Skip to main content
Log in

Impact of atrial fibrillation on the risk of ischemic stroke in patients on hemodialysis: BOREAS-HD3 Study

  • Original article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Atrial fibrillation (AF) is an established risk factor for ischemic stroke in a general population. However, its impact in patients on hemodialysis (HD), a group with a high risk for stroke, is still controversial. Here we examined this issue in a Japanese cohort.

Methods

This study was designed as a multicenter cohort study. HD patients (n = 1,067) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data (n = 196) or kidney transplantation (n = 4) were excluded, and 867 patients contributed to the analysis of the risk of new-onset of ischemic stroke.

Results

At baseline, AF was observed in 123 patients (14.2%, AF group) and not in the others (n = 744: 85.8%, non-AF group). During a follow-up period of 31.3 months, the cumulative incidence rate for ischemic stroke was significantly higher in the AF group than in the non-AF group (6.5% vs. 2.9%, p < 0.05). In Cox regression analysis, AF was a significant independent risk factor for new-onset of ischemic stroke after adjustment for age, sex, prior history of ischemic stroke, use of warfarin, dialysis vintage, comorbidity of diabetic nephropathy, and interdialytic weight gain (hazard ratio 2.17–2.68).

Conclusion

Present analyses using comprehensive adjustment for multiple confounders, including prior history of ischemic stroke, indicated that AF independently increases the risk of new-onset of ischemic stroke by more than twofold in Japanese HD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Seliger SL, Gillen DL, Longstreth WT Jr, et al. Elevated risk of stroke among patients with end-stage renal disease. Kidney Int. 2003;64:603–9.

    PubMed  Google Scholar 

  2. Iseki K, Kinjo K, Kimura Y, et al. Evidence for high risk of cerebral hemorrhage in chronic dialysis patients. Kidney Int. 1993;44:1086–90.

    CAS  PubMed  Google Scholar 

  3. Iseki K, Fukiyama K. Clinical demographics and long-term prognosis after stroke in patients on chronic haemodialysis. The Okinawa Dialysis Study (OKIDS) Group. Nephrol Dial Transplant. 2000;15:1808–13.

    CAS  PubMed  Google Scholar 

  4. Mattana J, Effiong C, Gooneratne R, et al. Outcome of stroke in patients undergoing hemodialysis. Arch Intern Med. 1998;158:537–41.

    CAS  PubMed  Google Scholar 

  5. Toyoda K, Fujii K, Fujimi S, et al. Stroke in patients on maintenance hemodialysis: a 22-year single-center study. Am J Kidney Dis. 2005;45:1058–66.

    PubMed  Google Scholar 

  6. Bansal N, Xie D, Tao K, et al. Atrial fibrillation and risk of ESRD in adults with CKD. Clin J Am Soc Nephrol. 2016;11:1189–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Kumar S, Lim E, Covic A, et al. Anticoagulation in concomitant chronic kidney disease and atrial fibrillation: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;74:2204–15.

    CAS  PubMed  Google Scholar 

  8. Horio T, Iwashima Y, Kamide K, et al. Chronic kidney disease as an independent risk factor for new-onset atrial fibrillation in hypertensive patients. J Hypertens. 2010;28:1738–44.

    CAS  PubMed  Google Scholar 

  9. Zimetbaum P. Atrial fibrillation. Ann Intern Med. 2017;166:ITC33–48.

    PubMed  Google Scholar 

  10. Zimmerman D, Sood MM, Rigatto C, et al. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol Dial Transplant. 2012;27:3816–22.

    CAS  PubMed  Google Scholar 

  11. Königsbrügge O, Posch F, Antlanger M, et al. Prevalence of atrial fibrillation and antithrombotic therapy in hemodialysis patients: cross-sectional results of the Vienna investigation of atrial fibrillation and thromboembolism in patients on hemodialysis (VIVALDI). PLoS ONE. 2017;12:e0169400.

    PubMed  PubMed Central  Google Scholar 

  12. Winkelmayer WC, Patrick AR, Liu J, et al. The increasing prevalence of atrial fibrillation among hemodialysis patients. J Am Soc Nephrol. 2011;22:349–57.

