Genetic Factors And Cholesterol

Overview

Cholesterol is a fatty substance that travels in your blood. Your body needs some of it to build cells and make hormones, but too much can build up inside blood vessels and narrow them. Part of your cholesterol level is down to your lifestyle, and part is decided by your genes — the instructions you inherit from your parents. Some people inherit gene changes that make the body clear cholesterol away more slowly, so their levels stay high even when they eat well and exercise. The best-known example is familial hypercholesterolaemia, often shortened to FH. 'Familial' means it runs in families, and 'hypercholesterolaemia' means high cholesterol in the blood. Genes can also affect your 'good' cholesterol and another blood fat called triglycerides.

Inherited high cholesterol is more common than many people realise. FH affects about 1 in 250 people around the world, which means several hundred thousand people in the UK alone, and most of them have not been diagnosed. Other patterns of inherited high cholesterol, caused by many small gene variations adding up together, are even more common.

Anyone can inherit high cholesterol — it affects men and women and people of all ethnic backgrounds, and it is present from birth. You are more likely to have it if a close relative has very high cholesterol or had a heart attack or stroke at a young age. Because it runs in families, once one person is found, brothers, sisters, parents and children can be offered a simple test too.

Symptoms

Common symptoms

• Most people have no symptoms at all — high cholesterol is usually found on a blood test.
• Some people with FH notice firm lumps on the tendons, such as the back of the heel or the knees. These are harmless but are a visible sign of very high cholesterol.
• Yellowish patches or soft lumps around the eyelids (called xanthelasmas) can appear in some people.
• A pale ring around the coloured part of the eye can develop, especially at a younger age than usual.
• The first sign may be a heart problem, such as chest pain or a heart attack, at an earlier age than expected.

Symptoms in children

• Children with inherited high cholesterol almost always feel completely well and have no symptoms.
• Rarely, a child may have firm lumps on the heels, knees or elbows, or yellowish patches near the eyes.
• Most children are only identified because a parent or another relative has been diagnosed and the family is offered testing.

Symptoms in older adults

• Adults often have no new symptoms, even when cholesterol has been high for many years.
• Some people first learn about it after tests for chest pain, a heart attack, a stroke, or poor circulation in the legs.
• A pale ring around the coloured part of the eye is more common with age and on its own does not always mean high cholesterol.

Causes

Main causes

• Inherited gene changes: in FH, a change in a gene that normally clears 'bad' cholesterol from the blood is passed down from a parent. A parent with FH has a 1 in 2 chance of passing it on to each child.
• Many small gene variations adding up together (sometimes called polygenic high cholesterol). Each one has a small effect, but combined they can push cholesterol higher than expected.
• Diet, weight and activity still matter. They add on top of your genes rather than replacing them — which is why someone with inherited high cholesterol can look fit and healthy and still have high levels.
• Other conditions can raise cholesterol too, such as an underactive thyroid, kidney or liver problems, and diabetes, so doctors sometimes check for these.
• Some medicines can raise cholesterol as a side effect.

Risk factors

• A close relative with very high cholesterol, or who was found to have FH
• A parent, brother, sister or child who had a heart attack, stroke or heart bypass before about age 55 (men) or 65 (women)
• Your own cholesterol staying high even though you eat well and stay active
• Already having heart or circulation problems at a younger age than expected
• Having a family member who needed cholesterol treatment from a young age
• Lifestyle factors that add extra risk on top of your genes: smoking, a diet high in saturated fat, little physical activity, carrying extra weight around the middle, diabetes and high blood pressure

When to see a doctor

See a doctor urgently if:

• Chest pain, pressure or tightness, especially with breathlessness, sweating or feeling sick — call your local emergency number
• Sudden weakness or numbness in the face, arm or leg, or trouble speaking — call your local emergency number
• A painful, swollen leg on one side, or sudden severe breathlessness — seek urgent medical help
• New chest tightness on exertion that settles with rest — arrange to be seen the same day

