Exercise-induced cardiac troponin release in athletes with versus without coronary atherosclerosis

Abstract

The magnitude of exercise-induced cardiac troponin (cTn) elevations is dependent on cardiovascular health status, and previous studies have shown that occult coronary atherosclerosis is highly prevalent among amateur athletes. We tested the hypothesis that middle-aged and older athletes with coronary atherosclerosis demonstrate greater cTn elevations following a controlled endurance exercise test compared with healthy peers. We included 59 male athletes from the Measuring Athletes’ Risk of Cardiovascular events 2 (MARC-2) study and stratified them as controls [coronary artery calcium score (CACS) = 0, n = 20], high CACS [≥300 Agatston units or ≥75th Multi-Ethnic Study of Atherosclerosis (MESA) percentile, n = 20] or significant stenosis (≥50% in any coronary artery, n = 19). Participants performed a cycling test with incremental workload until volitional exhaustion. Serial high-sensitivity cTn (hs-cTn) T and I concentrations were measured (baseline, after 30-min warm-up, and 0, 30, 60, 120, and 180 min postexercise). There were 58 participants (61 [58–69] yr) who completed the exercise test (76 ± 14 min) with a peak heart rate of 97.7 [94.8–101.8]% of their estimated maximum. Exercise duration and workload did not differ across groups. High-sensitivity cardiac troponin T (Hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) concentrations significantly increased (1.55 [1.33–2.14]-fold and 2.76 [1.89–3.86]-fold, respectively) over time, but patterns of cTn changes and the incidence of concentrations >99th percentile did not differ across groups. Serial sampling of hs-cTnT and hs-cTnI concentrations during and following an exhaustive endurance exercise test did not reveal differences in exercise-induced cTn release between athletes with versus without coronary atherosclerosis. These findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.

NEW & NOTEWORTHY Exercise-induced cardiac troponin (cTn) release is considered to be dependent on cardiovascular health status. We tested whether athletes with coronary atherosclerosis demonstrate greater exercise-induced cTn release compared with healthy peers. Athletes with coronary atherosclerosis did not differ in cTn release following exercise compared with healthy peers. Our findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.

INTRODUCTION

Physical activity and exercise are associated with significant reductions in cardiovascular events (1, 2) and increased longevity (3, 4), but recent studies reported a higher prevalence of coronary atherosclerosis among male (5–7), but not among female (8), lifelong athletes compared with control subjects. The Measuring Athletes’ Risk of Cardiovascular events 1 (MARC-1) study also revealed that up to 19% of asymptomatic, middle-aged male recreational athletes without abnormalities on sports medical examination had substantial coronary atherosclerosis (9). As most sudden cardiac deaths in middle-aged and older athletes are caused by occult coronary artery disease (CAD) (10, 11), early identification of individuals at risk is key.

An acute bout of exercise increases cardiac troponin (cTn) concentrations (12), the preferred biomarker to assess myocardial injury (13). The magnitude of exercise-induced elevations of cTn shows a large interindividual variability and is dependent on factors such as exercise intensity (14), exercise duration (15), and cardiovascular health status (12). Previous field studies assessing the association between exercise-induced cTn elevations and coronary atherosclerosis found inconsistent results (16–18), probably due to variation in exercise dose (i.e., duration and intensity), the timing of cTn assessment postexercise (i.e., missing peak cTn concentrations), and the severity of coronary atherosclerosis [i.e., coronary artery calcium score (CACS) and degree of stenosis] in the investigated cohort.

Therefore, we performed a controlled laboratory study to compare serial measures of cTn concentrations during and following an exhaustive exercise test between middle-aged and older athletes with versus without coronary atherosclerosis. We hypothesized that athletes with coronary atherosclerosis would show an exaggerated response of exercise-induced cTn release compared with athletes without coronary atherosclerosis.

