Ferritin levels and risk of heart failure—the Atherosclerosis Risk in Communities Study

Abstract

Aims Severe iron overload is associated with cardiac damage, while iron deficiency has been related to worse outcomes in subjects with heart failure (HF). This study investigated the relationship between ferritin, a marker of iron status, and the incidence of HF in a community-based cohort. Methods and results We examined 1,063 participants who were free of heart failure from the Atherosclerosis Risk in Communities (ARIC) study in whom ferritin serum levels were measured at baseline (1987–1989). The participants (mean age 52.7 ± 5.5 years, 62% women), were categorized in low (<30 ng/mL; n=153), normal (30–200 ng/mL in women and 30–300 ng/mL in men; n=663) and high (>200 ng/mL in women and >300 ng/mL in men; n=247) ferritin levels. Multivariable Cox proportional hazards models were used to evaluate the relationship between ferritin and incident HF. After 20.9±4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared to participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF (HR= 2.24, 95% CI= 1.15–4.35; p=0.02) as did those with high ferritin levels (HR=1.81, 95% CI=1.01–3.25; p=0.04), after adjusting for potential confounders. Notably, low ferritin levels remained associated with incident HF even after excluding subjects with anemia (HR= 2.28, 95% CI= 1.11–4.68; p= 0.03). Conclusion Derangements in iron metabolism, either low or high ferritin serum levels, were associated with higher risk of incident HF in a general population, even without concurrent anemia. These findings suggest that iron imbalance might play a role in the development of HF.

H-Ferritin is essential for macrophages’ capacity to store or detoxify exogenously added iron

“…On the other hand, iron needs to be strictly controlled and stored, due to its potential to cause cell damage 2 . Proteins like ferritin, transferrin, and ferroportin are essential to control the intracellular and intercellular iron fluxes and imbalances in their expression or function lead to severe health problems [3][4][5] . In particular, ferritin is essential to safely store iron inside cells, avoiding its harmful effects.…”

March 2017 at a glance: pathophysiology, imaging, biomarkers and devices

“…High serum ferritin levels were independent predictors of an increased risk of HF in both studies. In the first study, low ferritin levels were also associated with an increased risk of HF, compared to normal levels, whereas the association was significant only in women in the second study . These studies add data to the complex relationship between iron metabolism and cardiovascular disease, namely HF.…”

“…Two studies show the role of ferritin as an independent risk factor for HF development. These studies are based on two cohorts of subjects free of signs of cardiovascular disease at entry, one from the ARIC Study, with 1063 participants, and the other from PREVEND, with 6386 subjects . Mean age was 53 years in both cohorts.…”

Prevalence of iron deficiency in a total joint surgery population

“…Likewise, iron deficiency is defined as a ferritin concentration of <50 ng/ml in patients suffering from restless leg syndrome [14,15]. Ferritin levels less than 30 ng/ml were associated with higher risk of heart failure [16]. In surgery, inadequate stores of iron represented by a ferritin < 100 ng/ml, interfere with the bone marrows ability to sustain erythropoiesis after surgery.…”