Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs

Hamdi Cihan Emeksiz, Ayse Serdaroglu, Gürsel Biberoglu, Ozlem Gulbahar, Ebru Arhan, Ali Cansu, Mustafa Arga, Alev Hasanoglu
Seizure: the Journal of the British Epilepsy Association 2013, 22 (2): 124-7

PURPOSE: The aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, "hyperhomocysteinemia (HHcy)→asymmetric dimethylarginine (ADMA) increase→nitric oxide (NO) decrease", which is thought to contribute to the developmental process of atherosclerosis.

METHODS: The participants included 53 epilepsy patients who received either valproic acid (VPA, n=26) or oxcarbazepine (OXC, n=27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.

RESULTS: The differences in Hcy, ADMA, NO, vitamin B(12) and folate levels between VPA, OXC and control groups were all insignificant (p>0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p<0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p>0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r=+0.276, p<0.05).

CONCLUSION: HHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.

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