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Cardiovascular Biomarkers in Acute Myocardial Infarction

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Ischemic Heart Disease

Abstract

The use of a large number of cardiovascular biomarkers, meant to complement the use of the electrocardiogram, echocardiography cardiac imaging, and clinical symptom assessment, has become a routine in clinical diagnosis, differential diagnosis, risk stratification, and prognosis and guides the management of patients with suspected cardiovascular diseases. Accordingly, the aim of this chapter is to explore the literature on cardiac biomarkers, mainly focusing on the role and applications of cTn and NP in the diagnosis, risk stratification, and management of patients with AMI, discussing some additional available routine biomarkers and newer biomarkers with relevant potential clinical value in the future.

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Abbreviations

AACC:

American Association for Clinical Chemistry

ACC:

American College of Cardiology

AHA:

American Heart Association

AMI:

Acute myocardial infarction

ANP:

Atrial natriuretic peptide

AST:

Aspartate aminotransferase

AST:

Aspartate transaminase

BNP:

B-type (or brain) natriuretic peptide

CAD:

Coronary artery disease

CK:

Creatine kinase

CNP:

C-type natriuretic peptide

CRP:

C-reactive protein

c-Tn:

Cardiac troponins

CVD:

Cardiovascular disease

ESC:

European Society of Cardiology

HBT:

Heterophilic blocking tubes

HF:

Heart failure

IL:

Interleukin

LDH:

Lactate dehydrogenase

MB:

Myoglobin

miRNAs:

MicroRNAs

MPV:

Mean platelet volume

ncRNA:

Noncoding RNA

NLR:

Neutrophil-to-lymphocyte ratio

NP:

Natriuretic peptides

NT-proBNP:

N-terminal fragment of precursor BNP

PDW:

Platelet distribution width

PLR:

Platelet-to-lymphocyte ratio

POCT:

Point-of-care testing

RDW:

Red cell distribution width

WBC:

White blood cells

WHO:

World Health Organization

References

  1. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1.

  2. Seferović PM, Vardas P, Jankowska EA, Maggioni AP, Timmis A, Milinković I, Polovina M, Gale CP, Lund LH, Lopatin Y, Lainscak M, Savarese G, Huculeci R, Kazakiewicz D, Coats AJS, National Heart Failure Societies of the ESC member countries (see Appendix). The Heart Failure Association Atlas: Heart Failure Epidemiology and Management Statistics 2019. Eur J Heart Fail. 2021;23:906–14.

    Article  PubMed  Google Scholar 

  3. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, ALP C, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P, ESC Scientific Document Group. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017;2018(39):119–77.

    Google Scholar 

  4. Khan S, Rasool ST. Current use of cardiac biomarkers in various heart conditions. Endocr Metab Immune Disord Drug Targets. 2021;21:980–93.

    Article  CAS  PubMed  Google Scholar 

  5. Danese E, Montagnana M. An historical approach to the diagnostic biomarkers of acute coronary syndrome. Ann Transl Med. 2016;4:194.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Clerico A, Zaninotto M, Passino C, Padoan A, Migliardi M, Plebani M. High-sensitivity methods for cardiac troponins: the mission is not over yet. Adv Clin Chem. 2021;103:215–52.

    Article  CAS  PubMed  Google Scholar 

  7. Clerico A, Passino C, Franzini M, Emdin M. Natriuretic peptides as biomarkers of cardiac endocrine function in heart failure: new challenges and perspectives. Futur Cardiol. 2016;12:573–84.

    Article  CAS  Google Scholar 

  8. Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM, ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289–367. https://doi.org/10.1093/eurheartj/ehaa575. Erratum in: Eur Heart J. 2021 May 14;42(19):1908. Erratum in: Eur Heart J. 2021;42:1925.

    Article  PubMed  Google Scholar 

  9. Ladue JS, Wrŏblewski F, Karmen A. Serum glutamic oxaloacetic transaminase activity in human acute transmural myocardial infarction. Science. 1954;120:497–9.

    Article  CAS  PubMed  Google Scholar 

  10. Penttilä I, Penttilä K, Rantanen T. Laboratory diagnosis of patients with acute chest pain. Clin Chem Lab Med. 2000;38:187–97.

    Article  PubMed  Google Scholar 

  11. Ndrepepa G. Aspartate aminotransferase and cardiovascular disease—a narrative review. J Lab Precis Med. 2021;6:6.

    Article  Google Scholar 

  12. Schumann G, Bonora R, Ceriotti F, Clerc-Renaud P, Ferrero CA, Férard G, Franck PF, Gella FJ, Hoelzel W, Jørgensen PJ, Kanno T, Kessner A, Klauke R, Kristiansen N, Lessinger JM, Linsinger TP, Misaki H, Panteghini M, Pauwels J, Schimmel HG, Vialle A, Weidemann G, Siekmann L. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase. Clin Chem Lab Med. 2002;40:643–8.

    CAS  PubMed  Google Scholar 

  13. Wróblewski F, Ruegsegger P, LaDue JS. Serum lactic dehydrogenase activity in acute transmural myocardial infarction. Science. 1956;123:1122–3.

    Article  PubMed  Google Scholar 

  14. Galbraith LV, Leung FY, Jablonsky G, Henderson R. Time-related changes in the diagnostic utility of total lactate dehydrogenase, lactate dehydrogenase isoenzyme-1, and two lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction. Clin Chem. 1990;36:1317–2132.

    Article  CAS  PubMed  Google Scholar 

  15. McLeish MJ, Kenyon GL. Relating structure to mechanism in creatine kinase. Crit Rev Biochem Mol Biol. 2005;40:1–20.

    Article  CAS  PubMed  Google Scholar 

  16. Apple FS. The specificity of biochemical markers of cardiac damage: a problem solved. Clin Chem Lab Med. 1999;37:1085–9.

    Article  CAS  PubMed  Google Scholar 

  17. Cabaniss CD. Creatine Kinase. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. 3rd ed. Boston: Butterworths; 1990. Chapter 32.

    Google Scholar 

  18. Lin JC, Apple FS, Murakami MM, Luepker RV. Rates of positive cardiac troponin I and creatine kinase MB mass among patients hospitalized for suspected acute coronary syndromes. Clin Chem. 2004;50:333–8.

    Article  CAS  PubMed  Google Scholar 

  19. Rittoo D, Jones A, Lecky B, Neithercut D. Elevation of cardiac troponin T, but not cardiac troponin I, in patients with neuromuscular diseases: implications for the diagnosis of myocardial infarction. J Am Coll Cardiol. 2014;63:2411–20.

    Article  CAS  PubMed  Google Scholar 

  20. Perović A, Dolčić M. Influence of hemolysis on clinical chemistry parameters determined with Beckman Coulter tests—detection of clinically significant interference. Scand J Clin Lab Invest. 2019;79:154–9.

    Article  PubMed  Google Scholar 

  21. Achar SA, Kundu S, Norcross WA. Diagnosis of acute coronary syndrome. Am Fam Physician. 2005;72:119–26.

    PubMed  Google Scholar 

  22. Marwah SA, Shah H, Chauhan K, Trivedi A, Haridas N. Comparison of mass versus activity of creatine kinase MB and its utility in the early diagnosis of re-infarction. Indian J Clin Biochem. 2014;29:161–6.

