Ferritin and Cardiac Electrophysiology in End-Stage Renal Disease: Evaluating the Impact of Index of Cardio-Electrophysiological Balance

Year 2025, Volume: 7 Issue: 1, 37 - 44, 25.02.2025

Metin Çoksevim , Ömer Kertmen , Ufuk Yıldırım , Ercan Türkmen

https://doi.org/10.52827/hititmedj.1595243

Abstract

Objective: Ferritin is a critical protein involved in iron storage and functions as an acute-phase reactant, playing a significant role in chronic inflammation and the pathogenesis of cardiovascular diseases. Elevated ferritin levels in end-stage renal disease patients undergoing hemodialysis may influence cardiac electrophysiological parameters, such as the corrected index of cardio-electrophysiological balance, a marker of proarrhythmic risk. This study aimed to investigate the association between ferritin levels and the corrected index of cardio-electrophysiological balance in patients with end-stage renal disease undergoing hemodialysis.
Material and Method: This retrospective cross-sectional study included 438 patients with end-stage renal disease undergoing hemodialysis, categorized into two groups according to their ferritin levels: Group 1 (≥1000 ng/mL, n=254) and Group 2 (≤200 ng/mL, n=184). Demographic, biochemical, and electrocardiographic data, including corrected index of cardio-electrophysiological balance, were analyzed. The correlation between ferritin levels and the corrected index of cardio-electrophysiological balance was assessed.
Results: The index of cardio-electrophysiological balance was significantly higher in Group 1 compared to Group 2 (5.1 vs. 4.9, p=0.003). A moderate positive correlation between ferritin levels and the index of cardio-electrophysiological balance was identified (r=0.326, p<0.005). While significant differences were observed in heart rate, QRS duration, and PR intervals between the groups, other electrocardiographic parameters, such as Tp-e and QT intervals, did not show significant differences. The logistic regression analysis identified gender and ferritin levels as significant predictors of elevated iCEBc (≥4.5) (Ferritin odds ratio of 1.08 (95% CI: 1.03–1.12, p<0.005).
Conclusion: Elevated ferritin levels in end-stage renal disease patients undergoing hemodialysis are associated with an increased corrected index of cardio-electrophysiological balance, reflecting heightened proarrhythmic risk. These findings underscore the importance of ferritin as a potential marker for arrhythmia risk assessment in this population. Further research is warranted to explore strategies for mitigating cardiovascular risks associated with iron metabolism dysregulation.

Keywords

End-stage renal disease, ferritin, hemodialysis, Index of Cardio-Electrophysiological Balance

Ethical Statement

Approval for the study was obtained from Ondokuz Mayıs University Clinical Research Ethics Committee on 27/11/2024. Decision no: 2024/511.

Thanks

We extend our sincere gratitude to the assistant staff of the Cardiology Department at Ondokuz Mayıs University for their valuable contributions during the data collection phase. Additionally, we thank Dr. Önder Aydemir for his expert assistance with the statistical analysis.

Son Dönem Böbrek Yetersizliğinde Ferritin ve Kardiyak Elektrofizyoloji: Kardiyo-Elektrofizyolojik Denge İndeksinin Etkisinin Değerlendirilmesi

