Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function: The ARIC Study

Background: Whether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion. Objectives: The aim of this study was to estimate the associations of plasma ferritin level with incident HF overall, HF phenotypes, and cardiac structure and function measures in older adults. Methods: Participants in the ongoing, longitudinal ARIC (Atherosclerosis Risk In Communities) study who were free of prevalent HF and anemia were studied. The associations of plasma ferritin levels with incident HF overall and heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) were estimated using Cox proportional hazards regression models. Linear regression models estimated the cross-sectional associations of plasma ferritin with echocardiographic measures of cardiac structure and function. Results: The cohort included 3,472 individuals with a mean age of 75 ± 5 years (56% women, 14% Black individuals). In fully adjusted models, lower ferritin was associated with higher risk for incident HF overall (HR: 1.20 [95% CI: 1.08-1.34] per 50% lower ferritin level) and higher risk for incident HFpEF (HR: 1.28 [95% CI: 1.09-1.50]). Associations with incident HFrEF were not statistically significant. Lower ferritin levels were associated with higher E/e′ ratio and higher pulmonary artery systolic pressure after adjustment for demographics and HF risk factors but not with measures of left ventricular structure or systolic function. Conclusions: Among older adults without prevalent HF or anemia, lower plasma ferritin level is associated with a higher risk for incident HF, HFpEF, and higher measures of left ventricular filling pressure.