Short-term biological variation and diurnal rhythm of cardiac troponin I (Access hs-TnI) in healthy subjects

Abstract

Background: The availability of high-sensitivity cTnI (hs-cTnI) assays has improved the accuracy of cTn measurements at concentrations around and below the 99th percentile, allowing the evaluation of biological variation.

Methods: cTnI concentrations have been measured in blood samples of 35 reference subjects collected at time 0 (between 8 and 9 AM) and after 1,2,3 and 7 h using a high-sensitive assay (Access hs-TnI). Repeated measure ANOVA and lognormal transformation followed by Nested ANOVA were used to assess differences in cTnI concentration and to estimate biological variation components, respectively. Circadian variability was modelled by sine-wave functions fitting.

Results: At time 0, cTnI concentrations were significantly higher than those measured at other times in overall population, as well as in subjects subdivided by biological sex. The concentrations exhibit a strong circadian variability in males and females, with a predicted interval of around 5.4 h (R² 0.949 and 0.999 for males and females, respectively).

Conclusions: Troponin I demonstrates a diurnal rhythm with decreasing values throughout daytime and the peak concentrations in the morning. The circadian variability is statistically significant, but not relevant from a clinical viewpoint. The intra-individual variation (CV_I) is lower than that reported in the literature and the index of individuality lower than 0.6 suggests a scarce value of reference interval.

Keywords: Circadian variability; Diurnal rhythm; High-sensitivity troponin I; Index of individuality; Inter-individual variation; Intra-individual variation.