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]. CONCLUSION: 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.
RCT Entities:
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]. CONCLUSION: 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: Suetonia C Palmer; Sankar D Navaneethan; Jonathan C Craig; David W Johnson; Marcello Tonelli; Amit X Garg; Fabio Pellegrini; Pietro Ravani; Meg Jardine; Vlado Perkovic; Giusi Graziano; Richard McGee; Antonio Nicolucci; Gianni Tognoni; Giovanni F M Strippoli Journal: Ann Intern Med Date: 2010-06-24 Impact factor: 25.391
Authors: Preston S Klassen; Edmund G Lowrie; Donal N Reddan; Elizabeth R DeLong; Joseph A Coladonato; Lynda A Szczech; J Michael Lazarus; William F Owen Journal: JAMA Date: 2002-03-27 Impact factor: 56.272
Authors: Marit M Suttorp; Tiny Hoekstra; Moshe Mittelman; Ilka Ott; Casper F M Franssen; Friedo W Dekker Journal: PLoS One Date: 2013-12-31 Impact factor: 3.240
Authors: Francisca Johanna van den Oever; Carolien F M Heetman-Meijer; Erwin Birnie; Erwin C Vasbinder; Eleonora L Swart; Yvonne C Schrama Journal: Pharmacol Res Perspect Date: 2020-08
Authors: Suetonia C Palmer; Valeria Saglimbene; Dimitris Mavridis; Georgia Salanti; Jonathan C Craig; Marcello Tonelli; Natasha Wiebe; Giovanni F M Strippoli Journal: Cochrane Database Syst Rev Date: 2014-12-08