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For further information, see CMDT Part 40-18: Familial Hypercholesterolemia

Key Features

Essentials of Diagnosis

  • Elevated serum total cholesterol and low-density lipoprotein (LDL) cholesterol

  • Autosomal dominant inheritance

  • Mutation in LRL, PCSK9, or APOB

General Considerations

  • A group of autosomal dominant conditions that result in elevated LDL levels in the blood

  • High LDL predisposes to atherosclerosis, which leads to premature myocardial infarction or stroke

  • The incidence of these serious complications increases with age and when associated with the other common predispositions to atherosclerosis, such as smoking and hypertension


  • About 1 in 500 people in the United States have familial hypercholesterolemia

  • Worldwide prevalence is about 10 million

  • Familial hypercholesterolemia is diagnosed in only about 15% of people; even fewer are treated effectively

Clinical Findings

  • Yellow lipid deposits appear on tendons, especially the Achilles (tendon xanthoma)


  • Elevated total serum cholesterol with the LDL component particularly high

  • Detailed family history and genetic testing should be done in persons

    • Younger than 40 years with an LDL level > 200 mg/mL

    • Older than 40 years with a level > 250 mg/mL


  • Statins, usually at high doses, can reduce LDL levels (Table 28–3)

  • The younger the treatment is begun, the better the outcome in reducing mortality from atherosclerosis

  • In homozygous familial hypercholesterolemia, if high-dose statins do not reduce LDL sufficiently, an inhibitor of PCSK9 is an option

  • If all else fails, then plasmapheresis to reduce LDL is needed

Table 28–3.Effects of selected lipid-modifying drugs (listed alphabetically).

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