia or hypertriglyceridemia: elevation in serum cholesterol as a result of another disease process (i.e., nephrotic syndrome)

PATHOPHYSIOLOGY

Primary hypercholesterolemia:

Familial hypercholesterolemia (FH): defect of LDL receptor, resulting in the body’s inability to properly utilize circulating LDL cholesterol
Familial hypertriglyceridemia (FHTG): a severe elevation in serum triglycerides; can be associated with lipoprotein lipase deficiency or apolipoprotein C-II deficiency

GENETICS

Familial hypertriglyceridemia (FHTG): dominantly inherited disorder
Familial hypercholesterolemia (FH): dominantly inherited defect of LDL receptor
Familial combined hyperlipidemia (FCHL): dominantly inherited lipid disorder

EPIDEMIOLOGY

The incidence of familial hypercholesterolemia homozygotes is 1 in 1,000,000; heterozygotes, 1 in 500, with unknown cause resulting in hypercholesterolemia and/or hypertriglyceridemia occurring in 2% of the population

COMPLICATIONS

Hypercholesterolemia has been linked to premature coronary artery disease and vascular disease. Severe hypertriglyceridemia can cause pancreatitis. The presence of significant atherosclerotic vessel disease is unusual in most children; however, it can occur in the first decade of life in children with homozygous familial hypercholesterolemia.

PROGNOSIS

Familial hypercholesterolemia:
- Homozygotes: coronary artery disease in first or second decade of life
- Heterozygotes: Fifty percent of males develop premature heart disease by age 50 (females, age 60)
Familial combined hyperlipidemia: occurs in 1% to 2% of population and accounts for 10% of all premature heart disease. A reduction of LDL cholesterol by 1% reduces risk by 2%.

DIFFERENTIAL DIAGNOSIS

Hypercholesterolemia
- Primary hypercholesterolemia (see above)
- Hypothyroidism
- Nephrotic syndrome
- Liver disease (cholestatic)
- Renal failure
- Anorexia nervosa
- Acute porphyria
- Myelomatosis
- 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

DATA GATHERING

HISTORY

Question: Is there a family history of premature heart disease?
Significance: Almost all cases of primary hyperlipidemia are of dominant inheritance; thus, questions should be asked regarding the occurrence of premature heart disease and hyperlipidemia in parents and grandparents.

Question: Does your child smoke?
Significance: Smoking reduces HDL cholesterol levels and increases the risk of vascular disease.

Question: Does your daughter use oral contraceptives?
Significance: 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.

Question: Does your child exercise regularly?
Significance: Lower levels of cholesterol and triglycerides are generally found in children and adolescents who are physically fit.

PHYSICAL EXAMINATION

Eye examination:
- Arcus corneae: deposits of cholesterol, resulting in a thin, white circular ring located on the outer edge of the iris
Skin examination:
- Tendon xanthomas: thickened tissue surrounding the Achilles’ and extensor tendons
- Xanthelasma: yellowish deposits of cholesterol surrounding the eye
- Palmar xanthomas: pale lines in creases of palms
- Eruptive xanthomas: characteristic of hypertriglyceridemia; papular yellowish lesions with a red base that occur on the buttocks, elbows, and knees.

LABORATORY AIDS

TESTS

Fasting serum lipoprotein levels: total cholesterol, HDL cholesterol, and triglycerides
- Determine the type of hyperlipidemia
Calculated LDL cholesterol: LDL cholesterol = total cholesterol – [HDL cholesterol + triglycerides/5]
- Determines the level of LDL cholesterol Chemistry panel (ALT, AST, Bili, BUN, creatinine, urinalysis)
- Screening test for liver and kidney disease
Thyroid evaluation (T4, TSH)
- Determines the presence of hypothyroidism
- Three-day diet history
- Evaluates dietary intake of calories and cholesterol with 3-day diet

THERAPY

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 affect a reduction in elevated lipid levels.