METHODS

Participants

Participants of the Measuring Athletes’ Risk of Cardiovascular events 2 (MARC-2) study (19) were invited for this add-on study and stratified by their degree of coronary atherosclerosis. We aimed to recruit three distinct groups: 1) controls: athletes with CACS = 0 Agatston units (AU) and without plaques on coronary computed tomography angiography; 2) high CACS: athletes with CACS ≥ 300 AU or ≥75th Multi-Ethnic Study of Atherosclerosis (MESA) percentile (20) without significant stenosis; and 3) significant stenosis: athletes with a stenosis ≥50% of coronary artery lumen in any of the coronary arteries but cleared to perform exercise following a pharmacological stress test without signs of ischemia (21). We examined male athletes only, because 1) the higher prevalence of coronary atherosclerosis was found among male (5–7), but not among female (8), lifelong athletes; 2) men have a higher probability of exercise-related cardiac arrest (22); and 3) because the MARC cohort (9, 19) consisted of men only. Participants were eligible for this study if they were able to perform a ±1.5-h exercise test on a stationary bike. Participants were excluded when they had a stent in any coronary artery, had undergone coronary artery bypass surgery, or were not cleared for intense exercise training by a cardiologist following the MARC-2 coronary computed tomography scan findings. All participants provided written informed consent before participation. The Medical Research Ethical Committee region Arnhem-Nijmegen approved this study (NL74326.091.20), which was conducted in accordance with the 1975 Declaration of Helsinki.

Procedures and Materials

Participants came to our research center for a single-study visit (∼6 h) between October 2020 and January 2021. They were instructed to refrain from exercise ≥36 h before the measurements and all participants underwent a screening consisting of medical history taking and physical examination, including blood pressure measurements and a resting electrocardiogram.

The exercise test was performed on a stationary bike (Lode Excalibur Sport, Lode B.V. Medical Technology, Groningen, The Netherlands) in a room with standardized room temperature (18°C). The exercise protocol (see Supplemental Digital Content 1, which demonstrates an overview of the exercise protocol; https://doi.org/10.6084/m9.figshare.c.7077773.v1) started after 5 min of seated rest (baseline). Participants performed a 30-min warm-up with a gradually increasing workload at a cadence of 80–100 revolutions/min, until they reached a stable heart rate (HR) at 70% of their maximum heart rate, which was obtained from 1) training data, 2) a previously performed maximal exercise test, or 3) an estimation based on age (208 − 0.7 × age) (23). When 70% of maximum HR was reached, the workload was kept stable until 30 min of warm-up had passed. Thereafter, the workload increased every 3 min by 5% until volitional exhaustion, defining the end of the exercise test, followed by a cooldown of 3 min at 50 W. Lactate concentrations were assessed at baseline and 2 min after exercise cessation (Arkray Lactate Pro 2, Axon Lab, Baden, Switzerland). As a measure for cardiac workload during exercise, the mean rate pressure product (RPP) was calculated as mean systolic blood pressure during exercise (in mmHg) multiplied by mean heart rate during exercise (in beats/min) (24).

An electrocardiogram (Quark C12x, COSMED srl, Rome, Italy), heart rate (HR; Polar V800, Polar, Kempele, Finland), and peripheral oxygen saturation (MD300C22, Beijing Choice Electronic Technology, Beijing, China) were continuously monitored during the exercise test. Rating of perceived exertion was assessed using the Borg scale at baseline, every 10 min during the exercise test, at maximal exertion, and 2 min postexercise. Blood samples (±15 mL per withdrawal) were collected before exercise, after 30 min of warm-up exercise, and at 0, 30, 60, 120, and 180 min postexercise. Samples were collected in serum gel Vacutainer tubes and allowed to clot for a minimum of 45 min. After centrifugation, serum was aliquoted, frozen (all done directly on-site), and stored at −80°C until analysis.

High-sensitivity cardiac troponin T (hs-cTnT) concentrations were analyzed on a Cobas 6000 analyzer (Troponin T Gen 5 STAT, Roche Diagnostics, Mannheim, Germany). The limit of detection was 2.9 ng/L, the limit of quantification was 3.0 ng/L with a coefficient of variation of 10%, and the overall 99th-percentile upper reference limit (URL) was 14 ng/L, according to the package insert. High-sensitivity cardiac troponin I (hs-cTnI) concentrations were analyzed on an ALINITY ci-series analyzer (Alinity i STAT High Sensitive Troponin-I Reagent Kit, Abbott Diagnostics, Abbott Park, IL) with a limit of detection of 0.7–1.6 ng/L, limit of quantification of 3.7–5.1 ng/L, and an overall 99th-percentile URL of 26.2 ng/L, according to the package insert. Fold changes in cTn concentrations were calculated by dividing the highest cTn concentrations (ng/L) by baseline concentrations (ng/L). For explorative purposes, we also calculated the hs-cTnI:hs-cTnT ratio as a previous study demonstrated that the ratio of hs-cTnI to hs-cTnT is higher in acute myocardial injury than in chronic myocardial injury and might therefore be helpful to discriminate between acute and chronic myocardial injury (25). Assay performance was monitored using quality control samples. This also included samples in the normal range, for hs-cTnT at 6.1 ng/L [SD 0.7 ng/L, coefficient of variation (CV) 12%], and for hs-cTnI at 19 ng/L (SD 1.5 ng/L, CV 7.8%). The quality control data can be found in Supplemental Digital Content 2.

