A Possible Mechanism behind Faster Clearance and Higher Peak Concentrations of Cardiac Troponin I Compared with Troponin T in Acute Myocardial Infarction

Starnberg, Karin; Fridén, Vincent; Muslimović, Aida; Ricksten, Sven‐Erik; Nyström, Staffan; Forsgard, Niklas; Lindahl, Bertil; Vukusic, Kristina; Sandstedt, Joakim; Dellgren, Göran; Hammarsten, Ola

doi:10.1093/clinchem/hvz003

Cited by 33 publications

(24 citation statements)

References 35 publications

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“…No matter of the underlying release mechanism, before we knew the mechanisms of cTnT and cTnI release and clearance after necrotic events [3] , [4] , [11] , [48] , [49] it might be understandable that the different cTnI/cTnT ratio following exercise and MI have been overlooked. For instance, there is no obvious reason to believe that the ratio between cTnT and myoglobin or CK-MB would add information as the relative abundance, release kinetics and clearance are different.…”

Section: Discussionmentioning

confidence: 99%

“…cTnT and cTnI are therefore expressed to similar amounts in cardiac tissue. Once released into the circulation cTnT and cTnI are cleared by the liver and kidneys with similar kinetics [3] , [4] . Despite this fact, the level of cTnI often reach ten-times higher peak levels and decrease more quickly compared to cTnT following myocardial infarction [5] , [6] , [7] .…”

Section: Introductionmentioning

confidence: 99%

“…Experimental studies from our group indicate that this difference is due to fast cleavage and release of cTnI in necrotic cardiac tissue and that most cTnT remains bound to the insoluble muscle filaments. cTnT is therefore for the most part locally degraded without reaching the systemic circulation [3] , [5] , [8] . The faster and more complete release of cTnI result in considerably higher cTnI levels compared to cTnT levels in patients with MI [5] , [6] , [7] , a fact also experienced by our local clinicians when the hospital lab changed from cTnT to cTnI assays.…”

Section: Introductionmentioning

confidence: 99%

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The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients

Hammarsten

Ljungqvist

Redfors

et al. 2022

Clinica Chimica Acta

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Background Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise. Objective Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care. Results Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1-0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7-14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/TnT ratio 14, IQR: 12-23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/cTnT ratio of 5,5 (IQR: 1,9-8,3). Conclusions In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients

Hammarsten

Ljungqvist

Redfors

et al. 2022

Clinica Chimica Acta

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“…This extends our previous finding that cardiac troponin I has a greater specificity for future cardiovascular risk ( 7 , 16 ). Although the underlying mechanism of this divergence is not well understood and remains speculative, cardiac troponin T elevations appear more strongly related to chronic kidney and neuromuscular diseases ( 39 , 40 ). Furthermore, the curvilinear relationships between cardiovascular risk and cardiac troponin I and T concentrations differ.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Cardiac Troponin I and T and the Prediction of Cardiovascular Events in the General Population

et al. 2021

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Background Cardiac troponin concentrations differ in women and men, but how this influences risk prediction and whether a sex-specific approach is required is unclear. We evaluated whether sex influences the predictive ability of cardiac troponin I and T for cardiovascular events in the general population. Methods High-sensitivity cardiac troponin (hs-cTn) I and T were measured in the Generation Scotland Scottish Family Health Study of randomly selected volunteers drawn from the general population between 2006 and 2011. Cox-regression models evaluated associations between hs-cTnI and hs-cTnT and the primary outcome of cardiovascular death, myocardial infarction, or stroke. Results In 19 501 (58% women, mean age 47 years) participants, the primary outcome occurred in 2.7% (306/11 375) of women and 5.1% (411/8126) of men during the median follow-up period of 7.9 (IQR , 7.1–9.2) years. Cardiac troponin I and T concentrations were lower in women than men (P < 0.001 for both), and both were more strongly associated with cardiovascular events in women than men. For example, at a hs-cTnI concentration of 10 ng/L, the hazard ratio relative to the limit of blank was 9.7 (95% CI 7.6–12.4) and 5.6 (95% CI 4.7–6.6) for women and men, respectively. The hazard ratio for hs-cTnT at a concentration of 10 ng/L relative to the limit of blank was 3.7 (95% CI 3.1–4.3) and 2.2 (95% CI 2.0–2.5) for women and men, respectively. Conclusions Cardiac troponin concentrations differ in women and men and are stronger predictors of cardiovascular events in women. Sex-specific approaches are required to provide equivalent risk prediction.

