Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR

Background. Targeting a higher hemoglobinin patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesisstimulating agent (ESA) dose and in hemoglobinwere 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 Hemoglobinand Outcomes in Renal Disease ( CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobinwith changes in diastolic BP (DBP) and systolic BP (SBP). Poisson modeling was performed to determine whether changes in hemoglobinand 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 hemoglobinarm. Increases in ESA doses and in hemoglobinwere 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 ratioper 1000 U weekly dose per month increase 1.05, (1.02–1.08), P = 0.002 and event rate ratio1.70 (1.02– 2.85), P = 0.05, respectively]. However, increasing DBP was not associated with adverse outcomes [event rate ratio1.01 (0.98–1.03), P = 0.7]. Conclusion. Among CHOIRparticipants, higher hemoglobintargets, increases in ESA dose and in hemoglobinwere associated both with increases in DBP and with higher event rates; however, increasing DBP was not associated with adverse outcomes.