Sex-Related Aspects of Biomarkers in Cardiac Disease

  • Alma M. A. MingelsEmail author
  • Dorien M. Kimenai
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)


Biomarkers play an important role in the clinical management of cardiac care. In particular, cardiac troponins (cTn) and natriuretic peptides are the cornerstones for the diagnosis of acute myocardial infarction (AMI) and for the diagnosis of heart failure (HF), respectively. Current guidelines do not make a distinction between women and men. However, the commonly used “one size fits all” algorithms are topic of debate to improve assessment of prognosis, particularly in women. Due to the high-sensitivity assays (hs-cTn), lower cTn levels (and 99th percentile upper reference limits) were observed in women as compared with men. Sex-specific diagnostic thresholds may improve the diagnosis of AMI in women, though clinical relevance remains controversial and more trials are needed. Also other diagnostic aspects are under investigation, like combined biomarkers approach and rapid measurement strategies. For the natriuretic peptides, previous studies observed higher concentrations in women than in men, especially in premenopausal women who might benefit from the cardioprotective actions. Contrary to hs-cTn, natriuretic peptides are particularly incorporated in the ruling-out algorithms for the diagnosis of HF and not ruling-in. Clinical relevance of sex differences here seems marginal, as clinical research has shown that negative predictive values for ruling-out HF were hardly effected when applying a universal diagnostic threshold that is independent from sex or other risk factors. Apart from the diagnostic issues of AMI in women, we believe that in the future most sex-specific benefits of cardiac biomarkers can be obtained in patient follow-up (guiding therapy) and prognostic applications, fitting modern ideas on preventive and personalized medicine.


Acute myocardial infarction Age dependence Biomarkers Cardiac troponin I Cardiac troponin T Estrogen Heart failure Natriuretic peptides BNP NT-proBNP Pregnancy Review 


  1. 1.
    Abbas NA, John RI, Webb MC, et al. Cardiac troponins and renal function in nondialysis patients with chronic kidney disease. Clin Chem. 2005;51:2059–66.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Anwaruddin S, Lloyd-Jones DM, Baggish A, et al. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol. 2006;47:91–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Apple FS, Collinson PO, Biomarkers ITFoCAoC. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012a;58:54–61.CrossRefPubMedGoogle Scholar
  5. 5.
    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. 2012b;58:1574–81.CrossRefPubMedGoogle Scholar
  6. 6.
    Apple FS, Panteghini M, Ravkilde J, et al. Quality specifications for B-type natriuretic peptide assays. Clin Chem. 2005;51:486–93.CrossRefPubMedGoogle Scholar
  7. 7.
    Apple FS, Sandoval Y, Jaffe AS, Ordonez-Llanos J, Bio-Markers ITFoCAoC. Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care. Clin Chem. 2017;63:73–81.CrossRefPubMedGoogle Scholar
  8. 8.
    Apple FS, Wu AH, Jaffe AS, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine practice guidelines: analytical issues for biomarkers of heart failure. Circulation. 2007;116:e95–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Balmelli C, Meune C, Twerenbold R, et al. Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnostic of acute myocardial infarction and long-term prognosis between women and men. Am Heart J. 2013;166:30–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Bayes-Genis A, Lupon J, Jaffe AS. Can natriuretic peptides be used to guide therapy? EJIFCC. 2016;27:208–16.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Blankenberg S, Salomaa V, Makarova N, et al. Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium. Eur Heart J. 2016;37:2428–37.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Brunner-La Rocca HP, Eurlings L, Richards AM, et al. Which heart failure patients profit from natriuretic peptide guided therapy? a meta-analysis from individual patient data of randomized trials. Eur J Heart Fail. 2015;17:1252–61.CrossRefPubMedGoogle Scholar
  13. 13.
    Buiten MS, de Bie MK, Rotmans JI, et al. Serum cardiac troponin-I is superior to troponin-T as a marker for left ventricular dysfunction in clinically stable patients with end-stage renal disease. PLoS One. 2015;10:e0134245.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Canobbio MM, Warnes CA, Aboulhosn J, et al. Management of pregnancy in patients with complex congenital heart disease: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2017;135:e50–87.CrossRefPubMedGoogle Scholar
  15. 15.
