FH (Familial Hypercholesterolaemia) and increased cardiovascular risk (CV risk)

Last edited 11/2018

Facts and Figures

• in some people, a high cholesterol concentration in the blood is caused by an inherited genetic disorder known as familial hypercholesterolaemia (FH)
  
  
• FH affects approximately between 1 in 250 to 1 in 500 people in the UK, which is about 130,000 - 260,000 people, including children
  
  
• most people with FH have inherited a defective gene from only one parent and are therefore heterozygous. Less frequently, a person will inherit a genetic defect from both parents and will have homozygous FH
  
  
• FH is transmitted from generation to generation in such a way that siblings and children of a person with FH have a 50% risk of inheriting FH
  
  
• raised cholesterol concentration that characterises heterozygous FH leads to:
  • a greater than 50% risk of coronary heart disease in men by the age of 50 years and at least 30% in women by the age of 60 years (1)
  • patients with heterozygous FH are generally asymptomatic in childhood and early adulthood. About 5% of heart attacks under the age 60 and as many as 20% under age 45 are due to FH (2,3)
    
    
• homozygous or compound heterozygous FH (4)
  • has a severe and variable clinical presentation usually within the first decade of life - most of these individuals have extreme hypercholesterolemia with rapidly accelerated atherosclerosis when left untreated
  • variation depends of the amount of LDL receptor activity
  • coronary artery disease is the most common cause of premature death in these patients, but other cardiovascular disease including aortic and supravalvular aortic stenosis and aortic root disease is also common

Reference:

• Public Health England (August 2018).Familial Hypercholesterolaemia Implementing a systems approach to detection and management.
• Hopkins P, Toth P. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011 Jun;5(3 Suppl):S9-17.
• Nordestgaard B, Chapman M, Humphries S. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478-90a.
• Cuchel M, Bruckert E, Ginsberg H. Homozygous Familial Hypercholesterolaemia: New Insights and Guidance for Clinicians to Improve Detection and Clinical Management. Eur Heart J. 2014;35(32):2146-2157.