Statistical Analysis

Data are presented as means ± SD, medians [interquartile ranges], or frequencies (%). The normality of variables was tested using the Shapiro–Wilk tests. The homogeneity of variance between groups was tested using Levene’s tests. One-way ANOVA tests were used to compare the means of normally distributed continuous variables. Kruskal–Wallis tests were used to compare means when continuous variables violated the ANOVA assumptions. Categorical variables were compared using Pearson’s χ² tests or, in cases where the expected count for any cell was below 5, with Fisher’s exact tests. In case significant differences were found, pairwise comparisons with a Bonferroni correction for multiple testing were performed.

To test whether time-dependent changes in hs-cTnT and hs-cTnI concentrations differed between groups, we performed a mixed-model analysis using random intercepts. hs-cTnT and hs-cTnI concentrations were significantly skewed and therefore logarithmically transformed [log₁₀(hs-cTn concentration)] for mixed model analysis. Time was described as a categorical variable for baseline, after 30 min of exercise, and at 0, 30, 60, 120, and 180 min postexercise. The interaction effect (group × time) between changes in troponin concentrations over time was subsequently tested. All statistical tests were performed using IBM SPSS Statistics 27 (IBM, Armonk, NY) and P values <0.05 were considered statistically significant.

RESULTS

Participant Characteristics

A total of 59 participants were recruited: n = 20 controls, n = 20 high CACS, and n = 19 with significant stenoses. One participant from the significant stenosis group did not complete the exercise test because of a knee injury and was therefore excluded from further analyses. Subject characteristics such as age (61 [58–69] yr), height, body mass index, and blood pressure did not differ across study groups (Table 1). The high CACS group had a calcium score of 323 [195–610] AU corresponding to the 84th [80–92] age-related MESA percentile, whereas the significant stenosis group had a calcium score of 681 [64–1,312] AU corresponding with the 84th [72–94] age-related MESA percentile. In the significant stenosis group, a 50–69% stenosis was most common (n = 12) and a ≥70% stenosis was less common (n = 6). Other characteristics of the coronary artery stenosis, including the Coronary Artery Disease-Reporting and Data System (CAD-RADS) classification and anatomical location of the stenosis, can be found in Supplemental Digital Content 3.

Table 1.

