Predictive value of serum iron on heart failure in patients with acute ST‐segment elevation myocardial infarction

In clinical practice, heart failure often occurs after acute myocardial infarction, and a new biomarker for its early prediction is urgently needed. The aim of this study was to investigate the relationship between serum iron and heart failure after acute ST‐segment elevation myocardial infarction (STEMI).

and rehospitalization rates remain high, which is related to the severity of the disease and whether there is timely diagnosis and treatment of these patients. 2 Iron catalyzes redox reactions that maintain cell balance or drive toxic damage. It not only plays a central role in cardiac energetics, but can also cause the death of cardiac muscle cells through uncontrolled oxidative stress. 3 One study directly analyzed myocardial tissue samples from patients with and without HF and found that myocardial iron levels were lower in patients with HF. This was associated with reduced mitochondrial enzyme activity in HF patients, suggesting that iron plays a key role in myocardial function. 4 Patients with HF combined with iron deficiency have deteriorated muscle function due to reduced mitochondrial iron stores in myocytes, resulting in decreased cardiac function. 5 The incidence of HF after acute MI is increasing. Clinical observation found that the occurrence of HF was more than 24 h after acute MI.
Iron catalyzes redox reactions that maintain cell balance or drive toxic damage. It not only plays a central role in cardiac energetics, but can also cause the death of cardiac muscle cells through uncontrolled oxidative stress. 3 One study directly analyzed myocardial tissue samples from patients with and without HF and found that myocardial iron levels were lower in patients with HF. This was associated with reduced mitochondrial enzyme activity in HF patients, suggesting that iron plays a key role in myocardial function. 4 Patients with HF combined with iron deficiency have deteriorated muscle function due to reduced mitochondrial iron stores in myocytes, resulting in decreased cardiac function. 5 It had been shown that reduced serum iron levels in patients with acute HF are associated with poor prognosis, including 12-month mortality. 6 Ye Gang et al. showed that A lower admission serum iron level is an independent predictor of acute HF in STEMI patients during hospitalization. 7 The study also shown that low serum iron is an independent predictor of poor prognosis for acute decompensated HF regardless of hemoglobin or ferritin levels. 8 Determining whether serum iron levels can predict HF after STEMI could improve early recognition and management. The incidence of HF after acute MI is increasing. Clinical observation found that the occurrence of HF was more than 24 h after acute MI. Therefore, sensitive indicators are needed to assess risk factors for HF before onset. The aim of our study was to determine the association of serum iron with HF in patients with acute ST-segment elevation MI.

| Data collection
All data were obtained from the hospital's digital information system.

| Clinical measurements
On admission, blood samples were placed through an anterior axillary venipuncture into an ethylenediaminetetraacetic acid-treated test tube or a plain test tube. Complete blood counts were measured using an automated hematological analyzer (CAL8000; Mindray Corporation). The levels of NT-pro-BNP and Tn-I were measured using an automated fluorescent immunoassay (Getein1600; Geteinbiotech). Blood biochemical examination and serum iron were measured using an automated biochemical analyzer (CM-800; Geteinbiotech).

| Echocardiography
Echocardiography was performed in all patients using a Vivid 7 echocardiography device (General Electric). All patients underwent two-dimensional, M-mode, and Doppler echocardiography.

| Statistical analysis
The Kolmogorov-Smirnov test was used to demonstrate the normality of the included variables, and p > .05 was defined as normally distributed data. Continuous variables, expressed as mean ± 450 | CHEN ET AL. standard deviation, were compared between two normally distributed continuous variables using the independent samples t test, while the Mann-Whitney U test was used to compare differences between non-normally distributed continuous variables. Categorical variables, expressed as frequencies and percentages, were compared using χ 2 tests. Binary logistic regression analysis was used to identify potential independent associations between postinfarction HF and clinical parameters. Receiver operating characteristic (ROC) curves were analyzed to identify the best cutoff values for the prediction of postinfarction HF. p < .05 represents a statistically significant difference (two-tailed test). All statistical analyses were conducted using

| Comparison of clinical and echocardiographic parameters between the two groups
There were significant differences in serum Iron (11.35 ± 5.58 vs. 16 58.43 ± 7.35) between the HF and control group. There were no significant differences in terms of TC, HDL-C, LDL-C, uric acid, ALT, AST, hemoglobin, D-dimer, CRP, peak Tn-I (Table 2).

