NICE guideline [CG71] Familial hypercholesterolaemia: identification and management. Published: Aug 2008. Last updated: Oct 2019.
Article Last Updated: 18 September 2025
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Familial Hypercholesterolemia (FH)
Familial hypercholesterolaemia (FH) is an inherited genetic disorder that causes markedly raised low-density lipoprotein (LDL) cholesterol from birth, leading to accelerated atherosclerosis and premature cardiovascular disease. It is one of the most common inherited metabolic conditions seen in clinical practice.
This guide covers the genetics, signs/symptoms, investigation, diagnostic criteria and treatment of FH. It is based on NICE guideline [CG71] Familial hypercholesterolaemia: identification and management.
Background Information
Definition
FH is a genetic disorder of cholesterol metabolism characterised by markedly elevated LDL cholesterol levels. Aetiology
Inheritance pattern: autosomal dominant
FH is typically monogenic, involved genes include: [ref]
Most common: loss-of-function in the LDL receptor geneFunction of LDL receptor: LDL binds to LDL receptors on hepatocytes to enable endocytosis, thus removing LDL from the blood
Loss-of-function mutation in APOB geneFunction of APOB: main protein component of LDL that binds to LDL receptor Function of LDL receptor: LDL binds to LDL receptors on hepatocytes to enable endocytosis, thus removing LDL from the blood
Gain-of-function mutation in PCSK9 geneFunction of PCSK9: enzyme that promotes degradation of LDL receptor Function of LDL receptor: LDL binds to LDL receptors on hepatocytes to enable endocytosis, thus removing LDL from the blood
Heterozygous FH is much more common, while homozygous FH is rare.
Complications
Main complication is atherosclerosis → premature atherosclerotic cardiovascular disease[ref]
Coronary artery disease – most significant
Ischaemic stroke
Peripheral arterial disease
Diagnosis Guidelines
The author would like to acknowledge that NICE made recommendations specific to homozygous and heterozygous FH. However, that is excessive detail for a medical student, therefore not specified in this article.
Tendon xanthomataHard, non-tender, nodular enlargements of tendons. – most commonly found in Achilles and extensor hand tendons)
XanthelasmasYellowish plaques on the eyelids
Corneal arcusWhite / grey ring at the corneal margin
Note that the above findings are NOT specific to FH, they can also be seen in individuals with any form of hypercholesterolaemia or dyslipidaemia.
Tendon xanthomata are more specific for FH (thus included in diagnostic criteria), compared to xanthelasmas and corneal arcus.
Investigation and Diagnosis
When to Suspect FH
Suspect FH in adults with ANY of the following:
Total cholesterol >7.5 mmol/L
Personal or family Hx of premature coronary artery disease (in <60 y/o)
Homozygous FH causes much higher cholesterol levels, with onset typically in childhood or early adulthood, and has severe rapid disease progression.
NICE recommends suspecting homozygous FH if:
LDL cholesterol >13 mmol/L in adults
LDL cholesterol >11 mmol/L in children / young people
Assessing for CADCoronary artery disease age of onset, lipid levels and smoking history in these relatives
Also include deceased relatives
If Simon Broome criteria yield a possible or definitive OR DLCN score >5 → refer to specialist for DNA testing
DNA testing is the confirmatory test for FH
Note that a +ve DNA testing alone is diagnostic, even if LDL-C does not meet the diagnostic criteria
Absence of clinical signs of FH (e.g. tendon xanthomata) does NOT exclude FH.
Management Guidelines
FH in young people and children → always refer to specialist immediately
Approach – patients should receive ALL the following:
Lifestyle advice, and
Lipid-lowering therapy, and
Screening family members and offspring
1. Lifestyle Advice
Healthy eating (refer to https://www.nhs.uk/live-well/)
Offer individualised nutritional advice
Total fat intake ≤30% of total energy intake
Saturated fat intake ≤10% of total energy intake
Dietary cholesterol intake <300mg/day
Replace saturated fats with monounsaturated fatsOlive oil and rapeseed oil. Examples specified by NICE. and polyunsaturated fats
Encourage physical activityFor adults/ 150 min of moderate intensity activity or 75 min of vigorous intensity activity per week. Examples of moderate intensity activity: brisk walking or cycling Examples of vigorous intensity activity: running
Weight management
Smoking cessation
Advice on alcohol consumption<14 units of alcohol per week, spread evenly over 3 or more days.
2. Lipid-Lowering Therapy
Target ≥50% reduction in LDL-CLow-density lipoprotein concentration from baseline (adults)
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