• Relatively common inherited cause of premature coronary artery disease. 
• autosomal dominant inherited lipid disorder
• Untreated, men have a 50% chance of coronary heart disease (CHD) before the age of 50 years
• Untreated, women have a 30% risk by the age of 60 years
• High in Ashkenazi Jews from South Africa, Christian Lebanese and Dutch Afrikaaners, due to a genetic founder effect.
• In Australia, there are 45 000 cases of FH, with less than 10% of cases formally diagnosed.
• Need to exclude secondary causes of hypercholesterolaemia before phenotypic diagnosis
  • Hypothyroidism
  • Nephrosis
  • Cholestasis
  • use of steroids

When to consider familial hypercholesterolaemia

• FH should always be considered in adults with a 
  • total cholesterol level of ≥7.5 mmol/L OR
  • LDL-C ≥5.0 mmol/L OR
  • personal or family history of premature coronary heart disease

Types:

• heterozygous familial hypercholesterolaemia (HeFH)
  • autosomal dominant
  • hereditary disorder with high phenotypic penetrance that is present in approximately 1:250 people in the general population.
  • recognised worldwide as a major public health problem with 50% of first-degree relatives harbouring the disease.
  • 30% of patients with HeFH have elevated lipoprotein(a).
  • 5,13,14 Dominant forms of familial hypercholesterolaemia are also caused by APOB mutations and proprotein convertase subtilisin/kexin type 9 (PCSK9) gain-of-function mutations causing markedly elevated low-density lipoprotein cholesterol (LDL-C) levels related to defective LDL receptor activity in liver cells, leading to premature CVD and death if untreated

• Homozygous familial hypercholesterolaemia (HoFH) 
  • is a much more serious condition affecting 1:300,000 people. 
  • It results from the union of two HeFH carriers, with 25% of their offspring inheriting the homozygous form.
  • Such children have markedly elevated LDL-C from birth and rarely survive beyond teenage years unless aggressively treated from infancy

• Elevated lipoprotein(a) 
  • dominantly inherited disorder leading to accumulation in plasma of lipoprotein(a) particles affecting 20% of the population. 
  • A high level (>50 mg/dL) increases the risk of coronary and peripheral artery disease, calcific aortic stenosis and strokes. 
  • Testing is not listed on the Medical Benefits Schedule in Australia and is currently undertaken mostly by lipid specialists if there is a family history of heart disease.
  • There is currently no specific treatment other than lipoprotein(a) apheresis but RNA-based therapies that target the hepatic over-production of apolipoprotein(a) and the formation of lipoprotein(a) particles are under investigation

Criteria: 

Screening approach

• opportunistic screening for family history
• opportunistic screening of lipids, systematic searching of general practice electronic records, and universal screening of children. 
• The use of Absolute Cardiovascular Disease Risk Assessment tools are best avoided in patients with suspected FH. These patients are already at increased risk of CHD, and the relative risk from their lifelong cholesterol burden is so great that it overrides all other risk factors
• The role of specialist lipid clinics is important in the GP management of patients with FH

The most cost effective method of screening for FH is cascade screening family members of known ‘index cases’ of FH but at a population level this requires that an efficient method be adopted to detect index cases. 

Treatment

• children with HeFH commence lifelong treatment from the age of 8–10 years
• statins should be avoided in pregnancy
• High-risk adults with HeFH should commence maximally tolerated doses of high potency statins on diagnosis and continue for life
• recommended that relevant specialist advice is sought for the care of children and pregnant women