title: Inflammatory and thrombotic processes are associated with vascular dysfunction in children with familial hypercholesterolemia.
abstract: 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.
  
  
  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.
authors.affiliation: Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece. charakidadoc@hotmail.com
authors.forename: Marietta
authors.initials: M
authors.lastname: Charakida
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tousoulis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Skoumas
authors.forename: Christos
authors.initials: C
authors.lastname: Pitsavos
authors.forename: Carmen
authors.initials: C
authors.lastname: Vasiliadou
authors.forename: Elli
authors.initials: E
authors.lastname: Stefanadi
authors.forename: Charalambos
authors.initials: C
authors.lastname: Antoniades
authors.forename: George
authors.initials: G
authors.lastname: Latsios
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Siasos
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008074:Lipoproteins / Q000097:blood; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D002784:Cholesterol; D005996:Nitroglycerin