Objective. To study the effect of mutations of genes responsible for the development of familial hypercholesterolemia (FH) and lipid profile on the structural and morphological state of blood vessels based on the intima-media thickness (IMT) of the common carotid artery in children with heterozygous familial hypercholesterolemia.
Material and methods. The study was conducted in the period from 2019 to 2023 and included 214 children aged 2 to 17 years. The comparison group consisted of 107 children. The main group included 107 patients diagnosed with “familial hypercholesterolemia, heterozygous form”, who were divided into 3 groups depending on the phenotype and genotype of the disease: 2 – children with a positive phenotype and with identified mutations associated with FH: LDLR, APOB, PCSK9, LDLRAP1; 3 – children with a positive phenotype, but no identified mutations; 4 – children with a negative phenotype and a positive genotype.
All children underwent clinical and laboratory diagnostics, ultrasound of the neck vessels with an assessment of the IMT of the common carotid artery. Patients of the main group underwent next-generation sequencing using a gene panel: LDLR, APOB, PCSK9, LDLRAP1.
Results. In patients of groups 2 and 3, statistically significant increase in total cholesterol (TC), low-density lipoproteins (LDL) and IMT values was revealed relative to the comparison group. IMT values were significantly higher in children of group 2 relative to group 3, while lipid indices did not differ. In group 4, LDL and IMT values were significantly lower than similar indices in group 2.
The most common LDLR variants were: c.986G>A, c.906C>G, c.1187-10G>A. The increase in IMT was significantly higher in patients with c.1187-10G>A relative to c.906C>G.
Conclusion. Patients with FH were characterized by increased levels of TC, LDL and thickened IMC in contrast to healthy peers. In children with identified mutations in genes associated with FH, signs of vascular remodeling were established from the age of 8 years, compared with children with phenotypic FH.
The obtained results emphasize the importance of early diagnosis, including genetic, and continuous monitoring of the vascular wall condition of patients with FH to prevent progression.
