Analytical Validation of a High-Sensitivity Cardiac Troponin T Assay

BackgroundSubclinical myocardial injury, as measured by high‐sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus.Methods and ResultsWe randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT‐proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1–Q3) plasma concentration was 35.4 (15.7–86.3) ng/L for NT‐proBNP and 6.7 (4.6–10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT‐proBNP concentration was 20.7% (7.9–35.0) in the insulin arm compared with 0.13% (−10.8 to 12.5) in the no‐insulin arm (P=0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT‐proBNP was 7.8% (−3.7 to 20.7) compared with 13.0% (0.72–26.8) in the no‐metformin arm (P=0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms.ConclusionsInsulin glargine was associated with a significant 20.7% increase in NT‐proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301.

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“…The 10% coefficient of variation is less than this value 21, 22. In total, 93.2% of participants had hsTnT ≥3 ng/L.…”

Section: Methodsmentioning

confidence: 85%

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Srivastava

Pradhan

Cook

et al. 2017

JAHA

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“…Regarding the highly sensitive cTnT ECLIA method, variability among the 99th URL values reported in different studies and by manufacturers is very similar (Table 5) [9,12,26,41,124,[126][127][128]. Considering as a whole the clinical studies including a total of 10,078 individuals [9,12,26,47,124,[126][127][128], median (25th-75th percentiles) values of 99th URL results of highly sensitive cTnT ECLIA method are for the overall population 14.6 (13.2-18.0) ng/L, for men 16.0 (15.0-19.5) ng/L, and for women 12.0 (9.6-12.5) ng/L, respectively.…”

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

confidence: 83%

“…Considering as a whole the clinical studies including a total of 10,078 individuals [9,12,26,47,124,[126][127][128], median (25th-75th percentiles) values of 99th URL results of highly sensitive cTnT ECLIA method are for the overall population 14.6 (13.2-18.0) ng/L, for men 16.0 (15.0-19.5) ng/L, and for women 12.0 (9.6-12.5) ng/L, respectively. The results reported by Gaggin et al [128], including data related to two different populations (i.e.…”

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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“…[3] Miyokard enfarktüsü tanısının konulmasında troponin de¤erinin 0.014 ng/mL'nin üstünde olması en önemli parametrelerdendir. [4][5][6] Miyokard enfarktüsü geçiren hastaların ço¤unda düük yo¤unluklu lipoprotein (LDL) ve yüksek yo¤unluklu lipoprotein (HDL) de¤erlerine ait sorunlarda bulunabilmektedir. [7,8] Bu bilgilere dayanarak, troponin de¤eri 0.014 ng/mL'nin üstünde ve altında olan olguların LDL ve HDL de¤erleri arasında fark olup/olmadı¤ının gösterilmesinin amaçlandı¤ı bu çalıma planlandı.…”

Section: öZunclassified

“…Veriler troponin düzeyinin 0.014 ng/mL'nin [4][5][6] altında veya üstünde olmasına göre iki gruba ayrıldı. Olguların LDL, HDL ve trigliserid de¤erlerinin troponin gruplarına göre normal da¤ılıma uygunlu¤u Shapiro Wilk testiyle de¤erlendirildi.…”

Section: Hastalar Ve Yöntemlerunclassified

Evaluation of the effect size of low-density lipoprotein, high-density lipoprotein, and triglyceride levels of patients detected to have high troponin

Vehid¹

2018

FNG & Bilim Tıp Dergisi

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Objectives: This study aims to investigate the known methods showing whether there is any difference between low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride values based on troponin values being under or above 0.014 ng/mL in cases suspected of a diagnosis of myocardial infarction (MI) and the effect size of such values. Patients and methods:The study included 256 patients (135 males, 121 females; mean age 62.4±15.2 years; range, 46 to 78 years) who applied to the emergency department between 01 January 2013 and 31 December 2013 with suspected MI. Since the patients' data were not applicable for normal distribution, Box-Cox transformation was performed on the LDL, HDL, and triglyceride data. Confidence intervals and effect sizes of the data were evaluated to show if there is any difference between the two data groups created according to a troponin value under or above 0.014 ng/mL. Results: While comparison of the two Box-Cox transformed data groups did not demonstrate any difference in terms of LDL or triglyceride values, it revealed a difference in terms of HDL values. When the Box-Cox transformed data were transformed to their real values and reevaluated, the effect size was d=0.8356 and g=0.8331. Conclusion:In medical studies, no statistically significant difference is observed between the obtained evaluation results and the transformed evaluation results when data are not applicable for normal distribution. However, optimization of data for normal distribution through transformation is essential since this will allow other evaluations such as confidence interval and effect size, in particular, that assist in a more definite interpretation of any difference between the data of two independent groups. Keywords: High-density lipoprotein cholesterol; low-density lipoprotein cholesterol; triglyceride; troponin.Evaluation of the effect size of low-density lipoprotein, high-density lipoprotein, and triglyceride levels of patients detected to have high troponin

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Analytical Validation of a High-Sensitivity Cardiac Troponin T Assay

Abstract: BACKGROUND:We report the development of a novel high-sensitivity cardiac troponin T (hs-cTnT) assay, a modification of the Roche fourth-generation cTnT assay, and validation of the analytical performance of this assay.

Cited by 976 publications

References 21 publications

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis

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

Evaluation of the effect size of low-density lipoprotein, high-density lipoprotein, and triglyceride levels of patients detected to have high troponin

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