Association Between Iron Deficiency (With or Without Anemia) and Risk of Heart Failure in Adults: A Meta-Analysis of Observational and Clinical Studies

Abdul Rashid; Hashim Bani Hashim; Tanjeeda Parvin Toma; Awad Rahama Mustafa Elhussain; Syeda Fatima Andleeb Sherazi; Salaheldeen Elhassab Omar Elhassab; Abdalmonim Abdoalrhman Mohammed

doi:10.70749/ijbr.v3i4.1181

Authors

Abdul Rashid HOD, Department of Cardiology, POF Hospital/ Wah Medical College, National University of Medical Sciences, Wah Cantt, Pakistan. https://orcid.org/0009-0002-4868-4483
Hashim Bani Hashim Gajju Khan Medical College, Swabi, Pakistan.
Tanjeeda Parvin Toma Uttara Adhunik Medical College and Hospital, Dhaka, Bangladesh.
Awad Rahama Mustafa Elhussain Department of Physiology, Najran University, Najran, Saudi Arabia.
Syeda Fatima Andleeb Sherazi Sir Syed Medical College for Girls, Karachi, Pakistan.
Salaheldeen Elhassab Omar Elhassab Department of Physiology, Najran University, Najran, Saudi Arabia.
Abdalmonim Abdoalrhman Mohammed Department of Anatomy, Najran University, Najran, Saudi Arabia.

DOI:

https://doi.org/10.70749/ijbr.v3i4.1181

Keywords:

Heart Failure, Iron Deficiency, Anemia, Meta-Analysis, Cardiovascular Outcomes

Abstract

Background: Iron deficiency, even without anemia, worsens heart failure outcomes. Its independent role in heart failure progression remains unclear despite growing evidence. Objective: To assess the link between iron deficiency and adverse outcomes in heart failure via a systematic review and meta-analysis. Methods: This meta-analysis adhered to PRISMA guidelines. A comprehensive search of PubMed, Embase, Scopus, and the Cochrane Library was conducted to identify eligible studies evaluating iron deficiency and HF outcomes. Inclusion criteria comprised adult HF patients, iron deficiency defined by ferritin <100 ng/mL or 100–299 ng/mL with transferrin saturation <20%, and reported outcomes related to mortality, hospitalization, symptom burden, or functional capacity. Pooled hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated using a random-effects model. Subgroup and sensitivity analyses were performed, and risk of bias was assessed using Cochrane and Newcastle-Ottawa tools. Results: Six studies (n = 2,823) were included, comprising four RCTs and two observational cohorts. The pooled analysis showed that iron deficiency was associated with significantly worse HF outcomes (HR 0.85; 95% CI: 0.75–0.97). Subgroup analysis revealed favorable outcomes in RCTs (HR 0.76; 95% CI: 0.64–0.90), particularly among patients with concomitant anemia (HR 0.78; 95% CI: 0.65–0.93). Observational studies, in contrast, showed increased risk in iron-deficient patients (HR 1.68; 95% CI: 1.25–2.26). The association in non-anemic patients was not statistically significant (HR 0.88; 95% CI: 0.72–1.06). Conclusion: Iron deficiency, especially when accompanied by anemia, is a significant predictor of adverse clinical outcomes in heart failure. These findings support routine iron status screening and the consideration of iron repletion therapy as part of comprehensive HF management strategies.

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