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Published on: September 1, 2023
Vascular function and risk factors in children with epilepsy: associations with sodium valproate and carbamazepine
Ngaire Keenan1, Lynette G Sadlier1, Esko Wiltshire1
1Department of Paediatrics and Child Health, University of Otago Wellington, P.O. Box 7343, Wellington South, Wellington, New Zealand.
Insights
Children on epilepsy drugs like valproate and carbamazepine show no early vascular changes. Adequate dietary B vitamin intake may prevent risks, negating the need for supplementation in well-nourished populations.
Area of Science:
- Pediatric Neurology
- Cardiovascular Health
- Pharmacology
Background:
- Epilepsy is associated with increased cardiovascular disease risk factors, including lipid abnormalities and elevated homocysteine.
- Antiepileptic drugs (AEDs) may induce B-vitamin deficiencies, potentially contributing to vascular risk.
- Early detection of vascular dysfunction and atherosclerosis can be assessed via flow-mediated dilation (FMD) and intima-media thickness (IMT).
Purpose of the Study:
- To evaluate biochemical cardiovascular risk factors in children with epilepsy treated with AEDs.
- To assess vascular endothelial function and structure in pediatric epilepsy patients.
- To specifically investigate the effects of sodium valproate (VPA) and carbamazepine (CBZ) on vascular health.
Main Methods:
- Recruited 30 children with epilepsy on AEDs and 30 age- and sex-matched controls.
- Measured fasting homocysteine (tHcy), folate, pyridoxal-5-phosphate (PLP), vitamin B12, glucose, and lipids.
- Assessed vascular function (FMD of brachial artery) and structure (IMT of carotid/aortic arteries).
Main Results:
- No significant differences in tHcy, folate, PLP, lipids, FMD, or IMT were observed between epilepsy patients and controls.
- Children on VPA showed elevated vitamin B12 and reduced glucose levels.
- Children on CBZ exhibited elevated total cholesterol, cholesterol/HDL ratio, and triglycerides.
Conclusions:
- No early alterations in vascular function or structure were detected in children on valproate or carbamazepine.
- Previous findings of homocysteine abnormalities in this population were not confirmed.
- Adequate dietary B-vitamin intake may mitigate AED-induced deficiencies, suggesting supplementation is unnecessary for well-nourished children on these AEDs.
Aim:
To investigate biochemical cardiovascular risk factors and vascular endothelial function and structure in children with epilepsy on antiepileptic drugs (AEDs), particularly sodium valproate (VPA) and carbamazepine (CBZ).
Background:
Individuals with epilepsy have increased risk factors for vascular disease, particularly lipid abnormalities and elevated total plasma homocyst(e)ine (tHcy). AED induced B-vitamin deficiencies have been suggested to contribute to this risk. Vitamin B supplementation has consequently been recommended for children on AEDs. Early vascular endothelial dysfunction and atherosclerosis are detectable by measuring flow-mediated dilation (FMD) and intima-media thickness (IMT).
Methods:
Thirty children with epilepsy on AEDs (13.3±2.3 years, 14 male) and 30 controls (13.9±2.9 years, 14 male) were recruited. Fasting tHcy, folate, pyridoxal-5-phosphate (PLP), vitamin B12, glucose and lipids were measured. Vascular function and structure were assessed using FMD (brachial artery) and IMT (carotid/aortic arteries).
Results:
No differences were found between children with epilepsy and controls for tHcy, folate, PLP, lipids, FMD, carotid or aortic IMT. Vitamin B12 levels were elevated and glucose reduced in children treated with VPA. Elevated total cholesterol, cholesterol/HDL ratio and triglycerides occurred in children treated with CBZ. Aortic IMT correlated with weight (r=0.75, p<0.001), BMI (r=0.54, p=0.01), and HDL cholesterol (r=-0.58, p=0.006).
Conclusion:
We found no early changes in vascular function or structure in children on valproate or carbamazepine. We were also unable to confirm previous reports of tHcy abnormalities in this group. This may be due to higher B-vitamin intake, which compensates for loss of vitamins induced by this AED therapy. Vitamin supplementation in children with epilepsy on valproate and carbamazepine is not required in populations with adequate dietary intake of B vitamins.
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