Elevated hs-cTnT Research Articles

Joint effect of highly-sensitive cardiac troponin T and ankle-brachial index on incident cardiovascular events: The MESA and CHS

BackgroundElevated highly-sensitive cardiac troponin-T (hs-cTnT≥14 ng/L) and low ankle-brachial index (ABI<0.9) are risk factors for atherosclerotic cardiovascular diseases (ASCVD) but their joint effect on the risk of ASCVD events is unknown. MethodsWe used data from the two population-based cohort studies, the Multi-Ethnic study of Atherosclerosis (MESA) and Cardiovascular Heart Study (CHS) among 10,897 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident ASCVD was defined as CHD (fatal/non-fatal MI or revascularization), transient ischemic attack, or stroke,. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. ResultsAt baseline (2000–2002 for MESA and 1989–1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During a median follow-up of 13.6 years (interquartile range, 7.5–14.7 years), there were 2590 incident ASCVD and 1542 incident CHD events. The hazard of CHD and ASCVD was higher in participants with both elevated hs-cTnT and low ABI [HR(95% CI): CHD: 2.04 (1.45, 2.88), ASCVD: 2.05 (1.58, 2.66)] than those with only elevated hs-cTnT [CHD: 1.65 (1.37, 1.99), ASCVD: 1.67 (1.44, 1.99)] or only low ABI [CHD: 1.87 (1.52, 2.31), ASCVD: 1.67 (1.42, 1.97)]. Antagonistic multiplicative interaction was observed for CHD (LR test p-value=0.042) but not for ASCVD (LR test p-value =0.08). No significant additive interaction was detected for CHD and ASCVD (RERI p-value ≥0.23). ConclusionThe observed joint effect of elevated cTnT and low ABI on ASCVD risk was smaller (i.e., antagonistic interaction) than that expected by the combined independent effects of each risk factor.

Correlation of Mean Heart Dose and Cardiac Biomarkers with Electrocardiographic Changes in Patients Receiving Thoracic Radiation Therapy.

Cardiotoxicity is a well-recognized, serious adverse effect of thoracic radiation therapy. This study aimed to evaluate longitudinal electrocardiogram (ECG) changes in patients receiving thoracic radiation therapy and identify correlating factors that can predict the risk of cardiotoxicity. This retrospective study included 202 patients treated with thoracic radiation therapy, and chemotherapy and targeted therapy were allowed. Mean heart dose (MHD) was evaluated on dose-volume histograms. ECG, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal B-type natriuretic peptide (NT-proBNP) analyses were conducted before irradiation and during the follow-up period of 6-12 months (average 8 months). Chi square test and logistic regression analysis were applied to identify risk factors associated with ECG changes. At a median time of 3 months postirradiation, 46.5% of patients showed ECG changes, and 33.0% of patients achieved baseline ECG levels during the follow-up period at a median of 5 months postirradiation. Logistic regression analysis identified MHD, hs-cTnT and NT-pro BNP as significant factors associated with ECG changes (P < 0.05). Hs-cTnT and NT-proBNP were increased significantly after radiation therapy compared with baseline levels (P < 0.05), and these increases were observed as a median time of 2 months postirradiation, which was earlier than ECG changes. Higher MHD and elevated hs-cTnT and NT-proBNP levels correlated with an increased risk of ECG changes in patients receiving thoracic radiation therapy. Early identification of patients at high risk of cardiotoxicity and timely intervention might reduce the incidence of radiation-induced cardiac toxicity.

Prognostic value of interleukin-34 and interleukin-38 in patients with newly diagnosed atrial fibrillation.

Interleukin (IL)-34 and IL-38 are associated with cardiovascular disease (CVD). However, their involvement in atrial fibrillation (AF) and AF-associated adverse events remains uncertain. Therefore, we aimed to investigate their association with various AF prognostic factors in a cohort study and assessed their predictive value for the prognosis of patients with AF. Patients with new-onset non-valvular AF were consecutively enrolled between 2013 and 2015 at the Department of Cardiovascular Medicine of the Southwest Hospital of the Army Medical University (Third Military Medical University) in Chongqing, China. The endpoints included stroke and all-cause mortality. The baseline levels of plasma IL-34, IL-38, NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and GDF-15 were measured and their correlation with AF-related adverse events were analyzed in a Cox proportional-hazards regression model. The C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the performance of the AF prognostic models. Decision curve analysis (DCA) was used to evaluate the clinical net benefit of the original and modified models. A total of 299 patients with new-onset AF were enrolled. During the median follow-up time of 28 (IQR: 27, 29) months, the higher levels of IL-34 were associated with a lower risk of stroke, and the higher levels of IL-38 were associated with an increased risk of all-cause death (all adjusted P < 0.05). In addition, elevated hs-cTnT and NT-proBNP concentrations were associated with a higher risk of stroke and all-cause mortality (all adjusted P < 0.05). Furthermore, the CHA2DS2-VASc score combined with IL-38 and NT-proBNP significantly improved the C-statistic, IDI, and NRI (all P < 0.01). There was no statistically significant difference (all P > 0.05) in the discrimination power between the preference models and the ABC (age, biomarkers, and clinical history) score for the two prognostic outcomes. Our results suggested that IL-34 and IL-38 were independently associated with stroke and all-cause mortality in patients with AF. Moreover, adding IL-38 and NT-proBNP to the CHA2DS2-VASc score significantly improved its predictive ability of AF-related all-cause death. Finally, the preference model performed equally well as the ABC score in predicting AF prognosis.

