title: Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR.
abstract: BACKGROUND
  Targeting a higher hemoglobin in patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesis-stimulating agent (ESA) dose and in hemoglobin were predictive of changes in blood pressure (BP) and whether these changes were associated with cardiovascular outcomes.
  
  
  METHODS
  In this secondary analysis of 1421 Correction of Hemoglobin and Outcomes in Renal Disease (CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobin with changes in diastolic BP (DBP) and systolic BP (SBP). Poisson modeling was performed to determine whether changes in hemoglobin and BP were associated with the composite end point of death or cardiovascular outcomes.
  
  
  RESULTS
  Monthly average DBP, but not SBP, was higher in participants in the higher hemoglobin arm. Increases in ESA doses and in hemoglobin were significantly associated with linear increases in DBP, but not consistently with increases in SBP. In models adjusted for demographics and comorbid conditions, increases in ESA dose (>0 U) and larger increases in hemoglobin (>1.0 g/dL/month) were associated with poorer outcomes [event rate ratio per 1000 U weekly dose per month increase 1.05, (1.02-1.08), P = 0.002 and event rate ratio 1.70 (1.02-2.85), P = 0.05, respectively]. However, increasing DBP was not associated with adverse outcomes [event rate ratio 1.01 (0.98-1.03), P = 0.7].
  
  
  CONCLUSIONS
  Among CHOIR participants, higher hemoglobin targets, increases in ESA dose and in hemoglobin were associated both with increases in DBP and with higher event rates; however, increasing DBP was not associated with adverse outcomes.
authors.affiliation: Department of Medicine, Renal Division, Duke University Medical Center, Durham, NC, USA. jula.inrig@utsouthwestern.edu
authors.forename: Jula K
authors.initials: JK
authors.lastname: Inrig
authors.forename: Shelly
authors.initials: S
authors.lastname: Sapp
authors.forename: Huiman
authors.initials: H
authors.lastname: Barnhart
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.forename: Donal
authors.initials: D
authors.lastname: Reddan
authors.forename: Ajay
authors.initials: A
authors.lastname: Singh
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Lynda
authors.initials: L
authors.lastname: Szczech
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006397:Hematinics / Q000008:administration & dosage*; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D008297:Male; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012307:Risk Factors
chemical_list: D006397:Hematinics; D006454:Hemoglobins