cTn Concentrations Research Articles

Influence of Sex and Cardiometabolic Risk Factors on the High-Sensitivity Cardiac Troponins at the Concentrations Used as the Thresholds for Cardiovascular Risk Stratification in a Presumably Healthy Polish Population

Background: Low but detectable cardiac troponin (cTn) concentrations may reflect cardiovascular (CV) risk in a primary prevention setting. Using previously described thresholds for CV risk stratification, we assessed the influence of sex and cardiometabolic risk factors on the concentrations of high-sensitivity cTn in presumably healthy subjects. Methods: The prospective study included 597 presumably healthy individuals (313 women, 284 men). In all participants, hs-cTnI, hs-cTnT, lipid profile, C-reactive protein, glycated hemoglobin, estimated GFR (eGFR) and B-type naturetic peptide (BNP) were measured. Subjects were categorized into two groups of CV risk, based on hs-cTn non sex-specific cut-off of 5.0 ng/L. For hs-cTnI, sex-specific cut-off values were also used: ≥4.0 ng/L for females and ≥6.0 ng/L for males. Results: Increased CV risk, indicated by hs-cTn concentrations ≥ 5.0 ng/L, was significantly associated with age > 40 years, male sex, obesity and BNP concentrations ≥ 35 ng/L. Using the same 5.0 ng/L threshold, hs-TnT classified approximately twice as many individuals into the CV subgroup compared to hs-cTnI, particularly in males (31% vs. 13%, respectively). After applying sex-specific cut-offs for hs-cTnI, the proportion of females and males with increased risk became similar (8% vs. 9%, respectively). In contrast, using non-sex-specific cut-offs for hs-cTnI resulted in a proportion of 6% for females and 13% for males. BNP and eGFR had significant impact on CV risk stratification using sex-specific cut-offs for hs-cTnI. Conclusions: Our findings suggest the necessity of using sex-specific cut-offs for hs-cTn as a cardiovascular risk marker, in addition to other cardiometabolic factors, in the general population.

Exercise-induced cardiac troponins in long-distance walkers: a preliminary observation.

Abstract Background Elevated concentrations of cardiac troponin (cTnT and cTnI), the preferred biomarker to diagnose myocardial infarction, can be detected in other (cardiac) conditions and even post-exercise. Whether these exercise-induced elevations reflect a (patho)physiological process, as well as their clinical implications, is unknown. In this preliminary study, pre- and post-exercise high-sensitivity cTn (hs-cTnT and hs-cTnI) concentrations were investigated in long-distance walkers. Purpose Gain insight of elevated cTnT and cTnI concentrations post-exercise in long-distance walkers. Methods From 478 participants, walking 30-50 km on the first day of the 4Daagse 2023, blood-samples were collected pre- and <6h post-exercise. In addition, health and exercise questionnaires were conducted. Hs-cTnT (Roche) and hs-cTnI (Abbott) concentrations were determined and the unisex, female and male Upper Reference Limit (URL) were according to package inserts (Roche: 14 ng/L, 9 ng/L, 16 ng/L, Abbott: 26 ng/L, 16 ng/L, 34 ng/L). Results Participants (51% female) were 57±7.6 years (mean±SD). At baseline, median [IQR] hs-cTnT and hs-cTnI were 5.9 [4.5-8.0] and 1.7 [1.1-2.9] ng/L, which increased significantly post-exercise to 8.7 [6.4-12.4] ng/L (P<0.001) and 5.2 [3.1-9.5] ng/L (P<0.001). Pre-exercise, the unisex-URL for hs-cTnT was exceeded by 4.4% walkers and for sex-specific URLs, this resulted in 6.6% females and 3.8% males. For hs-cTnI, the unisex-URL was exceeded by 0.6%, as for sex-specific URLs, 0.8% females and 1.3 % males surpassed. Post-exercise, hs-cTnT URLs were exceeded by 18.2%, 35.1%, 16.5% and as for hs-cTnI post-exercise, 7.3%, 11.6%, 3.8% for unisex, female and male. Alternatively, the absolute median delta difference was 2.4 [0.9-4.6] ng/L for hs-cTnT and 3.0 [1.6-5.7] ng/L hs-cTnI. Conclusion Post-exercise long-distance walkers had significantly increased hs-cTnT and hs-cTnI concentrations, in particular in women when using sex-specific cutoffs. In order to understand clinical implications of these findings, status of cardiac vascular diseases, risk-factors and exercise characteristics will be analyzed in the future.

