Early statin therapy restores endothelial function in children with familial hypercholesterolemia

Jongh, Saskia de; Lilien, Marc R.; Roodt, Jos Op ‘t; Stroes, Erik S.G.; Bakker, Henk D.; Kastelein, John J.P.

doi:10.1016/s0735-1097(02)02593-7

Cited by 308 publications

(189 citation statements)

References 29 publications

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“…These results are similar to findings reported by other authors (De Jongh et al, 2003;Rodenburg et al, 2004), although significant reductions in LDL cholesterol values were also described in these studies. However, larger, less dense LDL particles appeared after the sterol-enriched diet in this study.…”

Section: Discussionsupporting

confidence: 93%

Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia

et al. 2007

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Background: Familial hypercholesterolemia (FH) is associated with a high risk of coronary heart disease. Pharmacological treatment and diet are both essential for the management of FH. Foods rich in plant sterols (PS) may play an important role in the treatment of patients with these disorders. Objective: To test the effect of the intake of PS on low-density lipoprotein (LDL) concentration, endothelial function (EF) and LDL particle size in 30 patients with FH. Design: Randomized and crossover dietary intervention study. Setting: Tertiary outpatient care. Subjects: Thirty-eight were recruited, but only 30 were subjected to four low-fat dietary intervention periods, each of 4 weeks. Methods: Each intervention had a different content of cholesterol (o150 or 300 mg/day) and sitosterol (o1 or 2 g/day). Lipid response, EF and LDL particle size were analysed after the intervention. Results: Plasma sitosterol/cholesterol ratio was higher during both plant sterol-rich periods than during the low plant sterols periods. Basal sitosterol concentrations predicted the LDL-cholesterol response during the intake of plant sterol-enriched diets. The change in LDL-cholesterol was significantly greater in subjects in the upper and intermediate tertiles of basal plasma sitosterol concentrations (À2178 mg/dl, P ¼ 0.03; À1977 mg/dl, P ¼ 0.04, respectively) than in subjects in the lower tertile (875 mg/dl) when they changed from a low cholesterol diet to a low cholesterol plus plant sterol diet. Conclusion: Our study demonstrates that basal sitosterol values can predict hypolipidemic response in patients with FH.

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Section: Discussionsupporting

confidence: 93%

Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia

et al. 2007

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“…18,20,23,[26][27][28] As can be seen in our results, nine of the adolescents were obese or dyslipidemic. This fact supports the figure of 6.7% (the 10th percentile in our study) endothelium-dependent vascular dilatation as the lower limit of normality in adolescents.…”

Section: Variablessupporting

confidence: 79%

“…However, all of these had patient samples that differed from ours, in particular in terms of age groups. 6,[18][19][20][21][22][23][24][25][26][27][28] While the studies found in the literature employed similar methodology for endothelial function assessment, the employed patient samples which, in addition to including individuals from wider age ranges than the age range of the adolescents in our study, also differ by not having exclusion criteria that could demonstrate that the patient sample was free from metabolic or functional bias.…”

