Effect of long term treatment with antiepileptic drugs on carotid intima-media thickness as an indicator of atherosclerosis

Elif Banu Söker; Selda Keskin Güler; Işık Conkbayır; Bülent Güven; Tahir Yoldaş

doi:10.17826/cumj.1489920

EN TR

Effect of long term treatment with antiepileptic drugs on carotid intima-media thickness as an indicator of atherosclerosis

Abstract

Purpose: The aim of current study was to investigate the possible relation between antiepileptic drugs (AEDs) and atheosclerotic risk factors and carotid intima media thickness (IMT) as a marker of atherosclerosis. Materials and Methods: Ninety-two patients, who had used carbamazepine (CBZ) and valproic acid (VPA) for three or more years and who had used a second AED (polytherapy) for two years in addition to CBZ or VPA monotherapy, were included in the study. The control group was composed of 31subjects with similiar demographics. Fasting blood glucose, liver and renal function tests, lipid profile, homocysteine, serum high sensitivity C-Reactive Protein (Hs-CRP), uric acid (UA), lipoprotein (a) (Lp (a)), folate and vitamine B12 levels were examined in both groups. Results: Homocysteine levels were higher in the VPA, CBZ and politherapy groups compared to the control group. UA levels were higher in the VPA monotherapy group when compared to the CBZ monotherapy and polytherapy group. In the CBZ monotherapy group, Hs-CRP levels were higher than in the VPA monotherapy, polytherapy and control groups. Total cholesterol levels were higher in the CBZ monotherapy group when compared to the VPA monotherapy and control groups. Conclusion: The findings showed no correlation between IMT values and duration of disease, duration of drug usage and dose, which suggests that long-term AED usage does not increase the development of atherosclerosis.

Keywords

antiepileptic drugs , intima media thickness , IMT , atherosclerosis , politherapy

Antiepileptik ilaçlarla uzun süreli tedavinin aterosklerozun bir göstergesi olarak karotis intima-media kalınlığı üzerine etkisi

Öz

Amaç: Bu çalışmada, antiepileptik ilaç (AED) ile aterosklerotik risk faktörleri ve aterosklerozun bir belirteci olarak karotis intima media kalınlığı (IMT) arasındaki olası ilişkiyi araştırmayı amaçladık. Gereç ve Yöntem: Üç yıl veya daha uzun süredir karbamazwpin (CBZ) ve valproik asit (VPA) kullanan ve CBZ veya VPA monoterapisine ek olarak iki yıl boyunca ikinci bir AEİ (politerapi) kullanan 92 hasta çalışmaya dahil edildi. Kontrol grubu benzer demografik özelliklere sahip 31 denekten oluşmuştur. Her iki grupta da açlık kan şekeri, karaciğer ve böbrek fonksiyon testleri, lipid profili, homosistein, serum yüksek hassasiyetli C-Reaktif Protein (Hs-CRP), ürik asit (UA), lipoprotein (a) (Lp (a)), folat ve vitamin B12 düzeyleri incelendi. Bulgular: Homosistein düzeyleri VPA, CBZ ve politerapi gruplarında kontrol grubuna göre daha yüksekti. ÜA düzeyleri VPA monoterapi grubunda CBZ monoterapi ve politerapi grubuna kıyasla daha yüksekti. CBZ monoterapi grubunda Hs-CRP düzeyleri VPA monoterapi, politerapi ve kontrol gruplarına göre daha yüksekti. Total kolesterol düzeyleri CBZ monoterapi grubunda VPA monoterapi ve kontrol gruplarına kıyasla daha yüksekti. Sonuç: Bulgular IMT değerleri ile hastalık süresi, ilaç kullanım süresi ve dozu arasında bir korelasyon olmadığını göstermiştir; bu da uzun süreli AEİ kullanımının ateroskleroz gelişimini artırmadığını düşündürmektedir.