Prevalence of elevated cardiac troponin in five non-cardiac diseases

Abstract Background Cardiac troponins (cTns) are regulatory proteins located in the cardiac muscle cells (cardiomyocytes). Since the 1990s, cTns have been the biochemical gold standard for detecting myocardial infarction. CTns are well studied among patients with cardiac illnesses and elevated concentrations are known to reflect myocardial injury. Still, high cTn concentrations are found in several non – cardiac conditions where signs of cardiac dysfunction are absent(1). This is especially found to be true for cardiac troponin T (cTnT) which is, more frequently than cardiac troponin I (cTnI), found to be elevated in patients with non – cardiac conditions(2,3). A study from 2016 of 1012 patients admitted to the emergency room, found troponin T elevations in 40.8% of patients without acute coronary syndrome vs. 7.4% with cTnI elevations(3). To our knowledge, no previous study has investigated cTn elevations across disease -groups where elevations of cTns are frequently detected. Purpose We aimed to investigate the prevalence of cTnT in five clinical non-cardiac disease-groups where frequent elevation of cTnT is previous described; Sepsis, rhabdomyolysis, end-stage renal disease (ESRD), stroke, and major non-cardiac surgery (MNCS). Methods Our study was a single-center prospective cross-sectional cohort study. Over a 6-month period, we included patients in the five above mentioned disease-groups. We excluded patients with any symptoms of cardiac disease or a prior history of cardiac diseases. All patients were included within 48 hours of admission and underwent clinical examination, vital signs, 12-lead electrocardiogram, echocardiography, and collections of blood samples. Cardiac troponin T was measured at patient’s bedside upon inclusion with the Cobas h232, cTnT point-of-care test. Results 89 patients were eligible for inclusion, 15 with sepsis, 18 with rhabdomyolysis, 11 with end-stage renal disease, 22 with stroke and 23 with major non-cardiac surgery. 53% were men. 17 patients (19%) had signs of cardiac disease confirmed on echocardiographic and/or electrocardiographic examinations and were excluded. Out of the 72 patients without signs of cardiac disease, elevated cTnT above the 99th percentile was found in 21 (29%) patients; 4 (36%) with sepsis, 6 (60%) with rhabdomyolysis, 4 (44%) with ESRD, 2 (9.5%) with stroke and 5 (24%) with MNCS. The median of cTnT in patients with elevated cTnT across all patient groups was 79.5 ng/L (IQR 52.5ng/L – 187.8 ng/L). Conclusions Cardiac troponin T elevations are frequent in the five non-cardiac diseases investigated. Elevations are most frequent in patients with rhabdomyolysis and end-stage renal disease. Further investigation is warranted to elucidate the underlying etiology contributing to the elevation of cardiac troponin in non-cardiac diseases.

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

A-019 Unexpectedly High Cardiac Troponin Values in Healthy Athletes after SARS-CoV-2 Infection

