High levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are all risk factors for coronary atherosclerosis. A link has been established between increased levels of triglycerides (TGs) and coronary heart disease as well. Cholesterol reduction results in reduced angiographic progression of CAD and even modest regression in some cases. Therefore controlling dyslipidemia has become a primary goal of reducing premature CAD. It has been established that the coronary arteriosclerosis begins to develop during childhood. In 2011, the Expert Panel convened by the National Heart Lung and Blood Institute (NHLBI) made recommendations on screening for dyslipidemia in children in an effort to reduce the prevalence of premature CAD.
I. Diagnosis of Dyslipidemia
The diagnosis of dyslipidemia is made by measuring blood lipid, lipoproteins, or apolipoprotein factors.
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The routine lipid profile typically includes: TC, HDL-C, LDL-C, and triglycerides (TG). A lipoprotein analysis is obtained after an overnight fast of 12 hours. The LDL level is usually estimated by the Friedewald formula:
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LDL = Total cholesterol − HDL − ( Triglyceride / 5 )
This formula is not accurate if the child is not fasting, if the TG level is >400 mg/dL, or if chylomicrons or dysbetalipoproteinemia (type III hyperlipoproteinemia) is present. Methods are currently available to measure LDL-C directly, which does not require a fasting specimen.
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An extended profile may also include very-low-density lipoprotein cholesterol (VLDL-C), non-HDL cholesterol (non-HDL-C), and the ratio of TC to HDL-C.
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Non-HDL-C: Serum non-HDL-C (TC − HDL-C) is considered a better screening tool than LDL-C for the assessment of CAD risk because it includes all classes of atherogenic (apolipoprotein B–containing) lipoproteins: VLDL-C, intermediate-density lipoproteins (IDLs), LDL-C, and lipoprotein (a) or Lp(a). Non-HDL-C from a nonfasting lipid profile is recommended in routine lipid screening.
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The ratio of the TC to HDL cholesterol (TC-to-HDL-C ratio) is a useful parameter for assessing risk for CVD. The usual TC-to-HDL-C ratio in children is approximately 3 (based on TC of 150 mg/dL and an HDL-C of 50 mg/dL). The higher the ratio, the higher is the risk of developing CVD.
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Small, dense LDL particles: In recent years, small, dense LDL particles have been shown to be more important than the total LDL levels in CAD. The size of LDL particles is not routinely measured because the presence of this phenotype is predictable. It occurs in association with elevated triglyceride levels (>140 mg/dL) and a decreased HDL-C level (<40 mg/dL in men; <50 mg/dL in women). Although not routinely measured, small, dense LDL can be measured directly by commercial laboratories.
II. Normal Levels of Lipids and Lipoproteins
Table 26.1 shows normal, borderline, and abnormal levels of lipid and lipoprotein levels in children. Table 26.2 shows those values for young adults. In children, TC ≥200 mg/dL; LDL-C ≥130 mg/dL; TGs ≥100 mg/dL for patients younger than 10 years and ≥130 mg/dL for 10- to19-year olds; and HDL-C <40 mg/dL are considered abnormal.
| Category | Low | Acceptable | Borderline | High |
|---|---|---|---|---|
| Total cholesterol | − | <170 | 170-199 | ≥200 |
| LDL cholesterol | − | <110 | 110-129 | ≥130 |
| Non-HDL cholesterol | − | <120 | 120-144 | ≥145 |
| Triglycerides: 0-9 years10-19 years | −− | <75<90 | 75-9990-129 | ≥100≥130 |
| HDL cholesterol | <40 | >45 | 40-45 | − |
| Apolipoprotein A1 | <115 | >120 | 115-120 | − |
| Apolipoprotein B | <90 | 90-109 | ≥110 |
| Category | Low | Borderline-low | Acceptable | Borderline-high | High |
|---|---|---|---|---|---|
| Total cholesterol | − | − | <190 | 190-224 | ≥225 |
| LDL cholesterol | − | − | <120 | 120-159 | ≥160 |
| Non-HDL cholesterol | − | − | <150 | 150-189 | ≥190 |
| Triglycerides | − | − | <115 | 115-149 | ≥150 |
| HDL cholesterol | <40 | 40-44 | >45 | − | − |
III. Classification of Dyslipidemia
Dyslipidemia can be classified as primary (genetic) or secondary dyslipidemia.
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Primary dyslipidemia is caused by single- or multiple-gene mutations that result in either overproduction or defective clearance of TGs and LDL-C or in underproduction or excessive clearance of HDL-C.
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Secondary dyslipidemia is caused by associated diseases or conditions. The majority of the cases found during screening are secondary forms.
A. Secondary Dyslipidemia
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Box 26.1 lists causes of secondary dyslipidemia.
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The most common cause of pediatric dyslipidemia is obesity.
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Medications such as oral contraceptives, isotretinoin (Accutane), anabolic steroids, diuretics, β-blockers, antipsychotics, and estrogens are uncommon causes of dyslipidemia.
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Medical conditions including hypothyroidism, renal failure, nephrotic syndrome, and alcohol usage are less common causes of secondary dyslipidemia.
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Most secondary causes of dyslipidemia raise TG and often lower HDL-C levels, with the exception of (1) increased levels of HDL-C seen with estrogen and (2) increased LDL-C seen with nephrosis, systemic lupus, primary biliary cirrhosis, protease inhibitors (for treatment of human immunodeficiency virus [HIV]), and hypothyroidism.
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Each child with dyslipidemia should have laboratory tests to help rule out secondary causes of dyslipidemia. The tests should include (1) fasting blood glucose or glycated hemoglobin (Hgb A1c), (2) renal function, (3) liver function, and (4) thyroid function.