    Canto JG, Goldberg RJ, Hand MM, et al. Symptom presentation of women with acute coronary syndromes: myth vs reality. Arch Intern Med. 2007;167:2405–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Cardinaels EP, Mingels AM, van Rooij T, et al. Time-dependent degradation pattern of cardiac troponin T following myocardial infarction. Clin Chem. 2013;59:1083–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Chang AY, Abdullah SM, Jain T, et al. Associations among androgens, estrogens, and natriuretic peptides in young women: observations from the Dallas Heart Study. J Am Coll Cardiol. 2007;49:109–16.CrossRefPubMedGoogle Scholar
  18. 18.
    Clerico A, Fontana M, Vittorini S, Emdin M. The search for a pathophysiological link between gender, cardiac endocrine function, body mass regulation and cardiac mortality: proposal for a working hypothesis. Clin Chim Acta. 2009;405:1–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Costello-Boerrigter LC, Boerrigter G, Redfield MM, et al. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol. 2006;47:345–53.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cullen L, Greenslade JH, Carlton EW, et al. 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.CrossRefPubMedGoogle Scholar
  21. 21.
    Dallmeier D, Denkinger M, Peter R, et al. Sex-specific associations of established and emerging cardiac biomarkers with all-cause mortality in older adults: the ActiFE study. Clin Chem. 2015;61:389–99.CrossRefPubMedGoogle Scholar
  22. 22.
    Daniels LB, Maisel AS. Cardiovascular biomarkers and sex: the case for women. Nat Rev Cardiol. 2015;12:588–96.CrossRefPubMedGoogle Scholar
  23. 23.
    de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503–12.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    de Simone G, Devereux RB, Daniels SR, Meyer RA. Gender differences in left ventricular growth. Hypertension. 1995;26:979–83.CrossRefPubMedGoogle Scholar
  25. 25.
    de Torbal A, Boersma E, Kors JA, et al. Incidence of recognized and unrecognized myocardial infarction in men and women aged 55 and older: the Rotterdam Study. Eur Heart J. 2006;27:729–36.CrossRefPubMedGoogle Scholar
  26. 26.
    deFilippi C, Seliger SL, Kelley W, et al. Interpreting cardiac troponin results from high-sensitivity assays in chronic kidney disease without acute coronary syndrome. Clin Chem. 2012;58:1342–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Dockery F, Bulpitt CJ, Agarwal S, et al. Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer. Clin Endocrinol (Oxf). 2008;68:59–65.CrossRefGoogle Scholar
  28. 28.
    Donaldson C, Eder S, Baker C, et al. Estrogen attenuates left ventricular and cardiomyocyte hypertrophy by an estrogen receptor-dependent pathway that increases calcineurin degradation. Circ Res. 2009;104:265–75. 211p following 275CrossRefPubMedGoogle Scholar
  29. 29.
    Eggers KM, Johnston N, Lind L, Venge P, Lindahl B. Cardiac troponin I levels in an elderly population from the community--The implications of sex. Clin Biochem. 2015;48:751–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Eggers KM, Lindahl B. Impact of sex on cardiac troponin concentrations-A critical appraisal. Clin Chem. 2017;63:1457–64.CrossRefPubMedGoogle Scholar
  31. 31.
    Eggers KM, Lindahl B, Melki D, Jernberg T. Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry. Eur Heart J. 2016;37:2417–24.CrossRefPubMedGoogle Scholar
  32. 32.
    Elsaesser A, Hamm CW. Acute coronary syndrome: the risk of being female. Circulation. 2004;109:565–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Felker GM, Ahmad T, Anstrom KJ, et al. Rationale and design of the GUIDE-IT study: guiding evidence based therapy using biomarker intensified treatment in heart failure. JACC Heart Fail. 2014;2:457–65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Felker GM, Anstrom KJ, Adams KF, et al. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318:713–20.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol. 2002;40:2065–71.CrossRefPubMedGoogle Scholar
  36. 36.
