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Prognostic evaluation of catalytic iron in patients with acute coronary syndromes
Dylan L Steen1, Christopher P Cannon, Suhas S Lele
1TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. steendy@gmail.com
Insights
Elevated levels of free iron, a catalyst for reactive oxygen species, were linked to increased mortality in patients with acute coronary syndromes. This suggests catalytic iron may play a role in cardiovascular death, though not for predicting recurrent ischemic events.
Area of Science:
- Cardiovascular Science
- Oxidative Stress Research
- Iron Metabolism
Background:
- The role of excess iron in atherosclerotic heart disease is a long-standing question due to iron's potential to generate reactive oxygen species.
- Circulating catalytic iron, unbound to transferrin or ferritin, can produce reactive oxygen species with potential vascular damage.
Purpose of the Study:
- To investigate the association between increased levels of catalytic iron and cardiovascular events.
- To test the hypothesis that higher catalytic iron levels correlate with increased cardiovascular mortality.
Main Methods:
- A study of 1701 patients with acute myocardial infarction (MI) or unstable angina.
- Follow-up for a median of 10 months, with all clinical endpoints adjudicated by a blinded committee.
- Measurement of circulating catalytic iron levels.
Main Results:
- Patients who died had significantly higher median catalytic iron levels (0.45 µmol/L) compared to survivors (0.37 µmol/L).
- Catalytic iron showed a stepwise increased risk of death, with the highest quartile associated with a nearly 4-fold increased risk (HR: 3.94, P=0.035), persisting after adjustments.
- No association was found between catalytic iron and the risk of MI, recurrent ischemia, heart failure, or bleeding.
Conclusions:
- Increasing levels of catalytic iron are associated with increased all-cause mortality in patients with acute coronary syndromes.
- Catalytic iron may not be a routine biomarker for stratifying risk of recurrent ischemic events.
- The association of catalytic iron with mortality warrants further investigation into potential iron-targeted cardiovascular therapeutics.
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.
Hypothesis:
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.
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