Abstract
Purpose of the Review
Markers of myocardial stress, including troponin, creatine kinase, and brain natriuretic peptide are frequently elevated after endurance athletic pursuits. Here, we summarize the current literature pertaining to the potential mechanism of cardiac enzyme release in athletes and seek to determine the clinical implications of these findings.
Recent Findings
Recent studies have highlighted the potential adverse cardiac effects of long-term extreme endurance exercise. While troponin release occurs in a pattern distinct from ischemic damage, BNP release has been correlated with right ventricular dysfunction and is likely related to wall stress from prolonged increases in cardiac output. Higher intensity pre-race training regimes are associated with lower race-day enzyme release.
Summary
While the holistic benefits of regular moderate exercise are indisputable, recent studies have raised concerns about the potential risks of extreme endurance exercise. Release of serum biomarkers suggesting myocardial damage was first described in the 1970s, yet our understanding of the implications of these findings remains incomplete. The mechanisms of release are complex but appear to be primarily physiological phenomena rather than pathologic.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the council on clinical cardiology (subcommittee on exercise, rehabilitation, and prevention) and the council on nutrition, physical. Circulation. 2003;107:3109–16. https://doi.org/10.1161/01.CIR.0000075572.40158.77.
Fletcher GF, Balady G, Blair SN, et al. Statement on exercise: benefits and recommendations for physical activity programs for all Americans. Circulation. 1996;94(4):857 LP-862. https://doi.org/10.1161/01.CIR.94.4.857.
Haskell WL, Nelson ME, Dishman RK, et al. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report. Washingt DC US 2008;67(2):683. https://doi.org/10.1111/j.1753-4887.2008.00136.x.
Dietz WH. The response of the US Centers for Disease Control and Prevention to the obesity epidemic. Annu Rev Public Health. 2015;36(1):575–96. https://doi.org/10.1146/annurev-publhealth-031914-122415.
Knechtle B, Knechtle P, Lepers R. Participation and performance trends in ultra-triathlons from 1985 to 2009. Scand J Med Sci Sport. 2011;21(6):e82–90. https://doi.org/10.1111/j.1600-0838.2010.01160.x.
Williams PT, Thompson PD. Increased cardiovascular disease mortality associated with excessive exercise in heart attack survivors. Mayo Clin Proc. 2014;89(9):1187–94. https://doi.org/10.1016/j.mayocp.2014.05.006.
Mons U, Hahmann H, Brenner H. A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coronary heart disease: evidence from a large cohort with repeated measurements. Heart. 2014;100(13):1043–9. https://doi.org/10.1136/heartjnl-2013-305242.
Armstrong MEG, Green J, Reeves GK, Beral V, Cairns BJ. Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom. Circulation. 2015;131(8):721–9. https://doi.org/10.1161/CIRCULATIONAHA.114.010296.
Schnohr P, O’Keefe JH, Marott JL, Lange P, Jensen GB. Dose of jogging and long-term mortality: the Copenhagen City heart study. J Am Coll Cardiol. 2015;65(5):411–9. https://doi.org/10.1016/j.jacc.2014.11.023.
• Eijsvogels TMH, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the extremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol. 2016;67:316–29. https://doi.org/10.1016/j.jacc.2015.11.034. Important review article summarizing the relationship between extreme exercise and cardiovascular health.
Siegel AJ, Silverman LM, Holman BL. Elevated creatine kinase MB isoenzyme levels in marathon runners. JAMA. 1981;246(18):2049–51. https://doi.org/10.1001/jama.1981.03320180041027.
Shave R, Ross P, Low D, George K, Gaze D. Cardiac troponin i is released following high-intensity short-duration exercise in healthy humans. Int J Cardiol. 2010;145:337–9. https://doi.org/10.1016/j.ijcard.2009.12.001.
La Gerche A, Burns AT, Mooney DJ, et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J. 2012;33(8):998–1006. https://doi.org/10.1093/eurheartj/ehr397.
James S, Armstrong P, Califf R, Simoons ML, Venge P, Wallentin L, et al. Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome: prospective verification in the GUSTO-IV trial. Am J Med. 2003;115(3):178–84. https://doi.org/10.1016/S0002-9343(03)00348-6.
Gallagher J, Watson C, Zhou S, Ryan F, Ledwidge M, McDonald K. B-type natriuretic peptide and ventricular dysfunction in the prediction of cardiovascular events and death in hypertension. Am J Hypertens. 2017;31:228–34. https://doi.org/10.1093/ajh/hpx153.
