Troponin antibodies and macrotroponin: a common cause of troponin I elevation in elite endurance athletes

Background and AimsElevations in cardiac troponin I (cTnI), a marker of myocardial injury, have been frequently observed in athletes after intense exercise. cTnI autoantibodies (cTnI Ab) and macrotroponin complexes can confound assessment, and we hypothesised that they may explain the paradox of repeated cTnI elevations in athletes. MethodsAthletes and non-athlete controls underwent high-sensitivity cTnI testing, cardiac magnetic resonance imaging (CMR), 24-hour ambulatory electrocardiographic monitoring and VO2peak assessment. Athletes with cTnI values >99th percentile sex-specific upper reference limit were assessed for cTnI Ab using polyethylene glycol (PEG) precipitation and troponin T (TnT)/TnI discordance. ResultsOverall, 456 participants were evaluated (387 athletes and 69 non-athletes). cTnI elevations were observed in 39 (10.1%) athletes and no (0%) control participants (p=0.002). Athletes with cTnI elevation demonstrated higher VO2peak and larger biventricular dimensions compared to athletes without cTnI elevations (p<0.001). Of the athletes with cTnI elevations, 31 of 39 (79%) had evidence of cTnI Ab; 26 (66.7%) met both criteria for cTnI Ab (low PEG recovery and normal cTnT), a further 5 (12.8%) met one criteria (low PEG recovery but slightly elevated cTnT out of keeping with cTnI elevation [median TnT/TnI=3.7%]) and the remaining 8 athletes met neither (high PEG recovery and cTnT elevation [median TnT/TnI=81.2%]). Four of these 8 athletes with TnI elevation but without cTnI Ab had evidence of possible myocardial injury on CMR. ConclusionscTnI elevations are commonly found in highly-trained endurance athletes, especially the fittest athletes with greatest cardiac remodelling, but are due to antibodies in a majority. Graphic Abstract Key QuestionO_LIWhat is the prevalence of cardiac troponin I (cTnI) elevation in highly-trained endurance athletes outside of competition and what proportion are due to cTnI antibodies? C_LIO_LIHow do elevated cTnI measures relate to exercise-induced cardiac remodelling and VO2peak? C_LI Key FindingO_LI1 in 10 endurance athletes had elevated cTnI with 80% due to cTnI antibodies as opposed to true cTnI elevations. C_LIO_LIcTnI elevation and antibodies were found in the fittest athletes with the greatest cardiac remodelling on cardiac magnetic resonance imaging. C_LI Take-home messageO_LIcTnI antibodies are highly prevalent in endurance athletes and are not associated with myocardial damage. C_LIO_LIAwareness of cTnI antibodies and appropriate testing will help avoid intensive investigation and misdiagnoses. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/25340346v1_ufig1.gif" ALT="Figure 1000"> View larger version (43K): org.highwire.dtl.DTLVardef@17273b1org.highwire.dtl.DTLVardef@10984e0org.highwire.dtl.DTLVardef@1f2c60dorg.highwire.dtl.DTLVardef@1a8859b_HPS_FORMAT_FIGEXP M_FIG C_FIG Non-standard abbreviations/acronymscTnI = cardiac troponin I cTnT = cardiac troponin T PEG = polyethylene glycol precipitation Ab = antibody LGE = late gadolinium enhancement NSVT = non-sustained ventricular tachycardia