    PubMed  PubMed Central  Google Scholar 

  13. Christiansen CB, Gerds TA, Olesen JB, et al. Atrial fibrillation and risk of stroke: a nationwide cohort study. Europace. 2016;18:1689–97.

    PubMed  Google Scholar 

  14. Wiesholzer M, Harm F, Tomasec G, et al. Incidence of stroke among chronic hemodialysis patients with nonrheumatic atrial fibrillation. Am J Nephrol. 2001;21:35–9.

    CAS  PubMed  Google Scholar 

  15. To AC, Yehia M, Collins JF. Atrial fibrillation in haemodialysis patients: do the guidelines for anticoagulation apply? Nephrology. 2007;12:441–7.

    PubMed  Google Scholar 

  16. Genovesi S, Vincenti A, Rossi E, et al. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis. 2008;51:255–62.

    PubMed  Google Scholar 

  17. Sánchez-Perales C, Vázquez E, García-Cortés MJ, et al. Ischemic stroke in incident dialysis patients. Nephrol Dial Transplant. 2010;25:3343–8.

    PubMed  Google Scholar 

  18. Findlay MD, Thomson PC, Fulton RL, et al. Risk factors of ischemic stroke and subsequent outcome in patients receiving hemodialysis. Stroke. 2015;46:2477–81.

    CAS  PubMed  Google Scholar 

  19. Shih CJ, Ou SM, Chao PW, et al. Risks of death and stroke in patients undergoing hemodialysis with new-onset atrial fibrillation: a competing-risk analysis of a nationwide cohort. Circulation. 2016;133:265–72.

    CAS  PubMed  Google Scholar 

  20. Hasegawa J, Bieber B, Larkina M, et al. Cardiovascular and stroke risk in Japanese hemodialysis patients with atrial fibrillation. Ther Apher Dial. 2016;20:608–14.

    PubMed  Google Scholar 

  21. Tanaka M, Yamashita T, Koyama M, et al. Impact of use of angiotensin II receptor blocker on all-cause mortality in hemodialysis patients: prospective cohort study using a propensity-score analysis. Clin Exp Nephrol. 2016;20:469–78.

    CAS  PubMed  Google Scholar 

  22. Tanaka M, Moniwa N, Ohnishi H, et al. Impact of the number of anti-thrombosis agents in hemodialysis patients: BOREAS-HD2 Study. Kidney Blood Press Res. 2017;42:553–64.

    CAS  PubMed  Google Scholar 

  23. Saran R, Bragg-Gresham JL, Rayner HC, et al. Nonadherence in hemodialysis: associations with mortality, hospitalization, and practice patterns in the DOPPS. Kidney Int. 2003;64:254–62.

    PubMed  Google Scholar 

  24. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    CAS  PubMed  Google Scholar 

  25. Kamel H, Okin PM, Elkind MS, et al. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke. 2016;47:895–900.

    PubMed  PubMed Central  Google Scholar 

  26. Abe M, Ogawa H, Ishii M, et al. Relation of stroke and major bleeding to creatinine clearance in patients with atrial fibrillation (from the Fushimi AF Registry). Am J Cardiol. 2017;119:1229–37.

    CAS  PubMed  Google Scholar 

  27. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41.

    PubMed  Google Scholar 

  28. Sozio SM, Armstrong PA, Coresh J, et al. Cerebrovascular disease incidence, characteristics, and outcomes in patients initiating dialysis: the choices for healthy outcomes in caring for ESRD (CHOICE) study. Am J Kidney Dis. 2009;54:468–77.

    PubMed  PubMed Central  Google Scholar 

  29. Diener HC, Hankey GJ. Primary and secondary prevention of ischemic stroke and cerebral hemorrhage: JACC Focus Seminar. J Am Coll Cardiol. 2020;75:1804–18.

    PubMed  Google Scholar 

  30. Kelly DM, Rothwell PM. Prevention and treatment of stroke in patients with chronic kidney disease: an overview of evidence and current guidelines. Kidney Int. 2020;97:266–78.

    PubMed  Google Scholar 

  31. Wang IK, Yen TH, Guo YC, et al. Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction. Eur J Neurol. 2020;27:572–8.

    PubMed  Google Scholar 

  32. Naganuma T, Uchida J, Tsuchida K, et al. Silent cerebral infarction predicts vascular events in hemodialysis patients. Kidney Int. 2005;67:2434–9.

