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article 2024 10 pages

Differences in Troponin I and Troponin T Release in High-Performance Athletes Outside of Competition

Jan C. Wuestenfeld, Tom Kastner, Judith Hesse, Leon Fesseler, Florian Frohberg, Cornelius Rossbach, Bernd Wolfarth

Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms25021062
Population
elite athletes
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Abstract

I and troponin T are critical biomarkers for myocardial infarction and damage and are pivotal in cardiological and laboratory diagnostics, including emergency settings. Rapid testing protocols have been developed for urgent care, particularly in emergency outpatient clinics. Studies indicate that strenuous physical activity can cause transient increases in these troponin levels, which are typically considered benign. This research focused on 219 elite athletes from national teams, evaluating their troponin I and T levels as part of routine sports medical exams, independent of competition-related physical stress. The results showed that 9.2% (18 athletes) had elevated troponin I levels above the reporting threshold, while their troponin T levels remained within the normal range. Conversely, only 0.9% (two athletes) had normal troponin I but raised troponin T levels, and 2.3% (five athletes) exhibited increases in both markers. No significant cardiovascular differences were noted between those with elevated troponin levels and those without. This study concludes that elevated troponin I is a common response to the intense physical training endured by high- performance endurance athletes, whereas troponin T elevation does not

normal troponin I but raised troponin T levels, and 2.3% (five athletes) exhibited increases in both markers. No significant cardiovascular differences were noted between those with elevated troponin levels and those without. This study concludes that elevated troponin I is a common response to the intense physical training endured by high- performance endurance athletes, whereas troponin T elevation does not seem to be directly linked to physical exertion in this group. For cardiac assessments, particularly when ruling out cardiac damage in these athletes, troponin T might be a more reliable indicator than troponin I. Keywords:troponin I; troponin T; sport; elite athletes; exercise; cardiac health 1. Introduction Moderate physical activity is generally considered to be healthy and is associated with a number of benefits [1,2]. It is well established that exercise can elevate cardiac troponin (cTn) levels [3–6]. Studies on marathon runners, ergometer tests, and ultramarathon runners have repeatedly shown that exercise results in elevations in blood cTn [3,6,7]. Although the pathogenesis of exercise-induced cTn release is not fully understood, its pathological relevance is generally considered low or irrelevant, a view not universally accepted [6]. The degree of troponin elevation post-exercise varies significantly among individuals, influenced by factors like training status, age, exercise duration, and sex [4]. However, no data have been published on the differences between different causes of troponin elevation in response to exercise. Furthermore, whether there is a difference in the exercise-induced increase in troponin I (cTnI) and troponin T (cTnT) is not yet known. The literature suggests that exercise-induced troponin elevation is more prevalent in men than women [8] and occurs more frequently in young and middle-aged athletes [7,9,10]. Prior intense exercise has been shown to significantly affect serum cTn levels, leading to increased detection of both cTnT and cTnI. However, most studies have not differentiated between the two troponins, often focusing on just one isoform [4,9,11–13]. This paper, therefore, aims to show the extent to which physical training activity in high-performance athletes has an impact on the detectability of both cTnI and cTnT. Int. J. Mol. Sci.2024,25, 1062.

cTnT and cTnI. However, most studies have not differentiated between the two troponins, often focusing on just one isoform [4,9,11–13]. This paper, therefore, aims to show the extent to which physical training activity in high-performance athletes has an impact on the detectability of both cTnI and cTnT. Int. J. Mol. Sci.2024,25, 1062.