Anahtar Kelimeler

Epilepsi , antiepileptik ilaçlar , ateroskleroz , karotis intima media kalınlığı

Kaynakça

Kanner AM, Bicchi MM. antiseizure medications for adults with epilepsy. JAMA. 2022;327:1269-81.
Kolekar VU, Sindgikar SP, Uppoor R, Shetty Km D, Shenoy VJ. Effects of long-term antiepileptic therapy on carotid artery ıntima- media thickness. Pediatr Neurosci. 2021;16:131-6.
Libby P. The changing landscape of atherosclerosis. Nature. 2021;592:524-33.
Tomasz J, Małgorzata MJ, Krzysztof L, Agnieszka J, Stanislaw JC. Atherosclerotic risk among children taking antiepileptic drugs. Pharmacol Rep. 2009;61:411-23.
Hamed SA, Hamed EA, Hamdy R, Nabeshima T. Vascular risk factors and oxidative stress as independent predictors of asymptomatic atherosclerosis in adult patients with epilepsy. Epilepsy Res. 2007;74:183–92.
Hamed SA, Nabeshima T. The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. J Pharmacol Sci. 2005;98:340–53.
Mintzer S, Miller R, Shah K, Chervoneva I, Nei M, Skidmore C, Sperling MR. Long-term effect of antiepileptic drug switch on serum lipids and C-reactive protein. Epilepsy Behav. 2016;58:127-32.
Eirís JM, Lojo S Del Río M C, Novo I, Bravo M, Pavón P et all. Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy. Neurology. 1995;45:1155–7.
Hamed S, Abdullah M. Trace elements and electrolytes homeostasis and their relation to antioxidant enzyme activity in brain hyperexcitability of epileptic patients. J Pharmacol Sci. 2004;96:349–59.
Morrow JD, Roberts LJ. The isoprostanes: unique bioactive products of lipid peroxidation. Prog Lipid Res. 1997;36:1–21.

Ferretti G, Bacchetti T, Moroni C, Vignini A, Nanetti L, Curatola G. Effect of homocysteinylation of low density lipoproteinson lipid peroxidation of human endothelial cells. J Cell Biochem. 2004;92:351–60.
Schwaninger M, Ringleb P, Annecke A, Winter R, Kohl B, Werle E, Fiehn W et al. Elevated plasma concentrations of lipoprotein(a) in medicated epileptic patients. J Neurol. 2000;24:687-90.
Tumer L, Serdaroğlu A, Hasanoğlu A, Biberoglu G, Aksoy E. Plasma homocysteine and lipoprotein (a) levels as risk factors for atherosclerotic vascular disease in epileptic children taking anticonvulsants. Acta Paediatr. 2002;91:923-6.
Voudris KA, Attilakos A, Katsarou E, Drakatos A, Dimou S, Mastroyianni S et all. Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy. Epilepsy Res. 2006;70:211-7.
Wakoh T, Tomohide O, Yohichi O, Kawada S, Takagi S. The role of high-sensitivity c-reactive protein in asymptomatic ıntra-and extracranial large artery diseases. Cerebrovasc Dis. 2008;26:549-55.
Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96:1432-7.
Cao L, Guo Y, Zhu Z. Study of the ınflammatory mechanisms in hyperhomocysteinemia on large-artery atherosclerosis based on hypersensitive c-reactive protein-a study from Southern China. J Stroke Cerebrovasc Dis. 2019;28:1816-23.
Tan TY, Lu CH, Chuang HY, Lin TK, Liou CW, Chang WN. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia. 2009;50:1579–86.
Elliott JO, Jacobson MP, Haneef Z. Cardiovascular risk factors and homocysteine in epilepsy. Epilepsy Res. 2007;76:113–23.
Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 2004;45:1613–22.
Shneker BF, Fountain NB. Epilepsy. Dis Mon. 2003;49:426-78.
Talaat FM, Kamel T, Rabah AM, Ahmed SM, El-Jaafary SI, Abdelaziz GH. Epilepsy and antiepileptic drugs: risk factors for atherosclerosis. Int J Neurosci. 2015;125:507-11.
Elliott JO, Jacobson MP, Haneef Z. Cardiovascular risk factors and homocysteine in epilepsy. Epilepsy Res. 2007;76:113–23.
Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 2004;45:1613–22.
Kaste M, Muuronen A, Nikkila EA, Neuvonen PJ. Increase of low serum concentrations of high-density lipoprotein (HDL) cholesterol in TIA-patients treated with phenytoin. Stroke. 1983;14:525–30.
Nilsson L, Tomson T, Farahmand BY, Diwan V, Persson PG. Cause-specific mortality in epilepsy: a cohort study of more than 9,000 patients once hospitalized for epilepsy. Epilepsia. 1997;38:1062–68.
Bleich S, Degner D, Sperling W, Bönsch D, Thürauf N, Kornhuber J. Homocysteine as a neurotoxin in chronicalcoholism. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:453-64.
Ono H, Sakamoto A, Mizoguchi N, Sakura N. The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyper-homocysteinemia in patients taking anticonvulsants. Brain Dev. 2002;24:223–6.
Verrotti A, Pascarella R, Trotta D, Giuva T, Morgese G, Chiarelli F. Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res. 2000;41:253–7.
Aycicek A, Iscan A. The effects of carbamazepine, volproic acid and phenobarbital on the oxidative and antioxidative balance in epileptic children. Eur Neurol. 2007;57:65-9.
Eirís J, Novo-Rodríguez MI, Del Río M, Meseguer P, Del Río MC, Castro-Gago M. The effects on lipid and apolipoprotein serum levels of long-term carbamazepine,valproic acid and phenobarbital therapy in children with epilepsy. Epilepsy Res. 2000;41:1–7.
Demircioglu S, Soylu A, Dirik E. Carbamazepine and valproic acid: effects on the serum lipids and liver functions in children. Pediatr Neurol. 2000;23:142–6.
Sozuer DT, Atakli D, Doğu O, Baybas S, Arpaci B. Serum lipids in epileptic children treated with carbamazepine and valproate. Eur J Pediatr. 1997;186:565–7.
Yılmaz E, Dosan Y, Gurgoze MK, Güngör S. Serum lipid changes during anticonvulsive treatment serum lipids in epileptic children. Acta Neurol Belg. 2001;101:217–20.
Verrotti A, Domizio S, Angelozzi B, Sabatino G, Morgese G, Chiarelli F. Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants. J Paediatr Child Health. 1997;33:242–5.
Tekgul H, Demir N, Gokben S. Serum lipid profile in children receiving anti-epileptic drug monotherapy: is it atherogenic? J Pediatr Endocrinol Metab. 2006;19:1151–5.
Sonmez FM, Demir E, Orem A, Yildirmis S, Orhan F, Aslan F, Topbas M. Effect of antiepileptic drugs onplasma lipids, lipoprotein (a), and liver enzymes. J ChildNeurol. 2006;21:70–4.
Biton V. Effect of antiepileptic drugs on bodyweight: overview and clinical implications for the treatment of epilepsy. CNS Drugs. 2003;17:781–91.
De Michele M, Panico S, Iannuzzi A, Celentano E, Ciardullo A, Galasso R et al. Association of obesity and central fat distribution with carotid artery wall thickening in mid-dle-aged women. Stroke. 2002;33:2923–8.
Sun Y, Lin CH, Lu CJ, Yip PK, Chen RC. Carotid atherosclerosis, intima media thickness and risk factors an analysis of 1781 asymptomatic subjects in Taiwan. Atherosclerosis. 2002;164:89–94.
Homma S, Hirose N, Ishida H, Ishii T, Araki G. Carotid plaque and intima-media thickness assessed by b-mode ultrasonography in subjects ranging from young adults to centenarians. Stroke. 2001;32:830–5

