Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia

Atherosclerosis. 2021 Jul:328:38-43. doi: 10.1016/j.atherosclerosis.2021.05.017. Epub 2021 May 27.

Abstract

Background and aims: Patients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients.

Methods: The study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups.

Results: Compared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = -0.54, p = 0.001), high-sensitivity CRP (r = -0.53, p = 0.001), HOMA-IR (r = -0.31, p = 0.01), CA-IMT (r = -0.22, p < 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = -0.022, p < 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001).

Conclusions: Our study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

Keywords: 21-Hydroxylase deficiency; Carotid intimal media thickness; Endothelial dysfunction; Flow-mediated dilation; Inflammation; Neopterin.

MeSH terms

  • Adolescent
  • Adrenal Hyperplasia, Congenital*
  • Brachial Artery / diagnostic imaging
  • Carotid Intima-Media Thickness
  • Child
  • Endothelium, Vascular
  • Female
  • Humans
  • Male
  • Neopterin
  • Tunica Media
  • Vascular Diseases*
  • Vasodilation

Substances

  • Neopterin