Advertisement

Troponina cTnT-hs: una questione di genere e di età? Valutazione di limiti decisionali differenziati per genere ed età in una popolazione afferente al Dipartimento di Emergenza

  • Maria Aurora Burgio
  • Giulio Marino
  • Dina Di Maria
Articolo originale

Riassunto

Premesse.

La determinazione della troponina ad alta sensibilità (cTnI-hs e cTnT-hs) rappresenta ormai un elemento essenziale nella pratica clinica della sindrome coronarica acuta (SCA), per la diagnosi, l’early rule-out, la stratificazione del rischio, la valutazione degli outcomes e anche nei pazienti con danni cardiaci non-SCA. Una letteratura sempre crescente, soprattutto con il grande studio multicentrico relativo alla cTnT-hs (TRAPID), suggerisce l’uso di limiti decisionali differenziati per genere e/o età per diagnosi più precise.

Metodi.

Nell’Unità Operativa di Patologia Clinica dell’ospedale “Barone Lombardo” di Canicattì abbiamo applicato cut-off differenziati per genere ed età, separatamente e in combinazione, alla popolazione afferente al Pronto Soccorso con possibile diagnosi di SCA nell’arco del 2016, utilizzando troponina ad alta sensibilità cTnT-hs Roche Elecsys®, determinata su Cobas 6000 Roche (ECLIA), proposta con unico cut-off pari a 14 pg/ml.

Risultati.

Sono stati studiati 3970 pazienti: 2111 maschi (M) e 1859 femmine (F) identificati con l’unico cut-off di 14 pg/ml; 105 casi di infarto miocardico acuto (IMA). Inserendo cut-off differenziati per genere (15,5 pg/ml per M, 9 pg/ml per F) si assiste a un miglioramento del rule-in e del rule-out (+4,2% rule-in per F; +4,5% rule-out per M). Tuttavia, la popolazione è meglio stratificata con un cut-off differenziato per età (9,12 pg/ml <65 anni; 24,47 pg/ml ≥65 anni): il rule-in nei pazienti sopra 65 anni diminuisce da 42% a 22%. La combinazione di cut-off differenziati per genere ed età (<65 anni due differenti cut-off per M e F; un solo cut-off a 28 pg/mL ≥65 anni) mostra la migliore performance nel rule-in/rule-out dei pazienti con SCA.

Conclusioni.

Dal lavoro svolto sulla popolazione in esame e con il metodo analitico in uso, si rileva che sarebbe auspicabile, per referti quanto più appropriati e personalizzati e per una migliore sorveglianza della malattia cardiaca ischemica nel genere femminile, inserire cut-off differenziati per genere e per età. Tuttavia, i migliori risultati si ottengono con l’utilizzo simultaneo di entrambi i criteri.

Parole chiave

cTnT-hs Troponina ad alta sensibilità Limiti decisionali specifici per genere Limiti decisionali specifici per età 

Troponin cTnT-hs: a matter of gender and age? Evaluation of differentiated cut-offs by gender and age in an Emergency Department population

Summary

Background.

The determination of high sensitivity Troponin (cTnI-hs and cTnT-hs) now represents the essential step in the clinical practice of acute coronary syndrome (ACS), for diagnosis, early rule-out, risk stratification, and evaluation of outcomes. It is used also in patients without ACS cardiac damage. Taking into consideration the stratification of the populations, differentiated cut-offs according to gender and age are recently proposed for a more precise diagnosis and supported by a growing literature and above all by the large multicenter study related to Troponin T (the TRAPID Study).

Methods.

In the Clinical Pathology of the Hospital “Barone Lombardo” in Canicattì, we implemented differentiated cut-offs by gender and age in the Emergency Department (ED) population of the year 2016 with a history suggestive of ACS, by analyzing the two age and sex variables both individually and simultaneously. The Troponin measured was high sensitivity troponin T (cTnT-hs Roche Elecsys®) on Cobas 6000 Roche (ECLIA) with a suggested cut-off of 14 pg/ml.

Results.

3970 patients were analyzed: 2111 males (M) and 1859 females (F); 105 cases of acute myocardial infarction (AMI) were identified with the single cut-off of 14 pg/ml. By inserting differentiated cut-offs (15.5 pg/ml for M; 9 pg/ml for F) we obtained an improvement in the rule-in and rule-out (+4.2% rule-in for F; +4.5% rule-out for M). Moreover, the population was better stratified using cut-offs by age (9.12 pg/ml for <65 years; 24.47 pg/ml >65 years): the rule-in population over 65 years decreased from 42% to 22%. Combined gender and age differentiated cut-offs (<65 years the 2 different cut-offs for M and F and a single cut-off of 28 pg/ml ≥65 years) showed the best performance for the in rule-in/rule-out.

