Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study

Abstract BACKGROUND Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. METHODS A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. RESULTS Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7–3.2) for hs-cTnI and 1.8 (95% CI, 1.3–2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2–2.2) for hs-cTnI and 2.3 (95 % CI, 1.7–3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. CONCLUSIONS Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.

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Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

Clinical Chemistry ◽

10.1373/clinchem.2013.206441 ◽

2014 ◽

Vol 60 (1) ◽

pp. 158-164 ◽

Cited By ~ 58

Author(s):

Erin A Bohula May ◽

Marc P Bonaca ◽

Petr Jarolim ◽

Elliott M Antman ◽

Eugene Braunwald ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Cardiovascular Death ◽

Cardiac Troponin I ◽

Fourth Generation ◽

Prognostic Performance ◽

Coronary Syndrome ◽

Low Concentrations ◽

Increased Risk

Abstract BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.

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P3648Detailed temporal patterns of high-sensitivity-cardiac troponin I and T during long-term follow-up after acute coronary syndrome

European Heart Journal ◽

10.1093/eurheartj/ehx504.p3648 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

V.J. Van Den Berg ◽

V.A.W.M. Umans ◽

K.M. Akkerhuis ◽

R.M. Oemrawsingh ◽

F.W. Asselbergs ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Cardiac Troponin ◽

Troponin I ◽

High Sensitivity ◽

Temporal Patterns ◽

Cardiac Troponin I ◽

Coronary Syndrome ◽

Long Term Follow Up

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Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0350 ◽

2017 ◽

Vol 56 (1) ◽

Cited By ~ 15

Author(s):

Giuseppe Lippi ◽

Anna Ferrari ◽

Giorgio Gandini ◽

Matteo Gelati ◽

Claudia Lo Cascio ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

Limit Of Detection ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Analytical Performance ◽

The Novel ◽

Reference Limit ◽

Automated Immunoassay ◽

Upper Reference Limit

AbstractBackground:This study was aimed to evaluate the analytical performance of the novel chemiluminescent and fully-automated Beckman Coulter Access hsTnI high-sensitivity immunoassay for measurement of cardiac troponin I (cTnI).Methods:The study, using lithium heparin samples, included assessment of limit of blank (LOB), limit of detection (LOD), functional sensitivity, linearity, imprecision (within run, between-run and total), calculation of 99th percentile upper reference limit (URL) in 175 healthy blood donors (mean age, 36±12 years; 47% women) and comparison with two other commercial cTnI immunoassays.Results:The LOB, LOD and functional sensitivity of Access hsTnI were 0.14, 0.34 and 1.35 ng/L, respectively. The within-run, between-run and total imprecision was 2.2%–2.9%, 4.6%–5.4%, and 5.4%–6.1%, respectively. The linearity was excellent in the range of cTnI values between 0.95 and 4195 ng/L (r=1.00). The 99th percentile URL was 15.8 ng/L. Measurable cTnI values were found in 173/175 healthy subjects (98.9%). Good agreement of cTnI values was found with AccuTnI+3 (r=0.97; mean bias, −9.3%), whereas less satisfactory agreement was found with Siemens Dimension Vista cTnI (r=0.95; mean bias, −55%).Conclusions:The results of our evaluation of the Beckman Coulter Access hsTnI indicate that the analytical performance of this fully-automated immunoassay is excellent.

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Temporal Evolution of Serum Concentrations of High‐Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission

Journal of the American Heart Association ◽

10.1161/jaha.120.017393 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Victor J. van den Berg ◽

Rohit M. Oemrawsingh ◽

Victor A. W. M. Umans ◽

Isabella Kardys ◽

Folkert W. Asselbergs ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Cardiac Troponin ◽

