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

Odilson M. Silvestre, Alexandra Gonçalves, Wilson Nadruz, Brian Claggett, David Couper, John H. Eckfeldt, James S. Pankow, Stefan D. Anker, Scott D. Solomon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 1063 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 21 ± 4.6 years of follow-up, HF occurred in 144 (13.5%) participants. When compared with participants with normal ferritin levels, participants with low ferritin levels had a higher risk of HF [hazard ratio (HR) = 2.24, 95% confidence interval (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 anaemia (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 anaemia. These findings suggest that iron imbalance might play a role in the development of HF.

Original languageEnglish (US)
Pages (from-to)340-347
Number of pages8
JournalEuropean Journal of Heart Failure
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2017

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). It is also supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK56918. This work was also supported NHLBI cooperative agreement NHLBI-HC-11?08 (S.D.S.). A.G. was supported by the Portuguese Foundation for Science and Technology Grant HMSP-ICS/007/2012. W.N. was supported by the Brazilian National Council for Scientific and Technological Development Grant 249481/2013?8. O.M.S. was supported by the J.P. Lemann Foundation as a Jorge Paulo Lemann Harvard Medical School Cardiovascular Fellow at Brigham and Women's Hospital. Conflict of interest: none declared. The authors thank the staff and participants of the ARIC study for their important contributions. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). It is also supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK56918. This work was also supported NHLBI cooperative agreement NHLBI-HC-11?08 (S.D.S.). A.G. was supported by the Portuguese Foundation for Science and Technology Grant HMSP-ICS/007/2012. W.N. was supported by the Brazilian National Council for Scientific and Technological Development Grant 249481/2013?8. O.M.S. was supported by the J.P. Lemann Foundation as a Jorge Paulo Lemann Harvard Medical School Cardiovascular Fellow at Brigham and Women's Hospital. Conflict of interest: none declared.

Keywords

  • Ferritin
  • Heart failure
  • Iron deficiency
  • Iron overload

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