    Article  CAS  PubMed  Google Scholar 

  23. Zafar Gondal A, Foris LA, Richards JR. Serum myoglobin. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2021.

    Google Scholar 

  24. Aydin S, Ugur K, Aydin S, Sahin İ, Yardim M. Biomarkers in acute myocardial infarction: current perspectives. Vasc Health Risk Manag. 2019;15:1–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ebashi S. Calcium binding and relaxation in the actomyosin system. J Biochem. 1960;48:150–1.

    CAS  Google Scholar 

  26. Greaser ML, Gergely J. Reconstitution of troponin activity from three protein components. J Biol Chem. 1971;246:4226–33.

    Article  CAS  PubMed  Google Scholar 

  27. Cummins B, Auckland ML, Cummins P. Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am Heart J. 1987;113:1333–44.

    Article  CAS  PubMed  Google Scholar 

  28. Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56:254–61.

    Article  CAS  PubMed  Google Scholar 

  29. Clerico A, Zaninotto M, Ripoli A, Masotti S, Prontera C, Passino C, Plebani M, on the behalf of the Study Group on Cardiovascular Risk Biomarkers of the Italian Society of Clinical Biochemistry (SIBioC). The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications. Clin Chem Lab Med. 2017;55:1634–51.

    Article  CAS  PubMed  Google Scholar 

  30. Marjot J, Kaier TE, Martin ED, Reji SS, Copeland O, Iqbal M, Goodson B, Hamren S, Harding SE, Marber MS. Quantifying the release of biomarkers of myocardial necrosis from cardiac myocytes and intact myocardium. Clin Chem. 2017;63:990–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chaulin A. Cardiac troponins: contemporary biological data and new methods of determination. Vasc Health Risk Manag. 2021;17:299–316.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zoltani CK. Chapter 11—Cardiovascular toxicity biomarkers. In: Gupta RC, editor. Biomarkers in toxicology. Academic Press; 2014. p. 199–215.

    Chapter  Google Scholar 

  33. Clerico A, Ripoli A, Masotti S, Musetti V, Aloe R, Dipalo M, Rizzardi S, Dittadi R, Carrozza C, Storti S, Belloni L, Perrone M, Fasano T, Canovi S, Correale M, Prontera C, Guiotto C, Cosseddu D, Migliardi M, Bernardini S. Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: a multicenter study. Clin Chim Acta. 2019;493:156–61.

    Article  CAS  PubMed  Google Scholar 

  34. Ko DH, Hyun J, Kim HS, Park MJ, Shin DH. Harmonization of Cardiac Troponin I: significance of sample types. Clin Lab. 2019;65.

    Google Scholar 

  35. Clerico A, Ripoli A, Masotti S, Prontera C, Storti S, Fortunato A, Buzzi P, Casagranda I, Franzini M, Ndreu R, Zucchelli GC, Zaninotto M, Plebani M. Pilot study on harmonization of cardiac troponin I immunoassays using patients and quality control plasma samples. On behalf of the Italian Section of the European Ligand Assay Society (ELAS) and of the Study Group on Cardiovascular Biomarkers of the Società Italiana di Biochimica Clinica (SIBioC). Clin Chim Acta. 2016;456:42–8.

    Article  CAS  PubMed  Google Scholar 

  36. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959–69.

    Article  CAS  PubMed  Google Scholar 

  37. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD, Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138:e618–51.

    Article  PubMed  Google Scholar 

  38. Apple FS, Collinson PO, IFCC Task Force on Clinical Applications of Cardiac Biomarkers. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012;58:54–61.

    Article  CAS  PubMed  Google Scholar 

  39. Wu AHB, Christenson RH, Greene DN, Jaffe AS, Kavsak PA, Ordonez-Llanos J, Apple FS. Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem. 2018;64:645–55.

    Article  CAS  PubMed  Google Scholar 

  40. Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem. 2012;58:1574–81.

    Article  CAS  PubMed  Google Scholar 

  41. Muzyk P, Twerenbold R, Morawiec B, Ayala PL, Boeddinghaus J, Nestelberger T, Mueller C, Kawecki D. Use of cardiac troponin in the early diagnosis of acute myocardial infarction. Kardiol Pol. 2020;78:1099–106.

    Article  PubMed  Google Scholar 

  42. Mueller-Hennessen M, Mueller C, Giannitsis E, Biener M, Vafaie M, deFilippi CR, Christ M, Ordóñez-Llanos J, Panteghini M, Plebani M, Verschuren F, Melki D, French JK, Christenson RH, Body R, McCord J, Dinkel C, Katus HA, Lindahl B, TRAPID-AMI Investigators. Serial sampling of high-sensitivity cardiac troponin T may not be required for prediction of acute myocardial infarction diagnosis in chest pain patients with highly abnormal concentrations at presentation. Clin Chem. 2016;63:542–51.

    Article  PubMed  Google Scholar 

  43. Heidenreich PA, Alloggiamento T, Melsop K, McDonald KM, Go AS, Hlatky MA. The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis. J Am Coll Cardiol. 2001;38:478–85.

    Article  CAS  PubMed  Google Scholar 

  44. Chatterjee S, Kim J, Dahhan A, Choudhary G, Sharma S, Wu WC. Use of high-sensitivity troponin assays predicts mortality in patients with normal conventional troponin assays on admission-insights from a meta-analysis. Clin Cardiol. 2013;36:649–53.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kontos MC, Turlington JS. High-sensitivity troponins in cardiovascular disease. Curr Cardiol Rep. 2020;22:30.

    Article  PubMed  Google Scholar 

  46. Park KC, Gaze DC, Collinson PO, Marber MS. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res. 2017;113:1708–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Brown AJ, Shah ASV, West NEJ, Costopoulos C, Orzalkiewicz M, Newby DE, Bennett MR, Mills NL, Calvert PA. High-sensitivity troponin I is associated with high-risk plaque and MACE in stable coronary artery disease. JACC Cardiovasc Imaging. 2017;10:1200–3.

    Article  PubMed  Google Scholar 

  48. Beatty AL, Ku IA, Christenson RH, DeFilippi CR, Schiller NB, Whooley MA. High-sensitivity cardiac troponin t levels and secondary events in outpatients with coronary heart disease from the heart and soul study. JAMA Intern Med. 2013;173:763–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. White HD, Tonkin A, Simes J, Stewart R, Mann K, Thompson P, Colquhoun D, West M, Nestel P, Sullivan D, Keech AC, Hunt D, Blankenberg S, LIPID Study Investigators. Association of contemporary sensitive troponin I levels at baseline and change at 1 year with long-term coronary events following myocardial infarction or unstable angina: results from the LIPID study (Long-Term Intervention with Pravastatin in Ischaemic Disease). J Am Coll Cardiol. 2014;63:345–54.

    Article  CAS  PubMed  Google Scholar 

  50. Kociol RD, Pang PS, Gheorghiade M, Fonarow GC, O’Connor CM, Felker GM. Troponin elevation in heart failure prevalence, mechanisms, and clinical implications. J Am Coll Cardiol. 2010;28:1071–8.

