Sources of Variability in Measurements of Cardiac Troponin T in a Community-Based Sample: The Atherosclerosis Risk in Communities Study

Abstract

Background The enhanced sensitivity of cardiac troponin T (cTnT) assays calls for its use as a prognostic marker in chronic heart failure, as an accurate and early marker of myocyte damage, and as a sensitive indicator of acute episodes in chronic disease. To facilitate these applications and inform required benchmarks, we estimated the variability in cTnT measurements, the sources of this variability, and the stability of cTnT using samples stored at −70 °C. Methods and Results Stored samples from the Atherosclerosis Risk in Communities Study (ARIC) study (1996–1998) and ARIC Carotid MRI study participants (2005–06) were assayed in 2009–10 to examine variability in cTnT attributable to laboratory (replicates after freeze thaw, n=29), processing (blind replicates from same blood draw, n = 87), short- (n = 40) and long-term biological variation (repeat visit, n = 38), and degradation in frozen storage (n = 10,870). The Elecsys Troponin T (Roche Diagnostics, Indianapolis, IN) was used to assay cTnT on an automated Cobas e411 analyzer. The lower limit of detection was 3 ng/L. Approximately 1/4th to 1/3rd of the participants had values below the detection limit. The paired correlation for all other comparisons exceeded 0.93 (except for samples drawn 8 years apart = 0.36). The coefficients of variation for individual sources of variation in cTnT were as follows: laboratory 2.1% in those with heart failure (HF) and 11.2% in those without HF; processing 18.3%; biological at six weeks 16.6%, and at eight years 48.4%. The reference change value at 6 weeks was 68.5% and would require 4 samples to determine homeostatic set point within ± 25%. Only modest degradation was detected in stored frozen samples for an average of 8 years. Conclusions cTnT is detectable in approximately 70% of community-dwelling men and women aged 53 to 75 years. The laboratory reliability was high: the reliability coefficient (r) was 0.99 in those with heart failure and 0.94 in those without heart failure. The intra-individual (biologic) variability was low on repeat testing after 6 weeks (r=0.94), and increased for measurements taken 8 years apart (R=0.36). Troponin T is stable in storage at −70° C and the variability in cTnT values attributable to one freeze-thaw cycle is of small magnitude.

Do Cardiac Biomarkers NT-proBNP and hsTnT Predict Microvascular Events in Patients With Type 2 Diabetes? Results From the ADVANCE Trial

“…The NRI models that we have constructed are necessarily based on somewhat artificial cutoffs, but they contain most of the pertinent information that might typically be used to estimate the cardiovascular risk of patients with diabetes. NT-proBNP and hsTnT were measured on stored serum samples, and although we cannot rule out the potential for differential sample degradation that biases our results, both of these markers appear fairly stable in long-term storage (34,35). …”

Circulating Troponin As Measured by a Sensitive Assay for Cardiovascular Risk Assessment in Primary Prevention

“…In line with this reasoning are recently published results with respect to the incremental value of measuring cTnT by use of a high-sensitivity assay (hs-cTnT) for risk prediction in the Atherosclerosis Risk in Communities (ARIC) study cohort, a general population of middle-aged to older adults (30 ). The ARIC cohort is significantly older than our cohort, and the prevalence of measurable hs-cTnT was 66.5%, indicating that the association of hs-cTnT concentrations with age translated into a significantly higher prevalence of measurable hs-cTnT (31 ). Finally, subjects lost to follow-up in the present study were significantly older, more frequently men, and had lower eGFR, all of which might have contributed to a lower prevalence of measurable cTnI in the study cohort available for analysis.…”

Sleep Apnea in Total Joint Arthroplasty Patients and the Role for Cardiac Biomarkers for Risk Stratification: an Exploration of Feasibility

“…In addition to underlying disease states, the variability in sample processing, differences in manufacturing methods and variation in the generation of cTn product measured (e.g., fourth generation cTnT or high sensitivity cTnT [hs-cTnT]) may all affect interpretation of results [105,128].…”

“…As with cTns, four studies showed that a rise in NT-proBNP levels after emergency TJA predicts in-hospital cardiac events [129,134] and increased 1- [128,129] and 2-year [130] mortality in patients aged 60-86 years, but did not predict 6-month mortality or cardiac complications in older adults aged 85 ± 9.6 years [132], who may have other competing co-morbidities. Table 5 summarizes data from studies that evaluated BNPs following elective TJA.…”