The clinical significance of exercise-induced cardiac biomarkers
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Background Physical exercise induces changes in cardiac biomarkers associated with cardiac injury and inflammation. The ability of these changes to identify subjects at risk of sport-related cardiac events is largely unknown. This project aimed to identify the physiological pattern and predictors of the exercise-induced cardiac troponin (cTn) and C-reactive protein (CRP) response to exercise. A potential pathological response to exercise was explored in a subset of subjects. Methods The exercise-induced increase in cTn and CRP were studied in two cohorts of presumably healthy recreational athletes; The North Sea Race Endurance Exercise Study (NEEDED) 2013 (n=97) and 2014 (n=1002). Both studies obtained data before and within 24 hours after a 91-kilometre cycling competition (“The North Sea Race”). Coronary computed tomography angiography was used in a subset of subjects to identify a possible association between exercise-induced cTn elevation and underlying coronary artery disease. Results In Paper 1 (n=97), we determined the magnitude and time-dependent changes in cTnI following the North Sea Race. There was a continued increase in cTnI between immediately after the race and 3 hours following the race. This finding was important for the design of the main study. Also, three of the four subjects with highest exercise-induced cTnI values had significant coronary artery pathology. In Paper 2 (n=1002), 84-92 % of subjects exceeded the 99th percentile of the cTn assay 3 hours post-race. At 24 hours post-race, 18-30 % still had cTn values above the 99th percentile. Lower race duration and higher systolic blood pressure were predictors of the exercise-induced cTn increase. In Paper 3 (n=120), subjects were assessed by coronary computed tomography angiography (CCTA). Subjects with obstructive CAD (n=9) had significantly higher cTn levels at 24 hours after the race, but not at 3 hours after the race. In paper 4 (n=97), the CRP response to exercise was determined. In this study, CRP continued to increase until 24 hours following the race. Physical fitness was found to significantly attenuate the exercise-induced CRP response. There was no association between exercise-induced levels of CRP and cTnI. Conclusion The present work identified the physiological pattern and predictors of exercise-induced cTn and CRP. More than 84 % of subjects had cTn levels above the 99th percentile cut-off. This finding supports the hypothesis that exercise-induced cTn increase is a physiological response in most subjects. Lower race duration and higher systolic blood pressure were consistent predictors of the exercise-induced cTn response. In a subset of subjects, a prolonged elevation of cTn was associated with occult obstructive CAD, suggesting a pathological pattern of cTn increase in these subjects. Lastly, physical fitness was inversely associated with the exercise-induced CRP response. No association between exercise-induced cTn- and CRP increase was identified.
Has partsPaper I: Skadberg Ø, Kleiven Ø, Bjørkavoll-Bergseth M, Melberg T, Bergseth R, Selvåg J,Auestad B, Greve OJ, Dickstein K, Aarsland T, Ørn S. (2017) Highly increased Troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: The North Sea Race Endurance Exercise Study (NEEDED) 2013. Eur J Prev Cardiol. 24(8):885-894. The article is not available in the thesis due to publisher restrictions. The published version is available at: https://doi.org/10.1177/2047487317693130.
Paper II: Kleiven Ø, Omland T, Skadberg Ø, Melberg TH, Bjørkavoll-Bergseth MF, Auestad B, Bergseth R, Greve OJ, Aakre KM, Ørn S. (2019) Race duration and blood pressure are major predictors of exercise-induced cardiac troponin elevation. Int J Cardiol. 283:1-8. The article is available in the main thesis. The article is also available at: https://doi.org/10.1016/j.ijcard.2019.02.044.
Paper III: Kleiven Ø, Omland T, Skadberg Ø, Melberg TH, Bjørkavoll-Bergseth MF, Auestad B, Bergseth R, Greve OJ, Aakre KM, Ørn S. (2019) Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise. Eur J Prev Cardiol. The article is not available in the thesis due to publisher restrictions. The published version is available at: https://doi.org/10.1177/2047487319852808.
Paper IV: Kleiven Ø, Bjørkavoll-Bergseth M, Melberg T, Skadberg Ø, Bergseth R, Selvåg J, Auestad B, Aukrust P, Aarsland T, Ørn S. (2018) High physical fitness is associated with reduction in basal- and exercise-induced inflammation. Scand J Med Sci Sports. 28(1):172-179. The article is available in the main thesis. The article is also available at: https://doi.org/10.1111/sms.12878.