Changes In hs-cTnT Research Articles

Abstract 16: Diabetes, Pre-diabetes, and Progression of Subclinical Myocardial Damage

Background: Persons with hyperglycemia even below the threshold for the diagnosis of diabetes are at increased risk for cardiovascular events. The relationships of pre-diabetes and undiagnosed diabetes with progression of subclinical myocardial damage are relatively uncharacterized. Objective: To characterize the associations of diabetes and pre-diabetes with 6-year progression of subclinical myocardial injury, as assessed by a novel highly sensitive assay for cardiac troponin T (hs-cTnT). Methods: We conducted a prospective analysis of hs-cTnT measured at two time points, 6 years apart, in 8446 participants of the community-based ARIC Study with hs-cTnT <14 ng/L and without a history of heart disease, stroke or heart failure at baseline (1990-92). We examined the associations of pre-diabetes and diabetes defined by HbA1c or fasting glucose with 6-year change in hs-cTnT after adjustment for traditional cardiovascular risk factors. Diagnosed diabetes was defined as self-reported physician diagnosis or medication use for diabetes. We used Poisson regression to evaluate the risk of progression of hs-cTnT from non-elevated (<14 ng/L) to elevated (≥14 ng/L) (“incident elevated hs-cTnT”) at 6 years of follow-up. Results: Baseline prevalence of elevated concentrations of hs-cTnT among persons with no diabetes (HbA1c<5.7%), prediabetes (HbA1c 5.7-6.4%), undiagnosed diabetes (≥6.5%), and diagnosed diabetes were 1.8%, 3.3%, 6.3% and 10.3%, respectively. Diagnosed diabetes, undiagnosed diabetes, and pre-diabetes were significantly associated with incident elevated hs-cTnT (Table). The associations of undiagnosed diabetes and pre-diabetes defined by diagnostic categories of HbA1c showed somewhat stronger associations compared to those clinical categories defined by fasting glucose. Conclusions: These results provide evidence for a progressive, deleterious effect of hyperglycemia on the myocardium, even below the threshold for a diagnosis of diabetes.

High-Sensitivity Troponin as a Predictor of Cardiac Events and Mortality in the Stable Dialysis Population

High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker used in diagnosing myocardial injury. The clinical utility and the variation of this biomarker over time remain unclear in hemodialysis (HD) and peritoneal dialysis (PD) patients. We sought to determine whether hs-cTnT concentrations were predictive of myocardial infarction (MI) and death and to examine hs-cTnT variability over a 1-year period. A total of 393 nonacute HD and PD patients (70% HD and 30% PD) were followed in a prospective observational study for new MI and death. Median hs-cTnT was 57 ng/L (interquartile range, 36-101 ng/L) with no observed difference between HD and PD patients (P = 0.11). Incremental increases in mortality (P = 0.024) and MI (P = 0.001) were observed with increasing hs-cTnT quartiles. MI incidence increased significantly across quartiles in both HD and PD patients (P = 0.012 and P = 0.025, respectively), whereas mortality increased only in HD patients (P = 0.015). For every increase of 25 ng/L in hs-cTnT, the unadjusted hazard ratio (HR) was 1.10 for mortality in the whole group (95% CI, 1.04-1.16, P = 0.001) and 1.16 for MI (95% CI, 1.08-1.23, P < 0.001). Adjusted HR for mortality was 1.07 (95% CI, 1.01-1.15, P = 0.04) and 1.14 for MI (95% CI, 1.06-1.22, P < 0.001). Changes in hs-cTnT from baseline concentrations after 1 year were minimal (55 ng/L vs 53 ng/L, P = 0.22) even in patients who had an MI (P = 0.53). hs-cTnT appears to have a useful role in predicting MI and death in the dialysis population. Over a 1-year period concentrations remained stable even in patients who sustained a new cardiac event.

Reproducibility of cardiac biomarkers response to prolonged treadmill exercise

We examined the reproducibility of alterations in cardiac biomarkers after two identical bouts of prolonged exercise in young athletes. Serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were assessed before and after exercise. Significant rises in median hs-cTnT and NT-proBNP occurred in both trials. While the absolute changes in hs-cTnT were smaller after trial 2, the pattern of change was similar and the delta scores were significantly related. However, the change in NT-proBNP was not correlated between trials. The hs-cTnT release demonstrates some consistency after exercise although the blunted hc-cTnT response requires further study.

