In this episode, Dr Kevin Fernando considers the case of Juliana, a 43-year-old journalist who requests a cholesterol check because her father experienced a heart attack in his early 50s. She has no past medical history of note. Her lipid profile returns as follows: total cholesterol (TC), 7.5 mmol/L; HDL-cholesterol, 1.4 mmol/L; triglycerides, 2.2 mmol/L; LDL-cholesterol, 2.9 mmol/L. What should we do next, and what do current guidelines recommend regarding the detection and management of familial hypercholesterolaemia (FH)?

Key references discussed in the episode:

• Cuchel M, McGowan MP. Lancet. 2021;398(10312):1667-1668. doi: 10.1016/S0140-6736(21)01372-6.
• EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet. 2021;398(10312):1713-1725. doi: 10.1016/S0140-6736(21)01122-3.
• Familial hypercholesterolaemia: identification and management. Clinical guideline [CG71]. 2008, updated 2019. https://www.nice.org.uk/guidance/cg71 (accessed 22 December 2021).
• NHS England and NHS Improvement London. Familial hypercholesterolaemia. https://www.england.nhs.uk/london/london-clinical-networks/our-networks/cardiac/familial-hypercholesterolaemia/ (accessed 22 December 2021).
• Nordestgaard BG, et al. Eur Heart J. 2013;34(45):3478-90a. doi: 10.1093/eurheartj/eht273.

Key resources discussed in the episode:

• PRIMIS FAMCAT2 tool
• Simon Broome diagnostic criteria

Key take-home messages from this episode:

• FH is diagnosed late.
• Guideline-recommended LDL-cholesterol concentrations are infrequently achieved with single-drug therapy.
• There is a disparity in care between men and women living with FH.
• Earlier detection and greater use of combination therapies are required to reduce the global burden of FH.
• FH is common, affecting up to 1 in 250 individuals in the UK.
• If untreated, FH can lead to coronary heart disease in >50% of men by age 50 and at least 30% of women by age 60.
• FH patients reach LDL-cholesterol threshold levels for chronic heart disease at an early age.
• Many people with FH are asymptomatic; therefore, case-finding is pivotal because the condition is not identified by cardiovascular disease assessment tools such as QRISK®3-2018.
• NICE suggests systematically searching primary care records for people with:
  • TC >7.5 mmol/L in those <30 years
  • TC >9 mmol/L in those ≥30 years
• The FAMCAT2 tool from PRIMIS can help us do this in primary care.
• Suspect FH in adults >16 years with:
  • TC >7.5mmol/L and/or
  • Personal history of premature coronary heart disease <60 years
  • Family history of premature CHD <60 years in a first-degree relative
• Secondary causes of hyperlipidaemia should also be considered:
  • Type 2 diabetes
  • Chronic kidney disease
  • Hypothyroidism
  • Medication such as steroids and beta-blockers
  • Obesity
  • Excessive alcohol consumption
• Once individuals are identified, NICE CG71 recommends assessing against standard FH diagnostic criteria, such as the Simon Broome criteria.
• Treatment:
  • Can be initiated by a specialist with on-going follow-up possible in primary care
  • High-intensity statin therapy to achieve LDL-cholesterol goals
    • Dose should be increased to the maximum licensed or tolerated dose to achieve a recommended reduction in baseline LDL-cholesterol of >50%
  • Reinforce lifestyle advice: smoking cessation, healthy diet and increasing physical activity