Vascular endothelial function in children with familial hypercholesterolemia

Impaired endothelial function is detectable in patients with disease associated with vascular complications, such as familial hypercholesterolemia (FH). Impaired endothelial function, assessed as flow mediated dilation (FMD) of the brachial artery, can predict future cardiovascular disease (CVD). In the present study we evaluate whether children with FH are characterized by an impairment of endothelial function and if there are differences between children with and without familial CVD.Fifteen heterozygous FH children (10 girls and 5 boys) age 9.31±3.39 yr., were enrolled in the study. In all subjects FH diagnosis was made by family history, clinical and laboratory findings, and it was confirmed by detection of a mutation in the LDL receptor gene. Vascular function of conduit arteries was assessed by measurement of endothelium-dependent vasodilation of the brachial artery using high-sensibility ultrasound system. FMD was expressed as percentage change of diameter following reactive hyperemia from baseline.Plasma total cholesterol and low-density lipoprotein levels were above the 95th percentile for age and gender (329.9±47.5 and 257.0±36.7 mg/dl, respectively). Only in 1 out of 15 children FMD impairment was demonstrated (FMD <7%; mean FMD 16.0±6.6%). Moreover, no difference in FMD between FH children with versus without CVD in the family history was revealed (13.5±6.78 and 20.1±4.78%, respectively; P=0.19). A significant correlation between FMD and chronological age of children was found (r=-0.75; P=0.03).Our data suggest that FH children have an endothelial function comparable to matched control children reported in other studies. We demonstrate that in childhood the degree of FMD is not already associated with the presence of a family history for CVD. However, the negative correlation between FMD and chronological age suggests a progressive damage of endothelial function that apparently appears in later life. Further studies are required to understand if there are factors able to delay the beginning of endothelial dysfunction.