Cardiospecific Troponins as Laboratory Biomarkers of Myocardial Cell Injury in Hypertension: A Mini-Review.

To date, it is well known that a significant number of diseases of cardiovascular genesis (coronary heart disease, myocardial infarction, cardiomyopathy, Takotsubo syndrome, heart failure, etc.) and extra-cardiac genesis (renal failure, chronic obstructive pulmonary disease, sepsis, diabetes mellitus, etc.) cause injury to contractile cells of the heart muscle (myocardial cells). The most sensitive and specific criteria for proving myocardial cell injury are cardiospecific troponins (CSTns) - CSTnI and CSTnT. According to the current clinical recommendations of the European, American, and Russian Cardiological Communities, CSTnI and CSTnT are the main biomarkers for early diagnosis of myocardial infarction. Hypertension is one of the most dangerous and common risk factors for the development of cardiovascular pathologies and is associated with a high risk of dangerous cardiovascular complications. Therefore, there is an urgent need to search for new biomarkers for the timely assessment of the prognosis of patients with hypertension. This mini-review aims to substantiate the possibilities of using the cardiomarkers (CSTnI and CSTnT) to assess the prognosis of patients suffering from hypertension and to discuss potential mechanisms that cause injury to myocardial cells and increase serum levels of CSTnI and CSTnT. This is a narrative mini-review, which was prepared using the following databases: Pubmed/Medline, PubMed Central, Embase, Scopus, and Web of Science. The following keywords were used in the literature search: "myocardial cells", "injury", "damage", and "hypertension" in combination with the terms "mechanisms of injury" "predictive significance", "cardiac troponins", or "cardiospecific troponins".

The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin.

The study of mechanisms underlying cardiotoxicity of doxorubicin and the development of strategies to mitigate doxorubicin-induced cardiotoxicity are the most relevant issues of modern cardio-oncology. This is due to the high prevalence of cancer in the population and the need for frequent use of highly effective chemotherapeutic agents, in particular anthracyclines, for optimal management of cancer patients. However, while being a potent agent to counteract cancer, doxorubicin also affects the cardiovascular systems of patients undergoing chemotherapy in a significant and unfavorable fashion. Consecutively reviewed in this article are risk factors and mechanisms of doxorubicin cardiotoxicity, and the essential strategies to mitigate cardiotoxic effects of doxorubicin treatment in cancer patients are discussed.

High-sensitive cardiospecific troponins: the role of sex-specific concentration in the diagnosis of acute coronary syndrome (mini-review).

Cardiospecific troponins are specifically localized in the troponin-tropomyosin complex and the cytoplasm of cardiac myocytes. Cardiospecific troponin molecules are released from cardiac myocytes upon their death (irreversible damage in acute coronary syndrome) or reversible damage to cardiac myocytes, for example, during physical exertion or the influence of stress factors. Modern high-sensitive immunochemical methods for detecting cardiospecific troponins T and I are extremely sensitive to minimal reversible damage to cardiac myocytes. This makes it possible to detect damage to cardiac myocytes in the early stages of the pathogenesis of many extra-cardiac and cardiovascular diseases, including acute coronary syndrome. So, in 2021, the European Society of Cardiology approved diagnostic algorithms for the acute coronary syndrome, which allow the diagnosis of acute coronary syndrome in the first 1-2 hours from the moment of admission of the patient to the emergency department. However, high-sensitive immunochemical methods for detecting cardiospecific troponins T and I may also be sensitive to physiological and biological factors, which are important to consider in order to establish a diagnostic threshold (99 percentile). One of the important biological factors that affect the 99 percentile levels of cardiospecific troponins T and I are sex characteristics. This article examines the mechanisms underlying the development of sex-specific serum levels of cardiospecific troponins T and I and the importance of sex-specific cardiospecific troponin concentrations in diagnosing acute coronary syndrome.

Modern View on the Role of Sex-Specific Levels of High-Sensitive Cardiospecific Troponins T and I in the Diagnosis of Myocardial Infarction.

