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Canadian Journal of Cardiology
Clinical Research| Volume 35, ISSUE 10, P1366-1376, October 2019

Circulating MIF Levels Predict Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction After Percutaneous Coronary Intervention

  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Qian Zhao
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Author Footnotes
    ∗ These authors contributed equally to this work.
    Li Men
    Footnotes
    ∗ These authors contributed equally to this work.
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Xiao-Mei Li
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Fen Liu
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Chun-Fang Shan
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Xin-Rong Zhou
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Ning Song
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Jia-Jun Zhu
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Xiao-Li Gao
    Affiliations
    College of Pharmacy, Xinjiang Medical University, Urumqi, China
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  • Yi-Tong Ma
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
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  • Xiao-Jun Du
    Affiliations
    Baker Heart and Diabetes Institute, Melbourne, Australia
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  • Xiao-Ming Gao
    Correspondence
    Corresponding authors: Dr Xiao-Ming Gao, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, 137 Liyushan South Road, Urumqi 830054, China. Tel.: +1-86-991-4362844; fax: +1-86-991-4362844.
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Medical Animal Model Research, Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, China
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  • Yi-Ning Yang
    Correspondence
    Dr Yi-Ning Yang, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi 830054, China. Tel.: +1-86-991-4361690; fax: +1-86-991-4365330.
    Affiliations
    State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

    Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
    Search for articles by this author
  • Author Footnotes
    ∗ These authors contributed equally to this work.

      Abstract

      Background

      The purpose of the study was to assess the value of admission macrophage migration inhibitory factor (MIF) levels in predicting clinical outcomes in ST-elevation myocardial infarction (STEMI) patients.

      Methods

      For this study we recruited 498 STEMI patients after they received percutaneous coronary intervention (PCI), 40 with stable angina pectoris and 137 healthy participants. Plasma MIF levels were measured at admission and after PCI. The primary end points were in-hospital mortality and major adverse cardio-and/or cerebrovascular events (MACCE) during hospitalization and 3.2-year follow-up period.

      Results

      Admission MIF levels were elevated in 88.4% of STEMI patients over the upper reference limit of healthy controls and it was 3- to 7-fold higher than that in stable angina pectoris and control groups (122 ± 61 vs 39 ± 19 vs 17 ± 8 ng/mL; P < 0.001). Admission MIF levels were significantly higher in patients who died after myocardial infarction vs survivors. For predicting in-hospital mortality using the optimal cutoff value (127.8 ng/mL) of MIF, the area under the receiver operating characteristic curve for MIF was 0.820, similar area under the receiver operating characteristic curve values for predicting short-term outcomes were observed for high-sensitivity troponin T, CK-MB, N-terminal probrain natriuretic peptide, and Global Registry of Acute Coronary Events (GRACE) score. Although peak high-sensitivity troponin T and N-terminal probrain natriuretic peptide also predicted MACCE during the follow-up period, only higher admission MIF levels predicted in-hospital mortality and MACCE during the 3.2-year follow-up. Multivariate regression analysis showed the independent predictive value of a higher admission MIF level (≥ 127.8 ng/mL) on in-hospital mortality (odds ratio, 9.1; 95% confidence interval, 1.7-47.2) and 3.2-year MACCE (hazard ratio, 2.8; 95% confidence interval, 1.5-5.6).

      Conclusions

      A higher admission MIF level is an independent predictor for in-hospital mortality and long-term MACCE in STEMI patients who underwent PCI.

      Résumé

      Contexte

      L’étude visait à évaluer l’utilité du dosage du facteur d’inhibition de la migration des macrophages (MIF) effectué lors de l’admission à l’hôpital aux fins de pronostic des résultats cliniques chez les patients ayant souffert d’un infarctus du myocarde avec élévation du segment ST (STEMI).

      Méthodologie

      Pour les besoins de cette étude, nous avons recruté 498 patients ayant souffert de STEMI après qu’ils eurent subi une intervention coronarienne percutanée (ICP), 40 patients atteints d’angine de poitrine stable et 137 sujets en bonne santé. Les concentrations plasmatiques de MIF ont été mesurées lors de l’admission à l’hôpital et après l’ICP. Les paramètres d’évaluation principaux étaient la mortalité intrahospitalière et la survenue d’événements cardiovasculaires et/ou cérébrovasculaires indésirables majeurs (MACCE) au cours de l’hospitalisation et d’une période de suivi de 3,2 ans.