Abstract Background Elevated levels of cardiac troponin I or T (cTnI, cTnT) in general have immediate clinical consequences including invasive cardiac imaging and rhythm monitoring. Macro-troponin is a complex of antitroponin autoantibodies and cTnI or cTnT and may result in falsely elevated values. In athletes, a reliable exclusion of cardiac disease is crucial to allow for intensive exercise. The prevalence and causes of falsely elevated cTn in professional athletes after SARS-CoV-2 infection are unknown. Methods These are preliminary results of an observational study including 35 professional athletes (16 -75 years old, median 24 years; 19 females, 16 males) who had post-Covid-19 check-ups at their practicing sports physician mostly in the year 2022 (6 athletes in 2023). One female athlete did not have a proven SARS-CoV-2 infection but vaccination. Divergences in high sensitivity (hs) cTn concentrations were investigated according to the sex-specific cut-off values of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostics, Atellica/Siemens Healthineers, Access/Beckman Coulter and hs-cTnT: Cobas/Roche Diagnostics). All athletes were advised to stop training 48h before routine blood drawing and if required underwent electrocardiography (ECG), echocardiography and magnetic resonance imaging to exclude myocardial involvement, particularly when suspicious symptoms were present. Athletes with divergent hs-cTn assay results were further analyzed for the presence of macro-troponin using the reference method sucrose gradient ultracentrifugation. Results The two main professional sports were cycling (mountain biking or road biking) and soccer, further sports comprised curling, swimming, running including marathon, floorball, cross-country skiing or rhythmic gymnastics. Athletes mostly suffered from postviral exhaustion, mild infectious symptoms like headache, sore throat, dry cough, subfebrile temperature, or sniffles or had atypical thoracic pain. There were two males with known secondary diagnoses, one 25 years old with diabetes mellitus type 1 and one 75 years old with atherosclerosis and hypercholesterolemia. Eighteen (18/35) athletes had hs-cTn concentrations within the sex-specific cut-off values in all assays and did not undergo further investigation for macro-troponin by sucrose gradient ultracentrifugation. However, in 17 athletes (17/35) hs-cTn was increased in at least one assay method which was mostly a hs-cTnI method (for 2/17 all assays elevated). The sucrose-gradient ultracentrifugation method proved macro-troponin in 15/17 with original hs-cTn values for Abbott Alinity: 5 - 170 ng/L; Siemens Atellica: 9.6 - 376 ng/L; Beckman Access: 0.5 - 55 ng/L and Roche Cobas 4 - 77 ng/L. However, 2/17 had the free troponin form, one with only a minor hs-cTnT increase above the sex-specific cut-off and the other with increased values in all hs-cTn assays but normal values in a 2- and 4-days control follow-up measurement. Notably, there were no ECG or cardiac imaging findings including echocardiography or cardiac magnetic resonance imaging suggestive of myocarditis in the investigated athletes. Conclusions After SARS-CoV-2 infection, cTn might be increased in athletes without a correlate in ECG or imaging reports. This should prompt physicians to consider an assay interference by macro-troponin, particularly if a second troponin method such as hs-cTnT remains normal. AHL & CK share first and OH & CM share last authorship

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans.

Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

Implications of Age for the Diagnostic and Prognostic Value of Cardiac Troponin T and I.

The influence of age on cardiac troponin is unclear and may vary between cardiac troponin T (cTnT) and I (cTnI). We aimed to compare the impact of age on the diagnostic and prognostic utility of cTnT and cTnI. This Danish nationwide, register-based cohort study included patients with at least one cardiac troponin (cTn) measurement from 2009 through June 2022, stratified into decades of age. We used peak cTn concentration during admission, dichotomized as positive/negative and normalized to the 99th percentile. Receiver operating characteristics for myocardial infarction (MI) and logistic regression were used to estimate the odds ratio (OR) for mortality at 1 year. We included 541 817 patients; median age 66 years (interquartile range [IQR] 51-77) and 256 545 (47%) female. A total of 40 359 (7.4%) had an MI, and 59 800 (14.1%) patients died within 1 year of admission. The predictive ability of both cTns for MI were highest for patients 30 to 50 years. This was most pronounced for cTnT, the specificity of which fell from 83% among patients 40 to 49 years to 4% for patients ≥90 years. The prognostic ability of both cTns for 1-year mortality declined with age. cTnT had stronger prognostic ability for all age-groups; OR for a positive cTnT 28.4 (95% CI, 20.1-41.0) compared with 9.4 (95% CI, 5.0-16.7) for cTnI among patients <30 years. The predictive and prognostic ability of cTnT and cTnI declined with age. cTnT had a low specificity for MI in elderly patients. However, cTnT was the strongest prognostic marker among all age groups.

High-sensitive troponin T, suPAR and Beta-2-microglobulin changes in concentration during hemodialysis

Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by −9.9% after dialysis (95% CI: −13.6% to −6.2%). The average (paired) difference were − 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by −58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by −9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers.

Cardiac troponin concentrations following exercise and the association with cardiovascular disease and outcomes: rationale and design of the prospective TREAT cohort study

Exercise can produce transient elevations of cardiac troponin (cTn) concentrations, which may resemble the cTn release profile of myocardial infarction. Consequently, clinical interpretation of postexercise cTn elevations (ie, values above...

Hemoglobin A1c control is an independent predictor of circulating troponin concentrations using machine learning

Abstract Diabetes mellitus (DM) is associated with multiple comorbidities that may precipitate cardiac damage and elevated cardiac troponin (cTn) concentrations including renal failure, hyperlipidemia (HLD), hypertension (HTN), coronary artery disease (CAD), and congestive heart failure (CHF). Diabetics &amp;gt;70 years old have a higher likelihood of adverse outcomes including major cardiovascular events and cardiac mortality. However, the risk to younger diabetic patients and the precipitating factor(s) that facilitate cardiac injury in those with DM are unknown. The objective of this study was to investigate factors predictive of cTn concentrations in young, relatively healthy diabetic patients. We collected 1,533 remnant plasma samples from outpatients between 06/22-09/22 with physician ordered hemoglobin A1c testing. cTn was measured using the Abbott ARCHITECT High Sensitivity Troponin-I assay (limit of detection = 1.7 ng/L, imprecision = 4.76% at 50 ng/L). Demographic information (sex, race, BMI) and pertinent medical history (diabetes, HTN, HLD, CAD, CHF) were collected from the electronic medical record, along with estimated glomerular filtration rate (eGFR) and hemoglobin A1c. Exclusion criteria included: patients with missing laboratory data, those undergoing cancer treatment, or a history of myocardial infarction/cardiomyopathy/ cardiac surgery. Troponin results were classified as normal- or high-risk using a cut-off of 10 ng/L for females and 12 ng/L for males, thresholds previously shown to correlate with incidence of cardiovascular disease risk within 15 years. Univariate statistics were calculated using bootstrap resampling. An XGBoost model was trained to predict high-risk troponinemia, and summary statistics were calculated on a held-out test set. Of the 1,135 patients that met inclusion criteria, 621 (54.7%) were female. The median age was 60 years (IQR: 49-69 years) and the median A1c was 6.2% (IQR: 5.8-7.0%). A total of 746 patients (65.7%) had a prior diabetes diagnosis, with 156 patients (13.7%) having prediabetes, 42 patients (3.7%) having Type 1, and 548 patients (48.3%) having Type 2. Median troponin concentration for patients with an A1c &amp;lt;5.7% was 1.6 ng/L (IQR: 0.8-3.4), 5.7-6.4% was 2.2 ng/L (IQR:1.3-4.8), and ≥6.5% was 2.9 ng/L (IQR: 1.6-6.7). Univariate analysis demonstrated significant differences in troponinemia by age (CI of difference: 4.4-8.9 years), A1c (0.2-0.7%), and eGFR (28-38mL/min/1.73m2). The machine learning model demonstrated strong predictive capacity (sensitivity: 0.74, specificity: 0.86, PPV: 0.5, NPV: 0.92, area under ROC curve: 0.91). The features with the greatest impact on area under the ROC curve when removed were eGFR, Age, A1c, and CHF, suggesting a combination of clinical and laboratory variables can be used to predict circulating troponin concentrations in outpatients. Results of both univariate and multivariate analyses suggest that A1c control is an independent contributor to cTn concentrations. Ultimately, this study provides evidence that glucose control may be associated with cardiac damage and future cardiovascular events, warranting longitudinal outcome studies.

Cardiac troponin is a strong prognostic biomarker for patients admitted with heart failure