Renal failure: a non-cardiac source of high sensitivity cardiac troponin T

Abstract Background Circulating high sensitivity cardiac troponin T (hs-cTnT) levels are frequently elevated in patients with end-stage renal disease (ESRD). The underlying pathophysiology is largely unknown. Currently, accumulation of hs-cTnT due to impaired renal clearance, as well as increased production caused by chronic cardiomyocyte injury is being discussed. Purpose The aim of this study was to assess the relative contribution of impaired renal clearance as a non-cardiac source of elevated hs-cTnT concentrations, using renal transplantation as an in vivo model of rapidly improved renal function and on a short-term basis rather unchanged cardiac pathology. Methods This single-centre study was a secondary analysis within a prospective active surveillance study program for perioperative myocardial infarction/injury (PMI). 42 consecutive high-risk patients undergoing renal transplantation without evidence of PMI were included. Serial creatinine and hs-cTnT (Elecsys, Roche) measurements were performed pre-transplant (baseline) and post-transplant on day (d) 1, between d2 and d5, and between d14 and d180. The effect of time and creatinine on hs-cTnT was estimated with a log-level non-linear mixed-effects model, where time and creatinine were treated as the fixed effects and subject as the random effect. Natural cubic splines were used to account for nonlinearity in the fixed effects. Results Baseline median serum creatinine concentration was 616 umol/L [interquartile range (IQR) 477–825], and significantly fell to 425 umol/L (IQR 313–619) on d1, 285 umol/L (IQR 194–509) on day2–5, and 116 umol/L (IQR 100–166) on d14–180 (p&amp;lt;0.001, p&amp;lt;0.001, and p=0.043, respectively; Figure 1A). Pre-transplant hs-cTnT concentrations were above the 99th percentile (14ng/L) in all patients, median hs-cTnT concentration was 50 ng/L (IQR 35–70). In parallel to the fall in serum creatinine from baseline to d1, hs-cTnT concentrations significantly fell to 28 ng/L (IQR 15–40) on d1 (p&amp;lt;0.001), and then remained constant on d2–5 (27 ng/L (IQR 18–35)), and on d14–180 (24 ng/L (IQR 19–28); Figure 1B). The mixed-effect model showed a significant decrease of hs-cTnT between baseline and d1 (p&amp;lt;0.001), whereas no significant change between d1 and d2 (p=0.82) occurred (Figure 2). Conclusion In contrast to the continuously falling serum creatinine levels, hs-cTnT concentrations reduced by about 50% only within the first 24 hours with a functional graft and then remained elevated above the 99th percentile. This suggests, that ESRD is a non-cardiac source of elevated circulating hs-cTnT concentrations, which contributes about 50%, while the other 50% seem related to chronic cardiomyocyte injury. Further studies assessing the long-term effect of renal transplantation on hs-cTnT levels and cardiac function are needed. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation

High-sensitivity Cardiac Troponin T in Sepsis:Prognostic Value and Risk Factors of Its Elevation

