Should we dump the metabolic syndrome? No

The Metabolic Syndrome has been a useful construct in clinical practice as well as a valuable model to understand the interactions of diverse CV risk factors. However the increasing importance of the circulatory system in particular the role of the endothelium, in both connecting and controlling organ function, has underlined the limitations of the Metabolic Syndrome definition.

Several epidemiologic evidence demonstrates that the cluster of the risk factors that has been involved in the metabolic syndrome is a part of a larger cluster of interacting risk factors. We have recently proposed “Circulatory Syndrome� as an attempt to refine the Metabolic Syndrome concept by the addition of recently documented markers of CV disease including renal impairment, microalbuminuria, arterial stiffness, ventricular dysfunction and anaemia to the previously known factors: hypertension, dyslipidemia and abnormal glucose metabolism; all of which are easily measured in clinical practice. These markers interact with each other as well as with other factors such as aging, obesity, physical inactivity, diet and smoking. The final common pathways of inflammation, oxidative stress and hypercoagulability thereby lead to endothelial damage and eventually CV disease. Circulatory syndrome is a cluster of risk markers with synergic effects. The proposed syndrome consists of eight major components, as follows [in the metabolic, arterial, renal, cardiac (“MARC�) order]:  Abnormal glucose metabolism  Dyslipidemia  Hypertension  Arterial stiffness  Microalbuminuria  Renal impairment  Anaemia  Left ventricular dysfunction

All of these “markers� occur on a background of oxidative stress, inflammation, hypercoagulability and endotheliopathy (underlying factors) and can be accelerated by factors such as aging, obesity, smoking and physical inactivity (predisposing factors). Furthermore they can be simply and non-invasively assessed in outpatient clinical settings. While the mechanisms underlying the circulatory syndrome are poorly understood, it must be strongly stated that vascular-endothelial pathways link all and are of pathological significance. Activation of the renin-angiotensin system, insulin resistance and increased sympathetic activation are all by -products of the underlying pathogenic process. Since these markers represent the extent of the underlying disease process, they could also manifest as risk factors for other components and thereby enhance their development. Considering the interrelationships, the final outcome in this model can be considered to be CV events, stroke or renal failure; all of which are associated with general circulatory health. Consequently the condition of the circulatory system and these markers is directly related to the mortality rate.

Consideration of this syndrome in clinical practice is expected to facilitate more effective prevention, early diagnosis and timely multidisciplinary treatment of diabetes consequences including renal and cardiovascular complications. Nevertheless, the Circulatory Syndrome, like its predecessor the metabolic syndrome, is only a small step toward a better understanding of these complex and as yet poorly understood markers of disease.

Competing interests: None declared