    Article  Google Scholar 

  51. Evans JDW, Dobbin SJH, Pettit SJ, Di Angelantonio E, Willeit P. High-sensitivity cardiac troponin and new-onset heart failure: a systematic review and meta-analysis of 67,063 patients with 4, 165 incident heart failure events. JACC Heart Fail. 2018;6:187–97.

    Article  PubMed  Google Scholar 

  52. Masson S, Anand I, Favero C, Barlera S, Vago T, Bertocchi F, Maggioni AP, Tavazzi L, Tognoni G, Cohn JN, Latini R, Valsartan Heart Failure Trial (Val-HeFT) and Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca–Heart Failure (GISSI-HF) Investigators. Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials. Circulation. 2012;125:280–8.

    Article  CAS  PubMed  Google Scholar 

  53. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation. 2002;106:2941–5.

    Article  CAS  PubMed  Google Scholar 

  54. Devereaux PJ, Szczeklik W. Myocardial injury after non-cardiac surgery: diagnosis and management. Eur Heart J. 2020;41:3083–91.

    Article  CAS  PubMed  Google Scholar 

  55. de Filippi CR, Herzog CA. Interpreting cardiac biomarkers in the setting of chronic kidney disease. Clin Chem. 2017;63:59–65.

    Article  Google Scholar 

  56. Dispenzieri A, Gertz MA, Kumar SK, Lacy MQ, Kyle RA, Saenger AK, Grogan M, Zeldenrust SR, Hayman SR, Buadi F, Greipp PR, Leung N, Russell SR, Dingli D, Lust JA, Rajkumar SV, Jaffe AS. High sensitivity cardiac troponin T in patients with immunoglobulin light chain amyloidosis. Heart. 2014;100:383–8.

    Article  CAS  PubMed  Google Scholar 

  57. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5:596–603.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Cardinale D, Ciceri F, Latini R, Franzosi MG, Sandri MT, Civelli M, Cucchi G, Menatti E, Mangiavacchi M, Cavina R, Barbieri E, Gori S, Colombo A, Curigliano G, Salvatici M, Rizzo A, Ghisoni F, Bianchi A, Falci C, Aquilina M, Rocca A, Monopoli A, Milandri C, Rossetti G, Bregni M, Sicuro M, Malossi A, Nassiacos D, Verusio C, Giordano M, Staszewsky L, Barlera S, Nicolis EB, Magnoli M, Masson S, Cipolla CM. ICOS-ONE Study Investigators. Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: the International CardioOncology Society-one trial. Eur J Cancer. 2018;94:126–37.

    Article  CAS  PubMed  Google Scholar 

  59. Vassalle C, Masotti S, Lubrano V, Basta G, Prontera C, Di Cecco P, Del Turco S, Sabatino L, Pingitore A. Traditional and new candidate cardiac biomarkers assessed before, early, and late after half marathon in trained subjects. Eur J Appl Physiol. 2018;118:411–7.

    Article  CAS  PubMed  Google Scholar 

  60. McEvoy JW, Chen Y, Nambi V, Ballantyne CM, Sharrett AR, Appel LJ, Post WS, Blumenthal RS, Matsushita K, Selvin E. High-sensitivity cardiac troponin t and risk of hypertension. Circulation. 2015;132:825–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McEvoy JW, Chen Y, Ndumele CE, Solomon SD, Nambi V, Ballantyne CM, Blumenthal RS, Coresh J, Selvin E. Six-year change in high-sensitivity cardiac troponin t and risk of subsequent coronary heart disease, heart failure, and death. JAMA Cardiol. 2016;1:519–28.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Collinson PO. The role of cardiovascular biomarkers in cardiovascular disease risk assessment. Curr Opin Cardiol. 2014;29:366–71.

    Article  PubMed  Google Scholar 

  63. Mair J, Lindahl B, Hammarsten O, Müller C, Giannitsis E, Huber K, Möckel M, Plebani M, Thygesen K, Jaffe AS. How is cardiac troponin released from injured myocardium? Eur Heart J Acute Cardiovasc Care. 2018;7:553–60.

    Article  PubMed  Google Scholar 

  64. Clerico A, Ripoli A, Zaninotto M, Masotti S, Musetti V, Ciaccio M, Aloe R, Rizzardi S, Dittadi R, Carrozza C, Fasano T, Perrone M, de Santis A, Prontera C, Riggio D, Guiotto C, Migliardi M, Bernardini S, Plebani M. Head-to-head comparison of plasma cTnI concentration values measured with three high-sensitivity methods in a large Italian population of healthy volunteers and patients admitted to emergency department with acute coronary syndrome: a multi-center study. Clin Chim Acta. 2019;496:25–34.

    Article  CAS  PubMed  Google Scholar 

  65. Harley K, Bissonnette S, Inzitari R, Schulz K, Apple FS, Kavsak PA, Gunsolus IL. Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays. Clin Chem Lab Med. 2021;59:1431–43.

    Article  CAS  PubMed  Google Scholar 

  66. Sodi R, Darn SM, Davison AS, Stott A, Shenkin A. Mechanism of interference by haemolysis in the cardiac troponin T immunoassay. Ann Clin Biochem. 2006;43:49–56.

    Article  CAS  PubMed  Google Scholar 

  67. Masimasi N, Means RT Jr. Elevated troponin levels associated with hemolysis. Am J Med Sci. 2005;330:201–3.

    Article  PubMed  Google Scholar 

  68. Saenger AK, Jaffe AS, Body R, Collinson PO, Kavsak PA, Lam CSP, Lefèvre G, Omland T, Ordóñez-Llanos J, Pulkki K, Apple FS. Cardiac troponin and natriuretic peptide analytical interferences from hemolysis and biotin: educational aids from the IFCC Committee on Cardiac Biomarkers (IFCC C-CB). Clin Chem Lab Med. 2019;57:633–40.

    Article  CAS  PubMed  Google Scholar 

  69. Vafaie M, Biener M, Mueller M, Schnabel PA, André F, Steen H, Zorn M, Schueler M, Blankenberg S, Katus HA, Giannitsis E. Analytically false or true positive elevations of high sensitivity cardiac troponin: a systematic approach. Heart. 2014;100:508–14.

    Article  PubMed  Google Scholar 

  70. Krintus M, Kozinski M, Boudry P, Capell NE, Köller U, Lackner K, Lefèvre G, Lennartz L, Lotz J, Herranz AM, Nybo M, Plebani M, Sandberg MB, Schratzberger W, Shih J, Skadberg Ø, Chargui AT, Zaninotto M, Sypniewska G. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay. Clin Chem Lab Med. 2014;52:1657–65.

    CAS  PubMed  Google Scholar 

  71. Gerhardt W, Nordin G, Herbert AK, Burzell BL, Isaksson A, Gustavsson E, Haglund S, Müller-Bardorff M, Katus HA. Troponin T and I assays show decreased concentrations in heparin plasma compared with serum: lower recoveries in early than in late phases of myocardial injury. Clin Chem. 2000;46:817–21.

