Endothelial dysfunction, but not structural atherosclerosis, is evident early in children with heterozygous familial hypercholesterolemia.

Children with heterozygous familial hypercholesterolemia (heFH) are prone to premature atherosclerosis. Vascular endothelial dysfunction may predict increased cardiovascular risk in children with heFH. The aim of this study was to assess for early functional and structural vascular changes in children with heFH. This cross-sectional study included 30 children with heFH (mean age 12 years) and 30 age- and sex-matched controls. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity, and large- and small vessel compliance were measured noninvasively. HeFH children exhibited significantly greater total and LDL cholesterol, apolipoprotein B, and lipoprotein (a) levels (p < 0.05 for all) and lower FMD (6.23 ± 3.88 vs. 9.46 ± 4.54 %, p < 0.004) compared with controls. When children were divided in age subgroups, FMD was found to be significantly decreased in heFH compared with control subjects only in ages >10 years (p < 0.05). However, FMD was found to be similarly impaired in heFH children in all age subgroups (two-way analysis of variance, p = 0.39). No differences in other vascular function indices were found. In heFH patients, but not in controls, FMD was inversely correlated with cIMT (r = -0.378, p = 0.036). In conclusion, endothelial dysfunction occurs early in heFH children indicating an increased risk for premature cardiovascular disease and reflecting probably the need for early initiation of anticholesterolemic treatment. Decreased FMD is detected before structural atherosclerotic changes occur.