It is well known that the molecules of cardiospecific troponins T and I are localized in the troponin-tropomyosin complex of the cytoplasm of cardiac myocytes and, due to the specific localization, these cardiospecific troponins are widely used as diagnostic biomarkers of myocardial infarction. Cardiospecific troponins are released from the cytoplasm of cardiac myocytes as a result of irreversible cell damage (for example, ischemic necrosis of cardiomyocytes in myocardial infarction or apoptosis of cardiac myocytes in cardiomyopathies and heart failure) or reversible damage (for example, intense physical exertion, hypertension, the influence of stress factors, etc.). Current immunochemical methods for determining cardiospecific troponins T and I have extremely high sensitivity to subclinical (minor) damage to myocardial cells and, thanks to modern high-sensitive methods, it is possible to detect damage to cardiac myocytes in the early (subclinical) stages of a number of cardiovascular pathologies, including myocardial infarction. So, recently, leading cardiological communities (the European Society of Cardiology, the American Heart Association, the American College of Cardiology, etc.) have approved algorithms for early diagnosis of myocardial infarction based on the assessment of serum levels of cardiospecific troponins in the first 1 - 3 h after the onset of pain syndrome. An important factor that may affect early diagnostic algorithms of myocardial infarction are sex-specific features of serum levels of cardiospecific troponins T and I. This manuscript presents a modern view on the role of sex-specific serum levels of cardiospecific troponins T and I in the diagnosis of myocardial infarction and the mechanisms of formation of sex-specific serum levels of troponins.

The negative effects of statin drugs on cardiomyocytes: current review of laboratory and experimental data (mini-review).

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipid-lowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Gender Specificities of Cardiac Troponin Serum Levels: From Formation Mechanisms to the Diagnostic Role in Case of Acute Coronary Syndrome.

Cardiac troponins T and I are the main (most sensitive and specific) laboratory indicators of myocardial cell damage. A combination of laboratory signs of myocardial cell damage (elevated levels of cardiac troponins T and I) with clinical (severe chest pain spreading to the left side of the human body) and functional (rise or depression of the ST segment, negative T wave or emergence of the Q wave according to electrocardiography and/or decrease in the contractility of myocardial areas exposed to ischemia according to echocardiography) signs of myocardial ischemia is indicative of the ischemic damage to cardiomyocytes, which is characteristic of the development of acute coronary syndrome (ACS). Today, with early diagnostic algorithms for ACS, doctors rely on the threshold levels of cardiac troponins (99th percentile) and on the dynamic changes in the serum levels over several hours (one, two, or three) from the moment of admission to the emergency department. That said, some recently approved highly sensitive methods for determining troponins T and I show variations in 99th percentile reference levels, depending on gender. To date, there are conflicting data on the role of gender specificities in the serum levels of cardiac troponins T and I in the diagnostics of ACS, and the specific mechanisms for the formation of gender differences in the serum levels of cardiac troponins T and I are unknown. The purpose of this article is to analyze the role of gender specificities in cardiac troponins T and I in the diagnostics of ACS, and to suggest the most likely mechanisms for the formation of differences in the serum levels of cardiac troponins in men and women.

Diagnostic Role and Methods of Detection of Cardiac Troponins: An Opinion from Historical and Current Points of View.

