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      Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP‐AF study)

      research-article
      , MRCP (UK) 1 , , MRCP (UK) 1 , , PhD 1 , , MSc 1 , , DPhil 2 , , BTech 1 , , BA (Hons) 2 , , BSc 3 , , PhD 4 , , MD 2 , , PhD 1 , , MD 1 , , PhD 1 , 5 , , FMedSci 4 , 5 , , MD 4 , , PhD 4 , , PhD 6 , , PhD 7 , 8 , 9 , , PhD 3 , , MB BChir 1 , , MD 1 , , MD 3 , , PhD 2 , , MD 7 , , MD 4 , , MD 1 ,
      Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
      John Wiley and Sons Inc.
      angiography, atrial fibrillation, coronary artery disease, mortality, troponin, Atrial Fibrillation, Biomarkers, Mortality/Survival, Coronary Artery Disease

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          Abstract

          Background

          Patients presenting with atrial fibrillation ( AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all‐cause mortality in real‐world patients presenting with AF.

          Methods and Results

          We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow‐up of 1462 (interquartile range, 929–1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01–1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9–3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42–0.89; P=0.01).

          Conclusions

          Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

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          Most cited references13

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          2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

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            Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.

            In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction. In a multicenter study, blood specimens from 1404 symptomatic patients were analyzed for cardiac troponin I, a serum marker not detected in the blood of healthy persons. The relation between mortality at 42 days and the level of cardiac troponin I in the specimen obtained on enrollment was determined both before and after adjustment for baseline characteristics. The mortality rate at 42 days was significantly higher in the 573 patients with cardiac troponin I levels of at least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0 percent; P or = 65 years). In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.
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              Identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort.

              The risk of stroke in patients with atrial fibrillation (AF) is not homogeneous, and various clinical risk factors have informed the development of stroke risk stratification schemes (RSS). Among anticoagulated cohorts, the emphasis should be on the identification of patients who remain at high risk for stroke despite anticoagulation. We investigated predictors of thromboembolism (TE) risk in an anticoagulated AF clinical trial cohort (n = 7329 subjects) and tested the predictive value of contemporary RSS in this cohort: CHADS₂, Framingham, NICE 2006, American College of Cardiology/American Heart Association/European Society of Cardiology 2006, the 8th American College of Chest Physicians guidelines and the CHA₂DS₂-VASc schemes. On multivariate analysis, significant predictors of TE were stroke/TIA (hazard ratio [HR], 2.24; P < 0.001), age 75 years or older (HR, 1.77; P = 0.0002), coronary artery disease (HR, 1.52; P = 0.0047), and smoking (HR, 2.10; P = 0.0005), whereas reported alcohol use (HR, 0.70; P = 0.02) was protective. Comparison of contemporary RSS demonstrated variable classification of AF patients into risk strata, although c-statistics for TE were broadly similar among the RSS tested and varied between 0.575 (NICE 2006) and 0.647 (CHA₂DS₂-VASc). CHA₂DS₂-VASc classified 94.2% as being at high risk, whereas most other RSS categorized two-thirds as being at high risk. Of the 184 TE events, 181 (98.4%) occurred in patients identified as being at high risk by the CHA₂DS₂-VASc schema. There was a stepwise increase in TE with increasing CHA₂DS₂-VASc score (P (trend) < 0.0001), which had the highest HR (3.75) among the tested schemes. The negative predictive value (ie, the percent categorized as "not high risk" actually being free from TE) for CHA₂DS₂-VASc was 99.5%. Coronary artery disease and smoking are additional risk factors for TE in anticoagulated AF patients, whereas alcohol use appears protective. Of the contemporary stroke RSS, the CHA₂DS₂-VASc scheme correctly identified the greatest proportion of AF patients at high risk, despite the similar predictive ability of most RSS evidenced by the c-statistic.
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                Author and article information

                Contributors
                j.mayet@imperial.ac.uk
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                26 March 2020
                07 April 2020
                : 9
                : 7 ( doiID: 10.1002/jah3.v9.7 )
                Affiliations
                [ 1 ] NIHR Imperial Biomedical Research Centre Imperial College London and Imperial College Healthcare NHS Trust London United Kingdom
                [ 2 ] NIHR Oxford Biomedical Research Centre University of Oxford and Oxford University Hospitals NHS Foundation Trust Oxford United Kingdom
                [ 3 ] NIHR King's Biomedical Research Centre King's College London and King's College Hospital NHS Foundation Trust London United Kingdom
                [ 4 ] NIHR University College London Biomedical Research Centre University College London and University College London Hospitals NHS Foundation Trust London United Kingdom
                [ 5 ] Health Data Research UK University College London London United Kingdom
                [ 6 ] NIHR Cambridge Biomedical Research Centre University of Cambridge and Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom
                [ 7 ] NIHR King's Biomedical Research Centre King's College London and Guy's and St Thomas’ NHS Foundation Trust London United Kingdom
                [ 8 ] Institute of Epidemiology and Biostatistics University of Ulm Germany
                [ 9 ] Faculty of Biology Medicine and Health University of Manchester United Kingdom
                Author notes
                [*] [* ] Correspondence to: Jamil Mayet, MD, Imperial College Healthcare NHS Trust, Hammersmith Hospital, National Heart and Lung Institute Offices, B Block Second Floor, Du Cane Road, London W12 0HS, United Kingdom. E‐mail: j.mayet@ 123456imperial.ac.uk
                [†]

                Dr Kaura and Dr Arnold contributed equally to this work.

                Article
                JAH34715
                10.1161/JAHA.119.013684
                7428631
                32212911
                96718bcd-99c0-4b44-826a-17a6b36f5f78
                © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 4, Tables: 2, Pages: 9, Words: 5800
                Product
                Funding
                Funded by: National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC) , open-funder-registry 10.13039/501100000272;
                Funded by: NIHR Oxford BRC , open-funder-registry 10.13039/501100000272;
                Funded by: NIHR University College London Hospitals BRC , open-funder-registry 10.13039/501100000272;
                Funded by: NIHR Guy's and St Thomas’ BRC , open-funder-registry 10.13039/501100000272;
                Funded by: NIHR Cambridge BRC , open-funder-registry 10.13039/501100000272;
                Categories
                Original Research
                Original Research
                Arrhythmia and Electrophysiology
                Custom metadata
                2.0
                09 April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:19.07.2020

                Cardiovascular Medicine
                angiography,atrial fibrillation,coronary artery disease,mortality,troponin,biomarkers,mortality/survival

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