BACKGROUND: Iron deficiency (ID) is currently defined as a serum ferritin level <
100 or 100 to 299 ng/mL with transferrin saturation (TSAT) <
20%. Serum ferritin and TSAT are currently used to define absolute and functional ID. However, individual markers of iron metabolism may be more informative than current arbitrary definitions of ID. METHODS: We assessed prognostic associations of ferritin, serum iron, and TSAT among 2050 participants with heart failure (HF) with reduced/mid-range (n=1821) or preserved (n=229) left ventricular ejection fraction enrolled in the PHFS (Penn HF Study), a prospective cohort study. We measured 4928 plasma proteins using an aptamer-based assay (SOMAScanv4) and assessed prognostic and proteomic associations of markers of iron metabolism. RESULTS: Ferritin concentrations were not associated with outcomes, whereas low TSAT and serum iron were associated with the risk of all-cause death (TSAT: standardized hazard ratio, 0.84 [95% CI, 0.76-0.93]
CONCLUSIONS: Low TSAT, but not ferritin concentrations, is significantly associated with adverse outcomes in HF. Low TSAT is more strongly associated with outcomes in HF with preserved ejection fraction. Pathways related to inflammation and lipid metabolism are associated with low TSAT in HF.