Abstract Background Cardiac troponin T (cTnT) and I (cTnI) are strong prognostic biomarkers in several diseases and play a key role in risk stratification of patients admitted with cardiac disease. Though viewed as equals, there are substantial differences in the biology and frequency of elevations among non-cardiac illnesses between cTnT and cTnI. A recent study of all comers with a measurement of cTn showed that the risk of mortality was highest for patients with low grade elevations of cTn, while high concentrations were associated with a paradoxical decrease in the risk. We aimed to investigate whether this pattern exists among patients with heart failure. Purpose To compare the prognostic ability of cTnT and cTnI among patients admitted with heart failure. Methods This nationwide cohort study includes patients admitted with heart failure who had cTn measurements from 2009-2022 using one of five different cTn assays: Roche high-sensitivity cTnT (hs-cTnT), Abbott Alinity high sensitivity cTnI (hs-cTnI), Siemens Vista Hs-cTnI, Siemens Atellica hs-cTnI and Beckman-Coulter hs-cTnI. We selected the peak concentration of cTn on admission and grouped patients into those with measurements of cTnI and those with cTnT. The primary outcome was all-cause mortality. We divided the peak cTn concentrations into groups based on the bands of concentrations of cTn from &amp;lt;1 times the 99th percentile, 1-2, 2-5, 5-100 and &amp;gt;100 times the 99th percentile and compared cumulative mortality using Kaplan-Meier analysis and the risk of mortality for each group using logistic regression for the 30-day mortality. Results A total of 9,344 patients were included in this study with a median age of 75 years (65-83) and 5,613 (60%) were males. Of these, 2,874 (31%) had a history of heart failure and 2,349 (25%) had a history of ischemic heart disease. When grouping for type of cTn used, there were more patients treated using hs-cTnT (n = 7,131 76%) than hs-cTnI (n = 2,213, 24%). The median age of patients treated who had a measurement of cTnI was slightly higher; 77 years (IQR 67-84) vs cTnT 74 years (64-83) p&amp;lt;0.001. Of the 9,344 patients, 1,096 (12%) died within 30 days of admission. Figure 1 shows the absolute risk of 1-year all-cause mortality for each band of cTn concentration for (panel A) hs-cTnI and (panel B) hs-cTnT. This showed an increase in the risk of mortality for patients up to 2-5 times the 99th percentile for cTnI and 5-100 times the 99th percentile for cTnT. Figure 2 shows the risk of 30-day mortality for patients for each concentration of cTn. There was a much higher risk of mortality associated with elevation of cTnT than cTnI for all bands of concentration. Conclusion Though both cTnI and cTnT are strong prognostic markers of mortality among patients admitted with heart failure, cTnT seemed to be the strongest prognostic marker. The risk of mortality increased with concentration of cTnT up to very high concentrations of &amp;gt;5 times the 99th percentile.Figure 1Figure 2

Prevalence and outcome of clinical misdiagnosis of non-ST-elevation myocardial infarction

Abstract Background The prevalence of clinical misdiagnosis of non-ST-elevation myocardial infarction (NSTEMI) and its impact on patient outcomes is largely unknown. Methods We prospectively enrolled adult patients presenting with suspected acute coronary syndromes at 12 sites in five European countries. All patients provided written informed consent and were managed as per local clinical care using conventional, sensitive or high-sensitivity cardiac troponin (hs-cTn) assays. Study blood samples were taken at presentation and serially thereafter for measurements of hs-cTn concentrations. Final diagnoses were adjudicated by two independent cardiologists according to current guidelines and the 4th universal definition of myocardial infarction using all information including serial hs-cTnT measurements and imaging. The primary diagnostic endpoint was the prevalence of clinical NSTEMI misdiagnosis. Co-primary prognostic endpoints were 30 day and two year all-cause and cardiovascular (CV) death. Results In 7,678 patients (median age 61 [IQR 48-73], 34% women), the prevalence of adjudicated and clinical NSTEMI was 17.8% and 12.3%, respectively (P&amp;lt;0.001). Among 1,363 patients with an adjudicated NSTEMI (77% type 1 MI, 23% type 2 MI), 470/1,363 (34%) had a clinical NSTEMI misdiagnosis. These patients were older, more often female, had lower median cTn concentrations, and were more likely managed at centers using non-hs-cTn assays at time of enrolment. Compared to patients with an adjudicated and clinical NSTEMI diagnosis, missed patients were less likely to undergo coronary angiography or revascularization and less often discharged on evidence-based treatment (dual antiplatelet therapy 24% vs 79%, statin 64% vs 92%, betablocker 68% vs 81%, all P&amp;lt;0.001). Finally, patients with a clinical NSTEMI misdiagnosis were at much higher risk of premature all-cause (HR 1.51, 95% CI 1.18-1.94, P&amp;lt;0.001) and CV (HR 1.93, 95%CI 1.42-2.63, P&amp;lt;0.001) death. Conclusion One out of three adjudicated NSTEMI patients was misdiagnosed in routine clinical care. Clinical NSTEMI misdiagnosis was associated with lower use of guideline-recommended therapies and a substantial increase in premature death.Alluvial plotAll-cause death at 2-years

Estimating the true half-life of cardiac troponins, a novel methodological approach

