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Short- and Long-Term Biological Variation in Cardiac Troponin I Measured with a High-Sensitivity Assay: Implications for Clinical Practice

¹ Department of Laboratory Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, CA; ² Singulex, Inc., Hayward, CA; ³ Bioscience Club of Heidelberg, Heidelberg, Germany; ⁴ Department of Pathology and Laboratory Medicine, University of Texas Southwestern Medical School, Dallas, TX.

^aAddress correspondence to this author at: San Francisco General Hospital, 1001 Potrero Ave., Rm. 2M27, San Francisco, CA 94110; e-mail wualan{at}labmed2.ucsf.edu.

Background: The improved detection limit and precision in new-generation commercial assays for cardiac troponin I (cTnI) have lowered the 99th-percentile cutoff value, yielding higher frequencies of positive test results. Because serial testing is important in interpreting low concentrations, we evaluated the biological variation of cTnI in both the short (hours) and long (weeks) terms and determined reference change values (RCVs) and the index of individuality (II) for cTnI.

Methods: To assess short- and long-term variation, we collected blood from 12 healthy volunteers hourly for 4 h and from 17 healthy individuals once every other week for 8 weeks, measured cTnI with a high-sensitivity assay (detection limit, 0.2 ng/L), and computed analytical, intraindividual, interindividual, and total CVs (CV_A, CV_I, CV_G, and CV_T, respectively; CV_T = CV_A + CV_I + CV_G) as well as the II. Because of the slight right-skewness of the data, RCVs were calculated with a lognormal approach.

Results: Within-day CV_A, CV_I, and CV_G values were 8.3%, 9.7%, and 57%, respectively; the corresponding between-day values were 15%, 14%, and 63%. Within- and between-day IIs were 0.21 and 0.39, respectively. Lognormal within-day RCVs were 46% and –32%, respectively; the corresponding between-day values were 81% and –45%.

Conclusions: The low II indicates that population-based reference intervals are less useful for interpreting cTnI values than following serial changes in values in individual patients. This criterion is particularly important for interpreting results from patients who show cTnI increases at low concentrations measured with very high-sensitivity assays, from patients presenting with chest pain (short term), and for evaluating drugs for cardiotoxicity (long term).

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