title: Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.
abstract: 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.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Kruzan
authors.affiliation: Department of Medicine, Division of Cardiology, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore,, MD, USA.
authors.forename: Aozhou
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sang
authors.affiliation: Departments of Medicine and Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore,, MD, USA.|Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Seungyoung
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore,, MD, USA.|Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Departments of Medicine and Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Powe
authors.affiliation: Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA. tshafi@jhmi.edu.|Department of Medicine, Division of Nephrology, Johns Hopkins University, 301 Mason Lord Drive, Suite, 2500, Baltimore, MD, USA. tshafi@jhmi.edu.
authors.forename: Tariq
authors.initials: T
authors.lastname: Shafi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D018570:Risk Assessment; D012307:Risk Factors; D019210:Troponin I / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain