The Global Need to Define Normality: The 99th Percentile Value of Cardiac Troponin

Sandoval, Yader; Apple, Fred S.

doi:10.1373/clinchem.2013.211706

Cited by 141 publications

(102 citation statements)

References 44 publications

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“…the criteria for considering the reference population "healthy") [17,[25][26][27][28][29], but also on the analytical performances of cTn methods, as well as on the mathematical algorithms used for calculating the 99th URL [10,14,15,17,18,25,26].…”

Section: Criteria For Calculating 99th Url Valuesmentioning

confidence: 99%

“…The approach for selecting a reference population for calculating the 99th percentile value for cTn assays has not yet been adequately defined [17]. The Third Universal Definition of Myocardial Infarction [3] reported that gender-dependent values might be recommended for highly sensitive troponin assays without specifying criteria for considering a population "healthy".…”

Section: Criteria For Selecting Reference Populationmentioning

confidence: 99%

“…10% CV) [NaN]. The Architect method can also detect cTnI levels that exceed LoD in more than 85% of healthy subjects including children and adolescents [14,15], as requested by some consensus documents [16][17][18]. These data, shown in Table 1 and Figure 1, clearly indicate that the Architect method has the analytical performance required for a true highly sensitive method for cTnI assay.…”

Section: Introductionmentioning

confidence: 98%

“…Only after 2006 some manufacturers set-up the first new generation of cTnI and cTnT immunoassays with improved analytical sensitivity in accordance with the quality specifications indicated in international guidelines and consensus documents [4,[6][7][8][9][10][11][12][13][14][15][16]. Importantly, highly sensitive methods should also be able to measure troponin levels in the majority of healthy adults subjects (>50%), as suggested in some consensus documents [16][17][18]. In order to measure the extremely low circulating levels of the biomarker in all healthy subjects, a highly sensitive method for cTnI or cTnT should have a low detection limit greatly lower than 5 ng/L [8].…”

Section: Introductionmentioning

confidence: 99%

“…Currently few methods able to completely meet the quality specifications recommended by international guidelines are commercially available for cTn assay [9,[16][17][18]. In one case, for example the manufacturer reports that the limit of blank (LoB) and limit of detection (LoD) for the highly sensitive cTnT method are 2.…”

Section: Introductionmentioning

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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Section: Criteria For Calculating 99th Url Valuesmentioning

confidence: 99%

Section: Criteria For Selecting Reference Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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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Acute Coronary Syndrome

Thadani¹,

Nguyen²,

Han³

2016

Management of Complex Cardiovascular Problems

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Determination of high‐sensitivity cardiac troponin T upper reference limits under the improved selection criteria in a Chinese population

Zhang

Han

Zhao

et al. 2019

Clinical Laboratory Analysis

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Background:There is no common consensus on how to define the reference population for determination of high-sensitivity cardiac troponin (hs-cTn) upper reference limit (URL). This study aimed to establish 99th percentile URLs of hs-cTnT under both 2018 AACC/IFCC criteria and improved selection criteria for further judging whether two URLs are different. Methods:Applying the stratified cluster sampling protocol, this study took 1848 apparently healthy subjects in communities of Shenyang China as the screening objects.We first followed 2018 AACC/IFCC criteria using surrogate biomarker for diabetes, myocardial dysfunction, renal dysfunction, and electrocardiogram. Then, we followed improved selection criteria to exclude hypertension, overweight and obesity, and dyslipidemia by physical examination and laboratory screening. Accordingly, 99th percentile URLs of hs-cTnT were established. Results: If the 2018 AACC/IFCC criteria were applied, 99th percentile URLs (90% confidence interval) of hs-cTnT male, female, and total were 19 (17-20) ng/L, 16 (15-17) ng/L, and 18 (16-19) ng/L, respectively. If added a single supplementary selection criteria, 99th percentile URLs of hs-cTnT total reduced to 16 ng/L, 17 ng/L, and 16 ng/L, respectively. If the improved selection criteria were applied, 99th percentile URLs (90% confidence interval) of hs-cTnT male, female, and total were 18 (14-24) ng/L, 13 (11-16) ng/L, and 16 (13-17) ng/L, respectively. The 99th percentile URLs of hs-cTnT male were higher than those of female in every age group. Conclusions: Improved selection criteria through questionnaire survey, physical examination, and laboratory screening to further exclude hypertension, overweight and obesity, and dyslipidemia can avoid overestimation of the 99th percentile URL of hs-cTnT. K E Y W O R D S 99th percentile, high-sensitivity cardiac troponin T, reference population, selection criteria This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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The Global Need to Define Normality: The 99th Percentile Value of Cardiac Troponin

Cited by 141 publications

References 44 publications

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

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

Acute Coronary Syndrome

Determination of high‐sensitivity cardiac troponin T upper reference limits under the improved selection criteria in a Chinese population

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