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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 -
Vascular Health and Risk Management 2021The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI)... (Review)
Review
The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis.
The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.
Topics: Acute Disease; Biomarkers; Humans; Myocardial Infarction; Physical Exertion; Pulmonary Embolism; Pulmonary Heart Disease; Renal Insufficiency; Sepsis; Troponin; Troponin I; Troponin T
PubMed: 34584417
DOI: 10.2147/VHRM.S327661 -
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 -
Clinical Chemistry and Laboratory... Jan 2022Apparently healthy children often complain of chest pain, especially after physical exercise. Cardiac biomarker levels are often measured, but the clinical relevance of... (Review)
Review
Apparently healthy children often complain of chest pain, especially after physical exercise. Cardiac biomarker levels are often measured, but the clinical relevance of these assays in children is still debated, even when a cardiac disease is present. Coronary artery disease is exceedingly rare in children, but elevated circulating levels of cardiac troponin I (cTnI) and T (cTnT) in an acute setting may help detect heart failure due to an unknown cardiac disorder, or worsening heart failure, particularly in combination with other biomarkers such as B-type natriuretic peptides. However, the interpretation of biomarkers is often challenging, especially when institutions transition from conventional cTn assays to high-sensitivity (hs-cTn) methods, as well demonstrated in the emergency setting for adult patients. From a clinical perspective, the lack of established reference values in the pediatric age is the main problem limiting the use of hs-cTn methods for the diagnosis and managements of cardiac diseases in infants, children and adolescents. This review aims to discuss the possibility to use hs-cTnI and hs-cTnT to detect cardiac disease and to explore age-related differences in biomarker levels in the pediatric age. We start from some analytical and pathophysiological considerations related to hs-cTn assays. Then, after a systematic literature search, we discuss the current evidence and possible limitations of hs-cTn assay as indicators of cardiac disease in the most frequently cardiac disease in pediatric setting.
Topics: Adolescent; Adult; Biomarkers; Child; Humans; Infant; Natriuretic Peptide, Brain; Reference Values; Troponin I; Troponin T
PubMed: 34679265
DOI: 10.1515/cclm-2021-0976 -
European Heart Journal Jul 2023Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test...
AIMS
Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality.
METHODS AND RESULTS
Among adults without cardiovascular disease in the 1999-2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13-1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02-1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14-1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21-1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19-1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09-1.53) for Abbott after adjustment for the Ortho assay.
CONCLUSION
This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population.
Topics: Adult; Humans; Troponin I; Troponin T; Nutrition Surveys; Cardiovascular Diseases; Proportional Hazards Models; Biomarkers; Prognosis
PubMed: 37264651
DOI: 10.1093/eurheartj/ehad328 -
Internal and Emergency Medicine Mar 2017The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial... (Review)
Review
The role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of acute coronary syndrome (ACS) is well established. Since the initial 1st-generation assays, 5th-generation high-sensitivity cardiac troponin (hs-cTn) assays have been developed, and are now widely used. However, its clinical adoption preceded guidelines and even best practice evidence. This review summarizes the history of cardiac biomarkers with particular emphasis on hs-cTn. We aim to provide insights into using hs-cTn as a quantitative marker of cardiomyocyte injury to help in the differential diagnosis of coronary versus non-coronary cardiac diseases. We also review the recent evidence and guidelines of using hs-cTn in suspected ACS.
Topics: Acute Coronary Syndrome; Biological Assay; Biomarkers; Early Diagnosis; Humans; Primary Prevention; Troponin
PubMed: 28188579
DOI: 10.1007/s11739-017-1612-1 -
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 Mar 2019The cardiac contraction-relaxation cycle is controlled by a sophisticated set of machinery. Of particular interest, is the revelation that allosteric networks transmit... (Review)
Review
The cardiac contraction-relaxation cycle is controlled by a sophisticated set of machinery. Of particular interest, is the revelation that allosteric networks transmit effects of binding at one site to influence troponin complex dynamics and structural-mediated signaling in often distal, functional sites in the myofilament. Our recent observations provide compelling evidence that allostery can explain the function of large-scale macromolecular events. Here we elaborate on our recent findings of interdomain communication within troponin C, using cutting-edge structural biology approaches, and highlight the importance of unveiling the unknown, distant communication networks within this system to obtain more comprehensive knowledge of how allostery impacts cardiac physiology and disease.
Topics: Allosteric Regulation; Amino Acid Sequence; Animals; Humans; Protein Binding; Structure-Activity Relationship; Troponin C; Troponin I
PubMed: 30584890
DOI: 10.1016/j.abb.2018.12.026 -
Future Cardiology Feb 2022There has been strong evidence of myocardial injury in COVID-19 patients with significantly elevated serum cardiac troponin (cTn). While the exact mechanism of injury is... (Review)
Review
There has been strong evidence of myocardial injury in COVID-19 patients with significantly elevated serum cardiac troponin (cTn). While the exact mechanism of injury is unclear, possible suggested pathological mechanisms of injury are discussed. These include increased susceptibility of the myocardium and endothelium to viral invasion, underlying hyperinflammatory state and subsequent cytokine storm, a hypercoagulable and prothrombotic state, and indirect myocardial injury due to hypoxemia. As a result of these pathological mechanisms in COVID-19 patients, cTn may be elevated largely due to myocarditis, microangiopathy or myocardial infarction. The utility of cTn as a biomarker for measuring myocardial injury in these patients and assessing its ability as a prognostic factor for clinical outcome is also discussed.
Topics: Biomarkers; COVID-19; Cardiovascular Diseases; Humans; Myocardial Infarction; Troponin
PubMed: 34476978
DOI: 10.2217/fca-2021-0054 -
International Journal of Molecular... Jul 2022Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on... (Review)
Review
Acute myocardial infarction (AMI) is considered as one of the main causes of death, threating human lives for decades. Currently, its diagnosis relies on electrocardiography (ECG), which has been proven to be insufficient. In this context, the efficient detection of cardiac biomarkers was proposed to overcome the limitations of ECG. In particular, the measurement of troponins, specifically cardiac troponin I (cTnI) and cardiac troponin T (cTnT), has proven to be superior in terms of sensitivity and specificity in the diagnosis of myocardial damage. As one of the most life-threatening conditions, specific and sensitive investigation methods that are fast, universally available, and cost-efficient to allow for early initiation of evidence-based, living-saving treatment are desired. In this review, we aim to present and discuss the major breakthroughs made in the development of cTnI and cTnT specific biosensor designs and analytical tools, highlighting the achieved progress as well as the remaining challenges to reach the technological goal of simple, specific, cheap, and portable testing chips for the rapid and efficient on-site detection of cardiac cTnI/cTnT biomarkers in order to diagnose and treat cardiovascular diseases at an incipient stage.
Topics: Biomarkers; Biosensing Techniques; Humans; Myocardial Infarction; Troponin I; Troponin T
PubMed: 35887073
DOI: 10.3390/ijms23147728