The laboratory methods for the determination of cardiac troponins (cTnI, cTnT) used nowadays are extremely diverse, which has a significant impact on our understanding of the biology and diagnostic the value of cTnI and cTnT as biomarkers. The main classification of methods for the determination of cTnI and cTnT is based on the sensitivity of the immunoassay. Low- and moderately sensitive detection methods are known to be relatively less sensitive, which leads to a relatively late confirmation of cardiomyocyte death. Due to the new highly sensitive methods used to determine cTnI and cTnT, designated as a highly or ultrasensitive immunoassays (hs-TnT and hs-TnT), we received new, revised data about the biology of cardiac troponin molecules. In particular, it became clear that they can be considered products of normal myocardium metabolism since hs-TnT and hs-TnT are detected in almost all healthy patients. It also turned out that hs-TnT and hs-TnT differ by gender (in men, troponin concentration in the blood is higher than in women), age (in elderly patients, the levels of troponins are higher than in young ones) and circadian cycles (morning concentrations of troponins are higher than in the evening). A large variety of methods for determining cTnI and cTnT, differing in their diagnostic capabilities, creates the need for tests to perform an unbiased assessment of the analytical characteristics of each method. This review focuses on the most pressing issues related to the discussion of the biological characteristics of cardiac troponin and the analytical characteristics of troponin immunoassays from a historical and contemporary point of view.

Modern Concepts of the Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Clinical and Epidemiological Data, the Main Pathophysiological Mechanisms.

Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow improving the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs. The aim of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage with the consideration of epidemiological and pathogenetic aspects. Materials and Methods: This narrative review is based on the analysis of publications in the Medline, PubMed, and Embase databases. The terms "fine particles" and "PM 2.5" in combination with "pathophysiological mechanisms," "cardiovascular diseases", "atherosclerosis", "cardiac troponins", "myocardial damage" and "myocardial injury" were used to search publications. Conclusion: According to the conducted narrative review, PM 2.5 should be regarded as the significant risk factor for the development of atherosclerotic CVDs. The pro-atherogenic effect of fine particulate matter is based on several fundamental and closely interrelated pathophysiological mechanisms: endothelial dysfunction, impaired lipid metabolism, increased oxidative stress and inflammatory reactions, impaired functioning of the vegetative nervous system and increased activity of the hemostatic system. In addition, PM 2.5 causes subclinical damage to cardiac muscle cells by several mechanisms: apoptosis, oxidative stress, decreased oxygen delivery due to coronary atherosclerosis and ischemic damage of cardiomyocytes. Highly sensitive cardiac troponins are promising markers for detecting subclinical myocardial damage in people living in polluted regions.

Hypertension as One of the Main Non-Myocardial Infarction-Related Causes of Increased Cardiospecific Troponins: From Mechanisms to Significance in Current Medical Practice.

It is well known that many pathological conditions of both cardiovascular diseases (CVDs) (coronary heart disease, myocardial infarction, arrhythmias, myocarditis, cardiomyopathy, etc.) and non-cardiac (sepsis, anemia, kidney diseases, diabetes mellitus, etc.) origin in the course of their development cause injury to contractile cardiac muscle cells - myocardial cells (MCs). One of the most sensitive and specific criteria for detecting MC injury are cardiospecific troponins (CTs), which are regulatory protein molecules that are released into the blood serum from MC upon their death or injury. Current methods for determining CTs are called high-sensitive ones, and their main advantage is a very low minimum detectable concentration (limit of detection) (average 1 - 10 ng/L or less), which allows early detection of minor MC injury at the earliest stages of CVDs, and therefore they can change the understanding of disease development mechanisms and open up new diagnostic possibilities. One of the most common and dangerous early diseases of the cardiovascular system is hypertension (HT). The novelty of this article lies in the discussion of a new diagnostic direction - predicting the risk of developing CVDs and their dangerous complications in patients with HT by determining the concentration of CTs. In addition, pathophysiological mechanisms underlying MC injury and the release of CTs into the bloodstream and the elimination of CTs into the urine are proposed. This information will contribute to additional fundamental and clinical research to verify the new diagnostic possibility of using CTs in clinical practice (for the management of patients with HT).

The Role of Fine Particles (PM 2.5) in the Genesis of Atherosclerosis and Myocardial Damage: Emphasis on Clinical and Epidemiological Data, and Pathophysiological Mechanisms.

Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow to improve the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs. The aim of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage.

Review of Recent Laboratory and Experimental Data on Cardiotoxicity of Statins.

