European Heart Journal Advance Access originally published online on February 27, 2008
European Heart Journal 2008 29(6):693-694; doi:10.1093/eurheartj/ehm642
Vascular consequences of metabolic syndrome in early life
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
Corresponding author. Tel. +31 88 755 5555, Fax +31 30 250 5488, Email: F.L.J.Visseren{at}umcutrecht.nl
This editorial refers to ‘Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study’
by N. Mattsson et al. on page 784
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
The presence of the metabolic syndrome, a clustering of metabolic risk factors closely associated with abdominal obesity, is accompanied by an increased risk for the development of cardiovascular diseases and type 2 diabetes mellitus. It is now generally accepted that insulin resistance together with abdominal obesity are key features in the pathophysiology of the metabolic syndrome. As a result of total body energy dysbalance, adipocytes in abdominal adipose tissue enlarge and start producing chemotactic factors, such as monocyte chemoattractant protein-1 (MCP-1) attracting monocytes/macrophages. This dysfunctional abdominal adipose tissue produces large quantities of free fatty acids, adipokines, and inflammatory cytokines, e.g. interleukin-6 (IL-6) and tumour necrosis factor-
(TNF-), that are secreted into the systemic circulation and contribute to pathophysiological processes leading to cardiovascular diseases and type 2 diabetes mellitus. Abdominal adipose tissue has a unique anatomical relationship with the liver. Cytokines produced by abdominal adipose tissue are released into the portal circulation, influencing liver production of haemostatic and proinflammatory proteins and cytokines [C-reactive protein (CRP), IL-6], further increasing systemic inflammation and activating haemostasis.
The cardiovascular risk associated with the metabolic syndrome has been shown in cohorts of middle-aged patients with1 and without2 clinically manifest vascular diseases. The study of Mattson et al.3 extends our knowledge of the vascular risk of metabolic syndrome to young adults. In their study, using different definitions of metabolic syndrome, it was shown that the presence of metabolic syndrome in early life is already associated with increased carotid intima-media thickness (cIMT) and decreased carotid artery compliance, established measures of subclinical atherosclerosis. Compared with young adults without metabolic syndrome, the subjects with metabolic syndrome were abdominally obese and, as a result, had higher blood pressure and triglycerides and lower high-density lipoprotein (HDL)-cholesterol plasma concentrations. In a recent study by Baker et al., it was shown that overweight in childhood was associated with an increased cardiovascular risk in later life.4 It is conceivable that overweight children have a high chance of developing metabolic syndrome in young adulthood, accompanied by subclinical atherosclerosis,3 and develop clinical manifestations of atherosclerosis in later life. The implications of these studies are that treatment of metabolic syndrome may need to be started in early life by reducing weight and increasing physical activity. Ideally, development of overweight is prevented by starting at a young age. This is not only the domain of clinical medicine but more a matter for society.
Although the case for metabolic syndrome is building up, there are several issues that still need to be addressed. First, there are several definitions for the ‘diagnosis’ of metabolic syndrome. In general, all definitions are based on similar clinical criteria but differ in the cut-off values used. In the study of Mattson et al., there was no difference between the different definitions of metabolic syndrome as to the presence of subclinical atherosclerosis.3 In studies with clinical vascular end-points, the metabolic syndrome based on criteria defined by ATPIII5 was associated with the highest risk for developing (recurrent) cardiovascular diseases.1,6 Although fairly arbitrary cut-off values have been used in the ATPIII-defined metabolic syndrome, this definition seems to work very well in identifying patients at high risk for developing cardiovascular diseases. Modification of diagnostic criteria for metabolic syndrome by advanced modelling using continuous variables rather than dichotomized criteria may further increase the prognostic abilities of the ATPIII definition. Critics point towards the lack of additive prognostic information for the syndrome compared with the individual components of metabolic syndrome. From a prognostic standpoint that may be the case, but from an aetiological point of view metabolic syndrome adds important information as to the cause of the clustering of important cardiovascular risk factors. The presence of metabolic syndrome therefore guides the choice for treatment strategies, namely weight reduction and increasing physical activity, instead of (pharmacological) treatment of individual vascular risk factors (high triglycerides, low HDL-cholesterol, elevated blood pressure, and elevated glucose).
The second issue is that the pathophysiology of metabolic syndrome is not fully clear. Insulin resistance, considered to be a key feature, is not present in all patients with metabolic syndrome. Not all obese subjects are insulin resistant, and lean patients may also become insulin resistant. The developing concept of adipocyte dysfunction may resolve some of these issues. Besides abdominal adiposity, insulin resistance has other causes including genetics, intra-uterine growth retardation, and sympathetic tone. Although obesity-related insulin resistance is most prominent in metabolic syndrome, it is likely that other mechanisms are also involved, leading to different phenotypes of metabolic syndrome.
Thirdly, the clinical applicability of metabolic syndrome needs to be further explored. Patients with clinical manifestations of vascular diseases are all regarded to be at high risk for developing a new vascular event or death. It is likely that there is a wide range of vascular risk in this group of patients. Currently, there is no risk algorithm for estimating the cardiovascular risk in these patients. Metabolic syndrome may be a tool, easy to use in clinical practice, to identify patients with established vascular diseases at the highest risk for a new vascular event or death profiting the most from intensive risk factor treatment.7 According to American guidelines, patients with established vascular diseases diagnosed with metabolic syndrome are considered to be at very high risk for developing new vascular events.8 Lower treatment targets for low-density lipoprotein (LDL)-cholesterol are recommended for these patients. In the recently issued European Guidelines on cardiovascular disease prevention, the place for metabolic syndrome is in risk estimation.9 The presence of components of the metabolic syndrome indicates a higher risk than indicated by the SCORE risk algorithm. A higher estimated cardiovascular risk may influence the decision to start (pharmacological) treatment of individual risk factors and/or combined treatment of the clustered risk factors by weight reduction and increasing physical activity.
Although several issues need to be resolved, metabolic syndrome has been shown to be associated with an increased cardiovascular risk in various groups of subjects and patients. The results of recent studies3,4 sent a strong health message to the public: cardiovascular disease prevention starts at a young age by prevention and/or treatment of obesity!
Conflict of interest: none declared.
Footnotes
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
doi:10.1093/eurheartj/ehm576 
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- Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study
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EHJ 2008 29: 784-791.[Abstract] [FREE Full Text]
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