Objective To explore the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) in predicting mortality within 28 days among sepsis patients,and to investigate the risk factors of hs-cTnT elevation. Methods The clinical and laboratory data of patients with sepsis or septic shock who were hospitalized at the Second Affiliated Hospital of Chongqing Medical University from December 2017 to September 2021 were collected and retrospectively analyzed.The patients were assigned into a hs-cTnT elevated group (hs-cTnT>0.1 ng/ml) and a hs-cTnT non-elevated group (hs-cTnT≤0.1 ng/ml).The prognosis was compared between the two groups and the risk factors of hs-cTnT elevation were determined. Results A total of 225 patients were included in this study,including 49 in hs-cTnT elevated group (21.8%) and 176 in hs-cTnT non-elevated group (78.2%).The receiver operating characteristic curve showed that maximum hs-cTnT had predictive value for death within 28 days (P<0.001).The maximum hs-cTnT showed the area under the receiver operating characteristic curve of 0.767 (95%CI=0.699-0.835),the sensitivity of 62.5%,and the specificity of 79.9%.The mortality within 28 days of hs-cTnT elevated group was higher than that of hs-cTnT non-elevated group (53.1% vs. 17.0%, χ2=26.595, P<0.001).Multivariate Logistic regression analysis revealed that the independent predictors of hs-cTnT elevation were age ≥75.5 years (OR=5.990, 95%CI=2.143-16.742, P=0.001),lactate ≥4.05 mmol/L (OR=4.982,95%CI=1.433-17.315,P=0.012),oxygenation index ≤169.15 mmHg (OR=5.052, 95%CI=1.888-13.514, P=0.001),B-type brain natriuretic peptide precursor ≥6 687.0 pg/ml (OR=5.991, 95%CI=2.226-16.128, P<0.001),fibrinogen ≤2.87 g/L (OR=3.325,95%CI=1.175-9.404, P=0.024),and International Society on Thrombosis and Haemostasis overt disseminated intravascular coagulation score ≥5.5 (OR=7.631, 95%CI=1.157-50.338, P=0.035). Conclusions hs-cTnT showed good performance in predicting mortality within 28 days among the patients with sepsis.Coagulation disorder,microthrombus formation,and myocardial oxygen supply-demand mismatch may be the risk factors of myocardial injury in sepsis.

Cognition impairment and risk of subclinical cardiovascular disease in older adults: The atherosclerosis risk in communities study.

BackgroundClinical cardiovascular disease (CVD) and cognition impairment are common and often coexist in aging populations, and CVD is associated with greater cognition impairment risk; however, the association between cognition impairment and CVD risk is inconsistent. It is unknown if pathways that contribute to CVD are caused by impaired cognition. We hypothesized that cognition impairment would be associated with greater subclinical CVD including subclinical myocardial damage [assessed by high-sensitivity cardiac troponin T (hs-cTnT)] and cardiac strain or dysfunction [assessed by N-terminal pro-B-type natriuretic peptide (NT-proBNP)].MethodsThis analysis included Atherosclerosis Risk in Communities Study (ARIC) participants who underwent global cognition z-score tests between 1991 and 1993. Cardiac biomarkers were measured from stored plasma samples collected between 1996 and 1999. Logistic regression models were used to determine the association of cognitive function with subclinical CVD risk.ResultsThere were 558/9216 (6.1%) and 447/9097 (5.0%) participants with incident elevated hs-CTnT (≥14 ng/L) and NT-proBNP (≥300 pg/mL) levels, respectively. Comparing the lowest and highest quartiles of global cognition z-scores, a higher incidence of elevated hs-CTnT [odds ratio (OR) = 1.511, 95% confidence interval (CI): 1.093–2.088, P = 0.013] and NT-proBNP (OR = 1.929, 95% CI: 1.350–2.755, P < 0.001) were observed, respectively. In structural equation modeling, the indirect effect of global cognition z-score on major adverse cardiac events was 42.1% (P < 0.05).ConclusionImpairments in baseline cognitive function were associated with subclinical myocardial damage or wall strain. Although future studies are warranted to investigate the pathophysiological mechanisms behind these associations, our study suggests common pathways between cognitive and cardiac dysfunction.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury

BackgroundHigh-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. MethodsThis is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. ResultsPatients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e′ medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. ConclusionsStructural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

1081-P: Blood Pressure Variability Is Associated with Risk of Heart Failure, Elevated NT-proBNP, and High-Sensitivity Troponin: Results from MESA