Due to the fact that statins are among the most high-demand therapeutic agents used for the treatment and prevention of the most common cardiovascular diseases, a significant amount of research is focused on these drugs. As a result, the study and discovery of new effects in statin drugs continues. Research methods are constantly being improved in terms of their sensitivity and specificity, which leads to a change in ideas. In addition to the main lipid-lowering effect, statins have a number of additional effects, which can be conditionally divided into positive (pleiotropic) and negative (side effects). Moreover, information about many of the pleiotropic effects of statins is controversial and may subsequently change as new data become available. To a large extent, this is due to the introduction of new and the improvement of old methods of study: clinical, laboratory and morphological ones. Recent studies report the possibility of statins having potential cardiotoxic properties, which is expressed by an increase in the concentration of highly sensitive cardiac troponins, as well as various adverse changes in cardiac myocytes at the ultrastructural and molecular levels. This paper discusses possible mechanisms of statin cardiotoxicity. This narrative review is based on an analysis of publications in the Medline, PubMed, PubMed Central and Embase databases. The terms "statins", "troponin", "troponin I", "troponin T" in combination with "cardiotoxicity", "false positive", "mechanisms of increase", "pathophysiological mechanisms", "oxidative stress" and "cardiomyocyte apoptosis" were used to search publications.

The Metabolic Pathway of Cardiac Troponins Release: Mechanisms and Diagnostic Role.

Modern methods of cardiac troponin determination have enabled early diagnosis of acute myocardial infarction (AMI) and selection of optimal treatment tactics for patients early from admission. It has markedly improved the further prognosis of these patients. Unfortunately, there are a number of problems arising from the use of high-sensitivity cardiac troponins: frequent and unexplained increases in serum troponin levels in a number of pathological conditions not associated with AMI; insufficient study of mechanisms of release and increase, features of circulation and elimination of cardiac troponins; inconsistent data on the influence of several factors (circadian, gender and age characteristics), on cardiac troponin levels. All this may be accompanied by difficulties and errors in differential diagnosis as well as insufficient use of the diagnostic potential of cardiac troponins. In general, these problems are due to our insufficient understanding of the metabolic pathway of cardiac troponins. This review briefly discusses the main stages of the metabolic pathway of cardiac troponins and focuses in detail on the first stage of metabolism (the release of cardiac troponins).

Cardiac Troponins as Biomarkers of Cardiac Myocytes Damage in Case of Arterial Hypertension: From Pathological Mechanisms to Predictive Significance.

BACKGROUND: Many pathological conditions of both cardiovascular and non-cardiac origin in the course of their development cause damage to contractile cardiac muscle cells-cardiac myocytes (CMCs). One of the most sensitive and specific criteria for detecting CMCs are cardiac troponins (CTs), which are regulatory protein molecules that are released into the blood serum from CMCs upon their death or damage. New (high-sensitive) methods for detecting CTs allow the detection of minor CMCs damages at the earliest stages of cardiovascular diseases and can therefore change the understanding of disease development mechanisms and open up new diagnostic possibilities. One of the most common and dangerous early diseases of the cardiovascular system is arterial hypertension. The purpose of this paper is to summarize the pathophysiological mechanisms underlying CMCs damage and CTs release into the bloodstream in the case of arterial hypertension and to state the clinical significance of increased CTs levels in patients with arterial hypertension. MATERIALS AND METHODS: This is a descriptive review, which was prepared using the following databases: Embase, Pubmed/Medline and Web of Science. The following key words were used in the literature search: "myocardial injury" and "arterial hypertension" in combination with the terms "cardiac troponins" and "mechanisms of increase". CONCLUSIONS: According to a literature analysis, CMCs damage and CTs release in the case of arterial hypertension occur according to the following pathophysiological mechanisms: myocardial hypertrophy, CMCs apoptosis, damage to the CMC cell membrane and increase in its permeability for CTs molecules, as well as changes in the glomerular filtration rate. Most often, increased CTs serum levels in case of arterial hypertension indicate an unfavorable prognosis. Data on the CTs predictive significance in case of arterial hypertension open the prospects for the use of these biomarkers in the choice of patient management plans.