    PubMed  Google Scholar 

  33. Herrington W, Haynes R, Staplin N, et al. Evidence for the prevention and treatment of stroke in dialysis patients. Semin Dial. 2015;28:35–47.

    PubMed  Google Scholar 

  34. Dahal K, Kunwar S, Rijal J, et al. Stroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies. Chest. 2016;149:951–9.

    PubMed  Google Scholar 

  35. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367:625–35.

    CAS  PubMed  Google Scholar 

  36. Chan KE, Lazarus JM, Thadhani R, et al. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009;20:2223–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int. 2010;77:1098–106.

    CAS  Google Scholar 

  38. Winkelmayer WC, Liu J, Setoguchi S, et al. Effectiveness and safety of warfarin initiation in older hemodialysis patients with incident atrial fibrillation. Clin J Am Soc Nephrol. 2011;6:2662–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Shah M, Avgil Tsadok M, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014;129:1196–203.

    CAS  PubMed  Google Scholar 

  40. Wakasugi M, Kazama JJ, Tokumoto A, et al. Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study. Clin Exp Nephrol. 2014;18:662–9.

    CAS  PubMed  Google Scholar 

  41. Genovesi S, Rossi E, Gallieni M, et al. Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation. Nephrol Dial Transplant. 2015;30:491–8.

    CAS  PubMed  Google Scholar 

  42. Randhawa MS, Vishwanath R, Rai MP, et al. Association between use of warfarin for atrial fibrillation and outcomes among patients with end-stage renal disease: a systematic review and meta-analysis. JAMA Netw Open. 2020;3:e202175.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank for all members of BOREAS-HD Study Investigators. The consortium includes Masatada Fukuoka, Koichi Hasegawa, Manabu Hayashi, Toshiya Ishiguro, Akira Ishimoto, Yosuke Itoh, Toshihiro Iwamoto, Hironori Kobayashi, Hiroshi Kobayashi, Atsushi Konno, Setsuko Kuroda, Tomoaki Matsumoto, Tamaki Matsumoto, Hiroya Mukai, Takahiro Nishitani, Fumio Obara, Toru Otomo, Takashi Sakamoto, Niro Sawai, Katsuo Suzuki, Yoshitoki Takagawa, Hideki Takizawa, Kazushi Tanaka, Nobuhiko Togashi, Takaaki Torii, Daisuke Yoshida, Mayumi Yoshihara and Atsushi Wada.

Author information

Authors and Affiliations

Authors

Contributions

Marenao Tanaka (M.T.) conceived this study, and M.T., Tomohisa Yamashita (T.Y.) and Masayuki Koyama (M.K.) designed the study. M.T., T.Y., M.K., Satoru Shibata (S.S.) and Yusuke Okazaki (Y.O.) collected data. Ayumu Kimura (A.K.) and M.T. performed statistical analysis of the data, prepared tables and figures and drafted manuscript. Norihito Moniwa (N.M.), Arata Osanami, Koki Abe, Daisuke Miyamori, Yufu Gocho, Makoto Terasawa, Masato Furuhashi (M.F.), Hirofumi Ohnishi (H.O.) and Tetsuji Miura (T.M.) contributed to interpretation of the data and to finalize the manuscript. H.O. and T.M. supervised the statistical analysis and the entire project, respectively. For authors who moved during the present study, affiliations at the time of commencement of the study and also current affiliations are described.

Corresponding author

Correspondence to Marenao Tanaka.

Ethics declarations

Conflict of interest

All of the authors have declared that no conflicts of interest exist.

Ethical approval

This study was performed in accordance with the guidelines contained within the Declaration of Helsinki and the protocol was licensed by the institutional ethical committee of Sapporo Medical University (number: 21-29).

Informed consent

Written informed consent was obtained from all of the subjects.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimura, A., Tanaka, M., Moniwa, N. et al. Impact of atrial fibrillation on the risk of ischemic stroke in patients on hemodialysis: BOREAS-HD3 Study. Clin Exp Nephrol 25, 297–304 (2021). https://doi.org/10.1007/s10157-020-01991-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-020-01991-9

Keywords

Navigation