Kobashigawa JA, Leaf DA, Lee N, et al. A controlled trial of exercise rehabilitation after heart transplantation. N Engl J Med. 1999;340(4):272–7. https://doi.org/10.1056/NEJM199901283400404.
Kavanagh T, Yacoub MH, Mertens DJ, Kennedy J, Campbell RB, Sawyer P. Cardiorespiratory responses to exercise training after orthotopic cardiac transplantation. Circulation. 1988;77(1):162–71. https://doi.org/10.1161/01.CIR.77.1.162.
Sullivan MJ, Higginbotham MB, Cobb FR. Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance. Circulation. 1989;79(2):324–9. https://doi.org/10.1161/01.CIR.79.2.324.
Hambrecht R, Niebauer J, Fiehn E, Kälberer B, Offner B, Hauer K, et al. Physical training in patients with stable chronic heart failure: effects on cardiorespiratory fitness and ultrastructural abnormalities of leg muscles. J Am Coll Cardiol. 1995;25(6):1239–49. https://doi.org/10.1016/0735-1097(94)00568-B.
Coats AJ, Adamopoulos S, Radaelli A, McCance A, Meyer TE, Bernardi L, et al. Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. Circulation. 1992;85(6):2119–31. https://doi.org/10.1161/01.CIR.85.6.2119.
Tran ZV, Weltman A. Differential effects of exercise on serum lipid and lipoprotein levels seen with changes in body weight. A meta-analysis. JAMA. 1985;254(7):919–24.
King AC, Haskell WL, Young DR, Oka RK, Stefanick ML. Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation. 1995;91(10):2596–604. https://doi.org/10.1161/01.CIR.91.10.2596.
Williams PT. High-density lipoprotein cholesterol and other risk factors for coronary heart disease in female runners. N Engl J Med. 1996;334:1298–303. https://doi.org/10.1056/NEJM199605163342004.
Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N Engl J Med. 1991;325(7):461–6. https://doi.org/10.1056/nejm199108153250703.
King DS, Dalsky GP, Clutter WE, et al. Effects of exercise and lack of exercise on insulin sensitivity and responsiveness. J Appl Physiol. 1988;64(5):1942–6. https://doi.org/10.1016/j.ypmed.2010.09.002.
Rosenthal M, Haskell WL, Solomon R, Widstrom A, Reaven GM. Demonstration of a relationship between level of physical training and insulin-stimulated glucose utilization in normal humans. Diabetes. 1983;32(5 I):408–11.
Stratton JR, Chandler WL, Schwartz RS, Cerqueira MD, Levy WC, Kahn SE, et al. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation. 1991;83(5):1692–7.
Joyner MJ, Green DJ. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol. 2009;587(23):5551–8. https://doi.org/10.1113/jphysiol.2009.179432.
Beere PA, Glagov S, Zarins CK. Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate. Arter Thromb. 1992;12(11):1245–53. https://doi.org/10.1161/01.ATV.12.11.1245.
Powell KE, Paluch AE, Blair SN. Physical activity for health: what kind? How much? How intense? On top of what? Annu Rev Public Health. 2011;32(1):349–65. https://doi.org/10.1146/annurev-publhealth-031210-101151.
Abdulla J, Nielsen JR. Is the risk of atrial fibrillation higher in athletes than in the general population? A systematic review and meta-analysis. Europace. 2009;11(9):1156–9. https://doi.org/10.1093/europace/eup197.
Merghani A, Maestrini V, Rosmini S, Cox AT, Dhutia H, Bastiaenan R, et al. Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile running title: Merghani et al.; coronary disease in master endurance athletes. Circulation. 2017;136:126–37. https://doi.org/10.1161/CIRCULATIONAHA.116.026964.
Möhlenkamp S, Lehmann N, Breuckmann F, Bröcker-Preuss M, Nassenstein K, Halle M, et al. Running: the risk of coronary events—prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J. 2008;29(15):1903–10. https://doi.org/10.1093/eurheartj/ehn163.
Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. J Appl Physiol. 2011;110(6):1622–6. https://doi.org/10.1152/japplphysiol.01280.2010.
Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005;26:1461–74. https://doi.org/10.1093/eurheartj/ehi258.
