Hypercholesterolemia, Familial

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

Demographics

• 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)

Diagnosis

• 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

Treatment

• 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, treatment with a monoclonal antibody (e.g. alirocumab and evolocumab) that blocks the action of the PCSK9 enzyme (which inactivates hepatic receptors that transport LDL into the liver for metabolism) can be an expensive adjunct to standard therapy

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