Conclusions.

For appropriate and personalized reports, in our population under examination and with the analytical method in use, differentiated cut-offs for age and for gender have positive effect on the rule-in/rule-out process in the ACS population. Gender-specific analysis, which often stresses the underestimation of AMI in women, demonstrates that a preventive and training approach towards cardiovascular risk prevention, especially for young women, is necessary in the general population. Nevertheless, the simultaneous use of both criteria shows the best performance.

Keywords

cTnT-hs High sensitivity troponin Gender-specific cut-off Age-specific cut-off 

Notes

Ringraziamenti

Cappelletti Piero (SIPMeL, Castelfranco Veneto, TV), per la collaborazione nella revisione del lavoro.

Galli Gianni Antonio (Estote Misericordes, FI), coordinatore del Gds MM.

Conflitti di interesse

Nessuno.

Studi condotti su esseri umani e animali

Per l’esecuzione dello studio è stata ottenuta l’approvazione del Comitato Etico ospedaliero.

Il presente studio non ha comportato l’utilizzo di animali da esperimento.

Per il Gruppo di Studio dei Marcatori Miocardici della Società Italiana di Patologia Clinica e Medicina di Laboratorio

  1. (1)

    Cassin Matteo (Cardiologia, AAS5, PN)

     
  2. (2)

    Malloggi Lucia (Lab. Analisi, AOU, PI)

     
  3. (3)

    Manno Massimiliano (Lab. Analisi, Città di Lecce Hospital-GVM Care & Research, LE)

     
  4. (4)

    Mazzei D. (Lab. Analisi, AOU, PI)

     
  5. (5)

    Morandini Margherita (Lab. Analisi, AAS5, PN)

     
  6. (6)

    Moretti Marco (Patologia Clinica A.O. Ospedali Riuniti Marche Nord, Pesaro, PU)

     
  7. (7)

    Rubin Daniela (Lab. Analisi ULSS7, Conegliano Veneto, TV)

     
  8. (8)

    Stenner Elisabetta (S.C. Patologia Clinica, ASUITS, TS)

     
  9. (9)

    Veneziani Francesca (Lab. Analisi, Ospedale SMN, USL Centro Toscana, FI)

     

