High-sensitivity cardiac troponin I in the general population – defining reference populations for the determination of the 99th percentile in the Gutenberg Health Study

AbstractThe 99th percentile of cardiac troponin levels, determined in a reference population, is accepted as threshold for diagnosis of acute myocardial infarction (AMI). However, there is no common consensus of how to define the reference population. The aim of the present study was to determine 99th percentile reference values, determined by a high-sensitivity assay (hsTnI), according to different health status and cardiovascular risk factor prevalence in a large population-based sample.Troponin I was determined using the Abbott ARCHITECT STAT highly sensitive troponin I immunoassay in 4138 participants of the Gutenberg Health Study.hsTnI was detectable in 81.6% of all individuals. The 99th percentile of the overall population was 27 ng/L. Age and gender had a prominent influence on these values. Exclusion of individuals with elevated natriuretic peptide levels or cardiac abnormalities resulted in lower 99th percentile values, whereas exclusion of individuals with an impaired estimated glomerular filtration rate (eGFR) or with prevalent coronary artery disease/myocardial infarction (CAD/MI) did not result in a meaningful change.Troponin I, measured by a high-sensitivity assay, can be reliably detected in the vast majority of the general population. hsTnI values were dependent on age, gender as well as structural and functional cardiac abnormalities.

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Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population

10.1101/2020.09.04.20187401 ◽

2020 ◽

Author(s):

Marta R Moksnes ◽

Helge Røsjø ◽

Anne Richmond ◽

Magnus N Lyngbakken ◽

Sarah E Graham ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

General Population ◽

Cardiac Troponin ◽

Troponin I ◽

Mendelian Randomization ◽

Cardiac Troponin I ◽

Health Study

AbstractCirculating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further used two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction and heart failure.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1283 phecodes and 274 continuous traits in UK Biobank showed associations between a polygenic risk score for cTnI and cardiac arrhythmias, aspartate aminotransferase 1 and anthropometric measures. Excluding individuals with a known history of comorbidities did not materially change associations with cTnI. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction (5 948 cases, 355 246 controls). We found some indications for a causal role of cTnI in heart failure (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals).Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for acute myocardial infarction and heart failure development in the general population. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population.

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Impact of Sex on the Prognostic Value of High-Sensitivity Cardiac Troponin I in the General Population: The HUNT Study

Clinical Chemistry ◽

10.1373/clinchem.2014.234369 ◽

2015 ◽

Vol 61 (4) ◽

pp. 646-656 ◽

Cited By ~ 56

Author(s):

Torbjørn Omland ◽

James A de Lemos ◽

Oddgeir L Holmen ◽

Håvard Dalen ◽

Jūratė Šaltytė Benth ◽

...

Keyword(s):

General Population ◽

Cardiac Troponin ◽

Prognostic Value ◽

Troponin I ◽

High Sensitivity ◽

Reference Interval ◽

Cardiovascular Death ◽

Cardiac Troponin I ◽

Health Study ◽

High Concentrations

Abstract BACKGROUND A new, high-sensitivity assay for cardiac troponin I (hs-cTnI) permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying pathophysiological mechanisms and prognostic implications are unclear. The aim of this study was to assess the potential impact of sex on the association between hs-cTnI and cardiovascular death. METHODS By use of the Architect STAT High-Sensitive Troponin assay, we measured hs-cTnI in 4431 men and 5281 women aged ≥20 years participating in the prospective observational Nord-Trøndelag Health Study (HUNT). RESULTS hs-cTnI was detectable in 98.5% of men and 94.7% of women. During a mean follow-up period of 13.9 years, 708 cardiovascular deaths were registered. hs-cTnI was associated with the incidence of cardiovascular death [adjusted hazard ratio (HR) per 1 SD in log hs-cTnI 1.23 (95% CI 1.15–1.31)], with higher relative risk in women than men [HR 1.44 (1.31–1.58) vs 1.10 (1.00–1.20); Pinteraction < 0.001]. This finding was mediated by both lower risk associated with low hs-cTnI concentrations in women than in men and higher risk associated with high concentrations of hs-cTnI in women than in men. Male sex was associated with a higher risk of cardiovascular death [HR 1.28 (1.11–1.49)], but after adjustment for hs-cTnI, this association disappeared [HR 0.87 (0.75–1.02)]. CONCLUSIONS The prognostic value of hs-cTnI concentrations in the general population is stronger in women than in men. Subtle impairment of cardiovascular status may contribute to higher hs-cTnI concentrations in men, reflecting sex-dependent differences in cardiovascular risk.