The association between blood pressure variability (BPv) and heart failure (HF) is incompletely studied. This association, and its links with biomarkers of HF and cardiac injury, were examined in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) . Resting seated BP was measured thrice; the average of the last two measures was used for analysis, and visit-to-visit BPv (coefficient of variation-CV) was assessed over 5 visits. Biomarkers of HF (N-terminal B-type natriuretic peptide: NT-proBNP) and cardiac injury (high-sensitivity troponin-T: hs-cTnT) , respectively, at exams 1, 3 and 5 were ascertained. With 9.4 years median follow-up in 6,785 individuals, 385 HF events occurred. In adjusted time-dependent models including CVD risk factors, BMI, BP medications, and cumulative mean BP, BPv (CV-SBP and CV-DBP) was associated with risk of clinical HF (e.g., CV-SBP HR=1.16, p=0.03) . Similar patterns were seen regardless of T2D status. The associations were stronger for HF with reduced ejection fraction (EF) vs. preserved EF. When excluding those with baseline NT-proBNP &amp;gt;450 pg/mL or hs-cTnT &amp;gt;14 ng/L, the association between BPv and HF became stronger. CV-SBP and CV-DBP were also associated with elevated exam 5 NT-proBNP (&amp;gt;450 pg/mL: OR=1.74, and OR = 1.32, p&amp;lt;0.001) . We saw a positive relationship between CV-SBP and exam 1 to exam 5 changes in NT-proBNP (p=0.001) and hs-cTnT (p&amp;lt;0.001) as well as elevated hs-cTnT (&amp;gt;14 ng/L; OR=1.18, p&amp;lt;0.001) . Our data strongly support an association between BPv and both clinical HF and elevated NT-proBNP, and the association was greater in those with reduced vs. preserved EF. The association between BPv and clinical HF was related to deleterious changes in subclinical markers of myocardial injury and heart failure. Disclosure D.S.Nuyujukian: None. J.Zhou: Research Support; Dexcom, Inc. J.Koska: None. C.Nwabuo: None. A.Bertoni: None. S.Shea: Research Support; National Heart, Lung, and Blood Institute. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. Funding NIH/NHLBI (F32HL156626) NIH/NHLBI (R21HL150374) NIH/NHLBI (R21HL150268) NIH/NHLBI (R01HL138969)

Elevation of cardiac biomarkers in stroke is associated with pathological findings on cardiac MRI-results of the HEart and BRain interfaces in Acute Stroke study.

Cardiac biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT), are frequently elevated in ischemic stroke patients but the mechanisms underlying this elevation are insufficiently understood. We determined the presence of cardiac damage, assessed using cardiac magnetic resonance imaging (CMR), in stroke patients with elevated hs-cTnT and brain natriuretic peptide (BNP). This is a post hoc analysis of the prospective, investigator-initiated, cross-sectional HEart and BRain interfaces in Acute Stroke (HEBRAS) study. All patients underwent the measurement of hs-cTnT and BNP as well as gadolinium-enhanced CMR in the acute phase of ischemic stroke. We performed unadjusted and adjusted logistic regression models to assess the association between hs-cTnT and BNP elevation and the presence of pathological CMR findings. Two hundred and thirty-three stroke patients (median age 67 years, 33% female) were included, of whom 43 (21%) had elevated hs-cTnT and 109 (47%) had elevated BNP. Hundred of the 233 (43%) patients had pathological findings on CMR had focal fibrosis as detected by late-gadolinium enhancement (LGE) in 51 (23%), left-ventricular hypertrophy (LVH) in 38 (16%), reduced LVEF in 32 (14%), and left-atrial dilatation in 34 (15%). After adjustment for potential confounders, both hs-cTnT (adjOR 5.0 (95%CI 2.1-11.7), p < 0.001) and BNP (adjOR 4.1 (95%CI 2.3-7.3), p < 0.001) were significantly associated with pathological findings on CMR. Hs-cTnT was associated with LGE, LVEF, and LVH, whereas BNP was associated with left-atrial dilatation and LVEF, LVH. Elevated cardiac biomarkers in acute stroke including CMR are strongly associated with pathological findings on CMR. In acute stroke patients, the elevation of cardiac biomarkers may identify patients who require a more thorough cardiology work-up.

Subclinical cardiovascular disease and frailty risk: the atherosclerosis risk in communities study

BackgroundCardiovascular disease (CVD) is associated with a greater frailty risk, but it remains unknown if pathways that contribute to CVD are associated with the frailty risk. Thus, we aimed to investigate whether elevations in high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for those without known CVD at baseline are associated with a higher frailty risk.MethodsThis study used data from the Atherosclerosis Risk in Communities study. Cardiac biomarkers were measured from stored plasma samples collected at Visit 2 (1991–1993). Frailty was recorded at Visit 5 (2011–2013). Cox regression models were used to determine the association of cardiac biomarkers with frailty risk.ResultsOverall, 360/5199 (6.9%) participants aged 55.1 ± 5.1 years developed frailty during a median follow-up of 21.7 years. The incidence of frailty was significantly higher in participants with hs-cTnT ≥14 ng/L (vs. < 14 ng/L: 17.9% vs. 6.7%) or NT-proBNP ≥300 pg/ml (vs. < 300 pg/ml: 19.7% vs. 6.8%) (all P < 0.001). Comparing higher vs. lower cut-off levels of either hs-cTnT (14 ng/l) or NT-proBNP (300 pg/ml) demonstrated a greater than two-fold higher frailty risk, with hazard ratios (HRs) of 2.13 (95% confidence interval (CI): 1.130–4.01, P = 0.020) and 2.61 (95% CI: 1.28–5.33, P = 0.008), respectively. Individuals with both elevated hs-cTnT and NT-proBNP had a higher frailty risk than those without it (HR: 4.15; 95% CI: 1.50–11.48, P = 0.006).ConclusionsHigh hs-cTnT and NT-proBNP levels are strongly associated with incident frailty in the community-dwelling population without known CVD. Subclinical cardiac damage (hs-cTnT) and/or wall strain (NT-proBNP) may be the key pathway of CVD patients developing frailty. Detection of hs-cTnT and NT-proBNP may help for early screening of high-risk frailty and providing individualised intervention.Trial registrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT00005131.

