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Biochemistry. Biokhimiia Dec 2013Troponin complex is a component of skeletal and cardiac muscle thin filaments. It consists of three subunits - troponin I, T, and C, and it plays a crucial role in... (Review)
Review
Troponin complex is a component of skeletal and cardiac muscle thin filaments. It consists of three subunits - troponin I, T, and C, and it plays a crucial role in muscle activity, connecting changes in intracellular Ca2+ concentration with generation of contraction. In spite of more than 40 years of studies, many aspects of troponin functioning are still not completely understood, and several models describing the mechanism of muscle contraction exist. Being a key factor in the regulation of cardiac muscle contraction, troponin complex is utilized in medicine as a target for some cardiotonic drugs used in the treatment of heart failure. A number of mutations in troponin subunits are associated with development of different types of cardiomyopathy. Moreover, for the last 25 years cardiac isoforms of troponin I and T have been widely used for immunochemical diagnostics of pathologies associated with cardiomyocyte death (myocardial infarction, myocardial trauma, and others). This review summarizes the existing evidence on the structure and function of troponin complex subunits, their role in the regulation of cardiac muscle contraction, and their clinical applications.
Topics: Animals; Heart Diseases; Humans; Myocardium; Troponin C; Troponin I; Troponin T
PubMed: 24490734
DOI: 10.1134/S0006297913130063 -
Circulation Jun 2019There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is... (Comparative Study)
Comparative Study
BACKGROUND
There is great interest in widening the use of high-sensitivity cardiac troponins for population cardiovascular disease (CVD) and heart failure screening. However, it is not clear whether cardiac troponin T (cTnT) and troponin I (cTnI) are equivalent measures of risk in this setting. We aimed to compare and contrast (1) the association of cTnT and cTnI with CVD and non-CVD outcomes, and (2) their determinants in a genome-wide association study.
METHODS
High-sensitivity cTnT and cTnI were measured in serum from 19 501 individuals in Generation Scotland Scottish Family Health Study. Median follow-up was 7.8 years (quartile 1 to quartile 3, 7.1-9.2). Associations of each troponin with a composite CVD outcome (1177 events), CVD death (n=266), non-CVD death (n=374), and heart failure (n=216) were determined by using Cox models. A genome-wide association study was conducted using a standard approach developed for the cohort.
RESULTS
Both cTnI and cTnT were strongly associated with CVD risk in unadjusted models. After adjusting for classical risk factors, the hazard ratio for a 1 SD increase in log transformed troponin was 1.24 (95% CI, 1.17-1.32) and 1.11 (1.04-1.19) for cTnI and cTnT, respectively; ratio of hazard ratios 1.12 (1.04-1.21). cTnI, but not cTnT, was associated with myocardial infarction and coronary heart disease. Both cTnI and cTnT had strong associations with CVD death and heart failure. By contrast, cTnT, but not cTnI, was associated with non-CVD death; ratio of hazard ratios 0.77 (0.67-0.88). We identified 5 loci (53 individual single-nucleotide polymorphisms) that had genome-wide significant associations with cTnI, and a different set of 4 loci (4 single-nucleotide polymorphisms) for cTnT.
CONCLUSIONS
The upstream genetic causes of low-grade elevations in cTnI and cTnT appear distinct, and their associations with outcomes also differ. Elevations in cTnI are more strongly associated with some CVD outcomes, whereas cTnT is more strongly associated with the risk of non-CVD death. These findings help inform the selection of an optimal troponin assay for future clinical care and research in this setting.
Topics: Adult; Aged; Cardiovascular Diseases; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Scotland; Time Factors; Troponin I; Troponin T
PubMed: 31014085
DOI: 10.1161/CIRCULATIONAHA.118.038529 -
Journal of the American College of... Apr 2018
Topics: Humans; Muscular Diseases; Troponin I; Troponin T
PubMed: 29622162
DOI: 10.1016/j.jacc.2018.01.068 -
Ugeskrift For Laeger May 2023With the increased sensitivity of the newest cardiac troponin assays, the risk of false positive cardiac troponin measurements has also increased. As summarised in this... (Review)
Review
With the increased sensitivity of the newest cardiac troponin assays, the risk of false positive cardiac troponin measurements has also increased. As summarised in this review, there are multiple possible causes of cardiac troponin release including several non-cardiac illnesses, particularly kidney disease. Further, there is a risk of analytical interference in which case repeated measurements with a different assay is a good tool. When there is a discrepancy between troponin measurement and clinical presentation of the patient, the clinician should consider the possibility of analytical interference.