Characteristics of the analytical study cohort

	Total Cohort	Controls	High CACS	≥50% Stenosis	P Value
n	58	20	20	18
Participant characteristics
Age, yr	61 [58–69]	60 [57–69]	60 [58–67]	65 [61–69]	0.24
Height, cm	183 ± 7	182 ± 6	184 ± 6	182 ± 8	0.51
Body mass, kg	84.9 ± 10.2	81.0 ± 8.0	89.0 ± 10.0†	84.6 ± 11.2	0.04*
BMI, kg/m2	25.3 ± 2.5	24.4 ± 2.0	26.2 ± 2.7	25.4 ± 2.5	0.08
CACS, AU	185 [0–648]	0 [0–0]	323 [195–610]†	681 [64–1312]†	<0.001*
CACS ≥ 300 AU, n (%)	21 (36.2)	0 (0.0)	10 (50.0)†	11 (61.1)†	<0.001*
MESA percentile	79 [0–88]	0 [0–0]	84 [80–92]†	84 [72–94]†	<0.001*
≥75th MESA percentile, n (%)	33 (56.9)	0 (0.0)	19 (95.0)†	14 (77.8)†	<0.001*
Stenosis, n (%)
Significant (≥50%)	18 (31.0)	0 (0.0)	0 (0.0)	18 (100.0)†‡	<0.001*
Stenosis (50–69%)	12 (20.7)	0 (0.0)	0 (0.0)	12 (66.7)†‡	<0.001*
Stenosis (≥70%)	6 (10.3)	0 (0.0)	0 (0.0)	6 (33.3)†‡	<0.001*
Blood pressure, mmHg
Systolic	144 ± 14	141 ± 12	145 ± 13	146 ± 16	0.39
Diastolic	88 ± 10	86 ± 8	89 ± 12	88 ± 11	0.67
Resting heart rate, beats/min	59 [55–70]	58 [52–64]	63 [55–71]	60 [55–72]	0.38
Expected maximum HR, beats/min	166 ± 10	168 ± 7	166 ± 10	163 ± 12	0.36
Cardiovascular risk factors, n (%)	27 (46.6)	0 (0.0)	13 (65.0)†	14 (77.8)†	<0.001*
Hypertension	5 (8.6)	0 (0.0)	2 (10.0)	3 (16.7)	0.18
Antihypertensive drug(s)	3 (6.5)	0 (0)	1 (5)	2 (11.1)	0.78
Hypercholesterolemia	23 (39.7)	0 (0)	11 (55.0)†	12 (66.7)†	<0.001*
Statin users	24 (41.4)	0 (0)	11 (55.0)†	13 (72.2)†	<0.001*
Diabetes mellitus	1 (1.7)	0 (0)	1 (5.0)	0 (0.0)	1.00
Family history of CVD, n (%)	9 (15.5)	2 (10.0)	3 (15.0)	4 (22.2)	0.60
Smoking, n (%)					0.43
Nonsmoker	53 (91.4)	19 (95.0)	19 (95.0)	15 (83.3)
Current/quit <2 years ago	5 (8.6)	1 (5.0)	1 (5.0)	3 (16.7)
Exercise test characteristics
Exercise duration, min	76 ± 14	77 ± 12	77 ± 17	75 ± 12	0.88
Mean SBP, mmHg	173 ± 18	168 ± 16	177 ± 16	173 ± 22	0.30
Mean heart rate, beats/min	135 ± 12	137 ± 10	133 ± 12	134 ± 14	0.51
Mean RPP, mmHg × beats/min	23,299 ± 3,020	23,048 ± 2,274	23,614 ± 3,315	23,227 ± 3,511	0.84
Peak heart rate, beats/min	164 ± 13	166 ± 12	160 ± 13	162 ± 17	0.43
Exercise intensity, %HRmax	98 [95–102]	99 [97–102]	96 [93–101]	99 [94–105]	0.20
Maximum workload, W	209 ± 38	215 ± 33	213 ± 43	198 ± 36	0.34
Maximal workload, W/kg body wt	2.5 ± 0.5	2.7 ± 0.4	2.4 ± 0.5	2.4 ± 0.5	0.13
Baseline lactate, mmol/L	1.8 [1.4–2.1]	1.8 [1.6–2.2]	1.6 [1.4–2.1]	1.8 [1.4–2.0]	0.50
Lactate 2-min postexercise, mmol/L	8.5 [6.6–13.1]	10.9 [6.9–14.0]	8.2 [5.8–11.9]	8.3 [6.8–13.3]	0.58
Maximal RPE	19 [19–20]	20 [19–20]	19 [19–20]	19 [18–20]	0.30

Values are means ± SD or n (%) or medians [interquartile ranges]. BMI, body mass index; AU, Agatston units; MESA, Multi-Ethnic Study of Atherosclerosis; HR, heart rate; CVD, cardiovascular disease; %HR_max, percentage of expected maximal heart rate; RPE, rating of perceived exertion scale [6 (very, very light)–20 (maximal exertion)]. *P < 0.05; †pairwise comparison, significantly different from controls; ‡pairwise comparison, significantly different from the high coronary artery calcium score (CACS) group.

Exercise Characteristics

HR and rating of perceived exertion gradually increased during the exercise test (P_time < 0.001) but did not differ across groups (P_group > 0.05, Fig. 1). None of the participants experienced clinical signs or symptoms of exercise-induced myocardial ischemia and no ischemic ECG changes were observed during the exercise tests. Participants were exercised for 76 ± 14 min and obtained a peak heart rate of 164 ± 13 beats/min (98 [95–102]% of maximum HR) and lactate concentration of 8.5 [6.6–13.1] mmol/L, which did not differ across groups. Peripheral oxygen saturation showed a small decrease during exercise in all groups but recovered following exercise cessation (P_time < 0.001, Fig. 1D). Mean systolic blood pressure, mean heart rate, and the mean rate pressure product during exercise did not differ across groups (P = 0.30, P = 0.51, and P = 0.84, respectively).