Cardiac biomarkers in pediatric CKD—a prospective follow-up study

BackgroundThe N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive cardiac-specific troponin T (hs-cTnT) are associated with abnormal cardiac structure and function and an increased risk of cardiovascular death in chronic kidney disease (CKD) patients. There is limited knowledge about these cardiac markers in pediatric CKD patients.MethodsLongitudinal levels of NT-proBNP and hs-cTnT were analyzed in 48 pediatric patients, 22 with CKD (GFR range 8.8–68 mL/min/1.73 m2) and 26 transplanted patients (CKD-T; GFR range 30–99 mL/min/1.73 m2). Follow-up was scheduled after 1 and 3 years. Longitudinal patterns and associations to kidney function, cardiovascular risk markers, and echocardiographic parameters were assessed.ResultsHigh NT-proBNP was present in 27% of CKD and 11% of CKD-T patients. Similarly 32% of CKD and 8% of CKD-T patients had elevated hs-cTnT levels. In longitudinal multivariate analyses, high log NT-proBNP was associated with low GFR (β = − 0.01, p = 0.01) and elevated left ventricular mass index (LVMI; β = 0.02, p = 0.05). The strong association to LVMI remained when using GFR-adjusted NT-proBNP in similar analysis. Patients with left ventricular hypertrophy (LVH) also had higher NT-proBNP (235 [146–301] ng/L) than patients without LVH (86 [11–477] ng/L), p = 0.02. High hs-cTnT over-time was also associated with low GFR (β = − 0.007, p = 0.01) and a low cc-TDI e´/a´, indicating a worse LV diastolic function (β = − 0.09, p = 0.05). This association did not persist for GFR-adjusted hs-cTnT.ConclusionsNT-proBNP and hs-cTnT are elevated in pediatric CKD and CKD-T patients. GFR-adjusted NT-proBNP was associated with longitudinal levels of elevated LVMI suggesting this might be a marker for early subclinical myocardial damage.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Abstract MP76: Association Of Elevated High-sensitive Cardiac Troponin T And Low Ankle-brachial Index With Incident Cardiovascular Events. The Multi-ethnic Study Of Atherosclerosis And The Cardiovascular Health Study

Introduction: Elevated high-sensitive cardiac troponin T (hs-cTnT&gt;14 ng/L) and low ankle-brachial index (ABI &lt; 0.9) are known to be associated with cardiovascular diseases (CVD) but their joint effect on the risk of CVD events is unknown. Methods: We used data from the MESA and CHS among 10,900 participants free of CVD events at baseline (mean age 66.3 years, 44.7% males). Incident coronary heart disease (CHD) was defined as fatal or non-fatal myocardial infarction or revascularization and incident CVD was defined as CHD, transient ischemic attack, stroke, or atrial fibrillation. Hazard ratio (HR) and 95% CI was calculated from a Cox regression model. Interaction on the additive scale was assessed using relative excess risk due to interaction (RERI) and interaction on the multiplicative scale was assessed by Likelihood ratio (LR) test. Results: At baseline (2000-2002 for MESA and 1989-1990 for CHS), 10.2% of participants had elevated hs-cTnT and 7.5% had low ABI. During 26.1 years of total follow-up (median follow-up 18.4 years), there were 3,911 incident CVD events. The risk of CHD and CVD was higher in participants with both elevated hs-cTnT and low ABI [CHD HR: 2.1 (1.5, 2.9), CVD HR: 2.1 (1.7, 2.5)], only elevated hs-cTnT [CHD HR: 1.7 (1.4, 2.0), CVD HR: 1.6 (1.5, 1.8)], and only low ABI [CHD HR: 1.8 (1.5, 2.2), CVD HR: 1.5 (1.3, 1.7)] than those with unelevated hs-cTnT and normal ABI. Interaction on the multiplicative scale was observe in both adjusted and unadjusted models for CHD (unadjusted LR test p-value=0.002, adjusted LR test p-value=0.042) and only in unadjusted model for CVD (LR test p-value=0.001). No significant additive interaction was detected for both CHD and CVD (RERI p-value≥0.25 for unadjusted and adjusted models). Conclusion: Having both elevated cTnT and low ABI was associated more strongly with CVD events than only elevated cTnT or low ABI. Antagonistic multiplicative interaction was found indicating the observed joint effect of elevated cTnT and low ABI was smaller than the expected combined individual effects.

