Soluble transferrin receptor as a marker of tissue iron deficiency: impact on health-related quality of life in patients with heart failure without systemic iron deficiency or anaemia

Abstract Background Soluble receptor of transferrin (sTfR) is a marker of tissue iron status and may help to inform on subtle iron depletion and increased iron demand of functional proteins at tissular level even in the absence of systemic iron deficiency or anaemia. Raised sTfR levels have been associated with of all-cause mortality and impaired exercise capacity in patients with heart failure (HF). However, the impact quality of life (QoL) has not been evaluated. Purpose The aim of our study was to describe the association between sTfR as a marker of increased iron demand and tissue iron deficiency and QoL in non-anaemic patients with HF and normal systemic iron status. Methods We conducted an observational, prospective, cohort study of 1120 consecutive patients with chronic HF (DAMOCLES study). For the current sub-study, we selected all patients form the DAMOCLES cohort that had normal haemoglobin levels and normal systemic iron and available QoL data. Tissue ID was defined as levels of sTfR> 75th percentile (1.63mg/L). To assess QoL, we used the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The primary endpoint was the overall summary score (OSS) of the MLHFQ instrument self-administered at inclusion in the study. The unadjusted parametric and non-parametric associations between sTfR and the MLHFQ OSS scores were explored using General Additive Models (GAM). Univariate and multivariate linear regression models were constructed to explore the associations between sTfR levels and tissue ID and the QoL scores. All models were adjusted by age, sex, and prognostic factors such as LVEF, NYHA, NT-proBNP levels and iron status parameters among other well-known determinants of HF severity. Results The final study cohort consisted in 206 patients. Mean age was 70±12 years, mean LVEF was 43±15% and 61 (30%) were women. Mean sTfR values were 1.42±0.66 mg/L. Tissue ID was present in 54 patients (26%). Mean MLHFQ OSS were 42±26. Global QoL was significantly worse in patients with tissue ID compared to patients without tissue ID (51±27 vs. 39±20, p-value=0.006, respectively). In unadjusted GAM models (Figure 1) showed a direct and significant association between increased iron demand and worse global QoL with a linear p-value<0.0001. As shown in Table 1, higher sTfR were associated with higher MLHFQ OSS scores in unadjusted models. These findings were confirmed in forward stepwise multivariate linear regression models (Table 1). Conclusions In a cohort of HF patients without iron deficiency or anaemia, higher levels of sTfR indicating increased iron demand and tissue ID were associated with worse QoL.