This is general health information only and is not a substitute for advice from your GP or healthcare professional.
1. What is familial hypercholesterolaemia?
Familial hypercholesterolaemia (FH) is an inherited condition that causes persistently high levels of LDL cholesterol (LDL-C) from an early age. The high LDL-C accelerates the development of atherosclerosis and significantly increases the risk of premature coronary artery disease, heart attack and other cardiovascular disease.
2. What causes familial hypercholesterolaemia?
FH is usually caused by a genetic variant affecting the body’s ability to remove LDL cholesterol from the bloodstream. The most common gene involved is LDLR, which codes for the LDL receptor. Less commonly, variants in APOB or PCSK9 are responsible. FH is usually inherited in an autosomal dominant pattern.
3. How high is the cholesterol in familial hypercholesterolaemia?
LDL-C is often markedly elevated, even when a person has a healthy diet and lifestyle. In adults, an untreated LDL-C of approximately ≥5.0 mmol/L is an important clinical clue to FH, although the diagnosis should not be based on LDL-C alone. LDL-C can be substantially higher in people with more severe forms of FH.
4. What are the signs of familial hypercholesterolaemia?
Many people have no symptoms until cardiovascular disease develops. Physical findings can include tendon xanthomas, particularly thickening or lumps of the Achilles tendons, and corneal arcus, especially when it occurs at a young age. A family history of markedly elevated cholesterol or premature coronary artery disease is another important clue.
5. How is familial hypercholesterolaemia diagnosed?
Diagnosis is based on the combination of LDL-C levels, personal and family history of premature cardiovascular disease, physical findings, and sometimes genetic testing. Clinical scoring systems such as the Dutch Lipid Clinic Network criteria can help determine the likelihood of FH. Genetic testing can confirm a pathogenic variant, but a negative genetic test does not completely exclude FH.
6. Why is early treatment of FH important?
People with FH are exposed to high LDL-C for many more years than the general population. This prolonged exposure substantially increases cumulative atherosclerotic burden and cardiovascular risk. Early and sustained LDL-C lowering can significantly reduce this excess risk.
7. How is familial hypercholesterolaemia treated?
Treatment usually involves intensive LDL-C lowering with a high-intensity statin, often combined with ezetimibe if the LDL-C target is not achieved. Depending on cardiovascular risk and the degree of LDL-C elevation, additional therapy such as a PCSK9 inhibitor may be considered. Lifestyle measures remain important but cannot compensate for the genetically driven LDL-C elevation.
8. Can lifestyle changes alone control familial hypercholesterolaemia?
Lifestyle measures such as a heart-healthy diet, regular physical activity, maintaining a healthy weight, avoiding smoking, and limiting saturated and trans fats are important for reducing overall cardiovascular risk. However, because FH is caused by an inherited defect in LDL cholesterol clearance, lifestyle changes alone are usually not sufficient to bring LDL-C down to the recommended target. Most people with FH require long-term cholesterol-lowering medication in addition to lifestyle measures.
9. Should family members be tested for FH?
Yes. Because FH is inherited, cascade screening of first-degree relatives is strongly recommended when FH is diagnosed or strongly suspected. Parents, siblings and children may have a significant risk of carrying the same genetic condition. Screening can involve lipid testing and, when a causative genetic variant has been identified, targeted genetic testing.
10. What LDL-C target should someone with FH aim for?
The appropriate target depends on the person’s overall cardiovascular risk and whether they already have atherosclerotic cardiovascular disease. People with FH and established cardiovascular disease generally require very intensive LDL-C lowering, while those without established disease still require substantially lower LDL-C than would be acceptable for the general population. Treatment should aim for both a sufficiently low LDL-C level and a substantial reduction from the untreated baseline.