Figure 1.

Time-dependent changes in workload (A), heart rate (HR; B), rating of perceived exertion (RPE; C), and peripheral oxygen saturation ($\mathrm{S}{\mathrm{p}}_{{\mathrm{O}}_2}$; D) for the control group (blue), high coronary artery calcium score (CACS) group (black), and significant stenosis group (red). Workload, HR, and RPE gradually increased over time, but responses did not differ across groups. $S{p}_{O_2}$ showed a minimal decrease during exercise but recovered postexercise and responses did not differ across groups. Data are presented at baseline and at 0, 20, 40, 60, 80, and 100% completion of the exercise test and at 30, 60, 120, and 180 min after exercise cessation (P30, P60, P120, and P180, respectively).

Cardiac Troponin Concentrations

Baseline hs-cTnT and hs-cTnI concentrations were detectable in all participants, with three participants (16.7%) of the significant stenoses group demonstrating a hs-cTnT concentration greater than URL (P = 0.026, Table 2). Exercise increased hs-cTnT and hs-cTnI concentrations (Fig. 2), but the magnitudes of the hs-cTnT and hs-cTnI elevations were not different across groups (P = 0.93 and P = 0.72, respectively). The highest concentrations of hs-cTnT and hs-cTnI were achieved at 180 min postexercise and did not differ across groups [P = 0.83 and P = 0.95, respectively, see Supplemental Digital Content 4, which demonstrates the individual hs-cTnT and hs-cTnI concentrations for the control group (in blue), high CACS group (in black), and significant stenosis group (in red)]. At 180 min postexercise, the proportion of participants with a cTn concentration greater than URL was 43.1% for hs-cTnT and 8.6% for hs-cTnI and did not differ across groups (P = 0.71 and P = 0.86, respectively). Also, time-dependent fold changes in hs-cTnT and hs-cTnI concentrations, or their ratio, did not differ across groups. hs-cTnT and hs-cTnI concentrations were strongly correlated (r = 0.97, P < 0.001 for the full analytical cohort and r = 0.70, P < 0.001 after exclusion of 2 outliers).

Table 2.

Baseline and peak cardiac troponin concentrations

Exercise Test Performance	Total Cohort	Controls	High CACS	≥50% Stenosis	P Value
n	58	20	20	18
Baseline
hs-cTnT, ng/L	8.3 [6.5–10.4]	8.0 [6.4–9.3]	8.1 [6.4–11.0]	8.6 [6.5–12.8]	0.54
>URL, n (%)	3 (5.2)	0 (0)	0 (0)	3 (16.7)†‡	0.026*
hs-cTnI, ng/L	2.0 [1.4–3.8]	1.9 [1.0–5.0]	2.2 [1.5–4.3]	1.9 [1.5–3.9]	0.77
>URL, n (%)	2 (3.4)	0 (0)	1 (5.0)	1 (5.6)	0.76
hs-cTnI:hs-cTnT ratio	0.27 [0.19–0.49]	0.26 [0.16–0.60]	0.28 [0.22–0.46]	0.26 [0.17–0.44]	0.69
Postexercise (180 min)#
hs-cTnT, ng/L	13.2 [10.0–18.2]	13.8 [9.4–17.0]	12.1 [10.0–21.5]	14.2 [9.8–20.4]	0.83
>URL, n (%)	25 (43.1)	9 (45.0)	7 (35.0)	9 (50.0)	0.71
hs-cTnI, ng/L	6.5 [4.2–12.9]	6.7 [3.6–11.7]	6.4 [3.9–15.9]	5.9 [4.2–13.4]	0.95
>URL, n (%)	5 (8.6)	1 (5.0)	2 (10.0)	2 (11.1)	0.86
hs-cTnI:hs-cTnT ratio	0.53 [0.37–0.70]	0.52 [0.36–0.67]	0.53 [0.41–0.71]	0.49 [0.37–0.72]	0.89
Δhs-cTnT, ng/L	4.7 [2.1–8.9]	4.6 [2.4–8.7]	4.2 [1.7–11.6]	5.6 [2.3–10.7]	0.93
Δhs-cTnI, ng/L	3.7 [2.2–7.0]	3.5 [1.5–7.6]	3.6 [2.1–8.0]	4.0 [3.1–7.5]	0.72
Fold change hs-cTnT	1.55 [1.33–2.14]	1.50 [1.32–2.01]	1.57 [1.23–2.34]	1.51 [1.34–2.86]	0.95
Fold change hs-cTnI	2.76 [1.89–3.86]	2.57 [1.66–5.35]	2.79 [1.88–3.39]	3.11 [2.03–3.87]	0.77

Values are means ± SD or n (%) or medians [interquartile ranges]. #Peak concentrations were measured at 180 min postexercise.