Abstract P090: Utility Of High-sensitivity Cardiac Troponin T For Short-term Cardiovascular Risk Monitoring In The General Population

Background: Cardiac troponins are the cornerstone for the detection of heart attacks. Beyond the acute setting, there is growing evidence that high-sensitivity cardiac troponin T (hs-cTnT) is associated with long-term cardiovascular disease (CVD) risk. The implications of minute elevations in hs-cTnT on short-term CVD risk in the general population has not been investigated. Methods: We included 12,632 adults (43% men, 25% black, mean age: 57 years) in the Atherosclerosis Risk in Communities (ARIC) study who had at least one measurement of hs-cTnT (Roche) across visits 2 (1990-1992), 3 (1996-1998), and 4 (2011-2013) without diagnosed CVD, defined as coronary heart disease, heart failure, or stroke. We used bootstrapping to generate confidence intervals for the cumulative incidence of CVD and generalized estimating equation log-binomial models to quantify the short-term relative rates of incident CVD. Results: Overall, 3.8% (n=479) had elevated hs-cTnT ≥ 14ng/L at their earliest visit; of whom 65% (n=311) had intermediate or lower predicted 10-year risk by the Pooled Cohort Equation. The cumulative 1-year incidence of CVD among those with hs-cTnT ≥ 14ng/L was 5.7% (95% CI: 4.0%, 7.4%) compared to 1.0% (0.9%, 1.1%) among those with hs-cTnT &lt; 6 ng/L and 1.7% (1.3%, 2.2%) among those with hs-cTnT between 6 to 14 ng/L. Among those with hs-cTnT ≥ 14ng/L, the cumulative incidence of CVD at 2 years was 9.6% (7.3%, 11.8%) and at 3-years was 12.7% (10.0%, 15/3%) (Figure 1A). After accounting for traditional CVD risk factors, hs-cTnT ≥ 14ng/L was associated with 2.9 (2.0, 4.1) times higher incidence of CVD at 1-year compared to 1.9 (1.5, 2.4) times incidence at 3-years (Figure 1B). Conclusions: Middle-aged adults in the general population without CVD who had an elevated hs-cTnT experienced a 5.7% 1-year risk of CVD compared to 1% among those with low hs-cTnT. The relative risk associated with elevations in hs-cTnT was most pronounced within the first year, supporting its use for short-term risk monitoring as part of annual preventive visits.

Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin

BackgroundCirculating biomarkers reflecting different mechanistic pathways may identify at-risk individuals with diabetes who may benefit from sodium-glucose cotransporter-2 (SGLT2) inhibitors. ObjectivesThe purpose of this study was to determine if high-sensitivity cardiac troponin T (hs-cTnT), soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor binding protein 7 (IGFBP7) levels, either alone or in combination, may modify the treatment benefits of canagliflozin. MethodsIn the CANVAS (CANagliflozin cardioVascular Assessment Study) biomarker substudy, we evaluated the prognostic significance of baseline biomarker measurements, the long-term trajectory of each, and response to canagliflozin on key cardiovascular and kidney outcomes. ResultsAmong the 4,330 study participants, baseline hs-cTnT, sST2, and IGFBP7 were available in 3,503 (81%), 3,084 (71%), and 3,577 (83%). In total, 39% had elevated hs-cTnT ≥14 pg/mL, 6% had sST2 >35 ng/mL, and 49% had IGFBP7 >96.5 ng/mL. Canagliflozin significantly slowed increases of hs-cTnT (P = 0.027) and sST2 (P = 0.033) through 6 years. Each biomarker was significantly associated with cardiovascular and kidney outcomes, independent of clinical covariates. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Patients with hs-cTnT ≥14 ng/L and those with sST2 >35 ng/mL derived greater relative benefit for major adverse cardiovascular events (MACE) (both Pinteraction ≤0.05). A panel of all 3 biomarkers predicted each cardiac and kidney outcome evaluated; participants with an increasing number of abnormal circulating biomarkers appeared to have greater relative reductions in MACE from canagliflozin treatment (Pinteraction trend = 0.005). ConclusionsCanagliflozin delays longitudinal rise in hs-cTnT and sST2 compared with placebo out to 6 years. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Elevated cardiovascular biomarkers, either alone or in combination, may identify individuals who may derive greater MACE benefit from SGLT2 inhibition. CANVAS (CANagliflozin cardioVascular Assessment Study; NCT01032629)