Abstract

Özet
Amaç: Ferritin, demir depolanmasında anahtar bir protein olup, aynı zamanda kronik inflamasyon ve kardiyovasküler hastalıklarla ilişkili bir akut faz reaktanıdır. Hemodiyaliz uygulanan son dönem böbrek yetmezliği hastalarında artan ferritin seviyelerinin, proaritmik riski yansıtan kardiyo-elektrofizyolojik denge indeksi gibi elektrokardiyografik parametreleri etkileyebileceği düşünülmektedir. Bu çalışma, hemodiyaliz alan son dönem böbrek yetersizliği hastalarında ferritin seviyeleri ile kardiyo-elektrofizyolojik denge indeksi arasındaki ilişkiyi değerlendirmeyi amaçlamaktadır.
Gereç ve Yöntem: Bu retrospektif, kesitsel çalışmada, hemodiyaliz uygulanan 438 son dönem böbrek yetersizliği hastası yer almıştır. Hastalar ferritin seviyelerine göre iki gruba ayrılmıştır: Grup 1 (≥1000 ng/mL, n=254) ve Grup 2 (≤200 ng/mL, n=184). Demografik, biyokimyasal ve elektrokardiyografik veriler (kardiyo-elektrofizyolojik denge indeksi dahil) analiz edilmiştir. Ferritin seviyeleri ile kardiyo-elektrofizyolojik denge indeksi arasındaki ilişki değerlendirilmiştir.
Bulgular: Kardiyo-elektrofizyolojik denge indeksi Grup 1'de Grup 2'ye kıyasla anlamlı derecede yüksek saptandı (5.1'e karşı 4.9, p=0.003). Ferritin düzeyleri ile kardiyo-elektrofizyolojik denge indeksi arasında orta düzeyde pozitif bir korelasyon tespit edilmiştir (r=0.326, p<0.005). Gruplar arasında kalp hızı, QRS süresi ve PR aralıklarında anlamlı farklılıklar gözlenirken, Tp-e ve QT aralıkları gibi diğer elektrokardiyografik parametreler anlamlı farklılıklar göstermemiştir. Lojistik regresyon analizi, cinsiyet ve ferritin düzeylerini yüksek iCEBc (≥4,5) için anlamlı öngörücüler olarak tanımlamıştır (Ferritin odds ratio 1,08 (%95 CI: 1,03-1,12, p<0.005).
Sonuç: Hemodiyaliz uygulanan son dönem böbrek yetersizliği hastalarında yüksek ferritin seviyeleri, proaritmik riski yansıtan kardiyo-elektrofizyolojik denge indeksi ile ilişkilendirilmiştir. Bu bulgular, ferritinin bu popülasyonda aritmi riski değerlendirmesinde potansiyel bir belirteç olarak önemini vurgulamaktadır. Çalışmamız ile demir metabolizmasının düzensizliği ile ilişkili kardiyovasküler riskleri azaltmaya yönelik stratejilerin araştırılması gerektiği sonucuna varılmıştır.

Keywords

Ferritin, hemodiyaliz, Kardiyo-Elektrofizyolojik Denge İndeksi, Son dönem böbrek hastalığı.

Ethical Statement

Çalışma için 27/11/2024 tarihinde Ondokuz Mayıs Üniversitesi Klinik Araştırmalar Etik Kurulu’ndan onay alınmıştır. Karar no: 2024/511.

Thanks

Veri toplama aşamasındaki değerli katkılarından dolayı Ondokuz Mayıs Üniversitesi Kardiyoloji Anabilim Dalı asistanlarına en içten teşekkürlerimizi sunarız. Ayrıca, istatistiksel analizlerdeki uzman yardımı için Dr. Önder Aydemir'e teşekkür ederiz.

