The Basics - Understanding hypercholesterolaemia

Hypercholesterolaemia can lead to an increased cardiovascular risk profile.

Coronary heart disease is associated with high LDL cholesterol (Photograph: SPL)

Lipids are fats derived from diet or synthesised within the liver. Lipoproteins include LDL, which is cholesterol rich and when raised is associated with atherosclerosis; and HDL, which is also rich in cholesterol but is associated with atherosclerosis when levels are low.

Atherosclerosis is a progressive and potentially occlusive disease of the arteries that can lead to coronary artery disease, cerebrovascular disease and peripheral vascular disease. The relationship between high total cholesterol, raised LDL cholesterol and cardiovascular disease is now well established.

There is a similar relationship between low HDL cholesterol and the risk of developing cardiovascular disease. Conversely, higher levels of HDL cholesterol are protective against vascular problems.

When looking at a fasting lipid result, consider that the bulk of that total will comprise of LDL cholesterol and a smaller proportion of HDL cholesterol.

1. Requesting a blood test
A GP should avoid measuring cholesterol levels within 12 weeks of an acute illness, times of weight fluctuation, pregnancy or untreated thyroid dysfunction, as these states may not accurately reflect the true cholesterol levels.

When requesting a blood test, it is important to provide relevant clinical information on the biochemistry request form.

2. Lipids and risk factors
It is important not to forget about other lipid problems and risk factors in cardiovascular disease. Measuring the cholesterol alone will not be enough for a full assessment.

Assessment should include a full lipid profile and cardiovascular risk assessment, which would include measuring features such as BP and BMI.

Some risk factors cannot be modified, such as age, sex and family history.

However, other risk factors can be, such as hypertension, diabetes control and lifestyle modifications, such as smoking cessation.

It is also important when requesting a full lipid profile to check whether the patient has fasted. If the patient has not fasted, the triglyceride level may well be elevated.

In addition, consider secondary causes of hyperlipidaemia, including obesity, renal and liver disease, hypothyroidism, diabetes, medication, such as steroids, and excessive alcohol intake.

Though a small number of patients will have clinical signs of either hypercholesterolaemia or hyperlipidaemia, many will be detected by screening.

It is important to have a strategy to detect patients who are high risk.

These include patients with a family history of a lipid disorder or cardiac disease (especially family members who are affected when young).

3. Polygenic hypercholesterolaemia
Polygenic hypercholesterolaemia is the commonest cause of primary hypercholesterolaemia and is thought to be caused by an interaction between several genetic abnormalities and environmental influences.

This leads to a moderate increase in LDL cholesterol which leads to an increased cardiovascular risk profile.

4. Familial hypercholesterolaemia
Familial hypercholesterolaemia (FH) is an autosomal dominant condition. Not surprisingly, those who are homozygous have a more severe manifestation of this disorder compared with those who are heterozygous.

Both phenotypes can lead to premature cardiovascular disease.

Homozygous FH has a prevalence of about one in 100,000 and can lead to childhood and young adult cardiovascular disease and without treatment may lead to a premature death.

Heterozygous FH is more common with an incidence rate of about one in 500. This condition may be associated with xanthomas and xanthelasma. It has been associated with a defect in the LDL cholesterol liver receptor. More than 150 different abnormalities have been described.

This obviously makes genetic screening difficult. Untreated, this condition can lead to premature cardiovascular disease in middle age.

5. Treatment
Lowering lipids is important in both the primary and secondary prevention of cardiovascular disease. Both cholesterol and lipid measurements should not be taken in isolation and should be considered as part of an overall cardiovascular risk assessment. Risk equations are available to calculate risk (see useful websites).

NICE does not have specific lipid targets set which must be achieved for an acceptable lipid profile in either primary or secondary prevention.

However, in secondary prevention, in specific situations there have been some suggestions about potential target levels but these are not written in stone and depend on the clinical situation.

6. Non-pharmacological treatment
This involves reducing the total fat and cholesterol intake, while increasing fibre consumption. Simple lifestyle measures, such as increasing physical activity and trying to achieve ideal body weight, are important. Similarly, advice about reducing smoking and alcohol intake is vital.

7. Pharmacological treatment
Statins (HMG CoA reductase inhibitors) are well known and are often used as first-line treatment to reduce the synthesis of cholesterol. Statins are well tolerated but are rarely associated with liver failure and rhabdomyolysis. More commonly, abnormal LFTs and myalgia are side-effects associated with statin therapy. Myalgia can present in up to 5 per cent of statin users. Pregnancy and breast feeding are contraindications to statin use.

Other groups of drugs that can be used include bile acid sequestrants, such as colestyramine, which prevent absorption of bile acids in the ileum. Ezetimibe is an example of a cholesterol absorption inhibitor and acts by inhibiting intestinal absorption of cholesterol. It can be used in conjunction with a statin. Nicotinic acid and fibrates can also be used to improve lipid profiles.

  • Dr Brown is a GP in Leeds
Key Points
  • If possible, avoid measuring cholesterol levels within 12 weeks of an acute illness, times of weight fluctuation, pregnancy or untreated thyroid dysfunction.
  • Polygenic hypercholesterolaemia is the commonest cause of primary hypercholesterolaemia.
  • Statins are generally well tolerated but can be associated with abnormal LFTs and myalgia.
  • Lifestyle modification is important to lower cholesterol level and improve cardiovascular health.

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