Screening and treatment of familial hypercholesterolemia - Lessons from the past and opportunities for the future (based on the Anitschkow Lecture 2014)

Atherosclerosis. 2015 Aug;241(2):597-606. doi: 10.1016/j.atherosclerosis.2015.06.011. Epub 2015 Jun 9.


In this review, we discuss the screening and treatment of familial hypercholesterolemia (FH), an autosomal dominant inherited disease, characterized by severely increased levels of low-density lipoprotein cholesterol (LDL-C) and increased risk for premature coronary heart disease (CHD). Genetic family based cascade screening for FH was shown to be cost-effective and a screening program with such an approach was carried out in the Netherlands from 1994 to 2014. Over 64,000 persons have participated in this program of whom 40.3% were found to carry an FH causing mutation. We will discuss the results of this screening program, as well as the scientific opportunities it has provided. Currently, statins and ezetimibe are the only registered LDL-C lowering treatment options for FH patients. Many of them do not attain the treatment goals that are recommended by treatment guidelines. In this review, we will also provide a comprehensive overview of promising new modalities that could lower LDL-C in FH patients.

Keywords: Cardiovascular disease; Cholesterol treatment; Familial hypercholesterolemia; Screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Apolipoproteins B / metabolism
  • Carrier Proteins / metabolism
  • Cholesterol Ester Transfer Proteins / metabolism
  • Coronary Disease / diagnosis*
  • Coronary Disease / genetics
  • Coronary Disease / therapy*
  • Cost-Benefit Analysis
  • Ezetimibe / therapeutic use
  • Genetic Predisposition to Disease
  • Humans
  • Hyperlipoproteinemia Type II / diagnosis*
  • Hyperlipoproteinemia Type II / genetics
  • Hyperlipoproteinemia Type II / therapy*
  • Mass Screening
  • Mutation
  • Netherlands
  • Proprotein Convertase 9
  • Proprotein Convertases / metabolism
  • Receptors, LDL / genetics
  • Risk
  • Serine Endopeptidases / metabolism


  • Anticholesteremic Agents
  • Apolipoproteins B
  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Receptors, LDL
  • microsomal triglyceride transfer protein
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Ezetimibe