La Gerche A, Connelly KA, Mooney DJ, MacIsaac AI, Prior DL. Biochemical and functional abnormalities of left and right ventricular function after ultra-endurance exercise. Heart. 2008;94(7):860–6. https://doi.org/10.1136/hrt.2006.101063.
Neilan TG, Januzzi JL, Lee-Lewandrowski E, Ton-Nu TT, Yoerger DM, Jassal DS, et al. Myocardial injury and ventricular dysfunction related to training levels among nonelite participants in the Boston Marathon. Circulation. 2006;114(22):2325–33. https://doi.org/10.1161/CIRCULATIONAHA.106.647461.
Aronson JK. Biomarkers and surrogate endpoints. Br J Clin Pharmacol. 2005;59(5):491–4. https://doi.org/10.1111/j.1365-2125.2005.02435.x.
McCarthy CP, Donnellan E, Phelan D, Griffin BP, Enriquez-Sarano M, McEvoy JW. High sensitivity troponin and valvular heart disease. Trends Cardiovasc Med. 2017;27:326–33. https://doi.org/10.1016/j.tcm.2017.01.004.
Yamashita K, Yoshioka T. Profiles of creatine kinase isoenzyme compositions in single muscle fibres of different types. J Muscle Res Cell Motil. 1991;12(1):37–44. https://doi.org/10.1007/BF01781172.
Siegel AJ, Silverman LM, Lopez RE. Creatine kinase elevations in marathon runners: relationship to training and competition. Yale J Biol Med. 1980;53(4):275–9.
Siegel AJ, Silverman LM, Evans WJ. Elevated skeletal muscle creatine kinase MB isoenzyme levels in marathon runners. JAMA J Am Med Assoc. 1983;250(20):2835–7. https://doi.org/10.1001/jama.1983.03340200069032.
Warhol MJ, Siegel AJ, Evans WJ, Silverman LM. Skeletal muscle injury and repair in marathon runners after competition. Am J Pathol. 1985;118(2):331–9.
Son HJ, Lee YH, Chae JH, Kim CK. Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run. Biol Sport. 2015;32(3):267–72. https://doi.org/10.5604/20831862.1163384.
Shave R, George KP, Atkinson G, Hart E, Middleton N, Whyte G, et al. Exercise-induced cardiac troponin T release: a meta-analysis. Med Sci Sports Exerc. 2007;39(12):2099–106. https://doi.org/10.1249/mss.0b013e318153ff78.
Wu AHB, Feng Y-J, Moore R, et al. Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. Clin Chem. 1998;44(6):1198–208. https://doi.org/10.1016/0009-9120(96)00016-1.
Fulda GJ, Giberson F, Hailstone D, Law A, Stillabower M. An evaluation of serum troponin T and signal-averaged electrocardiography in predicting electrocardiographic abnormalities after blunt chest trauma. J Trauma. 1997;43(2):302–4. https://doi.org/10.1097/00005373-199708000-00016.
Baig MA, Ali S, Khan MU, Rasheed J, Qadir A, Vasavada BC, et al. Cardiac troponin I release in non-ischemic reversible myocardial injury from parvovirus B19 myocarditis. Int J Cardiol. 2006;113(3):E109–10. https://doi.org/10.1016/j.ijcard.2006.06.048.
Gaze DC, Collinson PO. Cardiac troponins as biomarkers of drug- and toxin-induced cardiac toxicity and cardioprotection. Expert Opin Drug Metab Toxicol. 2005;1(4):715–25. https://doi.org/10.1517/17425255.1.4.715.
Mingels AMA, Jacobs LHJ, Kleijnen VW, Laufer EM, Winkens B, Hofstra L, et al. Cardiac troponin T elevations, using highly sensitive assay, in recreational running depend on running distance. Clin Res Cardiol. 2010;99(6):385–91. https://doi.org/10.1007/s00392-010-0134-x.
Tulloh L. Raised troponin T and echocardiographic abnormalities after prolonged strenuous exercise—the Australian ironman triathlon. Br J Sports Med. 2006;40(7):605–9. https://doi.org/10.1136/bjsm.2005.022319.
Neumayr G, Pfister R, Mitterbauer G, Maurer A, Gaenzer H, Sturm W, et al. Effect of the “race across the alps” in elite cyclists on plasma cardiac troponins I and T. Am J Cardiol. 2002;89(4):484–6. https://doi.org/10.1016/S0002-9149(01)02280-9.
McNeil PL, Khakee R. Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am J Pathol. 1992;140(5):1097–109.