    Giannubilo SR, Pasculli A, Tidu E, et al. Relationship between maternal hemodynamics and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia and fetal growth restriction. J Perinatol. 2017;37:484–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Gore MO, Seliger SL, Defilippi CR, et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol. 2014;63:1441–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Royal College of Obstetricians and Gynaecologists, National Collaborating Centre for Women’s and Children’s Health. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. London: National Institute for Health and Clinical Excellence: Guidance; 2010.Google Scholar
  39. 39.
    Jacobs EJH, Mingels AMA, Dieijen van-Visser MP. Cardiac biomarkers in end-stage renal disease. In: Sahay M, editor. Chronic kidney disease and renal transplantation. InTech Publication; 2012. p. 147–60.Google Scholar
  40. 40.
    Jaffe AS, Apple FS. High-sensitivity cardiac troponin assays: isn’t it time for equality? Clin Chem. 2014;60:7–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005;95:948–54.CrossRefPubMedGoogle Scholar
  42. 42.
    Kajimoto K, Minami Y, Sato N, et al. Gender differences in anemia and survival in patients hospitalized for acute decompensated heart failure with preserved or reduced ejection fraction. Am J Cardiol. 2017;120:435–42.CrossRefPubMedGoogle Scholar
  43. 43.
    Khan NA, Daskalopoulou SS, Karp I, et al. Sex differences in acute coronary syndrome symptom presentation in young patients. JAMA Intern Med. 2013;173:1863–71.PubMedGoogle Scholar
  44. 44.
    Kimenai DM, Henry RM, van der Kallen CJ, et al. Direct comparison of clinical decision limits for cardiac troponin T and I. Heart. 2016;102:610–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Kimenai DM, Martens RJH, Kooman JP, et al. Troponin I and T in relation to cardiac injury detected with electrocardiography in a population-based cohort – The Maastricht Study. Sci Rep. 2017;7:6610.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Krauser DG, Chen AA, Tung R, et al. Neither race nor gender influences the usefulness of amino-terminal pro-brain natriuretic peptide testing in dyspneic subjects: a ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy. J Card Fail. 2006;12:452–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Labugger R, Organ L, Collier C, Atar D, Van Eyk JE. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. Circulation. 2000;102:1221–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Lam CS, Cheng S, Choong K, et al. Influence of sex and hormone status on circulating natriuretic peptides. J Am Coll Cardiol. 2011;58:618–26.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lew J, Sanghavi M, Ayers CR, et al. Sex-based differences in cardiometabolic biomarkers. Circulation. 2017;135:544–55.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Luckenbill KN, Christenson RH, Jaffe AS, et al. Cross-reactivity of BNP, NT-proBNP, and proBNP in commercial BNP and NT-proBNP assays: preliminary observations from the IFCC Committee for Standardization of Markers of Cardiac Damage. Clin Chem. 2008;54:619–21.CrossRefPubMedGoogle Scholar
  51. 51.
    Lyngbakken MN, Rosjo H, Holmen OL, et al. Gender, high-sensitivity troponin I, and the risk of cardiovascular events (from the Nord-Trondelag Health Study). Am J Cardiol. 2016;118:816–21.CrossRefPubMedGoogle Scholar
  52. 52.
    Maffei S, Del Ry S, Prontera C, Clerico A. Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women. Clin Sci (Lond). 2001;101:447–53.CrossRefGoogle Scholar
  53. 53.
    Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–7.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Martens RJ, Kimenai DM, Kooman JP, et al. Estimated glomerular filtration rate and albuminuria are associated with biomarkers of cardiac injury in a population-based cohort study: The Maastricht study. Clin Chem. 2017;63:887–97.CrossRefPubMedGoogle Scholar
  55. 55.
    McCullough PA, Duc P, Omland T, et al. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study. Am J Kidney Dis. 2003;41:571–9.CrossRefPubMedGoogle Scholar
  56. 56.
