Circadian rhythm of blood cardiac troponin T concentration

Abstract

Introduction: High-sensitivity cardiac troponin assays have significantly improved the sensitivity of myocardial infarction detection by using cutoff values and early absolute changes. However, variation in repeated measures also depends on biological variability. This study aimed to assess the potential circadian component of this biological variability.

Methods: 17 healthy volunteers were recruited, and standardized conditions for physical activity, meals, exposure to light and duration of sleep were imposed. Blood samples were collected every 4 h and high-sensitivity troponin T assay with a limit of detection of 3 ng/l and a 99th percentile of 14 ng/l were used. Circadian variations were analyzed using the cosinor method.

Results: Statistically significant circadian variations were observed for body temperature, heart rate, and systolic/diastolic arterial blood pressures (p < 0.01 using both a non-adjusted cosinor model and a gender- and BMI-adjusted cosinor model). The amplitudes of the circadian variations were 18.93, 6, 15.35, and 1.92%, respectively. A statistically significant circadian biological variation of troponin blood concentrations was evidenced (p < 0.01 in both the non-adjusted cosinor model and the gender- and BMI-adjusted cosinor), with an amplitude of 20.5% (average: 4.39 ng/l; amplitude: 0.9 ng/l; peak at 06:00 and nadir at 18:00).

Discussion: This study demonstrates a circadian biological variation in blood troponin concentration in a healthy population. The amplitude of this variation challenges the cutoff value for instant rule-out of the rapid rule-in/rule-out of the recent European guidelines for the management of acute coronary syndromes. These findings deserve further investigation in a population at risk of myocardial infarction.

Keywords: Biomarker; Circadian rhythm; Troponin.