Longitudinal Studies of Cardiac Troponin I in a Large Cohort of Healthy Children

Koerbin, Gus; Potter, Julia M.; Abhayaratna, Walter P.; Telford, Richard D.; Badrick, Tony; Apple, Fred S.; Jaffe, Allan S.; Hickman, Peter E.

doi:10.1373/clinchem.2012.192054

Cited by 32 publications

(21 citation statements)

References 27 publications

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“…Apple and Collinson found that the short-term CV i was 15% (20 ), whereas Goldberg et al found that the shortterm CV i was 24% but the longer-term CV i (over 9 days) was 80% (21 ). A study looking at biological variation over several years in 453 healthy children found that the median CV i was 33% (13 ). Other than the study from Goldberg et al, these results are remarkably consistent in establishing that cTnI is an analyte with a small index of individuality.…”

Section: Discussionmentioning

confidence: 76%

Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values

Simpson¹,

Potter

Koerbin

et al. 2014

Clinical Chemistry

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BACKGROUND Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. METHODS We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CVT) and, knowing the assay analytical CV (CVA), we could calculate within-person biological variation (CVi), reference change values (RCVs), and absolute RCV delta cTnI concentrations. RESULTS We had data sets on 283 patients. Men and women had similar CVi values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5–17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. CONCLUSIONS With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.

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Section: Discussionmentioning

confidence: 76%

Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values

Simpson¹,

Potter

Koerbin

et al. 2014

Clinical Chemistry

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“…No studies found significant gender-related differences in cTnI values of pediatric age subjects (Table 2 and Figure 2) [15,33,34,50]. On the other hand, adult males usually present cTnI values that are, on average, twofold higher than those in women; in this age group, the calculated 99th URL values are strongly gender-dependent [14,29,49].…”

Section: Gendermentioning

confidence: 95%

“…concentration values higher than the LoD value of 1.3 ng/L) were clearly evidenced in more than 85% of a population of apparently healthy children (ages ranging from birth to adulthood) when a highly sensitive method was used for troponin measurement [15,33,34]. cTnI levels, at their highest in the first few weeks of life, tended to gradually decrease up to adulthood [15] (Table 2 and Figure 2).…”

Section: Agementioning

confidence: 98%

“…A more satisfactory definition of differences in cTnI circulating levels according to gender and age is now available thanks to the highly sensitive method using the ARCHITECT platform, able to measure biomarker values above the LoD value in the majority of healthy subjects from the day of birth to senescence [14,15,33,34,[49][50][51]. No studies found significant gender-related differences in cTnI values of pediatric age subjects (Table 2 and Figure 2) [15,33,34,50].…”

Section: Gendermentioning

confidence: 99%

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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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“…In recent years, technical improvements have led to the development of highsensitivity assays that are capable of measuring low concentrations of cardiac troponin with high precision. With such assays, we are now able to measure cardiac troponin in the serum of healthy individuals, including children, who have no evidence of cardiovascular disease (2)(3)(4). The advent of high-sensitivity assays has uncovered sexspecific differences in circulating cardiac troponin concentrations that were formerly unrecognized because previous assays could not measure cardiac troponin with sufficient precision at or below the 99th percentile.…”

confidence: 99%

Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction

et al. 2016

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BACKGROUND: High-sensitivity cardiac troponin I (hscTnI) assays show sex-dependent differences in the 99th percentile of healthy populations, with concentrations in women approximately 50% lower. The adoption of sex-specific cutoffs seems appropriate, although it is not yet clear what effect these will have on acute myocardial infarction (AMI) diagnosis and management. METHODS:We conducted a retrospective pre-and postchangeover analysis of troponin I testing in the 6 months before and after moving from the contemporary Abbott Architect TnI assay (cTnI) to hs-cTnI at 2 tertiary centers in Australia and New Zealand. The cTnI cutoff was 30 ng/L for both sexes, whereas a female-specific cutoff of 16 ng/L was adopted upon changeover to hsTnI. RESULTS:Changeover from the cTnI assay to the hs-cTnI assay increased the number of female patients with increased troponin I concentrations at both sites (from 29.7% to 34.9% and from 22.4% to 30.8%; P Ͻ 0.001). There was no statistically significant change in the number of men with increased concentrations in the same time period (P ϭ 0.09). The increased percentage of women with increased troponin I was not associated with an increase in the number of women with AMI diagnoses at either center. Angiographic data available from 1 center showed no change in the percentage of angiograms performed in women. CONCLUSIONS:Although increasing the proportion of women with increased troponin I, adopting sex-specific cutoffs with the hs-cTnI assay did not lead to an increase in AMI diagnoses in females, or in the number of women undergoing angiography. © 2016 American Association for Clinical ChemistryCardiac troponins are the preferred biomarkers for the detection of myocardial injury, and a rise and/or fall above the 99th percentile is an integral part of the universal consensus definition for diagnosis of acute myocardial infarction (AMI) 8 (1 ). In recent years, technical improvements have led to the development of highsensitivity assays that are capable of measuring low concentrations of cardiac troponin with high precision. With such assays, we are now able to measure cardiac troponin in the serum of healthy individuals, including children, who have no evidence of cardiovascular disease (2-4 ). The advent of high-sensitivity assays has uncovered sexspecific differences in circulating cardiac troponin concentrations that were formerly unrecognized because previous assays could not measure cardiac troponin with sufficient precision at or below the 99th percentile. It is now clear that the 99th percentile is substantially lower in females than it is in males (2,(5)(6)(7). Accordingly, several laboratories have implemented sex-specific reference intervals for cTnI, although the clinical impact is as yet unclear.The revelation of sex-dependent differences in circulating cardiac troponin raises several questions regarding the interpretation of cardiac troponin in women, and its possible downstream clinical effects. These are particularly pertinent given the large body of evidence suggest...

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Longitudinal Studies of Cardiac Troponin I in a Large Cohort of Healthy Children

Abstract: BACKGROUND:There is little information available on cardiac troponin concentrations in healthy young children.

Cited by 32 publications

References 27 publications

Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values

Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values

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

Impact of High-Sensitivity Troponin I Testing with Sex-Specific Cutoffs on the Diagnosis of Acute Myocardial Infarction

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