Inflammatory and thrombotic processes are associated with vascular dysfunction in children with familial hypercholesterolemia.
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.
Charakida
Marietta
M
Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece. charakidadoc@hotmail.com
Tousoulis
Dimitris
D
Skoumas
Ioannis
I
Pitsavos
Christos
C
Vasiliadou
Carmen
C
Stefanadi
Elli
E
Antoniades
Charalambos
C
Latsios
George
G
Siasos
Gerasimos
G
Stefanadis
Christodoulos
C
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
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