The additive burden of iron deficiency in the cardiorenal-anaemia axis: scope of a problem and its consequences

Aims Iron deficiency (ID), anaemia, and chronic kidney disease (CKD) are common co-morbidities in chronic heart failure (CHF) and all independent predictors of unfavourable outcome. The combination of anaemia and CKD in CHF has been described as the cardiorenal-anaemia syndrome. However, the role of ID within this complex interplay of co-existing pathologies is unclear. Methods and results We studied the clinical correlates of ID (defined as ferritin <100 mu g/L or 100-299 mu g/L in combination with a transferrin saturation <20%, anaemia) and renal dysfunction (defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2)) and their prognostic implications in an international pooled cohort, comprising 1506 patients with CHF. Mean age was 6413 years, 74.2% were male, and 47.3% were in NYHA functional class III. The presence of ID, anaemia, CKD, or a combination of these co-morbidities was observed in 69.3% of the patients. During a median (Q1-Q3) follow-up of 1.92 years (1.18-3.26 years), 440 patients (29.2%) died. Eight-year survival rates decreased significantly from 58.0% for no co-morbidities to 44.6, 33.0, and 18.4%, for one, two, or three co-morbidities, respectively (P < 0.001). Multivariate hazard models revealed ID to be the key determinant of prognosis, either individually (P=0.04) or in combination with either anaemia (P=0.006), CKD (P=0.03), or both (P=0.02). Conclusions Iron deficiency frequently overlaps with anaemia and/or CKD in CHF. The presence of ID amplifies mortality risk, either alone or in combination with anaemia, CKD, or both, making it a potential viable therapeutic target.