Iron deficiency in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention☆
Introduction
Primary percutaneous coronary intervention (pPCI) is the most effective strategy for reducing infarct size and ventricular dysfunction, demonstrating improved clinical outcomes in patients with ST-segment elevation acute myocardial infarction (STEMI) [1]. Myocardial reperfusion, however, can induce further injury to the myocardium, so that the benefit of pPCI may be partially thwarted [2].
Mitochondria play a key role in cardiac function. They supply the necessary biological energy to the cell by contributing to the production of myocardial adenosine-triphosphate (ATP), a process requiring iron availability [3]. In addition to its role in oxygen uptake and transport as an element of hemoglobin, iron has an important function in cellular oxygen metabolism, acting as a key mitochondrial enzymatic cofactor of the respiratory chain [4]. Thus, iron is crucial for the homeostasis of every cell, particularly for the highly energy-demanding cardiac myocytes [4]. As mitochondrial dysfunction has been identified as a central mechanism underlying myocardial ischemia-reperfusion injury [5], it can be hypothesized that iron deficiency (ID) may exacerbate myocardial damage in STEMI. Notably, ID has been shown to be a frequent condition in heart failure, even in non-anemic patients [6,7], and to be associated with poorer cardiac function and higher mortality [7,8]. However, no data are available on whether ID is also common in STEMI patients and is associated with mitochondrial dysfunction, impaired cardiac function, and worse in-hospital outcomes.
The purpose of this prospective study was to determine the prevalence, clinical predictors, and in-hospital clinical consequences of ID in unselected consecutive STEMI patients undergoing pPCI. In order to explore the possible association between ID and mitochondrial impairment, we also measured the plasma levels of circulating cell-free mitochondrial DNA (mtDNA) [9].
Section snippets
Study population
This prospective study was conducted at Centro Cardiologico Monzino, University of Milan between October 1, 2015 and September 30, 2018. During this time, we enrolled all the consecutive STEMI patients undergoing pPCI. Patients were included if they were admitted within 12 h (24 h for those with cardiogenic shock) from symptom onset, and had at least 1-mm ST-segment elevation in two or more contiguous leads or a new left bundle branch block. Patients with known hemochromatosis, history of
Results
A total of 420 consecutive STEMI patients undergoing pPCI (mean age 65 ± 12 years, 325 men) were included in the study. Of them, 237 (56%) had ID. Table 1 shows the baseline characteristics of patients with and without ID. The two groups were similar regarding clinical and laboratory parameters, except for diabetes mellitus and anemia, which were more likely in patients with ID. Moreover, patients with ID had significantly higher hs-TnI and mtDNA levels at hospital admission than those without
Discussion
The present study indicates that ID is a frequent condition in STEMI patients and is unexpectedly associated with a better in-hospital outcome.
Iron deficiency is now recognized as an important comorbidity in acute and chronic heart failure, and many studies have reported a high (30–50%) prevalence, even among patients without anemia [[6], [7], [8]]. In chronic heart failure, ID has been associated with impaired exercise capacity, reduced quality of life, and worse prognosis [[6], [7], [8]].
Funding sources
This work was supported by the Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy. This work was supported by the Centro Cardiologico Monzino, Italy. The study's sponsor had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.
Disclosures
None.
Conflict of interest
None.
Acknowledgments
We acknowledge Michela Palmieri, MA, for her precious help in revising the manuscript.
References (30)
- et al.
Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials
Lancet
(2003) - et al.
Nutritional iron deficiency
Lancet
(2007) - et al.
Iron status in the acute phase and six weeks after myocardial infarction
Free Radic. Biol. Med.
(1990) - et al.
Myocardial infarct size in patients on long-term statin therapy undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction
Am. J. Cardiol.
(2015) - et al.
Impact of cardiac and renal dysfunction on in-hospital morbidity and mortality of patients with acute myocardial infarction undergoing primary angioplasty
Am. Heart J.
(2007) - et al.
Iron deficiency in patients with acute coronary syndrome: prevalence and predisposing factors
Rev. Esp. Cardiol.
(2016) - et al.
Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out of-hospital cardiac arrest
Resuscitation
(2012) - et al.
5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction
J. Am. Coll. Cardiol.
(2010) - et al.
Iron metabolism and toxicity
Toxicol. Appl. Pharmacol.
(2005) - et al.
Iron induces protection and necrosis in cultured cardiomyocytes: role of reactive oxygen species and nitric oxide
Free Radic. Biol. Med.
(2010)
Association between haptoglobin phenotype and microvascular obstruction in patients with ST-segment elevation myocardial infarction: a cardiac magnetic resonance study
JACC Cardiovasc. Imaging
Microvascular obstruction after primary percutaneous coronary intervention: pathogenesis, diagnosis and prognostic significance
Curr. Vasc. Pharmacol.
Mitochondrial function, biology, and role in disease: a scientific statement from the American Heart Association
Circ. Res.
Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole
Cardiovasc. Res.
Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives
Eur. Heart J.
Cited by (0)
- ☆
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.