Hs-cTnT, high-sensitivity cardiac troponin T; URL, 99% upper reference limit; hs-cTnI, high-sensitive cardiac troponin I. *P < 0.05; †pairwise comparison, significantly different from controls; ‡pairwise comparison, significantly different from the high coronary artery calcium score (CACS) group.

Figure 2.

Exercise-induced elevations in high-sensitivity cardiac troponin T (hs-cTnT; A) and high-sensitivity cardiac troponin I (hs-cTnI; B) concentrations for the control group (blue), high coronary artery calcium score (CACS) group (black), and the significant stenosis group (red). hs-cTnT and hs-cTnI increased over time, but release patterns were similar across groups. URL, 99% upper reference limit (14.0 ng/L for hs-cTnT and 26.2 ng/L for hs-cTnI). Data are presented as medians with interquartile ranges [IQRs] at baseline (B0), after 30 min of warm-up exercise (E30), and at 0, 30, 60, 120, and 180 min after exercise cessation (P0, P30, P60, P120, and P180, respectively).

DISCUSSION

We compared exercise-induced elevations in hs-cTnT and hs-cTnI concentrations in athletes with versus without coronary atherosclerosis. In contrast to our hypothesis, no differences in hs-cTnT and hs-cTnI responses were found across groups. These findings indicate that the presence of coronary atherosclerosis, defined as high CACS or a >50% coronary stenosis, does not impact hs-cTnT and hs-cTnI concentrations sampled before, during, or 180 min after an exhaustive endurance exercise test in middle-aged and older athletes.

Our observation that exercise-induced cTn release did not differ between athletes with versus without coronary atherosclerosis is contradictory to some (16), but not all (17, 18, 26), previous studies. A potential explanation for these discrepant outcomes may relate to the exercise stimulus, as exercise-induced cTn release is associated with exercise intensity and duration (12). Although peak exercise intensity was largely comparable between participants of our study and the North Sea Race Endurance Exercise Study (NEEDED) study (16) (98 vs. 101% of maximum HR), exercise duration was substantially lower (∼1.3 vs. ∼3.6 h), which might explain the lower prevalence of cTn concentrations greater than URL at 3 h postexercise (43 vs. 98%). If demand ischemia is the underlying mechanism for exaggerated exercise-induced cTn release among athletes with coronary atherosclerosis, our exercise stimulus might accordingly have been too low to provoke ischemia. A longer exercise exposure time may, therefore, be needed to provoke a distinct cTn release pattern in athletes with coronary atherosclerosis.

An alternative explanation for our null findings may relate to the timing of the cTn assessment. Our approach with serial measures of hs-cTnT and hs-cTnI concentrations gave advanced insights into cTn release kinetics and it appeared that cTn concentrations were still rising at 180 min postexercise, indicating that peak values were potentially missed. We did not draw blood samples beyond 180 min postexercise to reduce the burden (i.e., duration) of study participation. However, additional samples at 12, 24, 36, and/or 48 h postexercise may be needed to uncover different release patterns across individuals with versus without coronary atherosclerosis. In fact, Kleiven et al. (16) found no difference in cTn concentrations between healthy athletes and athletes with occult obstructive coronary artery disease at 3 h postexercise, but significantly higher cTnI and cTnT concentrations were found at 24 h postexercise. These observations suggest that individuals with obstructive coronary artery disease have a prolonged cTn release or a delayed recovery of cTn elevations following exercise. Hence, delayed cTn sampling, rather than the assessment of immediate postexercise cTn concentrations, may be more appropriate to identify athletes with coronary atherosclerosis.

