Exercise-induced release of cardiac troponins in adolescent vs. Adult swimmers

In e na ional Jou nal o En i onmen al Resea ch and Public Heal h B ie Repo Exe cise-Induced Release o Ca diac T oponins in Adolescen s. Adul Swimme s Ra el Ci e -Sas e 1,* , F ancisco Co bi 1, Isaac López-La al 2, Luis En ique Ca anza-Ga cía3 and Joaquín Re e e -Masià4   Ci a ion: Ci e -Sas e, R.; Co bi, F.; López-La al, I.; Ca anza-Ga cía, L.E.; Re e e -Masià, J. Exe cise-Induced Release o Ca diac T oponins in Adolescen s. Adul Swimme s. In . J. En i on. Res. Public Heal h 2021,18, 1285. h ps://doi.o g/10.3390/ ije ph18031285 Academic Edi o : Tadeusz Amb ozy Recei ed: 28 Decembe 2020 Accep ed: 26 Janua y 2021 Published: 1 Feb ua y 2021 Publishe ’s No e: MDPI s ays neu al wi h ega d o ju isdic ional claims in published maps and ins i u ional a il- ia ions. Copy igh : © 2021 by he au ho s. Licensee MDPI, Basel, Swi ze land. This a icle is an open access a icle dis ibu ed unde he e ms and condi ions o he C ea i e Commons A ibu ion (CC BY) license (h ps:// c ea i ecommons.o g/licenses/by/ 4.0/). 1Ins i u Nacional d’EducacióFísica de Ca alunya (INEFC), Uni e si a de Lleida (UdL), 25192 Lleida, Spain; [email p o ec ed] 2Facul ad de Ciencias de la Salud y del Depo e, Uni e sidad de Za agoza, 50009 Za agoza, Spain; isaac@uniza .es 3Facul ad de O ganización Depo i a (FOD), Uni e sidad Au ónoma de Nue o León (UANL), San Nicolás de los Ga za 66455, Mexico; [email p o ec ed] 4Depa amen de Didàc iques Especí iques, Uni e si a de Lleida (UdL), 25003 Lleida, Spain; [email p o ec ed] *Co espondence: [email p o ec ed]; Tel.: +34-973-27-20-22 Abs ac : To examine he exe cise-induced elease o ca diac oponin T (cTnT) in adolescen and adul swimme s. Thi y- wo ained male (18 adolescen s, 14 adul s) swam a maximal pace in a 45 min dis ance ial, and blood samples we e d awn be o e, immedia ely and 3 h a e exe cise o subsequen cTnT analysis and compa ison. Ha ing compa able aining expe ience and baseline alues o cTnT (p= 0.78 and p= 0.13), adul s exe cised a lowe absolu e and ela i e in ensi y (p< 0.001 and p< 0.001, espec i ely), bu p esen ed highe immedia e cTnT a e exe cise han adolescen s (p< 0.001). Despi e ha , peak concen a ions we e obse ed a 3 h pos exe cise and peak ele a ions we e compa able be ween g oups (p= 0.074). Fou een (44%) appa en ly heal hy subjec s exceeded he cu o alue o myoca dial in a c ion (MI). Adolescen s p esen ed a delayed ele a ion o cTnT compa ed wi h adul s, bu achie ed simila peak alues. Keywo ds: bioma ke s; hea damage; swimming; g ow h 1. In oduc ion Ele a ions o se um ca diac oponin (cTn) a e he p e e ed c i e ia o diagnose my- oca dial inju y [ 1 ]. Conc e ely, he elease o cTn in o he bloods eam has been ela ed o di e en clinical scena ios and explained by mechanisms o elease such as myoca dial ischemia, in lamma o y and immunological p ocesses, auma, d ugs o oxins [ 1 , 2 ]. I is o pa icula in e es hough ha exe cise equen ly e okes ele a ions o se um ca diac oponin (cTn), ha peak app oxima ely 3 h a e exe cise and e u n o basal concen a- ions wi hin he subsequen 24 h [ 3 ]. Fu he mo e, a g owing body o e idence sugges s ha cTn ele a ions induced by exe cise occu in appa en ly heal hy a hle es and migh espond o a physiological acu e esponse o exe cise a he han pa hological sign [ 2 – 4 ]. Al hough he mechanisms unde lying he elease o cTn ollowing exe cise in appa en ly heal hy indi iduals a e no comple ely unde s ood, p