Troponin I ◽

Temporal Evolution ◽

High Sensitivity ◽

Interindividual Variation ◽

Mixed Effect ◽

Reference Limit ◽

Coronary Syndrome ◽

Upper Reference Limit

Background Detailed insights in temporal evolution of high‐sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post‐ACS kinetics of high‐sensitivity cardiac troponin I (hs‐cTnI) and high‐sensitivity cardiac troponin T (hs‐cTnT), and to determine their intra‐ and interindividual variation in clinically stable patients. Methods and Results We determined hs‐cTnI (Abbott) and hs‐cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1‐year follow‐up. Post‐ACS kinetics were studied by linear mixed‐effect models. Using the samples collected in the 6‐ to 12‐month post‐ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs‐cTnI and average hs‐cTnT concentration, and the intra‐ and interindividual variation for both biomarkers. Compared with hs‐cTnT, hs‐cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P <0.001) and was quicker below the biomarker‐specific upper reference limit (16 versus 19 days; P <0.001). In the post–6‐month samples, hs‐cTnI and hs‐cTnT showed modest correlation ( r spearman =0.60), whereas the average hs‐cTnT concentration was 5 times more likely to be above the upper reference limit than hs‐cTnI. The intraindividual variations of hs‐cTnI and hs‐cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs‐cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post–6‐month samples, hs‐cTnI and hs‐cTnT were clearly not interchangeable, and average hs‐cTnT concentrations were much more often above the upper reference limit than hs‐cTnI. For both markers, the within‐patient variation fell largely below beween‐patient variation. Registration URL: https://www.trialregister.nl ; unique identifiers: NTR1698 and NTR1106.

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Potential impact of a novel pathway for suspected myocardial infarction utilising a new high-sensitivity cardiac troponin I assay

Emergency Medicine Journal ◽

10.1136/emermed-2020-210812 ◽

2021 ◽

pp. emermed-2020-210812

Author(s):

Rob Meek ◽

Louise Cullen ◽

Zhong Xian Lu ◽

Arthur Nasis ◽

Lisa Kuhn ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Limit Of Detection ◽

High Sensitivity ◽

Routine Care ◽

Primary Objective ◽

Cardiac Troponin I ◽

Post Discharge ◽

Reference Limit

BackgroundHigh-sensitivity cardiac troponin I (hs-cTnI) assays promise high diagnostic accuracy for myocardial infarction (MI). In an ED where conventional cTnI was in use, we evaluated an assessment pathway using the new Access hsTnI assay.MethodsThis retrospective analysis recruited ED patients with suspected MI between June and September 2019. All patients received routine care with a conventional cTnI assay (AccuTnI +3: limit of detection (LoD) 10 ng/L, 99th centile upper reference limit (URL) 40 ng/L, abnormal elevation cut-point 80 ng/L). Arrival, then 90-minute or 360-minute cTnI levels for low and non-low risk patients, respectively (ED Assessment of Chest pain score) guided diagnosis and disposition which was at treating physician discretion. The same patients had arrival and 90-minute or 180-minute samples drawn for hs-cTnI levels (Access hsTnI: LoD 2 ng/L, 99th centile URL 10 ng/L (females) and 20 ng/L (males); abnormal elevation above the URL and delta >30%). Treating physicians were blinded to the hs-cTnI results. Using the hs-cTnI values, investigators retrospectively assigned likely diagnosis, disposition and likelihood of a 30-day major adverse cardiac event (MACE). Admission was recommended for significantly rising hs-cTnI elevations. The primary objective was to demonstrate an acceptable unexpected 30-day post-discharge MACE rate of <1%. cTnI elevation rates, diagnostic outcomes and ED disposition were also compared between pathways.ResultsFor the 935 patients, unexpected 30-day post-discharge MACE rates were 0/935 (0%, 95% CI 0% to 0.4%) with the conventional or novel pathway. For the high-sensitivity and conventional assays, respectively, abnormal elevation rates were 29% (95% CI 26% to 32%) and 19% (95% CI 17% to 22%), for MI were 9% (95% CI 8% to 11%) and 8% (95% CI 6% to 10%), and for hospital admission were 42% (95% CI 39% to 45%) and 43% (95% CI 40% to 47%).ConclusionThe novel pathway using the Access hsTnI assay has an acceptably low 30-day MACE rate.

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Prognostic implications of detectable cardiac troponin I below the 99th percentile in patients admitted to an emergency department without acute coronary syndrome

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-1140 ◽

2018 ◽

Vol 56 (11) ◽

pp. 1954-1961 ◽

Cited By ~ 5

Author(s):

Alfredo Bardají ◽

Gil Bonet ◽

Anna Carrasquer ◽

Maribel González-del Hoyo ◽

Fernando Domínguez ◽

...