    Article  CAS  PubMed  Google Scholar 

  72. Warner JV, Marshall GA. High incidence of macrotroponin I with a high-sensitivity troponin I assay. Clin Chem Lab Med. 2016;54:1821–9.

    Article  CAS  PubMed  Google Scholar 

  73. Katrukha IA, Katrukha AG. Myocardial injury and the release of troponins I and T in the blood of patients. Clin Chem. 2021;67:124–30.

    Article  PubMed  Google Scholar 

  74. Damen SAJ, Vroemen WHM, Brouwer MA, Mezger STP, Suryapranata H, van Royen N, Bekers O, Meex SJR, Wodzig WKWH, Verheugt FWA, de Boer D, Cramer GE, Mingels AMA. Multi-site coronary vein sampling study on cardiac troponin T degradation in non-ST-segment-elevation myocardial infarction: toward a more specific cardiac troponin T assay. J Am Heart Assoc. 2019;8:e012602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Vroemen WHM, Mezger STP, Masotti S, Clerico A, Bekers O, de Boer D, Mingels A. Cardiac troponin T: only small molecules in recreational runners after marathon completion. J Appl Lab Med. 2019;3:909–11.

    Article  CAS  PubMed  Google Scholar 

  76. Madsen LH, Christensen G, Lund T, Serebruany VL, Granger CB, Hoen I, Grieg Z, Alexander JH, Jaffe AS, Van Eyk JE, Atar D. Time course of degradation of cardiac troponin I in patients with acute ST-elevation myocardial infarction: the ASSENT-2 troponin substudy. Circ Res. 2006;99:1141–7.

    Article  CAS  PubMed  Google Scholar 

  77. Cardinaels EP, Mingels AM, van Rooij T, Collinson PO, Prinzen FW, van Dieijen-Visser MP. Time-dependent degradation pattern of cardiac troponin T following myocardial infarction. Clin Chem. 2013;59:1083–90.

    Article  CAS  PubMed  Google Scholar 

  78. Bolstad N, Warren DJ, Nustad K. Heterophilic antibody interference in immunometric assays. Best Pract Res Clin Endocrinol Metab. 2013;27:647–61.

    Article  CAS  PubMed  Google Scholar 

  79. Bhoi S, Verma P, Vankar S, Galwankar S. High sensitivity troponins and conventional troponins at the bedside. Int J Crit Illn Inj Sci. 2014;4:253–6.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Clerico A, Zaninotto M, Plebani M. High-sensitivity assay for cardiac troponins with POCT methods. The future is soon. Clin Chem Lab Med. 2021;59:1477–8.

    Article  CAS  PubMed  Google Scholar 

  81. Collinson P. Cardiac biomarker measurement by point of care testing—development, rationale, current state and future developments. Clin Chim Acta. 2020;508:234–9.

    Article  CAS  PubMed  Google Scholar 

  82. Tate JR, Bunk DM, Christenson RH, Barth JH, Katrukha A, Noble JE, Schimmel H, Wang L, Panteghini M, IFCC Working Group on Standardization of Cardiac Troponin I. Evaluation of standardization capability of current cardiac troponin I assays by a correlation study: results of an IFCC pilot project. Clin Chem Lab Med. 2015;53:677–90.

    Article  CAS  PubMed  Google Scholar 

  83. van der Linden N, Hilderink JM, Cornelis T, Kimenai DM, Klinkenberg LJJ, van Doorn WP, Litjens EJR, van Suijlen JDE, van Loon LJC, Bekers O, Kooman JP, Meex SJR. Twenty-four-hour biological variation profiles of cardiac troponin I in individuals with or without chronic kidney disease. Clin Chem. 2017;63:1655–6.

    Article  PubMed  Google Scholar 

  84. Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, Rubini Gimenez M, Puelacher C, Daniel Neuhaus J, Hillinger P, Nestelberger T, Boeddinghaus J, Grimm K, Sabti Z, Bons JA, van Suijlen JD, Tan FE, Ten Kate J, Bekers O, van Loon LJ, van Dieijen-Visser MP, Mueller C, Meex SJ. Diurnal rhythm of cardiac troponin: consequences for the diagnosis of acute myocardial infarction. Clin Chem. 2016;62:1602–11.

    Article  CAS  PubMed  Google Scholar 

  85. Wildi K, Singeisen H, Twerenbold R, Badertscher P, Wussler D, Klinkenberg LJJ, Meex SJR, Nestelberger T, Boeddinghaus J, Miró Ò, Martin-Sanchez FJ, Morawiec B, Muzyk P, Parenica J, Keller DI, Geigy N, Potlukova E, Sabti Z, Kozhuharov N, Puelacher C, du Fay de Lavallaz J, Rubini Gimenez M, Shrestha S, Marzano G, Rentsch K, Osswald S, Reichlin T, Mueller C, APACE Investigators. Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction. Int J Cardiol. 2018;270:14–20.

    Article  CAS  PubMed  Google Scholar 

  86. Zaninotto M, Padoan A, Mion MM, Marinova M, Plebani M. Short-term biological variation and diurnal rhythm of cardiac troponin I (Access hs-TnI) in healthy subjects. Clin Chim Acta. 2020;504:163–7.

    Article  CAS  PubMed  Google Scholar 

  87. Eggers KM, Lind L, Ahlström H, Bjerner T, Ebeling Barbier C, Larsson A, Venge P, Lindahl B. Prevalence and pathophysiological mechanisms of elevated cardiac troponin I levels in a population-based sample of elderly subjects. Eur Heart J. 2008;29:2252–8.

    Article  CAS  PubMed  Google Scholar 

  88. de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, Hashim I, Berry JD, Das SR, Morrow DA, McGuire DK. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. J Am Med Assoc. 2010;304:2503–12.

    Article  Google Scholar 

  89. Wallace TW, Abdullah SM, Drazner MH, Das SR, Khera A, McGuire DK, Wians F, Sabatine MS, Morrow DA, de Lemos JA. Prevalence and determinants of troponin T elevation in the general population. Circulation. 2006;113:1958–65.

    Article  CAS  PubMed  Google Scholar 

  90. de Simone G, Devereux RB, Daniels SR, Meyer RA. Gender differences in left ventricular growth. Hypertension. 1995;26:979–83.

    Article  PubMed  Google Scholar 

  91. Mueller T, Egger M, Peer E, Dieplinger B. 5th generation cardiac troponin I and T assays in clinical routine—a head-to-head comparison with data from the Linz troponin (LITROP) study. Clin Chim Acta. 2018;485:195–204.

    Article  CAS  PubMed  Google Scholar 

  92. Mueller T, Egger M, Peer E, Jani E, Dieplinger B. Evaluation of sex-specific cut-off values of high-sensitivity cardiac troponin I and T assays in an emergency department setting—results from the Linz Troponin (LITROP) study. Clin Chim Acta. 2018;487:66–74.

