Carotid Extra-Media Thickness in Children: Relationships With Cardiometabolic Risk Factors and Endothelial Function

Background: Emerging evidence suggests that structural adventitial modifications andperivascular adipose tissue (PAT) may have a role in early atherogenesis. In a cohortof children and adolescents, we explored (1) the association of carotid extra-mediathickness (cEMT), an ultrasoundmeasure whosemain determinants are arterial adventitiaand PAT, with obesity and its cardiometabolic complications; and (2) the interplaybetween cEMT and endothelial function.Methods: The study participants included 286 youths (age, 6-16 years; 154 boys,and 132 girls). Anthropometric and laboratory parameters, liver ultrasound, vascularstructure measures [cEMT and carotid intima-media thickness (cIMT)], endothelialfunction [brachial artery flow-mediated dilation (FMD)] were obtained in all subjects.Non-alcoholic fatty liver disease (NAFLD) was diagnosed in the presence of hepaticfat on ultrasonography, in the absence of other causes of liver disease. Diagnosisof metabolic syndrome (MetS) was established on the basis of three or more ofthe following cardiovascular disease (CVD) risk variables: abdominal obesity, hightriglycerides, low high-density lipoprotein cholesterol, elevated blood pressure (BP), andimpaired fasting glucose.Results: cEMT demonstrated significant associations with body-mass index (BMI)and waist circumference (WC), BP, insulin resistance, NAFLD, and inflammation. Noassociation was found between cEMT and lipid values, and between cEMT and MetS. Astepwise multivariate linear regression analysis indicated that WC (b coefficient, 0.35; P <0.0001) was the only determinant of cEMT, independently of other major cardiometabolicrisk factors. Further adjustment for cIMT did not significantly alter this association. FMDwas correlated to age, Tanner stage, total and abdominal obesity, BP, NAFLD, and cEMT.The association between FMD and cEMT was independent of age, sex, Tanner stage,WC, and BMI (b coefficient, -0.14; P = 0.027). After controlling for CVD risk factorsand basal brachial artery diameter, cEMT remained associated with FMD (b coefficient,-0.11; P = 0.049).Conclusions: In youths, cEMT is associated with abdominal fat, a well-established bodyfat depot with important implications for cardiovascular diseases. Furthermore, cEMT isrelated to FMD, suggesting that arterial adventitia and PAT may be involved in the earlychanges in endothelial function.