The soluble receptor for advanced glycation end products is independently associated with systolic blood pressure values and hypertension in children

Background and aim: The advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) axis is a pro-inflammatory pathway promoting endothelial dysfunction and vascular remodelling. The soluble RAGE form (sRAGE), by blocking circulating AGE, protects against AGE-induced detrimental effects. We investigated the role of sRAGE as a marker of high blood pressure and hypertension risk in children. Methods and results: sRAGE was quantified in 284 children/adolescents (mean age (SD) 11.1 (2.5); 52.1 % male) referred for high-normal blood pressure (systolic and/or diastolic values ≥ 90th, but both <95th percentile) or hypertension (systolic and/or diastolic blood pressure ≥95th percentile) and/or other cardiovascular risk factors (excess weight, dyslipidaemia and insulin resistance). In 22.2 % of the sample, systolic and/or diastolic blood pressure values were above the 90th percentile. The prevalence of excess weight (overweight/obesity), central obesity (waist-to-height-ratio >50%), and insulin resistance (HOMA-index ≥90th percentile) was high (82.7 %, 70.8 %, and 70.5 %, respectively). Few children had altered LDL cholesterol, triglyceride, and HDL cholesterol values (15.7 %, 15.4 %, and 13.6 %, respectively). The lowest sRAGE tertile was associated with the highest risk of having hypertension (p = 0.028), obesity (p < 0.001), central obesity (p = 0.007), and insulin resistance (p < 0.001). sRAGE levels were inversely associated with systolic blood pressure (p < 0.01) and BMI (p = 0.022) z-scores and waist-to-height-ratio (p = 0.001). sRAGE values were inversely associated with the presence of hypertension (p = 0.036) and obesity (p = 0.038). Conclusions: The independent relationship between sRAGE, systolic blood pressure, and hypertension in children suggests that the AGE-RAGE axis may be altered early in life, and that sRAGE could be a compelling marker for pediatric cardiovascular risk stratification.