    Article  CAS  PubMed  Google Scholar 

  93. Mueller-Hennessen M, Lindahl B, Giannitsis E, Biener M, Vafaie M, deFilippi CR, Christ M, Santalo-Bel M, Panteghini M, Plebani M, Verschuren F, Jernberg T, French JK, Christenson RH, Body R, McCord J, Dilba P, Katus HA, Mueller C, TRAPID-AMI Investigators. 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.

    Article  PubMed  Google Scholar 

  94. Shah AS, Griffiths M, Lee KK, McAllister DA, Hunter AL, Ferry AV, Cruikshank A, Reid A, Stoddart M, Strachan F, Walker S, Collinson PO, Apple FS, Gray AJ, Fox KA, Newby DE, Mills NL. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. Br Med J. 2015;350:g7873.

    Article  Google Scholar 

  95. Cullen L, Greenslade JH, Carlton EW, Than M, Pickering JW, Ho A, Greaves K, Berndt SL, Body R, Ryan K, Parsonage WA. Sex-specific versus overall cut points for a high sensitivity troponin I assay in predicting 1-year outcomes in emergency patients presenting with chest pain. Heart. 2016;102:120–6.

    Article  CAS  PubMed  Google Scholar 

  96. Clerico A, Vittorini S, Passino C. Circulating forms of the b-type natriuretic peptide prohormone: pathophysiologic and clinical considerations. Adv Clin Chem. 2012;58:31–44.

    Article  CAS  PubMed  Google Scholar 

  97. Vasile VC, Jaffe AS. Natriuretic Peptides and Analytical Barriers. Clin Chem. 2017;63:50–8.

    Article  CAS  PubMed  Google Scholar 

  98. Lyngbakken MN, Myhre PL, Røsjø H, Omland T. Novel biomarkers of cardiovascular disease: applications in clinical practice. Crit Rev Clin Lab Sci. 2019;56:33–60.

    Article  CAS  PubMed  Google Scholar 

  99. Tello-Montoliu A, Marín F, Roldán V, Mainar L, López MT, Sogorb F, Vicente V, Lip GY. A multimarker risk stratification approach to non-ST elevation acute coronary syndrome: implications of troponin T, CRP, NT pro-BNP and fibrin D-dimer levels. J Intern Med. 2007;262:651–8.

    Article  CAS  PubMed  Google Scholar 

  100. Choi HI, Lee MY, Oh BK, Lee SJ, Kang JG, Lee SH, Lee JY, Kim BJ, Kim BS, Kang JH, Sung KC. Effects of age, sex, and obesity on N-terminal pro B-type natriuretic peptide concentrations in the general population. Circ J. 2021;85:647–54.

    Article  CAS  PubMed  Google Scholar 

  101. Hogenhuis J, Voors AA, Jaarsma T, Hillege HL, Boomsma F, van Veldhuisen DJ. Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT-ANP and BNP/NT-proBNP. Eur J Heart Fail. 2005;7:81–6.

    Article  CAS  PubMed  Google Scholar 

  102. Luchner A, Hengstenberg C, Löwel H, Riegger GA, Schunkert H, Holmer S. Effect of compensated renal dysfunction on approved heart failure markers: direct comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP. Hypertension. 2005;46:118–23.

    Article  CAS  PubMed  Google Scholar 

  103. Bachmann KN, Huang S, Lee H, Dichtel LE, Gupta DK, Burnett JC Jr, Miller KK, Wang TJ, Finkelstein JS. Effect of testosterone on natriuretic peptide levels. J Am Coll Cardiol. 2019;73:1288–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Firmes LB, Belo NO, Reis AM. Conjugated equine estrogens and estradiol benzoate differentially modulate the natriuretic peptide system in spontaneously hypertensive rats. Menopause. 2013;20:554–60.

    Article  PubMed  Google Scholar 

  105. Yao M, Nguyen TV, Rosario ER, Ramsden M, Pike CJ. Androgens regulate neprilysin expression: role in reducing beta-amyloid levels. J Neurochem. 2008;105:2477–88. https://doi.org/10.1111/j.1471-4159.2008.05341.x.

    Article  CAS  PubMed  Google Scholar 

  106. Chang AY, Abdullah SM, Jain T, Stanek HG, Das SR, McGuire DK, Auchus RJ, de Lemos JA. Associations among androgens, estrogens, and natriuretic peptides in young women: observations from the Dallas Heart Study. J Am Coll Cardiol. 2007;49:109–16.

    Article  CAS  PubMed  Google Scholar 

  107. Suthahar N, Meijers WC, Ho JE, Gansevoort RT, Voors AA, van der Meer P, Bakker SJL, Heymans S, van Empel V, Schroen B, van der Harst P, van Veldhuisen DJ, de Boer RA. Sex-specific associations of obesity and N-terminal pro-B-type natriuretic peptide levels in the general population. Eur J Heart Fail. 2018;20:1205–14.

    Article  CAS  PubMed  Google Scholar 

  108. Luchner A, Hengstenberg C, Löwel H, Trawinski J, Baumann M, Riegger GA, Schunkert H, Holmer S. N-terminal pro-brain natriuretic peptide after myocardial infarction: a marker of cardio-renal function. Hypertension. 2002;39:99–104.

    Article  CAS  PubMed  Google Scholar 

  109. Mayr A, Mair J, Schocke M, Klug G, Pedarnig K, Haubner BJ, Nowosielski M, Grubinger T, Pachinger O, Metzler B. Predictive value of NT-pro BNP after acute myocardial infarction: relation with acute and chronic infarct size and myocardial function. Int J Cardiol. 2011;147:118–23.

    Article  PubMed  Google Scholar 

  110. Steen H, Futterer S, Merten C, Jünger C, Katus HA, Giannitsis E. Relative role of NT-pro BNP and cardiac troponin T at 96 hours for estimation of infarct size and left ventricular function after acute myocardial infarction. J Cardiovasc Magn Reson. 2007;9:749–58.

    Article  PubMed  Google Scholar 

  111. Arakawa N, Nakamura M, Aoki H, Hiramori K. Relationship between plasma level of brain natriuretic peptide and myocardial infarct size. Cardiology. 1994;85:334–40.

    Article  CAS  PubMed  Google Scholar 

  112. Mueller T, Gegenhuber A, Dieplinger B, Poelz W, Haltmayer M. Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples. Clin Chem Lab Med. 2004;42:942–4.

    Article  CAS  PubMed  Google Scholar 

  113. Wu AH, Shea E, Lu QT, Minyard J, Bui K, Hsu JC, Agee SJ, Todd J. Short- and long-term cardiac troponin I analyte stability in plasma and serum from healthy volunteers by use of an ultrasensitive, single-molecule counting assay. Clin Chem. 2009;55:2057–9.

    Article  CAS  PubMed  Google Scholar 

  114. Melzi d’Eril G, Tagnochetti T, Nauti A, Klersy C, Papalia A, Vadacca G, Moratti R, Merlini G. Biological variation of N-terminal pro-brain natriuretic peptide in healthy individuals. Clin Chem. 2003;49:1554–5.

    Article  PubMed  Google Scholar 

  115. Nordenskjöld AM, Ahlström H, Eggers KM, Fröbert O, Venge P, Lindahl B. Short- and long-term individual variation in NT-proBNP levels in patients with stable coronary artery disease. Clin Chim Acta. 2013;422:15–20.

