Gender Differences in the Clinical and Metabolic Manifestations of Anemia in Chronic Heart Failure

Background/Objectives: Anemia and abnormalities in iron-related biomarkers are common in chronic heart failure (CHF), but their relationships with biological sex and left ventricular ejection fraction (LVEF) remain incompletely understood. This study assessed sex-related differences in hematological, iron-related, oxidative stress, and purine metabolism biomarkers across CHF phenotypes. Methods: This cross-sectional observational study included 180 patients with CHF, classified according to sex, anemia status based on World Health Organization sex-specific hemoglobin thresholds, and LVEF category: heart failure with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmrEF), or reduced ejection fraction (HFrEF). Hematological parameters, serum iron, ferritin, plasma and erythrocyte purine metabolites, oxidative modification of proteins (OMB), and advanced oxidation protein products (AOPPs) were evaluated. Group comparisons were performed using the Kruskal–Wallis and Mann–Whitney U tests, with Benjamini–Hochberg false discovery rate correction for multiple testing. Results: After multiple-testing correction, none of the biomarker comparisons across LVEF categories remained statistically significant when women and men were analyzed separately. Among women with HFpEF, median ferritin was 33.0 μg/L overall and 20.35 μg/L among those with anemia; however, these values could not be used to determine the mechanism of iron deficiency. Among men, anemia was associated with a higher platelet count in HFpEF (287 versus 203 × 109/L; q < 0.009) and lower serum iron concentrations in HFpEF (8.8 versus 18.1 μmol/L; q = 0.029) and HFrEF (5.5 versus 12.0 μmol/L; q = 0.036). In direct comparisons between sexes, only the higher hemoglobin concentration in men with HFmrEF remained statistically significant after correction (148 versus 121 g/L; q < 0.036). Nominal differences in plasma purines, hypoxanthine, and xanthine between anemic men and women with HFrEF did not remain statistically significant after correction (all q = 0.147). Conclusions: The findings demonstrate exploratory associations between sex, anemia status, LVEF category, and selected laboratory biomarkers but do not establish sex-specific mechanisms of anemia or purine metabolism alterations in CHF. Because transferrin saturation, transferrin-related indices, soluble transferrin receptor, hepcidin, and inflammatory biomarkers were not measured, the observed iron-related patterns cannot be classified as absolute iron deficiency or inflammation-associated functional iron restriction. Larger studies incorporating formal interaction testing, multivariable adjustment, and comprehensive assessment of iron status are required.