The clinical value of serial measurement of high-sensitivity cardiac troponin T in acute exacerbations ofchronic obstructive pulmonary disease

ObjectiveTo assess the prevalence and long-term prognostic value of a dynamic (rise/fall) pattern of cardiac troponin T (hs-cTnT) elevation during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) compared with...

Small Changes in Troponin T Levels Are Common in Patients With Non–ST-Segment Elevation Myocardial Infarction and Are Linked to Higher Mortality

The purpose of this study was to examine the extent of change in troponin T levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Changes in cardiac troponin T (cTnT) levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20% to 230% and an absolute change of 7 to 9 ng/l have been suggested as cutoff points. In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitivity cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1,178 patients with a final diagnosis of NSTEMI presenting <24 h after symptom onset. After 6 h of observation, the relative change in the hs-cTnT level remained <20% in 26% and the absolute change <9 ng/l in 12% of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p = 0.002) and in multivariate analyses (hazard ratio: 1.61 [95% confidence interval: 1.17 to 2.21], p = 0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change. Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays

Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality. In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain. Patients were followed up 2 years regarding mortality. Eighty-two (7.3%) patients died during the follow-up. The 2-year prognostic accuracy of hs-cTn was most accurate for hs-cTnT [area under the receivers operating characteristic curve (AUC) 0.78 (95% CI: 0.73-0.83) and outperformed both hs-cTnI (Beckman-Coulter, 0.71 (95% CI: 0.65-0.77; P = 0.001 for comparison), hs-cTnI (Siemens) 0.70 (95% CI: 0.64-0.76; P < 0.001 for comparison)] and cTnT 0.67 (95% CI: 0.61-0.74; P < 0.001 for comparison). Absolute changes of hs-cTnT were more accurate than relative changes in predicting mortality, but inferior to presentation values of hs-cTnT. Combining changes of hs-cTnT within the first 6 h with their presentation values did not further improve prognostic accuracy. Similar results were obtained for both hs-cTnI assays regarding the incremental value of changes. Hs-cTn concentrations remained predictors of death in clinically challenging subgroups such as patients with pre-existing coronary artery disease, impaired renal function, and patients older than 75 years. High-sensitivity cardiac Troponin T is more accurate than hs-cTnI in the prediction of long-term mortality. Changes of hs-cTn do not seem to further improve risk stratification beyond initial presentation values.

High-sensitivity cardiac troponin T in prediction and diagnosis of myocardial infarction and long-term mortality after noncardiac surgery

Perioperative myocardial infarction (MI) is a serious complication after noncardiac surgery. We hypothesized that preoperative cardiac troponin T detected with a novel high-sensitivity (hs-cTnT) assay will identify patients at risk for acute MI and long-term mortality after major noncardiac surgery. This was a prospective cohort study within the VINO trial (n = 608). Patients had been diagnosed with or had multiple risk factors for coronary artery disease and underwent major noncardiac surgery. Cardiac troponin I (contemporary assay) and troponin T (high-sensitivity assay) and 12-lead electrocardiograms were obtained before and immediately after surgery and on postoperative days 1, 2, and 3. At baseline before surgery, 599 patients (98.5%) had a detectable hs-cTnT concentration, and 247 (41%) were >14 ng/L (99th percentile). After surgery, 497 patients (82%) had a rise in hs-cTnT (median change in hs-cTnT +2.7 ng/L [interquartile range 0.7-6.8]). During the first 3 postoperative days, there were 9 patients (2.5%) with a preoperative hs-cTnT <14 ng/L with acute MI, compared with 21 patients (8.6%) with a preoperative hs-cTnT >14 ng/L (odds ratio 3.67, 95% CI 1.65-8.15). During long-term follow-up, 80 deaths occurred. The 3-year mortality rate was 11% in patients with a preoperative hs-cTnT concentration <14 ng/L compared with 25% in patients with a preoperative hs-cTnT >14 ng/L (adjusted hazard ratio 2.17, 95% CI 1.19-3.96). In this cohort of high-risk patients, preoperative hs-cTnT concentrations were significantly associated with postoperative MI and long-term mortality after noncardiac surgery.