    Article  PubMed  Google Scholar 

  116. Radosavljevic-Radovanovic M, Radovanovic N, Vasiljevic Z, Marinkovic J, Mitrovic P, Mrdovic I, Stankovic S, Kružliak P, Beleslin B, Uscumlic A, Kostic J. Usefulness of NT-proBNP in the follow-up of patients after myocardial infarction. J Med Biochem. 2016;35:158–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Clerico A, Passino C. Predictive value of NT-proBNP in patients with acute myocardial infarction. Clin Chem. 2017;63:1045–6.

    Article  CAS  PubMed  Google Scholar 

  118. Gong X, Zhang T, Feng S, Song D, Chen Y, Yao T, Han P, Liu Y, Li C, Song Z, Gao J, Cui Z, Ma J, Liu Y. Association between N-terminal pro-BNP and 12 months major adverse cardiac events among patients admitted with NSTEMI. Ann Palliat Med. 2021;10:5231–43.

    Article  PubMed  Google Scholar 

  119. Wolsk E, Claggett B, Pfeffer MA, Diaz R, Dickstein K, Gerstein HC, Lawson FC, Lewis EF, Maggioni AP, McMurray JJV, Probstfield JL, Riddle MC, Solomon SD, Tardif JC, Køber L. Role of B-type natriuretic peptide and N-terminal prohormone BNP as predictors of cardiovascular morbidity and mortality in patients with a recent coronary event and type 2 diabetes mellitus. J Am Heart Assoc. 2017;6:e004743.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Chen M, Li Y, Zhang D, Wu Y. Gender difference in the association between smoking and lung function: exploring the role of C-reactive protein as a mediating factor. Public Health. 2020;183:88–93.

    Article  CAS  PubMed  Google Scholar 

  121. Mangnus L, van Steenbergen HW, Nieuwenhuis WP, Reijnierse M, van der Helm-van Mil AHM. Moderate use of alcohol is associated with lower levels of C reactive protein but not with less severe joint inflammation: a cross-sectional study in early RA and healthy volunteers. RMD Open. 2018;4:e000577.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Hammonds TL, Gathright EC, Goldstein CM, Penn MS, Hughes JW. Effects of exercise on c-reactive protein in healthy patients and in patients with heart disease: a meta-analysis. Heart Lung. 2016;45:273–82.

    Article  PubMed  PubMed Central  Google Scholar 

  123. McConnell JP, Branum EL, Ballman KV, Lagerstedt SA, Katzmann JA, Jaffe AS. Gender differences in C-reactive protein concentrations confirmation with two sensitive methods. Clin Chem Lab Med. 2002;40:56–9.

    Article  CAS  PubMed  Google Scholar 

  124. Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W, Wians FH Jr, Grundy SM, de Lemos JA. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol. 2005;46:464–9.

    Article  CAS  PubMed  Google Scholar 

  125. Vigna L, Vassalle C, Tirelli AS, Gori F, Tomaino L, Sabatino L, Bamonti F. Gender-related association between uric acid, homocysteine, γ-glutamyltransferase, inflammatory biomarkers and metabolic syndrome in subjects affected by obesity. Biomark Med. 2017. https://doi.org/10.2217/bmm-2017-0072. Epub ahead of print.

  126. Ma QQ, Yang XJ, Yang NQ, Liu L, Li XD, Zhu K, Fu Q, Wei P. Study on the levels of uric acid and high-sensitivity C-reactive protein in ACS patients and their relationships with the extent of the coronary artery lesion. Eur Rev Med Pharmacol Sci. 2016;20:4294–8.

    PubMed  Google Scholar 

  127. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med. 2000;343:1139–47.

    Article  CAS  PubMed  Google Scholar 

  128. Zhang X, Wang S, Fang S, Yu B. Prognostic role of high sensitivity C-reactive protein in patients with acute myocardial infarction. Front Cardiovasc Med. 2021;8:659446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Mani P, Puri R, Schwartz GG, Nissen SE, Shao M, Kastelein JJP, Menon V, Lincoff AM, Nicholls SJ. Association of initial and serial C-reactive protein levels with adverse cardiovascular events and death after acute coronary syndrome: a secondary analysis of the VISTA-16 trial. JAMA Cardiol. 2019;4:314–20.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Morrow DA, Rifai N, Antman EM, Weiner DL, McCabe CH, Cannon CP, Braunwald E. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A Substudy. J Am Coll Cardiol. 1998;31:1460–5.

    Article  CAS  PubMed  Google Scholar 

  131. Jia L, Yuan JQ, Zhu L, Zhang Y. High high-sensitivity C-reactive protein/BMI ratio predicts future adverse outcomes in patients with acute coronary syndrome. Coron Artery Dis. 2019;30:448–54.

    Article  PubMed  Google Scholar 

  132. O’Donoghue ML, Morrow DA, Cannon CP, Jarolim P, Desai NR, Sherwood MW, Murphy SA, Gerszten RE, Sabatine MS. Multimarker risk stratification in patients with acute myocardial infarction. J Am Heart Assoc. 2016;5:e002586.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Sabatine MS, Morrow DA, de Lemos JA, Gibson CM, Murphy SA, Rifai N, McCabe C, Antman EM, Cannon CP, Braunwald E. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation. 2002;105:1760–3.

    Article  CAS  PubMed  Google Scholar 

  134. Klingenberg R, Aghlmandi S, Räber L, Gencer B, Nanchen D, Heg D, Carballo S, Rodondi N, Mach F, Windecker S, Jüni P, von Eckardstein A, Matter CM, Lüscher TF. Improved risk stratification of patients with acute coronary syndromes using a combination of hsTnT, NT-proBNP and hsCRP with the GRACE score. Eur Heart J Acute Cardiovasc Care. 2018;7:129–38.

    Article  PubMed  Google Scholar 

  135. Budzianowski J, Pieszko K, Burchardt P, Rzeźniczak J, Hiczkiewicz J. The role of hematological indices in patients with acute coronary syndrome. Dis Markers. 2017;2017:3041565.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Azab B, Torbey E, Singh J, Akerman M, Khoueiry G, McGinn JT, Widmann WD, Lafferty J. Mean platelet volume/platelet count ratio as a predictor of long-term mortality after non-ST-elevation myocardial infarction. Platelets. 2011;22:557–66.

    Article  CAS  PubMed  Google Scholar 

  137. Pizzulli L, Yang A, Martin JF, Lüderitz B. Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain. Eur Heart J. 1998;19:80–4.

    Article  CAS  PubMed  Google Scholar 

  138. Sivri N, Tekin G, Yalta K, Aksoy Y, Senen K, Yetkin E. Statins decrease mean platelet volume irrespective of cholesterol lowering effect. Kardiol Pol. 2013;71:1042–7.

    Article  PubMed  Google Scholar 

  139. Wan ZF, Zhou D, Xue JH, Wu Y, Wang H, Zhao Y, Zhu L, Yuan ZY. Combination of mean platelet volume and the GRACE risk score better predicts future cardiovascular events in patients with acute coronary syndrome. Platelets. 2014;25:447–51.