Int. J. Mol. Sci.2024,25, 1062 2 of 10 The reasons behind the detectability of troponins in the blood post-exercise are not yet fully understood. Katus et al. found no explanation for elevated resting cTnT values following 12 weeks of HIIT and CAT training [14], but they were reproduced by Legaz- Arrese et al. [9]. In addition, higher post-exercise cTnT levels were found to be associated with increasing exercise capacity without a strong association between the two parameters. One theory for these data is that adaptive processes in the heart as a result of training explain the higher cTn values. Contrary to this, Nie et al. showed in two papers that 12 weeks of training led to lower post-exercise cTnT values [13]. The author concluded that this could be due to reduced mechanical load on the heart as it adapts to the training stimulus. This conclusion can be drawn from the lower heart rate during exercise and the shorter exercise duration. The training probably did not lead to the lower post-exercise cTn values but rather shifted the absolute exercise threshold for troponin elevations due to the improved fitness of the subjects [13]. No correlation could be found between previous exercise experience and post-exercise troponin levels. Eijsvogels et al. [7] recognized in marathon runners that older age correlates with training experience and exercise intensity, but their statistical model isolated training experience and showed that this was not a relevant factor for the level of post-exercise cTn values. The differences in the exercise-induced increases in cTnI and cTnT have not been fully elucidated so far. If apparent differences between stress-induced increases in cTnI and cTnT are shown, this must be considered when diagnosing ACS, myocardial infarction, or myocarditis. To date, no distinction has been made between cTnI and cTnT [15]. This study was conducted to enhance our understanding of troponin increases due to physical activity, particularly to highlight any differences in the rise of various troponins among high-performance athletes. 2. Results In this study, 219 high-performance athletes, averaging 23.7 years old (female: 23.8 years, male: 23.6 years) from 36 different sports (see Supplementary

been made between cTnI and cTnT [15]. This study was conducted to enhance our understanding of troponin increases due to physical activity, particularly to highlight any differences in the rise of various troponins among high-performance athletes. 2. Results In this study, 219 high-performance athletes, averaging 23.7 years old (female: 23.8 years, male: 23.6 years) from 36 different sports (see Supplementary Materials), were analyzed. The majority, particularly from endurance sports (total: 154, males: 85, females: 60), underwent resting ECGs that typically showed non-pathological results, with sport- specific changes in some cases. With a high proportion of top athletes from endurance disciplines, this corresponds to the expected results. The mean heart rate of 56.4 bpm across all athletes was slightly bradycardic. There was no significant PQ time prolongation over 200 ms or signs of atrioventricular shortened conduction. However, the QRS duration was slightly prolonged, averaging 106 ms across genders and notably longer in males (112.7 ms), suggesting physiological changes related to intensive training (see Table). Echocardiographic assessments revealed no pathological abnormalities, with many athletes showing expected sport-related cardiac adaptations, particularly noted in the relative heart size as per Dickhuth’s formula [16]. Male athletes generally had a slightly larger heart size relative to their body weight compared to females. Other parameters, including the diame- ter of the intraventricular septum, left ventricular internal diameter in diastole, and left atrial diameter in atrial diastole, were within the upper normal range or slightly increased, indicating typical athletic heart adaptations (see Table). Inz the cTnT and cTnI analyses performed on the elite athletes, a total of 18 athletes (8.2%, 12 females, 6 males) were found to have elevated cTnI values and normal cTnT values. An increase in troponin levels was found exclusively in endurance sports (biathlon (eight), middle-distance running (two), cross-country skiing (seven), and triathlon (one)). With an average troponin increase of 92.6 ng/mL, this value was approximately double the upper standard limit, whereas the maximum cTnI increase of 399.5 ng/mL corresponds almost tenfold to the upper standard limit. In the differentiated analysis of the results of both sexes, no significant differences were found concerning the troponin

middle-distance running (two), cross-country skiing (seven), and triathlon (one)). With an average troponin increase of 92.6 ng/mL, this value was approximately double the upper standard limit, whereas the maximum cTnI increase of 399.5 ng/mL corresponds almost tenfold to the upper standard limit. In the differentiated analysis of the results of both sexes, no significant differences were found concerning the troponin mean values and maximum measured values. However, with 12 female athletes showing an elevated cTnI value, there were twice as many women in this group as men (6 athletes). While cross-country skiers with elevated cTnI values were found in both genders, this was only