    McKie PM, Cataliotti A, Lahr BD, et al. The prognostic value of N-terminal pro-B-type natriuretic peptide for death and cardiovascular events in healthy normal and stage A/B heart failure subjects. J Am Coll Cardiol. 2010;55:2140–7.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Meijers WC, van der Velde AR, Muller Kobold AC, et al. Variability of biomarkers in patients with chronic heart failure and healthy controls. Eur J Heart Fail. 2017;19:357–65.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Mingels A, Jacobs L, Michielsen E, et al. Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays. Clin Chem. 2009;55:101–8.CrossRefPubMedGoogle Scholar
  59. 59.
    Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–360.CrossRefGoogle Scholar
  60. 60.
    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.CrossRefPubMedGoogle Scholar
  61. 61.
    Neeland IJ, Drazner MH, Berry JD, et al. Biomarkers of chronic cardiac injury and hemodynamic stress identify a malignant phenotype of left ventricular hypertrophy in the general population. J Am Coll Cardiol. 2013;61:187–95.CrossRefPubMedGoogle Scholar
  62. 62.
    Oliver JM, Gallego P, Gonzalez AE, et al. Impact of age and sex on survival and causes of death in adults with congenital heart disease. Int J Cardiol. 2017;245:119–24.CrossRefPubMedGoogle Scholar
  63. 63.
    Omland T, de Lemos JA, Holmen OL, et al. Impact of sex on the prognostic value of high-sensitivity cardiac troponin I in the general population: the HUNT study. Clin Chem. 2015;61:646–56.CrossRefPubMedGoogle Scholar
  64. 64.
    Ouwerkerk W, Voors AA, Zwinderman AH. Factors influencing the predictive power of models for predicting mortality and/or heart failure hospitalization in patients with heart failure. JACC Heart Fail. 2014;2:429–36.CrossRefPubMedGoogle Scholar
  65. 65.
    Pagidipati NJ, Peterson ED. Acute coronary syndromes in women and men. Nat Rev Cardiol. 2016;13:471–80.CrossRefPubMedGoogle Scholar
  66. 66.
    Pfisterer M, Buser P, Rickli H, et al. BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA. 2009;301:383–92.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Piro M, Della Bona R, Abbate A, Biasucci LM, Crea F. Sex-related differences in myocardial remodeling. J Am Coll Cardiol. 2010;55:1057–65.CrossRefPubMedGoogle Scholar
  68. 68.
    Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefGoogle Scholar
  69. 69.
    Rahimi K, Bennett D, Conrad N, et al. Risk prediction in patients with heart failure: a systematic review and analysis. JACC Heart Fail. 2014;2:440–6.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Raymond I, Groenning BA, Hildebrandt PR, et al. The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population. Heart. 2003;89:745–51.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Redfield MM, Rodeheffer RJ, Jacobsen SJ, et al. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol. 2002;40:976–82.CrossRefPubMedGoogle Scholar
  72. 72.
    Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267–315.CrossRefPubMedGoogle Scholar
  73. 73.
    Rubini Gimenez M, Twerenbold R, Boeddinghaus J, et al. Clinical effect of sex-specific cutoff values of high-sensitivity cardiac troponin T in suspected myocardial infarction. JAMA Cardiol. 2016;1:912–20.CrossRefPubMedGoogle Scholar
  74. 74.
    Saenger AK, Dalenberg DA, Bryant SC, Grebe SK, Jaffe AS. Pediatric brain natriuretic peptide concentrations vary with age and sex and appear to be modulated by testosterone. Clin Chem. 2009;55:1869–75.CrossRefPubMedGoogle Scholar
  75. 75.
    Saenger AK, Rodriguez-Fraga O, Ler R, et al. Specificity of B-type natriuretic peptide assays: cross-reactivity with different BNP, NT-proBNP, and proBNP peptides. Clin Chem. 2017;63:351–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Sandoval Y, Smith SW, Schulz KM, et al. Diagnosis of type 1 and type 2 myocardial infarction using a high-sensitivity cardiac troponin I assay with sex-specific 99th percentiles based on the third universal definition of myocardial infarction classification system. Clin Chem. 2015;61:657–63.CrossRefPubMedGoogle Scholar
  77. 77.
