Hypercholesterolaemia is one of the major causes of atherosclerosis. Although there are many causes, hypercholesterolaemia is the permissive factor that allows other risk factors to operate.1 The incidence of coronary heart disease is usually low where population plasma cholesterol concentrations are low.2 In Britain coronary heart disease is a major cause of mortality, and a recent Department of Health survey suggested that the average plasma cholesterol concentration in the United Kingdom was 5.9 mmol/l, much higher than the 4 mmol/l seen in rural China and Japan, where heart disease is uncommon.3 Many studies before and after the introduction of statins have indicated that reducing the prevalence of hypercholesterolaemia is an important means of decreasing coronary risk.
Cholesterol plays an important role as the precursor for steroid hormones and bile acids and it is essential for the structural integrity of cell membranes. It is transported in the body in lipoproteins. Figure 1⇓ shows the role of cholesterol in lipoprotein metabolism.
Fig 1 The role of cholesterol in the metabolism of lipoprotein. Adapted from Charlton-Menys4
Conventionally the upper limit for laboratory reference ranges is based on the 95th or 90th centile for a healthy population. This does not apply to plasma cholesterol, however, as several studies show that the epidemiological relation between plasma cholesterol and risk of coronary heart disease extends to the lower end of the cholesterol distribution. Although the relation becomes progressively steeper, there is no obvious threshold below which it ceases to exist.5 Therefore, it is more rational to base a desirable or healthy concentration of plasma cholesterol on the value at which coronary risk is considered unacceptably high. Most patients developing coronary heart disease have plasma cholesterol concentrations that are likely to be between the 30th and 90th centile for their population …