Int. J. Mol. Sci.2024,25, 1062 3 of 10 the case for female athletes in biathlons. In contrast, only two male athletes with elevated cTnI levels were found in middle-distance running (see Table). Table 1.Baseline resting ECG data of all athletes. ECG Duration (ms) All Female Male PQ Duration 146.20 144.72 147.33 SD 31.50 26.68 33.57 QRS Duration 106.3 97.9 112.7 SD 10.9 7.3 8.6 QTc time (Bazett) 402.08 419.67 406.26 SD 24.02 23.53 22.83 Mean heart rate 56.4 56.4 56.4 SD 10.5 11.7 9.6 Table 2.Baseline echocardiographic data of all athletes. Value All Female Male Ejection fraction (%) >65% >65% >65% Heart volume/weight (mL/kg) 12.47 11.68 12.93 SD 2.03 1.72 2.12 Diameter interventr. Septum (iVSDd/cm) 1.01 0.94 1.07 SD 0.12 0.11 0.10 Left atrium (diameter cm) 3.67 3.43 3.85 SD 0.41 0.35 0.36 Left ventricle (diameter cm) LviDd 5.17 4.83 5.43 SD 0.47 0.32 0.40 Table 3.Athletes with elevated troponin I and normal troponin T values. Value All (18) Female (12) Male (6) cTnI mean ng/mL 92.6 98.1 94.6 Min/Max ng/mL 46.2/399.8 46.2/399.8 53.2/321.7 Disciplines Biathlon (8), middle-distance running (2), cross-country skiing (7), triathlon (1) Biathlon (8), cross-country skiing (3), triathlon (1) Middle-distance running (2), cross-country skiing (4) In five athletes (2.3%, two females and three males), elevated values for cTnT and cTnI were found. The mean cTnI value of 528.2 was found to be increased by a factor of 11.7. Although this is almost ten times higher compared to the group of athletes with an exclusive cTnI increase, it is due to the maximum measured value of 967.8 ng cTnI of one athlete, which leads to this increase in the mean value. This maximum cTnI value of a female athlete (track and field athlete) corresponds to a 21.4-fold increase in the upper normal value. Similarly, a differentiated analysis of both sexes in the group of male athletes shows one athlete (a biathlete) with a 17.3-fold increase in the upper normal range for cTnI. While the other two male athletes showed comparatively low cTnI increases (61.2 ng/mLand 71.55 ng/mL, respectively), the cTnI increases of the female athletes, who also showed

in the upper normal value. Similarly, a differentiated analysis of both sexes in the group of male athletes shows one athlete (a biathlete) with a 17.3-fold increase in the upper normal range for cTnI. While the other two male athletes showed comparatively low cTnI increases (61.2 ng/mLand 71.55 ng/mL, respectively), the cTnI increases of the female athletes, who also showed an increase in cTnT, were significantly higher (784.89 ng/mL and 967.8 ng/mL). The increase

Int. J. Mol. Sci.2024,25, 1062 4 of 10 in cTnT found in this group of athletes was very moderate for all athletes. With a mean troponin value of 19 ng/mL, this value was only increased by a factor of 1.4 above the upper normal range. Furthermore, with a maximum cTnT increase of 21 ng/mL, this value was only 1.5 times higher than the upper normal range. The differentiated analysis of females and males showed no significant differences in the cTnT measured values with an overall small group size (both absolute group size and gender-related group size). In contrast to the group of athletes with only cTnI elevation, the group with cTnI and cTnT elevation included one athlete from a duel sport (wrestling) in addition to the athletes from endurance disciplines (see Table). Table 4.Athletes with elevated troponin I and elevated troponin T levels. Value All (5) Female (2) Male (3) cTnI mean ng/mL 528.2 937.46 306.0 Min/Max ng/mL cTnI 61.2/967.8 907.12/967.8 61.2/784.9 cTnT mean ng/mL 19 18.3 20.5 Min/Max ng/mL cTnT 15/21 15/21 20/21 Disciplines Biathlon (2), middle distance running (1), finswimming (1), wrestling (1) Biathlon (1), middle distance running (1) Biathlon (1), finswimming (1), wrestling (1) In two athletes (0.9%, one female, one male), elevated values for cTnT were found with normal values for cTnI. The female athlete with elevated cTnT and normal cTnI is a known carrier of Duchenne–Becker disease and was repeatedly found to have solitary elevated cTnT during the course of measurements. Since patients with Duchenne–Becker muscular dystrophy are known to have a permanent troponin elevation in the blood, according to the literature [17], it can be assumed that the elevation of cTnT in this female athlete is not due to competitive sports training but rather to an underlying genetic predisposition. With a value of 18 ng/mL (the corresponding cTnI value was 5.56 ng/mL), the male athlete with an exclusive cTnT increase shows a slight increase in cTnT of 1.3 times the upper normal value. However, it must also be pointed out that this is, again, an athlete from an endurance sport (cross-country skiing) (see Table).

