Low serum iron and transferrin saturation are associated with new-onset heart failure

Abstract Background Iron deficiency (ID) is prevalent in patients with heart failure (HF) (1,2), but its causes and the temporal relationship between ID and HF is unknown. It is unclear whether ID precedes the onset of HF or develops as a secondary condition. Animal studies show that ID can induce cardiac changes emulating HF (3), while HF can lead to the development of ID (4). Purpose We aimed to evaluate if low serum iron (S-iron) and transferrin saturation (TSAT) are associated with an increased risk of incident HF. Methods We investigated subjects without HF, from a population-based cohort (5), that had at least three measurements of either S-iron or TSAT. The primary outcome was hospital diagnosis of new-onset HF or death due to new-onset HF in the Swedish patient register. Results In all, 127 037 individuals were included in the analysis of S-iron and 125 482 in the analysis of TSAT. Mean age was 52 ±14 years and 51% were men. During a median follow-up of 24.9 years (interquartile range 19.4-27.2), 9324 (7.3%) individuals in the S-iron cohort and 9209 (7.3%) in the TSAT cohort were diagnosed with new-onset HF. The individuals within the lowest quartile (Q1) of S-iron (15.0 µmol/L) and TSAT (0.25) had the highest risk for new-onset HF. The hazard ratio for Q1 was 1.29 (95% confidence interval CI 1.17, 1.42) for S-iron and 1.32 (CI 1.20, 1.46) for TSAT, compared to the third quartile when adjusting for risk factors for HF. Conclusion Low S-iron and TSAT were associated with new-onset HF, suggesting that preexisting ID contribute to the high prevalence of ID in HF.