Anemia and Prognosis in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent clinical syndrome associated with substantial morbidity and mortality, while effective treatment options remain comparatively limited. Anemia is a common comorbidity in HFpEF and may be linked to adverse outcomes through impaired oxygen delivery, systemic inflammation, and neurohormonal activation. However, the magnitude and consistency of its prognostic significance remain uncertain because prior studies have differed in definitions, clinical settings, and patient characteristics. This systematic review and meta-analysis synthesized data from six studies, including one post hoc randomized trial analysis, prospective registries, and observational cohorts, to evaluate the association between anemia and all-cause mortality in HFpEF. A pooled random-effects analysis yielded very low-certainty evidence suggesting that anemia may be associated with increased all-cause mortality, although considerable between-study heterogeneity was present. Narrative synthesis suggested broadly similar directional trends across geographic regions and clinical contexts, including hospitalized and stable HFpEF populations. Sensitivity analyses showed that the direction of association was generally consistent, although the magnitude of the effect varied with the exclusion of influential studies. Overall, these findings suggest that anemia may represent a potential adverse prognostic marker in HFpEF, while highlighting the need for prospective studies and interventional trials to clarify mechanisms and determine whether targeted treatment strategies improve outcomes.