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

2018 ◽  
Vol 56 (5) ◽  
pp. 685-696 ◽  
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.

scholarly journals High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2386-2394 ◽  
Author(s):  
Jan F. Scheitz ◽  
Guillaume Pare ◽  
Lesly A. Pearce ◽  
Hardi Mundl ◽  
W. Frank Peacock ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Embolic Stroke ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
End Point ◽  
Upper Reference Limit

Background and Purpose: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. Methods: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. Results: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41–1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25–0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification ( P =0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment ( P =0.3). Conclusions: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02313909.

scholarly journals The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States

2020 ◽  
Vol 504 ◽  
pp. 172-179
Author(s):  
Robert L. Fitzgerald ◽  
Judd E. Hollander ◽  
W. Frank Peacock ◽  
Alexander T. Limkakeng ◽  
Nancy Breitenbeck ◽  
...  
Keyword(s):  
United States ◽  
Cardiac Troponin ◽  
Troponin T ◽  
The United States ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
Upper Reference Limit

scholarly journals 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

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Rainer Haeckel ◽  
Werner Wosniok ◽  
Antje Torge ◽  
Ralf Junker ◽  
_ _
Keyword(s):  
Detection Limit ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Present Report ◽  
Age Groups ◽  
Specific Reference ◽  
Cardiac Troponin T ◽  
Decision Limit ◽  
Reference Limits ◽  
Age And Sex

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.

scholarly journals Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e052004
Author(s):  
Alexander Dietl ◽  
Martina E Zimmermann ◽  
Caroline Brandl ◽  
Stefan Wallner ◽  
Ralph Burkhardt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Troponin T ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Cardiac Troponin T ◽  
Cross Sectional ◽  
Reference Limit ◽  
Mobile Population ◽  
Upper Reference Limit

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference distribution and to assess the specificity of the 14 ng/L cut-off value in the mobile population ≥70 years of age.DesignA cross-sectional analysis was performed in the German AugUR study (Altersbezogene Untersuchungen zur Gesundheit der University of Regensburg).SettingStudy population was the mobile population aged 70+ years living in the city and county of Regensburg, Germany.ParticipantsA random sample was derived from the local population registries of residence. Of the 5644 individuals invited, 1133 participated (response ratio=20.1%). All participants came to the study centre and were mentally and physically mobile to conduct the protocol (face-to-face interview, blood draw and standardised transthoracic echocardiography). None of the participants was in an acute state of myocardial infarction.ResultsAmong the 1129 individuals with hsTnT measurements (overall median=10.0 ng/L(25th, 75th percentile)=(7.0, 15.0 ng/L)), hsTnT was higher among the older individuals and higher among men (men 70–74 years median=9.6 ng/L (7.2, 13.1 ng/L); men 90–95 years median=21.2 ng/L (14.6, 26.0 ng/L); women 70–74 years median=6.3 ng/L (4.7, 8.7 ng/L); and women 90–95 years median=18.0 ng/L (11.0, 21.0 ng/L)). In participants with impaired kidney function (eGFRcrea <60 mL/min/1.73 m2), hsTnT was elevated (median=13.6 ng/L (9.4, 20.6 ng/L)).Specificity of recommended upper reference limit, 14 ng/L, is 68%. Most false positives were among men aged >79 years (specificity=34%). In a healthy subgroup (n=96, none of the following: overt heart disease, impaired renal function, blood pressure >160/100 mm Hg, left ventricular hypertrophy and diastolic/systolic dysfunction), specificity was 90%.ConclusionIn the elderly population without acute myocardial infarction, hsTnT further increases with age showing different levels for men and women. The specificity of the 14 ng/L cut-off is considerably lower than 99%, even in healthy subjects.

Measurement of Serum Troponin T, Creatine Kinase MB Isoenzyme, and Total Creatine Kinase following Arduous Physical Training

1995 ◽  
Vol 32 (5) ◽  
pp. 450-453 ◽  
Author(s):  
Paul O Collinson ◽  
Henry A Chandler ◽  
Peter J Stubbs ◽  
David S Moseley ◽  
David Lewis ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Physical Training ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Myocardial Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
Creatine Kinase Mb ◽  
Upper Reference Limit

We have compared measurement of cardiac troponin T by enzyme linked immunosorbent assay with creatine kinase MB isoenzyme (CK-MB) concentration measurement in 219 Royal Marine commandos with no evidence of cardiovascular disease who have elevated creatine kinase (CK) produced by arduous physical training. CK was elevated up to 22.6 times and CK-MB mass up to 6.6 times the upper reference limit. Only two commandos had detectable cardiac troponin T, with neither exceeding the upper reference limit of 0.2 μg/L. At decision thresholds optimized for diagnosis of acute myocardial infarction in previous published work, 58.3% of the total CK activity, 13.8% of the CK-MB concentration/CK activity ratio and 1.6% of CK-MB concentration measurements showed elevated values but no elevations in cardiac troponin T occurred. Cardiac troponin T is currently the investigation of choice for the differential diagnosis of patients with an elevated CK due to skeletal muscle trauma to exclude myocardial damage.

