Clustering of Metabolic Syndrome Traits Is Associated With Maladaptive Carotid Remodeling and Stiffening

Abstract

Abstract-Maladaptive arterial remodeling may constitute a mechanism underlying the risk of stroke in individuals with the metabolic syndrome (MetS), but evidence supporting this contention derives from cross-sectional studies only. We, therefore, investigated, in apparently healthy adults, whether changes in MetS status between the ages of 36 and 42 years (never [nϭ207, reference group], incident [nϭ31], recovery [nϭ23], and persistent [nϭ32]) were associated with changes in carotid interadventitial diameter, lumen diameter, intima-media thickness, circumferential wall tension and stress, and Young's elastic modulus. All data analyses were adjusted for sex, height, and (changes in) age, lifestyle variables, low-density lipoprotein cholesterol, and use of antihypertensive medication. At baseline and as compared with the reference group, individuals with persistent MetS had significantly higher interadventitial diameter, circumferential wall tension, circumferential wall stress, and Young's elastic modulus but not intima-media thickness. In the course of follow-up, these individuals (versus reference group) displayed significantly steeper increases in intima-media thickness (0.011 versus 0.005 mm/y), which were accompanied by significantly steeper increases in interadventitial diameter (0.077 versus 0.032 mm/y) and lumen diameter (0.055 versus 0.023 mm/y) but not circumferential wall stress, which decreased (Ϫ0.34 versus 0.12 kPa/y). These findings suggest that increases in intima-media thickness in young adults with the MetS may primarily reflect an adaptive mechanism that attempts to restore local hemodynamic conditions to an equilibrium rather than atherosclerosis, per se. However, carotid adaptations did not restore circumferential wall stress to levels comparable with those of the reference group, and, therefore, outward remodeling was maladaptive. Importantly, individuals who recovered from the MetS restored carotid properties to levels comparable to the reference group, emphasizing the potential for reversibility. 1 However, the underlying pathophysiology of the MetS-stroke relationship remains poorly understood.Numerous studies have linked the MetS to increased carotid intima-media thickness (IMT) 2 and or stiffness, 3 and both higher levels of carotid IMT and stiffness predict incident cardiovascular disease, in particular, stroke.4,5 Maladaptive arterial remodeling may also constitute a mechanism linking the MetS to increased risk of stroke. Arterial remodeling, that is, the change of structural arterial properties over time in response to hemodynamic and/or metabolic factors operating within the arterial environment, is thought to be an adaptive mechanism aiming at keeping shear stress within certain limits. 6 It is characterized by widening of the interadventitial diameter (IAD) and increases in IMT. This process is considered to be maladaptive when, despite remodeling, circumferential wall tension (CWT) and stress (CWS; also designated as tensile stress) remain elevated. Maladaptive arterial remodeli...

The Relationship between the Blood Pressure Responses to Exercise following Training and Detraining Periods

“…They found that the progression of prehypertension to hypertension positively correlated with resting SBP (p = 0.002) and the MetS (p = 0.009) among 98 men and women 30 to 63 years with the MetS and prehypertension over 3 years. Ferriera et al [27] found apparently healthy individuals between 36 and 42 years with prehypertension at baseline and that had persistent MetS over 6 years exhibited the maladaptive arterial remodeling changes that were related to changes in SBP and DBP. However, these maladaptive arterial changes were reversed in individuals with prehypertension who recovered from the MetS.…”

Aging, Arterial Stiffness, and Hypertension

“…A longitudinal study showed that clustering of metabolic syndrome is associated with maladaptive carotid remodeling and stiffening. 17 Notably, a recovery from the metabolic syndrome restored carotid properties to normal levels, indicating that metabolic syndrome-induced arterial remodeling and stiffening is reversible. 17 In an animal model of diet-induced obesity, normalization of the metabolic state by weight loss leads to a return of arterial stiffness and high blood pressure to normal, 14 emphasizing that metabolic syndrome is a potential interventional target for arterial stiffening and hypertension.…”

“…17 Notably, a recovery from the metabolic syndrome restored carotid properties to normal levels, indicating that metabolic syndrome-induced arterial remodeling and stiffening is reversible. 17 In an animal model of diet-induced obesity, normalization of the metabolic state by weight loss leads to a return of arterial stiffness and high blood pressure to normal, 14 emphasizing that metabolic syndrome is a potential interventional target for arterial stiffening and hypertension. Hyperglycemia and dyslipidemia cause vascular endothelial dysfunction and oxidative stress which activates extracellular matrix metalloproteinases (MMPs) leading to vascular remodeling and arterial stiffening.…”

Arterial Function in Cardio-Metabolic Diseases: From the Microcirculation to the Large Conduits

“…5,8 A recent longitudinal study confirmed that the transition from being healthy to having MetS coincides with an increase in cIMT (0.011 vs. 0.005 mm/year), and lumen diameter (0.055 vs. 0.023 mm/year). 9 The remodeling of the large arteries in response to disease is largely due to an increase in circumferential wall stress and flow-mediated shear stress. 10 Thus, the arteries undergo either changes in lumen size and/ or arterial wall thickness to maintain tensile wall stress within ideal limits (i.e., described by the Law of Laplace).…”