Abstract Introduction Cardiac troponins (cTn) are key when diagnosing myocardial injury (MI) and are used worldwide. Still, the half-life (T½) of cTn in the bloodstream is largely unknown. Previously, T½ has been estimated to 7-20 hours following MI. However, in the clinical setting the true T½, i.e. the decay of cTn, cannot be estimated due to ongoing leakage of cTn from cardiomyocytes. Identification of the true T½ is essential to improve estimation of how long cTn leak from cardiomyocytes due to MI and to understand the pathophysiology of all diseases in the myocardium associated with raised cTn levels. Purpose To determine T½ of cTnI and cTnT in the human blood stream. Methods Patients with ST elevation myocardial infarction (STEMI) were included within 24 hours after acute reperfusion therapy and underwent plasmapheresis to "harvest" plasma with a high cTn concentration. Three to 17 weeks later patients received a re-transfusion of autologous plasma. Blood samples were drawn at 22 fixed time points over eight hours from re-transfusion. A two phased model was used to estimate T½ of cTnI and cTnT for all patients. An alpha level of &amp;lt;0.05 was considered statistically significant and differences were tested by Wilcoxon matched pairs signed rank test. Results A total of 20 participants received a re-transfusion of their own plasma. Median age was 63 years (IQR 58-70), and four participants were women (20%). Prior to re-transfusion the participants’ median concentration of cTnI was 16 ng/l (interquartile range (IQR) 12-24) and of cTnT 12 ng/l (IQR 11-18). Following re-transfusion of 180-679 ml autologous plasma, participants’ concentration of cTn was measured again. Median concentration of cTnI was 3,355 ng/l (IQR 2,135-4,690) and of cTnT 237 ng/l (IQR 160-303 ng/l). Decay of cTnI and cTnT from injection to eight hours after followed a two-phased exponential decline with a primary fast and secondary slow phase as presented in figures 1-2. Each colored curve represents a participant. Median T½ during the first phase was 11 min for cTnI (IQR 6-13 min) and 15 min for cTnT (IQR 7-18 min). The fast decline in the first phase was thought to be due to re-distribution in the extracellular space. The second phase had a median T½ of 65 min for cTnI (IQR 56-80 min) and 67 min for cTnT (IQR 51-92 min). The second phase represents the human, biological T½ of cTn. No significant difference was found between T½ of cTnI and cTnT. Conclusions This novel study design showed seven to 20-fold shorter T½ of cTnI and cTnT compared to previous estimates in the acute, clinical setting, indicating that the duration of cTn leakage from the myocardium during MI has previously been grossly underestimated. This finding challenges our understanding and interpretation of the clinical course of MI and may translate into changes in the perceived window of opportunity for myocardial salvage by interventions.Figure 1:Cardiac troponin IFigure 2:Cardiac troponin T

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Abstract 15219: High-Sensitivity Cardiac Troponins and Sex-Differences in Prognostic Value for Cardiovascular Events and All-Cause Mortality

Background: Cardiac troponin (cTn) concentrations and the associated long-term cardiovascular risk differ between women and men in the general population. Research question: In patients with acute chest pain, does the prognostic value of cTn differ between sexes as assessed by different cTn assays? Methods: This prospective cohort study included 1500 patients (906 men and 594 women) admitted with suspected NSTE-ACS. Admission cTn was measured with three different high-sensitivity assays: hs-cTnT (Roche), hs-cTnI (Siemens) and hs-cTnI (Abbott). Patients were followed for a median of 1687 (range 4-2208) days. The primary endpoint was a composite of all-cause mortality, myocardial infarction, revascularization and heart failure. The secondary endpoint was all-cause mortality. Discriminatory performance was calculated by the receiver-operating characteristics area under the curve (ROC-AUC) whilst prognostic value was calculated by hazard ratios (HR) in unadjusted and adjusted Cox proportional hazard models. Results: The primary endpoint occurred in 18.1% of men and 15.0% of women. The secondary endpoint occurred in 10.3% of men and 8.9% of women. Women were older than men (median 65 years vs. 59 years, P&lt;0.001), and had higher cTn concentrations (P&lt;0.001 for all assays). All cTn assays had significantly higher discriminatory value in women compared to men for both endpoints (Table 1). Ln-transformed cTn for all assays were associated with increased risk of the primary endpoint and all-cause mortality in both sexes. Unadjusted HRs were higher in women than men with increasing hs-cTn, while in multivariate Cox model the adjusted HRs exhibited similar values between sexes (both endpoints) with no interaction between sex (P&gt;0.05 for all) (Table 1). Conclusions: In patients with suspected with NSTE-ACS, there is a difference in the discriminatory value of hs-cTn, but no clear trend between sexes regarding its prognostic in adjusting for a range of factors, including age.