DIAGNOSTIC PERFORMANCE OF RISING, FALLING, OR RISING AND FALLING KINETIC CHANGES OF HIGH-SENSITIVITY CARDIAC TROPONIN T IN AN UNSELECTED EMERGENCY DEPARTMENT POPULATION

BACKGROUND: Current ESC guidelines for the diagnosis of myocardial infarction consider a rise and/or fall of cardiac biomarkers. However, whether rising or falling patterns of high-sensitivity cardiac troponin T (hs-cTnT) improve the discrimination of ST-elevation myocardial infarction (non-STEMI) from non-acute coronary syndromes (ACS) has not been evaluated yet. METHODS: We compared protocols of rising and falling absolute and relative hs-cTnT changes in an unselected emergency department population. RESULTS: A total of 635 patients with unstable angina pectoris (UAP), non-STEMI, or acute symptoms and increased hs-cTnT (>99th percentile) were enrolled. Of these, 572 patients met the inclusion criteria of consistently rising patterns (n=254, 44.4%), consistently falling patterns (n=224, 39.2%), or falling patterns after an initial rise (n=94, 16.4%). Final diagnoses included 66 (11.5%) patients with UAP, 141 (24.7%) patients with non-STEMI, and 365 (63.8%) patients with hs-cTnT elevations not due to ACS. Rising values were found more frequently in patients with non-STEMI, as compared to non-ACS (OR 3.69, 95% CI 2.46–5.53; p<0.0001), and falling patterns were observed more frequently in patients with non-ACS conditions (OR 3.56, 95% CI 2.24–5.63; p<0.001). Addition of rising but not falling changes increased diagnostic performance of hs-cTnT concentrations at presentation: positive: AUC 0.680 (95% CI 0.618–0.742) vs. 0.861 (95% CI 0.822–0.900; p<0.0001), negative: AUC 0.678 (95% CI 0.545–0.812) vs. 0.741 (95% CI 0.635–0.847). A 20% criterion as proposed by ESC guidelines performed equally for positive and negative changes only when admission hs-cTnT values were considered: AUC 0.785 (95% CI 0.726–0.845) vs. AUC 0.763 (95% CI 0.681–0.845); p=ns. CONCLUSIONS: Detection of rising but not falling hs-cTnT values improves discrimination of non-STEMI from non-ACS in an unselected emergency department population.

High-Sensitivity Cardiac Troponin in the Distinction of Acute Myocardial Infarction From Acute Cardiac Noncoronary Artery Disease

We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and its early change are useful in distinguishing acute myocardial infarction (AMI) from acute cardiac noncoronary artery disease. In a prospective, international multicenter study, hs-cTn was measured with 3 assays (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI Siemens) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists. AMI was the adjudicated final diagnosis in 127 patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 μg/L [interquartile range, 0.049-0.246 μg/L] versus 0.012 μg/L [interquartile range, 0.006-0.034 μg/L]; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019 μg/L [interquartile range, 0.007-0.067 μg/L] versus 0.001 μg/L [interquartile range, 0-0.003 μg/L]; P<0.001) than patients with cardiac noncoronary artery disease. Similar findings were obtained with the hs-cTnI assays. Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnI assays). Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease. These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and validated in an independent validation cohort. The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Absolute and Relative Kinetic Changes of High-Sensitivity Cardiac Troponin T in Acute Coronary Syndrome and in Patients with Increased Troponin in the Absence of Acute Coronary Syndrome

We evaluated kinetic changes of high-sensitivity cardiac troponin T (hs-cTnT) in patients with acute coronary syndrome (ACS) and patients with hs-cTnT increases not due to ACS to rule in or rule out non-ST-segment elevation myocardial infarction (STEMI). hs-cTnT was measured serially in consecutive patients presenting to the emergency department. Patients with ACS who had at least 2 hs-cTnT measurements within 6 h and non-ACS patients with hs-cTnT concentrations above the 99th percentile value (14 ng/L) were enrolled to compare absolute and relative kinetic changes of hs-cTnT. For discrimination of non-STEMI (n=165) in the entire study population (n=784), the absolute δ change with the ROC-optimized value of 9.2 ng/L yielded an area under the curve of 0.898 and was superior to all relative δ changes (P<0.0001). The positive predictive value for the absolute δ change was 48.7%, whereas the negative predictive value was 96.5%. In a specific ACS population with exclusion of STEMI (n=342), the absolute δ change with the ROC-optimized value of 6.9 ng/L yielded a positive predictive value of 82.8% and a negative predictive value of 93.0%. In comparison to the ≥20% relative δ change, the ROC-optimized absolute δ change demonstrated a significantly added value for the entire study population and for the ACS cohort (net reclassification index 0.331 and 0.499, P<0.0001). Absolute δ changes appear superior to relative δ changes in discriminating non-STEMI. A rise or fall of at least 9.2 ng/L in the entire study population and 6.9 ng/L in selected ACS patients seems adequate to rule-out non-STEMI. However, δ-values are useful to rule-in non-STEMI only in a specific ACS population.

