University of Oulu

Edina Hadziselimovic, Anders M. Greve, Ahmad Sajadieh, Michael H. Olsen, Y. Antero Kesäniemi, Christoph A. Nienaber, Simon G. Ray, Anne B. Rossebø, Kristian Wachtell, Olav W. Nielsen, Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial, eClinicalMedicine, Volume 58, 2023, 101875, ISSN 2589-5370,

Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis : a post-hoc substudy of the SEAS trial

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Author: Hadziselimovic, Edina1; Greve, Anders M.2; Sajadieh, Ahmad1,3;
Organizations: 1Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark
2Department of Clinical Biochemistry, 3011, Rigshospitalet, Copenhagen, Denmark
3Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
4Department of Internal Medicine 1, Holbæk Hospital, Denmark
5Department of Regional Health Research, University of Southern Denmark, Denmark
6Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
7Royal Brompton and Harefield NHS Foundation Trust, Imperial College, London, UK
8Manchester University Hospitals, Manchester, UK
9Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway
10Division of Cardiology, Weill Cornell Medicine, New York, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
Persistent link:
Language: English
Published: Elsevier, 2023
Publish Date: 2023-09-25


Background: High-sensitivity Troponin T (hsTnT), a biomarker of cardiomyocyte overload and injury, relates to aortic valve replacement (AVR) and mortality in severe aortic stenosis (AS). However, its prognostic value remains unknown in asymptomatic patients with AS. We aimed to investigate if an hsTnT level >14 pg/mL (above upper limit of normal 99th percentile) is associated with echocardiographic AS-severity, subsequent AVR, ischaemic coronary events (ICE), and mortality in asymptomatic patients with non-severe AS.

Methods: In this post-hoc sub-analysis of the multicentre, randomised, double-blind, placebo-controlled SEAS trial (, NCT00092677), we included asymptomatic patients with mild to moderate-severe AS. We ascertained baseline and 1-year hsTnT concentrations and examined the association between baseline levels and the risk of the primary composite endpoint, defined as the first event of all-cause mortality, isolated AVR (without coronary artery bypass grafting (CABG)), or ICE. Multivariable regressions and competing risk analyses examined associations of hsTnT level >14 pg/mL with clinical correlates and 5-year risk of the primary endpoint.

Findings: Between January 6, 2003, and March 4, 2004, a total of 1873 patients were enrolled in the SEAS trial, and 1739 patients were included in this post-hoc sub-analysis. Patients had a mean (SD) age of 67.5 (9.7) years, 61.0% (1061) were men, 17.4% (302) had moderate-severe AS, and 26.0% (453) had hsTnT level >14 pg/mL. The median hsTnT difference from baseline to 1-year was 0.8 pg/mL (IQR, −0.4 to 2.3). In adjusted linear regression, log(hsTnT) did not correlate with echocardiographic AS severity (p = 0.36). In multivariable Cox regression, a hsTnT level >14 pg/mL vs. hsTnT ≤14 pg/mL was associated with an increased risk of the primary composite endpoint (HR, 1.41; 95% CI, 1.18–1.70; p = 0.0002). In a competing risk model of first of the individual components of the primary endpoint, a hsTnT level >14 pg/mL was associated with ICE risk (HR 1.71; 95% CI, 1.23–2.38; p = 0.0013), but not with isolated AVR (p = 0.064) or all-cause mortality (p = 0.49) as the first event.

Interpretation: hsTnT level is within the reference range (≤14 pg/mL) in 3 out of 4 non-ischaemic patients with asymptomatic mild-to-moderate AS and remains stable during a 1-year follow-up regardless of AS-severity. An hsTnT level >14 pg/mL was mainly associated with subsequent ICE, which suggest that hsTnT concentration is primarily a risk marker of subclinical coronary atherosclerotic disease.

Funding: Merck & Co., Inc., the Schering-Plough Corporation, the Interreg IVA program, Roche Diagnostics Ltd., and Gangstedfonden. Open access publication fee funding provided by prof. Olav W. Nielsen and Department of Cardiology, Bispebjerg University Hospital, Denmark.

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Series: EClinicalMedicine
ISSN: 2589-5370
ISSN-E: 2589-5370
ISSN-L: 2589-5370
Volume: 58
Article number: 101875
DOI: 10.1016/j.eclinm.2023.101875
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The SEAS study received financial support from Merck & Co., Inc., and the Schering-Plough Corporation. Roche Diagnostics International Ltd, Switzerland, provided the products for the hsTnT analyses as an unrestricted research grant. This study was supported by a grant from the Interreg IVA program, a part of the European Union, and Gangstedfonden, Denmark. Open access publication fee funding provided by prof. Olav W. Nielsen and Department of Cardiology, Bispebjerg University Hospital, Denmark.
Copyright information: © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (