Lipid profile peculiarities and matrix Gla protein concentration in Ukrainian pediatric patients with heterozygous familial hypercholesterolemia

Abstract

Atherosclerotic changes in the vascular walls begin early in childhood, especially in association with familial hypercholesterolemia (FH). The process may be subclinical, which nevertheless requires therapeutic and preventive measures. Purpose - to evaluate baseline lipid profiles, the thickness of carotid intima-media complexes, blood pressure indices and the association with concentration changes of dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP) as a marker of subclinical arterial lesions in different age groups of pediatric patients with FH. Materials and methods. Children with heterozygous FH (n=15), stratified by age and sex, were included in the study. The control group consisted of healthy peers (n=21). Blood samples were analyzed to determine levels of total (TC), low-density (LDL-C), very-low-density (VLDL-C), high-density (HDL-C), remnant (rC) and non-high-density (non-HDL-C) cholesterol, triglycerides (TG), apolipoproteins A1 (apoA1) and B (apoB), lipoprotein (a), and dp-uc MGP. The intima-media complex thickness of the common carotid artery and blood pressure were measured in all study subjects. The obtained data were processed using the accepted methods of medical statistics and SAS® OnDemand for Academics. Results. Lipid profile changes in pediatric patients with FH were characterized by high levels of LDL-C, non-HDL-C and lipoprotein (a) in the 5-9 years age group; in the 10-14 years age group - high levels of LDL-C, TG, rC, non-HDL-C and lipoprotein (a); in the 15-18 years age group - high levels of LDL-C, TG, non-HDL-C and lipoprotein (a). At the same time, the most marked dyslipidemia changes were evident in children aged 10-14 years in the FH group. apoA1 levels were significantly decreased in all FH children. Elevated levels of lipoprotein (a) (>30 mg/dL) in FH children were found in all age groups, suggesting that elevated lipoprotein (a) levels can be used as a factor for cardiovascular risk stratification. Dp-uc MGP levels were significantly elevated in all age groups of FH children compared to healthy peers. Conclusions. A lipid profile examination is necessary to diagnose FH in children, along with family health history and cascade screening. As atherosclerotic changes at 5-18 years of age remain subclinical, and the instrumental tests available in routine medical practice are not sensitive enough to detect them, therefore, preventive or therapeutic measures cannot be initiated promptly. The evaluation of circulating matrix Gla protein in pediatric patients with FH can be used as a marker of vascular wall calcification, which may allow early preventive measures against microcalcification to be developed. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.