My Approach to the Patient With Familial Hypercholesterolemia

Mayo Clin Proc. 2016 Jun;91(6):770-86. doi: 10.1016/j.mayocp.2016.04.013.


Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C-lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / prevention & control
  • Child
  • Cholesterol, HDL / analysis
  • Early Diagnosis
  • Family Health*
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods
  • Genetic Testing / standards
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipoproteinemia Type II* / diagnosis
  • Hyperlipoproteinemia Type II* / epidemiology
  • Hyperlipoproteinemia Type II* / physiopathology
  • Hyperlipoproteinemia Type II* / therapy
  • Liver Transplantation
  • Male
  • Mass Screening / methods
  • Mass Screening / standards
  • Middle Aged
  • Portacaval Shunt, Surgical
  • Prevalence
  • Primary Prevention / methods
  • Sex Distribution
  • Triglycerides / blood


  • Cholesterol, HDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Triglycerides