Guidelines for Diagnosis and Treatment of Familial Hypercholesterolemia 2017

Abstract

Statement1. Familial hypercholesterolemia (FH) is an autosomal hereditary disease with the 3 major clinical features of hyper-LDL-cholesterolemia, premature coronary artery disease and tendon and skin xanthomas. As there is a considerably high risk of coronary artery disease (CAD), in addition to early diagnosis and intensive treatment, family screening (cascade screening) is required (Recommendation level A) 2. For a diagnosis of FH, at least 2 of the following criteria should be satisfied:① LDL-C ≥180 mg/dL, ② Tendon/skin xanthomas, ③ History of FH or premature CAD within 2nd degree blood relatives (Recommendation level A) 3. Intensive lipid-lowering therapy is necessary for the treatment of FH. First-line drug should be statins. (Recommendation level A, Evidence level 3) 4. Screening for CAD as well as asymptomatic atherosclerosis should be conducted periodically in FH patients. (Recommendation level A) 5. For homozygous FH, consider LDL apheresis and treatment with PCSK9 inhibitors or MTP inhibitors. (Recommendation level A) 6. For severe forms of heterozygous FH who have resistant to drug therapy, consider PCSK9 inhibitors and LDL apheresis. (Recommendation level A) 7. Refer FH homozygotes as well as heterozygotes who are resistant to drug therapy, who are children or are pregnant or have the desire to bear children to a specialist. (Recommendation level A).

Keywords: Adult; Diagnosis criteria; Drug therapy; Familial hypercholesterolemia; Heterozygote; Homozygote; LDL apheresis; Lifestyle habits; Treatment guidelines.

Fig. 1.

Combination of genetic mutation showing a clinical phenotype of FH homozygote.

Fig. 2.

Distribution of serum total cholesterol levels in normal subjects, and heterozygous and homozygous patients with FH (modified by adding patients of Reference 11).

Fig. 3.

Cumulative number of patients with myocardial infarction by age in male and female heterozygous FH patients (patients were add to Reference 11, and the form of indication was modified).

Fig. 4.

Skin and tuberous xanthomas in a 22-year-old man (A) Finger tuberous xanthomas, (B) Xanthoma planum on the knees, (C) Xanthoma planum on the elbows, (D) Xanthoma planum on the buttocks. Skin xanthomas in a 3-year-old boy (E, F).

Fig. 5.

Corneal arcus in FH patients.

Fig. 6.

Achilles tendon thickening in an FH patient.

Fig. 7.

Radiograms of the Achilles tendon in FH patients. (A) Achilles tendon in a 40-year-old man (maximun thickness: 22 mm), (B) Achilles tendon in a 29-year-old man (maximum thickness: 19 mm).

Fig. 8.

Treatment flow chart for adult (15 years or over) heterozygous FH.

Fig. 9.

Treatment flow chart for adult (15 years or over) homozygous FH.