to an underlying genetic predisposition. With a value of 18 ng/mL (the corresponding cTnI value was 5.56 ng/mL), the male athlete with an exclusive cTnT increase shows a slight increase in cTnT of 1.3 times the upper normal value. However, it must also be pointed out that this is, again, an athlete from an endurance sport (cross-country skiing) (see Table). Table 5.Athletes with normal troponin I and elevated troponin T levels. Value All (2) Female (1) Male (1) cTnT mean ng/mL 20 22.0 18.0 Min/Max ng/mL cTnT 18.0/22.0 / / Disciplines Cross-country skiing (2) Cross-country skiing (1) Cross-country skiing (1) No significant differences in anthropometric, echocardiographic, or ECG data were observed among the different groups categorized by their troponin levels (1. normal cTnI/cTnT, 2. elevated cTnI with normal cTnT, 3. normal cTnI with elevated cTnT, and 4. elevated cTnT and cTnI) (see Table).

Int. J. Mol. Sci.2024,25, 1062 5 of 10 Table 6.Comparison of anthropometric, echocardiographic, and ECG values in athletes with different troponin levels. Normal cTnI and cTnT Elev. cTnI, norm. cTnT Norm. cTnI, elev. cTnT Elevated cTnI and cTnT Female Male Female Male Female Male Female Male p-Value Age 24.33 23.81 21.42 21.83 21 21 21.0 20.3 n.s. Height 169.90 185.19 170.62 183.58 166.4 185.2 165.0 186.87 n.s. Weight 62.23 81.54 60.98 75.43 59.3 82.70 53.45 80.47 n.s. BMI 21.86 23.66 20.94 22.35 21.4 24.1 19.70 23.00 n.s. Fat % 14.48 11.24 14.89 10.0 14.8 9.7 12.0 10.5 n.s. Fat mass 9.55 9.53 9.13 7.50 8.7 8.0 6.40 8.87 n.s. LBM 53.69 72.01 51.86 67.93 50.60 74.70 47.05 72.07 n.s. HV rel 11.77 12.90 12.34 13.86 11.60 14.84 12.82 11.85 n.s. iVSd 0.93 1.07 0.95 1.03 0.80 1.07 0.98 1.03 n.s. LViDd 4.83 5.42 4.91 5.44 4.89 5.78 4.32 5.45 n.s. LA 3.42 3.87 3.53 3.62 3.83 4.0 3.40 3.57 n.s. PQ time 144.77 146.87 158.0 145.17 119 174 155 157 n.s. QRS time 98.0 112.3 97.7 119.8 101.0 107.0 94.0 115.3 n.s. QTc time 420.38 406.07 412.75 400.33 430 421 428 420 n.s. Rest HR 57.3 56.4 52.8 52.0 43 62 50 63.3 n.s. Finally, it was statistically analyzed whether there is a correlation between cTn increase and physical findings such as heart rate, LV mass, etc. The Spearman correlation analysis between the values of troponin I and the other variables shows a slight to moderate negative correlation with troponin I, but none of the p-values are low enough to indicate a statistically significant correlation, except for IVSd. IVSd shows a moderate negative correlation (−0.22) with troponin I, and the p-value (0.0042) suggests a statistically significant correlation. The Spearman correlation analysis between troponin T and various variables predominantly showed non-significant correlations with slight to moderate negative or positive tendencies. Notably, body weight, LBM, and several other measurements indicated no correlation. A few variables, like body fat mass, exhibited a stronger positive correlation, yet the results were just above the threshold for statistical significance. Overall, no clear or statistically significant relationships

analysis between troponin T and various variables predominantly showed non-significant correlations with slight to moderate negative or positive tendencies. Notably, body weight, LBM, and several other measurements indicated no correlation. A few variables, like body fat mass, exhibited a stronger positive correlation, yet the results were just above the threshold for statistical significance. Overall, no clear or statistically significant relationships were established, indicating a generally weak association between troponin T and the measured variables in this dataset. Due to the lack of statistically significant correlations, further elaboration on this matter in the paper is not pursued (compare Table). Table 7.Statistical analysis. Parameter F-Value p-Value Age 2.59 0.054 Weight 1.69 0.170 Height 0.91 0.437 Fat Mass 0.45 0.715 Fat % 0.32 0.811

Description

This study evaluates troponin levels in elite athletes during routine medical exams.