A correlation has been clearly shown between inflammation markers and subclinical atherosclerosis markers in the early stages of atherogenesis in subjects with familial hypercholesterolemia (FH). The aim of this study was to investigate potential inflammation markers in the diagnosis of atherosclerosis in children with FH. A total of 48 dyslipidemic children and 24 healthy age-matched control subjects were taken into study. Inflammation and macrophage activation markers (hsCRP, myeloperoxidase, chitotriosidase, YKL-40, TNF-α, IL-6, IL-18, MMP-1 and MMP-9) and lipid parameters of all patients were measured. Carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) levels were determined. Our data suggested that clinically evidenced (by cIMT and FMD levels) atherosclerosis starts in the early ages in hypercholesterolemic children. Higher cholesterol levels strongly correlated with macrophage activation markers (ChT, YKL-40 and myeloperoxidase). ChT and YKL-40 seem to be the more predictable markers of atherosclerosis even in early ages (<6 years old) than other classical inflammation markers such as hs-CRP, IL-6 and TNF-α.

Background Inflammation and hypercholesterolaemia contribute to atherosclerotic changes which can start in childhood. Children with hyperlipidaemias are at high risk for early coronary atherosclerosis. This study evaluates the relationship between lipoprotein-associated phospholipase A (Lp-PLA), carotid intima-media thickness (CIMT) and flow-mediated dilatation in hypercholesterolaemic dyslipidaemic children. Methods We performed a case-control study consisting of 43 cases, aged 2 to 17 years, and 24 age-matched controls. Fasting blood samples were obtained from both groups for the measurement of a lipid profile (total cholesterol, LDL-C, HDL-C and triglycerides) and Lp-PLA in mass units. The latter was determined with a turbidimetric immunoassay method (PlacTest, DiaDexus Inc.) applied to an automated analyser. CIMT and flow-mediated dilatation measurements were undertaken by a paediatric cardiologist, using high-resolution B-mode ultrasonography. Results Total cholesterol, LDL-C and Lp-PLA concentrations were significantly higher in the cases than in the controls ( p < 0.001 for all three parameters). While CIMT values were also significantly higher in the patients compared to the controls ( P = 0.001), flow-mediated dilatation values were significantly lower ( P = 0.001). We found positive correlations between Lp-PLA and total cholesterol ( r = 0.41, P = 0.001), Lp-PLA and LDL-C ( r = 0.36, P = 0.004), Lp-PLA and CIMT ( r = 0.44, P = 0.019) and LDL-C and CIMT ( r = 0.41, P = 0.032); there were negative correlations between Lp-PLA and flow-mediated dilatation ( r = -0.15, P = 0.045), total cholesterol and flow-mediated dilatation ( r = -0.45, P = 0.017), LDL-C and flow-mediated dilatation ( r = -0.51, P = 0.006) and CIMT and flow-mediated dilatation ( r = -0.45, P = 0.016). Conclusion Lp-PLA concentrations are significantly elevated in hypercholesterolaemic dyslipidaemic children. Given the association of Lp-PLA with markers of atherosclerosis (total cholesterol, LDL-C, CIMT and flow-mediated dilatation), the finding of increased concentrations of Lp-PLA could be used to identify early atherosclerotic changes in hypercholesterolaemic dyslipidaemic children and may inform their clinical management.

Objective: The aim of this study was to determine the parameters of endothelial function and platelet activation in children with familial hypercholesterolemia by measuring plasma homocysteine, asymmetrical dimethyl arginine (ADMA), nitrotyrosine and P-selectin levels. Methods: Thirty-five heterozygous familial hypercholesterolemic patients on statin therapy, 10 homozygous familial hypercholesterolemic patients treated by LDL apheresis and lipid-lowering drugs, and 25 healthy children, all aged between 2 to 16 years were enrolled in this study. Echocardiography was performed and intima-media thickness (IMT), and endotheliumdependent vasodilation parameters were evaluated. LDL apheresis was performed by adsorption method using double-membrane filtration technique. Plasma nitrotyrosine, homocysteine, P-selectin and ADMA levels were determined with an enzyme-linked immunosorbent assay (ELISA) using a commercial kit. Results: Plasma homocysteine (p=0.000), ADMA (p=0.005), nitrotyrosine (p=0.808), p-selectin (p=0.466) levels were lowest in the LDL apheresis group. A positive correlation was detected between homocysteine and intima/media thickness (r=0.334, p=0.043). Showed that LDL apheresis therapy might decrease plasma levels of homocysteine, ADMA, and nitrotyrosine, and might eventually play an important role in the improvement of endothelial dysfunction and platelet activity. Conclusion: Our data showed that at post-LDL apheresis status the homozygous hyperlipidemic children have lower levels of homocysteine, ADMA, and nitrotyrosine, compared with the heterozygous hyperlipidemic children.

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