    Article  CAS  PubMed  Google Scholar 

  140. Chan D, Ng LL. Biomarkers in acute myocardial infarction. BMC Med. 2010;8:34.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Chen Y, Tao Y, Zhang L, Xu W, Zhou X. Diagnostic and prognostic value of biomarkers in acute myocardial infarction. Postgrad Med J. 2019;95:210–6.

    Article  CAS  PubMed  Google Scholar 

  142. Wang XY, Zhang F, Zhang C, Zheng LR, Yang J. The biomarkers for acute myocardial infarction and heart failure. Biomed Res Int. 2020;2020:2018035.

    PubMed  PubMed Central  Google Scholar 

  143. Gong XJ, Song XY, Wei H, Wang J, Niu M. Serum S100A4 levels as a novel biomarker for detection of acute myocardial infarction. Eur Rev Med Pharmacol Sci. 2015;19:2221–5.

    PubMed  Google Scholar 

  144. Ho MY, Wang CY. Role of irisin in myocardial infarction, heart failure, and cardiac hypertrophy. Cell. 2021;10:2103.

    Article  CAS  Google Scholar 

  145. Wang J, Tan GJ, Han LN, Bai YY, He M, Liu HB. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol. 2017;14:135–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Yan L, Liu Z, Zhang C. Uric acid as a predictor of in-hospital mortality in acute myocardial infarction: a meta-analysis. Cell Biochem Biophys. 2014;70:1597–601.

    Article  CAS  PubMed  Google Scholar 

  147. Wang Y, Zhen C, Wang R, Wang G. Growth-differentiation factor-15 predicts adverse cardiac events in patients with acute coronary syndrome: a meta-analysis. Am J Emerg Med. 2019;37:1346–52.

    PubMed  Google Scholar 

  148. Kamińska J, Koper OM, Siedlecka-Czykier E, Matowicka-Karna J, Bychowski J, Kemona H. The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes. Saudi J Biol Sci. 2018;25:1263–71.

    Article  PubMed  Google Scholar 

  149. Wernly B, Fuernau G, Masyuk M, Muessig JM, Pfeiler S, Bruno RR, Desch S, Muench P, Lichtenauer M, Kelm M, Adams V, Thiele H, Eitel I, Jung C. Syndecan-1 predicts outcome in patients with ST-segment elevation infarction independent from infarct-related myocardial injury. Sci Rep. 2019;9:18367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Armstrong EJ, Morrow DA, Sabatine MS. Inflammatory biomarkers in acute coronary syndromes: part III: biomarkers of oxidative stress and angiogenic growth factors. Circulation. 2006;113:e289–92.

    CAS  PubMed  Google Scholar 

  151. Gaggini M, Sabatino L, Vassalle C. Conventional and innovative methods to assess oxidative stress biomarkers in the clinical cardiovascular setting. BioTechniques. 2020;68:223–31.

    Article  CAS  PubMed  Google Scholar 

  152. Cosentino N, Campodonico J, Moltrasio M, Lucci C, Milazzo V, Rubino M, De Metrio M, Marana I, Grazi M, Bonomi A, Veglia F, Lauri G, Bartorelli AL, Marenzi G. Mitochondrial biomarkers in patients with ST-elevation myocardial infarction and their potential prognostic implications: a prospective observational study. J Clin Med. 2021;10:275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Hayek A, Paccalet A, Mechtouff L, Da Silva CC, Ivanes F, Falque H, Leboube S, Varillon Y, Amaz C, de Bourguignon C, Prieur C, Tomasevic D, Genot N, Derimay F, Bonnefoy-Cudraz E, Bidaux G, Mewton N, Ovize M, Bochaton T. Kinetics and prognostic value of soluble VCAM-1 in ST-segment elevation myocardial infarction patients. Immun Inflamm Dis. 2021;9:493–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Freitas IA, Lima NA, Silva GBD Jr, Castro RL Jr, Patel P, Lima CCV, Lino DODC. Novel biomarkers in the prognosis of patients with atherosclerotic coronary artery disease. Rev Port Cardiol (Engl Ed). 2020;39:667–72.

    Article  PubMed  Google Scholar 

  155. Šabanović-Bajramović N, Hodžić E, Iglica A, Begić E, Resić N, Aganović K, Halilčević M, Bajramović S. Neutrophil gelatinase-associated lipocalin is a predictor of complications in the early phase of ST-elevation myocardial infarction. Med Glas (Zenica). 2020;17:328–34.

    PubMed  Google Scholar 

  156. Stöhr R, Schuh A, Heine GH, Brandenburg V. FGF23 in cardiovascular disease: innocent bystander or active mediator? Front Endocrinol (Lausanne). 2018;9:351. https://doi.org/10.3389/fendo.2018.00351. Erratum in: Front Endocrinol (Lausanne). 2018;9:422.

    Article  PubMed  Google Scholar 

  157. Szabo D, Sarszegi Z, Polgar B, Saghy E, Nemeth A, Reglodi D, Makkos A, Gorbe A, Helyes Z, Ferdinandy P, Herczeg R, Gyenesei A, Cziraki A, Tamas A. PACAP-38 in acute ST-segment elevation myocardial infarction in humans and pigs: a translational study. Int J Mol Sci. 2021;22:2883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Vassalle C. New biomarkers and traditional cardiovascular risk scores: any crystal ball for current effective advice and future exact prediction? Clin Chem Lab Med. 2018;56:1803–5.

    Article  CAS  PubMed  Google Scholar 

  159. Vassalle C. Oxidative stress and cardiovascular risk prediction: the long way towards a “radical” perspective. Int J Cardiol. 2018;273:252–3.

    Article  Google Scholar 

  160. Aldous SJ. Cardiac biomarkers in acute myocardial infarction. Int J Cardiol. 2013;164:282–94.

    Article  PubMed  Google Scholar 

  161. Young JM, Pickering JW, George PM, Aldous SJ, Wallace J, Frampton CM, Troughton RW, Richards MA, Greenslade JH, Cullen L, Than MP. Heart fatty acid binding protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction. BMC Emerg Med. 2016;16.

    Google Scholar 

  162. Reiter M, Twerenbold R, Reichlin T, Mueller M, Hoeller R, Moehring B, Haaf P, Wildi K, Merk S, Bernhard D, Mueller CZ, Freese M, Freidank H, Campodarve Botet I, Mueller C. Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction. Heart. 2013;99:708–14.

    Article  CAS  PubMed  Google Scholar 

  163. Carroll C, Al Khalaf M, Stevens JW, Leaviss J, Goodacre S, Collinson PO, Wang J. Heart-type fatty acid binding protein as an early marker for myocardial infarction: systematic review and meta-analysis. Emerg Med J. 2013;30:280–6.

    Article  PubMed  Google Scholar 

  164. Colli A, Josa M, Pomar JL, Mestres CA, Gherli T. Heart fatty acid binding protein in the diagnosis of myocardial infarction: where do we stand today? Cardiology. 2007;108:4–10.