On the Effect of Heterophilic Antibodies on Serum Levels of Cardiac Troponins: A Brief Descriptive Review.

Serum levels of cardiac troponins can be increased both with myocardial damage and in the absence of myocardial damage. In the second case, this is due to the influence of false-positive factors, among which heterophilic antibodies play a significant role. Understanding the causes of the formation of heterophilic antibodies, the features and mechanisms of their effect on serum levels of cardiac troponins, is an important condition for interpreting a false-positive result due to the influence of heterophilic antibodies. This brief, descriptive review presents the causes of heterophilic-antibodies formation and discusses their effect on serum levels of cardiac troponins.

Current Understanding of Cardiac Troponins Metabolism: A Narrative Review.

BACKGROUND AND AIMS: Current methods (highly sensitive and ultra-sensitive) of cardiospecific troponins detection have enabled early diagnosis of myocardial infarction (MI) and selection of optimal treatment tactics for patients early from admission. The use of these methods in real clinical practice helps to choose the most optimal treatment tactics for patients in the early stages after admission, and this significantly improved the further prognosis of patients suffering from MI. However, there are a number of problems that arise when using highly sensitive or ultra-sensitive methods for determining cardiospecific troponins: frequent and unexplained increases in serum levels of cardiospecific troponins in a number of pathological conditions unrelated to MI; insufficient knowledge and understanding of the mechanisms of release and increase in the levels of cardiospecific troponins; poorly understood features and mechanisms of circulation and elimination of cardiospecific troponins; the presence of conflicting information about the influence of several factors (gender, age and circadian characteristics) on the levels of cardiospecific troponins in blood serum; undisclosed diagnostic potential of cardiospecific troponins in non-invasive human biological fluids. These problems cause great difficulties and increase the risk of errors in the differential diagnosis of MI, and also do not allow to fully unlock the diagnostic potential of cardiospecific troponins. In general, these problems are associated with a lack of understanding of the fundamental mechanisms of the metabolism of cardiospecific troponins. The main purpose of this narrative review is to summarize and provide detailed information about the metabolism of cardiospecific troponins and to discuss the potential impact of metabolic features on the diagnostic value of cardiospecific troponins and their diagnostic capabilities. MATERIALS AND METHODS: This narrative review is based on the analysis of publications in the Medline, PubMed, and Embase databases. The terms "cardiac troponins", "troponin T", and "troponin I" in combination with "mechanisms of increase", "mechanisms of release", "circulation", "proteolytic cleavage", "elimination", "circadian rhythms", "saliva", and "urine" were used to search publications. RESULTS: It has been reported that the metabolic features (mechanisms of release, circulation, and elimination) of cardiospecific troponins may have an important influence on the diagnostic value of cardiospecific troponins in a number of physiological and pathological conditions that cause cardiomyocyte damage. The main mechanisms of cardiac troponin release are: cardiomyocyte apoptosis; myocardial cell regeneration and renewal; increased cell membrane permeability; release of troponins by vesicular transport; increased proteolytic degradation of cardiospecific troponin molecules within the cell which may facilitate their release from intact myocardial cells or in the initial phase of those pathological conditions that increase the activity of enzymes that degrade cardiospecific troponins. Besides, the formation of small fragments (troponin molecules) may facilitate their penetration into other body fluids such as urine and/or oral fluid which may provide researchers and practitioners with a new diagnostic opportunity. It should be noted that in addition to release mechanisms, cardiospecific troponin elimination mechanisms may play an important diagnostic role. The contribution of release and elimination mechanisms to different pathologies may differ significantly. Circadian rhythms of cardiospecific troponins may be associated with fluctuations in the activity of those organ systems which influence the mechanisms of cardiospecific troponin release or elimination. Such major systems include: neuroendocrine, urinary, and hemostasis. CONCLUSION: Cardiospecific troponins metabolism has an important influence on diagnostic value and diagnostic capabilities. Further study of the features of cardiac troponin metabolism (mechanisms of release, circulation and elimination) is required to improve diagnosis and differential diagnosis of diseases causing cardiomyocyte damage. The data on the influence of circadian rhythms of cardiospecific troponins on the diagnostic value and the possibility of determining cardiospecific troponins in body fluids that can be obtained by noninvasive methods are very interesting. However, so far this information and valuable capabilities have not been applied in clinical practice because of the paucity of studies conducted.

