Lieke J J Klinkenberg1, Jan-Willem van Dijk2, Frans E S Tan3, Luc J C van Loon2, Marja P van Dieijen-Visser1, Steven J R Meex4. 1. Department of Clinical Chemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands. 2. Department of Human Movement Sciences, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands. 3. Department of Methodology and Statistics, Maastricht University, Maastricht, the Netherlands. 4. Department of Clinical Chemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC), Maastricht, the Netherlands. Electronic address: steven.meex@mumc.nl.
Abstract
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).
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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