How is hypercholesterolaemia diagnosed?

Findings such as tendon xanthomas, xanthelasmas or early corneal arcus (see page 40) may suggest that hypercholesterolaemia is present, but the only way to be sure is to take a blood sample and measure blood cholesterol levels.

What is high?

The average total cholesterol level in blood in the UK is around 5.2 millimoles per litre (mmol/l). About 20 per cent of people have a level above 6.5 mmol/l.

The more your cholesterol level is above average, the higher your risk of cardiovascular disease (CVD). What cholesterol level is regarded as ‘high’ is determined by the association between the risk of CVD and blood cholesterol levels (see page 12).

The risk of CVD doubles as the blood cholesterol concentration increases from 5.2 mmol/l (expressed as 200 mg/100 ml in America) to 6.5 mmol/l (250 mg/100 ml) and is about three times higher if the cholesterol level is 7.8 mmol/l (300 mg/100 ml).

So the relative risk of dying from a heart attack is doubled if your total cholesterol is 6.5 mmol/l rather than 5.2 mmol/l. This sounds a very significant increase in risk, although it is important to understand this in absolute as well as in relative terms.

For example, if no other risk factors are present, a young adult with a cholesterol level of 5.2 mmol/l has a very small risk of dying from CVD (0.08 per cent per year or 1 in 1,250). This increases to 0.16 per cent (1 in 625) if the cholesterol level is 6.5 mmol/l. Although the risk has doubled, it still remains very small, but relatively high compared with the person’s peers. It increases again to 0.24 per cent (1 in 417) if the cholesterol level is 7.8 mmol/l.

In terms of these risks, it is clearly desirable to have higher levels would almost certainly benefit from diet and lifestyle changes aimed at reducing cholesterol. A blood total cholesterol level of 6.5 mmol/l or more is considered ‘high’, although the absolute risk at this level is not considered high enough to require treatment with drugs unless other risk factors, such as high blood pressure and smoking, are present and the overall risk of CVD is high. For those whose risk is high current treatment targets are to reduce the total cholesterol level to below 4 mmol/l or the LDL-cholesterol to less than 2 mmol/l.

Assessment of cardiovascular risk

If you have previously had a heart attack, your risk of a further attack is six times higher, because it suggests that blood flow to your heart has already been affected. Under these circumstances, the absolute risk of dying from CVD associated with a cholesterol level of 6.5 mmol/l is over 3 per cent (1 in 33) in middle age.

Most people with angina face a similar risk, and preventing further coronary disease is a high priority. Most angina and heart attack patients will benefit by lowering their cholesterol. The aim is to reduce total cholesterol levels as low as possible, and certainly to below 4 mmol/l.

The risk of CVD is increased by about three times in cigarette smokers and a similar risk is associated with high blood pressure or hypertension. These and other risks multiply together, so that the risk of CVD in a hypertensive patient who smokes is nine times higher than in a person without these risk factors.

Other risk factors, such as high blood cholesterol levels and increasing age, cause this risk to increase steeply, so treatment to reduce cholesterol levels may be suggested even if there is no history of CVD.

Cardiovascular risk calculators

It is difficult to arrive at an estimate of coronary risk by juggling risk factors in your head, but help is available in the shape of CVD risk calculators. Many of the CVD risk factors identified in the box on page 10 have been included in risk prediction charts, which relate these risk factors to blood cholesterol levels.

Separate charts are available for men and women, reflecting their different cardiovascular risk. The charts (shown on pages 57–9) present the risk of developing CVD over the next 10 years. Patients whose risk falls within the red zone (CVD risk greater than 20 per cent over the next 10 years or 2 per cent per annum) should reduce their risk factors.

Charts are convenient for seeing at a glance whether your risk of CVD is high. Doctors use them, but they can also put the values for the various risk factors into a spreadsheet to calculate the risk more precisely.

Not all risk factors are included. A family history of CVD is a risk factor that is usually left out of risk calculators. Ethnicity is not included and most risk factor calculators are unsuitable for patients with diabetes.

Who should have blood cholesterol measured?

General screening of the whole adult population for hypercholesterolaemia would prove expensive, not only for the screening programme itself, but also for the extensive facilities needed for effective treatment and follow-up. Mass cholesterol screening is therefore not feasible. In addition, some people could be identified as having ‘high’ cholesterol levels when their absolute risk of CVD was not particularly great. This would have adverse effects, such as increased anxiety, because such people might perceive themselves as unhealthy.

Blood cholesterol levels are usually measured only when there is an indication to do so, such as signs of:

hypercholesterolaemia (for example, tendon xanthomas, xanthelasmas or early corneal arcus)
a personal history of heart disease
the presence of other CVD risk factors
a family history of early coronary disease
a family history of hypercholesterolaemia

When should blood cholesterol levels be measured?

Measurements should form part of an overall assessment of coronary risk, and blood cholesterol levels are ideally measured in settings where this is available. In addition to CVD risk assessment, advice about diet and lifestyle, and more active treatment measures are needed. This is usually done by your doctor (GP) or by occupational health services at your place of work.
The main points that should be covered in CVD risk assessment are outlined in the box on page 62.

Home cholesterol testing kits and pharmacy testing are not usually accompanied by assessment of other risk factors and on their own may not be helpful. If you suspect that your cholesterol levels are high, it is important to see your GP.

How is blood cholesterol measured?

Your doctor or nurse will usually take a blood sample from a vein and send it to an accredited laboratory for analysis. Blood levels of total cholesterol are not affected by a recent meal and you would not have to fast overnight for a simple cholesterol measurement.