Features of the Metabolisms of Cardiac Troponin Molecules-Part 1: The Main Stages of Metabolism, Release Stage.

Cardiac troponins (cTns) have long been the most valuable and specific biomarkers for detecting ischemic myocardial cells (MCs) injury, which is one of the key signs of myocardial infarction (MI). Modern methods (highly sensitive and ultra-sensitive immunoassays (hs-cTns)) of detection are an important and indispensable tool for the early diagnosis of MI and the choice of patient management protocols. Timely diagnosis of MI can significantly improve the prognosis of patients. However, in real clinical practice, doctors often face a significant problem when using cTns-the difficulty of differential diagnosis due to frequent and unexplained increases in the concentration of cTns in blood serum. In addition, there is conflicting information that may potentially affect the diagnostic capabilities and value of cTns: the influence of certain biological factors (diurnal rhythm, gender and age) on serum cTns levels; extra-cardiac expression of cTns; the possibilities of non-invasive diagnosis of MI; and other pathological conditions that cause non-ischemic injury to MCs. To solve these problems, it is necessary to concentrate on studying the metabolism of cTns. The review of our current knowledge about cTns metabolism consists of two parts. In this (first) part of the manuscript, the main stages of cTns metabolism are briefly described and the mechanisms of cTns release from MCs are considered in detail.

Metabolic Pathway of Cardiospecific Troponins: From Fundamental Aspects to Diagnostic Role (Comprehensive Review).

Many molecules of the human body perform key regulatory functions and are widely used as targets for the development of therapeutic drugs or as specific diagnostic markers. These molecules undergo a significant metabolic pathway, during which they are influenced by a number of factors (biological characteristics, hormones, enzymes, etc.) that can affect molecular metabolism and, as a consequence, the serum concentration or activity of these molecules. Among the most important molecules in the field of cardiology are the molecules of cardiospecific troponins (Tns), which regulate the processes of myocardial contraction/relaxation and are used as markers for the early diagnosis of ischemic necrosis of cardiomyocytes (CMC) in myocardial infarction (MI). The diagnostic value and diagnostic capabilities of cardiospecific Tns have changed significantly after the advent of new (highly sensitive (HS)) detection methods. Thus, early diagnostic algorithms of MI were approved for clinical practice, thanks to which the possibility of rapid diagnosis and determination of optimal tactics for managing patients with MI was opened. Relatively recently, promising directions have also been opened for the use of cardiospecific Tns as prognostic markers both at the early stages of the development of cardiovascular diseases (CVD) (arterial hypertension (AH), heart failure (HF), coronary heart disease (CHD), etc.), and in non-ischemic extra-cardiac pathologies that can negatively affect CMC (for example, sepsis, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), etc.). Recent studies have also shown that cardiospecific Tns are present not only in blood serum, but also in other biological fluids (urine, oral fluid, pericardial fluid, amniotic fluid). Thus, cardiospecific Tns have additional diagnostic capabilities. However, the fundamental aspects of the metabolic pathway of cardiospecific Tns are definitively unknown, in particular, specific mechanisms of release of Tns from CMC in non-ischemic extra-cardiac pathologies, mechanisms of circulation and elimination of Tns from the human body, mechanisms of transport of Tns to other biological fluids and factors that may affect these processes have not been established. In this comprehensive manuscript, all stages of the metabolic pathway are consistently and in detail considered, starting from release from CMC and ending with excretion (removal) from the human body. In addition, the possible diagnostic role of individual stages and mechanisms, influencing factors is analyzed and directions for further research in this area are noted.

