High cholesterol is inevitable for some


Introduction to familial hypercholesterolaemia

If you have very high cholesterol levels in your blood it may be due to a gene defect. This form of inherited high cholesterol is called familial hypercholesterolaemia (FH). This problem affects 1 in 500 people and can cause cholesterol levels higher than 7.5mmol/L (desired level is less than 5mmol/L) in an adult and can lead to early heart disease in the form of angina or heart attack.

Not all cholesterol in the blood is bad. High density lipoprotein (HDL) cholesterol is the good cholesterol and protects your heart by mopping up excessive cholesterol and returning to the liver for breakdown. A level of HDL cholesterol more than 1mmol/L is desirable and it is easy to remember that this is the happy fraction and should be high. Low density lipoprotein (LDL) cholesterol on the other hand is the bad cholesterol – remembered as the lousy one and responsible for depositing cholesterol in the lining of the arteries. The higher the LDL cholesterol, the higher the risk for heart disease.

Research shows that 50% of men and 40% of women with FH develop heart disease by the age of 60. The risk of fatal heart attack before 40 years old is significantly higher in those with FH compared to general population.

On the cells of our body, including the liver cells, there is a receptor that helps us clear the bad cholesterol – LDL from the blood stream. Total absence or reduction in the number of these receptors causes the LDL cholesterol to accumulate and contribute to fatty deposits thus restricting blood flow to the heart, brain or legs. People with FH have a gene defect in the LDL receptor and the genetic basis is well established with over 800 different gene defects.

A person cannot feel when they have high cholesterol, as it can be asymptomatic until the person gets a heart attack or stroke. However, cholesterol deposits can occur in Achilles tendons or the tendons at the back of your hand called xanthomata. It is also possible that some people may develop fatty lumps around the eyes called xanthelesmata.

How is a diagnosis of familial hypercholesterolaemia made?

A blood test, normally fasting, to measure cholesterol is essential. If cholesterol levels are higher than 7.5mmol/L and LDL cholesterol is higher than 4.9mmol/L it is likely that the person may have inherited FH. If he/she also has tendon xanthoma or a positive family history for premature vascular disease along with a cholesterol and LDL level as above they are more likely to have a diagnosis of FH.

How is familial hypercholesterolaemia inherited?

A high cholesterol level due to FH can be inherited from your father or mother. The inheritance pattern is called ‘autosomal dominant pattern’. If a disease is autosomal dominant it means that you only need to get the abnormal gene from one parent in order to inherit the disease and both men and women are equally affected by this mode of inheritance. The siblings of the affected person have a 50% chance of having FH and their children also have a 50% risk of inheriting this problem. Often in the specialist clinics managing this condition, access to family screening called cascade testing for the family members is available. Genetic testing can be done to find out the type of gene defect in majority of the cases.

At the Royal Free Hampstead NHS trust over 800 subjects with this particular form of inherited high cholesterol are cared for. A Nurse specialist is available for advice by any family member suspected to have this form of high cholesterol. The centre receives several phone calls for advice a day and this is likely to increase as the roll out of NHS health checks is likely to pick up more people with this diagnosis. The awareness of this condition is poor amongst the general public as well as the professionals. Of the estimated 120,000 subjects likely to have this disorder, only up to 15,000 people are known to the system. It is essential that the general population is aware of this condition to improve access to treatment.

Treatment for familial hypercholesterolaemia

People with FH should eat a healthy low fat diet including fresh fruits and vegetables. Moderate alcohol consumption may be allowed and smoking needs to be discouraged altogether. An active lifestyle should be recommended to prevent further problems.

This form of high cholesterol invariably requires treatment with medication. Statins, which inhibit an enzyme responsible for synthesising cholesterol in the liver, are often the drug of choice. This type of medication is well tolerated and life-saving with a very small percentage developing muscle pain and muscle stiffness which settles on stopping the medication. A modern non-statin drug called ezetemibe and bile acid sequestrants which block absorption of bile salts in the intestine thus reducing cholesterol, can also be used to acquire an additional reduction of LDL levels and be used instead of statins for those people who cannot tolerate the latter.