Bibliografia

  1. 1.
    Roffi M, Patrono C, Collet JP et al. (2016) 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 37:267–315 CrossRefPubMedGoogle Scholar
  2. 2.
    Mueller-Hennessen H, Lindahl B, Giannitsis E et al. (2016) 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 209:26–33 CrossRefPubMedGoogle Scholar
  3. 3.
    European Heart Network (2012) European Cardiovascular Disease Statistics. https://www.escardio.org/static_file/Escardio/Press-media/press-releases/2013/EU-cardiovascular-disease-statistics-2012.pdf (Accesso 5 gennaio 2018)
  4. 4.
    European Heart Network (2017) European Cardiovascular Disease Statistics. http://www.ehnheart.org/cvd-statistics.html (Accesso 5 gennaio 2018)
  5. 5.
    Gregg EW (2007) Mortality trends in men and women with diabetes, 1971 to 2000. Ann Intern Med 147:149–155 CrossRefPubMedGoogle Scholar
  6. 6.
    Regitz-Zagrosek V, Oertelt-Prigione S, Prescott E et al. (2016) Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes. Eur Heart J 37:24–34 CrossRefPubMedGoogle Scholar
  7. 7.
    Perrone G, Brunelli R, Morozzi C et al. (2012) La prevenzione e il trattamento dei fattori di rischio per la malattia cardiovascolare nella donna in pre- e post-menopausa: linee guida a confronto. Giorn It Ost Gin XXXIV:509–515 Google Scholar
  8. 8.
    Franconi F, Cantelli Forti G (2014) Manuale di medicina sesso-genere. Bonomia University Press, Bologna Google Scholar
  9. 9.
    Legato MJ (2009) Principles of gender-specific medicine, 2nd ed. Academic Press, London Google Scholar
  10. 10.
    Patel H, Rosengren A, Ekman I (2004) Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J 148:27–33 CrossRefPubMedGoogle Scholar
  11. 11.
    Spatz ES, Curry LA, Masoudi FA et al. (2015) The variation in recovery: role of gender on outcomes of young AMI patients (VIRGO) classification system: a taxonomy for young women with acute myocardial infarction. Circulation 132:1710–1718 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Zuin G, Parato VM, Groff P et al. (2016) Documento di consenso ANMCO/SIMEU: Gestione intraospedaliera dei pazienti che si presentano con dolore toracico. G Ital Cardiol 17:416–446 Google Scholar
  13. 13.
    Bank IEM, de Hoog VC, de Kleijn DPV et al. (2017) Sex-based differences in the performance of the HEART score in patients presenting to the emergency department with acute chest pain. J Am Heart Assoc 6:e005373.  https://doi.org/10.1161/JAHA.116.005373 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Modena MG, Volpe M (2010) Prevenzione dell’infarto del miocardio nella donna. Documento del Gruppo di Lavoro SIPREC (Società Italiana per la Prevenzione Cardiovascolare). http://careonline.it/wp-content/uploads/2011/09/dossier.pdf (Accesso 5 gennaio 2018)
  15. 15.
    Caselli C, Cangemi G, Masotti S et al. (2016) Plasma cardiac troponin I concentrations in healthy neonates, children and adolescents measured with a high sensitive immunoassay method: high sensitive troponin I in pediatric age. Clin Chim Acta 458:68–71 CrossRefPubMedGoogle Scholar
  16. 16.
    Olivieri F, Galeazzi R, Giavarina D et al. (2012) Aged-related increase of high sensitive Troponin T and its implication in acute myocardial infarction diagnosis of elderly patients. Mech Ageing Dev 133:300–305 CrossRefPubMedGoogle Scholar
  17. 17.
    Apple FS, Cullen L, Felker GM et al. (2017) Cardiovascular disease: impact of biomarkers, proteomics, and genomics. Clin Chem 63:1–4 CrossRefPubMedGoogle Scholar
  18. 18.
    Cullen LA, Mills NL (2017) Point: the use of sex-specific cutpoints for high-sensitivity cardiac troponin assays. Clin Chem 63:261–263 CrossRefPubMedGoogle Scholar
  19. 19.
    Cullen L, Greenslade JH, Carlton EW et al. (2016) 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 102:120–126 CrossRefPubMedGoogle Scholar
  20. 20.
    Mehta LS, Beckie TM, DeVon HA et al. (2016) Acute myocardial infarction in women: a scientific statement from the American Heart Association. Circulation 133:916–947 CrossRefPubMedGoogle Scholar
  21. 21.
    Gore MO, Seliger SL, Defilippi CR et al. (2014) Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 63:1441–1448 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Shah AS, Griffiths M, Lee KK et al. (2015) High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ 350:g7873 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Franzini M, Lorenzoni V, Masotti S et al. (2015) The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: a multicenter study in Italy. Clin Chim Acta 438:376–381 CrossRefPubMedGoogle Scholar
  24. 24.
    Sergi G, Veronese N, Fontana L et al. (2015) Pre-frailty and risk of cardiovascular disease in elderly men and women. J Am Coll Cardiol 65:976–983 CrossRefPubMedGoogle Scholar
  25. 25.
    Mosca L, Benjamin EJ, Berra K et al. (2011) Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the american heart association. Circulation 123:1243–1262 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Thygesen K, Alpert JS, Jaffe AS et al. (2012) Third universal definition of myocardial infarction. Circulation 126:2020–2035 CrossRefPubMedGoogle Scholar
  27. 27.
    Giannitsis E (2017) Counterpoint: potential concerns regarding the use of sex-specific cutpoints for high-sensitivity troponin assays. Clin Chem 63:264–266 CrossRefPubMedGoogle Scholar
  28. 28.
    Jaffe AS, Apple FS (2013) High-sensitivity cardiac troponin assays: isn’t it time for equality? Clin Chem 60:7–9 CrossRefPubMedGoogle Scholar
  29. 29.
    Monod JL (1970) Il caso e la necessità. Saggio sulla filosofia naturale della biologia contemporanea. Mondadori, Milano Google Scholar

Copyright information

© Società Italiana di Patologia Clinica e Medicina di Laboratorio 2018

Authors and Affiliations

  1. 1.Patologia Clinica, Ospedale Barone LombardoCanicattì-ASP (AG)CanicattìItalia
  2. 2.Laboratorio Analisi, Ospedale di VergatoAUSL BolognaVergatoItalia
  3. 3.Lab. Analisi PolimedicaRavanusaItalia

Personalised recommendations