Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population

Division of Cardiology, University of Texas Southwestern Medical Center, 5909 Harry Hines Blvd, Dallas, TX 75390-9047, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 12/2010; 304(22):2503-12. DOI: 10.1001/jama.2010.1768
Source: PubMed


Detectable levels of cardiac troponin T (cTnT) are strongly associated with structural heart disease and increased risk of death and adverse cardiovascular events; however, cTnT is rarely detectable in the general population using standard assays.
To determine the prevalence and determinants of detectable cTnT in the population using a new highly sensitive assay and to assess whether cTnT levels measured with the new assay associate with pathological cardiac phenotypes and subsequent mortality.
Cardiac troponin T levels were measured using both the standard and the highly sensitive assays in 3546 individuals aged 30 to 65 years enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic, population-based cohort study. Mortality follow-up was complete through 2007. Participants were placed into 5 categories based on cTnT levels.
Magnetic resonance imaging measurements of cardiac structure and function and mortality through a median of 6.4 (interquartile range, 6.0-6.8) years of follow-up.
In Dallas County, the prevalence of detectable cTnT (≥0.003 ng/mL) was 25.0% (95% confidence interval [CI], 22.7%-27.4%) with the highly sensitive assay vs 0.7% (95% CI, 0.3%-1.1%) with the standard assay. Prevalence was 37.1% (95% CI, 33.3%-41.0%) in men vs 12.9% (95% CI, 10.6%-15.2%) in women and 14.0% (95% CI, 11.2%-16.9%) in participants younger than 40 years vs 57.6% (95% CI, 47.0%-68.2%) in those 60 years and older. Prevalence of left ventricular hypertrophy increased from 7.5% (95% CI, 6.4%-8.8%) in the lowest cTnT category (<0.003 ng/mL) to 48.1% (95% CI, 36.7%-59.6%) in the highest (≥0.014 ng/mL) (P < .001); prevalence of left ventricular systolic dysfunction and chronic kidney disease also increased across categories (P < .001 for each). During a median follow-up of 6.4 years, there were 151 total deaths, including 62 cardiovascular disease deaths. All-cause mortality increased from 1.9% (95% CI, 1.5%-2.6%) to 28.4% (95% CI, 21.0%-37.8%) across higher cTnT categories (P < .001). After adjustment for traditional risk factors, C-reactive protein level, chronic kidney disease, and N-terminal pro-brain-type natriuretic peptide level, cTnT category remained independently associated with all-cause mortality (adjusted hazard ratio, 2.8 [95% CI, 1.4-5.2] in the highest category). Adding cTnT categories to the fully adjusted mortality model modestly improved model fit (P = .02) and the integrated discrimination index (0.010 [95% CI, 0.002-0.018]; P = .01).
In this population-based cohort, cTnT detected with a highly sensitive assay was associated with structural heart disease and subsequent risk for all-cause mortality.

