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Dyslipidemias


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.

  • 1.

    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:


    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.

  • 2.

    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.

  • 3.

    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.

  • 4.

    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.

  • 5.

    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.

Table 26.1
Concentrations of Plasma Lipid, Lipoprotein, and Apolipoprotein in Children and Adolescents (Mg/Dl): Low, Acceptable, Borderline, and High
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.
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
HDL, high-density lipoprotein ; LDL, low-density lipoprotein .

Table 26.2
Recommended Cut Points for Lipid and Lipoprotein Levels in Young Adults (Mg/Dl)
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.
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 − −
HDL, high-density lipoprotein ; LDL, low-density lipoprotein .

III. Classification of Dyslipidemia

Dyslipidemia can be classified as primary (genetic) or secondary dyslipidemia.

  • 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.

  • Secondary dyslipidemia is caused by associated diseases or conditions. The majority of the cases found during screening are secondary forms.

A. Secondary Dyslipidemia

  • 1.

    Box 26.1 lists causes of secondary dyslipidemia.

    • a.

      The most common cause of pediatric dyslipidemia is obesity.

    • b.

      Medications such as oral contraceptives, isotretinoin (Accutane), anabolic steroids, diuretics, β-blockers, antipsychotics, and estrogens are uncommon causes of dyslipidemia.

    • c.

      Medical conditions including hypothyroidism, renal failure, nephrotic syndrome, and alcohol usage are less common causes of secondary dyslipidemia.

    • d.

      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.

    • e.

      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.

    • f.

      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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