Time-Dependent Degradation Pattern of Cardiac Troponin T Following Myocardial Infarction

Cardinaels, Eline P.M.; Mingels, Alma M.A.; Rooij, Tom van; Collinson, Paul; Prinzen, Frits W.; Dieijen-Visser, Marja P. van

doi:10.1373/clinchem.2012.200543

Cited by 84 publications

(58 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, based on their molecular weight, free cTnT (37 kDa), free cTnI (24 kDa), and their fragments may be (partly) filtered by the glomeruli and catabolized by the tubules (25,26 ). Indeed, after myocardial infarction, cTnT and cTnI have been observed as free cTnT and cTnI, larger cTnT-I-C (77 kDa) and cTnI-C (40 kDa) complexes, and fragments (27)(28)(29)(30)(31). In contrast, in renal failure, cTnT circulates primarily as fragments (32 ), whereas the circulating form of cTnI in renal failure is unknown.…”

Section: Discussionmentioning

confidence: 99%

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study

et al. 2017

Self Cite

View full text Add to dashboard Cite

BACKGROUND Chronic kidney disease (CKD) is associated with an increased cardiovascular disease mortality risk. It is, however, less clear at what point in the course from normal kidney function to CKD the association with cardiovascular disease appears. Studying the associations of estimated glomerular filtration rate (eGFR) and albuminuria with biomarkers of (subclinical) cardiac injury in a population without substantial CKD may clarify this issue. METHODS We examined the cross-sectional associations of eGFR and urinary albumin excretion (UAE) with high-sensitivity cardiac troponin (hs-cTn) T, hs-cTnI, and N-terminal probrain natriuretic-peptide (NT-proBNP) in 3103 individuals from a population-based diabetes-enriched cohort study. RESULTS After adjustment for potential confounders, eGFR and UAE were associated with these biomarkers of cardiac injury, even at levels that do not fulfill the CKD criteria. For example, eGFR 60–<90 mL · min−1 ·(1.73 m2)−1 [vs ≥90 mL · min−1 · (1.73 m2)−1] was associated with a [ratio (95% CI)] 1.21 (1.17–1.26), 1.14 (1.07–1.20), and 1.19 (1.12–1.27) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. The association of eGFR with hs-cTnT was statistically significantly stronger than that with hs-cTnI. In addition, UAE 15–<30 mg/24 h (vs <15 mg/24 h) was associated with a 1.04 (0.98–1.10), 1.08 (1.00–1.18), and 1.07 (0.96–1.18) times higher hs-cTnT, hs-cTnI, and NT-proBNP, respectively. CONCLUSIONS eGFR and albuminuria were already associated with biomarkers of (subclinical) cardiac injury at levels that do not fulfill the CKD criteria. Although reduced renal elimination may partly underlie the associations of eGFR, these findings support the concept that eGFR and albuminuria are, over their entire range, associated with cardiac injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…One possibility is that the fast clearance of Myo and CK may result from extensive local degradation, because many clinical assays do not detect degraded CK. In contrast, the clinical cTnT assay recognizes several degradation products (20 ) that could prolong the apparent clearance of cTnT.…”

Section: Discussionmentioning

confidence: 99%

Revision of the Troponin T Release Mechanism from Damaged Human Myocardium

Starnberg¹,

Jeppsson

Lindahl

et al. 2014

Clinical Chemistry

View full text Add to dashboard Cite

BACKGROUND Cardiac troponin T (cTnT) is released from damaged heart tissue in patients with acute myocardial infarction. It is presumed that most cTnT is tightly bound and released following the degradation of myofibrils in necrotic cardiomyocytes, resulting in sustained increases in circulating cTnT. Evidence of a large irreversibly bound fraction is based on the inability to extract most cTnT from cardiac tissue in cold low-salt extraction buffers. METHODS Here we examined in vitro extraction of cTnT from human cardiac tissue in serum at 37 °C. RESULTS We found that over 80% of the cTnT can be extracted from human cardiac tissue in 90 min using large volumes of human serum at 37 °C. The release ratio was highly dependent on the extraction volume and was only 3% if an equal volume of serum and heart tissue was used. In contrast, extraction of the cytoplasmic cardiac damage markers myoglobin and creatinine kinase was much less affected by changing these conditions. Purified cTnT was poorly soluble in a low-salt extraction buffer at 0 °C, previously used to define the free cTnT fraction. CONCLUSIONS Our data indicate that the diffusible fraction of cTnT is likely substantially larger in vivo than previously reported and likely is not fixed but dependent on local plasma flow. It is therefore possible that the sustained increase in circulating cTnT after myocardial infarction is at least in part due to a slow washout of cTnT that interacts reversibly with tropomyosin in myofibrils.

show abstract

“…Furthermore, since cTnI and cTnT are present in the sarcomeric complex in a molecular ratio of 1:1, these differences between the circulating cTns are probably related to differences in intra- [130] or extra-cellular [131][132][133] catabolism and the peripheral turnover of cTnI and cTnT. A recent study [134] found that circulating levels of cTnT, unlike cTnI, have a diurnal rhythm, thus bearing out the hypothesis that there are some differences in the release from cardiomyocytes and/or peripheral turnover between cTnI and cTnT.…”

Section: Do Differences In Troponin-dependent 99th Url Values Depend mentioning

confidence: 99%

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Clerico

Zaninotto

Ripoli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision ≤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/ calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines.

show abstract

Time-Dependent Degradation Pattern of Cardiac Troponin T Following Myocardial Infarction

Cited by 84 publications

References 33 publications

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study

Estimated Glomerular Filtration Rate and Albuminuria Are Associated with Biomarkers of Cardiac Injury in a Population-Based Cohort Study: The Maastricht Study

Revision of the Troponin T Release Mechanism from Damaged Human Myocardium

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Contact Info

Product

Resources

About