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Association of high-sensitivity assayed troponin I with cardiovascular phenotypes in the general population: the population-based Gutenberg health study

Clinical Research in Cardiology ◽

10.1007/s00392-013-0640-8 ◽

2013 ◽

Vol 103 (3) ◽

pp. 211-222 ◽

Cited By ~ 25

Author(s):

Christoph Sinning ◽

◽

Till Keller ◽

Tanja Zeller ◽

Francisco Ojeda ◽

...

Keyword(s):

General Population ◽

Troponin I ◽

High Sensitivity ◽

Population Based ◽

Health Study ◽

Gutenberg Health Study

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1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study

Diabetes ◽

10.2337/db19-1461-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1461-P

Author(s):

PAUL WELSH ◽

DAVID PREISS ◽

ARCHIE CAMPBELL ◽

DAVID J. PORTEOUS ◽

NICHOLAS L. MILLS ◽

...

Keyword(s):

General Population ◽

Cardiac Troponin ◽

Troponin I ◽

Troponin T ◽

Family Health ◽

Incident Diabetes ◽

Health Study ◽

Cardiac Troponin T ◽

Generation Scotland

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Faculty Opinions recommendation of One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725420089.793507697 ◽

2015 ◽

Author(s):

Patrick Ray

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Rule Out

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Acceptable Analytical Variation May Exceed High-Sensitivity Cardiac Troponin I Cutoffs in Early Rule-Out and Rule-In Acute Myocardial Infarction Algorithms

Clinical Chemistry ◽

10.1373/clinchem.2016.255448 ◽

2016 ◽

Vol 62 (6) ◽

pp. 887-889 ◽

Cited By ~ 36

Author(s):

Peter A Kavsak ◽

Andrew C Don-Wauchope ◽

Stephen A Hill ◽

Andrew Worster

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Analytical Variation ◽

Rule Out

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Clinical Use of a New High-Sensitivity Cardiac Troponin I Assay in Patients with Suspected Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2019.304725 ◽

2019 ◽

Vol 65 (11) ◽

pp. 1426-1436 ◽

Cited By ~ 12

Author(s):

Jasper Boeddinghaus ◽

Raphael Twerenbold ◽

Thomas Nestelberger ◽

Luca Koechlin ◽

Desiree Wussler ◽

...

Keyword(s):