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ show that cTn in the circulation has a half-life of less than one hour the kinetics of cTn after myocardial infarction 20 is likely dominated by its slow and necrotic volume-dependent release and does not serve as a way to study cTn clearance. From our previous studies we know that cTn is cleared in the kidneys in humans 2,20 but no other information concerning cTn clearance in humans exist.…”

Section: Discussionmentioning

confidence: 99%

The Liver and Kidneys mediate clearance of cardiac troponin in the rat

Muslimović

Fridén

Tenstad

et al. 2020

Sci Rep

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Cardiac-specific troponins (cTn), troponin T (cTnT) and troponin I (cTnI) are diagnostic biomarkers when myocardial infarction is suspected. Despite its clinical importance it is still not known how cTn is cleared once it is released from damaged cardiac cells. The aim of this study was to examine the clearance of cTn in the rat. A cTn preparation from pig heart was labeled with fluorescent dye or fluorine 18 (18 F). The accumulation of the fluorescence signal using organ extracts, or the 18 F signal using positron emission tomography (PET) was examined after a tail vein injection. The endocytosis of fluorescently labeled cTn was studied using a mouse hepatoma cell line. Close to 99% of the cTnT and cTnI measured with clinical immunoassays were cleared from the circulation two hours after a tail vein injection. The fluorescence signal from the fluorescently labeled cTn preparation and the radioactivity from the 18F-labeled cTn preparation mainly accumulated in the liver and kidneys. The fluorescently labeled cTn preparation was efficiently endocytosed by mouse hepatoma cells. In conclusion, we find that the liver and the kidneys are responsible for the clearance of cTn from plasma in the rat. Cardiac troponin (cTn) is a ternary complex consisting of three distinct subunits: cardiac troponin T (cTnT), cardiac troponin I (cTnI) and cardiac troponin C (cTnC). cTn binds thin filaments within the cardiomyocyte sarcomere and, with tropomyosin, makes muscular contraction dependent on calcium ions 1. Both cTnT and cTnI are released into the circulation following cardiac damage 2 and are the preferred cardiac biomarkers when myocardial infarction (MI) is suspected 3. The use of cTn assays with low diagnostic cutoffs improve diagnostic accuracy for MI on the emergency departments 4,5 and reduce hospital spending 6. However, low diagnostic cutoffs have been accompanied by an accumulation of patients presenting with stable cTn levels above the accepted cutoff point without MI 7,8. A third of older emergency department patients without MI on emergency departments have stable cTn elevations 7 , often for unknown reasons 9 , and are generally admitted to have their workup done 6,10. Even if MI can be excluded during the hospital stay, patients with stable cTn elevations still constitute a significant health care problem, as a stable cTn elevation is a strong risk factor for the development of heart disease and death 11-14. The reason behind stable cTn elevations, where sample-to-sample variation is often 10% 7 but can be as large as 40-50% 15 , is still unclear but is typically found at old age, in patients with decreased renal function or with comorbidities 10. It is possible that, in addition to necrosis, cTnT and cTnI are also released from living cardiomyocytes under ischemic stress 16 and possibly from normal cardiomyocytes as well 17. To understand the possible mechanisms that link stable cTn elevations to mortality, we need to know how cTn is released and cleared from the circulation 10,18,19. Surprisingly little is know...

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A Possible Mechanism behind Faster Clearance and Higher Peak Concentrations of Cardiac Troponin I Compared with Troponin T in Acute Myocardial Infarction

Cited by 33 publications

References 35 publications

The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients

The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients

Sex Differences in Cardiac Troponin I and T and the Prediction of Cardiovascular Events in the General Population

The Liver and Kidneys mediate clearance of cardiac troponin in the rat

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