Hepcidin, Incident Heart Failure and Cardiac Dysfunction in Older Adults: the ARIC Study.

Abstract

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study who were free from prevalent anemia and HF at Visit 5 (2011-2013) and had available hepcidin and covariate data. Associations of plasma hepcidin levels with overall adjudicated incident HF, HF with reduced and HF with preserved ejection fraction (HFrEF and HFpEF) were assessed using multivariable Cox proportional hazards regression models. Cross-sectional associations of hepcidin with echocardiographic measures of cardiac structure and function were estimated using multivariable linear regression models.

Results: The mean age was 75±5 years old and 56% were women. In fully adjusted models, lower hepcidin levels were associated with a higher risk of overall incident HF (HR [95% CI] per 50% lower hepcidin: 1.15 [1.05-1.26]; P=0.003) and HFpEF (HR [95% CI]: 1.25 [1.10-1.42]; P=0.001). Plasma hepcidin level was not significantly associated with the risk of incident HFrEF (HR [95% CI]: 1.08 [0.94-1.24]; P=0.30). Lower hepcidin levels were associated with higher E wave (P=0.046), higher E/e' ratio (P=0.002), higher left atrial volume index (P=0.005) and higher pulmonary artery systolic pressure (P=0.02).

Conclusion: In community-dwelling older adults without anemia, lower plasma hepcidin levels associate with a higher risk of incident HF (particularly HFpEF) and diastolic dysfunction. The findings imply the importance of monitoring iron metabolism dysregulation, even in absence of anemia, in late life.