Exercise-Induced Troponin Increases May Not Be Benign

This is the link to my PracticeUpdate commentary on the significance of troponin increases with exercise. You can also access it via the following link, which takes you directly to the content, without registering, but consider registering because it’s free and quite good. I also reproduced the piece below so you can read it here.

Exercise-Induced Troponin Levels — Not Be as Benign as We Thought

Paul D. Thompson, MD

Arthur Siegel, MD, and co-workers from Harvard reported that the average CK levels of 15 physicians completing the 1979 Boston Marathon, a 42 km foot race, was 3424 U/L.1 That report predated separating CK into its myocardial (CK-MB) and other bands, but Siegel and colleagues subsequently demonstrated that marathoners also increase their CK-MB levels after the race.2 The CK-MB increase raised the possibility of myocardial injury, but these authors subsequently documented that gastrocnemius muscle samples from marathon runners had >2 times the concentration of CK-MB than skeletal muscle samples from sedentary controls.3 This increased CK-MB was likely due to the presence of skeletal muscle repair cells or “satellite cells”, which are pleuri potential cells capable of regenerating skeletal muscle and of generating CK-MB.3 So the concept emerged that athletes in training are constantly injuring skeletal muscle which is repaired by satellite cells which are themselves injured during prolonged exercise and release CK-MB.

This explanation was reassuring that prolonged endurance exercise did not injure cardiac muscle until Rob Shave, PhD and colleagues demonstrated increased cardiac troponin T (cTnT) levels in London marathon participants.4 I and others dismissed these results because the authors measured the less specific cTnT using early, less specific assays. But subsequently we and others using highly specific measurements of cardiac troponin I (cTnI) documented increases in every one of 71 Boston Marathon participants studied.5 Only about half of the runners exceeded the cTnI level for diagnosing myocardial infarction, but these cTnI increases raised the possibility that prolonged endurance exercise could injure cardiac muscle.

But do increases in cTnI after prolonged exercise matter? Do they have prognostic significance? To address this, I and a group of Dutch researchers lead by Thijs Eijsvogels, PhD followed 735 participants who had cTnI levels measured before and immediately walking 30 to 55 km. Participants walked for an average of 8.3 hours at 68% of their maximum heart rate. 9 participants (1%) had baseline cTnI values >0.040 mcg/L, the 99th percentile for the assay and the level used to diagnose acute myocardial injury and infarction (MI) in the right clinical context, and 63 subjects (9%) had post exercise cTnI values above this level. Theseparticipants were older, more often male, heavier, more often had cardiovascular disease (CV) or CV risk factors, had higher baseline cTnI values, walked at a higher exercise heart rate, and lost more body mass during walking. During an average of 43 months of follow-up, 62 participants developed a study endpoint of death, myocardial infarction, stroke, heart failure, revascularization, or sudden cardiac arrest. Only 7% of those with post exercise troponins < 0.040 had an event, whereas 27% of those with troponins > 0.040 experienced an endpoint. After adjusting for age, sex, hypertension, hypercholesterolemia, diabetes, prior cardiovascular disease, and baseline cTnI concentrations, the hazard ratio was 2.48 (95% confidence limits 1.29–4.78) for those with post-exercise cTnI >99th percentile value.

Increases in cTn after exercise have been considered benign, but this study challenges this concept and is the first to my knowledge to address the prognostic significance of exercise-induced cTn increases. It is possible that the increase in cTnI is due to subclinical disease. This hypothesis is supported by the observation that cTnI increases were greater in subjects with known disease as well as the observation that cTnI increases were more strongly associated with cardiac events than with mortality. Alternatively, exercise-induced cTn increases could result from exercise-induced myocardial injury. There is increasing evidence that life-long, endurance exercise is associated with deleterious cardiac effects including myocardial fibrosis detected by late gadolinium enhancement.6

This study has limitations. cTnI was not measured with the latest high sensitivity assay because samples were obtained and measured before such testing was available. The study examined walking exercise so may not be applicable to the majority of prior studies examining changes in cTn with exercise. Post-exercise cTn levels exceeding the MI diagnostic threshold are observed in approximately 50% of marathon runners, but were observed in only 9% of the walkers in this study. Consequently, it is likely that the prognostic significance of increased Tn levels after marathon participation will be different and probably much lower than for these walkers. Nevertheless, this study may prove to be a “proof of concept” report, with the concept being that exercise-induced cTn is not benign.

The clinical implications of this study are not clear and require further investigation, but clinicians should not assume that exercise-induced Tn increases are benign and should consider additional studies or CVD risk factor modification as appropriate.

1. Siegel AJ, Silverman LM, Lopez RE. Creatine kinase elevations in marathon runners: Relationship to training and competition. Yale J Biol Med. 1980;53(4):275–279.

2. Siegel AJ, Silverman LM, Evans WJ. Elevated skeletal muscle creatine kinase MB isoenzyme levels in marathon runners. JAMA. 1983;250(20):2835–2837.

3. Warhol MJ, Siegel AJ, Evans WJ, Silverman LM. Skeletal muscle injury and repair in marathon runners after competition. Am J Pathol. 1985;118(2):331–339.

4. Shave RE, Whyte GP, George K, Gaze DC, Collinson PO. Prolonged exercise should be considered alongside typical symptoms of acute myocardial infarction when evaluating increases in cardiac troponin T. Heart. 2005;91(9):1219–1220. doi: 91/9/1219 [pii].

5. Eijsvogels TM, Januzzi JL, Taylor BA, et al. Impact of statin use on exercise-induced cardiac troponin elevations. Am J Cardiol. 2014;114(4):624–628. doi: 10.1016/j.amjcard.2014.05.047 [doi].

6. Eijsvogels TM, Fernandez AB, Thompson PD. Are there deleterious cardiac effects of acute and chronic endurance exercise? Physiol Rev. 2016;96(1):99–125. doi: 10.1152/physrev.00029.2014 [doi].

6. Aengevaeren VL, Hopman MTE, Thompson PD, et al. Exercise-Induced Cardiac Troponin I

Paul D. Thompson, MD

Chief of Cardiology — Emeritus, Hartford Hospital

Professor of Medicine, University of Connecticut

Telephone: 860–972–1793

Blog — https://medium.com/@pthomps1947

Twitter — @pauldthompson5


Chief of Cardiology — Emeritus & Director of Sports Cardiology, Hartford Hospital

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Paul D. Thompson, MD

Chief of Cardiology — Emeritus & Director of Sports Cardiology, Hartford Hospital