Circulating cardiac troponin T exhibits a diurnal rhythm
Lieke J J Klinkenberg1, Jan-Willem van Dijk2, Frans E S Tan3
1Department of Clinical Chemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands.
Insights
Chronically elevated cardiac troponin T (cTnT) levels exhibit a diurnal rhythm, not random fluctuations. Understanding this biological variation is key for accurate diagnosis and risk stratification in cardiovascular disease.
Area of Science:
- Cardiology
- Biomarker Research
- Clinical Chemistry
Background:
- High-sensitivity cardiac troponin (cTn) assays enhance acute myocardial infarction (AMI) detection.
- Many positive cTn results do not indicate AMI, necessitating serial testing and kinetic interpretation.
- Understanding cTn biological variation is crucial for accurate diagnosis.
Purpose of the Study:
- To challenge the assumption of random fluctuation in chronically elevated cardiac troponin T (cTnT).
- To investigate the presence and characteristics of a diurnal rhythm in cTnT levels.
Main Methods:
- Two studies assessed cTnT biological variation and diurnal rhythm in 23 male type 2 diabetes patients without cardiovascular disease.
- Study 1 involved 11-hour serial blood sampling (8:30 am - 7:30 pm).
- Study 2 utilized hourly sampling over 25 hours to confirm diurnal rhythm.
Main Results:
- A significant diurnal rhythm of cTnT was observed, with peak levels in the morning.
- cTnT concentrations gradually decreased during the day and rose overnight.
- The decrease was most pronounced in individuals with higher baseline cTnT.
Conclusions:
- The identified diurnal cTnT rhythm supports interpreting dynamic changes alongside clinical presentation.
- Standardized sampling times are recommended for epidemiological studies and risk stratification using cTnT.
- Findings highlight the non-random biological variation of cTnT.
Objectives:
The goal of this study was to test the unverified assumption that chronically elevated cardiac troponin T (cTnT) levels fluctuate randomly around a homeostatic set point.
Background:
The introduction of high-sensitivity cardiac troponin (cTn) assays has improved sensitivity for acute myocardial infarction (AMI). However, many patients with a single positive cTn test result do not have AMI. Therefore, the diagnosis of AMI relies strongly on serial testing and interpretation of cTn kinetics. Essential in this regard is a profound understanding of the biological variation of cTn.
Methods:
Two studies were conducted to assess biological cTnT variation and to investigate the presence of a diurnal rhythm of cTnT. Study 1 comprised 23 male subjects with type 2 diabetes, with no acute cardiovascular disease. Serial venous blood samples were drawn over an 11-h period (8:30 am to 7:30 pm). In study 2, the presence of a diurnal cTnT rhythm was investigated by hourly sampling of 7 subjects from study 1 over 25 h.
Results:
In study 1, we observed a gradual decrease in cTnT concentrations during the day (24 ± 2%). This decrease was present in all participants and was most prominent in subjects with the highest baseline cTnT values (Pearson's R 0.93). Diurnal variation of cTnT, as assessed in study 2, was characterized by peak concentrations during morning hours (8:30 am, 17.1 ± 2.9 ng/l), gradually decreasing values during daytime (8:30 pm, 11.9 ± 1.6 ng/l), and rising concentrations during nighttime (8:30 am the next day, 16.9 ± 2.8 ng/l).
Conclusions:
A diurnal cTnT rhythm substantiates the recommendation that all dynamic changes in cTnT should be interpreted in relation to the clinical presentation. Epidemiological studies and risk-stratification protocols with the use of cTnT may benefit from standardized sampling times. (Exercise and Glycemic Control in Type 2 Diabetes; NCT00945165).
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