Familial hypercholesterolaemia (FH): inherited high cholesterol

Cholesterol is carried in the blood in particles, and low-density lipoprotein (LDL) is the type that can deposit in artery walls. The liver normally removes LDL from the blood using receptors on its surface. In FH a change in one of several genes weakens this clearing system. The British Heart Foundation explains that the result is extremely high cholesterol that is usually present from birth, and a gradual build-up of fatty material (atheroma) in the arteries, raising the risk of coronary heart disease, heart attack and stroke, often at a younger age than usual.

The NHS Genomics Education Programme describes FH as the most common genetic cause of premature atherosclerotic cardiovascular disease and notes that it is generally silent until such disease develops. That is why its approach is screening to prevent complications. Because many people do not know they have FH, the numbers recognised are far lower than the estimated 270,000 people in the UK who carry it.

Three main genes are involved: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and PCSK9. All three share the dominant pattern. A parent with FH has one changed and one working copy of the gene, and passes on one of them to each child by chance. The British Heart Foundation puts it plainly: if one of your parents has FH there is a 50% (1 in 2) chance you could inherit the same variant, and if you have FH there is a 50% chance of passing it on to each of your children.

Rare forms exist. In homozygous FH, a person inherits a changed gene from each parent, cholesterol levels are very much higher and heart disease can begin before age 30. The NHS Genomics Education Programme gives its prevalence as around 1 in 300,000. A recessive form involving other genes such as LDLRAP1 is rarer still, and in recessive conditions each pregnancy of two carrier parents has a 25% chance of an affected child.

Most people have no visible signs. When there are, the British Heart Foundation lists lumps on tendons around the knuckles, knees or Achilles (tendon xanthomata), a pale ring around the coloured part of the eye (corneal arcus), and yellow patches around the eyelids (xanthelasmas). A doctor may suspect FH if a routine blood test shows high cholesterol, if someone has a heart attack or stroke young, or if relatives have heart disease at a younger age or a diagnosis of FH.

The first step is a cholesterol blood test through the GP, along with questions about family history. The NHS Genomics Education Programme gives thresholds that raise suspicion, for example total cholesterol above 7.5 mmol/L with LDL above 4.9 mmol/L, together with early heart disease or a family history. Clinicians may use a scoring system such as the Simon Broome criteria and refer to a specialist, where genetic testing on a blood sample or cheek swab looks for a variant in the FH genes.

The programme adds that no gene change is found in every person who clinically has FH, so a negative genetic result does not on its own rule out the condition.

Because each first-degree relative has a 1 in 2 chance, the British Heart Foundation advises that parents, siblings and children of someone diagnosed should be assessed as soon as possible, and that anyone with an affected first-degree relative should be assessed too. This approach, called cascade testing, works outwards from the first person diagnosed. When a gene variant is known in the family, a single targeted test can show who has it.

FH is present from birth, so children of a person with FH can be affected. HEART UK says current national guidelines recommend that children of a parent with a confirmed diagnosis are tested at the earliest opportunity and, if possible, before they are 10, with a genetic test for the same gene as the parent. A child who does not carry that gene will not have FH unless a faulty gene came from the other parent, which HEART UK calls possible but very unlikely. The British Heart Foundation also mentions a pilot screening programme for children.

The British Heart Foundation says FH cannot be treated through diet alone, but a healthy way of living plays an important part. The medicine most often used is a statin. If statins do not lower cholesterol enough or cannot be taken, other medicines can be used instead or alongside, including ezetimibe, bempedoic acid, PCSK9 inhibitors such as alirocumab and evolocumab, inclisiran, and bile acid sequestrants. The NHS Genomics Education Programme notes that statins and ezetimibe are effective in reducing cardiovascular events, with newer injectable agents added as third-line options.

A very small number of people, mainly those with the homozygous form, may be offered LDL apheresis, which removes cholesterol from the blood by passing it through a filtering machine in a similar way to dialysis.

• Diet: low in saturated fat and dietary cholesterol. The British Heart Foundation suggests limiting dietary cholesterol to no more than 300 mg a day, ideally under 200 mg.

• Foods with added plant stanols or sterols can sit alongside prescribed medicines but are not a replacement for them.

• Other measures: keep a healthy weight, be active, stop smoking and reduce alcohol.

• Pregnancy: FH should not affect the chance of getting pregnant, but the British Heart Foundation advises speaking to a doctor beforehand so medicines can be checked and the risk of the baby inheriting FH discussed.