Article Text

Download PDFPDF
Familial hypercholesterolaemia and emerging therapeutics
  1. Francisco I Farias1,
  2. Samuel M Kim2,
  3. Michael D Shapiro3
  1. 1 Department of Medicine, University of Washington Medical Center, Seattle, Washington, USA
  2. 2 Cardiology, New York-Presbyterian Weill Cornell Medical Center, New York, New York, USA
  3. 3 Cardiovascular Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
  1. Correspondence to Dr Samuel M Kim, Cardiology, NewYork-Presbyterian Weill Cornell Medical Center, New York, NY 07650, USA; smk9018{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Learning objectives

  • To review prevalence, genetics and current guidelines for the diagnosis and treatment of familial hypercholesterolaemia.

  • To assess cardiac and extracardiac complication of familial hypercholesterolaemia.

  • To understand the management of familial hypercholesterolaemia including emerging pharmacological and non-pharmacological therapies.


Familial hypercholesterolaemia (FH) is an inherited lipid disorder which dramatically increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). FH is caused by one or more mutations affecting the low-density lipoprotein (LDL) receptor or associated proteins, leading to impaired clearance of circulating LDL with subsequent elevation of plasma LDL-cholesterol (LDL-C) beginning at birth.1 FH affects individuals of all ethnicities and contemporary studies demonstrate that it is the most common monogenic disorder in humans, with an estimated prevalence of approximately 1:300 in most global populations for heterozygous FH (HeFH) and 1:300 000 for homozygous FH (HoFH).2

The risk for premature ASCVD in both HeFH and HoFH is due to both the magnitude and duration of exposure to elevated LDL-C levels.3 Patients with FH are frequently underdiagnosed and undertreated, often presenting with clinically significant ASCVD.4 5 This review will explore the diagnosis and treatment recommendations to reduce progression of atherosclerotic cardiovascular disease in this high-risk population.


FH is an autosomal dominant form of severe hypercholesterolaemia due to mutations in three canonical genes. These mutations involve either: (1) a loss of function (LOF) in the LDL receptor (LDLR) or apolipoprotein B (ApoB)100 or (2) gain of function of proprotein convertase subtilisin kexin 9 gene (PCSK9). By far, mutations in LDLR are most common. The LDLR is found on the surface of hepatocytes and binds circulating LDL particles and clears them by a process known as receptor-mediated endocytosis. ApoB is the major surface protein on atherogenic lipoproteins (LDL being quantitatively the most important) and serves as the ligand to the LDLR. While not as …

View Full Text


  • Twitter @DrMichaelShapir

  • Contributors All authors contributed equally in the conceptualisation and draft manuscript preparation. All authors reviewed the results and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

  • Author note References which include a * are considered to be key references.