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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 µg/L or 100-299 µg/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 64 ± 13 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., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: Iron deficiency (ID) is an emerging problem in patients with chronic heart failure (HF) and can be a potential therapeutic target. However, not much is known about the prevalence, predictors, and prognosis of ID in patients with chronic HF., Methods: In an international pooled cohort comprising 1,506 patients with chronic HF, we studied the clinical associates of ID and its prognostic consequences., Results: Iron deficiency (defined as a ferritin level <100 μg/L or ferritin 100-299 μg/L with a transferrin saturation <20%) was present in 753 patients (50%). Anemic patients were more often iron deficient than nonanemic patients (61.2% vs 45.6%, P < .001). Other independent predictors of ID were higher New York Heart Association class, higher N-terminal pro-brain-type natriuretic peptide levels, lower mean corpuscular volume levels, and female sex (all P < .05). During follow-up (median 1.92 years, interquartile range 1.18-3.26 years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as a strong predictor for mortality (log rank χ(2) 10.2, P = .001). In multivariable hazard models, ID (but not anemia) remained a strong and independent predictor of mortality (hazard ratio 1.42, 95% confidence interval 1.14-1.77, P = .002). Finally, the presence of ID significantly enhanced risk classification and integrated discrimination improvement when added to a prediction model with established risk factors., Conclusions: Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia., (Copyright © 2013 Mosby, Inc. All rights reserved.)