Abstract 1464: Inflammatory and Thrombotic Processes are Implicated in Vascular Dysfunction in Children With Familial Hypercholesterolemia
Background: Evidence suggests that children with familial hypercholesterolaemia (FH) have endothelial dysfunction. Inflammatory and haemostatic abnormalities are associated with advanced atherosclerosis and increased cardiovascular events. However, it is unknown whether these abnormalities contribute to arterial disease progression in FH children.
Methods: We studied 38 children with FH (FH; 19m, 19f aged 14.8±0.9 years mean±SE) and 41 healthy control children (C; 22m, 19f aged 15.4±0.7years). Endothelium dependent (EDD) and independent (EID) dilatation were measured as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual 0.4 mg nitroglycerin, respectively. Serum levels of tumour necrosis factor alpha (TNF-a), interleukin 1β (IL-1β) vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) were determined using ELISA. Plasma levels of von willebrand factor (vWF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were also determined by ELISA.
Results: EDD and EID were significantly reduced in FH compared to C (91.3±9.3 vs120.4±10.6% and 53.6±3.8 vs 74.5±7.4%, p<0.05 for both). Total cholesterol and lipoprotein (a) were significantly increased in FH children compared to C (282.3±8.8 vs 163.8±4.6mg/dl and 11.0[4.6, 30.7] vs 5.24[2.63, 11.0] mg/dl median [IQR] respectively; p<0.001 for both). Serum ICAM-1and IL-1β levels were significantly increased in FH compared to C children (p<0.05 and p<0.001 respectively). PAI-1 levels were also higher in the FH children (p<0.001). Multivariate analysis (adjusting for cardiovascular risk factors) revealed that EID (β=0.37, p<0.01), PAI-1 (β=−0.24, p<0.07, fibrinogen (β=−0.27, p<0.05) and IL1β (β=−0.29, p<0.05) were the only independent determinants of EDD.
Conclusions: Inflammatory and haemostatic abnormalities are present in FH children by the end of the first decade of life and contribute to the endothelial dysfunction in these children. Early detection of these abnormalities may prove important for risk stratification of these children.