Adopting a whole-body composition (i.e. examining also the independent contribution of muscle mass in addition to body fat) rather than a body fat/fat distribution-only model has revealed that also appendicular muscle mass may be an independent beneficial determinant of arterial stiffness, particularly though not confined to the elderly [19, 46, 49, 52–55]. Currently, there is a great concern about the cardiometabolic consequences of the increasing prevalence of (central) obesity and sarcopenia (i.e. the degenerative loss of skeletal muscle mass and strength) associated with ageing, especially when occurring in combination – i.e. sarcopenic obesity [56]. How decreases in lean mass may affect arterial stiffness is not clear as the evidence so far has been mainly derived from cross-sectional studies [19, 46, 52–55]. It is possible that the relationship is not causal in the sense that higher muscle mass may simply reflect higher (lifelong) physical activity and/or less sedentary habits, better nutrient intake status and/or better glucose uptake/insulin sensitivity, all of which protect against arterial stiffness [57–61]. Alternatively, arterial stiffness may promote sarcopenia by reducing limb blood flow and inducing rarefaction and dysfunction in the microcirculation, thereby affecting muscle contraction and ultimately leading to muscle mass rarefaction. This hypothesis was supported by a recent prospective study from the Health, Aging and Body Composition Study, showing that older individuals with higher cfPWV at baseline had poorer levels of leg lean mass and sarcopenic index at baseline and over a 6-year follow-up period, independently of age, BMI, BP, diabetes, physical activity, smoking, total fat mass, low-grade inflammation, peripheral artery disease and CHD status [62]. Further longitudinal and intervention studies are needed to clarify the role of muscle mass on arterial stiffening (or vice versa), if any. Nevertheless, the existence of a link between muscle mass and arterial stiffness retains relevant clinical implications because it stresses the need to carefully monitor and secure that weight-loss interventions do not occur at the expense of muscle mass, particularly among the elderly.

Increased arterial stiffness has been consistently reported in individuals with the MetS or with increasing clustered load or number of traits of the MetS (reviewed in [7]). Like for (central) fatness, a major force underlying the MetS risk factor clustering, such adverse arterial changes have been shown across all ages [63, 64], including young children and adolescents, with [65] or without overt obesity [12, 66], and young [67–71] and older adults [72], including those treated [73] or untreated for hypertension [74, 75]. The increased arterial stiffness in the MetS thus seems to be caused by subtle metabolic abnormalities that characterise prediabetic states but not necessarily fully developed diabetes. In addition, the recent findings from the Cardiovascular Risk in Young Finns Study showing higher levels of arterial stiffness among young adults who had the MetS during youth but also of arterial stiffness reduced to levels similar to those who had never had the MetS throughout the life course among those who, by adulthood, recovered from the MetS [76], support the potential reversibility of the adverse effects of the MetS if prevented/targeted early in life.

Confirming the suggestions derived from cross-sectional observations showing that the increases in arterial stiffness with advancing age were accentuated in the presence of the MetS [68, 64], recent prospective cohort studies have shown that individuals with the MetS not only have higher arterial stiffness at baseline but also display steeper increases in arterial stiffness with ageing as compared with those without the MetS [70, 77–80]. In addition, analyses of the impact of changes in MetS status among young [80, 81] and middle-aged [82] adults showed that those with incident and persistent MetS over the course of time displayed the steepest increases in arterial stiffness as compared with their peers who remained MetS-free throughout. Importantly, increases in arterial stiffness with ageing among those who recovered from the MetS tended to be somewhat less steep than those with persistent MetS [80] or even comparable to those who remained MetS-free throughout [82, 81]. An important observation in one of these longitudinal studies was that the MetS-related increase in carotid stiffness seemed to have preceded structural and local haemodynamic changes consistent with maladaptive (outward) carotid remodelling, an important process that may explain the increase risk of stroke in individuals with the MetS [80]. Taken together, the longitudinal data reviewed above [70, 76–82] demonstrate accelerated arterial stiffening and maladaptive remodelling, which may explain, at least in part, the increased CVD risk in individuals with the MetS [7]. These findings also emphasise the importance of primary prevention given the observed reversibility of the adverse impact of MetS on arterial structural and functional properties among those individuals who recovered from the MetS.

The adverse association of the critical axis (central) obesity – MetS with arterial stiffness raises important questions about the potential underlying molecular processes. These may include some of the effects central obesity and related insulin resistance are known to exert at the vascular wall level, for instance, through inflammatory reactions, endothelial dysfunction and sympathetic activation [34, 32, 85]. These abnormalities are interrelated and affect vascular tone and stimulate vascular smooth muscle cell proliferation. In addition, changes in the type or structure of elastin and/or collagen in the arterial wall due to hyperglycaemia, particularly the formation of cross-links through nonenzymatic glycosylation of proteins that generate advanced glycation end products, could constitute another mechanism [7]. Several of these putative mediators are thus likely to account for the obesity- or MetS-related increases in arterial stiffness, but currently we have only fragments of insight among a likely large set of players involved [5]. Teasing apart their individual contribution and/or identification of predominant operative pathways may provide key information for tailored interventions aiming at the treatment of arterial stiffening and related cardiovascular sequelae [6]. A comprehensive analysis of these issues in the context of representative prospective cohort studies or RCTs is still lacking and thus most warranted.

In this chapter, recent epidemiological evidence pertaining to the role of (central) obesity and the MetS on arterial stiffness was reviewed. Reinforced by recent prospective data, there is convincing evidence that these interrelated risk factors increase arterial stiffness, a mechanism that may explain the associated higher CVD risk. However, there is still relatively few data on (1) the molecular basis of greater arterial stiffness associated with these risk factors, (2) the prognostic significance of arterial stiffness indices in individuals with these risk factors and (3) the extent to which intervention on these risk factors improves cardiovascular outcome through beneficial impact on arterial stiffness. Given the high and increasing prevalence of obesity and the MetS, these questions constitute an important research agenda.