Tobacco Consumption and High‐Sensitivity Cardiac Troponin I in the General Population: The HUNT Study

Background Cardiac troponins represent a sensitive index of subclinical myocardial injury and are associated with increased risk of cardiovascular events in the general population. Despite positive associations with cardiovascular risk of both cardiac troponins and cigarette smoking, concentrations of cardiac troponin I measured by high‐sensitivity assays (hs‐cTnI) are paradoxically lower in current smokers than in never‐smokers. The impact of smoking intensity and time from smoking cessation on hs‐cTnI remains unknown. Methods and Results hs‐cTnI concentrations were measured in 32028 subjects free from cardiovascular disease enrolled in the prospective, population‐based HUNT (Trøndelag Health Study). Tobacco habits were self‐reported and classified as never (n=14 559), former (n=14 248), and current (n=3221) smokers. Current smokers exhibited significantly lower concentrations of hs‐cTnI than never‐smokers ( P <0.001). In adjusted models, both current smoking (−17.3%; 95% CI, −20.6 to −13.9%) and former smoking (−6.6%; 95% CI, −8.7 to −4.5%) were associated with significantly lower hs‐cTnI concentrations. Among former smokers, higher smoking burden (>10 pack‐years) were associated with lower concentrations of hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI in a dose‐dependent manner ( P for trend<0.001), and subjects who quit smoking >30 years ago had concentrations of hs‐cTnI comparable with those of never‐smokers. Conclusions In the general population, both current and former cigarette smoking is associated with lower concentrations of hs‐cTnI. In former smokers, there was a dose‐response relationship between pack‐years of smoking, and hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI, indicating a continuum of hs‐cTnI from current smoker to never‐smokers.

A szívtroponinok laboratóriumi mérési módszereinek fő analitikai jellemzői: történeti és modern nézőpont

Összefoglaló. A cardialis troponinok biomarkerként való alkalmazása az akut myocardialis infarctus diagnosztikájában nagy múltra tekint vissza, és ez idő alatt jelentősen megváltoztak a cardialis troponinok diagnosztikai jelentőségével kapcsolatos elképzelések. Ez pedig a szívtroponinok és mindenekelőtt az érzékenység mérésére szolgáló laboratóriumi módszerek fejlődésének köszönhető. A legelső laboratóriumi módszerek, amelyeket több mint 30 évvel ezelőtt fejlesztettek ki a cardialis troponinok vérszérumban való kimutatására, még rendkívül alacsony érzékenységűek voltak, ezért csak 12–24 órával az akut myocardialis infarctus jelentkezése után tudták kimutatni a diagnózis felállításában jelentőséggel bíró troponinszintet. Ezenkívül a szívtroponin molekuláinak diagnosztikai reagensei nem specifikus módon kölcsönhatásba léphetnek a vázizombeli troponin molekuláival, ami a vázizmok betegségei és sérülései esetén a cardialis troponin koncentrációjának gyakori hamis pozitív növekedéséhez vezetett. Ahogy a cardialis troponinok mérési módszerei javultak, érzékenységük növekedésével (nagy érzékenységű cardialis troponinok) új lehetőségek nyíltak meg az akut myocardialis infarctus korai diagnózisának felállítására, és többek között modern diagnosztikai algoritmusokat is kifejlesztettek: 0–1 órás, 0–2 órás, 0–3 órás. Ez a korai diagnózis felállítását engedte meg azoknál a betegeknél, akiknek mellkasi fájdalmaik voltak, s ezzel korábban dönthettek a páciens gyógyításának optimális taktikájáról. Miután bevezetésre kerültek a cardialis troponin szintjének nagy érzékenységű mérési módszerei, a cardialis troponin molekuláinak biológiájával kapcsolatos elképzeléseink némileg megváltoztak, különösképpen, hogy innentől kezdve már nem tekinthetők szigorúan intracelluláris molekuláknak, mivel minden egészséges emberben kimutathatók, valamint nemi, életkori és cirkadián tulajdonságokat is felfedeztek a cardialis troponin koncentrációiban, amelyek ugyancsak szerepet játszhatnak az akut myocardialis infarctus diagnózisának felállításában. Arról nem is beszélve, hogy a nagy érzékenységű cardialis troponinok alkalmazási lehetőségei messze túlmutatnak az akut myocardialis infarctus diagnózisán. A jelen cikk egy történeti és egy modern perspektívát kíván bemutatni a cardialis troponinok legfontosabb analitikai jellemzőiről, érintve az azok biológiájára vonatkozó új adatokat és felhasználásuk új diagnosztikai lehetőségeit is. Orv Hetil. 2022; 163(1): 12–20. Summary. Throughout a very long history of using cardiac troponins in clinical practice as biomarkers of acute myocardial infarction, there have been significant changes in ideas about their diagnostic value. Such a circumstance is caused by the improvement of laboratory methods of cardiac troponin determination and, first of all, sensitivity. Thus, the very first laboratory methods designed to detect cardiac troponins in serum, developed over 30 years ago, had extremely low sensitivity, due to which they could detect diagnostically significant levels of troponins only 12–24 hours after the development of acute myocardial infarction. In addition, diagnostic antibodies directed against cardiac troponin molecules could interact nonspecifically with skeletal troponin molecules, leading to frequent false-positive increases in cardiac troponin concentrations in skeletal muscle disease and injury. As the methods of determining cardiac troponins improved, increasing their sensitivity (high-sensitivity cardiac troponins), the prospects for early diagnosis of acute myocardial infarction opened up, in particular, modern diagnostic algorithms: 0–1 hour, 0–2 hours, 0–3 hours. This allowed earlier diagnosis of patients who came with chest pain, and earlier decision-making on the choice of optimal tactics for the treatment of patients. With the introduction of high-sensitivity cardiac troponin assays, our understanding of the biology of cardiac troponin molecules has changed somewhat, in particular, they are no longer considered strictly intracellular molecules, as they are now detectable in all healthy individuals, and gender, age and circadian patterns in cardiac troponin concentrations have been discovered, which may have an impact on the diagnosis of acute myocardial infarction. Moreover, the possibilities of using highly sensitive cardiac troponins go far beyond the diagnosis of acute myocardial infarction. This article presents a view of the main analytical characteristics from a historical and contemporary perspective, covering some new data on the biology of cardiac troponins and new diagnostic possibilities for their use. Orv Hetil. 2022; 163(1): 12–20.

