title: Serum ferritin and risk for new-onset heart failure and cardiovascular events in the community.
abstract: Heart failure (HF) is a common manifestation of patients with primary and secondary causes of iron overload, whereas in patients with established HF iron deficiency impairs outcome. Whether iron stores, either depleted or in overload, amplify the risk for new-onset HF among healthy individuals is unknown. The present study aimed to assess whether markers of iron status or the iron-regulatory hormone hepcidin are associated with new-onset HF or cardiovascular (CV) events in the general population.
  
  
  
  In 6386 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) trial, a prospective, community-based, cohort study, markers of iron status and the iron-regulatory hormone hepcidin were measured. Mean age was 53.1 ± 12.0 years, and 50.7% of the cohort was female. During a median follow-up of 8.3 (interquartile range 7.8-8.9) years, 199 subjects (3.1%) were newly diagnosed with HF, 456 (7.1%) experienced a CV event, and 356 (5.6%) died from all causes. A higher annual HF incidence per ferritin quartile was observed in women (P < 0.001), but not in men (P for interaction 0.032). Multivariable analyses demonstrated ferritin levels to remain independently predictive for new-onset HF in women only (P = 0.024). This association persisted within strata defined by markers of the metabolic syndrome, markers of inflammation, or other markers of iron homeostasis, including hepcidin. No association between ferritin or hepcidin and incident CV events or all-cause mortality was observed in either sex.
  
  
  
  Increased serum ferritin levels independently amplify the risk for new-onset HF in women in the community.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: IJsbrand T
authors.initials: IT
authors.lastname: Klip
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.affiliation: Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kootstra-Ros
authors.affiliation: Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Lam
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D002423:Cause of Death; D002561:Cerebrovascular Disorders / Q000097:blood / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000097:blood / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D017202:Myocardial Ischemia / Q000097:blood / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D014656:Vascular Surgical Procedures / Q000706:statistics & numerical data
chemical_list: D064451:Hepcidins; D005293:Ferritins
keywords: Cardiovascular disease; Epidemiology; Heart failure; Hepcidin; Iron