Unstable Angina Pectoris With Myocardial Injury Versus Myocardial Infarction in the Era of High-Sensitivity Cardiac Troponin

It is unknown whether outcomes in patients with unstable angina pectoris (UAP) and myocardial injury are different from outcomes in patients with non-ST-segment myocardial infarction (NSTEMI) with low peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT). This study aimed to compare the prognosis in patients with UAP and evidence of myocardial injury, with prognosis in patients with NSTEMI and different peak hs-cTnT concentrations. All visits to 7 different emergency departments in Sweden from December 9, 2009 to December 31, 2016 were identified (n=5,225,075). We included all hospitalized patients with hs-cTnT >14ng/L and a diagnosis of UAP or NSTEMI, with ≥2hours-cTnT measurements. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for all-cause mortality and cardiovascular events, in patients with NSTEMI categorized according to peak hs-cTnT concentrations, compared with patients with UAP. Altogether, 11,944 patients were included, of whom 1,253 (10%) received a diagnosis of UAP. During a median follow-up of 3.0 years (interquartile [IQR] 1.6 to 4.7), 3,297 patients died. There was no difference comparing patients with NSTEMI with peak hs-cTnT of 15 to 49ng/L to patients with UAP, with regards to long-term cardiovascular mortality (HR 1.15; 95% CI, 0.85 to 1.56), but the risk of recurrent myocardial infarction was higher in patients with NSTEMI (HR, 1.61; 95% CI, 1.29 to 2.00), and the risk of heart failure hospitalization slightly lower (HR 0.80, 95% CI, 0.64 to 0.99). In conclusion, patients with UAP and myocardial injury have a similar risk of death after discharge, but a lower risk of recurrent myocardial infarction and a marginally higher risk of heart failure, compared with patients with NSTEMI with moderately elevated hs-cTnT levels.

Abstract 14363: Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC)

Introduction: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. The association of diabetes duration with subclinical myocardial injury is unknown. Hypothesis: Longer duration of diabetes is associated with a higher likelihood of myocardial injury, as reflected by elevated levels of high sensitivity cardiac troponin T (hs-cTnT). Methods: We performed a cross-sectional analysis of 9,243 participants without heart failure or coronary heart disease (mean age 63, 58% female, 20% Black) at ARIC Visit 4 (1996-98). Diabetes duration was calculated based on diabetes status at Visits 1 (1987-89) through 4, with additional use of self-reported age of diabetes diagnosis for those with a diagnosis prior to Visit 1. We used logistic regression to determine the association of diabetes duration with elevated (≥14 ng/L) and measurable (≥5 ng/L) hs-cTnT, adjusted for demographics and cardiovascular risk factors. Results: The prevalence of elevated hs-cTnT was higher in persons with longer diabetes duration, from 5% among those without diabetes, to 9% for those with diabetes 0-&lt;5 years, up to 31% among those with diabetes for 15 years (p&lt;0.0001). There was a robust association between longer diabetes duration and myocardial injury, with a diabetes duration of 15 years: adjusted OR 6.39 (95% CI 4.17-9.79) for elevated hs-cTnT compared to no diabetes ( Figure ). Diabetes duration of 15 years was also associated with measurable hs-cTnT (OR 2.83 [95% CI: 1.92-4.17], relative to no diabetes). Among those with diabetes, each additional 5 years of diabetes duration was associated with higher odds of elevated hs-cTnT (OR 1.46, 95% CI 1.35-1.57). Conclusions: Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether prevention and delay of diabetes onset can mitigate early myocardial damage.