The Importance of Cardiac Troponin Metabolism in the Laboratory Diagnosis of Myocardial Infarction (Comprehensive Review).

The study of the metabolism of endogenous molecules is not only of great fundamental significance but also of high practical importance, since many molecules serve as drug targets and/or biomarkers for laboratory diagnostics of diseases. Thus, cardiac troponin molecules have long been used as the main biomarkers for confirmation of diagnosis of myocardial infarction, and with the introduction of high-sensitivity test methods, many of our ideas about metabolism of these cardiac markers have changed significantly. In clinical practice, there are opening new promising diagnostic capabilities of cardiac troponins, the understanding and justification of which are closely connected with the fundamental principles of the metabolism of these molecules. Our current knowledge about the metabolism of cardiac troponins is insufficient and extremely disconnected from various literary sources. Thus, many researchers do not sufficiently understand the potential importance of cardiac troponin metabolism in the laboratory diagnosis of myocardial infarction. The purpose of this comprehensive review is to systematize information about the metabolism of cardiac troponins and during the discussion to focus on the potential impact of cTns metabolism on the laboratory diagnosis of myocardial infarction. The format of this comprehensive review includes a sequential consideration and analysis of the stages of the metabolic pathway, starting from possible release mechanisms and ending with elimination mechanisms. This will allow doctors and researchers to understand the significant importance of cTns metabolism and its impact on the laboratory diagnosis of myocardial infarction.

Some Common Causes of False Positive Increases in Serum Levels of Cardiac Troponins.

Cardiac troponin molecules (cTnI and cTnT) are the most valuable and in-demand biomarkers for detecting various types of myocardial damage (reversible and irreversible, ischemic, inflammatory, toxic, etc.) in current clinical practice. These biomarkers are widely used for early diagnosis of acute myocardial infarction (AMI) and risk stratification of patients suffering from a number of cardiac (such as myocarditis, heart failure, cardiomyopathy, etc.) and extra-cardiac diseases (such as sepsis, renal failure, pulmonary embolism, neurological pathologies, etc.) that negatively affect the cells of cardiac muscle tissue. However, in daily routine clinical activities, internists and cardiologists often encounter cases of false increases in the concentrations of cardiospecific troponins. A false increase in the concentration of troponins contributes to an incorrect diagnosis and incorrect therapy, which can harm the patient. A false increase in the concentration of troponins contributes to an incorrect diagnosis and incorrect therapy, which can harm the patient, therefore, internists and cardiologists should be well aware of the main reasons and mechanisms for false-positive results cTnI and cTnT. This review article mainly focuses on the causes of falsepositive increases in serum levels of cTnI and cTnT, which provide helpful clues for the accurate diagnosis of AMI and evidence for the differential diagnosis.

False-Positive Causes in Serum Cardiac Troponin Levels.

Cardiac troponins (cTns) are the most valuable and specific markers of cardiovascular diseases, including acute myocardial infarction. These biomarkers can also be used to assess the degree of myocardial damage in non-cardiac diseases that can negatively affect the cells of cardiac muscle tissue. However, in everyday clinical practice, doctors often encounter with false-positive cases of increased cTns. False-positive cases of increased cTns can contribute to incorrect diagnosis and subsequent inadequate treatment, which causes significant harm to the patient. This review discusses some common causes of a false-positive increase in the level of cTns in the blood serum. Such causes are fibrin clots, heterophilic antibodies, alkaline phosphatase, rheumatoid factor, and cross-reactions of diagnostic (anti-cTn) antibodies with skeletal troponins. Detailed attention is focused on the mechanisms of false-positive increase, and ways to identify and combat these false-positive causes of increased cTns. This has an important practical significance in modern clinical practice.