Disordered Iron Homeostasis in Chronic Heart Failure: Prevalence, Predictors, and Relation to Anemia, Exercise Capacity, and Survival

• Published in: Journal of the American College of Cardiology Vol. 58; no. 12; pp. 1241 - 1251
• Main Authors: OKONKO, Darlington O, MANDAL, Amit K. J, MISSOURIS, Constantinos G, POOLE-WILSON, Philip A
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 13.09.2011; Elsevier Limited
• Subjects: Aged; Aged, 80 and over; Anemia; Anemia - metabolism; Anemia, Iron-Deficiency - metabolism; Anemia, Iron-Deficiency - mortality; Anemias. Hemoglobinopathies; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Chronic Disease; Chronic illnesses; Diseases of red blood cells; Enzymes; Exercise Tolerance - physiology; Female; Heart; Heart failure; Heart Failure - complications; Heart Failure - metabolism; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hematologic and hematopoietic diseases; Homeostasis; Humans; Iron; Iron - metabolism; Iron Metabolism Disorders - complications; Iron Metabolism Disorders - epidemiology; Iron Metabolism Disorders - metabolism; Iron Metabolism Disorders - mortality; Male; Medical sciences; Middle Aged; Mortality; Prevalence; Prognosis; Prospective Studies; United Kingdom > UK; Physical exercise; Heart failure; Prognosis; Prevalence; Anemia; Predictor; Homeostasis; Cardiovascular disease; Hemopathy; Iron; Epidemiology; Survival; Chronic; Capacity; Heart disease; Exercise tolerance test; Circulatory system; Cardiology; Predictive factor
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2011.04.040

The aim of this study was to comprehensively delineate iron metabolism and its implications in patients with chronic heart failure (CHF). Iron deficiency is an emerging therapeutic target in CHF. Iron and clinical indexes were quantified in 157 patients with CHF. Several observations were made. First, iron homeostasis was deranged in anemic and nonanemic subjects and characterized by diminished circulating (transferrin saturation) and functional (mean cell hemoglobin concentration) iron status in the face of seemingly adequate stores (ferritin). Second, while iron overload and elevated iron stores were rare (1%), iron deficiency (transferrin saturation <20%) was evident in 43% of patients. Third, disordered iron homeostasis related closely to worsening inflammation and disease severity and strongly predicted lower hemoglobin levels independently of age, sex, erythrocyte sedimentation rate, New York Heart Association (NYHA) functional class, and creatinine. Fourth, the etiologies of anemia varied with disease severity, with an iron-deficient substrate (anemia of chronic disease and/or iron-deficiency anemia) evident in 16%, 72%, and 100% of anemic NYHA functional class I or II, III, and IV patients, respectively. Although anemia of chronic disease was more prevalent than iron-deficiency anemia, both conditions coexisted in 17% of subjects. Fifth, iron deficiency was associated with lower peak oxygen consumption and higher ratios of ventilation to carbon dioxide production and identified those at enhanced risk for death (hazard ratio: 3.38; 95% confidence interval: 1.48 to 7.72; p = 0.004) independently of hemoglobin. Nonanemic iron-deficient patients had a 2-fold greater risk for death than anemic iron-replete subjects. Disordered iron homeostasis in patients with CHF relates to impaired exercise capacity and survival and appears prognostically more ominous than anemia.