      Résultats

      Lors de l’admission à l’hôpital, les concentrations de MIF étaient élevées chez 88,4 % des patients qui avaient souffert de STEMI; elles se situaient au-delà de la limite supérieure de référence mesurée chez les sujets témoins en bonne santé et étaient de 3 à 7 fois plus élevées que celles notées chez les patients atteints d’angine de poitrine stable et les sujets témoins (122 ± 61 vs 39 ± 19 vs 17 ± 8 ng/ml, p < 0,001). Les concentrations de MIF lors de l’admission à l’hôpital étaient significativement plus élevées chez les patients qui sont décédés après avoir souffert d’un infarctus du myocarde que chez les survivants. Pour le pronostic de mortalité intrahospitalière en fonction de la concentration de MIF constituant la valeur seuil optimale (127,8 ng/ml), l’aire sous la courbe ROC était de 0,820. Une aire sous la courbe ROC similaire a été observée pour le pronostic des résultats à court terme en fonction des concentrations de troponine T hypersensible, de CK-MB et de NT-proBNP (propeptide natriurétique de type B N-terminal) et en fonction du score GRACE (Global Registry of Acute Coronary Events). Même si les concentrations maximales de troponine T hypersensible et de NT-proBNP étaient aussi prédictives des MACCE durant la période de suivi, seules les concentrations plus élevées de MIF lors de l’admission à l’hôpital constituaient un marqueur pronostique de mortalité intrahospitalière et de MACCE durant la période de suivi de 3,2 ans. L’analyse de régression multivariée a montré qu’une concentration plus élevée de MIF lors de l’admission à l’hôpital (≥ 127,8 ng/ml) constitue un marqueur pronostique indépendant de mortalité intrahospitalière (rapport des risques instantanés de 9,1; intervalle de confiance à 95 % de 1,7 à 47,2) et de MACCE sur une période de 3,2 ans (rapport de cotes de 2,8; intervalle de confiance à 95 %, de 1,5 à 5,6).

      Conclusions

      Une concentration plus élevée de MIF lors de l’admission à l’hôpital constitue un marqueur pronostique indépendant de mortalité intrahospitalière et de MACCE à long terme chez les patients qui ont souffert d’un STEMI et subi une ICP.
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      References

