title: Prognostic evaluation of catalytic iron in patients with acute coronary syndromes.
abstract: BACKGROUND
  The potential of iron to generate reactive oxygen species has motivated a long-standing interest in whether excess iron is causally linked to atherosclerotic heart disease. Circulating catalytic iron ("free" iron) is that which is not bound to transferrin or ferritin and is available to generate reactive oxygen species that may have deleterious vascular effects.
  
  
  OBJECTIVE
  We hypothesized that increased levels of catalytic iron would be associated with increased cardiovascular events.
  
  
  METHODS
  We investigated the association of catalytic iron with clinical outcomes in 1701 patients with unstable angina, non-ST-segment elevation myocardial infarction (MI), or ST-segment elevation MI who were followed for a median of 10 months. All endpoints were adjudicated by a blinded Clinical End Points Committee.
  
  
  RESULTS
  The median catalytic iron level was significantly higher in those who died, 0.45 µmol/L (0.37, 0.57), compared with survivors, 0.37µmol/L (0.31, 0.46; P = 0.016). Catalytic iron was associated with a stepwise increased risk of death, with the highest quartile at an almost 4-fold risk compared with baseline (hazard ratio: 3.94, P = 0.035), which persisted after adjustment for age, diabetes, prior MI, prior congestive heart failure, ST-segment deviation, creatinine clearance, B-type natriuretic peptide, smoking, and Killip class (adjusted hazard ratio: 3.97, P = 0.036). There was no association between catalytic iron and risk of MI, recurrent ischemia, heart failure, or bleeding.
  
  
  CONCLUSIONS
  Increasing catalytic iron levels were associated with increased all-cause mortality. Although our findings suggest that catalytic iron is not likely to add to available tools as a routine biomarker for risk stratification of recurrent ischemic events, its association with mortality is intriguing and leaves open the question of whether cardiovascular therapeutics aimed at catalytic iron may be useful. The TIMI Study Group has received research grant support from the Muljibhai Patel Society for Research in Nephro-Urology.
authors: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. steendy@gmail.com
authors: Dylan L
authors: DL
authors: Steen
authors: Christopher P
authors: CP
authors: Cannon
authors: Suhas S
authors: SS
authors: Lele
authors: Mohan M
authors: MM
authors: Rajapurkar
authors: Banibrata
authors: B
authors: Mukhopadhyay
authors: Benjamin M
authors: BM
authors: Scirica
authors: Sabina A
authors: SA
authors: Murphy
authors: David A
authors: DA
authors: Morrow
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D000368:Aged; D000789:Angina, Unstable / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002384:Catalysis; D005260:Female; D006801:Humans; D007194:India; D007501:Iron / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood; D010084:Oxidation-Reduction; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017382:Reactive Oxygen Species / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D007501:Iron
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