In severe cases where people inherit two defective genes and present with a cholesterol level between 20-30mmol/L, treatments to remove cholesterol by apheresis are carried out. LDL-apheresis is a procedure that removes LDL cholesterol from the blood. An intravenous (IV) line is inserted into the arm; blood is drawn from the body, filtered through a special machine that removes LDL particles, and then blood is returned through a vein into the body.

In summary

An estimated 120,000 subjects are thought to have familial hypercholesterolaemia, a form of inherited high cholesterol. This leads to cholesterol levels greater than 7.5mmol/L and LDL cholesterol greater than 4.9mmol/L. Whilst an active and healthy lifestyle can reduce cholesterol levels in most people, in those with FH treatment with medication is often necessary. The most popular drugs to reduce cholesterol levels tend to be statins, although alternate drugs can also be used to lower cholesterol if patient has intolerance to statins or side effects to statins. People with FH should be managed in a specialist clinic with access to family screening and genetic screening. The National Institute of Clinical Excellence (NICE) have brought out a Guideline for managing people with FH. A recent audit by the Royal College of Physicians has shown gaps in management of FH due to funding issues and this needs to be addressed in order to improve cardiovascular outcome in these patients.

The tendon that connects the heel to the muscles of the lower leg. Full medical glossary
A central chest pain caused by insufficient oxygen supply to the heart. Full medical glossary
A fluid produced by the liver, which helps the fat ingested in food to combine with the digestive juices in the gut. Full medical glossary
Substances present in the bile, which help to emulsify fats in the small intestine so that they can be more easily digested. Full medical glossary
A fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. Full medical glossary
The basic unit of all living organisms. Full medical glossary
A substance present in many tissues and an important constituent of cell membranes although high concentrations of a certain type of cholesterol in the blood are unhealthy. Full medical glossary
The process of determining which condition a patient may have. Full medical glossary
A protein that speeds up chemical reactions in the body without being used up itself. Full medical glossary
One of the three main food constituents (with carbohydrate and protein), and the main form in which energy is stored in the body. Full medical glossary
The basic unit of genetic material carried on chromosomes. Full medical glossary
Relating to the genes, the basic units of genetic material. Full medical glossary
The death of a section of heart muscle caused by an interruption in its blood supply. Also called a myocardial infarction. Full medical glossary
High levels of cholesterol in the blood. Full medical glossary
intermittent claudication Full medical glossary
The section of gut, or gastrointestinal tract, from the stomach to the anus. Full medical glossary
Within a vein. Full medical glossary
One of a group of compounds that consist of a protein combined with a lipid, and help to transport lipids in the blood and lymphatic system. Full medical glossary
A large abdominal organ that has many important roles including the production of bile and clotting factors, detoxification, and the metabolism of proteins, carbohydrates and fats. Full medical glossary
Tiny, harmless, hard, white spots that usually occur in clusters around the nose and on the upper cheeks in newborn babies and also in young adults. Full medical glossary
Tissue made up of cells that can contract to bring about movement. Full medical glossary
A type of gentle vomiting when a baby burps and brings up milk at the same time. Full medical glossary
Compounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. Full medical glossary
A way to identify people who may have a certain condition, among a group of people who may or may not seem to Full medical glossary
One of a class of drugs that inhibit cholesterol formation in the liver. Full medical glossary
A class of drugs that inhibit cholesterol formation in the liver. Full medical glossary
Any sudden neurological problem caused by a bleed or a clot in a blood vessel. Full medical glossary
Relating to blood vessels. Full medical glossary
A blood vessel that carries blood towards the heart. Full medical glossary
Relating to the veins. Full medical glossary
A yellowish deposit of fatty material in the skin. Full medical glossary
A yellowish-orange, lipid-filled nodule in the skin. Full medical glossary