Frank Sacks
Harvard School of Public Health; Brigham & Women's Hospital, Harvard Medical School, USA

For many years, it has been recognised that several risk factors for cardiovascular disease cluster together. These factors are low HDL-cholesterol and high triglyceride concentrations, overweight, hyperglycaemia, and high blood pressure.

The Metabolic Syndrome is now accepted as the term to define this condition. The key concept is that these risk factors combine to increase cardiovascular disease, even when they are just slightly abnormal. This is why the definition of the Metabolic Syndrome sets cut-off points for these risk factors that include a large portion of the population.

For example, in the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition, the cut-off point for high triglycerides is >150 mg/dL (approximately 1.7 mmol/L), which is about the average for the population over age 50 years. The cut-off point for low HDL-cholesterol is <40 mg/dL (1 mmol/L) for men and <50 mg/dL (1.3 mmol/L) for women, which includes about 35% of the population. Thus, the definition of Metabolic Syndrome recognises that these lipids continuously increase risk throughout their ranges in the population. Even mild abnormalities in triglyceride and HDL levels, when coexisting with other risk factors of the Metabolic Syndrome, become an important indicator of high risk.

It is very important to recognise that high LDL or high total cholesterol are not components of the Metabolic Syndrome. In fact, LDL is often below average in patients with the Metabolic Syndrome. Thus, physicians must be aware that patients can still have a high risk of cardiovascular disease even if they have low LDL or total cholesterol. In essence, one can conceptualise the Metabolic Syndrome as a "non-LDL" type of risk, and just as important as LDL to recognise and to treat.

The incidence of the Metabolic Syndrome has been increasing throughout Europe and North America, in parallel with an increase in overweight, obesity, and diabetes. Since LDL has been emphasised in treatment guidelines quite effectively, it is now time to turn the attention of clinicians to the Metabolic Syndrome. If this epidemic of overweight and diabetes is not stopped, cardiovascular disease will soon increase, and we will lose the progress we have made in the past 20 years.

The Metabolic Syndrome requires a multi-factorial approach to treatment, since all of its components combine to increase the risk of cardiovascular disease. Firstly, diet and exercise will improve all components by lowering triglycerides, glucose and blood pressure, and raising HDL. In fact, much of the Metabolic Syndrome can be attributed to "over nutrition". Secondly, pharmacological therapy for improving the components of the Metabolic Syndrome should be individualised in each patient.