Book a routine appointment if:

• A parent, brother, sister or child has been told they have FH, or has very high cholesterol
• You have a strong family history of early heart attacks or strokes
• You have never had a cholesterol check and you are over 40, or your doctor has offered you an NHS Health Check
• You have a long-term condition such as diabetes, high blood pressure, an underactive thyroid or kidney disease
• You are thinking about pregnancy or are pregnant and have FH — speak to your team early so your care can be planned
• A child in the family may be at risk — ask your doctor when testing should start

Diagnosis

Doctors start with a simple blood test that measures your cholesterol and other blood fats. They then look at the pattern of results, your family history and your own health to judge whether genes are likely to be playing a part. In the UK, GPs use a set of standard questions and checks — sometimes called the Simon Broome or Dutch Lipid Clinic criteria — to estimate how likely it is that you have FH. If it looks likely, you may be referred to a specialist lipid clinic (a service that specialises in cholesterol and fats in the blood), where genetic testing can confirm it and your family can be offered testing too.

Tests that may be done

• A lipid profile: a blood test that measures total cholesterol, 'bad' cholesterol (LDL), 'good' cholesterol (HDL) and triglycerides
• A review of your family history, and if possible cholesterol results from relatives
• A physical examination, looking for signs such as tendon lumps or yellowish patches around the eyes
• Genetic testing, usually through a specialist clinic, to look for a known gene change
• Cascade testing: offering a cholesterol test, and possibly a genetic test, to your parents, brothers, sisters and children
• Other tests to rule out different causes, such as thyroid, kidney and liver blood tests, blood pressure and blood sugar

What to expect at your appointment

You will usually need to avoid eating for a few hours before the cholesterol blood test, so check with your GP surgery when you book. Results often come back within a week or two. If FH is suspected, you may be invited to a specialist clinic, and a genetic result can take a few weeks longer. Being offered family testing is a normal part of the process, not a sign that anything is seriously wrong. Ask as many questions as you like — it helps to bring someone with you or write your questions down beforehand.

Treatment

Treatment aims to bring your cholesterol down enough to protect your heart and blood vessels over the long term. For inherited high cholesterol, healthy living alone is usually not enough, because the body clears cholesterol slowly no matter what you eat. Most people therefore need cholesterol-lowering medicines alongside a healthy lifestyle, and treatment is usually lifelong. The earlier treatment starts, the better the protection — which is why finding it in childhood or early adulthood matters.

Self-care at home

• Eat a heart-healthy pattern: plenty of vegetables, fruit, beans, wholegrains, nuts and oily fish, and less saturated fat from fatty meat, butter, cream, pastries and coconut products
• Choose unsaturated oils such as olive or rapeseed oil instead of butter or lard
• Aim for at least 150 minutes of moderate activity a week — brisk walking, cycling, swimming or anything that makes you a little warm and out of breath
• If you smoke, stopping is the single biggest thing you can do for your heart. Your GP or pharmacist can offer free support
• Keep alcohol within the recommended limits and watch portion sizes if you are carrying extra weight
• Take any prescribed medicine every day, even when you feel well, and reorder before you run out
• Go for your review appointments and repeat blood tests so your treatment can be adjusted if needed

Medical treatments

Your doctor will usually suggest a cholesterol-lowering medicine, most often from a group that works by helping the liver clear 'bad' cholesterol from the blood. The exact choice and strength depend on your cholesterol level, your age, your other health conditions and any medicines you already take. Some people need a second medicine added if their levels are still too high. Children with FH are usually cared for by a specialist team, and treatment may begin in childhood. Everyone on treatment has regular blood tests to check that it is working and that it suits them. Your doctor or pharmacist will explain the benefits and possible side effects, and will help you find something you can take comfortably long term.

When is surgery considered?