Topics: Humans; Troponin; Troponin T; Biomarkers
PubMed: 37264867
DOI: No ID Found -
Archives of Biochemistry and Biophysics Jan 2011Troponin-mediated Ca²(+)-regulation governs the actin-activated myosin motor function which powers striated (skeletal and cardiac) muscle contraction. This review... (Review)
Review
Troponin-mediated Ca²(+)-regulation governs the actin-activated myosin motor function which powers striated (skeletal and cardiac) muscle contraction. This review focuses on the structure-function relationship of troponin T, one of the three protein subunits of the troponin complex. Molecular evolution, gene regulation, alternative RNA splicing, and posttranslational modifications of troponin T isoforms in skeletal and cardiac muscles are summarized with emphases on recent research progresses. The physiological and pathophysiological significances of the structural diversity and regulation of troponin T are discussed for impacts on striated muscle function and adaptation in health and diseases.
Topics: Animals; Evolution, Molecular; Humans; Protein Isoforms; Protein Processing, Post-Translational; Protein Structure, Tertiary; Species Specificity; Troponin T
PubMed: 20965144
DOI: 10.1016/j.abb.2010.10.013 -
Heart Failure Clinics Apr 2017Chemotherapy-related cardiac dysfunction (CRCD) has challenged clinicians to hesitate in using cardiotoxic agents such as anthracycline and several protein kinase... (Review)
Review
Chemotherapy-related cardiac dysfunction (CRCD) has challenged clinicians to hesitate in using cardiotoxic agents such as anthracycline and several protein kinase inhibitors. As early detection of CRCD and timely cessation of cardiotoxic agents became a strategy to avoid CRCD, cardiac troponin and natriuretic peptide are measured to monitor cardiotoxicity; however, there are inconsistencies in their predictability of CRCD. Alternative biomarkers have been researched extensively for potential use as more sensitive and accurate biomarkers. The mechanisms of CRCD and previous studies on traditional and novel biomarkers for CRCD are examined to enlighten future direction of investigation in this combined biology.
Topics: Antineoplastic Agents; Biomarkers; Early Diagnosis; Heart Diseases; Humans; Natriuretic Peptide, Brain; Neoplasms; Translational Research, Biomedical; Troponin T
PubMed: 28279423
DOI: 10.1016/j.hfc.2016.12.009 -
Circulation Jun 2022Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare...
BACKGROUND
Cardiac troponin (cTn) T and cTnI are considered cardiac specific and equivalent in the diagnosis of acute myocardial infarction. Previous studies suggested rare skeletal myopathies as a noncardiac source of cTnT. We aimed to confirm the reliability/cardiac specificity of cTnT in patients with various skeletal muscle disorders (SMDs).
METHODS
We prospectively enrolled patients presenting with muscular complaints (≥2 weeks) for elective evaluation in 4 hospitals in 2 countries. After a cardiac workup, patients were adjudicated into 3 predefined cardiac disease categories. Concentrations of cTnT/I and resulting cTnT/I mismatches were assessed with high-sensitivity (hs-) cTnT (hs-cTnT-Elecsys) and 3 hs-cTnI assays (hs-cTnI-Architect, hs-cTnI-Access, hs-cTnI-Vista) and compared with those of control subjects without SMD presenting with adjudicated noncardiac chest pain to the emergency department (n=3508; mean age, 55 years; 37% female). In patients with available skeletal muscle biopsies, mRNA differential gene expression was compared with biopsies obtained in control subjects without SMD.
RESULTS
Among 211 patients (mean age, 57 years; 42% female), 108 (51%) were adjudicated to having no cardiac disease, 44 (21%) to having mild disease, and 59 (28%) to having severe cardiac disease. hs-cTnT/I concentrations significantly increased from patients with no to those with mild and severe cardiac disease for all assays (all <0.001). hs-cTnT-Elecsys concentrations were significantly higher in patients with SMD versus control subjects (median, 16 ng/L [interquartile range (IQR), 7-32.5 ng/L] versus 5 ng/L [IQR, 3-9 ng/L]; <0.001), whereas hs-cTnI concentrations were mostly similar (hs-cTnI-Architect, 2.5 ng/L [IQR, 1.2-6.2 ng/L] versus 2.9 ng/L [IQR, 1.8-5.0 ng/L]; hs-cTnI-Access, 3.3 ng/L [IQR, 2.4-6.1 ng/L] versus 2.7 ng/L [IQR, 1.6-5.0 ng/L]; and hs-cTnI-Vista, 7.4 ng/L [IQR, 5.2-13.4 ng/L] versus 7.5 ng/L [IQR, 6-10 ng/L]). hs-cTnT-Elecsys concentrations were above the upper limit of normal in 55% of patients with SMD versus 13% of control subjects (<0.01). mRNA analyses in skeletal muscle biopsies (n=33), mostly (n=24) from individuals with noninflammatory myopathy and myositis, showed 8-fold upregulation of , encoding cTnT (but none for , encoding cTnI) versus control subjects (n=16, <0.001); the expression correlated with pathological disease activity (=0.59, <0.001) and circulating hs-cTnT concentrations (=0.26, =0.031).