References

• Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: past, present and future. Biochimica et Biophysica Acta (BBA)-General Subjects 2010;1800:760-769.
• Altieri C, Pisano C, Vincenzo L et al. Circulating levels of ferritin, RDW, PTLs as predictive biomarkers of postoperative atrial fibrillation risk after cardiac surgery in extracorporeal circulation. International Journal of Molecular Sciences 2022;23:14800.
• Israel A, Bornstein G, Gilad L et al. Clinical and prognostic significance of elevated ferritin levels in hospitalized adults. Postgraduate Medical Journal 2022;98:622-625.
• Kuragano T, Joki N, Hase H et al. Low transferrin saturation (TSAT) and high ferritin levels are significant predictors for cerebrovascular and cardiovascular disease and death in maintenance hemodialysis patients. PLoS One 2020;15:e0236277.
• McCullough K, Bolisetty S. Ferritins in kidney disease. Seminars in nephrology: Elsevier, 2020:160-172.
• Mikkelsen LF, Nordestgaard BG, Schnohr P, Ellervik C. Increased ferritin concentration and risk of atrial fibrillation and heart failure in men and women: three studies of the Danish general population including 35799 individuals. Clinical Chemistry 2019;65:180-188.
• Aboelsaad IA, Claggett BL, Arthur V et al. Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function: The ARIC Study. Heart Failure 2024;12:539-548.
• Yilmaz E, Aydin E. The effect of low iron storage without Anaemia on electrocardiography. Journal of Electrocardiology 2021;64:76-79.
• Erdogan G, Yontar OC, Yenercag M, Gul S, Arslan U. Frontal QRS-T angle predicts syntax score in patients with non-ST elevation myocardial infarction. Journal of Electrocardiology 2020;61:86-91.
• Lin Y, Zhou F, Wang X, Guo Y, Chen W. Effect of the index of cardiac electrophysiological balance on major adverse cardiovascular events in patients with diabetes complicated with coronary heart disease. PeerJ 2023;11:e15969.
• Yenerçağ M, Arslan U. Tp-e interval and Tp-e/QT ratio and their association with left ventricular diastolic dysfunction in Fabry disease without left ventricular hypertrophy. Journal of Electrocardiology 2020;59:20-24.
• Yenerçağ M, Arslan U, Doğduş M et al. Evaluation of electrocardiographic ventricular repolarization variables in patients with newly diagnosed COVID-19. Journal of Electrocardiology 2020;62:5-9.
• Laudanski K, Ali H, Himmel A, Godula K, Stettmeier M, Calvocoressi L. The relationship between serum ferritin levels and electrocardiogram characteristics in acutely ill patients. Experimental & Clinical Cardiology 2009;14:38.
• Gordan R, Fefelova N, Gwathmey J, Xie L-H. Iron overload promotes arrhythmias via ROS production and mitochondrial membrane potential depolarization. Biophysical Journal 2015;108:273a.
• Karadeniz C, Özdemir R, Demirol M et al. Low iron stores in otherwise healthy children affect electrocardiographic markers of important cardiac events. Pediatric Cardiology 2017;38:909-914.
• Yan J, Pan Y, He Y, Wang R, Shao W, Dong S. The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease complicated with chronic heart failure: a retrospective cohort study. Heart and Vessels 2020;35:1419-1428.
• Hintze KJ, Theil EC. DNA and mRNA elements with complementary responses to hemin, antioxidant inducers, and iron control ferritin-L expression. Proceedings of the National Academy of Sciences 2005;102:15048-15052.
• Kuragano T, Matsumura O, Matsuda A et al. Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kidney International 2014;86:845-854.
• Lotfy Ahmed A, Hamed Hassan F, Mohamed Rashed E-S, Ahmed Mosaad M, Fathy Esmaeel N. Relation between serum ferritin and left ventricular functions in hemodialysis patients. Al-Azhar Medical Journal 2021;50:2177-2184.
• Lu HR, Yan G-X, Gallacher DJ. A new biomarker–index of Cardiac Electrophysiological Balance (iCEB)–plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs). Journal of Pharmacological and Toxicological Methods 2013;68:250-259.
• Yücetas SC, Kaya H, Kafadar S, Kafadar H, Tibilli H, Akcay A. Evaluation of index of cardiac-electrophysiological balance in patients with subarachnoid hemorrhage. BMC Cardiovascular Disorders 2022;22:477.
• Özdemir L, Sökmen E. Effect of habitual cigarette smoking on the index of cardiac electrophysiological balance in apparently healthy individuals. Journal of Electrocardiology 2020;59:41-44.
• Chen X, Wang Z, Liu L et al. Prognostic value of index of cardiac electrophysiological balance among US middle-aged adults. Front Cardiovasc Med 2023;10:1139967.
• Kaya H, Suner A, Koparal M, Yucetas SC, Kafadar S. Evaluation of Tp-e interval, Tp-e/QT ratio and index of cardiac-electrophysiological balance in patients with tinnitus. BMC Cardiovascular Disorders 2021;21:415.
• Nafakhi H, Al-Mosawi AA, Alareedh M, Al-Nafakh HA. Index of cardiac electrophysiological balance and transmural dispersion of the repolarization index relationships with pericardial fat volume and coronary calcification. Biomarkers in Medicine 2018;12:321-328.