e ious esea ch sugges ed po en ial mechanisms, among hem: changes in memb ane pe meabili y allowing unbound cTn om cy osol o di use ou side he cells, no mal u no e o myoca dial cells, cTn deg ada ion p oducing cellula elease, memb anous blebs, myocy e apop osis/nec osis esul ing in genuine ca diac inju y o c oss- eac ion wi h skele al oponin [3,5]. Pos -exe cise ele a ions o cTn ha e been no ed also in adolescen a hle es [ 6 ]. How- e e , di e ences be ween adolescen s and adul s a e inconsis en [ 4 , 6 – 8 ]. In his ega d, i has been p e iously sugges ed ha highe exe cise-induced ele a ions o cTn in he younge migh be a ibu able o he imma u i y o adolescen s myoca dium, since i In . J. En i on. Res. Public Heal h 2021,18, 1285. h ps://doi.o g/10.3390/ije ph18031285 h ps://www.mdpi.com/jou nal/ije ph In . J. En i on. Res. Public Heal h 2021,18, 1285 2 o 6 would expe ience g ea e s ess in esponse o an inc eased myoca dial wo kload com- pa ed wi h he adul s [ 9 ]. Based on his hypo hesis, i is possible ha younge a hle es espond o exe cise wi h highe ele a ions o his bioma ke han adul s. No wi hs anding ha , p io li e a u e has also linked exe cise-induced ele a ions o cTn abo e he uppe e e ence limi o highe mo ali y and ca dio ascula e en s in olde a hle es [ 10 ]. In his case, highe ele a ions in he olde migh be ela ed o unde lying, subclinical, ca diac pa hology [11]. Unde s anding how, when, and why cTn ele a es a e exe cise is ele an o he iage o a hle es who de elop ches pain ha mimics ca diac inju y a e exe cise, and who migh ha e se um cTn d awn in he eme gency depa men s (EDs). Fu he mo e, a be e knowledge o he ela ionship be ween exe cise-induced ele a ions o cTn and pa icipan s’ age migh con ibu e o a be e unde s anding o he phenomenon and i s mechanisms. Fo hese easons, he pu pose o his s udy was o compa e he elease o cTnT a e a dis ance- ial es o 45 min swimming be ween wo coho s o adolescen and adul swimme s. Based on p e ious s udies, ou hypo hesis was ha adolescen s would espond o exe cise wi h highe peak ele a ions o cTn, suppo ing he heo y ha he imma u e myoca dium expe iences highe wo kload compa ed wi h he adul s. 2. Ma e ials and Me hods 2.1. Pa icipan s A con enience sample o hi y- wo ained male swimme s we e ec ui ed o his s udy. All pa icipan s and pa en s o hose unde he age o 18 p o ided hei in o med consen . All swimme s ained in he same club and compe ed a he egional le el. Pa icipan s we e di ided in o adolescen (<18 yea s) and adul ( ≥ 18 yea s) g oups (see pa icipan cha ac e is ics in Table 1). The s udy was app o ed by he E hical Commi ee o Clinical Resea ch o Spo s Adminis a ion o Ca alonia (02/2018/CEICGC). Table 1. Summa y o pa icipan s’ cha ac e is ics and exe cise load. Adolescen s (n= 18) Adul s (n= 14) Be ween-G oups Pa icipan Cha ac e is ics Age (yea s) 14 ±3 [11–17] 35 ±9 [23–52] p < 0.001 T aining expe ience (yea s) 7 ±2 [2–11] 6 ±2 [4–9]p= 0.78 Body heigh (cm) 172.3 ±9.6 [151–187] 177.4 ±5.5 [169–187] p= 0.065 Body mass (kg) 60.6 ±10.2 [44.5–77.8] 71 ±4.4 [66–81] p < 0.001 Body mass index 20.3 ±2.2 [16.9–24.3] 26.6 ±1.3 [20–24.8] p= 0.001 Exe cise Load Dis ance (m) 1862 ±276 [1250–2300] 1650 ±239 [1320–2060] p= 0.027 Mean ela i e hea a e (% HRmax) 89 ±5 [75–99] 82 ±4 [75–88] p< 0.001 Peak ela i e hea a e (% HRmax) 95 ±6 [82–110] 91 ±4 [82–96] p= 0.037 Ra ing o pe cei ed exe ion 7 ±2 [3–10] 8 ±1 [6–10] p= 0.24 Ca diac T oponin Basal cTnT (ng/L) 5.39 (2.15) [1.5–8.09] 3.93 (3.97) [1.5–6.07] p= 0.13 ∆0 h pos -exe cise cTnT (ng/L) 0.38 (0.62) [−0.46–2.41] 3.69 (2.78) [0.57–9.25) p< 0.001 ∆3 h pos -exe cise cTnT (ng/L) 5.08 (6.37) [1.07–34.67) 11.64 (13.62) [2.83–38.84] p= 0.074 Pa icipan cha ac e is ics and exe cise load da a a e desc ibed as mean ± s anda d de ia ion [ ange], whe eas cTn da a a e desc ibed as median (in e qua ile ange) [ ange]. ∆ 0 h pos -exe cise cTnT, absolu e change om baseline o immedia ely a e exe cise; ∆ 3 h pos -exe cise cTnT, absolu e change om baseline o 3 h pos -exe cise. 2.2. P ocedu es Be o e he in e en ion, pa icipan s unde wen an h opome ic assessmen and a es ing 12-lead elec oca diog am (Click ECG BT 12 channel, Milano, I aly). Swimme s pe o med a sel -paced 5 min swimming wa m-up (<60% o %HRmax) [ 6 ], ollowed by a dis ance- ial es o 45 min con inuous swimming, and enous blood samples we e d awn be o e, immedia ely and a 3 h a e exe cise. Pa icipan s we e asked o a oid igo ous In . J. En i on. Res. Public Heal h 2021,18, 1285 3 o 6 exe cise du ing he 48 h p io o he in e en ion. Se um cTnT was de e mined using a T oponin T hs STAT immunoassay in a Cobas E 601 analyze (Roche Diagnos ics, Penzbe g, Ge many, ange 3–10,000 ng/L). The uppe e e ence limi o cTnT was 13.5 ng/L [ 11 ]. Concen a ions below he limi o de ec ion we e se o 1.5 ng/L o s a is ical analyses. Hea a e du ing he es was eco ded using Pola OH1 ™ op ical hea a e senso s (Pola Elec o Oy, Kempele, Finland). Maximum hea a e o ela i e in ensi ies was calcula ed using Tanaka’s o mula o 208 − (0.7 × Age). A yea a e he in e en ion, pa icipan s we e in e iewed o iden i y cases o ca diac signs o symp oms. 2.3. S a is ical Analysis Analyses we e pe o med using R e sion 3.5.1 (R Founda ion o S a is ical Com- pu ing, Vienna, Aus ia). Da a we e isually inspec ed o de ec abno mal alues, and Shapi o-Wilk es was used o assess no mali y. Acco dingly, da a we e p esen ed as mean ± SD [ ange] o median (in e qua ile ange) [ ange], as app op ia e. Pa icipan cha ac e - is ics and exe cise load we e compa ed among g oups using - es o independen samples. Then, ime di e ences wi hin each g oup we e compa ed using non-pa ame ic F iedman es o epea ed measu es and pai wise compa isons be ween momen s we e made wi h Wilcoxon signed ank es s applying Bon e oni co ec ions. Di e ences be ween g oups in absolu e cTn and i s changes ( ∆ 0 h and ∆ 3 h) we e analyzed using K uskal-Wallis ank sum es . Associa ions be ween cTn ele a ions and he es o he a iables we e assessed using Spea man co ela ion coe icien s ( ρ ). S a is ical signi icance in all compa isons was assumed when p< 0.05. 3. Resul s Pa icipan cha ac e is ics and exe cise load du ing he dis ance ial a e summa ized in Table 1. The e we e g oup di e ences in age, body mass, body mass index and maximal hea a e, and aining expe ience was compa able be ween g oups. Du ing he dis ance ial, adolescen s co e ed mo e dis ance and achie ed highe ca diac in ensi y han adul s, hough he a ing o pe cei ed exe ion was compa able be ween g oups. Concen a ions o cTnT changed signi ican ly o e ime ( χ2 = 59.5, p< 0.001). Con- c e ely, baseline concen a ions we e compa able be ween adolescen s and adul s ( χ2= 2.2; p= 0.13), and in bo h g oups i aised immedia ely a e and a 3 h pos exe cise. Fu - he mo e, immedia e changes ( ∆ 0 h) we e di e en be ween g oups ( χ2 = 18.1; p< 0.001), sligh ly highe in he adul s (Figu e 1). Peak changes ( ∆ 3 h), howe e , we e compa able be ween