Binary logistic regression analyses demonstrated that serum iron and
Tn-I were independent predictors for HF (p < .05, respectively) ( Table 3).

| ROC curve
For the prediction of HF, ROC analysis showed that the area under the curve for serum iron was 0.808 (95% confidence interval [CI]: 0.707-0.908, p < .01). The best cutoff value of serum iron was 11.87 μmol/L (sensitivity: 87.1%; specificity: 68.3%) (Figure 1). patients at a single medical center in China. Our study showed that serum iron levels were lower in patients with HF than in controls, but the left atrium was larger than in controls. Serum iron and Tn-I were independently associated with HF. In addition, ROC analysis revealed that the best cutoff value of serum iron to predict HF occurrence was 11.87 μmol/L with a sensitivity of 87.1% and a specificity of 68.3%.
There was relatively little information on the epidemiology of postinfarction HF in China. The BRIGHT study found that the incidence of HF on admission in patients with acute infarction who underwent emergency PCI was 14.3%, of whom 88% were STEMI patients. 10 Data from the China PEACE study showed that the incidence of in-hospital early onset HF in STEMI patients was decreasing from 2001 to 2011, but was still 12.7%. 2 Myocardial cell loss was an important cause of cardiac remodeling and the development of HF after infarction. Cardiomyocytes in the ischemic zone activated apoptotic signaling pathways in response to oxidative stress, inflammatory response, and other injury factors, which in turn mediated cardiomyocyte apoptosis. 11 Iron was involved in the synthesis and function of a variety of enzymes and proteins involved in oxygen transport and storage, electron transfer, and oxidation-reduction. 12 Iron deficiency leaded to a reduction in mitochondrial oxidative capacity. 13 Decreased cardiac function may be caused by a systemic iron deficiency that compromises the cardiac energy metabolism. 14 Studies had shown that patients with HF had reduced myocardial iron levels, leading to decreased myocardial function. 15 Iron had also been shown to be involved in the pathogenesis of atherosclerotic coronary artery disease. 16 Free iron promoted the oxidation of low-density lipoprotein. Uptake of low-density lipoprotein by low-density lipoprotein receptors on macrophages leaded to the recruitment of foam cells, whose infiltration and necrotic core expansion were key to coronary atherosclerosis. 17 Serum iron concentration was a measure of circulating iron bound to transferrin and serves as a proxy for iron status. Serum iron may not be as easily stored as serum ferritin, but it is a measure of iron supply to bone marrow and other tissues, and is one of the primary biochemical indicators of iron status.
Moreover, serum iron had shown a strong negative correlation between iron concentrations and cardiovascular disease. 18 Several studies had shown that serum iron levels may be a good marker for short-term risk of cardiovascular disease in older adults. [19][20][21] The PREDIMED trial shown that, among Spanish adults aged 55-80 years at high cardiovascular disease risk, low iron concentrations in serum were associated with increased short-term risk of cardiovascular disease, and these associations were stronger in women. 22 Although the relationship between serum iron deficiency and myocardial iron deficiency is not fully understood, systemic iron deficiency was observed in two of the last three patients with HF. 14 Moreover, iron deficiency in MI predicts a poor prognosis. 23

| CONCLUSIONS
Patients with HF after STEMI have lower serum iron levels than patients without HF after STEMI. Serum iron levels are a risk factor for HF after STEMI. Though the study is small, it could lead to further studies on the relationship between iron levels, cardiovascular events, and decisions on management.
T A B L E 3 binary logistic regression analysis to detect the independent predictors of heart failure. F I G U R E 1 Receiver operating curve characteristics of serum iron for predicting heart failure.