Assessment of atherosclerotic risk among patients with epilepsy on valproic acid, lamotrigine, and carbamazepine treatment

Discussion

In the present study, epileptic patients had significantly increased body weight and BMI. Numerous studies have reported variable effects of AEDs on body weight. Three studies observed weight gain with VPA,11-13 and both weight gain14 and no change in weight12,13 have been linked with CBZ. However, no change in weight was reported with LTG.13,15 In our study, it was observed that the levels of TC, TG, and LDL-c significantly increased in CBZ- and VPA-treated patients compared with the LTG-treated and control groups, while no substantial difference was observed between LTG-treated and control groups. Several similar and dissimilar results were found in the literature. Results of several studies have shown that CBZ and phenytoin (PHT) (enzyme-inducing AEDs) significantly elevate the levels of TC, LDL-c, and triglycerides.7,16,17 They further suggested that enhancement in the thickness of intima-media of the common carotid artery in patients treated with PHT or CBZ could be due to deposition of TC and LDLs. Chuang et al7 reported that the length of treatment with CBZ, PHT, and VPA shows a significant difference in the speeding up of atherosclerosis, and constitutes the main role in this process.7

The alteration in lipid profile is considered a significant threatening factor for atherosclerosis because elevated levels of LDLs play an imperative role in atherosclerotic development by increasing endothelial permeability, withholding lipoproteins inside the intima of blood vessels, conscripting inflammatory cells, and creating foam cells.3,18 In the present study, the results of LTG effects on lipid profile are similar to other studies7,19,20 these studies also showed no effects of LTG on lipid profile. Moreover, a study reported an improvement in vascular risk factors when a patient is shifted from an enzyme-inducing AED to LTG (a non-enzyme inducing AED).19

A few studies documented no noteworthy differences in lipid profile parameters among the different AED groups; only HDL-c level reduced in patients taking VPA.21,22 In the epileptic literature, derangement in lipid profile by VPA treatment is found debatable.5,7-10 Some studies observed no effect,7,8 while others established a noteworthy alteration in lipid profile.9,10,23,24 One study9 reported a considerable elevation in total cholesterol and LDLs after 12 months of VPA treatment, but levels of TG and HDLs remained the same.9 In our study, the HDL-c significantly decreased in VPA-, CBZ- and LTG-treated patients compared with controls. The present results are compatible with several studies.21,22

The deranged lipid levels in adult patients with epilepsy can be explained by the fact that such patients usually do less exercise and are physically less active, and this could be a reason for low HDL-c concentration in epileptic patients. People with epilepsy, and sometimes physicians themselves are reluctant to include physical exercise programs as a supportive treatment because of the fear that exercise would trigger seizures, or it may be due to lack of information.25 On the contrary, the literature recommends inclusion of exercise while treating epileptic patients because it has a positive outcome for epileptic control and for improving the quality of life of epileptic subjects.

The ratio of TC/HDL-c and LDL-c/HDL-c significantly increased in the VPA- and CBZ-treated groups compared with controls and the LTG-treated group, while the ratio also significantly increased in the CBZ-treated group compared with the VPA-treated group. It is considered that the ratio amongst the different fractions of cholesterol (TC/HDL-c; LDL-c/HDL-c) is an important forecaster of atherosclerosis development. Decreased ratios of TC/HDL-c and LDL-C/HDL-c have potent protecting effects against atherosclerosis and vice versa.26 In our epileptic patients, the elevated ratios of TC/HDL-c and LDL-c/HDL-c indicate a higher atherosclerosis risk.

Diet affects the lipid profile levels; therefore, to exclude the influence of diet, we collected all samples from only one public sector hospital. In a country like Pakistan, for several reasons, almost all people who use the public sector hospitals’ facilities are from the low socio-economic class. Therefore, their dietary patterns are almost similar, and it seems that the change in lipid profile in patients with epilepsy was due to AEDs.

There are several limitations to our study. First, we did not measure other biochemical vascular risk factors. Second, the thickness of the intima-media of the carotid artery was not determined because of unavailability of the facilities. Third, a history of the subject’s physical activities could not be taken. Fourth, detailed information on possible differences in dietary habits among groups was not collected, and it is also a single center study so our results cannot be generalized.

In conclusion, patients with epilepsy on CBZ or VPA have changed vascular risk markers that may lead to atherosclerosis while LTG-treated patients have less alteration in lipid profile. Antiepileptic drug treatment also increases body weight and BMI. Hence, careful monitoring of body weight and lipid profile is needed to detect and manage any significant change. The choice of drug when treating patients should also be taken into consideration.