Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome

Kuan Ken Lee; Amy V. Ferry; Atul Anand; Fiona E. Strachan; Andrew R. Chapman; Dorien M. Kimenai; Steven J. R. Meex; Colin Berry; Iain Findlay; Alan Reid; Anne Cruickshank; Alasdair Gray; Paul O. Collinson; Fred S. Apple; David A. McAllister; Donogh Maguire; Keith A. A. Fox; David E. Newby; Chris Tuck; Catriona Keerie; Christopher J. Weir; Anoop S. V. Shah; Nicholas L. Mills; High-STEACS Investigators

doi:10.1016/j.jacc.2019.07.082

Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome

Kuan Ken Lee, Amy V. Ferry, Atul Anand, Fiona E. Strachan, Andrew R. Chapman, Dorien M. Kimenai, Steven J. R. Meex, Colin Berry, Iain Findlay, Alan Reid, Anne Cruickshank, Alasdair Gray, Paul O. Collinson, Fred S. Apple, David A. McAllister, Donogh Maguire, Keith A. A. Fox, David E. Newby, Chris Tuck, Catriona KeerieChristopher J. Weir, Anoop S. V. Shah, Nicholas L. Mills^*, High-STEACS Investigators

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.

OBJECTIVES The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.

METHODS Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.

RESULTS A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p <0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).

CONCLUSIONS Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (C) 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Original language	English
Pages (from-to)	2032-2043
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	74
Issue number	16
DOIs	https://doi.org/10.1016/j.jacc.2019.07.082
Publication status	Published - 22 Oct 2019

Keywords

acute coronary syndrome
high-sensitivity cardiac troponin
myocardial infarction
sex-specific threshold
3RD UNIVERSAL DEFINITION
CARDIAC TROPONIN
MYOCARDIAL-INFARCTION
I ASSAY
WOMEN
METAANALYSIS
DIAGNOSIS
CUTOFFS
RISK

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10.1016/j.jacc.2019.07.082Licence: CC BY

Cite this

Lee, K. K., Ferry, A. V., Anand, A., Strachan, F. E., Chapman, A. R., Kimenai, D. M., Meex, S. J. R., Berry, C., Findlay, I., Reid, A., Cruickshank, A., Gray, A., Collinson, P. O., Apple, F. S., McAllister, D. A., Maguire, D., Fox, K. A. A., Newby, D. E., Tuck, C., ... High-STEACS Investigators (2019). Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome. Journal of the American College of Cardiology, 74(16), 2032-2043. https://doi.org/10.1016/j.jacc.2019.07.082

@article{26a5324b7f4745cdb0acf62bd5e1adf9,

title = "Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome",

abstract = "BACKGROUND Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.OBJECTIVES The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.METHODS Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.RESULTS A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p <0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).CONCLUSIONS Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (C) 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.",

keywords = "acute coronary syndrome, high-sensitivity cardiac troponin, myocardial infarction, sex-specific threshold, 3RD UNIVERSAL DEFINITION, CARDIAC TROPONIN, MYOCARDIAL-INFARCTION, I ASSAY, WOMEN, METAANALYSIS, DIAGNOSIS, CUTOFFS, RISK",

author = "Lee, {Kuan Ken} and Ferry, {Amy V.} and Atul Anand and Strachan, {Fiona E.} and Chapman, {Andrew R.} and Kimenai, {Dorien M.} and Meex, {Steven J. R.} and Colin Berry and Iain Findlay and Alan Reid and Anne Cruickshank and Alasdair Gray and Collinson, {Paul O.} and Apple, {Fred S.} and McAllister, {David A.} and Donogh Maguire and Fox, {Keith A. A.} and Newby, {David E.} and Chris Tuck and Catriona Keerie and Weir, {Christopher J.} and Shah, {Anoop S. V.} and Mills, {Nicholas L.} and {High-STEACS Investigators}",

note = "Funding Information: This trial was funded by a Special Project Grant from the British Heart Foundation (BHF) (SP/12/10/29922) with additional support from a BHF-Turing Cardiovascular Data Science Award (BCDSA/100003) and a BHF Research Excellence Award (RE/18/5/34216). Drs. Lee, Shah, and Mills are supported by a Clinical Research Training Fellowship (FS/18/25/33454), an Intermediate Clinical Research Fellowship (FS/19/17/34172), and the Butler Senior Clinical Research Fellowship (FS/16/14/32023) from the BHF. Dr. Weir was supported by National Health Service Lothian through the Edinburgh Clinical Trials Unit. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge. Drs. Shah, Chapman, and Lee have received honoraria from Abbott Diagnostics. Dr. Berry has received a research grant awarded to the University of Glasgow from AstraZeneca outside the submitted work. Dr. Apple has received research grants awarded to the Minneapolis Medical Research Foundation from Abbott Diagnostics, Siemens Diagnostics, Ortho-Clinical Diagnostics, and Beckman Coulter outside the submitted work; and has received personal fees from HyTest. Dr. Mills has received research grants awarded to the University of Edinburgh from Abbott Diagnostics and Siemens Diagnostics outside the submitted work; and has received honoraria from Abbott Diagnostics, Siemens Diagnostics, Roche Diagnostics, and Singulex. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = oct,

