Reference limits of high-sensitive cardiac troponin T indirectly estimated by a new approach applying data mining. A special example for measurands with a relatively high percentage of values at or below the detection limit

AbstractA new model for the indirect estimation of reference limits (RLs) has been proposed recently and was coined TMC approach (truncated minimum chi-square estimation) which can be performed with R statistic. A spline function is applied to the RLs to get a continuous function if age is graphically presented vs. the RLs avoiding artificial “jumps” between different age groups. Most indirect models assume a power normal distribution and fail if this assumption is not fulfilled as e.g. if a relatively high percentage of measured values is below the detection limit and the data are distributed extremely skewed. This problem is handled by the TMC model. High-sensitive cardiac troponin T (hs cTnT) was chosen as an example. The hs cTnT concentration in serum or plasma is well accepted as a valuable marker in the diagnosis of acute myocardial infarction. Currently, the 99th percentile derived from a “healthy” subpopulation is the decision limit recommended by consensus groups. However, this decision limit is questioned by several authors for many reasons. In the present report, the 97.5th and the 99th percentile limits were reinvestigated by the TMC model with different subpopulations stratified according to age and sex and were finally compared to presently recommended decision limits. In summary, the generally recommended 99th percentile as a fixed decision limit should be reconsidered. It is suggested to apply more specific reference limits stratified for age and sex instead of a fixed decision limit.

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Age- and Sex-Dependent Upper Reference Limits for the High-Sensitivity Cardiac Troponin T Assay

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2013.12.032 ◽

2014 ◽

Vol 63 (14) ◽

pp. 1441-1448 ◽

Cited By ~ 183

Author(s):

M. Odette Gore ◽

Stephen L. Seliger ◽

Christopher R. deFilippi ◽

Vijay Nambi ◽

Robert H. Christenson ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin T ◽

High Sensitivity ◽

Cardiac Troponin T ◽

Reference Limits ◽

Age And Sex

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Upper Reference Limits of High-Sensitivity Cardiac Troponin T in a General Population: Comparison with those of Sensitive Cardiac Troponin I

Clinical Laboratory ◽

10.7754/clin.lab.2012.120230 ◽

2013 ◽

Vol 59 (03+04/2013) ◽

Cited By ~ 7

Author(s):

Camille Chenevier-Gobeaux ◽

Sophie Bailleul ◽

Alexandre Mzabi ◽

Marie-Céline Blanc ◽

Guillaume Lefevre

Keyword(s):

General Population ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Cardiac Troponin T ◽

Population Comparison ◽

Reference Limits

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Revisited Upper Reference Limits for Highly Sensitive Cardiac Troponin T in Relation to Age, Sex, and Renal Function

Journal of Clinical Medicine ◽

10.3390/jcm10235508 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5508

Author(s):

Christiane Gärtner ◽

Romy Langhammer ◽

Maria Schmidt ◽

Martin Federbusch ◽

Kerstin Wirkner ◽

...

Keyword(s):

Renal Function ◽

Cardiac Troponin ◽

Troponin T ◽

Large Population ◽

Population Based ◽

Cardiac Diseases ◽

Cardiac Troponin T ◽

Reference Limit ◽

Highly Sensitive ◽

Reference Limits

(1) Background: Highly sensitive cardiac troponin T (hs-cTnT) plays an essential role in the diagnosis of myocardial injury. The upper reference limit of the respective assay is generally applied, irrespective of age, renal function, or sex. We aimed to identify age-adjusted and sex-adjusted upper reference limits in relation to renal function in a large population-based cohort without cardiac diseases. (2) Methods: We included 5428 subjects of the population-based LIFE-Adult cohort, free of diagnosed cardiac diseases. Sex-adjusted and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained. (3) Results: The hs-cTnT values were higher in men of all age groups. In both sexes, an increasing age positively correlated with higher hs-cTnT values. Hs-cTnT weakly correlated with serum creatinine. The three-dimensional analysis of age, creatinine, and hs-cTnT showed no relevant additional effect of creatinine on hs-cTnT. In men aged above 60 and women above 70, the calculated 99th percentiles clearly exceeded the commonly applied thresholds. (4) Conclusion: Age and sex have a major impact on the serum concentration of hs-cTnT, while renal function does not. We propose to consider age-adjusted and sex-adjusted reference values.

