Haemoglobin concentration and survival of haemodialysis patients before and after experiencing cardiovascular disease: a cohort study from Japanese dialysis outcomes and practice pattern study (J-DOPPS)

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.