Circulating calcification inhibitors are associated with arterial damage in pediatric patients with primary hypertension

Abstract

Background: Circulating calcification inhibitors: fetuin A (FA) and osteoprotegerin (OPG) together with soluble ligand of receptor activator of nuclear factor kappa-B (sRANKL) have been linked to vascular calcifications and arterial damage. This study aimed to evaluate relationships between FA, OPG, sRANKL, and arterial damage in children with primary hypertension (PH). Methods: In this cross-sectional single-center study, calcification inhibitors (FA, OPG, sRANKL) levels were measured in blood samples of 60 children with PH (median age 15.8, IQR: [14.5–16.8] years) and 20 age-matched healthy volunteers. In each participant, peripheral and central blood pressure evaluation (BP) and ambulatory BP monitoring (ABPM) were performed. Arterial damage was measured using common carotid artery intima media thickness (cIMT), pulse wave velocity (PWV), augmentation index (AIx75HR), and local arterial stiffness (ECHO-tracking—ET) analysis. Results: Children with PH had significantly higher peripheral and central BP, BP in ABPM, thicker cIMT, higher PWV, and AIx75HR. FA was significantly lower in patients with PH compared to healthy peers without differences in OPG, sRANKL, and OPG/sRANKL and OPG/FA ratios. In children with PH, FA level correlated negatively with cIMT Z-score and ET AIx; sRANKL level correlated negatively with ABPM systolic blood pressure (SBP), SBP load, diastolic BP load, and AIx75HR; OPG/sRANKL ratio correlated positively with SBP load, while OPG/FA ratio correlated positively with ET AIx. In multivariate analysis, FA was a significant determinant of cIMT (mm) and cIMT Z-score. Conclusions: This study reveals that in children with primary hypertension, arterial damage is related to lower fetuin A concentrations. Graphical abstract: [Figure not available: see fulltext.].