Postoperative Myocardial Injury and Inflammatory Biomarkers in Patients Undergoing Vascular Surgery: A Subanalysis of the Platelet Reactivity and Postoperative Myocardial Injury after Major Vascular Surgery (PROMISE) Study

BackgroundPostoperative myocardial injury (PMI) is associated with morbidity and mortality, but the aetiology remains unclear. We studied whether PMI is associated with perioperative systemic inflammation. ObjectiveTo examine the relationship between inflammatory biomarkers (Interleukin 6[IL-6], C-reactive protein [CRP]) and PMI, detected by elevated cardiac troponin (cTn), in patients undergoing elective open abdominal aortic surgery. MethodsThis prospective, single-centre, observational, cohort study included 54 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. IL-6 and CRP were measured pre-operatively, directly after surgery, 24h and 48h post-operative. The primary outcome was cTn release assessed by a fifth generation high-sensitive cTn assay. Multivariable generalized linear regression models were used to evaluate the association between inflammatory biomarkers and cTn concentrations. ResultsFifteen patients (27.8%) developed PMI. IL-6 directly and 24h post-operatively was associated with elevated cTn concentrations (1.28 [1.07-1.54], p=0.009)) and 1.75 [1.18-2.59], p=0.006, respectively). Also, CRP directly and 24h post-operatively was associated with elevated cTn concentrations (1.25 [1.06-1.47], p=0.009)) and 1.61 [1.1-2.33], p=0.013, respectively). No association was found between IL-6 or CRP and cTn concentrations when measured at 48h post-surgery. ConclusionBiomarkers of inflammation are associated with elevated post-operative cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

A-015 Hemoglobin A1c Control is An Independent Predictor of Circulating Troponin Concentrations Using Machine Learning

Abstract Background Diabetes mellitus (DM) is associated with multiple comorbidities that may precipitate cardiac damage and elevated cardiac troponin (cTn) concentrations including renal failure, hyperlipidemia (HLD), hypertension (HTN), coronary artery disease (CAD), and congestive heart failure (CHF). Diabetics &amp;gt;70 years old have a higher likelihood of adverse outcomes including major cardiovascular events and cardiac mortality. However, the risk to younger diabetic patients and the precipitating factor(s) that facilitate cardiac injury in those with DM are unknown. The objective of this study was to investigate factors predictive of cTn concentrations in young, relatively healthy diabetic patients. Methods We collected 1533 remnant plasma samples from outpatients between 06/22–09/22 with physician ordered hemoglobin A1c testing. cTn was measured using the Abbott ARCHITECT High Sensitivity Troponin-I assay (limit of detection = 1.7 ng/L, imprecision = 4.76% at 50 ng/L). Demographic information (sex, race, BMI) and pertinent medical history (diabetes, HTN, HLD, CAD, CHF) were collected from the electronic medical record, along with estimated glomerular filtration rate (eGFR) and hemoglobin A1c. Exclusion criteria included: patients with missing laboratory data, those undergoing cancer treatment, or a history of myocardial infarction/cardiomyopathy/cardiac surgery. Troponin results were classified as normal- or high-risk using a cut-off of 10 ng/L for females and 12 ng/L for males, thresholds previously shown to correlate with incidence of cardiovascular disease risk within 15 years. Univariate statistics were calculated using Wilcoxon rank sum tests. An XGBoost model was trained to predict high-risk troponinemia, and summary statistics were calculated on a held-out test set. Results Of the 1135 patients that met inclusion criteria, 621 (54.7%) were female. The median age was 60 years (IQR: 49–69 years) and the median A1c was 6.2% (IQR: 5.8%–7.0%). A total of 746 patients (65.7%) had a prior diabetes diagnosis, with 156 patients (13.7%) having prediabetes, 42 patients (3.7%) having Type 1, and 548 patients (48.3%) having Type 2. Median troponin concentration for patients with an A1c &amp;lt;5.7% was 1.6 ng/L (IQR: 0.8–3.4), 5.7%–6.4% was 2.2 ng/L (IQR: 1.3–4.8), and ≥6.5% was 2.9 ng/L (IQR: 1.6–6.7). Univariate analysis demonstrated significant differences in troponinemia by age (CI of difference: 4.4–8.9 years), A1c (0.2%–0.7%), and eGFR (28–38 mL/min/1.73 m2). The machine learning model demonstrated strong predictive capacity (sensitivity: 0.74, specificity: 0.86, PPV: 0.5, NPV: 0.92, area under ROC curve: 0.91). The features with the greatest impact on area under the ROC curve when removed were eGFR, Age, A1c, and CHF. Conclusion A combination of clinical and laboratory variables can be used to predict circulating troponin concentrations in outpatients. A1c control was an independent contributor to cTn concentrations, both in univariate and multivariate analyses. This study provides evidence that glucose control may be associated with cardiac damage and future cardiovascular events, warranting longitudinal outcome studies.