g oups ( χ2 = 3.2; p= 0.074). Peak cTnT concen a ions we e obse ed a 3 h pos - exe cise in all pa icipan s, and 14 (44%) subjec s exceeded he cu o alue o myoca dial in a c ion (MI) (6 (33%) adolescen s, 8 (57%) adul s). Peak changes ( ∆ 3 h) we e unco ela ed wi h age ( ρ = 0.19, p= 0.29), aining expe ience ( ρ = − 0.21, p= 0.24), body mass index ( ρ= 0.05 ,p= 0.8), dis ance ( ρ = − 0.1, p= 0.59), peak hea a e ( ρ = 0.06, p= 0.74 ), and mean hea a e (ρ= 0.06, p= 0.73). In . J. En i on. Res. Public Heal h 2021,18, 1285 4 o 6 In . J. En i on. Res. Public Heal h 2021, 18, x 4 o 6 Figu e 1. Indi idual poin s o cTnT by g oup. Red ho izon al line and ed do s deno e he cu o alue o myoca dial in a c ion (MI) o 13.5 ng/L and abo e alues, espec i ely. 4. Discussion The pu pose o his s udy was o compa e he exe cise-induced elease o cTnT be- ween adolescen s and adul s. Ou main inding was ha , al hough ha ing compa able aining expe ience and baseline alues o cTnT, adul s exe cised a lowe absolu e and ela i e in ensi y, bu p esen ed highe immedia e concen a ions o cTnT a e exe cise han adolescen s. Howe e , peak concen a ions we e obse ed a 3 h pos exe cise in all pa icipan s and we e compa able be ween g oups. Re e ence alues o cTn seem o be lowe in he young, and his migh be explained by a posi i e associa ion be ween age and he p e alence o ca dio ascula diseases [4,11]. Howe e , ou esul s did no suppo hose p e ious s a emen s since swimme s had compa able basal concen a ions o cTnT. E en hough his s udy was limi ed by a small sample size, i is no he i s esea ch inding no age-di e ences in appa en ly heal hy, ained, young pa icipan s [7]. In e es ingly hough, al hough peak cTnT was ound in all pa icipan s a 3 h pos exe cise, we de ec ed highe ele a ions immedia ely a e exe - cise in he adul s. Since peak ele a ions we e compa able among g oups, his sugges s ha se ological cTnT ele a ions migh appea ea lie a e exe cise in adul s compa ed wi h adolescen s. I has been sugges ed ha highe concen a ions o pos -exe cise cTn in he olde may ep esen myoca dial inju y because o unde lying, subclinical, ca diac pa hology [11]. Howe e , all pa icipan s in his s udy had no mal es ing ECG a he beginning o he s udy. Fu he mo e, one yea a e he in e en ion, none o hem epo ed o ha e had ca diac symp oms o e en s du ing his pe iod. Assuming ha ou pa icipan s we e heal hy, hese e idences align wi h he heo y o ansien ele a ions o cTnT a e exe cise being a physiological acu e esponse o exe cise a he han a sign o myoca dial inju y [3]. Howe e , his s udy did no include o he examina ions o myoca dial heal h such as echoca diog aphies o o he bioma ke assessmen s such as N- e minal p oho mone o b ain na iu e ic pep ide (NT-p oBNP), c ea ine kinase myoca dial band (CK-MB), o c- eac i e p o ein (CRP). Due o his limi a ion, we canno be ce ain o disca d a possible ole o unde lying, unde ec ed scena ios such as ca diac hype ophy and hy oid dys- unc ion [12]. In he p esen s udy, cTnT aised in all pa icipan s a e exe cise, and peak ele a ions a 3 h pos exe cise we e compa able among g oups. This is con a y o ou expec a ions, since p e ious au ho s sugges ed ha he less ma u e myoca dium in he younge migh Figu e 1. Indi idual poin s o cTnT by g oup. Red ho izon al line and ed do s deno e he cu o alue o myoca dial in a c ion (MI) o 13.5 ng/L and abo e alues, espec i ely. 4. Discussion The pu pose o his s udy was o compa e he exe cise-induced elease o cTnT