        • Benjamin E.J.
        • Blaha M.J.
        • Chiuve S.E.
        • et al.
        Heart disease and stroke statistics-2017 update: a report from the American Heart Association.
        Circulation. 2017; 135: e146-e603
        • Nishimura R.A.
        • Otto C.M.
        • Bonow R.O.
        • et al.
        2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2017; 70: 252-289
        • Hartman M.H.T.
        • Eppinga R.N.
        • Vlaar P.J.J.
        • et al.
        The contemporary value of peak creatine kinase-MB after ST-segment elevation myocardial infarction above other clinical and angiographic characteristics in predicting infarct size, left ventricular ejection fraction, and mortality.
        Clin Cardiol. 2017; 40: 322-328
        • Haaf P.
        • Reichlin T.
        • Twerenbold R.
        • et al.
        Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays.
        Eur Heart J. 2014; 35: 365-375
        • Mueller-Hennessen M.
        • Lindahl B.
        • Giannitsis E.
        • et al.
        Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study.
        Int J Cardiol. 2016; 209: 26-33
        • Roos A.
        • Bandstein N.
        • Lundback M.
        • et al.
        Stable high-sensitivity cardiac troponin T levels and outcomes in patients with chest pain.
        J Am Coll Cardiol. 2017; 70: 2226-2236
        • Groth T.
        • Hakman M.
        • Sylven C.
        Prediction of myocardial infarct size from early serum myoglobin observations.
        Scand J Clin Lab Invest. 1987; 47: 599-603
        • Richards A.M.
        • Nicholls M.G.
        • Espiner E.A.
        • et al.
        B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction.
        Circulation. 2003; 107: 2786-2792
        • Chew P.G.
        • Frost F.
        • Mullen L.
        • et al.
        A direct comparison of decision rules for early discharge of suspected acute coronary syndromes in the era of high sensitivity troponin.
        Eur Heart J Acute Cardiovasc Care. 2019; 8: 421-431
        • Morand E.F.
        • Leech M.
        • Bernhagen J.
        MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis.
        Nat Rev Drug Discov. 2006; 5: 399-410
        • Zernecke A.
        • Bernhagen J.
        • Weber C.
        Macrophage migration inhibitory factor in cardiovascular disease.
        Circulation. 2008; 117: 1594-1602
        • Burger-Kentischer A.
        • Goebel H.
        • Seiler R.
        • et al.
        Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis.
        Circulation. 2002; 105: 1561-1566
        • Muller II,
        • Muller K.A.
        • Schonleber H.
        • et al.
        Macrophage migration inhibitory factor is enhanced in acute coronary syndromes and is associated with the inflammatory response.
        PLoS One. 2012; 7e38376
        • Chan W.
        • White D.A.
        • Wang X.Y.
        • et al.
        Macrophage migration inhibitory factor for the early prediction of infarct size.
        J Am Heart Assoc. 2013; 2e000226
        • Gao X.M.
        • Liu Y.
        • White D.
        • et al.
        Deletion of macrophage migration inhibitory factor protects the heart from severe ischemia-reperfusion injury: a predominant role of anti-inflammation.
        J Mol Cell Cardiol. 2011; 50: 991-999
        • Pohl J.
        • Rammos C.
        • Totzeck M.
        • et al.
        MIF reflects tissue damage rather than inflammation in post-cardiac arrest syndrome in a real life cohort.
        Resuscitation. 2016; 100: 32-37
        • White D.A.
        • Fang L.
        • Chan W.
        • et al.
        Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.
        PLoS One. 2013; 8e76206
        • White D.A.
        • Su Y.
        • Kanellakis P.
        • et al.
        Differential roles of cardiac and leukocyte derived macrophage migration inhibitory factor in inflammatory responses and cardiac remodelling post myocardial infarction.
        J Mol Cell Cardiol. 2014; 69: 32-42
        • Miller E.J.
        • Li J.
        • Leng L.
        • et al.
        Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart.
        Nature. 2008; 451: 578-582
        • Jneid H.
        • Anderson J.L.
        • Wright R.S.
        • et al.
        2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2012; 60: 645-681
      1. Working Group of the SEC on the 2013 ESC Guidelines on the Management of Stable Coronary Artery Disease; Reviewers for the 2013 ESC Guidelines on the Management of Stable Coronary Artery Disease; SEC Guidelines Committee. Comments on the 2013 ESC guidelines on the management of stable coronary artery disease.
        Rev Esp Cardiol (Engl Ed). 2014; 67: 80-86
        • Gensini G.G.
        A more meaningful scoring system for determining the severity of coronary heart disease.
        Am J Cardiol. 1983; 51: 606
        • Gong P.
        • Luo S.H.
        • Li X.L.
        • et al.
        Relation of ABO blood groups to the severity of coronary atherosclerosis: a Gensini score assessment.
        Atherosclerosis. 2014; 237: 748-753
        • Levine G.N.
        • Bates E.R.
        • Blankenship J.C.
        • et al.
        2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Society for Cardiovascular Angiography and Interventions.
        Circulation. 2016; 133: 1135-1147
      2. Obesity: preventing and managing the global epidemic. Report of a WHO consultation.
        World Health Organ Tech Rep Ser. 2000; 894: 1-253
      3. Joint Committee for Developing Chinese guidelines on Prevention and Treatment of Dyslipidemia in Adults. Chinese guidelines on prevention and treatment of dyslipidemia in adults [in Chinese].
        Zhonghua Xin Xue Guan Bing Za Zhi. 2007; 35: 390-419
        • Khan S.Q.
