Iron deficiency's association with stroke and TIA in patients with heart failure

Introduction

Heart failure (HF) is a global health problem that affects millions of individuals worldwide and contributes profoundly to morbidity, mortality, as well as to an impaired quality of life (QoL). Iron deficiency (ID) in HF, defined by the ESC as a serum iron < 100 ng/mL or as 100-299 ng/mL with a transferrin saturation (TSAT) < 20%, is a frequent comorbidity in patients with HF, occurring in about half of this patient population. In the setting of HF, ID is linked with poorer clinical outcomes including increased hospitalisation rates, diminished QoL, reduced exercise tolerance, and increased risk of mortality.

Purpose

This study aims to determine the prevalence of ID in HF patients, regardless of the ejection fraction (EF) as well as to explore comorbidities which are associated with ID in HF in the studied population with a strong focus on cerebrovascular events like stroke/transient ischaemic attacks (TIA).

Methods

A retrospective cohort was analysed of 259 patients (126 females and 133 males) of whom 51% had ID with the median age of 72 [IQR: 66-79], and all who were hospitalised between 2018-2025. ID was defined according to the ESC criteria based on serum ferritin and TSAT saturation.

Results

The analysis demonstrated significant differences between HF patients with and without ID, with the ID group showing lower GFR, red blood cell (RBC) parameters, uric acid, 6MWT (259.00 m [IQR: 195.10-307.50] vs 280.00 m [IQR: 239.00-344.00], p=0.0423), and higher stroke/TIA prevalence (15.83% vs 6.67%, p=0.0204) and proton pump inhibitor (PPI) usage (45.32% vs 25.00%, p=0.0007).

In the analysis related to anaemia in the ID population, in patients with anaemia, comparison showed significant differences in RBC parameters, iron parameters, GFR (52.05 [IQR: 41.00-63.75] vs 58,30 [IQR: 46.90-73.90], p=0.0087), and NT-proBNP values (1408.00 [IQR: 651.90-2970.00] vs 652.05 [IQR: 285.10-1726.00], p=0.0034). Additionally, patients with anaemia had higher values of pulmonary artery systolic pressure (PASP) (43.00 mmHg [IQR: 34.00-68.00] vs 40.00 mmHg [IQR: 30.00-47.50], p=0.0211), a higher prevalence of moderate or severe pathologies of the tricuspid valve (35.85% vs 20.39%, p=0.0173) and were more likely to be taking PPIs (50.94% vs 32.04%, p=0.0105).

Conclusion

Iron deficiency in patients with HF is associated with a higher prevalence of stroke/TIA, lower uric acid levels, and reduced 6MWT results, with stroke/TIA occurring more than twice as frequently in this group. Additionally, ID is more prevalent among patients receiving PPIs, suggesting a link between PPI therapy and ID. Lastly, concomitant anaemia with ID in HF is associated with higher NT-proBNP values, lower GFR, and higher values of PASP.