Myocardial Infarction ◽

Diagnostic Accuracy ◽

Cardiac Troponin ◽

Troponin I ◽

Clinical Performance ◽

High Sensitivity ◽

Primary Objective ◽

Cardiac Troponin I ◽

Primary Analysis ◽

Derivation Cohort

Abstract BACKGROUND We aimed to validate the clinical performance of the high-sensitivity cardiac troponin I [VITROS® Immunodiagnostic Products hs Troponin I (hs-cTnI-VITROS)] assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists considering all clinical information, including cardiac imaging: first, using serial hs-cTnT-Elecsys (primary analysis) and, second, using hs-cTnI-Architect (secondary analysis) measurements in addition to the clinically used (hs)-cTn. hs-cTnI-VITROS was measured at presentation and at 1 h in a blinded fashion. The primary objective was direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI-VITROS vs hs-cTnT-Elecsys and hs-cTnI-Architect, and in a subgroup also hs-cTnI-Centaur and hs-cTnI-Access. Secondary objectives included the derivation and validation of an hs-cTnI-VITROS-0/1-h algorithm. RESULTS AMI was the adjudicated final diagnosis in 158 of 1231 (13%) patients. At presentation, the AUC for hs-cTnI-VITROS was 0.95 (95% CI, 0.93–0.96); for hs-cTnT-Elecsys, 0.94 (95% CI, 0.92–0.95); and for hs-cTnI-Architect, 0.92 (95% CI, 0.90–0.94). AUCs for hs-cTnI-Centaur and hs-cTnI-Access were 0.95 (95% CI, 0.94–0.97). Applying the derived hs-cTnI-VITROS-0/1-h algorithm (derivation cohort n = 519) to the validation cohort (n = 520), 53% of patients were ruled out [sensitivity, 100% (95% CI, 94.1–100)] and 14% of patients were ruled in [specificity, 95.6% (95% CI, 93.4–97.2)]. Patients ruled out by the 0/1-h algorithm had a survival rate of 99.8% at 30 days. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI-Architect. CONCLUSIONS The hs-cTnI-VITROS assay has at least comparable diagnostic accuracy with the currently best validated hs-cTnT and hs-cTnI assays. ClinicalTrials.gov Identifier NCT00470587.

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P5595Clinical effect of sex-specific cutoff values of high-sensitivity cardiac troponin I in suspected myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehy566.p5595 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

M Rubini Gimenez ◽

P Badertscher ◽

R Twerenbold ◽

J Boeddinghaus ◽

T Nestelberger ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Cutoff Values

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PD41 Use Of High-Sensitivity Cardiac Troponin Assays In Real-Practice Within Emergency Departments

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462318003082 ◽

2018 ◽

Vol 34 (S1) ◽

pp. 143-143

Author(s):

Marco Marchetti ◽

Laura Camoni ◽

Luz Irene Urbina ◽

Alessia Biondi ◽

Tiziana Grassi ◽

...

Keyword(s):

Myocardial Infarction ◽

Real World ◽

Emergency Departments ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Real World Data ◽

Multicenter Observational Study ◽

Number Of Patients ◽

Rule Out

Introduction:Acute myocardial infarction (AMI) is one of the leading causes of death and disability worldwide. The European Society of Cardiology Guidelines have established a new definition of myocardial infarction and have strengthened the central role of cardiac troponins in cardiology diagnostics for rule-in and rule-out of non ST-elevation myocardial infarction (NSTEMI). High-sensitivity cardiac troponin I assays (hsTnI) should increase diagnostic sensitivity, and a shorter interval for ruling-in and ruling-out AMI. This analysis aims to provide an overview of the clinical, economic, organizational and ethical impact of the use of hsTnI in clinical practice of Emergency Departments (ED) in Italy.Methods:HsTnl for rule-in and rule-out of AMI in the ED is being evaluated using the EUnetHTA Core Model® framework for health technology assessment. The hsTnI HTA assessment will be completed with real-world evidence derived from a multicenter observational study which has been designed to be conducted in 12 Italian EDs, enrolling 6000 patients with chest pain of suspected cardiac origin, aiming to provide data from the Italian context on clinical, organizational and economic aspects of the use of the test in the ED. Endpoints of the study include: time lapses related to diagnosis, admission, treatment and discharge of patients; number of tests performed; and number of patients diagnosed with AMI.Results:Initial results from a literature review confirm the usefulness of the hsTnI assay in diagnosing AMI. Generated real-world data will be collected, analyzed and integrated to existing evidence to assess the utility of the test in real contexts, providing details relevant for organizational aspects of the use of the test in the ED.Conclusions:The use of hsTnl could improve diagnosis of AMI by allowing a faster ruling-in or ruling-out, and reducing inappropriate hospitalizations. Furthermore, this technology could represent an opportunity to reduce overall costs for the healthcare system.

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