Obesity and vascular stiffness: when body fat has an adverse impact on arterial dynamics

There are a number of reasons explaining why investigators and physicians are interested in assessing the structural and functional vascular alterations characterizing human obesity. First, alterations in arterial dynamics and morphology may promote and accelerate the cascade of events leading to the appearance and progression of atherosclerotic plaque [1]. Second, a reduction in arterial distensibility may represent a key factor involved in the pathophysiology of the cardiac structural alterations (i.e. left ventricular hypertrophy) complicating the obese state [2]. Third, the vascular alterations characterizing this condition may promote blood pressure elevation and thus the development of the hypertensive state, which is frequently detectable in overweight individuals [3]. Fourth, obese subjects are exposed to coronary artery disease to a greater extent than are individuals of normal weight, with the incidence of myocardial infarction and angina being two- to four-fold greater in the former versus the latter group [4,5]. Finally, other frequent complications of the obese state, such as ischaemic cerebrovascular disease and renal failure, have also been suggested to share a similar pathophysiological hallmark (i.e. vascular dysfunction leading to atherosclerotic plaque) [6–9]. In the present issue of the journal, Zebekakis et al. [10] add to the data that have already been acquired regarding the relationship between being overweight, obesity and the vascular system [10]. The authors report the results of a cross-sectional study, employing a pulsed ultrasound wall tracking device, in which pulse wave velocity, cross-sectional compliance, arterial distensibility and diameter were measured at the level of the carotid, brachial and femoral arteries in a large group of subjects (age range 10–86 years). There are three main study findings. First, obesity exerts adverse effects on the arterial system at any age. Second, the vascular alterations induced by an increased body mass index appear to be of early appearance, with their presence already being detectable in the second decade of life. Finally, the relationships between body mass index and arterial dynamics do not appear to be homogeneously distributed along the vascular tree, with muscular arteries being more markedly affected than elastic arteries. Some of the study results will be discussed further here, especially the implications of the study findings and the issues that remain unsolved. Body fat distribution and arterial stiffness In the population of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), Zebekakis et al. [10] make use of body mass index (i.e. a parameter which, although easily obtainable, represents an approximate and somewhat aspecific marker of body fatness) to definine normal weight, overweight and obese status. This study limitation is recognized by the authors, who properly emphasize the importance of approaches based on dual X-ray absorptiometry or computer tomography to more precisely quantify the body fat depot. However, there is no doubt that a simpler approach for characterizing body adiposity would be one based on the measurement of waist and hip circumferences. The use of this approach in the study by Zebekakis et al. [10] would have allowed them to examine whether and to what extent central (or abdominal) obesity has an adverse impact on vascular function of a greater magnitude than peripheral obesity. The background for this question is represented by the evidence that central obesity is accompanied by a sympathetic activation and an insulin resistance state greater in magnitude than that displayed by peripheral obesity [11,12]. Because both sympathetic activity and insulin sensitivity are important determinants of arterial dynamics and arterial wall thickness [1,13–15], it is likely that central adiposity is characterized by a more pronounced arterial impairment than peripheral obesity. This possibility is supported by the results of the Amsterdam Growth and Health Longitudinal Study [16], which also provided evidence that augmented subcutaneous trunk fat is linked to a greater arterial stiffness in patients with metabolic syndrome [17]. It is also, although indirectly, supported by the finding that an increased waist circumference is associated with a reduced peripheral wave reflection [18]. Pathophysiological mechanisms As depicted schematically in Figure 1, a number of factors may participate in the impairment of arterial distensibility reported in the obese individuals. As previously mentioned, it is likely that adrenergic (sympathetic overactivity) and metabolic (insulin resistance and hyperleptinemia) variables play a major role. However, the contribution of other factors, such as endothelial dysfunction and alterations in the haemocoagulative process, as well as the proatherogenic profile of the obese individuals, should also be taken into account. It is thus likely that the arterial dysfunction characterizing an individual as being markedly overweight represents a multifactorial alteration involving neural, metabolic and haemodynamic variables. Reflex mechanisms may also participate because a chemoreflex dysfunction, associated with the phenomenon known as sleep apnoea syndrome, has been reported to accompany increased arterial stiffness in specific populations of children [19].Fig. 1A further intriguing result of their study is represented by the heterogeneous behaviour of muscular and elastic arteries in the obese state. However, the phenomenon does not appear to be specific for this condition because a dissociation of the mechanical properties of the carotid and femoral arteries has been demonstrated in experimental animal models of hypertension [20]. Interestingly, the dissociation appears to be in some way linked to the heterogeneity of the sympathetic function in different cardiovascular districts, and this finding has also been reported in physiological and pathological conditions [21–23]. Therapeutic implications The study by Zebekakis et al. [10] leaves room for future investigations addressing a number of intriguing questions. For example, are the observed vascular alterations reversible by appropriate treatment? Are non-pharmacological interventions capable of improving arterial function? Does the hypothesized improvement in vascular function homogeneously affect muscular and elastic arteries? What is the relative weight of the metabolic, neuroadrenergic and haemodynamic factors in the arterial function improvement possibly elicited by weight loss? Some of these questions appear to be adressed, at least in part, by already published data. Weight loss has been shown to improve arterial distensibility, insulin sensitivity and sympathetic function in obese individuals [24,25]. These results, although obtained in studies of small size, once again underline the close relationships between vascular function, metabolic factors and neuroadrenergic mechanisms.