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. 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.

Plasma Catalytic Iron, AKI, and Death among Critically Ill Patients

“…Although AKI is a well known risk factor for increased hospital mortality (30), five of the nine patients who died in the hospital did not have AKI, raising the possibility that catalytic iron may be toxic to multiple organ systems and not just the kidneys. Consistent with this possibility, elevated plasma catalytic iron levels are associated with increased mortality in other settings, including patients with acute coronary syndrome (15,16).…”

“…In humans, the release of intracellular stores of iron under conditions of tissue injury (3) or hemolysis (11) results in elevated circulating levels of catalytic iron. High plasma catalytic iron levels, in turn, may have a pathologic role in a variety of disease states, including coronary artery disease (12,13) and acute coronary syndrome (14)(15)(16); however, the association with AKI has not been well studied in humans.…”

N-acetylcysteine Plus Deferoxamine Improves Cardiac Function in Wistar Rats After Non-reperfused Acute Myocardial Infarction

“…However, it is suggested that only the catalytic iron pool is involved on iron-induced oxidative stress through the Fenton reaction. Catalytic iron levels in plasma are two orders of magnitude below the levels found for total plasma iron [34,35]. Thus, despite evidencing effects of NAC/DFX on plasma iron levels, we suggest that a more accurate assay should be employed in order to unveil the effects of the treatments in the catalytic iron pool.…”

Chronic thromboembolic pulmonary hypertension is not associated with iron overload

“…And total body iron status has a positive association with risk of premature acute myocardial infarction [13]. While in patients with acute coronary syndrome, increased iron levels are associated with increased all-cause mortality [14]. Iron chelation could improve endothelial function in patients with coronary artery disease [15].…”