Prognostic impact of cardio-renal-anemia syndrome in heart failure - a report from the JROADHF database

Background Anemia is a common comorbidity in patients with heart failure (HF) and an independent risk factor for long-term outcomes. In addition to anemia, renal dysfunction (RD) is a significant risk factor in both acute and chronic HF. HF, anemia, and RD interact negatively, resulting in the cardio-renal-anemia syndrome (CRAS). Recently, moderate/severe anemia [Hb <10g/dL] is recommended to be treated in patients with renal anemia. However, the optimal therapeutic target for Hb levels in patients with CRAS is unknown. Purpose This study aimed to investigate the impact of severity of anemia associated with RD (eGFR<60 mL/min/1.73 m2) in HF patients. Methods We analyzed 13,098 HF patients from the Japanese Registry of Acute Decompensated Heart Failure (JROADHF) database. Patients were classified based on the severity of admission anemia in the presence/absence of RD. Results In the JROADHF database, 13,098 patients were identified to have creatinine and Hb levels at admission. Of these, 3,478 patients had normal renal function and 9,620 patients had RD. Hb levels in non- (14.2 ± 1.4g/dL vs. 14.0 ± 1.5 g/dL, P<0.0001), mild (11.4 ± 0.8 g/dL vs. 11.2 ± 0.8 g/dL, P<0.0001), and moderate/severe anemia groups (8.6 ± 1.3 g/dL vs. 8.6 ± 1.1 g/dL, P=0.30) were similar between patients with and without RD. Patients with Patients with RD and moderate/severe anemia were older, more likely to be female, and had a history of HF admission. In addition, they had lower eGFR levels compared with those with RD and non/mild anemia (29.3 ± 14.3g/dL vs. 38.0 ± 14.2 g/dL, P<0.001). The composite outcome of cardiovascular death or HF rehospitalization was higher in patients with RD and moderate/severe anemia (adjusted hazard ratio [aHR]: 1.57, 95% confidential interval [CI]: 1.36–1.82, p < 0.001) compared to those with RD and no/mild anemia (Hb ≥10 g/dL), non-RD and moderate/severe anemia, and non-RD and no/mild anemia (reference). The risks of cardiovascular death (aHR: 2.02, 95%CI: 1.61–2.53, p < 0.001), HF rehospitalization (aHR: 1.57, 95%CI: 1.34–1.83, p < 0.001), and all-cause death (aHR: 1.85, 95%CI: 1.59–2.16, p < 0.001) were also higher in n patients with RD and moderate/severe anemia. Conclusions Moderate/severe anemia has a prognostic impact in HF patients with RD and may be an appropriate therapeutic target in HF. Management of anemia during hospitalization may be important for improving long-term outcomes for HF patients.