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Available from: Anand Rohatgi, Feb 12, 2014
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    • "Second, other cardiac biomarkers, such as N-terminal pro-brain natriuretic peptide, and echocardiographic parameters, were not used as variables in the statistical analysis in the present study although it is known that the presence of heart failure and elevated levels of brain natriuretic peptide are associated with the elevation of hs-TnT levels [7] [21] [22]. Third, it is possible that the hazard of elevated hs-TnT may have been underestimated because patients in the OACIS registry with hs-TnT levels of 0.008 ng/mL were used as reference group, in contrast to several studies that have used patients with undetectable hs-TnT (<0.003 ng/mL) as a reference [9] [10] [11]. Finally, the optimal bloodsampling period for hs-TnT measurements after STEMI should be evaluated, because hs-TnT was negatively correlated with the blood-sampling period which indicated that about 21% (r = À0.46, "
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    ABSTRACT: Background: It is unclear whether serum high-sensitive troponin T (hs-TnT) levels at the convalescent stage of ST-elevation myocardial infarction (STEMI) are associated with long-term mortality. Methods: This study enrolled a total of 2944 consecutive STEMI patients who were registered in the Osaka Acute Coronary Insufficiency Study between 2000 and 2009, and whose hs-TnT levels were evaluated at the convalescent stage. Patients were divided into four hs-TnT category groups according to the results of survival classification and regression tree (CART) analysis. The impact of hs-TnT levels on 5-year mortality was evaluated using multivariate Cox regression analysis. Results: Only one patient had hs-TnT level below the detection limit of the assay (<0.003 ng/mL). The median hs-TnT level was 0.025 (quartile 0.011–0.083) ng/mL. During the median follow-up period of 1782 days, 188 patients died. Survival CART analysis revealed that the 1st, 2nd, and 3rd discriminating hs-TnT levels to discern 5-year mortality were 0.028, 0.008, and 1.340 ng/mL, respectively. The adjusted hazard ratios for the medium-low (0.009–0.028 ng/mL), medium-high (0.029–1.340 ng/mL), and high-risk (�1.341 ng/mL) groups were 3.03 (95% confidence interval 1.18–7.77, p = 0.021), 4.29 (1.63–11.28, p = 0.003), and 8.68 (2.20– 34.27, p = 0.002), respectively. Integrated discrimination improvement (IDI) analysis revealed that incorporation of this hs-TnT classification scheme with other clinical variables statistically improved the discriminatory accuracy for 5-year mortality, with a time-dependent IDI of 0.0076 (p = 0.033). Conclusions: hs-TnT levels at the convalescent stage were associated with long-term mortality in STEMI patients. Even subclinical elevation of hs-TnT levels was associated with increased 5-year mortality.
    Full-text · Article · Sep 2015 · Journal of Cardiology
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    • "However, not one patient in our study had severe renal dysfunction or autoimmune disease. Currently, there is no evidence that one can distinguish between cell death by necrosis [24] reflecting irreversible myocardial damage or apoptosis [25], but an increased hs-TnT is associated with adverse prognosis in other cardiac conditions [8] [9] [16]. Fig. 2. High-sensitive TnT and the relationship with NT-proBNP and hs-CRP. "
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    ABSTRACT: Adult congenital heart disease (ACHD) patients are at risk of late complications including arrhythmias, heart failure and sudden death. High-sensitive troponin-T (hs-TnT) is the standard for diagnosing acute coronary syndrome, but is also associated with cardiac function and prognosis in other cardiac diseases. We aimed to describe hs-TnT level in ACHD patients, and determine its relationship with cardiac function and other biomarkers. Consecutive ACHD patients, visiting the outpatient clinic, underwent echocardiography, exercise testing and venipuncture on the same day. In total 587 patients were included (median age 33 [IQR 25-41] years, 58% male, 90% NYHA class I). hs-TnT was above the detection limit of 5ng/L in 241 patients (41%), of whom 47 (8%) had hs-TnT levels above the 99th percentile of normal of 14ng/L. hs-TnT levels were highest in patients with a systemic RV or pulmonary hypertension. Patients with normal or non-detectable hs-TnT were younger (32 [IQR 24-40] years) than patient with elevated hs-TnT (42 [IQR 36-60] years, p<0.001). The prevalence of hs-TnT ≥14ng/L was higher in patients with NYHA ≥II (36%, p<0.001), systemic systolic dysfunction (38%, p<0.001), non-sinus rhythm (43%, p<0.001) and elevated pulmonary pressures (39%, p<0.001). hs-TnT was correlated with NT-proBNP (r=0.400, p<0.001). hs-TnT above the 99th percentile of normal is observed in a non-trivial portion of stable ACHD patients, especially in those with a systemic RV or elevated pulmonary pressures. Since this biomarker of myocardial damage is related to NT-proBNP and ventricular function, its potential predictive value in ACHD patients seems promising and further investigation of underlying mechanisms is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · International Journal of Cardiology
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    • "The increasing use of highly sensitive troponin assays needs to be considered. It has been shown that a quarter of the general population and nearly all patients with stable coronary artery disease have troponins detectable with these new assays [22] [23]. Hence with these assays, it would be important to consider not simply the presence of serum troponin but the magnitude of elevation, for example, adopting a cut-off value to categorise patients as we have in this study (ie 99 th percentile for a normal Australian population). "
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    ABSTRACT: Background Cardiac troponins are frequently measured as part of the pre-operative work-up of patients prior to coronary artery bypass graft surgery (CABG). The utility of measuring these levels in elective patients, and the clinical implication of an abnormal result are unclear. The following study investigates the relationship between cardiac troponin I (cTnI) measured as part of a routine pre-operative work-up and outcomes following CABG. Methods From January 2010 to December 2012, 378 patients underwent isolated, elective CABG and had cTnI measured prospectively, as part of their pre-operative work-up. Patients were divided into normal (Group I) and elevated (Group II) cTnI groups. Pre-operative, operative and post-operative data were obtained from our institution's prospectively collected database. Results Elevated cTnI was present in 47 patients (12.4%) pre-operatively. Intra-operative variables did not differ between the elevated cTnI and control groups. Both 30-day mortality (Group I: 0.9% v Group II: 6.4%, p = 0.03) and cardiac arrest (Group I: 1.5% v Group II: 8.5%, p = 0.01) were significantly more frequent in the elevated cTnI group. In multivariable analysis, elevated cTnI remained a predictor for cardiac arrest (OR 5.8, 95% CI 1.2–29.2). Conclusions Patients presenting for elective CABG frequently have elevated cTnI on pre-operative work-up. These patients may be at a greater risk of 30-day mortality and cardiac arrest. Routine pre-operative measurement of cTnI may alert clinicians to a higher operative risk.
    Full-text · Article · Aug 2014 · Heart, Lung and Circulation
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