FOR PRIMARY HYPERLIPIDEMIA

Dietary management (recommended dietary intake):

Total calories: age-appropriate to promote normal growth (do not limit children <3 years)
Total fat: <20% total fat <30% of calories
Saturated fat: 10% of calories
Cholesterol: up to 100 mg/1,000 calories
Protein: approximately 15% to 20% of calories
Carbohydrates: approximately 55% of calories

NOTE: Hypertriglyceridemia almost always responds to strict dietary management (10–15 g/d of fat) and weight loss.

Risk Factors

The following are factors that contribute to heart disease:

Smoking
Excessive weight gain: <110% ideal body weight
Hypertension
Diabetes mellitus
Low HDL cholesterol (35 mg/dL)
Physical inactivity (bedridden)
Family history of premature heart disease (55 years of age)

Patient education: Instruct patients on risk factors of premature heart disease, American Heart Association STEP I diet, and the need for adequate exercise and routine follow-up.

NOTE: Therapy is indicated if hyperlipidemia is caused by a dominantly inherited lipid disorder and the child is over 10 years of age and either LDL cholesterol greater than 190 mg/dL after dietary trial (6 months) or LDL cholesterol greater than 160 mg/dL after dietary trial and two or more additional risk factors exist. When drug therapy is considered, a referral to a pediatric lipid specialist is necessary.

DRUG OF CHOICE

Cholestyramine (bile acid resins) is the drug of choice for the initial treatment of primary hypercholesterolemia. It is not indicated for hypertriglyceridemia. It is contraindicated in patients with biliary obstruction or in patients with prior allergic reaction. All causes of secondary hyperlipidemia should be ruled out before starting therapy. Side effects include foul taste, constipation, nausea, and possible vitamin K deficiency. Cholestyramine may reduce or delay the absorption of concomitant oral medications secondary to drug binding.

ALTERNATIVE DRUGS

Lovastatin (HMG-CoA reductase inhibitor) is an effective drug in adults and may prove to be beneficial in children in the future. Side effects include hepatitis and myositis.
Niacin in megavitamin doses has been effective in the reduction of both serum LDL cholesterol and triglycerides; however, side effects occur in more than 50% of individuals, including flushing, itching, and headache.
Experimental gene therapy has been shown to be effective in an animal model for familial hypercholesterolemia and may be the treatment of choice in the future for genetic disorders of lipid metabolism; it has been used recently in adult patients.

FOLLOW-UP

For patients with primary hyperlipidemia who are off medication, follow-up should be performed every 1 to 2 years with lipoprotein profile evaluation. For those patients on medication, follow-up should be conducted every 3 months.

PREVENTION

Avoid other risk factors (see above).
Limit dietary intake of fat and cholesterol (see above).
Increase exercise.
Become educated about heart disease and atherosclerosis.

POSSIBLE COMPLICATIONS

Hypercholesterolemia
- Premature heart disease
- Stroke
- Carotid artery disease
Hypertriglyceridemia:
- Pancreatitis

CLINICAL PEARLS

Serum total cholesterol is inaccurate when serum triglycerides are greater than 400 mg/dL.

ICD-9-CM 272.4

BIBLIOGRAPHY

Cortner JA, Coates PM, Tershakovec AM. Disorders of lipoprotein metabolism and transport. In: Berman R, ed. Nelson textbook of pediatrics, 14th ed. Philadelphia: Saunders, 1992: 352–359.

Havel RJ. Approach to the patient with hyperlipidemia. Med Clin North Am 1982; 66:319.

National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics 1992; 89[Suppl]:525–584.

Newman WP, Freedman DS, Voors AW, et al. Relation of serum lipopotein levels and systolic blood pressure to early atherosclerosis: the Bogalusa Heart Study. N Engl J Med 1986; 314:138.

Poskitt EME, ed. Practical paediatric nutrition. London: Butterworths, 1988.

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