Objectives Differences in the association of haemoglobin concentration with mortality or adverse cardiovascular events in haemodialysis patients before and after experiencing cardiovascular disease are unclear. We aimed to assess the influence of cardiovascular-comorbid condition on the association between haemoglobin concentration and mortality.
Design A prospective cohort study.
Setting The Dialysis Outcomes and Practice Patterns Study Dialysis in phases 2 to 4 (2002 to 2011), including 80 randomly selected dialysis facilities in Japan (J-DOPPS).
Participants 5515 adult haemodialysis patients.
Primary and secondary outcome measures Primary outcome was all-cause mortality. Cardiovascular mortality and adverse cardiovascular events were also evaluated. The association of these outcomes with haemoglobin concentration, categorised into six classes by 1.0 g/dL units, and cardiovascular-comorbid condition, treated as a time-dependent variable updated every 4 months, was evaluated. Adjusted hazard ratios (aHRs) were computed using a time-dependent Cox model with interaction test for cardiovascular comorbidity.
Results Over a median 2.0 years, 847 all-cause and 326 cardiovascular deaths, and 1000 adverse cardiovascular events occurred. Compared with haemoglobin 11.0 to 11.9 g/dL, the aHRs of mortality at the lowest range (<9.0 g/dL) were 1.29 (95% CI 0.95 to 1.76) and 2.11 (95% CI 1.47 to 3.06) in cardiovascular-comorbid and non-cardiovascular-comorbid patients, respectively (p=0.04 for cardiovascular-comorbid interaction), with increased cardiovascular mortality in both groups. At the second-lowest range (9.0 to 9.9 g/dL), mortality was increased only in non-cardiovascular-comorbid patients. Respective risks for mortality and adverse cardiovascular events at the second-highest range (12.0 to 12.9 g/dL) were non-significant but increased in both groups, while adverse cardiovascular events were increased at the highest range (≥13.0 g/dL) in non-cardiovascular-comorbid patients.
Conclusions The association of low haemoglobin concentration with all-cause mortality differed between haemodialysis patients with and without cardiovascular comorbidity. Cardiovascular-comorbid condition should be considered when the association of haemoglobin concentration with mortality is addressed.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Contributors Research question and design of this study: RK; Statistical analysis of the study: RK; Data interpretation: RK, TA, SF; Manuscript writing: RK; Reviewing and critical revision of the manuscript for intellectual content: TA, SF; Supervision of this study: TA, SF. Each author contributed important intellectual content during article drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Funding The J-DOPPS data were provided by the Arbor Research Collaborative for Health and supported by scientific research grants from Kyowa Hakko Kirin Co., Ltd. (KHK), without restrictions on publication.
Competing interests TA reports consultant fees from Astellas, JT Pharmaceuticals, Torii Pharmaceutical, Kyowa Hakko Kirin, Nipro Medical, Ono Pharmaceutical, Bayer HealthCare, Fuso Pharmaceutical, GlaxoSmithKline and Kissei Pharmaceutical; and lecture fees from Chugai Pharmaceutical, Kyowa Hakko Kirin, Bayer HealthCare, Torii Pharmaceutical, Kissei Pharmaceutical and Ono Pharmaceutical.
Patient consent for publication Not required.
Ethics approval J-DOPPS was approved by a central ethics committee (Tokyo Women’s Medical University, approval no. 678 and 1527 for phase 3 and 4, respectively). For phase 2, the steering committee of J-DOPPS decided not to be required ethical approval by a central ethics committee because no interventional study using anonymised data was performed after patient consent forms were obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The J-DOPPS data were provided already anoymised by the Arbor Research Collaborative for Health, only for researchers who belong to facilities participating in the J-DOPPS and had permission from the steering committee of J-DOPPS to analyse the data.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.