Your doctor may want to check all your blood lipids at the same time (full blood lipid profile), to assess high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Triglycerides are affected by a recent meal and you would therefore be asked to fast overnight before the test. Some portable machines (desk-top analysers) sample the blood from a fingerprick; they can measure lipids and are available in some general practices. If they are used, the results are known during your visit so your coronary risk can be assessed on the spot. Appropriate advice can then be given immediately rather than waiting a few days for information from a laboratory.

CVD risk assessment

In addition to taking a blood sample to measure your blood cholesterol levels your doctor will need to note the following:

Gender
Weight and height
Personal medical history (diabetes, hypertension, previous heart attack, angina)
Family history of early CVD or a blood lipid disorder
Smoking habits
Alcohol intake
Diet and exercise patterns
Blood pressure measurement
For men, if you are of south Asian origin

When should HDL-cholesterol be measured?

Quite often, your doctor will first get your blood tested for your total cholesterol level – the sum total of all the cholesterol-containing particles in your circulation including LDL- and HDL-cholesterol. If this is satisfactory, no further investigations are required other than to advise a repeat measurement after a few years, just to check whether things have changed.

If your total cholesterol is high, then your HDL-cholesterol is measured as part of a full lipid profile.

This is necessary to find out as much as possible about your lipid abnormality. The average HDL-cholesterol levels in blood are 1.3 mmol/l in men and 1.5 mmol/l in women – this difference is probably the result of differences in the sex hormones.

Your total cholesterol level may be high as a result of a high level of HDL-cholesterol (greater than 2 mmol/l), in which case you are fortunate in that your risk of CVD is not increased. Your CVD risk is increased if your high total cholesterol level is caused by a low HDL-cholesterol concentration (that is, your LDL is high).

Risk calculators for CVD allow for this by expressing the risk from cholesterol as a ratio of total cholesterol to HDL-cholesterol. For example, someone with a total cholesterol level of 8.1 mmol/l and an HDL of 2.1 mmol/l has a total cholesterol:HDL ratio of 8.1/2.1 = 3.8. A total cholesterol:HDL ratio above 6 is associated with increased risk of CVD.

I don’t understand why my cholesterol level has changed

If you have your cholesterol measured regularly, it is quite common to find that the level has changed unexpectedly, without any difference in diet or lifestyle, or changes in therapy. The most probable reason is that, as with all laboratory tests, there is variability in the measurement that cannot be eliminated. Some of this is the result of the measurement process itself (analytical variability) and some is the result of factors inherent in all of us (biological variability).

Analytical variability

The variation in cholesterol measurement in most accredited laboratories is small, between 1 and 2 per cent. For someone with a cholesterol level of 6.0 mmol/l, such variability would lead to the reading varying from 5.9 to 6.1 mmol/l should no other factor have changed. There is an international programme to ensure that the cholesterol level measured in one accredited laboratory is comparable to one from a second laboratory. Cholesterol levels measured using desk-top analysers are less precise than laboratory measurements and therefore a greater analytical variation results from their use.

Biological variability

Biological variability causes bigger changes than analytical variability, and cholesterol levels can vary by up to 8 per cent within an individual. A total cholesterol level of 6.0 mmol/l could vary between 5.5 and 6.5 mmol/l as a result of this variability. Biological variability can result from a number of factors. These are outlined in the box on the previous page.

Biological variability in cholesterol measurement

Variation in taking the blood sample

For instance, prolonged application of a tourniquet. Blood is taken from a vein after compressing the arm with a tourniquet to make the vein prominent, thus making it easier to insert the needle. If it is difficult to find a vein, the tourniquet is applied for longer than usual and this can lead to apparently higher cholesterol levels because water temporarily filters out of the veins as a result of the pressure.

Physiological variation

Age and gender can affect it. Blood cholesterol levels increase with age, although the pattern of this increase is different in men and women. For men, the average blood cholesterol level rises until the age of 50 years when it starts falling slightly. Levels are relatively constant in women until they reach menopause when they increase to levels higher than those seen in men.

Season

Some seasonal changes in cholesterol levels occur, with values around 3 per cent higher in winter than in summer. The reasons for this are not completely clear, but diet seems to be partly responsible.

Menstrual cycle

Levels vary by as much as 9 per cent during the menstrual cycle, the highest values being seen in the first half of the cycle. This cyclical variation is consistent with the known effects of oestrogens on fat metabolism.

Pregnancy

Cholesterol levels rise quite significantly during pregnancy, again as a result of hormonal changes.

Lifestyle changes (diet, exercise, alcohol, coffee)
The effect of diet and related lifestyle factors on cholesterol levels is considered later.

Illness

For example, infection, surgery, heart attack. Any illness can affect cholesterol levels. A heart attack leads to a fall in the blood total cholesterol concentration within 24 hours, the effect lasting several weeks. The reason for this is thought to be stress; this also explains the falls that occur after surgery and major trauma. Even relatively mild illnesses, such as viral infections, can lead to reductions in blood cholesterol levels of up to 15 per cent.

Malignancy

If a patient has any form of cancer, the blood cholesterol level usually falls. This is probably because tumours grow in an uncontrolled manner and have increased requirements for the building blocks of cells, which include cholesterol.

Medicines

Some drugs given for other purposes affect cholesterol and other blood fat levels. These are discussed later.

KEY POINTS

Screening everybody for hypercholesterolaemia is not cost-effective
Cholesterol should be measured as a part of overall CVD risk assessment
Cholesterol levels are quite variable within an individual