A final explanation for our findings may be due to the selection of study participants. We recruited participants from the MARC-2 study (19) to allocate athletes to the control, high CACS, or significant stenosis group. The latter group underwent a cardiac stress test following their computed tomography scan and only individuals without ischemia on a myocardial perfusion scan were eligible to participate in the present add-on study. Hence, we included a selected subgroup of athletes that did not experience a functional limitation during cardiac stress testing despite the stenoses in their coronary arteries. This may be partially attributed to their exercise regimen, as coronary artery size and dilating capacity are increased among athletes compared with control subjects (27), further providing support for a lack of hemodynamic consequences. Participants with a significant stenosis might not have experienced a cardiac oxygen supply demand mismatch during the exercise test, leading to similar exercise-induced cTn release patterns as healthy controls and individuals with high CACS.

Strengths and Limitations

To our knowledge, this is the first prospective, controlled study in a laboratory setting that combines serial measurements of exercise-induced hs-cTn elevations and cardiac computed tomography scan data, which enable us to investigate the association between the degree of coronary atherosclerosis and postexercise hs-cTn release. Nevertheless, our study has a few limitations. First, due to safety reasons, only participants with significant stenoses who were cleared by a cardiologist to perform unrestricted exercise were eligible for inclusion in the present study. This may limit the generalizability of our findings, as athletes with a more severe coronary stenosis and functional limitation may demonstrate exaggerated exercise-induced elevations in hs-cTn concentrations because of demand ischemia. Indeed, Tonino et al. (28) demonstrated that of 50–70% stenoses, only 35% are hemodynamically relevant (fractional flow reserve ≤0.80), whereas of 71–90% stenoses, 80% are hemodynamically relevant. Second, our study was performed in white males aged 53 yr or older. Therefore, it is unclear whether our findings can be extended to females and/or a younger population, despite the fact that coronary artery disease is more prevalent in males and older individuals (5, 29). Future studies should also enroll female athletes and athletes from other races/ethnicities to increase the diversity and improve the generalizability of findings (30). Third, our sample size is limited compared with field studies assessing exercise-induced hs-cTnT elevations (31, 32), but significantly larger than previous laboratory-based studies (33–35). Fourth, we assessed cTn release kinetics using only two different commercial assays, which may limit the extrapolation of our findings to other cTn assays.

Conclusions

Serial sampling of hs-cTnT and hs-cTnI concentrations during and following an exhaustive endurance exercise test did not reveal differences in exercise-induced cTn release between athletes with versus without coronary atherosclerosis. These findings suggest that the presence of a high CACS or a >50% coronary stenosis in any coronary artery does not aggravate exercise-induced cardiac troponin release in asymptomatic middle-aged and older athletes.

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

SUPPLEMENTAL DATA

According to the Contributor Roles Taxonomy (CRediT), the author’s contributions are listed in Supplemental Digital Content 5. Supplemental Digital Content 1.tiff, Supplemental Digital Content 2.doc, Supplemental Digital Content 3.doc, Supplemental Digital Content 4.tiff, and Supplemental Digital Content 5.doc: https://doi.org/10.6084/m9.figshare.c.7077773.v1.

GRANTS

S.L.J.E.J. is financially supported by grants from Radboud University Medical Center and the Academic Alliance Fund. A.M.A.M. received Dutch Research Council (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) VENI Grant 09150161810155. V.L.A. was financially supported by Dutch Heart Foundation Grant 2017T088.

DISCLAIMERS

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Abbott Diagnostics and Roche Diagnostics had no role in the study’s design, the data analysis, the article’s preparation, or the decision to submit the article for publication. The sponsors had no role in the study’s design, the data analysis, the article's preparation, or the decision to submit the article for publication. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sport Medicine.

DISCLOSURES

A.M.A.M. has received nonfinancial support from Abbott Diagnostics and Roche Diagnostics. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.

AUTHOR CONTRIBUTIONS

F.d.V., V.L.A., and T.M.H.E. conceived and designed research; S.L.J.E.J., F.d.V., G.K., and V.L.A. performed experiments; S.L.J.E. analyzed data; S.L.J.E., A.M.A.M., V.L.A., and T.M.H.E. interpreted results of experiments; S.L.J.E.J. prepared figures; S.L.J.E.J. drafted manuscript; F.d.V., A.M.A.M., G.K., M.T.E.H., A.M., B.K.V., V.L.A., and T.M.H.E. edited and revised manuscript; S.L.J.E.J., F.d.V., A.M.A.M., G.K., M.T.E.H., A.M., B.K.V., V.L.A., and T.M.H.E. approved final version of manuscript.