Sex Differences in the Prognostic Value of Circulating Biomarkers in Patients Presenting With Acute Chest Pain

Gard Mikael Sæle Myrmel; Nasir Saeed; Ole Thomas Steiro; Hilde Lunde Tjora; Jørund Langørgen; Rune Oskar Bjørneklett; Øyvind Skadberg; Vernon Vijay Singha Bonarjee; Øistein Rønneberg Mjelva; Eva Ringdal Pedersen; Kjell Vikenes; Torbjørn Omland; Kristin Moberg Aakre

doi:10.1016/j.jacadv.2024.101567

Sex Differences in the Prognostic Value of Circulating Biomarkers in Patients Presenting With Acute Chest Pain

JACC Adv. 2025 Feb;4(2):101567. doi: 10.1016/j.jacadv.2024.101567. Epub 2025 Jan 21.

Affiliations

¹ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
² Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Emergency Care Clinic, Haukeland University Hospital, Bergen, Norway.
⁴ Emergency Care Clinic, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
⁵ Laboratory of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway.
⁶ Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
⁷ Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
⁸ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
⁹ K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Akershus University Hospital, Oslo, Norway.
¹⁰ Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway. Electronic address: Kristin.moberg.aakre@helse-bergen.no.

Abstract

Background: Biomarkers are used for long-term risk prediction of cardiovascular (CV) events in patients presenting with suspected acute coronary syndromes.

Objectives: This study investigated whether there are sex differences in the long-term prognostic value of biomarkers in patients presenting with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

Methods: High-sensitivity cardiac troponin T (hs-cTnT), hs-cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, and C-reactive protein (CRP) concentrations were measured in 1,476 patients admitted with suspected NSTE-ACS. Patients were followed up for a median of 1,547 (IQR: 873-1,842) days until a primary composite endpoint of all-cause mortality, incident myocardial infarction, or heart failure hospitalization. A secondary endpoint of CV death was also registered.

Results: For the primary endpoint, a log2 increase of hs-cTnT and hs-cTnI concentration was associated with a higher adjusted HR in women (hs-cTnT: 1.3, 95% CI: 1.2-1.5; hs-cTnI: 1.2, 95% CI: 1.1-1.2) than in men (hs-cTnT: 1.1, 95% CI: 1.0-1.2; hs-cTnI: 1.0, 95% CI: 1.0-1.1); P for interaction with sex = 0.009 (hs-cTnT) and 0.005 (hs-cTnI). A similar interaction was shown for NT-proBNP (P for interaction = 0.043). GDF-15 and CRP were independent predictors of the primary endpoint, but the interaction by sex was nonsignificant.

Conclusions: In contrast to CRP and GDF-15, increasing concentrations of hs-cTnT, hs-cTnI, and NT-proBNP are associated with higher risk of death and CV events in female than in male patients presenting with suspected NSTE-ACS. Sex-adjustment of hs-cTn and NT-proBNP may increase the accuracy of long-term CV prognostication in women and men.

Keywords: acute chest pain; biomarkers; risk stratification; sex differences.