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      Cardiac Troponins: Contemporary Biological Data and New Methods of Determination

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          Abstract

          Laboratory diagnosis plays one of the key roles in the diagnosis of many diseases, including cardiovascular diseases (CVD). The methods underlying the in vitro study of many CVD biomarkers, including cardiac troponins (cTnI and cTnT), are imperfect and are continually being improved to enhance their analytical performance, with sensitivity and specificity being the most important. Recently developed improved cTnI and cTnT detection methods, referred to as highly sensitive methods (hs-cTnI, hs-cTnT), have changed many of our ideas about the biology of cardiac troponins and opened up a number of additional diagnostic capabilities for practical healthcare. This article systematizes some relevant data on the biology of cardiac troponins as well as on methods for determining cTnI and cTnT with an analysis of the diagnostic value of their analytical characteristics (limit of blank, limit of detection, 99th percentile, coefficient of variation, and others). Data on extracardiac expression of cTnI and cTnT, mechanisms of formation and potential clinical significance of gender, age, and circadian characteristics of hs-cTnI and hs-cTnT content in serum are discussed. Considerable attention is paid to the discussion of new diagnostic capabilities of hs-cTnI, hs-cTnT, including consideration of promising possibilities for their study in biological fluids that can be obtained by non-invasive methods. Also, some possibilities of using hs-cTnI and hs-cTnT as prognostic laboratory biomarkers in healthy people (for example, to assess the risk of developing CVD) and in patients suffering from a number of pathological conditions that cause damage to cardiomyocytes are examined, and the potential mechanisms underlying the increase in hs-cTnI and hs-cTnT are discussed.

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          Most cited references124

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          2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).

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            Limit of blank, limit of detection and limit of quantitation.

            * Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) are terms used to describe the smallest concentration of a measurand that can be reliably measured by an analytical procedure. * LoB is the highest apparent analyte concentration expected to be found when replicates of a blank sample containing no analyte are tested. LoB = mean(blank) + 1.645(SD(blank)). * LoD is the lowest analyte concentration likely to be reliably distinguished from the LoB and at which detection is feasible. LoD is determined by utilising both the measured LoB and test replicates of a sample known to contain a low concentration of analyte. * LoD = LoB + 1.645(SD (low concentration sample)). * LoQ is the lowest concentration at which the analyte can not only be reliably detected but at which some predefined goals for bias and imprecision are met. The LoQ may be equivalent to the LoD or it could be at a much higher concentration.
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              High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study

              Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers. Funding British Heart Foundation and Chief Scientist Office (Scotland).
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vasc Health Risk Manag
                vhrm
                vhriskman
                Vascular Health and Risk Management
                Dove
                1176-6344
                1178-2048
                03 June 2021
                2021
                : 17
                : 299-316
                Affiliations
                [1 ]Department of Cardiology and Cardiovascular Surgery, Samara State Medical University , Samara, 443099, Russia
                [2 ]Department of Histology and Embryology, Samara State Medical University , Samara, 443099, Russia
                Author notes
                Correspondence: Aleksey Chaulin Department of Cardiology and Cardiovascular Surgery, Samara State Medical University , 89 Chapaevskaya Street, Samara Region, Samara, 443099, Russia Tel +7 (927) 770 25 87 Email alekseymichailovich22976@gmail.com
                Author information
                http://orcid.org/0000-0002-2712-0227
                Article
                300002
                10.2147/VHRM.S300002
                8184290
                34113117
                3571d1ea-31ce-4b09-bc13-dd86360154d8
                © 2021 Chaulin.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 31 December 2020
                : 21 April 2021
                Page count
                Figures: 3, Tables: 7, References: 126, Pages: 18
                Categories
                Review

                Cardiovascular Medicine
                laboratory diagnostics,cardiovascular diseases,acute myocardial infarction,biomarkers,cardiac troponins,ctni,ctnt highly sensitive methods,hs-ctni,hs-ctnt,analytical characteristics,99th percentile,limit of detection,coefficient of variation

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