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. 2025 May 17:S1885-5857(25)00147-1.
doi: 10.1016/j.rec.2025.05.003. Online ahead of print.

Clinical implications of sex-specific upper reference limits for high-sensitivity cardiac troponin I in myocardial infarction diagnosis

[Article in English, Spanish]
María Rubini Giménez  1 , Luca Koechlin  2 , Pedro López-Ayala  3 , Carlos Spagnuolo  3 , Jasper Boeddinghaus  1 , Karin Wildi  3 , Thomas Nestelberger  2 , Hanna Tkachenko  3 , Daniel Basic  4 , Emel Kaplan  3 , Jude Formambuh  3 , Paolo Bima  5 , Jonas Glaeser  3 , Luca Crisanti  6 , Óscar Miró  7 , F Javier Martín-Sánchez  8 , Michael Christ  9 , Dagmar I Keller  10 , Danielle M Gualandro  3 , Damian Kawecki  11 , Katharina Rentsch  12 , Andreas Buser  13 , Ivo Strebel  4 , Felix Mahfoud  3 , Christian Mueller  14 ; APACE Investigators; Gabrielle Hure  15 , Klara Rumora  15 , Tamar Muench-Gerber  15 , Noemi Glarner  15 , Christian Puelacher  15 , Raphael Twerenbold  15 , Desiree Wussler  15 , Jeanne du Fay de Lavallaz  15 , Tobias Zimmermann  16 , Julia Reinhardt  17 , Beata Morawiec  18 , Piotr Munzk  18 , Nicolas Geigy  19 , Samyut Shrestha  16 , Gemma Martinez-Nadal  20 , Carolina Fuenzalida  20 , Sofia Calderón  20 , Esther Rodriguez Adrada  21 , Eva Ganovská  22 , Jiri Parenica  22 , Arnold von Eckardstein  23
Affiliations

Clinical implications of sex-specific upper reference limits for high-sensitivity cardiac troponin I in myocardial infarction diagnosis

[Article in English, Spanish]
María Rubini Giménez et al. Rev Esp Cardiol (Engl Ed). .

Abstract

Introduction and objectives: It is unclear whether applying sex-specific rather than uniform upper reference limits (URLs) for high-sensitivity cardiac troponin I (hs-cTnI) improves diagnostic equity between women and men with suspected myocardial infarction (MI). We compared the diagnostic performance of these 2 approaches.

Methods: In an international, prospective, multicenter study of patients presenting with suspected MI, the final diagnosis was centrally adjudicated twice by 2 independent cardiologists using all available information, including serial measurements of hs-cTnI-Architect, once using the uniform URL (26.2 ng/L) and once using sex-specific URLs (women: 15.6 ng/L; men: 34.2 ng/L). The primary outcome was the diagnostic performance of uniform vs sex-specific URLs at presentation for MI.

Results: Among 7137 eligible patients, 2434 were women (34%), median age 65 years, and 4703 were men (66%), median age 59 years. Using the uniform URL, 348 women and 880 men were adjudicated as having MI. At presentation, the sensitivity and specificity of hs-cTnI were high and similar in women (77%; 95%CI, 72-81, and 93%; 95%CI, 92-94, respectively) and men (79%; 95%CI, 77-82, and 94%; 95%CI, 93-94). Using sex-specific URLs, the sensitivity and specificity were 85% (95%CI, 81-89) and 91% (95%CI, 89-92) in women vs 74% (95%CI, 71-77), and 95% (95%CI, 94-95) in men (P<.001). Using sex-specific URLs, diagnostic reclassification occurred in 27 patients, 12 women (upgrade to MI) and 15 men (downgrade from MI), representing 0.4%, (95%CI, 0.3-0.6) of all patients.

Conclusions: Using a uniform URL for hs-cTnI provides high and similar diagnostic sensitivity and specificity in women and men. Contrary to expectations, sex-specific URLs introduced sex-related disparities. These findings support the use of a uniform rather than sex-specific URL in the diagnosis of MI.

Keywords: Desigualdades de sexo; High-sensitivity troponin; Infarto agudo de miocardio; Myocardial infarction; Sex inequalities; Troponina ultrasensible.

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