Surgery is not used to treat high cholesterol itself. Some people with FH who also have narrowed heart arteries may need procedures such as a stent or bypass operation to improve blood flow to the heart — but this is treatment for the arteries, not for the cholesterol, and it does not replace cholesterol-lowering medicine.

Living with this condition

Most of the time, living with inherited high cholesterol just means taking a tablet each day, keeping up with review appointments and blood tests, and eating in a heart-friendly way most of the time. It should not stop you working, travelling, exercising or doing anything else you enjoy. It helps to build a simple routine — keep medicines somewhere you will see them, set a phone reminder, and ask your pharmacy about repeat prescriptions so you never run out.

Lifestyle tips

• Keep a copy of your cholesterol results so you can see your progress over time
• Tell your dentist, pharmacist and any other health professional about your treatment and other medicines
• If you smoke, get support to stop — this makes a bigger difference than almost anything else
• Keep active in a way you enjoy, so it becomes part of your week rather than a chore
• Look after your blood pressure and blood sugar too, as these work alongside cholesterol to affect heart risk
• Ask your GP surgery to check that your close relatives have been offered testing — it is one of the most helpful things you can do for your family

Diet and exercise

A heart-healthy way of eating does not mean boring food. Build meals around vegetables, beans, lentils, wholegrains, fruit, nuts and oily fish, and swap saturated fats for unsaturated ones. Oily fish such as mackerel, sardines or salmon a couple of times a week is a good habit. Foods with added plant stanols or sterols, such as some spreads and yoghurts, can lower cholesterol a little and are worth discussing with your doctor or dietitian. For activity, aim for something that raises your heartbeat for about 30 minutes on most days — walking briskly counts. Two sessions a week of strength work, like carrying shopping or body-weight exercises, help too. If you have heart symptoms, get checked before starting a new intense exercise plan.

Mental health and emotional wellbeing

It is very normal to feel shocked, worried or even guilty when you learn that high cholesterol runs in your family — especially if a relative has had a heart attack. Some people feel anxious about their children being tested. Remember that this is a gene you were born with, not something you caused, and that knowing about it puts you in a stronger position. Talking things through with your GP, specialist clinic or a counsellor can help. If you ever feel you cannot cope, or have thoughts of harming yourself, contact your local emergency number or a crisis support service straight away — you deserve help right away, and it is available.

Prevention

You cannot change the genes you inherit, so inherited high cholesterol itself cannot be prevented. What can be prevented is the harm it does. Finding it early, treating it, and lowering your other heart risks gives you much of your protection back. If you already know high cholesterol runs in your family, the most useful thing you can do is get tested early rather than waiting for symptoms — there usually are none.

Screening programmes

Cholesterol testing is offered in several ways. In England, an NHS Health Check is offered every five years to adults aged 40 to 74, and it includes a cholesterol test. In families where FH is known, close relatives are offered 'cascade' testing — a cholesterol test, and sometimes a genetic test, for parents, brothers, sisters and children. Children in an affected family are often tested before puberty, and your specialist team will advise on the right age. If you are unsure whether you are due a check, ask your GP surgery.

Complications

If left untreated

• A build-up of fatty deposits in the arteries (atherosclerosis), which narrows them and reduces blood flow
• Coronary heart disease and angina — chest pain caused by reduced blood flow to the heart
• Heart attack, sometimes at a much younger age than usual
• Stroke or a transient ischaemic attack (a 'mini stroke')
• Peripheral arterial disease — narrowed leg arteries causing pain when walking
• Narrowing of the aortic valve or the aorta, which may need monitoring or treatment

Long-term outlook

The outlook is genuinely encouraging. When inherited high cholesterol is found and treated early, the extra risk to the heart falls a great deal, and many people with FH live into old age without heart problems. Treatment today is well understood, closely monitored and usually well tolerated. The biggest hurdle is simply that most people with FH do not know they have it — which is why testing family members matters so much. If you have been diagnosed, you have already taken the most important step.

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