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Endothelial dysfunction occurs in children with two genetic hyperlipidemias: improvement with antioxidant vitamin
1Department of Pediatrics, University of California at San Francisco 94143-0130, USA.
Insights
Children with familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCH) show impaired vascular relaxation. Antioxidant vitamins improved this endothelial dysfunction, suggesting oxidized lipoproteins contribute to vasoregulation issues in pediatric hyperlipidemia.
Area of Science:
- Pediatric Cardiology
- Vascular Biology
- Nutritional Science
Background:
- Genetic hyperlipidemias, such as familial hypercholesterolemia (FH) and familial combined hyperlipoproteinemia (FCH), are associated with increased cardiovascular risk.
- Endothelial dysfunction, a precursor to atherosclerosis, may be present even in childhood in these conditions.
- The role of oxidative stress in pediatric hyperlipidemia-related endothelial dysfunction requires further investigation.
Purpose of the Study:
- To evaluate endothelium-dependent vasodilation in children diagnosed with FH and FCH.
- To determine the impact of antioxidant vitamin supplementation on endothelial function in this pediatric population.
- To explore the potential contribution of reactive oxygen species to impaired vasoregulation in hyperlipidemic children.
Main Methods:
- Vascular reactivity was assessed using high-resolution two-dimensional ultrasonography of the brachial artery.
- The study included 45 participants aged 6-21 years: 18 with FH, 15 with FCH, and 12 healthy controls.
- A subset of 11 children received 6 weeks of antioxidant therapy (tocopherol and ascorbic acid) followed by repeat vascular assessments.
Main Results:
- Children with FH and FCH exhibited significantly impaired endothelium-dependent vasodilation compared to control subjects (p < 0.001).
- Brachial artery dilation during reactive hyperemia was markedly reduced in both hyperlipidemia groups.
- Antioxidant vitamin supplementation led to a significant improvement in vascular reactivity (mean percent dilation increased from 2.8% to 9.1%, p < 0.001).
Conclusions:
- Endothelial-dependent vasoregulation is impaired in children with both familial hypercholesterolemia and familial combined hyperlipoproteinemia.
- Supplementation with antioxidant vitamins effectively improved vascular reactivity in these children.
- These findings suggest that reactive oxygen species, potentially from oxidized lipoproteins, play a significant role in the endothelial dysfunction observed in pediatric hyperlipidemia.
Objective:
To measure endothelium-dependent vascular relaxation in children with two genetic hyperlipidemias and to assess the effect of antioxidant vitamins on endothelial dysfunction.
Study Design:
Vascular reactivity in the brachial artery was measured in 45 individuals between 6 and 21 years of age (18 with familial hypercholesterolemia [FH], 15 with familial combined hyperlipoproteinemia [FCH], 12 control subjects) with the use of high-resolution two-dimensional ultrasonography. Follow-up studies were done for 11 children after 6 weeks of treatment with tocopherol (400 IU twice a day) and ascorbic acid (500 mg twice a day).
Results:
The mean percent change in diameter during reactive hyperemia was 2.1 +/- 2.2 (SD) and 2.7 +/- 4.4, in FH and FCH, respectively, compared with 12. +/- 4.9 among control subjects (p < 0.001 in each case). The mean percent dilation was significantly increased (2.8 +/- 1.6 to 9.1 +/- 2.3) (p < 0.001) after antioxidant therapy.
Conclusions:
Impaired endothelium-dependent vasoregulation occurs in children with FCH as well as in those with FH. The improvement in vascular reactivity observed during supplementation with antioxidant vitamins suggests that reactive oxygen species derived from oxidized lipoproteins may be responsible for the impairment of vasoregulation in subjects with hyperlipidemia.