The present study shows for the first time that PWV and SBPc can differentiate between obese and non-obese children. In addition, we identified the predictors of increased PWV, SBPc, and PPc in this population.
PWV has been suggested as a noninvasive measurement to assess vascular health, especially in pediatric patients at risk for cardiovascular disease . Corroborating the studies by Koopman et al. and Urbina et al. [28, 29], the present study demonstrated a significantly higher PWV in the obese group. Contrary to these findings, Charakida et al., Lurb et al., and Dangardt et al. [30–32] found significantly lower PWV in obese children compared to the control group. According to Dangardt et al., a lower PWV may reflect general vasodilation.
ROC curve analysis demonstrated the discriminatory strength of PWV in distinguishing obese from non-obese children, with maximum sensitivity and specificity at 4.09 m/s. Several PWV reference equations have been created for children and adolescents considered healthy [10, 27, 33]. Reusz et al.  evaluated PWV in 1,008 children and adolescents (6–20 years old) and observed that PWV was positively correlated with age, height, weight, and blood pressure, and negatively correlated with heart rate, but only age, height, and blood pressure remained as the main PWV predictors in multiple regression analysis. Fischer et al.  also evaluated children and adolescents (5–19.6 years old) and observed that PWV was positively correlated with age, height, weight, SBP, mean arterial pressure, and sex. Multiple regression analysis identified age, sex, and mean arterial pressure as independent predictors of PWV, explaining 42% of the overall variability. In addition to predictors such as age, height, and weight, Thurn et al.  also reported an association of PWV with BMI and body surface area, paternal hypertension, maternal obesity, and passive smoking. The present study analyzed associated factors and predictors of increased PWV in obese children. PWV correlated directly with age, BMI, WHtR, body fat percentage, and vascular pressures (SBPc, SBPp, PPc, and PPp). AIx@75 and augmentation pressure, indirect indices of arterial stiffness and direct of reflection wave are also positively associated with PWV. Amplification pressure represents an increased SBPc due to increased wave reflection reaching the heart. Unlike previous studies, in the present study only vascular variables (SBPp, PPp, and PPc) remained in the multiple regression model and explained 98% of the increased PWV. SBPp had the greatest effect (highest standardized coefficient) on PWV. In a systematic review and meta-analysis, Hudson et al.  reported that PWV varied in obese children according to the evaluated site, with increased stiffness in the carotid arteries and aorta. These findings may have important clinical implications as target organs are more exposed to central rather than peripheral blood pressure .
In the present study, peripheral and central vascular pressures were higher in obese children. Stabouli et al.  demonstrated that arterial stiffness is higher in overweight and obese children in the presence of arterial hypertension. These authors reported that peripheral and central blood pressures, BMI, and hemodynamic parameters including stroke volume, cardiac output, total peripheral vascular resistance, and cardiac index were all associated with increased 24-hour PWV. However, in multiple regression analysis, only 24-hour peripheral and central blood pressures and cardiac index were independent predictors of 24-hour PWV. Li et al.  presented a possible explanation for the correlation between hypertension, arterial stiffness, and childhood obesity. According to the authors, sympathetic activation leads to increased left ventricular ejection, leading to increased PPc and PWV. Increased heart rate and stroke volume can lead to increased cardiac output, which leads to increased mean arterial pressure. In the present study, obese children had higher cardiac output and stroke volume values without heart rate changes.
We also evaluated the SBPs ROC curve, which showed that the maximum SBPc sensitivity and specificity to differentiate obese and non-obese children occurred at 86.17 mmHg and area under the curve (AUC) of 0.744. Measured at the aortic root, the SBPc is the result of the interaction between the stroke volume ejected by the left ventricle, the damping capacity of the great arteries, and the pressure waves propagated and reflected in the arterial tree . The behavior of the aorta as a blood reservoir prevents an overly increased SBPc and a sharp flow drop during diastole, due to elastic recoil favoring coronary artery filling at this stage . In the present study, SBPc was significantly higher in the group of obese children than in the control group. Age, BMI, and body fat percentage showed a direct and moderate correlation with SBPc. SBPp and PWV showed direct and high-intensity correlations with SBPc in the group of obese children. Peluso et al.  reported that children and adolescents with high SBPc presented a higher association with vascular changes (increased carotid intima-media thickness and arterial stiffness) compared with high SBPp. Increased SBPc in children and adolescents can be explained by an increased amplitude of incident and reflected wave components associated with an increased stroke volume and/or aortic arterial stiffness . In line with these data, in the present study the obese group had increased stroke volume.
Corroborating the study by Castro et al., in our study the PPc was higher in obese than in normal-weight children. PPp, augmentation pressure, PWV, AIx@75, and reflection coefficient were factors associated with this increase. In multiple regression analysis, augmentation pressure, PPp, and reflection coefficient explained 87.3% of the increased PPc. As expected, PPA was negatively correlated with PPc. Garcia-Espinosa et al. also reported increased PPc in obese children, in addition to increased PWV and SBPc associated with BMI.
In this study, we compared hemodynamic parameters between obese and control group. Despite the stroke volume and cardiac output being significantly higher in the obese group, when these data were normalized by the body surface, the cardiac index was significantly lower in the obese group compared to the control group. Our results corroborate those found by Castro et al. . These authors observed that stroke volume and cardiac output were significantly higher in obese children and adolescents aged 5–15 years. On the other hand, the cardiac index was significantly lower in this population. According to Castro et al., the higher stroke volume may be related to a state of hyperdynamic circulation. Cardiac index changes are associated with clinically critical alterations of the cardiac functioning of obese people as a result of body composition variations, and low cardiac index is related to poor tissue perfusion.
Obesity represents a chronic hypoxic state associated with decreased nitric oxide (NO) bioavailability. These decreased NO levels lead to the increased production of hypoxia-inducible factor-1α (HIF-1α), which is involved in the regulation of several metabolic pathway genes, including pro-inflammatory adipokines, endothelial NO synthase (eNOS), and insulin signaling components . Our results suggest that the low cardiac index observed in obese patients can cause vascular tissue hypoxia, and this decreased NO bioavailability may contribute to inducing greater expression of pro-inflammatory cytokines. The metabolic and inflammatory pathogenesis caused by low cardiac index may be related to vascular and cardiac dysfunctions observed in obese patients.
Some limitations of our analyses must be taken into account. First, it is possible that some variable that has not been evaluated may be a predictor of arterial stiffness indices. Second, this study was limited to a single center, reducing the external applicability of the data. Third, the data were collected in the period of pandemic COVID-19, leading a sedentary lifestyle, eating habits and psychological problems which may have influenced arterial stiffness measures.
In conclusion, this is the first study to show that PWV and SBPc can discriminate obese from non-obese children. In addition, we have highlighted the associated factors and predictors of arterial stiffness indices: PWV, PPc and SBPc, in obese children. These results show that, in addition to an increased BMI, a simple, rapid, and noninvasive measurement of arterial stiffness adds prognostic information on cardiovascular risk.