        • Narayan H.
        • Ng K.H.
        • et al.
        N-terminal pro-B-type natriuretic peptide complements the GRACE risk score in predicting early and late mortality following acute coronary syndrome.
        Clin Sci (Lond). 2009; 117: 31-39
        • Tang E.W.
        • Wong C.K.
        • Herbison P.
        Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome.
        Am Heart J. 2007; 153: 29-35
        • Jurado-Roman A.
        • Agudo-Quilez P.
        • Rubio-Alonso B.
        • et al.
        Superiority of wall motion score index over left ventricle ejection fraction in predicting cardiovascular events after an acute myocardial infarction.
        Eur Heart J Acute Cardiovasc Care. 2019; 8: 78-85
        • White H.D.
        • Chew D.P.
        Acute myocardial infarction.
        Lancet. 2008; 372: 570-584
        • Fan F.
        • Fang L.
        • Moore X.L.
        • et al.
        Plasma macrophage migration inhibitor factor is elevated in response to myocardial ischemia.
        J Am Heart Assoc. 2016; 5e003128
        • Stoppe C.
        • Rex S.
        • Goetzenich A.
        • et al.
        Interaction of MIF family proteins in myocardial ischemia/reperfusion damage and their influence on clinical outcome of cardiac surgery patients.
        Antioxid Redox Signal. 2015; 23: 865-879
        • Hao Y.
        • Yi S.L.
        • Zhong J.Q.
        Serum macrophage migration inhibitory factor levels are associated with angiographically complex coronary lesions in patients with coronary artery disease.
        Genet Test Mol Biomarkers. 2015; 19: 556-560
        • Stoppe C.
        • Grieb G.
        • Rossaint R.
        • et al.
        High postoperative blood levels of macrophage migration inhibitory factor are associated with less organ dysfunction in patients after cardiac surgery.
        Mol Med. 2012; 18: 843-850
        • de Mendonca-Filho H.T.
        • Gomes R.V.
        • de Almeida Campos L.A.
        • et al.
        Circulating levels of macrophage migration inhibitory factor are associated with mild pulmonary dysfunction after cardiopulmonary bypass.
        Shock. 2004; 22: 533-537
        • Schmeisser A.
        • Marquetant R.
        • Illmer T.
        • et al.
        The expression of macrophage migration inhibitory factor 1alpha (MIF 1alpha) in human atherosclerotic plaques is induced by different proatherogenic stimuli and associated with plaque instability.
        Atherosclerosis. 2005; 178: 83-94
        • Lodi S.
        • Phillips A.
        • Fidler S.
        • et al.
        Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
        PLoS One. 2013; 8e75608
        • Makino A.
        • Nakamura T.
        • Hirano M.
        • et al.
        High plasma levels of macrophage migration inhibitory factor are associated with adverse long-term outcome in patients with stable coronary artery disease and impaired glucose tolerance or type 2 diabetes mellitus.
        Atherosclerosis. 2010; 213: 573-578
        • Herder C.
        • Illig T.
        • Baumert J.
        • et al.
        Macrophage migration inhibitory factor (MIF) and risk for coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.
        Atherosclerosis. 2008; 200: 380-388
        • Boekholdt S.M.
        • Peters R.J.
        • Day N.E.
        • et al.
        Macrophage migration inhibitory factor and the risk of myocardial infarction or death due to coronary artery disease in adults without prior myocardial infarction or stroke: the EPIC-Norfolk Prospective Population study.
        Am J Med. 2004; 117: 390-397
        • Deng X.N.
        • Wang X.Y.
        • Yu H.Y.
        • et al.
        Admission macrophage migration inhibitory factor predicts long-term prognosis in patients with ST-elevation myocardial infarction.
        Eur Heart J Qual Care Clin Outcomes. 2018; 4: 208-219
        • Dayawansa N.H.
        • Gao X.M.
        • White D.A.
        • Dart A.M.
        • Du X.J.
        Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and experimental findings.
        Clin Sci (Lond). 2014; 127: 149-161
        • Witteveen S.A.
        • Hemker H.C.
        • Hollaar L.
        • Hermens W.T.
        Quantitation of infarct size in man by means of plasma enzyme levels.
        Br Heart J. 1975; 37: 795-803
        • Ryan W.
        • Karliner J.S.
        • Gilpin E.A.
        • et al.
        The creatine kinase curve area and peak creatine kinase after acute myocardial infarction: usefulness and limitations.
        Am Heart J. 1981; 101: 162-168
        • Dissmann R.
        • Linderer T.
        • Schroder R.
        Estimation of enzymatic infarct size: direct comparison of the marker enzymes creatine kinase and alpha-hydroxybutyrate dehydrogenase.
        Am Heart J. 1998; 135: 1-9

      Linked Article

      • When the Myocardium Gets MIFfed: Macrophage Inhibitory Factor as a Biomarker in Acute Coronary Artery Disease
        Canadian Journal of CardiologyVol. 35Issue 10
        • Preview
          Survival after acute myocardial infarction has improved significantly in the past years and decades. Besides the developments in interventional treatment options, the increasing public awareness of typical symptoms has contributed to a reduced time lag between the onset of symptoms and intervention. However, the differential diagnosis of acute or chronic myocardial ischemia in patients who present with atypical symptoms can be much less straightforward.1 Despite current guidelines that allow for 1-hour ruling in or out of non–ST-elevation myocardial infarction for certain high-sensitivity troponin assays, patients are often left anxious and stressed during the waiting period for the second troponin measurement.
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