Section: Discussionmentioning

confidence: 99%

Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial

Andrade¹,

Carvalhaes²,

Taddei³

et al. 2005

J. Pediatr. (Rio J.)

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Objective: To define standards for normal endothelial function in adolescents by high-resolution ultrasound measurement of endothelium-dependent vascular dilatation.Methods: This was a cross-sectional, descriptive, observational study and part of the thematic project Clinical Study of Growth, Behavior, Arterial Hypertension, Obesity and Oral Health (ECCCHOS) that was developed by the Discipline of Nutrition at the Universidade Federal de São Paulo. Thirty-one adolescents, eight male and 23 female, with no risk factors for systemic arterial hypertension were selected from 1,420 high-school students. The students were daytime pupils at a school in the southeastern district of the city of São Paulo, the capital of São Paulo state, located in the Southeast region of Brazil. All results are presented in the form of means with standard deviations and percentiles.Results: For male students, endothelium-dependant dilation 90 seconds after the cuff was released was 20.9±6,7% [mean ±1 standard deviation] with a 10th percentile of 12.5 and for females these figures were 18.8±12.9% with a 10th percentile of 6.6%. Values for the whole group of subjects were 19.3±11.7% and 6.7%, respectively.Conclusion: Endothelium-dependant vascular dilation of 6.7%, after 90 seconds, which corresponds to the 10th percentile, can be considered the lower limit of normality for this age group. Knowledge of this limit is important for the diagnosis of endothelium dysfunction that appears before cardiovascular disease.J Pediatr (Rio J). 2005;81(5):395-9: Adolescents, endothelium, and ultrasound.

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“…Interventional trials are warranted to test if this is the case and also to prove that a reduction of hsCRP levels lowers cardiovascular risk. In this context, statin therapy was shown to restore endothelial function in children with familial hypercholesterolemia 56 and has also demonstrated to be safe. 57 In conclusion, our cross-sectional data demonstrate that obese children have elevated blood levels of the inflammation markers hsCRP and hsIL-6 and of E-selectin, a specific endothelial activation marker.…”

Section: Discussionmentioning

confidence: 99%

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

Kapiotis

Holzer

Schaller

et al. 2006

ATVB

193

149

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Background-Obesity is generally accepted as a risk factor for premature atherosclerosis. Subclinical inflammation as quantified by blood levels of C-reactive protein (CRP) contributes to the development and progression of atherosclerosis. We hypothesized that inflammation in obese children is related to functional and early morphological vascular changes. Methods and Results-Blood levels of high sensitivity (hs) CRP, hsIL-6, the soluble intercellular adhesion molecule1 (ICAM-1), vascular cell adhesion molecule (VCAM)-1, and E-selectin were measured in 145 severely obese (body mass index [BMI], 32.2Ϯ5.8 kg/m 2 ) and 54 lean (BMI, 18.9Ϯ3.2 kg/m 2 ) children 12Ϯ4 years old. Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measured by high-resolution ultrasound as markers of early vascular changes were assessed in 92 (77 obese and 15 lean) and 59 (50 obese and 9 lean) children, respectively. Obese children had significantly higher levels of hsCRP, hsIL-6, and E-selectin than healthy controls (4.1Ϯ4.8 versus 0.9Ϯ1.5 mg/L, PϽ0.001 for hsCRP; 1.99Ϯ1.30 versus 1.42Ϯ1.01 pg/mL, Pϭ0.05 for hsIL-6; and 78Ϯ38 versus 59Ϯ29 ng/mL, Pϭ0.01 for E-selectin). There were no differences in the levels of ICAM-1 and VCAM-1 between groups. Obese children had lower peak FMD response (7.70Ϯ6.14 versus 11.06Ϯ3.07%, Pϭ0.006) and increased IMT (0.37Ϯ0.04 versus 0.34Ϯ0.03 mm, Pϭ0.03) compared with controls. Morbidly obese children (nϭ14, BMI 44.1Ϯ3.9 kg/m 2 ) had highest levels of hsCRP (8.7Ϯ0.7 mg/L), hsIL-6 (3.32Ϯ1.1 pg/mL), and E-selectin (83Ϯ40 ng/mL). Conclusions-A proinflammatory state is detectable in obese children, which is accompanied by impaired vascular endothelial function and early structural changes of arteries, even in young subjects at risk. It remains to be determined whether high hsCRP in obese children predicts cardiovascular events.

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Early statin therapy restores endothelial function in children with familial hypercholesterolemia

Cited by 308 publications

References 29 publications

Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia

Basal plasma concentrations of plant sterols can predict LDL-C response to sitosterol in patients with familial hypercholesterolemia

Função endotelial de adolescentes normotensos sem fatores de risco para hipertensão arterial

A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes

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