Special cases

Familial hypercholesterolaemia: implications for the family

The chances of passing on the gene responsible for familial hypercholesterolaemia to a child are one in two. As the risk of developing early coronary heart disease (CHD) in familial hypercholesterolaemia is very high, it is sensible to identify affected children by measuring their blood cholesterol level. If the total cholesterol level is greater than 6.8 millimoles per litre (mmol/l) in childhood, there is a high probability of familial hypercholesterolaemia.

The abnormality can usually be detected from infancy onwards, although the age at which testing is undertaken depends on the wishes of the parents and the likely age of onset of CHD in the family. Testing may be delayed if the whole family is receiving an appropriate diet but ought to be undertaken by 10 years of age for two reasons. First, compliance with diet is better when introduced early and, second, some children may benefit from drug treatment.
Other conditions with raised blood cholesterol levels, such as polygenic hypercholesterolaemia, are not apparent in early childhood and little is gained by testing blood levels until after puberty.

Treatment of children with familial hypercholesterolaemia

As with adults, diet forms the basis of treatment, although it is important that any dietary approach supports normal growth and development. In practice, it is important to ensure that the intake of energy is sufficient but not excessive, as even moderate obesity may exacerbate hypercholesterolaemia. The intake of saturated fats should be as low as possible through the measures shown in the box on page 85. Advice should also be given on avoiding other risk factors for CHD, such as smoking.

Drug treatment is sometimes recommended in children, particularly when there is a history of early onset CHD in the family. Resins are usually recommended, because they are not absorbed and thus have less potential for side effects. However, children may not like taking them and they can cause indigestion and altered bowel function. Statins are usually avoided because little is known about their effects on growth and development. There are some reports on the use of statins that suggest that they are effective and well tolerated, and don’t interfere with growth and development. However, these were for short periods of time and included relatively few patients.

Cholesterol-lowering drugs in pregnancy

There is no evidence that cholesterol-lowering drugs affect the development of an unborn baby. However, it is not worth taking any risks and it is usually recommended that women of child-bearing age should use an effective method of contraception if taking cholesterol-lowering drugs.

If a woman with familial hypercholesterolaemia wishes to start a family, she should stop any drug treatment until after the baby is born. This ensures that there is no risk to the baby, and the mother’s risk of CHD is unlikely to increase significantly as a result of the period without drugs. Total cholesterol and LDL-cholesterol levels increase in the final stages of pregnancy and during breast-feeding, although they return to previous levels after weaning. It is not known whether these relatively short-term changes increase CHD risk.

Oral contraception

Early combined oral contraceptives (including oestrogens and progestogens) increase blood levels of cholesterol and triglycerides. However, newer preparations use lower doses and different types of hormones, which do not affect cholesterol levels. Some types produce small increases in triglycerides.

Rare types of hypercholesterolaemia

The common primary forms of hypercholesterolaemia are familial hypercholesterolaemia, polygenic hypercholesterolaemia and familial combined hyperlipidaemia. Rarer forms also occur, some of which relate to abnormalities of the protein components of lipoprotein particles. In general, these rarer abnormalities are associated with an increased risk of early CHD, similar to that seen in familial hypercholesterolaemia. They are picked up by measuring blood cholesterol levels using the principles outlined earlier.

Severe hypertriglyceridaemia

Most of this book has been concerned with hypercholesterolaemia and hypertriglyceridaemia has been mentioned where it is associated with what is primarily a problem with cholesterol. Blood triglyceride levels are usually less than 2 mmol/l, although higher levels commonly occur after a meal, particularly if the meal contains a lot of fat. These levels rarely exceed 5 mmol/l.

More severe hypertriglyceridaemia can occur, with levels over 20 mmol/l. These can be the result of some other problem, such as diabetes mellitus, particularly when this is poorly controlled, type 1 (early onset) diabetes. Blood triglyceride levels usually improve when the diabetes is well controlled. Alcohol abuse can also cause extremely high blood triglyceride levels, the treatment being severely curtailing alcohol intake.

Very rarely, severe hypertriglyceridaemia can be the result of a defective gene, the one that controls the removal of dietary fat from the bloodstream and its storage in adipose tissue. As triglycerides are not removed from the blood in this condition, the blood serum contains more fat and looks very milky. This is sometimes picked up when a blood sample is taken for another test. The condition is treated by very-low-fat diets.

Risks of severe hypertriglyceridaemia

Severe hypertriglyceridaemia (blood triglyceride levels greater than 10 mmol/l) increases the risk of pancreatitis. The pancreas is a large gland at the back of the abdomen that produces enzymes to digest food and also hormones such as insulin. The pancreas may become damaged and the enzymes that are normally secreted into the gut are activated within the gland, leading to its partial destruction, pancreatitis. This is a serious condition that is extremely painful.

Raised blood triglycerides as a risk factor for cardiovascular disease

Blood triglyceride levels are usually less than 2 mmol/l and are considered to be raised if they exceed 2.3 mmol/l in a sample taken after fasting for at least 12 hours. The risks of severe hypertriglyceridaemia (levels greater than 10 mmol/l) are considered above.

Severe hypertriglyceridaemia is uncommon. There has been uncertainty about whether more modestly raised triglyceride levels, seen more commonly, are a risk factor for CVD. In some studies, raised blood triglyceride levels are associated with CVD, although it is difficult to be sure whether this relationship is independent of other risk factors. This is because blood total cholesterol levels are often raised when triglyceride concentrations are increased and HDL-cholesterol levels are usually low under these circumstances.

Using the statistical technique of meta-analysis (combining the results of many studies) it appears that triglycerides are an independent risk factor, particularly in women and patients with diabetes, after adjusting for the risk from low HDL levels.

The most appropriate advice is that blood triglyceride levels should be less than 2 mmol/l. Weight reduction and avoiding fatty foods may be necessary to achieve this, and sometimes treatment with drugs will be appropriate, should dietary measures not be sufficient.

KEY POINTS

• Children with familial hypercholesterol­aemia should follow a low-fat diet and avoid other CVD risk factors

• Severe hypertriglyceridaemia predisposes to pancreatitis

• Raised triglyceride levels are a risk for CVD in women and people with diabetes