Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction

Klinkenberg, Lieke J.J.; Wildi, Karin; Linden, Naomi van der; Kouw, Imre W. K.; Niens, Marijke; Twerenbold, Raphael; Giménez, María Rubini; Puelacher, Christian; Neuhaus, Jean Daniel; Hillinger, Petra; Nestelberger, Thomas; Boeddinghaus, Jasper; Grimm, Karin; Sabti, Zaid; Bons, J; Suijlen, Jeroen D.E. van; Tan, Frans E. S.; Kate, Joop ten; Bekers, Otto; Dieijen-Visser, Marja P. van; Meex, Steven J.R.

doi:10.1373/clinchem.2016.257485

Cited by 78 publications

(91 citation statements)

References 29 publications

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“…The mechanism of chronic cardiac troponin release is not elucidated, but recent observations suggest differences in release patterns of cardiac troponin T and I. [36] Third, postrelease modification such as fragmentation, complex formation, and elimination of cardiac troponins may differ between both cardiac troponins. [37,38] …”

Section: Discussionmentioning

confidence: 99%

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population

et al. 2016

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“…Another possible explanation may be related to the rhythmic diurnal variation of hs-cTnT, which shows higher levels in the morning and at nighttime and lower levels during the day. [22][23][24] While rhythmic diurnal variation is characteristic for hs-cTnT, it has not been observed in hs-cTnI.…”

Section: Difference Between Hs-ctnt and Hs-ctnimentioning

confidence: 99%

High‐Sensitivity Cardiac Troponin After Cardiac Stress Test: A Systematic Review and Meta‐Analysis

Samaha

Avila

Helwani

et al. 2019

JAHA

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Background-The recent introduction of high-sensitivity cardiac troponin (hs-cTn) assays has allowed clinicians to measure hs-cTn before and after cardiac stress testing, but the hs-cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta-analysis to improve our understanding of hs-cTn release associated with exercise and pharmacological stress testing. Methods and Results-Studies published between January 2008 and July 2016 that reported hs-cTn change values (highsensitivity cardiac troponin T [hs-cTnT] or high-sensitivity cardiac troponin I [hs-cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs-cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta-analysis included 11 studies (n=2432 patients). After exercise stress testing, hs-cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs-cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs-cTnT by 1.1 ng/L or 18% (8 studies, n=629; P=0.29) and hs-cTnI by 1.8 ng/L or 72% (4 studies, n=831; P=0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs-cTnT changed by À0.1 ng/L or À0.4% (6 studies, n=251) and hs-cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs-cTnT by 0.7 ng/L or 11% (5 studies, n=443, P=0.44) and hs-cTnI by 1.7 ng/L or 38% (2 studies, n=116; P=0.62) in patients who did not develop inducible myocardial ischemia. Conclusions-hs-cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.

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“…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)

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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.

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Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction

Abstract: 1. Circadian Variation of Cardiac Troponin, NCT02091427, www.clinicaltrials.gov/ct2/show/NCT02091427. 2. Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) Study, NCT00470587, www.clinicaltrials.gov/ct2/show/NCT00470587.

Cited by 78 publications

References 29 publications

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population

High‐Sensitivity Cardiac Troponin After Cardiac Stress Test: A Systematic Review and Meta‐Analysis

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

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