Estimation of age- and comorbidities-adjusted percentiles of high-sensitivity cardiac troponin T levels in the elderly

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Nils Kuster ◽  
Karine Monnier ◽  
Gregory Baptista ◽  
Anne-Marie Dupuy ◽  
Stéphanie Badiou ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Rating Scale ◽  
Troponin T ◽  
High Sensitivity ◽  
The Elderly ◽  
Elderly Subjects ◽  
Reference Limit ◽  
Reactive Protein ◽  
Ctnt Level ◽  
Upper Reference Limit

AbstractCardiac troponin level measured by high-sensitivity assays (hs-cTn) in the elderly is frequently found higher than the 99th percentile upper reference limit, making the diagnosis of acute coronary syndromes (ACS) difficult. This study aimed at: 1) identifying determinants of hs-cTnT levels in an unselected population of elderly subjects; and 2) assessing the prognosis value of increased hs-cTnT in elderly people free of ACS.Hs-cTnT was measured in 591 individuals aged over 65 years without suspicion of ACS. Comorbidities were assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). C-reactive protein, αAge, gender, cardiac CIRS-G, estimated glomerular filtration rate (p<0.001 for all), albumin (p<0.028) and αHs-cTnT level is associated with inflammation and renal function in the elderly. Independently of comorbidities, hs-cTnT concentration increases exponentially with age after 65 years. Decision limits adapted to age and sex may be useful to patient management.

Cardiac troponin assays: a review of quantitative point-of-care devices and their efficacy in the diagnosis of myocardial infarction

2015 ◽  
Vol 53 (5) ◽  
Author(s):  
Beret E. Amundson ◽  
Fred S. Apple
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Troponin ◽  
Point Of Care ◽  
Hospital Costs ◽  
Sample Type ◽  
Clinical Sensitivity ◽  
Reference Limit ◽  
Negative Results ◽  
Analytical Imprecision ◽  
Upper Reference Limit

AbstractCardiac troponin (cTn) I and T are released from myocardial cells following necrosis, i.e., cell death. An accurate measure of cTn concentrations in a patient’s blood following ischemia/chest pain can enable providers to determine whether or not a myocardial infarction (MI) has occurred. Point-of-care (POC) devices that measure blood cTn concentrations in under 30 min may help to significantly reduce hospital costs by managing and triaging patients out of the emergency department as quickly as possible. The use of POC devices that measure cTnI and cTnT with a coefficient of variation (CV) ≤20% at the 99th percentile upper reference limit (URL) limits both false positive and negative results and provides clinically acceptable findings to assist in appropriate diagnoses. This article reviews nine POC devices that measure cTn in terms of their clinical sensitivity and specificity, analytical imprecision, sample type and preparation, and each assay’s principle of analysis.

scholarly journals High‐Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke

2021 ◽  
Author(s):  
Jan F. Scheitz ◽  
Jess Lim ◽  
Leonie H. A. Broersen ◽  
Ramanan Ganeshan ◽  
Shufan Huo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cardiac Troponin ◽  
Primary Outcome ◽  
Troponin T ◽  
High Sensitivity ◽  
Hazard Ratio ◽  
Cardiac Troponin T ◽  
Vascular Events ◽  
Reference Limit ◽  
Upper Reference Limit

Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high‐sensitivity cardiac troponin T (hs‐cTnT) are associated with recurrent vascular events and death in patients with first‐ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS‐B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs‐cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all‐cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs‐cTnT above upper reference limit, 39.2%). During a mean follow‐up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all‐cause death. The primary outcome occurred more often in patients with hs‐cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3–3.3), with a dose‐response relationship when the highest and lowest hs‐cTnT quartiles were compared (15.2 versus 1.8 events per 100 person‐years; adjusted hazard ratio, 4.8; 95% CI, 1.9–11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs‐cTnT is dose‐dependently associated with an increased risk of recurrent vascular events and death within 3 years after first‐ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs‐cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01363856.

scholarly journals Cardiac Troponin T Release after Football 7 in Healthy Children and Adults

2020 ◽  
Vol 17 (3) ◽  
pp. 956 ◽  
Author(s):  
Rafel Cirer-Sastre ◽  
Alejandro Legaz-Arrese ◽  
Francisco Corbi ◽  
Isaac López-Laval ◽  
Juan José Puente-Lanzarote ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin T ◽  
Football Players ◽  
Cardiac Troponin T ◽  
Healthy Children ◽  
Training Experience ◽  
Exercise Load ◽  
Reference Limit ◽  
Exercise Induced ◽  
Upper Reference Limit

The objective of this study was to compare the release of cardiac troponin T (cTnT) after a football 7 match between two cohorts of children and adult players. Thirty-six male football players (children = 24, adult = 12) played a football 7 match, and cTnT was measured before, and 3 h after exercise. Concentrations of cTnT were compared between groups and time, and correlated with participants’ characteristics, as well as internal and external exercise load. Cardiac troponin T was elevated in all participants (p < 0.001), and exceeded the upper reference limit for myocardial infarction in 25 (~70%) of them. Baseline concentrations were higher in adults (p < 0.001), but the elevation of cTnT was comparable between the groups (p = 0.37). Age (p < 0.001), body mass (p = 0.001) and height (p < 0.001), and training experience (p = 0.001) were associated to baseline cTnT values, while distance (p < 0.001), mean speed (p < 0.001), and peak (p = 0.013) and mean (p = 0.016) heart rate were associated to the elevation of cTnT. The present study suggests that a football 7 match evoked elevations of cTnT during the subsequent hours in healthy players regardless of their age. However, adults might present higher resting values of cTnT than children. In addition, results suggest that the exercise-induced elevations of cTnT might be mediated by exercise load but not participant characteristics.

scholarly journals Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy

2018 ◽  
Vol 64 (9) ◽  
pp. 1370-1379 ◽  
Author(s):  
Peder L Myhre ◽  
Torbjørn Omland ◽  
Sebastian I Sarvari ◽  
Heikki Ukkonen ◽  
Frank Rademakers ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Wall Motion ◽  
Troponin T ◽  
Left Ventricular ◽  
Reference Limit ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Perfusion Defects ◽  
Stable Cad ◽  
Upper Reference Limit

Abstract BACKGROUND Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8–11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (&gt;14 ng/L). Patients with hs-cTnT &gt;14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P &lt; 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P &lt; 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

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