be- ween adolescen s and adul s. Ou main inding was ha , al hough ha ing compa able aining expe ience and baseline alues o cTnT, adul s exe cised a lowe absolu e and ela i e in ensi y, bu p esen ed highe immedia e concen a ions o cTnT a e exe cise han adolescen s. Howe e , peak concen a ions we e obse ed a 3 h pos exe cise in all pa icipan s and we e compa able be ween g oups. Re e ence alues o cTn seem o be lowe in he young, and his migh be explained by a posi i e associa ion be ween age and he p e alence o ca dio ascula diseases [ 4 , 11 ]. Howe e , ou esul s did no suppo hose p e ious s a emen s since swimme s had compa able basal concen a ions o cTnT. E en hough his s udy was limi ed by a small sample size, i is no he i s esea ch inding no age-di e ences in appa en ly heal hy, ained, young pa icipan s [ 7 ]. In e es ingly hough, al hough peak cTnT was ound in all pa icipan s a 3 h pos exe cise, we de ec ed highe ele a ions immedia ely a e exe cise in he adul s. Since peak ele a ions we e compa able among g oups, his sugges s ha se ological cTnT ele a ions migh appea ea lie a e exe cise in adul s compa ed wi h adolescen s. I has been sugges ed ha highe concen a ions o pos -exe cise cTn in he olde may ep esen myoca dial inju y because o unde lying, subclinical, ca diac pa hology [ 11 ]. Howe e , all pa icipan s in his s udy had no mal es ing ECG a he beginning o he s udy. Fu he mo e, one yea a e he in e en ion, none o hem epo ed o ha e had ca diac symp oms o e en s du ing his pe iod. Assuming ha ou pa icipan s we e heal hy, hese e idences align wi h he heo y o ansien ele a ions o cTnT a e ex- e cise being a physiological acu e esponse o exe cise a he han a sign o myoca dial inju y [ 3 ]. Howe e , his s udy did no include o he examina ions o myoca dial heal h such as echoca diog aphies o o he bioma ke assessmen s such as N- e minal p oho - mone o b ain na iu e ic pep ide (NT-p oBNP), c ea ine kinase myoca dial band (CK-MB), o c- eac i e p o ein (CRP). Due o his limi a ion, we canno be ce ain o disca d a pos- sible ole o unde lying, unde ec ed scena ios such as ca diac hype ophy and hy oid dys unc ion [12]. In he p esen s udy, cTnT aised in all pa icipan s a e exe cise, and peak ele a ions a 3 h pos exe cise we e compa able among g oups. This is con a y o ou expec a ions, since p e ious au ho s sugges ed ha he less ma u e myoca dium in he younge migh be mo e suscep ible o exe cise-induced ele a ions o cTn [ 8 , 9 ]. In e es ingly hough, a ecen In . J. En i on. Res. Public Heal h 2021,18, 1285 5 o 6 s udy epo ed highe exe cise-induced ele a ions o cTnT in la e pube y, sugges ing ha his migh be explained by he highe ela i e in ensi ies du ing exe cise achie ed in his g oup [ 13 ]. In line wi h his s udy, ou adolescen s g oup also achie ed highe ca diac in ensi ies du ing he es . In spi e o ha , we ound no associa ion be ween exe cise in ensi y and peak ele a ions o cTnT. This inding seems in e es ing, since we expec ed pos -exe cise cTnT concen a ions o be di ec ly associa ed wi h exe cise in ensi y, as has been epo ed in p e ious s udies [ 4 ]. Thus, ou esul s no only sugges ha adul s ele a e cTn be o e adolescen s, bu also ha he associa ion be ween cTnT ele a ions and exe cise in ensi y migh no depend on age. Almos one-hal o he pa icipan s in his s udy (44%) exceeded he uppe e e ence limi o cTnT in he hi d blood ex ac ion. P e ious s udies in ol ing simila assessmen s and exe cise exposu es also ound high a