72-h Kinetics of High-Sensitive Troponin T and Inflammatory Markers after Marathon

Strenuous exercise induces significant increases in cardiac biomarkers. However, it is still unclear whether this is caused by cardiomyocyte necrosis or secondary mechanisms such as ischemia, cardiac energy deficiency, increased inflammation, or renal dysfunction. Therefore, we investigated cardiac biomarkers (high-sensitive cardiac troponin T (hs-cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (h-FABP)), inflammation markers (high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10, tumor necrosis factor-α), and renal function (cystatin C) in 102 healthy men age 42 ± 9 yr before and 0, 24, and 72 h after a marathon. Kinetics of hs-cTnT revealed a peak immediately after the race (V3) that decreased rapidly to pretest values within 72 h (V5) (median (interquartile range) = 31.07 (19.25-46.86) ng·L(-1) at V3 and 3.61 (3.20-6.70) ng·L(-1) at V5, P < 0.001). NT-proBNP and h-FABP kinetics showed a similar pattern (NT-proBNP = 92.6 (56.9-149.7) ng·L(-1) at V3 and 34.9 (21.7-54.5) ng·L(-1) at V5; h-FABP = 44.99 (32.19-64.42) μg·L(-1) at V3 and 7.66 (5.64-10.60) μg·L(-1) at V5; always P < 0.001). Proinflammatory markers, such as IL-6 and hs-CRP, and renal dysfunction were significantly augmented immediately after the race (before the race compared with maximum after the race: IL-6 = 15.5-fold, hs-CRP = 28-fold, cystatin C = 1.22-fold, all P < 0.001). These increases were not related to the increase of hs-cTnT. Similarly, training history, finishing time, and exercise intensity were not associated with changes of hs-cTnT. Cardiac biomarkers were increased immediately after a marathon race. Interestingly, values returned to normal levels within 72 h. These kinetics with a sharp peak indicate that cardiac necrosis during marathon running seems very unlikely but may be explained by altered myocyte metabolism.

A three dimensional mid sagittal plane for brain asymmetry measurement

Patterns and determinants of temporal change in highly-sensitivity troponin-T (hs-cTNT), a novel measure of subclinical myocardial injury, among asymptomatic persons have not been well characterized.We studied 8571 ARIC Study participants, free of cardiovascular disease, who had hs-cTNT measured at two time-points, 6 years apart (1990–1992 and 1996–1998). We examined the association of baseline 10-year atherosclerotic cardiovascular (ASCVD) risk-group (< 5%, 5–7.4%, ≥ 7.5%) and individual cardiac risk-factors with change across hs-cTNT categories using Poisson and Multinomial Logistic regression and with mean continuous hs-cTNT change using linear regression.Mean age was 57 years and 43% were male. Mean (SD) 6-year hs-cTNT change was higher across increasing ASCVD risk-groups; + 1.2 (6.1) ng/L [< 5%], + 2.1 (5.4) ng/L [5–7.4%], and + 2.8 (8.8) ng/L [≥ 7.5%]. Major baseline determinants of temporal hs-cTNT increases were: age, male gender, hypertension, diabetes, and obesity. In addition, the relative risk (RR) of incident elevated hs-cTNT (≥ 14 ng/L) was 1.46 (95% CI 1.1–2.0) for persons with sustained hypertension compared to those who remained normotensive. Results for sustained obesity (RR 1.65 [1.19–2.29]) and hyperglycemia (RR 1.76 [1.16–2.67]) were similar. These associations were generally stronger after accounting for survival bias. However, smoking, LDL-cholesterol and triglycerides were not associated with hs-cTNT change. HDL-cholesterol was associated with declining hs-cTNT.Persons in higher ASCVD risk-groups were more likely to have increases in hs-cTNT over 6 years of follow-up. The modifiable risk-factors primarily driving this association were diabetes, hypertension, and obesity; particularly when they were persistently elevated over follow-up. Future studies are needed to determine whether modifying these risk factors can prevent progression of subclinical myocardial injury.