Laboratory for Applied Research of Cardiovascular System, Department of Heart Diseases, Faculty of Health Sciences, Wroclaw Medical University, ul. Weigla 5, 50-981 Wroclaw, Poland.
Eur Heart J. 2013 Mar;34(11):827-34. doi: 10.1093/eurheartj/ehs377. Epub 2012 Nov 23.
The changes in iron status occurring during the course of heart failure (HF) and the underlying pathomechanisms are largely unknown. Hepcidin, the major regulatory protein for iron metabolism, may play a causative role. We investigated iron status in a broad spectrum of patients with systolic HF in order to determine the changes in iron status in parallel with disease progression, and to associate iron status with long-term prognosis.
Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 321 patients with chronic systolic HF [age: 61 ± 11 years, men: 84%, left ventricular ejection fraction: 31 ± 9%, New York Heart Association (NYHA) class: 72/144/87/18] at a tertiary cardiology centre and 66 age- and gender-matched healthy subjects. Compared with healthy subjects, asymptomatic HF patients had similar haematological status, but increased iron stores (evidenced by higher serum ferritin without distinct inflammation, P < 0.01) with markedly elevated serum hepcidin (P < 0.001). With increasing HF severity, patients in advanced NYHA classes had iron deficiency (ID) (reduced serum ferritin, low Tsat, high sTfR), iron-restricted erythropoiesis (reduced haemoglobin, high red cell distribution width), and inflammation (high serum high-sensitivity-C-reactive protein and interleukin 6), which was accompanied by decreased circulating hepcidin (all P < 0.001). In multivariable Cox models, low hepcidin was independently associated with increased 3-year mortality among HF patients (P < 0.001).
Increased level of circulating hepcidin characterizes an early stage of HF, and is not accompanied by either anaemia or inflammation. The progression of HF is associated with the decline in circulating hepcidin and the development of ID. Low hepcidin independently relates to unfavourable outcome.
心力衰竭（HF）过程中铁状态的变化及其潜在的病理机制在很大程度上尚不清楚。铁调素是铁代谢的主要调节蛋白，可能起因果作用。我们研究了广泛的收缩性心力衰竭患者的铁状态，以确定铁状态随疾病进展的变化，并将铁状态与长期预后相关联。
在一家三级心脏病中心，我们评估了 321 例慢性收缩性 HF 患者（年龄：61±11 岁，男性：84%，左心室射血分数：31±9%，纽约心脏协会[NYHA]分级：72/144/87/18）和 66 名年龄和性别匹配的健康对照者的血清铁蛋白、转铁蛋白饱和度（Tsat）、可溶性转铁蛋白受体（sTfR）和铁调素作为铁状态的生物标志物。与健康对照组相比，无症状 HF 患者具有相似的血液学状态，但铁储存增加（表现为血清铁蛋白升高而无明显炎症，P＜0.01），且血清铁调素明显升高（P＜0.001）。随着 HF 严重程度的增加，处于晚期 NYHA 级别的患者出现缺铁（ID）（血清铁蛋白降低，Tsat 低，sTfR 高）、铁限制红细胞生成（血红蛋白降低，红细胞分布宽度高）和炎症（高敏 C 反应蛋白和白细胞介素 6 高），同时伴有循环铁调素降低（均 P＜0.001）。多变量 Cox 模型表明，低铁调素与 HF 患者 3 年死亡率增加独立相关（P＜0.001）。
循环铁调素水平升高是 HF 的早期阶段，且不伴有贫血或炎症。HF 的进展与循环铁调素水平下降和 ID 的发展有关。低铁调素与不良预后独立相关。
