Paediatric Obesity and Cardiovascular Dysfunction: Searching for Early Markers of Damage

Background Childhood obesity causes a wide range of severe complications, increasing the risk of premature morbidity and mortality and raising public-health concerns. In addition, obese children are more prone to become obese adults, with higher risk of cardiovascular diseases (CVD). A cluster of CVD risk factors has been identified in children as young as 5 years of age. Furthermore, among adolescents and young adults, the presence of CVD risk factors correlates with asymptomatic coronary atherosclerosis. Childhood obesity has been related to an impaired cardiac structure and function.

Atherogenesis and arterial wall damage begin during childhood and, there is evolving evidence that clinical indicators of atherosclerosis such as carotid artery intima-media thickness (CIMT), arterial stiffness, and endothelial function are altered in obese children. In addition, little is known on the potential association between early cardiovascular alterations and metabolic abnormalities in obese children. Metabolic syndrome (MetS) is a cluster of features, which includes dyslipidemia, hypertension, and visceral obesity, conferring with a higher risk of CVD and type 2 diabetes. Few studies investigated the association of MetS with cardiovascular changes during childhood. Hyperuricemia has been recognized as a risk factor for CVD in adults with a negative impact on longevity. However, data in pediatric age are still lacking and the association between hyperuricaemia and cardiovascular abnormalities in obese children is still unknown. Furthermore, obesity is a state of chronic low-level inflammation and increased oxidative stress. Oxidative stress plays an important role in the pathogenesis of cardiovascular alterations by either triggering or exacerbating the biochemical processes accompanying endothelial dysfunction.

Moreover, adipose tissue acts as a secretory gland, releasing hormones and adipokines with pro- or anti-inflammatory activity. Clinical studies of obese adults have observed an association between plasma levels of adipokines and markers of inflammation and/or oxidative stress. Among various adipokines, adiponectin seems to play an important role. Indeed, in contrast to other adipokines which are up-regulated in obesity, secretion of adiponectin is markedly reduced in obese subjects. Second, adiponectin seems to exert mainly positive activities on metabolism, vascular tone and inflammatory reaction. Consequently, in contrast to other adipokines, which circulate in excess in obese subjects and exert unbeneficial effects when chronically elevated, deficiency rather than excess of adiponectin is implicated in obesity-associated complications. Finally, serum concentration of adiponectin is very high in comparison to other hormones and cytokines, which suggests that apart from binding to specific high-affinity receptors, this protein may also have some less specific low affinity targets. Adiponectin has been associated with endothelial improvement and vascular protection through the activation of an endothelial isoform of nitric oxide (eNOS)-related signalling and with anti-inflammatory properties and antiatherogenic effects. Thus, an impaired production of adipokines may be a key mechanism linking obesity with inflammation and oxidative stress. The understanding of these complex mechanisms and the identification of possible early markers of cardiovascular damage are therefore necessary in order to establish preventive and therapeutic measures in childhood and to decrease cardiovascular morbidity and mortality in adulthood.

Subjects and methods This study is a single-centre longitudinal study. Subjects were recruited at Division of Pediatrics, Department of Health Sciences, University of Piedmont Orientale, Novara (Italy). The study protocol was in accordance with the ethical guidelines of the Declaration of Helsinki and has been approved by the local Ethical Committee. Informed written consent was obtained from all subjects and their parents before study. The investigators consecutively enrolled 80 Caucasian obese (OB) children and adolescents, aged 6 to 16 years, and 20 normal weight, age and sex matched controls (NW). NW patients were evaluated only at baseline while OB subjects will be evaluated at baseline and after 6 (T6) and 12 months (T12) of an isocaloric Mediterranean balanced diet plus aerobic training.

Assessment in both groups (OB and NW)