Is asymmetric dimethylarginine responsible for the vascular events in patients under antiepileptic drug treatment?☆

Some recent studies indicated that administration of antiepileptic drugs (AEDs) is associated with occlusive vascular diseases. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and increased plasma ADMA levels are associated with cardiovascular morbidity. We hypothesized that elevated plasma ADMA concentrations exist in patients receiving AEDs and administration of AEDs may result in an increased risk of occlusive vascular disease. Thirty five newly diagnosed epilepsy patients participated, patients were classified into two groups according to their antiepileptic drug regimen. In the first group patients were treated with valproic acid (VPA, n=17) (500–1500mg/day), and in the second group with carbamazepine (CBZ, n=18) (400–1200mg/day). ADMA levels significantly increased after treatment in both VPA (p=0.002) and CBZ (p=0.024) groups. Homocysteine levels increased in both groups, but the difference was significant only in VPA group (p=0.005). Serum folate levels did not differ in VPA group, but significantly decreased in CBZ group (p=0.006). Vitamin B12 levels significantly increased in VPA group (p=0.001) but did not differ in CBZ group. Correlation analysis showed that the increases in ADMA and homocysteine levels in the VPA group were higher however the differences between the groups were insignificant. The correlations of the changes between ADMA and other parameters were all insignificant in both VPA and CBZ groups. In conclusion our data suggest that elevated ADMA levels may be responsible for the increased cardiovascular risk in patients with epilepsy under AED therapy.