Background

Endothelial activation is an early sign of atherosclerosis detectable in childhood and predictive of vascular disease in adults. Limitations in current measures have made it challenging to assess endothelial health in youth. Circulating endothelial cells (CEC) are novel, early biomarkers that characterize endothelial health. Our goal was to examine CEC number and activation across a spectrum of adiposity groups in children and adolescents.

Methods

Children and adolescents (N=271) between 8-20 years old with normal weight (BMI% < 85th; N=114), obesity (BMI%≥ 95th to < 120% of the 95th; N=63), and severe obesity (BMI% ≥ 120% of the 95th; N=94) were recruited from the Minneapolis/St. Paul metropolitan area. CEC number per mL of whole blood was determined using immunohistochemical examination of buffy coat smears, and activated CEC (% Vascular Cell Adhesion Molecule-1 expression) was assessed using immunofluorescent staining. Generalized linear models were used to compare CEC number and activation across BMI classes, adjusting for Tanner stage, sex, and race.

Results

There were no significant differences in CEC number across BMI groups (p>0.05 all). Youth with severe obesity expressed higher levels of CEC activation (β =8.3% [95% CI:1.09, 15.57]; p=0.024) compared to youth with normal weight. CEC number was higher with greater total body fat (β =0.018 [95% CI:0.003, 0.034]; p=0.02) and systolic blood pressure percentile (β =0.007 [95% CI:0, 0.013]; p=0.035). CEC activation was higher with elevated visceral fat (β =0.006% [95% CI:0,0.011]; p=0.034).

Conclusions

CEC activation, but not CEC number, was elevated in the context of severe obesity and excess visceral adiposity. Higher CEC number was associated with higher total body fat and higher systolic blood pressure percentile. Findings suggest that the endothelium in youth with severe obesity is abnormally activated, perhaps reflecting accelerated atherosclerosis. Thus, CEC may be a useful risk-prediction biomarker in children and adolescents.