Guidelines for the screening, diagnosis and management of familial hypercholesterolemia

Familial hypercholesterolemia is one of the most common genetic metabolic disorders in the US and Europe, occurring in about 1 in 300 to 1 in 500 individuals. Yet, it is estimated that 80% of individuals with familial hypercholesterolemia remain undiagnosed. As a result, most are not on any lipid-lowering therapy, or other therapies at all. If familial hypercholesterolemia is left untreated, the long-term prognosis is poor. Without treatment, only 50% of individuals with familial hypercholesterolemia will survive to age 60 years and only 20% survive to age 70 years. With early diagnosis and aggressive treatment, however, the long-term prognosis for people with familial hypercholesterolemia can approach that of the general population.

The NICE guidelines for the identification and management of familial hypercholesterolemia were released in the UK in August 2008. Until recently, however, there were no guidelines for familial hypercholesterolemia in the US. The National Lipid Association released expert consensus guidelines for the screening, diagnosis and management of pediatric and adult patients with familial hypercholesterolemia, which were published as a supplement in the June issue of the Journal of Clinical Lipidology.

Although space prevents me from reviewing these guidelines fully, some key points are as follows:

Universal screening for hypercholesterolemia is recommended.
Familial hypercholesterolemia should be suspected when untreated fasting LDL or non- HDL levels are at or above the following:
- Adults older than 20 years: LDL ≥190 mg/dL or non-HDL ≥220 mg/dL
- Children, adolescents and young adults younger than 20 years: LDL ≥160 mg/dL or non-HDL ≥190 mg/dL.

Cholesterol screening should be considered, starting at age 2 years, for children with a family history of premature cardiovascular disease or elevated cholesterol. All individuals should be screened by age 20 years. Although not present in everyone with familial hypercholesterolemia, the following physical findings strongly raises suspicion of having the diagnosis:
- Tendon xanthomas at any age.
- Arcus corneae under age 45 years.
- Tuberous xanthomas or xanthelasma under age 20 to 25 years.

Formal diagnosis of familial hypercholesterolemia can be made using any one of the clinical criteria including the US Make Early Diagnosis Prevent Early Death (MEDPED), the Dutch Lipid Clinic Network and/or the Simon-Broome Registry criteria.
Genetic screening for familial hypercholesterolemia is generally not needed for diagnosis or management, but may be useful when the diagnosis is uncertain. A negative genetic test does not exclude familial hypercholesterolemia, as approximately 20% of familial hypercholesterolemia patients will not have a mutation.
Both children and adults with LDL ≥ 190 mg/dL or non-HDL ≥220 mg/dL after lifestyle changes require drug therapy. Patients at higher CV risk need to be treated more aggressively.
Adult familial hypercholesterolemia patients (≥20 years), drug treatment to achieve an LDL reduction ≥50% is advised.
Statins are the initial treatment for all adults with familial hypercholesterolemia. Ezetimibe (Zetia, Merck), niacin, and bile acid sequestrants may be used in combination with statins for further LDL-lowering or in those who are statin intolerant.
Statins are also the preferred drugs for the management of children older than age 8 years after dietary and lifestyle modification.
Risk factors such as hypertension should be treated aggressively. Regular physical activity, avoidance of tobacco and a healthy diet should be encouraged.
Ten-year coronary heart disease risk calculators do not adequately predict the high CV risk for patients with familial hypercholesterolemia and should not be used.
In patients who do not respond to maximum tolerated drug therapy after 6 months, LDL apheresis is indicated according to these guidelines:
- Functional homozygous familial hypercholesterolemia patients with LDL ≥300 mg/dL (or non-HDL ≥330 mg/dL).
- Functional heterozygous familial hypercholesterolemia patients with LDL ≥300 mg/dL (or non-HDL ≥330 mg/dL) and zero to one risk factors.
- Functional heterozygous familial hypercholesterolemia patients with LDL ≥200 mg/dL (or non-HDL ≥230 mg/dL) and high-risk characteristics such as two or more risk factors or high lipoprotein(a) >50 mg/dL using an isoform insensitive assay.
- Functional heterozygotes with LDL ≥160 mg/dL (or non-HDL ≥190 mg/dL) and very high-risk characteristics (established CHD, other CV disease or diabetes).

If you manage people with familial hypercholesterolemia and you are as passionate about CV prevention as I am, I encourage you to read these guidelines in detail.

For more information:

Goldberg AC. J Clin Lipidol. 2011;5:133-140.