Familial Hypercholesterolemia

  • Masa-aki KawashiriEmail author
  • Daniel J. Rader


Familial hypercholesterolemia (FH) is the most severe form of monogenic hypercholesterolemia, and is mainly caused by defect or loss of function of the low-density lipoprotein (LDL) receptor. FH is autosomal-dominant hereditary disorder and the frequencies of heterozygous and homozygous FH are estimated as 1 in 200-300 and 1 in 160,000-360,000 general populations, respectively. FHs present tendon xanthoma, especially in Achilles tendon, and systemic atherosclerotic diseases if effective cholesterol-lowering therapy is not administered. Statins (HMG-CoA reductase inhibitors) and other lipid-lowering medicines including ezetimibe (selective cholesterol absorption inhibitor) and PCSK9 inhibitors effectively reduce LDL-cholesterol and cardiovascular events of heterozygous FH. However, homozygous FH is refractory to conventional lipid-lowering medicines. Innovative therapies, such as regenerative medicine or gene therapy, are needed for homozygous FH.


Atherosclerosis Cholesterol Familial hypercholesterolemia Low-density lipoprotein Low-density lipoprotein receptor 


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Cardiovascular and Internal MedicineKanazawa University Graduate School of Medical ScienceKanazawaJapan
  2. 2.Departments of Genetics, Perelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA

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