Normal Serum Lipid Concentrations & Therapeutic Thresholds

Whereas the average serum concentrations of most substances, for example, sodium or fasting glucose, are much the same in all parts of the world, cholesterol displays considerable variation. In the UK, the median serum cholesterol for a middle-aged man (aged 55-64 years) is 5.8 mmol/L (224 mg/dL) [Primatesta, 2000] and deaths from CHD comprise around 40% of total mortality at this age. In contrast, the average level in middle-aged men in China is 4 mmol/L (155 mg/dL) or less, and CHD accounts for less than 5% of their deaths.

What is normal?

Conventionally, the normal range for a variable in a particular population is chosen to include values between the 2.5 and 97.5 percentiles, or sometimes the 1 and 99 percentile, on the assumption that 19 out of 20 of the population, or 49 out of 50, respectively, are normal. To be rational, the implication in a medical context must also be that those people in the normal range are healthy. In the case of cholesterol, which is clearly linked to CHD, the healthy range must, therefore, be that of a society in which CHD is uncommon, such as China or Japan.

Healthy cholesterol level limits
The above has led the US National Institutes of Health (NIH) and the European Atherosclerosis Society to define healthy limits for serum cholesterol based on the risk of CHD. Thus, an optimal serum cholesterol level is defined as 5.2 mmol/L (200 mg/dL) or less. A level of 5.2-6.2 mmol/L (200-239 mg/dL) is considered to indicate 'borderline high', while values greater than 6.2 mmol/L (>240 mg/dL), which is around the 90th percentile in the USA [Rifkind, 1983], indicate 'high' [Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001]. Targets set jointly by the British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society and British Diabetic Association state that ideally for those patients with CHD or other atherosclerotic disease or at high risk of CHD (>15% over 10 years), total serum cholesterol levels must be reduced to either less than 5 mmol/L (<200 mg/dL) or by 20-25%, whichever is greater.

When should cholesterol-lowering medication be used?

Whether or not to introduce cholesterol-lowering medication does not only depend on the cholesterol levels, but also on the individual patient's cardiovascular risk. People with a history of acute myocardial infarction or angina, or who have other clinically significant atherosclerotic diseases, such as peripheral arterial or cerebrovascular disease, are at a considerably increased risk of myocardial infarction and should generally receive lipid-lowering therapy. So too should those who clearly possess a clinical syndrome associated with dyslipidaemia carrying a high risk of CHD, such as familial hypercholesterolaemia, familial combined hyperlipidaemia, type III hyperlipoproteinaemia or diabetes. For other patients possessing no obvious clinical syndrome to indicate their CHD risk, clinical judgement about whether the level of risk might justify lipid-lowering medication for primary prevention can be assisted by using one of the available methods for calculating CHD risk (see later).

Is treatment of benefit?

In clinical trials with CHD events as end points, significant benefit from statin treatment was evident in people with initial LDL-C levels of 3.0 mmol/L (120 mg/dL), in which therapeutic targets for LDL-C of less than 2.6 mmol/L (<100 mg/dL) were achieved [Athyros, 2002; Heart Protection Study Collaborative Group, 2002; Downs, 1998; Hebert, 1997]. The relative reduction in CHD risk is similar regardless of absolute risk. The likelihood that an individual will benefit from a statin or other lipid-lowering medication is, thus, going to be determined by their absolute risk. Therefore, once the level of risk has been established there is no scientific reason for choosing a different LDL-C threshold for the introduction of lipid-lowering treatment in different patients. Therefore, current recommendations for the level of lowering may not go far enough for some patients. In the Heart Protection Study, patients with serum cholesterol levels as low as 3.5 mmol/L (135 mg/dL) were randomised [Heart Protection Study Collaborative Group, 2002].

Healthy limits for triglycerides
An upper limit of normality for fasting serum triglycerides is often regarded as 2.2 mmol/L (200 mg/dL). This is close to the 90th percentile for men and the 95th percentile for women.

Healthy limits for HDL-C
For serum HDL-C, a lower limit of normality of 0.9 mmol/L (35 mg/dL) is frequently quoted, a value close to the 10th percentile for men and between the 5th and 10th percentile for women.