day = "22",

doi = "10.1016/j.jacc.2019.07.082",

language = "English",

volume = "74",

pages = "2032--2043",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Science",

number = "16",

}

Lee, KK, Ferry, AV, Anand, A, Strachan, FE, Chapman, AR, Kimenai, DM, Meex, SJR, Berry, C, Findlay, I, Reid, A, Cruickshank, A, Gray, A, Collinson, PO, Apple, FS, McAllister, DA, Maguire, D, Fox, KAA, Newby, DE, Tuck, C, Keerie, C, Weir, CJ, Shah, ASV, Mills, NL & High-STEACS Investigators 2019, 'Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome', Journal of the American College of Cardiology, vol. 74, no. 16, pp. 2032-2043. https://doi.org/10.1016/j.jacc.2019.07.082

TY - JOUR

T1 - Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome

AU - Lee, Kuan Ken

AU - Ferry, Amy V.

AU - Anand, Atul

AU - Strachan, Fiona E.

AU - Chapman, Andrew R.

AU - Kimenai, Dorien M.

AU - Meex, Steven J. R.

AU - Berry, Colin

AU - Findlay, Iain

AU - Reid, Alan

AU - Cruickshank, Anne

AU - Gray, Alasdair

AU - Collinson, Paul O.

AU - Apple, Fred S.

AU - McAllister, David A.

AU - Maguire, Donogh

AU - Fox, Keith A. A.

AU - Newby, David E.

AU - Tuck, Chris

AU - Keerie, Catriona

AU - Weir, Christopher J.

AU - Shah, Anoop S. V.

AU - Mills, Nicholas L.

AU - High-STEACS Investigators

N1 - Funding Information: This trial was funded by a Special Project Grant from the British Heart Foundation (BHF) (SP/12/10/29922) with additional support from a BHF-Turing Cardiovascular Data Science Award (BCDSA/100003) and a BHF Research Excellence Award (RE/18/5/34216). Drs. Lee, Shah, and Mills are supported by a Clinical Research Training Fellowship (FS/18/25/33454), an Intermediate Clinical Research Fellowship (FS/19/17/34172), and the Butler Senior Clinical Research Fellowship (FS/16/14/32023) from the BHF. Dr. Weir was supported by National Health Service Lothian through the Edinburgh Clinical Trials Unit. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge. Drs. Shah, Chapman, and Lee have received honoraria from Abbott Diagnostics. Dr. Berry has received a research grant awarded to the University of Glasgow from AstraZeneca outside the submitted work. Dr. Apple has received research grants awarded to the Minneapolis Medical Research Foundation from Abbott Diagnostics, Siemens Diagnostics, Ortho-Clinical Diagnostics, and Beckman Coulter outside the submitted work; and has received personal fees from HyTest. Dr. Mills has received research grants awarded to the University of Edinburgh from Abbott Diagnostics and Siemens Diagnostics outside the submitted work; and has received honoraria from Abbott Diagnostics, Siemens Diagnostics, Roche Diagnostics, and Singulex. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2019

PY - 2019/10/22

Y1 - 2019/10/22

N2 - BACKGROUND Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.OBJECTIVES The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.METHODS Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.RESULTS A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p <0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).CONCLUSIONS Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (C) 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.

AB - BACKGROUND Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.OBJECTIVES The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.METHODS Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.RESULTS A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p <0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).CONCLUSIONS Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (C) 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.

KW - acute coronary syndrome

KW - high-sensitivity cardiac troponin

KW - myocardial infarction

KW - sex-specific threshold

KW - 3RD UNIVERSAL DEFINITION

KW - CARDIAC TROPONIN

KW - MYOCARDIAL-INFARCTION

KW - I ASSAY

KW - WOMEN

KW - METAANALYSIS

KW - DIAGNOSIS

KW - CUTOFFS

KW - RISK

U2 - 10.1016/j.jacc.2019.07.082

DO - 10.1016/j.jacc.2019.07.082

M3 - Article

C2 - 31623760

SN - 0735-1097

VL - 74

SP - 2032

EP - 2043

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 16

ER -