Guideline adherence to statin therapy and association with short-term and long-term cardiac complications following noncardiac surgery: A cohort study.

Peri-operative complications are common and associated with high morbidity and mortality. Optimising the use of statins might be of important benefit in peri-operative care and reduce morbidity and mortality. To evaluate adherence to current guideline recommendations regarding statin therapy and its association with peri-operative and long-term cardiac complications. Prospective cohort study. Multicentre study with enrolment from October 2014 to February 2018. Eight thousand one hundred and sixteen high-risk inpatients undergoing major noncardiac surgery who were eligible for the institutional peri-operative myocardial injury/infarction (PMI) active surveillance and response program. Class I indications for statin therapy were derived from the current ESC Clinical Practice Guidelines during the time of enrolment. PMI was prospectively defined as an absolute increase in cTn concentration of the 99th percentile in healthy individuals above the preoperative concentration within the first three postoperative days. Long-term cardiac complications included cardiovascular death and spontaneous myocardial infarction (MI) within 120 days. The mean age was 73.7 years; 45.2% were women. Four thousand two hundred and twenty-seven of 8116 patients (52.1%) had a class I indication for statin therapy. Of these, 2440 of 4227 patients (57.7%) were on statins preoperatively. Adherence to statins was lower in women than in men (46.9 versus 63.9%, P < 0.001). PMI due to type 1 myocardial infarction/injury (T1MI; n = 42), or likely type 2 MI (lT2MI; n = 466) occurred in 508 of 4170 (12.2%) patients. The weighted odds ratio in patients on statin therapy was 1.15 [95% confidence interval (CI) 1.01 to 1.31, P = 0.036]. During the 120-day follow-up, 192 patients (4.6%) suffered cardiovascular death and spontaneous MI. After multivariable adjustment, preoperative use of statins was associated with reduced risk; weighted hazard ratio 0.59 (95% CI 0.41 to 0.86, P = 0.006). Adherence to guideline-recommended statin therapy was suboptimal, particularly in women. Statin use was associated with an increased risk of PMI due to T1MI and lT2MI but reduced risk of cardiovascular death and spontaneous MI within 120 days. Clinicaltrials.gov identifier NCT02573532.

Value of Cardiac Troponin, Myoglobin Combined with Heart-type Fatty Acid-binding Protein Detection in Diagnosis of Early Acute Myocardial Infarction.

To evaluate the value of cardiac troponin(cTn), myoglobin(Myo) combined with heart-type fatty acid-binding protein(H-FABP) detection in the diagnosis of early acute myocardial infarction(AMI). This study was a clinical comparative study. Eighty patients with AMI hospitalized in Tangshan Workers' Hospital were selected as study group, and another 80 individuals receiving normal physical examination were selected as control group from September 20, 2021 to September 20, 2022. The concentrations of cTn, Myo and H-FABPP, diagnostic indicators, the sensitivity and specificity of combined diagnosis, as well as the diagnostic efficacy for AMI were compared between the two groups. The levels of cTn, Myo and H-FABPP in the study group were significantly higher than those in the control group(P= 0.00). Multivariate logistic regression analysis showed that cTn, Myo and H-FABP were all relevant indicators for AMI. H-FABP alone has better diagnostic efficacy for AMI. The area under the curve of their combined detection, the specificity, and the sensitivity were higher than those of cTn, Myo and H-FABP alone, indicating that their combined application has the best diagnostic efficiency. cTn, Myo and H-FABP levels were positively correlated with Glu, TC, LDL-C and hs-CRP levels(P< 0.01), while negatively correlated with HDL level(P< 0.01). The combined detection of cardiac markers such as cTn, Myo and H-FABP presents higher sensitivity and specificity in the diagnosis of AMI compared with any single detection, and can provide better data support for the definite diagnosis of AMI, with high clinical application value.

Association between troponin level and medium-term mortality in 20 000 hospital patients

IntroductionCardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and...