Contents
- Introduction to familial hypercholesterolaemia
- How is a diagnosis of familial hypercholesterolaemia made?
- How is familial hypercholesterolaemia inherited?
- Treatment for familial hypercholesterolaemia
- Summary
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.