    Saunders JT, Nambi V, de Lemos JA, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation. 2011;123:1367–76.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Savarese G, Trimarco B, Dellegrottaglie S, et al. Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2686 patients in 12 randomized trials. PLoS One. 2013;8:e58287.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Scheven L, de Jong PE, Hillege HL, et al. High-sensitive troponin T and N-terminal pro-B type natriuretic peptide are associated with cardiovascular events despite the cross-sectional association with albuminuria and glomerular filtration rate. Eur Heart J. 2012;33:2272–81.CrossRefPubMedGoogle Scholar
  80. 80.
    Schofer N, Brunner FJ, Schluter M, et al. Gender-specific diagnostic performance of a new high-sensitivity cardiac troponin I assay for detection of acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2017;6:60–8.CrossRefPubMedGoogle Scholar
  81. 81.
    Shah AS, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015;350:g7873.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Sze J, Mooney J, Barzi F, Hillis GS, Chow CK. Cardiac troponin and its relationship to cardiovascular outcomes in community populations – a systematic review and meta-analysis. Heart Lung Circ. 2016;25:217–28.CrossRefPubMedGoogle Scholar
  83. 83.
    Tanous D, Siu SC, Mason J, et al. B-type natriuretic peptide in pregnant women with heart disease. J Am Coll Cardiol. 2010;56:1247–53.CrossRefPubMedGoogle Scholar
  84. 84.
    Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012;33:2551–67.CrossRefPubMedGoogle Scholar
  85. 85.
    Trambas C, Pickering JW, Than M, et al. Impact of high-sensitivity troponin I testing with sex-specific cutoffs on the diagnosis of acute myocardial infarction. Clin Chem. 2016;62:831–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Twerenbold R, Boeddinghaus J, Nestelberger T, et al. Clinical use of high-sensitivity cardiac troponin in patients with suspected myocardial infarction. J Am Coll Cardiol. 2017;70:996–1012.CrossRefPubMedGoogle Scholar
  87. 87.
    Wallace TW, Abdullah SM, Drazner MH, et al. Prevalence and determinants of troponin T elevation in the general population. Circulation. 2006;113:1958–65.CrossRefPubMedGoogle Scholar
  88. 88.
    Westerman S, Wenger NK. Women and heart disease, the underrecognized burden: sex differences, biases, and unmet clinical and research challenges. Clin Sci (Lond). 2016;130:551–63.CrossRefGoogle Scholar
  89. 89.
    Wildi K, Gimenez MR, Twerenbold R, et al. Misdiagnosis of myocardial infarction related to limitations of the current regulatory approach to define clinical decision values for cardiac troponin. Circulation. 2015;131:2032–40.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Willeit P, Welsh P, Evans JDW, et al. High-sensitivity cardiac troponin concentration and risk of first-ever cardiovascular outcomes in 154,052 participants. J Am Coll Cardiol. 2017;70:558–68.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Wu AH, Jaffe AS, Apple FS, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines: use of cardiac troponin and B-type natriuretic peptide or N-terminal proB-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure. Clin Chem. 2007;53:2086–96.CrossRefPubMedGoogle Scholar
  92. 92.
    Wu AH, Smith A. Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure. Eur J Heart Fail. 2004;6:355–8.CrossRefPubMedGoogle Scholar
  93. 93.
    Wu AH, Smith A, Wieczorek S, et al. Biological variation for N-terminal pro- and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Am J Cardiol. 2003;92:628–31.CrossRefPubMedGoogle Scholar
  94. 94.
    Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;23:628–51.Google Scholar
  95. 95.
    Yeo KT, Wu AH, Apple FS, et al. Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay. Clin Chim Acta. 2003;338:107–15.CrossRefPubMedGoogle Scholar
  96. 96.
    Zeller T, Tunstall-Pedoe H, Saarela O, et al. High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort. Eur Heart J. 2014;35:271–81.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical Chemistry, Central Diagnostic LaboratoryMaastricht University Medical CenterMaastrichtThe Netherlands

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