Ayrıntılar

Birincil Dil

İngilizce

Konular

Nöroloji ve Nöromüsküler Hastalıklar

Bölüm

Araştırma Makalesi

Yazarlar

Elif Banu Söker ^*
0000-0003-0315-901X
Türkiye

Selda Keskin Güler
0000-0003-1976-7319
Türkiye

Işık Conkbayır
0000-0003-2768-4871
Türkiye

Bülent Güven
0000-0002-4816-9257
Türkiye

Tahir Yoldaş
0000-0002-3752-1825
Türkiye

Yayımlanma Tarihi

30 Aralık 2024

Gönderilme Tarihi

26 Mayıs 2024

Kabul Tarihi

22 Kasım 2024

Yayımlandığı Sayı

Yıl 2024 Cilt: 49 Sayı: 4

DOI

https://doi.org/10.17826/cumj.1489920

IZ

https://izlik.org/JA49DG76YL

MLA

Söker, Elif Banu, vd. “Effect of long term treatment with antiepileptic drugs on carotid intima-media thickness as an indicator of atherosclerosis”. Cukurova Medical Journal, c. 49, sy 4, Aralık 2024, ss. 947-5, doi:10.17826/cumj.1489920.

Bu eser Creative Commons Atıf-Gayriticari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

Effect of long term treatment with antiepileptic drugs on carotid intima-media thickness as an indicator of atherosclerosis

Abstract

Keywords

Antiepileptik ilaçlarla uzun süreli tedavinin aterosklerozun bir göstergesi olarak karotis intima-media kalınlığı üzerine etkisi

Öz

Anahtar Kelimeler

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

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