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Determination of age- and sex-specific 99th percentiles for high-sensitive troponin T from patients: an analytical imprecision- and partitioning-based approach

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0256 ◽

2018 ◽

Vol 56 (5) ◽

pp. 685-696 ◽

Cited By ~ 10

Author(s):

Denis Monneret ◽

Martin Gellerstedt ◽

Dominique Bonnefont-Rousselot

Keyword(s):

Cardiac Troponin ◽

Polynomial Regression ◽

Troponin T ◽

Age Groups ◽

Reference Limit ◽

Proportion Method ◽

Analytical Imprecision ◽

Upper Reference Limit ◽

Age And Sex

AbstractBackground:Detection of acute myocardial infarction (AMI) is mainly based on a rise of cardiac troponin with at least one value above the 99th percentile upper reference limit (99th URL). However, circulating high-sensitive cardiac troponin T (hs-cTnT) concentrations depend on age, sex and renal function. Using an analytical imprecision-based approach, we aimed to determine age- and sex-specific hs-cTnT 99th URLs for patients without chronic kidney disease (CKD).Methods:A 3.8-year retrospective analysis of a hospital laboratory database allowed the selection of adult patients with concomitant plasma hs-cTnT (<300 ng/L) and creatinine concentrations, both assayed twice within 72 h with at least 3 h between measurements. Absence of AMI was assumed when the variation between serial hs-cTnT values was below the adjusted-analytical change limit calculated according to the inverse polynomial regression of analytical imprecision. Specific URLs were determined using Clinical and Laboratory Standards Institute (CLSI) methods, and partitioning was tested using the proportion method, after adjustment for unequal prevalences.Results:After outlier removal (men: 8.7%; women: 6.6%), 1414 men and 1082 women with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2were assumed as non-AMI. Partitioning into age groups of 18–50, 51–70 and 71–98 years, the hs-cTnT 99th URLs adjusted on French prevalence were 18, 33, 66 and 16, 30, 84 ng/L for men and women, respectively. Age-partitioning was clearly required. However, sex-partitioning was not justified for subjects aged 18–50 and 51–70 years for whom a common hs-cTnT 99th URLs of about 17 and 31 ng/L could be used.Conclusions:Based on a laboratory approach, this study supports the need for age-specific hs-cTnT 99th URLs.

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Kinetics, Moderators and Reference Limits of Exercise-Induced Elevation of Cardiac Troponin T in Athletes: A Systematic Review and Meta-Analysis

Frontiers in Physiology ◽

10.3389/fphys.2021.651851 ◽

2021 ◽

Vol 12 ◽

Author(s):

Feifei Li ◽

Will G. Hopkins ◽

Xuejing Wang ◽

Julien S. Baker ◽

Jinlei Nie ◽

...

Keyword(s):

Systematic Review ◽

Cardiac Troponin ◽

Troponin T ◽

Meta Analysis ◽

Exercise Duration ◽

Cardiac Troponin T ◽

Reference Ranges ◽

Reference Limits ◽

The Mean ◽

Exercise Induced

Background: Kinetics, moderators and reference limits for exercise-induced cardiac troponin T (cTnT) elevations are still unclear.Methods: A systematic review of published literature was conducted adhering to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies reporting high-sensitivity cardiac troponin T (hs-cTnT) concentrations before and after a bout of exercise in athletes were included and analyzed. The final dataset consisted of 62 estimates from 16 bouts in 13 studies of 5–1,002 athletes (1,421 in total). Meta-analysis was performed using general linear mixed modeling and Bayesian inferences about effect magnitudes. Modifying fixed-effect moderators of gender, age, baseline level, exercise duration, intensity and modalities were investigated. Simulation was used to derive 99th percentile with 95% limits of upper reference ranges for hs-cTnT of athletic populations.Results: The mean and upper reference limits of hs-cTnT before exercise were 4.4 and 19 ng.L−1. Clear increases in hs-cTnT ranging from large to very large (factor changes of 2.1–7.5, 90% compatibility limits, ×/÷1.3) were evident from 0.7 through 25 h, peaking at 2.9 h after the midpoint of a 2.5-h bout of running, when the mean and upper reference limit for hs-cTnT were 33 and 390 ng L−1. A four-fold increase in exercise duration produced a large clear increase (2.4, ×/÷1.7) in post-exercise hs-cTnT. Rowing exercise demonstrated an extremely large clear reduction (0.1 ×/÷2.4).Conclusions: The kinetics of cTnT elevation following exercise, the positive effect of exercise duration, the impact of exercise modality and 99th upper reference limits for athletic populations were reasonably well defined by this meta-analysis.

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