title: Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease.
abstract: BACKGROUND
  Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored.
  
  
  METHODS
  Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes.
  
  
  RESULTS
  Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reduction patients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reduction patients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067).
  
  
  CONCLUSIONS
  Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke.
authors.affiliation: Department of Veterans Affairs Medical Center, White River Jct., VT 05009, USA. leo.r.zacharski@dartmouth.edu
authors.forename: Leo R
authors.initials: LR
authors.lastname: Zacharski
authors.forename: Galina
authors.initials: G
authors.lastname: Shamayeva
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000367:Age Factors; D000368:Aged; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D008297:Male; D058729:Peripheral Arterial Disease / Q000097:blood / Q000401:mortality / Q000628:therapy*; D018962:Phlebotomy; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014728:Veterans
chemical_list: D005293:Ferritins