Endothelial activation, inflammation and premature atherosclerosis in children with familial dyslipidemia.
OBJECTIVE
Prospective studies demonstrated an increased cardiovascular risk in subjects with high levels of either the endothelial-platelet activation marker P-selectin or high-sensitivity C-reactive protein (hs-CRP). Both children with heterozygous familial hypercholesterolemia (FH) and those with familial combined hyperlipidemia (FCHL) are prone to premature atherosclerosis. Our objective was to investigate in children with either FH or FCHL whether P-selectin and hs-CRP contribute to carotid intima-media thickness (IMT), along with increased plasma lipid levels.


METHODS
Carotid IMT, serum lipids and soluble P-selectin and hs-CRP levels were measured in 88 children (mean age 10.5+/-4.3 years) including 44 dyslipidemic children (25 with FH and 19 with FCHL) and 44 non-dyslipidemic controls.


RESULTS
Carotid IMT was significantly higher among dyslipidemic than in control children (0.46+/-0.06mm vs 0.43+/-0.06mm, p=0.003) and serum P-selectin levels as well [129(50-254)ng/mL vs 50(24.5-130)ng/mL, p<0.001]. FH but not FCHL children had higher hs-CRP levels than controls [0.7(0.01-6.9)mg/L vs 0.3(0.1-1.2)mg/L, p=0.006]. In the entire sample of dyslipidemic children, carotid IMT was positively associated with soluble P-selectin levels (rho=0.30, p=0.049), but not with hs-CRP. The association between P-selectin and carotid IMT was independent from confounders, including plasma lipid levels.


CONCLUSIONS
Endothelial-platelet activation, more than low-grade systemic inflammation, correlates with premature atherosclerosis among children with familial dyslipidemia, this association being independent from plasma lipid levels.
Guardamagna
Ornella
O
Department of Pediatrics, University of Torino, Torino, Italy. ornella.guardamagna@unito.it
Abello
Francesca
F
Saracco
Paola
P
Baracco
Viviana
V
Rolfo
Elio
E
Pirro
Matteo
M
D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000276:immunology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000000981:diagnostic imaging / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography
D015415:Biomarkers; D018836:Inflammation Mediators; D008055:Lipids; D019007:P-Selectin; D002097:C-Reactive Protein