Presentation: Patient with raised cholesterol

A 42-year-old man presents for an NHS health check. His cholesterol results show a total cholesterol of 9.3mmol/L and LDL of 6.2mmol/L. He is fit and healthy, a non-smoker, with a normal BMI. He states that his father developed angina at the age of 56.

• Elevated cholesterol (total cholesterol of more than 7.5mmol/L and LDL of more than 4.9mmol/L) raises the possibility of a genetic cause – namely, FH.
• FH confers a significant risk of premature CVD.
  • For men, the risk is 50% by the age of 50.
  • For women, the risk is 30% by the age of 60.
  • Do not use the QRISK calculator algorithm for these patients because it will underestimate their CVD risk.
• Raised cholesterol in conjunction with either a family history of raised cholesterol or premature CVD suggests a possible clinical diagnosis of FH.
• FH follows an autosomal dominant inheritance pattern, meaning that first-degree relatives of an affected person have a 50% chance of also being affected.
• Flags for an underlying genetic diagnosis include:
  • an absence of secondary causes of raised cholesterol, such as renal or hepatic disease, diabetes, thyroid disease or alcohol misuse;
  • a family history of premature CVD (below the age of 60 in a first-degree relative, or below the age of 50 in a second-degree relative);
  • a family history of raised cholesterol; and
  • clinical features of raised cholesterol, such as corneal arcus, xanthelasma and/or tendon xanthoma.

• Enquire about the patient’s family history and alcohol intake.
• Ask about any symptoms of ischaemic heart disease and, if present, refer as per usual management.
• Repeat blood sample testing (urea and electrolyte testing, liver function testing, thyroid function testing, haemoglobin A1c (HbA1c) testing and lipid profile) to confirm raised cholesterol and exclude secondary causes and mixed raised lipids.
• Use Simon Broome criteria or Dutch Lipid Clinical Network criteria to assess the patient’s clinical diagnosis and eligibility for referral for genotyping, and refer along regional pathways.
• Provide the patient with lifestyle advice, addressing modifiable risk factors.
• Start high-intensity statin. Refer to the NICE guidance for dosage and titrate to achieve 50% reduction in LDL level.
• Advise the patient’s first-degree relatives to seek a blood test for lipid profile.
• Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• FH Wales: FH Web Tool
• Lipid Tools: Dutch Lipid Clinical Network (DLCN) score
• NICE: Management of adults with heterozygous familial hypercholesterolaemia
• MDCalc: Simon Broome diagnostic criteria for familial hypercholesterolemia

For patients

• Heart UK
• Heart UK: Understanding cholesterol (PDF, five pages)