Keyword(s):

Emergency Department ◽

Acute Coronary Syndrome ◽

Cardiac Troponin ◽

Troponin I ◽

Total Mortality ◽

Reference Population ◽

Multivariate Regression Analysis ◽

Reference Limit ◽

Coronary Syndrome

Abstract Background: Detectable troponin below the 99th percentile may reflect an underlying cardiac abnormality which might entail prognostic consequences. This study aimed to investigate the prognosis of patients admitted to an emergency department (ED) with detectable troponin below the 99th percentile reference limit who did not present with an acute coronary syndrome (ACS). Methods: We analysed the clinical data of all consecutive patients admitted to the ED during the years 2012 and 2013 in whom cardiac troponin was requested by the attending clinician (cTnI Ultra Siemens, Advia Centaur). Patients with troponin below the 99th percentile of the reference population (40 ng/L) and who did not have a diagnosis of ACS were selected, and their mortality was evaluated in a 2-year follow-up. Results: A total of 2501 patients had a troponin level below the reference limit, with 43.9% of those showing detectable levels (>6 ng/L and <40 ng/L). Patients with detectable levels were elderly and had a higher prevalence of cardiovascular history and more comorbidities. The total mortality in the 2-year follow-up was 12.4% in patients with detectable troponin and 4.5% in patients with undetectable troponin (p<0.001). In the Cox multivariate regression analysis, the detectable troponin was an independent marker of mortality at 2 years (HR 1.62, 95% CI 1.07–2.45, p=0.021). Conclusions: Detectable troponin I below the 99th percentile is associated with higher mortality risk at 2-year follow-up in patients admitted to the ED who did not present with ACS.

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Cardiac Troponin Assays: Guide to Understanding Analytical Characteristics and Their Impact on Clinical Care

Clinical Chemistry ◽

10.1373/clinchem.2016.255109 ◽

2017 ◽

Vol 63 (1) ◽

pp. 73-81 ◽

Cited By ~ 142

Author(s):

Fred S Apple ◽

Yader Sandoval ◽

Allan S Jaffe ◽

Jordi Ordonez-Llanos

Keyword(s):

Clinical Practice ◽

Cardiac Troponin ◽

Troponin I ◽

Limit Of Detection ◽

Troponin T ◽

Clinical Care ◽

High Sensitivity ◽

Reference Population ◽

Limit Of Quantification ◽

Coronary Syndrome

Abstract BACKGROUND Cardiac troponin I (cTnI) and cardiac troponin T (cTnT) determinations are fixtures in clinical practice and research. Cardiac troponin testing has been the standard of practice for the diagnosis of acute myocardial infarction (AMI), early rule-out, risk stratification, and outcomes assessment in patients presenting with acute coronary syndrome (ACS) and non-ACS myocardial injury. We recognize from reading the literature over the past several years how poorly understood the analytical characteristics are for cTnI and cTnT assays by laboratorians, clinicians, and scientists who use these assays. CONTENT The purposes of this mini-review are (a) to define limit of blank, limit of detection, limit of quantification, and imprecision, (b) overview the analytical characteristics of the existing cardiac troponin assays, (c) recommend approaches to define a healthy (normal) reference population for determining the 99th percentile and the appropriate statistic to use for this calculation, (d) clarify how an assay becomes designated as “high sensitivity,” and (e) provide guidance on determining delta (Δ) change values. SUMMARY This review raises important educational information regarding cTnI and cTnT assays, their 99th percentile upper reference limits (URL) differentiated by sex, and specifically addresses high-sensitivity (hs)-assays used to measure low concentrations. Recommendations are made to help clarify the nomenclature and analytical and clinical characteristics to define hs-assays. The review also identifies challenges for the evolving implementation of hs-assays into clinical practice. It is hoped that with the introduction of these concepts, laboratorians, clinicians and researchers can develop a more unified view of how these assays should be used worldwide.

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Evaluating Rapid Rule-out of Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay at Presentation

Clinical Chemistry ◽

10.1373/clinchem.2017.283887 ◽

2018 ◽

Vol 64 (5) ◽

pp. 820-829 ◽

Cited By ~ 15

Author(s):