CONCLUSIONS
In patients with active chronic SMD, elevations in cTnT concentrations are common and not attributable to cardiac disease in the majority. This was not observed for cTnI and may be explained in part by re-expression of cTnT in skeletal muscle.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03660969.
Topics: Biomarkers; Case-Control Studies; Female; Heart Diseases; Humans; Male; Middle Aged; Muscular Diseases; Prospective Studies; RNA, Messenger; Reproducibility of Results; Troponin I; Troponin T
PubMed: 35389756
DOI: 10.1161/CIRCULATIONAHA.121.058489 -
Biochemia Medica Oct 2018The high-sensitivity cardiac troponin T assay of Roche Diagnostics is known to have interference with high concentrations of biotin as this assay uses...
INTRODUCTION
The high-sensitivity cardiac troponin T assay of Roche Diagnostics is known to have interference with high concentrations of biotin as this assay uses biotin-streptavidin binding as detection method. As studies so far have not shown if different biotin concentrations could have diverse influence on various troponin concentrations and whether interference could be removed by available protocol within corresponding turnaround time we aimed to investigate it.
MATERIALS AND METHODS
Plasma samples were spiked with different concentration of biotin solution. Troponin T concentrations were tested on a Roche Cobas® 8000 module 602 analyser. Final concentrations of biotin and troponin T were 50, 100, 500 and 1000 μg/L and 18, 59, 201 and 6423 ng/L, respectively. Impact of different incubation times following biotin neutralization protocol described by Piketty was also tested.
RESULTS
We observed a mean of negative biases of 24, 56, 97, and 98% of the troponin T expected value at biotin concentrations of 50, 100, 500, 1000 μg/L. Neutralization protocol was applied on the sample with initial concentration of TnT of 59 ng/L at a biotin concentration of 1000 μg/L. Same results across different incubation times from 60 to 0 minutes were obtained (mean value 56.8 ng/L, coefficient of variation of 1.31%). We demonstrated that neutralization process had a dilution effect of the troponin concentration (loss of 4.5% to 9.6% of initial troponin value).
CONCLUSIONS
Biotin interference is not dependent of initial troponin value. Interference could be successfully neutralized within a time frame compatible with emergency but results still should be carefully interpreted due to possible dilution effect.
Topics: Biotin; Blood Chemical Analysis; Humans; Limit of Detection; Myocardium; Time Factors; Troponin T
PubMed: 30429682
DOI: 10.11613/BM.2018.030901 -
Pediatric Cardiology Dec 2019In this prospective cohort study of healthy full-term infants, we hypothesized that high-sensitivity cardiac troponin T (hs-cTnT) would be elevated in cord blood,...
In this prospective cohort study of healthy full-term infants, we hypothesized that high-sensitivity cardiac troponin T (hs-cTnT) would be elevated in cord blood, compared with adult reference values, and that it would further increase over the first days of age. Cardiac troponin T has been shown to be significantly increased in healthy full-term newborns compared with adult reference values, but there is no established reference range. Most studies of cTnT in newborns have been performed before the introduction of high-sensitivity cTnT (hs-cTnT) assay. We conducted a study including 158 full-term newborns, at Stockholm South General Hospital. High-sensitivity cTnT was analyzed in umbilical cord blood and at 2-5 days of age. Median hs-cTnT (interquartile range) in cord blood was 34(26-44) ng/L; 99th percentile 88 ng/L. Median hs-cTnT at 2-5 days of age was 92(54-158) ng/L; 99th percentile 664 ng/L. We conclude that hs-cTnT is elevated in cord blood in healthy, full-term newborn infants compared with adult reference values, and that it increases significantly during the first days of life. Our findings further underline the need of caution when using hs-cTnT as a measurement of cardiac impact in newborns.
Topics: Adult; Aged; Biomarkers; Female; Fetal Blood; Heart; Humans; Infant, Newborn; Male; Middle Aged; Pregnancy; Prospective Studies; Reference Values; Term Birth; Troponin T
PubMed: 31489446
DOI: 10.1007/s00246-019-02199-9 -
Journal of the American College of... Mar 2020
Topics: Early Diagnosis; Humans; Myocardial Infarction; Point-of-Care Systems; Troponin I; Troponin T
PubMed: 32164885
DOI: 10.1016/j.jacc.2019.12.064