Hoffmann, Michał

Abstract Objective: The risk of premature deaths in patients with epilepsy (approx. 50 mln. patients worldwide) is about 2–3 times higher as compared to general population. This phenomenon is mainly explained by cardiovascular causes as well as sudden unexpected deaths in epilepsy (SUDEP). Epilepsy is associated with sympathetic overdrive and renin-angiotensin-system abnormalities all of which may be implicated in organ damage (both directly and indirectly via high blood pressure; BP). In our study, we aimed at the evaluation of several cardiovascular risk factors and organ damage in patients with epilepsy; its’ relation to disease control and comorbid hypertension. Design and method: A total of 48 patients and matched controls were included in the study. Anthropometry, biochemical assessment, office and ambulatory blood pressure, structural and/ or functional vascular changes were recorded. One-way ANOVA and ANCOVA were employed (mean ± SE). Results: Patients were comparable in terms of age and BMI. Hypertensives were aware of high BP in 50% of cases. Study subgroups were comparable in terms of heart rate, serum uric acid, triglicerides, HDL, glucose, serum creatinine and eGFR, serum potassium (P = NS for all comparisons). Total cholesterol was the lowest in well-controlled epileptic patients which was followed by refractory disease and epilepsy with comorbid hypertension (167.6 ± 6.7 vs. 196.9 ± 7.4 vs. 223.5 ± 8.9; respectively). Patients with refractory epilepsy had comparable serum LDL and PWV to hypertensive well-controlled epileptics; both contrasted with values recorded in patients with well-controlled epilepsy who were free of hypertension (LDL: 121.7 ± 6.8 vs. 140.9 ± 8.2 vs. 99.2 ± 6.1; respectively, and PWV: 6.4 ± 0.24 vs. 6.8 ± 0.30 vs. 5.5 ± 0.22; respectively). Reported differences were valid after adjustment for age and BMI. Conclusions: Except for BP values, patients with refractory epilepsy who are free of hypertension have similar CV risk profile to patients with high BP. These findings along with underdiagnosed hypertension may explain higher CV mortality and morbidity documented in epilepsy.

Objective— There is increasing evidence of an association between leptin and increased cardiovascular risk. Higher leptin levels are associated with increased levels of C-reactive protein (CRP), which itself elicits proatherogenic effects in the vascular endothelium. We tested the hypothesis that leptin induces CRP expression in human coronary artery endothelial cells (HCAECs). Methods and Results— We confirmed the presence of both long and short isoforms of the leptin receptor in cultured HCAECs. Leptin but not IFNαA/D nor tumor necrosis factor (TNF) α, induced expression of CRP. A dose dependent increase of CRP mRNA and protein was observed with increasing concentration of leptin (0 to 400 ng/mL). This increased CRP expression was attenuated in the presence of anti-leptin receptor antibodies and also by inhibition of ERK1/2 by PD98059 (20 to 40 μmol/L). Time (0 to 60 minutes) and leptin concentration (0 to 200 ng/mL)-dependence of ERK1/2 phosphorylation were evident in response to leptin treatment. Leptin also elicited ROS generation. Inhibition of ROS by catalase (200 μg/mL) prevented ERK1/2 phosphorylation and CRP mRNA transcription. Conclusion— Leptin induces CRP expression in HCAECs via activation of the leptin receptor, increased ROS production, and phosphorylation of ERK1/2. These studies suggest a mechanism for the proatherogenic effects of leptin.