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Prognostic Role of Tissue Iron Deficiency Measured by Stfr Levels in Heart Failure Patients Without Systemic Iron Deficiency or Anemia

Raul Ramos-Polo, Maria del Mar Ras-Jimenez, Josep Francesch Manzano, Silvia Jovells-Vaque, Herminio Morillas Climent,Alexandra Pons-Riverola,Sergi Yun Viladomat,Pedro Moliner Borja,Carles Diez-Lopez,Jose Gonzalez-Costello,Elena Garcia-Romero, Lorena Herrador, Fernando de Frutos Seminario,Cristina Enjuanes Grau,Marta Tajes Orduna,Josep Comin-Colet

JOURNAL OF CLINICAL MEDICINE(2024)

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Abstract
Background. Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods. This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results. The sTfR level (HR 1.48, 95% CI 1.13–1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22–3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.
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Key words
chronic heart failure,comorbidities,iron deficiency,biomarkers,clinical outcomes
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