es o posi i e de ec ion in bo h young and adul ained pa icipan s [ 4 , 6 – 8 , 13 ]. This is pa icula ly ele an o he iage o a hle es who de elop ches pain ha mimics ca diac inju y a e exe cise, and who migh ha e se um cTn d awn in he EDs. Fo hese easons, u u e s udies should add ess he limi a ions p esen in his esea ch, including a mo e exhaus i e clinical sc eening o he pa icipan s in o de o disca d o iden i y a po en ial ole o unde lying pa hology. Finally, in he au ho s’ opinion, he main s eng h o his s udy is ha ha we could compa e he ele a ions o cTnT in a coho o ained swimme s ha allowed compa isons be ween age g oups, and his made i possible o us o iden i y an ea lie ele a ion in he adul s compa ed wi h he adolescen s. The main limi a ions in his s udy, by con as , ha e been men ioned in he abo e pa ag aphs. We could no pe o m an exhaus i e ca diac sc eening including echoca diog aphy, addi ional biochemical analyses, o assessmen s o ma u a ional s a us, as has been done o men ioned in some p e ious s udies [6,12,13] . Addi ionally, we did no pe o m cTnT measu emen s beyond he 3 h pos exe cise. Conse- quen ly, he limi ed sampling poin s in ou design imply a po en ial unde -es ima ion e o in he peak cTnT concen a ions, as has been p e iously sugges ed by o he s [14,15]. 5. Conclusions In conclusion, in his s udy we obse ed age di e ences in he immedia e ele a ion o cTnT a e exe cise, bu no in i s peak ele a ions, a 3 h pos exe cise. Al hough pa icipan s we e appa en ly heal hy based on es ing ECG and a 1 yea e m ollow-up, u u e wo ks migh con inue his line o esea ch and explo e he associa ion be ween immedia e ele a ions o cTnT, age, and heal h. Au ho Con ibu ions: Concep ualiza ion, R.C.-S., F.C. and J.R.-M.; Da a cu a ion, R.C.-S. and I.L.-L.; Fo mal analysis, R.C.-S.; Funding acquisi ion, F.C. and J.R.-M.; In es iga ion, R.C.-S., I.L.-L., and L.E.C.-G.; Me hodology, R.C.-S. and F.C.; P ojec adminis a ion, R.C.-S. and J.R.-M.; Resou ces, R.C.-S., F.C. and I.L.-L.; So wa e, R.C.-S.; Supe ision, F.C. and J.R.-M.; Valida ion, R.C.-S. and L.E.C.-G.; Visualiza ion, R.C.-S.; and W i ing— e iew and edi ing, R.C.-S., L.E.C.-G., F.C., and J.R.-M. All au ho s ha e ead and ag eed o he published e sion o he manusc ip . Funding: This esea ch was unded by he Na ional Ins i u e o Physical Educa ion o Ca alonia, g an numbe 2016-PINEF-00007 and Ins i u de Desen olupamen Social i Te i o ial (INDEST), g an numbe 2018CRINDESTABC. Ins i u ional Re iew Boa d S a emen : The s udy was conduc ed acco ding o he guidelines o he Decla a ion o Helsinki, and app o ed by he E hical Commi ee o Clinical Resea ch o Spo s Adminis a ion o Ca alonia (02/2018/CEICGC). In o med Consen S a emen : In o med consen was ob ained om all subjec s in ol ed in he s udy. Da a A ailabili y S a emen : The da a p esen ed in his s udy a e a ailable on eques o he au ho s. Some a iables a e es ic ed o p ese e he anonymi y o s udy pa icipan s. Con lic s o In e es : The au ho s decla e no con lic o in e es . In . J. En i on. Res. Public Heal h 2021,18, 1285 6 o 6 Re e ences 1. Thygesen, K.; Alpe , J.S.; Ja e, A.S.; Chai man, B.R.; Bax, J.J.; Mo ow, D.A.; Whi e, H.D. Fou h Uni e sal De ini ion o Myoca dial In a c ion (2018). J. Am. Coll. Ca diol. 2018,33, 2551–2567. [C ossRe ] 2. Mai , J.; Lindahl, B.; Hamma s en, O.; Mülle , C.; Gianni sis, E.; Hube , K.; Möckel, M.; Plebani, M.; Thygesen, K.; Ja e, A.S. 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