Goette A, Bukowska A, Dobrev D, Pfeiffenberger J, Morawietz H, Strugala D, et al. Acute atrial tachyarrhythmia induces angiotensin II type 1 receptor-mediated oxidative stress and microvascular flow abnormalities in the ventricles. Eur Heart J. 2009;30(11):1411–20. https://doi.org/10.1093/eurheartj/ehp046.
Hessel MHM, Atsma DE, Van Der Valk EJM, Bax WH, Schalij MJ, Van Der Laarse A. Release of cardiac troponin I from viable cardiomyocytes is mediated by integrin stimulation. Pflugers Arch Eur J Physiol. 2008;455(6):979–86. https://doi.org/10.1007/s00424-007-0354-8.
Tian Y, Nie J, Huang C, George KP. The kinetics of highly sensitive cardiac troponin T release after prolonged treadmill exercise in adolescent and adult athletes. J Appl Physiol. 2012;113(3):418–25. https://doi.org/10.1152/japplphysiol.00247.2012.
Middleton N, George K, Whyte G, Gaze D, Collinson P, Shave R. Cardiac troponin T release is stimulated by endurance exercise in healthy humans. J Am Coll Cardiol. 2008;52:1813–4. https://doi.org/10.1016/j.jacc.2008.03.069.
• Klinkenberg LJJ, Luyten P, Van Der Linden N, et al. Cardiac troponin T and i release after a 30-km run. Am J Cardiol. 2016;118(2):281–7. https://doi.org/10.1016/j.amjcard.2016.04.030. Demonstrated that the pattern of troponin release in athletes is different to that associated with acute myocardial infarction.
Mousavi N, Czarnecki A, Kumar K, Fallah-Rad N, Lytwyn M, Han SY, et al. Relation of biomarkers and cardiac magnetic resonance imaging after marathon running. Am J Cardiol. 2009;103(10):1467–72. https://doi.org/10.1016/j.amjcard.2009.01.294.
Maeder MT, Mueller C, Pfisterer ME, Buser PT, Brunner-La Rocca HP. Use of B-type natriuretic peptide outside of the emergency department. Int J Cardiol. 2008;127:5–16. https://doi.org/10.1016/j.ijcard.2007.10.018.
Maeder MT, Brutsche MH, Christ A, Reichlin T, Staub D, Noveanu M, et al. Natriuretic peptides for the prediction of severely impaired peak VO2 in patients with lung disease. Respir Med. 2009;103(9):1337–45. https://doi.org/10.1016/j.rmed.2009.03.015.
Kruger S, Graf J, Kunz D, Stickel T, Hanrath P, Janssens U. Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure. J Am Coll Cardiol. 2002;40(4):718–22. https://doi.org/10.1016/S0735-1097(02)02032-6.
Passino C, Poletti R, Bramanti F, Prontera C, Clerico A, Emdin M. Neuro-hormonal activation predicts ventilatory response to exercise and functional capacity in patients with heart failure. Eur J Heart Fail. 2006;8(1):46–53. https://doi.org/10.1016/j.ejheart.2005.05.007.
Maeder MT, Thompson BR, Kaye DM. Inverse association between myocardial B-type natriuretic peptide release and functional capacity in healthy humans. Hear Lung Circ. 2017; https://doi.org/10.1016/j.hlc.2017.08.014.
La Gerche A, Heidbüchel H, Burns AT, et al. Disproportionate exercise load and remodeling of the athlete’s right ventricle. Med Sci Sports Exerc. 2011;43(6):974–81. https://doi.org/10.1249/MSS.0b013e31820607a3.
Aengevaeren VL, Hopman MTE, Thijssen DHJ, van Kimmenade RR, de Boer MJ, Eijsvogels TMH. Endurance exercise-induced changes in BNP concentrations in cardiovascular patients versus healthy controls. Int J Cardiol. 2017;227:430–5. https://doi.org/10.1016/j.ijcard.2016.11.016.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Eoin Donnellan and Dermot Phelan declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
This article is part of the Topical Collection on Biomarkers of Heart Failure
Rights and permissions
About this article
Cite this article
Donnellan, E., Phelan, D. Biomarkers of Cardiac Stress and Injury in Athletes: What Do They Mean?. Curr Heart Fail Rep 15, 116–122 (2018). https://doi.org/10.1007/s11897-018-0385-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11897-018-0385-9