Iron Deficiency in Chronic Heart Failure
Iron Deficiency in Chronic Heart Failure
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 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.
Despite improvements in chronic heart failure (HF) treatment over the years, normal daily activities of many patients remain restricted. Anemia, a common comorbidity in HF, is associated with increased disease severity and may contribute to a worse outcome. The mechanism through which anemia contributes to adverse outcome in chronic HF patients is complex and multifactorial. Important factors include renal failure, bone marrow resistance to erythropoietin, chronic inflammation, medication use and hematinic deficiencies, in particular iron deficiency (ID).
Traditionally, the presence of ID is only considered clinically relevant in the presence of anemia. However, a reduced hemoglobin levels can be viewed as the end result of a process beginning with gradual depletion of iron stores. Even if patients are not anemic, ID may already be common in chronic HF. Iron deficiency, with or without anemia, is associated with decreased aerobic performance and exercise intolerance, recently also shown in chronic HF.
In recent years, a number of studies have shown that correction of ID through intravenous iron supplementation in patients with chronic HF may improve functional status and quality of life. This was observed in both anemic and nonanemic patients with chronic HF, shifting the focus for anemia in HF away from hemoglobin and toward iron. The prevalence and potential importance of ID per se, irrespective of hemoglobin, are currently a subject of interest in HF. However, data on this topic are scarce and only a few studies have reported on ID as a predictor of outcome in chronic HF. These studies show conflicting data regarding the prognostic value of ID with or without anemia. Therefore, the current study was initiated by a European iron consortium to investigate the prevalence, clinical determinants, and prognostic significance of ID in a large international pooled cohort of 1,506 chronic HF patients.
Abstract and Introduction
Abstract
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 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.
Introduction
Despite improvements in chronic heart failure (HF) treatment over the years, normal daily activities of many patients remain restricted. Anemia, a common comorbidity in HF, is associated with increased disease severity and may contribute to a worse outcome. The mechanism through which anemia contributes to adverse outcome in chronic HF patients is complex and multifactorial. Important factors include renal failure, bone marrow resistance to erythropoietin, chronic inflammation, medication use and hematinic deficiencies, in particular iron deficiency (ID).
Traditionally, the presence of ID is only considered clinically relevant in the presence of anemia. However, a reduced hemoglobin levels can be viewed as the end result of a process beginning with gradual depletion of iron stores. Even if patients are not anemic, ID may already be common in chronic HF. Iron deficiency, with or without anemia, is associated with decreased aerobic performance and exercise intolerance, recently also shown in chronic HF.
In recent years, a number of studies have shown that correction of ID through intravenous iron supplementation in patients with chronic HF may improve functional status and quality of life. This was observed in both anemic and nonanemic patients with chronic HF, shifting the focus for anemia in HF away from hemoglobin and toward iron. The prevalence and potential importance of ID per se, irrespective of hemoglobin, are currently a subject of interest in HF. However, data on this topic are scarce and only a few studies have reported on ID as a predictor of outcome in chronic HF. These studies show conflicting data regarding the prognostic value of ID with or without anemia. Therefore, the current study was initiated by a European iron consortium to investigate the prevalence, clinical determinants, and prognostic significance of ID in a large international pooled cohort of 1,506 chronic HF patients.
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