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When the diagnosis of secondary dyslipidemia is made, one should treat the associated disorder (such as diabetes, obesity, or nephritic syndrome) that is producing the dyslipidemia first and then treat the dyslipidemia using the same guidelines as in primary dyslipidemia.
Box 26.1
Causes of Secondary Dyslipidemia
Metabolic
Metabolic syndrome, diabetes, lipodystrophies, glycogen storage disorders
Renal disease
Chronic renal failure, nephrotic syndrome, glomerulonephritis, hemolytic uremic syndrome
Hepatic
Biliary atresia, cirrhosis
Hormonal
Estrogen, progesterone, growth hormone, hypothyroidism, corticosteroids
Lifestyle
Obesity, physical inactivity, diets rich in fat and saturated fat, alcohol intake
Medications
Isotretinoin (Accutane), certain oral contraceptives, anabolic steroids, thiazide diuretics, β-adrenergic blockers, antipsychotics, anticonvulsants, glucocorticoids, estrogen, testosterone, immunosuppressive agents (cyclosporine), antiviral agents (HIV protease inhibitor)
Others
Kawasaki disease, anorexia nervosa, post–solid organ transplantation, childhood cancer survivor, progeria, idiopathic hypercalcemia, Klinefelter syndrome, Werner syndrome
HIV, human immunodeficiency virus.
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B. Selected Primary Dyslipidemias
Primary (genetic) dyslipidemias are far less commonly found in the screening process. Five well-known primary dyslipidemias are presented in summary format in Table 26.3 .
| Lipid disorders | Clinical information |
|---|---|
| Familial hypercholesterolemia (FH): FH heterozygotes |
|
| FH homozygotes |
|
| Familial combined hyperlipidemia (FCH) |
|
| Familial hypertriglyceridemia |
|
| Dysbetalipoproteinemia (type III hyperlipoproteinemia) |
|
| Familial hypoalphalipoproteinemia (low-HDL syndrome) |
|
IV. Lipid Screening
In 2011, the Expert Panel convened by the NHLBI made the following recommendations. These recommendations are major changes from the past recommendations of selective screening of children and adolescents with a family history of premature CVD or those with at least one parent with high serum cholesterol levels (by the Expert Panel of 1991).
The new recommendations are as follows.
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Universal screening is recommended for children 9-11 years old and patients 17-21 years old (see Box 26.2 ).
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For universal screening, either nonfasting lipid profile (non-FLP) or fasting lipid panel (FLP) is acceptable.
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When non-FLP is obtained, non-HDL-C is calculated (by subtracting HDL-C from TC. Non-HDL-C has been shown to be as powerful a predictor of atherosclerosis as any other lipoprotein cholesterol measurement in children and adolescents.
Box 26.2
Recommendations for Lipid Assessment According to Age Group
BMI , body mass index; FLP , fasting lipid panel; HDL , high-density lipoprotein; LDL , low-density lipoprotein; Non-FLP , non-fasting lipid profile; TC , total cholesterol.From Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescent, National Heart, Lung, and Blood Institute. (2011). Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: Summary report. Pediatrics, 128 (suppl 5), S213-S256.
Age group
<2 years
No lipid screening
2 to 8 years
Selective screening. Measure FLP twice and average the result if any of the following applies:
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Positive family history (see below)
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Parent with TC ≥240 mg/dL or known dyslipidemia
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Child has diabetes, hypertension, BMI ≥95th%, or smokes cigarettes
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Child has a moderate- or high-risk medical condition (see Box 26.3 )
9 to 11 years
Universal screening (by either non-FLP or FLP)
Non-FLP: Calculate non-HDL cholesterol (non-HDL cholesterol=TC−HDL cholesterol).
If non-HDL cholesterol≥145 mg/dL or±HDL <40 mg/dL, measure FLP twice and average results.
OR
FLP:
If LDL cholesterol≥130 mg/dL; ±non-HDL cholesterol ≥145 mg/dL; ±HDL cholesterol <40 mg/dL; ±triglycerides ≥100 mg/dL if <10 years; or ≥130 mg/dL if ≥10 years, repeat FLP and average results.
Interpret the results according to Table 26.1 .
12 to 16 years
Selective screening
Measure FLP twice and average results if any of the following applies:
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Positive family history (see Box 26.3 )
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Parent with TC ≥240 mg/dL or known dyslipidemia
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Child has diabetes, hypertension, BMI ≥85th percentile, or smokes cigarettes
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Child has a moderate- or high-risk medical condition (see following)
17 to 21 years
Universal screening once in this time period (by either non-FLP or FLP)
For 17-19 yr:
Non-FLP: Calculate non-HDL-cholesterol.
If non-HDL cholesterol ≥145 mg/dL or ±HDL <40 mg/dL, measure FLP twice and average results
OR
FLP:
If LDL cholesterol ≥130 mg/dL; or non-HDL-cholesterol ≥145 mg/dL; ±HDL cholesterol <40 mg/dL or ±triglycerides ≥130 mg/dL, repeat FLP and average results.
Interpret the results according to Table 26.1 .
For 20-21 years:
Non-FLP: Calculate non-HDL cholesterol
If non-HDL cholesterol ≥190 mg/dL or ±HDL cholesterol <40 mg/dL, measure FLP twice and average results.
OR
FLP:
If LDL cholesterol ≥160 mg/dL; ±non-HDL cholesterol ≥190 mg/dL; ±HDL cholesterol <40 mg/dL or ±triglycerides ≥150 mg/dL, repeat FLP and average results.
Interpret the results according to Table 26.1 or Table 26.2 .
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