    Article  CAS  PubMed  Google Scholar 

  165. Xu LQ, Yang YM, Tong H, Xu CF. Early diagnostic performance of heart-type fatty acid binding protein in suspected acute myocardial infarction: evidence from a meta-analysis of contemporary studies. Heart Lung Circ. 2018;27(4):503–12.

    Article  PubMed  Google Scholar 

  166. Liou K, Ho S, Ooi SY. Heart-type fatty acid binding protein in early diagnosis of myocardial infarction in the era of high-sensitivity troponin: a systematic review and meta-analysis. Ann Clin Biochem. 2015;52:370–81.

    Article  CAS  PubMed  Google Scholar 

  167. Mueller C, Möckel M, Giannitsis E, Huber K, Mair J, Plebani M, Thygesen K, Jaffe AS, Lindahl B. ESC Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care AssociationUse of copeptin for rapid rule-out of acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2018;7:570–6.

    Article  PubMed  Google Scholar 

  168. Oemrawsingh RM, Lenderink T, Akkerhuis KM, Heeschen C, Baldus S, Fichtlscherer S, Hamm CW, Simoons ML, Boersma E, CAPTURE Investigators. Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome. Heart. 2011;97:1061–6.

    Article  CAS  PubMed  Google Scholar 

  169. Schernthaner C, Lichtenauer M, Wernly B, Paar V, Pistulli R, Rohm I, Jung C, Figulla HR, Yilmaz A, Cadamuro J, Haschke-Becher E, Pernow J, Schulze PC, Hoppe UC, Kretzschmar D. Multibiomarker analysis in patients with acute myocardial infarction. Eur J Clin Investig. 2017;47:638–48.

    Article  CAS  Google Scholar 

  170. Ali M, Pulli B, Courties G, Tricot B, Sebas M, Iwamoto Y, Hilgendorf I, Schob S, Dong A, Zheng W, Skoura A, Kalgukar A, Cortes C, Ruggeri R, Swirski FK, Nahrendorf M, Buckbinder L, Chen JW. Myeloperoxidase inhibition improves ventricular function and remodeling after experimental myocardial infarction. JACC Basic Transl Sci. 2016;1:633–43.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Lindsey ML, Gannon J, Aikawa M, Schoen FJ, Rabkin E, Lopresti-Morrow L, Crawford J, Black S, Libby P, Mitchell PG, Lee RT. Selective matrix metalloproteinase inhibition reduces left ventricular remodeling but does not inhibit angiogenesis after myocardial infarction. Circulation. 2002;105:753–8.

    Article  CAS  PubMed  Google Scholar 

  172. Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, Wen J, Takeshita A. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation. 2002;105:868–73.

    Article  CAS  PubMed  Google Scholar 

  173. Ridker PM, Everett BM, Thuren T, JG MF, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, JJP K, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31.

    Article  CAS  PubMed  Google Scholar 

  174. Fung EC, Butt AN, Eastwood J, Swaminathan R, Sodi R. Circulating microRNA in cardiovascular disease. Adv Clin Chem. 2019;91:99–122.

    Article  CAS  PubMed  Google Scholar 

  175. Feinberg MW, Moore KJ. MicroRNA regulation of atherosclerosis. Circ Res. 2016;118:703–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Hullinger TG, Montgomery RL, Seto AG, Dickinson BA, Semus HM, Lynch JM, Dalby CM, Robinson K, Stack C, Latimer PA, Hare JM, Olson EN, van Rooij E. Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res. 2012;110:71–81.

    Article  CAS  PubMed  Google Scholar 

  177. Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324:1710–3.

    Article  CAS  PubMed  Google Scholar 

  178. Icli B, Wara AK, Moslehi J, Sun X, Plovie E, Cahill M, Marchini JF, Schissler A, Padera RF, Shi J, Cheng HW, Raghuram S, Arany Z, Liao R, Croce K, MacRae C, Feinberg MW. MicroRNA-26a regulates pathological and physiological angiogenesis by targeting BMP/SMAD1 signaling. Circ Res. 2013;113:1231–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Li J, Li Y, Jiao J, Wang J, Li Y, Qin D, Li P. Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis. Mol Cell Biol. 2014;34:1788–99.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Piubelli C, Meraviglia V, Pompilio G, D’Alessandra Y, Colombo GI, Rossini A. microRNAs and cardiac cell fate. Cell. 2014;3:802–23.

    Article  Google Scholar 

  181. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010;31:659–66.

    Article  PubMed  Google Scholar 

  182. Devaux Y, Mueller M, Haaf P, Goretti E, Twerenbold R, Zangrando J, Vausort M, Reichlin T, Wildi K, Moehring B, Wagner DR, Mueller C. Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain. J Intern Med. 2015;277:260–71.

    Article  CAS  PubMed  Google Scholar 

  183. Wang X, Tian L, Sun Q. Diagnostic and prognostic value of circulating miRNA-499 and miRNA-22 in acute myocardial infarction. J Clin Lab Anal. 2020;34:2410–7.

    Article  CAS  PubMed  Google Scholar 

  184. Badacz R, Kleczyński P, Legutko J, Żmudka K, Gacoń J, Przewłocki T, Kabłak-Ziembicka A. Expression of miR-1-3p, miR-16-5p and miR-122-5p as possible risk factors of secondary cardiovascular events. Biomedicine. 2021;9:1055.

    CAS  Google Scholar 

  185. Tanase DM, Gosav EM, Ouatu A, Badescu MC, Dima N, Ganceanu-Rusu AR, Popescu D, Floria M, Rezus E, Rezus C. Current knowledge of microRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI). Life (Basel). 2021;11:1057.

    CAS  PubMed  Google Scholar 

  186. Hodgkinson CP, Kang MH, Dal-Pra S, Mirotsou M, Dzau VJ. MicroRNAs and cardiac regeneration. Circ Res. 2015;116:1700–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Eulalio A, Mano M, Dal Ferro M, Zentilin L, Sinagra G, Zacchigna S, Giacca M. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012;492:376–81.

    Article  CAS  PubMed  Google Scholar 

  188. Yang Y, Cheng HW, Qiu Y, Dupee D, Noonan M, Lin YD, Fisch S, Unno K, Sereti KI, Liao R. MicroRNA-34a plays a key role in cardiac repair and regeneration following myocardial infarction. Circ Res. 2015;117:450–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Yin L, Tang Y, Jiang M. Research on the circular RNA bioinformatics in patients with acute myocardial infarction. J Clin Lab Anal. 2021;35:e23621.

    Article  CAS  PubMed  Google Scholar 

  190. Wang S, Wang E, Chen Q, Yang Y, Xu L, Zhang X, Wu R, Hu X, Wu Z. Uncovering potential lncRNAs and mRNAs in the progression from acute myocardial infarction to myocardial fibrosis to heart failure. Front Cardiovasc Med. 2021;8:664044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Vassalle, C., Sabatino, L., Pepe, A. (2023). Cardiovascular Biomarkers in Acute Myocardial Infarction. In: Concistrè, G. (eds) Ischemic Heart Disease. Springer, Cham. https://doi.org/10.1007/978-3-031-25879-4_9

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