Implementation of more sensitive cardiac troponin T assay in a state-wide health service

AimsExplore the impact of deploying high-sensitivity (hs) cardiac troponin T (cTnT) assay across a state-wide health service. Methods and resultsPresentations to emergency departments of six tertiary hospitals between January 2008 and August 2019 were included; standard cTnT assay was superseded by hs-cTnT in June 2011 without changing the reference range (≥30 ng/L reported as elevated), despite cTnT level of 30 ng/L being equivalent to ∼44 ng/L with hs-cTnT. Clinical outcomes were captured using state-wide linked health records. Interrupted time series analyses were used adjusted for seasonality and multiple co-morbidities using propensity score matching allowing for correlation within hospitals.In total, 614,847 presentations had ≥1 troponin measurement. Clinical ordering of troponin decreased throughout the study with no increase in elevated measurements amongst those tested with hs-cTnT. Small but statistically significant changes in index myocardial infarction (MI) diagnosis (−0.36%/year, 95%CI [confidence interval]:–0.48, −0.24,p < 0.001) and invasive coronary angiography (0.12%/year,95%CI:0, 0.24,p = 0.02) were seen, with no impact on death/MI at 30 days or 3-year survival in episodes of care (EOCs) with elevated cTnT after hs-cTnT implementation. Length of stay (LOS) was shorter among those with an elevated hs-cTnT (−4.44 h/year, 95%CI:–5.27, −3.60, p < 0.001). Non-elevated cTnT EOCs demonstrated shorter total LOS and improved 3-year survival (adjusted hazard ratio:0.90, 95%CI:0.83, 0.97,p = 0.008) although death/MI at 30 days was unchanged using hs-cTnT. ConclusionWidespread implementation of hs-cTnT without altering clinical thresholds reported to clinicians provided significantly shorter LOS without a clinically significant impact on clinical outcomes. A safer cohort with non-elevated cTnT was identified by hs-cTnT compared to the standard cTnT assay.

The Prognostic Value of Cardiac Biomarkers and Echocardiography in Critical COVID-19.

Background: Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores.Methods: Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 h of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index.Results: A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value = 0.011) were significantly associated with mortality, while other biomarkers (D-dimer, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7).Conclusion: Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.

Elevation of Highly Sensitive Cardiac Troponin T Among End-Stage Renal Disease Patients Without Acute Coronary Syndrome.

BackgroundIn end-stage renal disease (ESRD), troponin T concentrations can be elevated even without cardiac ischaemia, which hampers the diagnosis of acute myocardial infarction (AMI). The objectives of our study were to determine the proportion of dialysisdependent ESRD patients without acute coronary syndrome (ACS) but with highly sensitive cardiac troponin T (hs-cTnT) levels above the 99th percentile upper reference limit and to evaluate the range of hs-cTnT among this population.MethodsA cross-sectional study was conducted at the haemodialysis (HD) unit of a tertiary hospital in Malaysia from January 2018 to February 2019. Dialysis-dependent ESRD patients were included and those with a recent history of ACS (within 30 days) were excluded. Pre-dialysed serum hs-cTnT levels were measured using Cobas e411. The upper limit of the 99th percentile value for troponin T was 14 ng/L.ResultsA total of 150 patients were recruited as study participants. The majority were female (62%) and of Malay ethnicity (94%), and the mean (SD) age was 45.19 (16.36) years old. The hs-cTnT range (min, max) was 11.39–738.30 ng/L and the median (interquartile range [IQR]) of hs-cTnT was 59.20 (83.41) ng/L. Elevated hs-cTnT levels were observed in 149/150 (99%) of the study participants (54/55 [98.2%] of the patients were on HD, and 95/95 [100.0%] of the patients were on continuous ambulatory peritoneal dialysis).ConclusionThis study supports prior research showing that even without ACS, most ESRD patients have elevated concentrations of cardiac troponin. Furthermore, our study illustrates the need to revisit the use of absolute troponin values when making a diagnosis of ACS in ESRD patients.

Cardiac Troponin and Recurrent Major Vascular Events after Minor Stroke or Transient Ischemic Attack.

This study was undertaken to investigate whether high-sensitivity cardiac troponin T (hs-cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD2 ) score. INSPiRE-TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs-cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD2 score (lower risk=0-5 vs higher risk=6-7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs-cTnT and MACE (stroke/nonfatal coronary event/vascular death). Among 889 patients (mean age=70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow-up of 3.2 years. hs-cTnT was associated with MACE (9.3%/yr, >URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13-2.35], adjusted HR [Q4 vs Q1 ] = 2.57 [95% CI=1.35-4.97], adjusted HR [log-transformed] = 2.31 [95% CI=1.37-3.89]). This association remained after PSM (adjusted HR=1.76 [95% CI=1.14-2.72]). There was a significant interaction between hs-cTnT and ABCD2 category for MACE occurrence (pinteraction =0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs-cTnT > URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. hs-cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high-risk individuals otherwise deemed at lower risk based on the ABCD2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs-cTnT. ANN NEUROL 2021;90:901-912.