Background: Evidence suggests that children with familial hypercholesterolemia (FH) have endothelial dysfunction. Inflammatory and haemostatic abnormalities are associated with advanced atherosclerosis and increased cardiovascular events. However, it is unknown whether these abnormalities present in FH children and contribute to their vascular dysfunction.
Methods and results: We studied 38 children with FH (19 males, 19 females aged 14.8+/-0.9 years mean+/-S.E.) and 41 healthy children (controls; 22 males, 19 females aged 15.4+/-0.7 years). Endothelium-dependent reactive hyperemia (RH%) and endothelium-independent nitrate hyperemia dilatation (NH%) were measured by strain gauge plethysmography. Inflammatory and haemostatic parameters were assessed by ELISA. RH% and NH% were significantly reduced in FH compared to controls (91.3+/-9.3% vs. 120.4+/-10.6% and 53.6+/-3.8% vs. 74.5+/-7.4%, p<0.05 for both). Total cholesterol and lipoprotein (a) were increased in FH children compared to controls (282.3+/-8.8 mg/dl vs. 163.8+/-4.6 mg/dl and 11.0[4.6, 30.7]mg/dl vs. 5.24[2.63, 11.0]mg/dl median [IQR] respectively; p<0.001 for both). Intercellular cell adhesion molecule (ICAM-1) and interleukin 1 beta (IL-1 beta) serum levels were increased in FH compared to controls (p<0.05 and <0.001, respectively). Plasminogen activator inhibitor 1 (PAI-1) levels were also higher in FH children (p<0.001). Multivariate analysis revealed that reactive hyperemia was independently associated with nitrate-dependent reactive hyperemia (beta=0.597(0.199), p<0.01), PAI-1(beta=-6.78(2.65), p<0.05), log IL-1 beta (beta=-102.8 (30.2), p<0.01), age (beta=-5.06 (2.35), p<0.05) and FH status (beta=-25.2(10.6), p<0.05) (R(2) for the model: 0.63, p=0.001).
Conclusions: Inflammatory and haemostatic abnormalities are present in FH children and contribute to the endothelial dysfunction observed in these children.