Jaimi Greenslade ◽

Elizabeth Cho ◽

Christopher Van Hise ◽

Tracey Hawkins ◽

William Parsonage ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin I ◽

Limit Of Detection ◽

High Sensitivity ◽

Cardiac Troponin I ◽

Coronary Syndrome ◽

Number Of Patients ◽

Rule Out

Abstract BACKGROUND Low concentrations of cardiac troponin (cTn) have been recommended for rapid rule-out of acute myocardial infarction (AMI). We examined the Beckman Coulter Access high-sensitivity cardiac troponin I (hs-cTnI) assay to identify a single test threshold that can safely rule out AMI. METHODS This analysis used stored samples collected in 2 prospective observational studies. In all, 1871 patients presenting to a tertiary emergency department with symptoms of acute coronary syndrome had blood taken for measurement of cTnI on presentation. The endpoint was type 1 myocardial infarction (T1MI). Sensitivity and negative predictive value (NPV) were calculated for hs-cTnI values below the 99th percentile. RESULTS Ninety-eight patients had T1MI (5.2%), and 638 (34.1%) patients had an hs-cTnI <2 ng/L (limit of detection), with sensitivity of 99.0% (95% CI, 94.4%–100%) and NPV of 99.8% (95% CI, 99.1%–100%). No hs-cTnI value above a concentration of 2 ng/L achieved sensitivity of 99%. However, an NPV of 99.5% was achieved at values <6 ng/L. A cutoff <6 ng/L enabled 1475 (78.8%) patients to be ruled out on presentation with sensitivity of 93.9% (95% CI, 87.1%–97.7%). CONCLUSIONS A single baseline cTn <2 ng/L measured with the Access hs-cTnI assay performed well for rule-out of AMI. This cutoff concentration identified 99% of patients with AMI and could reduce the number of patients requiring lengthy assessment. A cutoff of <6 ng/L yielded a high NPV but missed more cases of AMI than would be acceptable to clinicians.

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Convalescent troponin and cardiovascular death following acute coronary syndrome

Heart ◽

10.1136/heartjnl-2019-315084 ◽

2019 ◽

Vol 105 (22) ◽

pp. 1717-1724 ◽

Cited By ~ 7

Author(s):

Philip D Adamson ◽

David McAllister ◽

Anna Pilbrow ◽

John William Pickering ◽

Katrina Poppe ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Cardiac Troponin ◽

Troponin I ◽

Prognostic Significance ◽

High Sensitivity ◽

Cardiovascular Death ◽

Therapeutic Interventions ◽

Coronary Syndrome ◽

Increased Risk

ObjectivesHigh-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome.MethodsIn a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death.ResultsTroponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7).ConclusionsConvalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions.Trial registration numberACTRN12605000431628;Results.

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Long-Term Health Outcomes Associated with Detectable Troponin I Concentrations

Clinical Chemistry ◽

10.1373/clinchem.2006.076885 ◽

2007 ◽

Vol 53 (2) ◽

pp. 220-227 ◽

Cited By ~ 53

Author(s):

Peter A Kavsak ◽

Alice M Newman ◽

Viliam Lustig ◽

Andrew R MacRae ◽

Glenn E Palomaki ◽

...

Keyword(s):

Troponin I ◽

Limit Of Detection ◽

Hospital Discharges ◽

Men And Women ◽

Coronary Syndrome ◽

Kaplan Meier ◽

Increased Risk ◽

Frozen Plasma

Abstract Background: Recent data suggest that older men with detectable cardiac troponin I (cTnI) concentrations that remain below the 99th percentile concentration cutoff are at increased risk for subsequent cardiovascular events. We designed this study to extend this observation by examining risk prediction in both men and women presenting to an emergency department with chest discomfort. Methods: We obtained data for all-cause mortality and hospital discharges associated with either acute myocardial infarction (AMI) or congestive heart failure (CHF) for up to 8 years after the initial presentation in 448 patients who originally presented in 1996 with acute coronary syndrome (ACS). We performed retrospective analysis for cTnI (AccuTnI™; Beckman Coulter) in frozen plasma samples based on the patients’ reported time from onset of symptoms. Peak cTnI concentration was used for risk assessment. Results: Patients with cTnI concentrations ≥0.02 μg/L (i.e., limit of detection), including those whose peak values remained below the 99th percentile (0.04 μg/L), were at greater risk for death and AMI/CHF readmissions at 2, 5, and 8 years of follow-up compared with those with peak cTnI <0.02 μg/L. All results were statistically significant (P <0.05) except for death within 2 years among patients with normal but detectable cTnI (0.02 to 0.03 μg/L), relative to the group with values <0.02 μg/L. Kaplan–Meier analyses indicated that both men and women with cTnI ≥0.02 μg/L had worse outcomes (P <0.001). Conclusion: Both men and women who present with possible ACS with detectable cTnI concentrations that remain below the 99th percentile are at a greater risk for future adverse events.

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