Intrinsic Iron Release Is Associated with Lower Mortality in Patients with Stable Coronary Artery Disease-First Report on the Prospective Relevance of Intrinsic Iron Release.

Julia Ruhe,Stefan Blankenberg,Sarina Schäfer,Mahir Karakas,Alev Altay,Renate Schnabel,Christoph Waldeyer,Karl Lackner,Francisco Ojeda,Tanja Zeller

doi:10.3390/biom8030072

Abstract

Intrinsic iron release is discussed to have favorable effects in coronary artery disease (CAD). The aim of this study was to evaluate the prognostic relevance of intrinsic iron release in patients with CAD. Intrinsic iron release was based on a definition including hepcidin and soluble transferrin receptor (sTfR). In a cohort of 811 patients with angiographically documented CAD levels of hepcidin and sTfR were measured at baseline. Systemic body iron release was defined as low levels of hepcidin (<24 ng/mL) and high levels of sTfR (≥2 mg/L). A commercially available ELISA (DRG) was used for measurements of serum hepcidin. Serum sTfR was determined by using an automated immunoassay (). Cardiovascular mortality was the main outcome measure. The criteria of intrinsic iron release were fulfilled in 32.6% of all patients. Significantly lower cardiovascular mortality rates were observed in CAD patients with systemic iron release. After adjustment for body mass index, smoking status, hypertension, diabetes, dyslipidemia, sex, and age, the hazard ratio for future cardiovascular death was 0.41. After an additional adjustment for surrogates of the size of myocardial necrosis (troponin I), anemia (hemoglobin), and cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide), this association did not change (Hazard ratio 0.37 (95% confidence interval 0.14–0.99), p = 0.047). In conclusion, significantly lower cardiovascular mortality rates were observed in CAD patients with intrinsic iron release shown during follow-up.

Highlights

Iron is an essential component for the transport and utilization of oxygen and for appropriate mitochondrial function [1,2]
As mammals in general, have no capacity of active iron excretion, iron homeostasis is completely regulated through hepcidin [6]
C-Reactive protein (CRP), N-terminal pro B-type natriuretic peptide (NT-proBNP,) troponin I, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol measurements were done by routine methods in the participating hospitals [14,15,16,17]

Summary

Introduction

Iron is an essential component for the transport and utilization of oxygen and for appropriate mitochondrial function [1,2]. Intrinsic systemic body iron release is defined as concomitance of low hepcidin and high soluble transferrin levels (sTfR) levels and mirrors a state of maximum bioavailability of iron in the circulation (low hepcidin), as well as increased utilization and high turnover of iron by demanding cells (high sTfR) [4]. Hepcidin is secreted by hepatocytes and orchestrates systemic iron metabolism [5]. As mammals in general, have no capacity of active iron excretion, iron homeostasis is completely regulated through hepcidin [6]. After the cellular uptake of iron through the transferrin receptor on the cell surface, the plasma-bound transferrin receptor is released into serum by proteolytic cleavage [4]: high circulating levels of sTfR reflect high turnover and increased utilization of circulating iron [8]. STfR levels are not affected by concomitant chronic disease and inflammation [9]

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