Rationale:
Reports of elevated lipid fractions and other markers of vascular risk associated with anti-seizure medication (ASM) use have been present in the literature for over two decades, including total cholesterol, high density cholesterol (HDL), low density cholesterol (LDL), triglycerides, homocysteine, and C-reactive protein (CRP). While carbamazepine (CBZ) and valproic acid (VPA) are widely used ASMs, existing evidence on their impact on lipid profiles is conflicting, with some studies suggesting CBZ elevates lipid fractions and VPA may reduce them. This study aimed to perform a meta-analysis and systematic review to confirm the association of these vascular risk markers with the use of CBZ and VPA monotherapy in epileptic patients with a focus on the lesser-studied markers, apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), as no comprehensive meta-analysis on all these markers previously existed.
Methods:
A systematic literature search was conducted across MEDLINE, Google Scholar, and SCOPUS databases. The initial search yielded 431 titles. Studies were selected based on PRISMA guidelines, with exclusions for irrelevance, no control group, non-human subjects, or polytherapy use, resulting in a final analysis of 69 studies published between 1983 and 2019. Methodological variables extracted included serum lipid levels. Demographic and clinical variables such as age, gender, and treatment duration were extracted as moderator variables. Meta-analysis was performed using Comprehensive Meta-Analysis software, employing a random-effects model to account for heterogeneity. Study quality was assessed using the Newcastle-Ottawa Scale.
Results:
The meta-analysis revealed a significant positive association between CBZ use and ApoA1 levels with a positive association also noted in female patients. CBZ use was positively associated with increased homocysteine and CRP levels. HDL, LDL, and triglyceride levels displayed a positive association with CBZ use. The LDL/HDL ratio also showed a positive association with CBZ, further correlated with treatment duration. CBZ was positively associated with VLDL as age increased. For VPA, a negative association was found with ApoA1 levels based on patient age, but no overall or gender correlation. A negative association was found between ApoB levels and duration of VPA use. VPA use showed a positive overall association with increased homocysteine levels, alongside a positive association with treatment duration.
Conclusions:
This meta-analysis confirms significant associations between CBZ use and elevated levels of various lipid markers. The findings for VPA were more varied, showing age-dependent negative associations with ApoA1 and duration-dependent negative associations with ApoB, alongside a positive association with homocysteine. These results underscore the importance of monitoring lipid fractions and vascular risk markers in patients on CBZ and VPA monotherapy, particularly given the long-term implications for cardiovascular and cerebrovascular health. This study highlights the need for individualized lipid monitoring and management in patients treated for epilepsy to mitigate potential dyslipidemia and cardiovascular issues.
Funding:
No disclosures.