The Metabolic Syndrome: is it an important medical issue in your opinion (and specialty)? Why?

Marja-Riitta Taskinen
Helsinki University Central Hospital, Helsinki, Finland

Recent studies have provided convincing evidence that the Metabolic Syndrome is a serious health hazard worldwide and constitutes a major challenge for healthcare professionals. Clinicians are confronting a rise in obesity of epidemic proportions as a result of sedentary, affluent lifestyles. The rapid increase in the prevalence of the Metabolic Syndrome portends an equally daunting increase in both type 2 diabetes and cardiovascular disease (CVD). Recent prospective studies have confirmed that the Metabolic Syndrome predicts the development of type 2 diabetes and an increased CVD risk emphasising the clinical significance of the Metabolic Syndrome. These harmful consequences of the Metabolic Syndrome represent a substantial economic burden at population level worldwide. Consequently, the identification and treatment of the Metabolic Syndrome become critical in the prevention of both type 2 diabetes and CVD.

The typical subject is characterised by abdominal obesity and overweight defined by a large waist circumference or body mass index, dyslipidaemia, a varying degree of glucose intolerance, and elevated blood pressure. These components of the Metabolic Syndrome are commonly associated with insulin-resistance. However, the cluster of metabolic abnormalities is growing rapidly. New components include low-grade inflammation, a pro-thrombotic state, endothelial dysfunction, and non-alcoholic fatty liver disease (NAFLD). The formal criteria by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and by WHO provide tools to identify high-risk subjects in clinical practice. The benefits of the NCEP definition are that it can be applied without an oral glucose tolerance test and includes simple markers commonly assessed in clinical practice. However, it should be recognised that the clinical spectrum of the Metabolic Syndrome is variable and influenced by gender, ethnicity, and genetic susceptibility. A universally accepted definition with validated population-based cut-off values is needed for clinical and epidemiological studies, but the ATP III criteria provide a straight forward approach to identify subjects with the Metabolic Syndrome in every day clinical practice.

Dyslipidaemia linked to the Metabolic Syndrome is characterised by an elevation of serum triglycerides, an exaggerated post-prandial lipidaemia, low HDL-cholesterol levels, and small dense LDL-particles. This cluster of lipid abnormalities is considered highly atherogenic. These components are not isolated abnormalities but metabolically closely linked to each other. Significantly, these abnormalities of lipoprotein metabolism are related to insulin-resistance, which seems to be the driving force, even in the absence of visceral fat accumulation. Recent observations suggest that the atherogenic lipid profile is a very early component of the Metabolic Syndrome. Notably, the malignant nature of dys-lipidaemia is not completely revealed by the lipid measures used in clinical practice.

Atherogenic dyslipidaemia is a logical target for lipid management. Fibrates have a beneficial action on each feature of dyslipidaemia. Hence, fibrates seem to be the optimal drug for correcting dyslipidaemia in patients with the Metabolic Syndrome who have low LDL-cholesterol. In fact, fibrate studies have shown that treatment with fibrates is highly effective in reducing coronary event rates in people with such features of the Metabolic Syndrome as overweight, elevated baseline triglycerides, or low baseline HDL-cholesterol. Unfortunately, in clinical practice the management of these subjects is commonly neglected despite their increased risk of CVD. In the future, a better understanding of the complex mechanism linking dys-lipidaemia and insulin-resistance will hopefully provide novel targets for pharmacological therapy, in order to correct dyslipidaemia and relieve the burden of metabolic syndrome-linked cardiovascular disease.