@article{97231fd36aa94d3f86ff10e84268c508,
title = "Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres",
abstract = "OBJECTIVE: To determine the relation between age and troponin level and its prognostic implication.DESIGN: Retrospective cohort study.SETTING: Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).PARTICIPANTS: 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017.MAIN OUTCOME MEASURE: All cause mortality.RESULTS: 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively.CONCLUSIONS: A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks.STUDY REGISTRATION: ClinicalTrials.gov NCT03507309.",
keywords = "Adult, Aged, Aged, 80 and over, Aging/blood, Biomarkers/blood, Cardiovascular Diseases/blood, Cohort Studies, Conservative Treatment/statistics & numerical data, Female, Humans, Male, Middle Aged, Mortality, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Risk Factors, Troponin/blood, United Kingdom/epidemiology",
author = "Amit Kaura and Vasileios Panoulas and Benjamin Glampson and Jim Davies and Abdulrahim Mulla and Kerrie Woods and Joe Omigie and Shah, {Anoop D} and Channon, {Keith M} and Weber, {Jonathan N} and Thursz, {Mark R} and Paul Elliott and Harry Hemingway and Bryan Williams and Folkert Asselbergs and Michael O'Sullivan and Rajesh Kharbanda and Lord, {Graham M} and Narbeh Melikian and Patel, {Riyaz S} and Divaka Perera and Shah, {Ajay M} and Francis, {Darrel P} and Jamil Mayet",
note = "Funding Information: A raised troponin level was associated with a clinically important increased mortality, regardless of age, even if raised only slightly above normal, with the excess mortality associated with a raised troponin level concentrated in the first few weeks An unexpected inverted U shaped relation between troponin level and mortality was seen in patients admitted with an acute coronary syndrome The paradoxical decline in mortality at very high troponin levels may be driven in part by the changing case mix as troponin levels increase; a higher proportion of patients with very high troponin levels received invasive management This research has been conducted using National Institute for Health Research Health Informatics Collaborative (NIHR HIC) data resources. The NIHR HIC is a joint initiative between the NIHR Biomedical Research Centres at Imperial, Oxford, University College London Hospitals, Guy{\textquoteright}s and St Thomas{\textquoteright}, and Cambridge, which has provided data services, infrastructure, and expertise. The manuscript follows the STROBE guidelines for the reporting of observational studies. Contributors: AK and VP contributed equally to this manuscript. AK, VP, DPF, and JM conceived the hypotheses and wrote the study protocol. BG, JD, AM, JO, and AK carried out the programming to extract the data from electronic healthcare records. AK, VP, and DPF undertook all data analyses. AK and VP drafted the manuscript. JM, DPF, AMS, DP, RSP, NM, GML, RK, MOS, FA, BW, HH, PE, MRT, JNW, KMC, ADS, JO, KW, AM, JD and BG provided a critical review of the manuscript. All authors read and approved the final version of the manuscript. JM is guarantor for this paper. JM, RK, RSP, DP, and AMS were the leads for their respective institutions. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. Funding: This paper reports independent research led and funded by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC), as part of the NIHR Health Informatics Collaborative with the NIHR Oxford BRC, the NIHR University College London Hospitals BRC, the NIHR Guy{\textquoteright}s and St Thomas{\textquoteright} BRC, and the NIHR Cambridge BRC. RSP is funded by a British Heart Foundation intermediate fellowship (FS/14/76/30933). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health. PE and HH received Health Data Research (HDR) funding. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the NIHR BRC for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: This study was approved by the London-South East Research Ethics Committee (REC reference: 16/HRA/3327). Data sharing: The datasets generated or analysed, or both during this study are not publicly available owing to ethical restrictions. The guarantor (JM) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained. 1 Katus HA Remppis A Neumann FJ . Publisher Copyright: {\textcopyright} Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2019",
month = nov,
day = "20",
doi = "10.1136/bmj.l6055",
language = "English",
volume = "367",
pages = "l6055",
journal = "BMJ (Clinical research ed.)",
issn = "1756-1833",
publisher = "BMJ Publishing Group",
}