Cardiac troponins: current information on the main analytical characteristics of determination methods and new diagnostic possibilities

The methods used to diagnose cardiovascular diseases are constantly being improved, leading to an expanded perception of the diagnostic value of biomarkers and their new diagnostic possibilities. One striking example are the main biomarkers used to diagnose acute myocardial infarction: cardiac troponins. The first methods for determining cardiac troponins (proposed 30 years ago) were characterized by extremely low sensitivity. Therefore, they could only detect large acute myocardial infarctions. These methods were also characterized by low specificity, expressed as a high probability of cross-reactivity with skeletal troponin isoforms, which generated false-positive results in the presence of skeletal myopathies and skeletal muscle lesions. With the introduction of high-sensitivity cardiac troponins into clinical practice, the possibility of early diagnosis and exclusion of acute myocardial infarction by assessing troponin concentrations in the first few hours (from admission to the first hour, second hour, or third hour) has become more specific. Our knowledge about cardiac troponins has changed over the years and promising new medical uses have emerged. This paper reviews current data on the diagnostic value of cardiac troponins, the main methods used for their determination, and their analytical characteristics from historical and modern insights.

Evaluation and Comparison of the STIMUL Extended and Simplified Risk Scores for Predicting Two-Year Death in Patients Following ST-Segment Elevation Myocardial Infarction

Background and Objectives: The management of ST-segment elevation myocardial infarction (STEMI) requires a patient’s long-term risk to be estimated. The objective of this study was to develop extended and simplified models of two-year death risk estimation following STEMI that include and exclude cardiac troponins as prognostic factors and to compare their performance with each other. Materials and Methods: Extended and simplified multivariable logistic regression models were elaborated using 1103 patients with STEMI enrolled and followed up in the STIMUL (ST-segment elevation Myocardial Infarctions in Ukraine and their Lethality) registry. Results: The extended STIMUL risk score includes seven independent risk factors: age; Killip class ≥ II at admission; resuscitated cardiac arrest; non-reperfused infarct-related artery; troponin I ≥ 150.0 ng/L; diabetes mellitus; and history of congestive heart failure. The exclusion of cardiac troponin in the simplified model did not influence the predictive value of each factor. Both models divide patients into low, moderate, and high risk groups with a C-statistic of 0.89 (95% CI 0.84–0.93; p < 0.001) for the extended STIMUL model and a C-statistic of 0.86 (95% CI 0.83–0.99; p < 0.001) for the simplified model. However, the addition of the level of troponin I to the model increased its prognostic value by 10.7%. Conclusions: The STIMUL extended and simplified risk estimation models perform well in the prediction of two-year death risk following STEMI. The simplified version may be useful when clinicians do not know the value of cardiac troponins among the population of STEMI patients.

Mechanisms for Cardiac Troponin Increase in Arterial Hypertension

Despite the fact that cardiac troponins (cTnI and cTnT) are cardiospecific, they can be elevated in many systemic and non-cardiac physiological and pathological conditions. The diagnostic value of cTnI and cTnT significantly depends on the method of their determination. Thus, previously used low- and moderate-sensitivity immunoassays detected only serious myocardial damage and did not determine troponins in patients suffering from certain chronic pathologies. High-sensitivity troponin assays can detect minor damage to cardiac muscle cells in many pathological conditions, and troponin levels have a high predictive value. Among the early pathological conditions requiring the attention of clinicians is arterial hypertension (AH), which is also accompanied by an increase in the levels of hsTn in serum and urine. Currently, mechanisms responsible for increased levels of cardiac troponins in the blood serum and urine in hypertension are not well covered in the scientific literature. This article discusses in detail the presumptive mechanisms that cause increased levels of cTnI and cTnT in AH.

684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (&gt;99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P &lt; 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P &lt; 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P &lt; 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Elevation Mechanisms and Diagnostic Consideration of Cardiac Troponins under Conditions Not Associated with Myocardial Infarction. Part 2

This article proceeds with a discussion of the causes and mechanisms of an elevation in cardiac troponins in pathological conditions not associated with acute myocardial infarction. The second part of the article discusses the causes and mechanisms of cardiac troponins elevation in diabetes mellitus, arterial hypertension, hereditary cardiomyopathies, cardiac arrhythmias (atrial fibrillation, supraventricular tachycardia), acute aortic dissection, and diseases of the central nervous system (strokes, subarachnoidal hemorrhage). The final chapter of this article discusses in detail the false-positive causes and mechanisms of elevated cardiac troponins.