Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: The Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study

Rachel M. Kruzan, Charles A. Herzog, Aozhou Wu, Yingying Sang, Rulan S. Parekh, Kunihiro Matsushita, Seungyoung Hwang, Alan Cheng, Josef Coresh, Neil R. Powe, Tariq Shafi

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Background: Sudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N-terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients. Methods: We measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI). Results: Patients' mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13-1.43; p < 0.001). In categorical models, the risk of SCD was 3-fold higher in the highest tertile of NTproBNP (>7,350 pg/mL) compared with the lowest tertile (<1,710 pg/mL; HR for the highest tertile, 3.03; 95 % CI, 1.56-5.89; p = 0.001). Higher cTnI showed a trend towards increased risk of SCD in fully adjusted models, but was not statistically significant (HR, 1.17 per doubling; 95 % CI, 0.98-1.40; p = 0.08). Sensitivity analyses using competing risk models showed similar results. Improvement in risk prediction by adding cardiac biomarkers to conventional risk factors was greater with NTproBNP (C-statistic for 3-year risk: 0.810; 95 % CI, 0.757 to 0.864; and continuous NRI: 0.270; 95 % CI, 0.046 to 0.495) than with cTnI. Conclusions: NTproBNP is associated with the risk of SCD in hemodialysis patients. Further research is needed to determine if biomarkers measurement can guide SCD risk prevention strategies in dialysis patients.

Original languageEnglish (US)
Article number18
JournalBMC Nephrology
Issue number1
StatePublished - Feb 20 2016

Bibliographical note

Funding Information:
RK and TS conceived the study design and drafted the manuscript. TS, AW, SH conducted statistical analyses. All authors interpreted the data, read the manuscript, made meaningful changes and approved the final manuscript. Dr. Shafi was supported by K23-DK-083514 and National Kidney Foundation of Maryland Professional Development Award. Dr. Powe was supported by R01-DK-080123. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The reagents for troponin I and NTproBNP were provided by Siemens to the University of Maryland, where the measurements were performed. Siemens had no role in the design, analysis, and interpretation of data or the preparation of this manuscript. Parts of this work were presented at the National Kidney Foundation’s Spring Clinical Meeting April 22–26, 2014 at Las Vegas, NV.

Funding Information:
Dr. Shafi reports receiving an honorarium from Siemens. Remaining authors declare that they have no relevant financial interests. CHOICE was supported by R01-HS-008365 (Agency for Healthcare Quality and Research AHRQ) from 7/1994 to 6/1999, by RO1-HL-62985 (National Heart, Lung, and Blood Institute (NHLBI) from 9/00 to 6/06, R01-DK-059616 (National Institute of Diabetes & Digestive & Kidney Diseases NIDDK) from 9/2000 to 6/2005 and by R01-DK-080123 from 8/2008 to 6/2015 (National Institute of Diabetes & Digestive & Kidney Diseases NIDDK).

Publisher Copyright:
© 2016 Kruzan et al.


  • Hemodialysis
  • NTproBNP
  • Sudden Cardiac Death
  • Troponin I


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