The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

Myocardial inefficiency is an early indicator of exercise-induced myocardial fatigue.

Background: The effect of prolonged, high-intensity endurance exercise on myocardial function is unclear. This study aimed to determine the left ventricular (LV) response to increased exercise duration and intensity using novel echocardiographic tools to assess myocardial work and fatigue. Materials and methods: LV function was assessed by echocardiography before, immediately, and 24 h after a cardiopulmonary exercise test (CPET) and a 91-km mountain bike leisure race. Cardiac Troponin I (cTnI) was used to assess myocyte stress. Results: 59 healthy recreational athletes, 52 (43-59) years of age, 73% males, were included. The race was longer and of higher intensity generating higher cTnI levels compared with the CPET (p < 0.0001): Race/CPET: exercise duration: 230 (210, 245)/43 (40, 45) minutes, mean heart rate: 154 ± 10/132 ± 12 bpm, max cTnI: 77 (37, 128)/12 (7, 23) ng/L. Stroke volume and cardiac output were higher after the race than CPET (p < 0.005). The two exercises did not differ in post-exercise changes in LV ejection fraction (LVEF) or global longitudinal strain (GLS). There was an increase in global wasted work (p = 0.001) following the race and a persistent reduction in global constructive work 24 h after exercise (p = 0.003). Conclusion: Increased exercise intensity and duration were associated with increased myocardial wasted work post-exercise, without alterations in LVEF and GLS from baseline values. These findings suggest that markers of myocardial inefficiency may precede reduction in global LV function as markers of myocardial fatigue.

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance.

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.

Determinants of Interindividual Variation in Exercise-Induced Cardiac Troponin I Levels.

Background Postexercise cardiac troponin levels show considerable interindividual variations. This study aimed to identify the major determinants of this postexercise variation in cardiac troponin I (cTnI) following 3 episodes of prolonged high-intensity endurance exercise. Methods and Results Study subjects were recruited among prior participants in a study of recreational cyclists completing a 91-km mountain bike race in either 2013 or 2014 (first race). In 2018, study participants completed a cardiopulmonary exercise test 2 to 3 weeks before renewed participation in the same race (second race). Blood was sampled before and at 3 and 24 hours following all exercises. Blood samples were analyzed using the same Abbot high-sensitivity cTnI STAT assay. Fifty-nine individuals (aged 50±9 years, 13 women) without cardiovascular disease were included. Troponin values were lowest before, highest at 3 hours, and declining at 24 hours. The largest cTnI difference was at 3 hours following exercise between the most (first race) (cTnI: 200 [87-300] ng/L) and the least strenuous exercise (cardiopulmonary exercise test) (cTnI: 12 [7-23] ng/L; P<0.001). The strongest correlation between troponin values at corresponding times was before exercise (r=0.92, P<0.0001). The strongest correlations at 3 hours were between the 2 races (r=0.72, P<0.001) and at 24 hours between the cardiopulmonary exercise test and the second race (r=0.83, P<0.001). Participants with the highest or lowest cTnI levels showed no differences in race performance or baseline echocardiographic parameters. Conclusions The variation in exercise-induced cTnI elevation is largely determined by a unique individual cTnI response that is dependent on the duration of high-intensity exercise and the timing of cTnI sampling. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Regular consumption of cod liver oil is associated with reduced basal and exercise-induced C-reactive protein levels; a prospective observational trial : A NEEDED (The North Sea Race Endurance Exercise Study) 2014 sub-study.

BACKGROUND: Dietary supplement use among recreational athletes is common, with the intention of reducing inflammation and improving recovery. We aimed to describe the relationship between omega-3 fatty acid supplement use and inflammation induced by strenuous exercise. METHODS: C-reactive protein (CRP) concentrations were measured in 1002 healthy recreational athletes before and 24 h after a 91-km bicycle race. The use of omega-3 fatty acid supplements was reported in 856 out of 1002 recreational athletes, and the association between supplement use and the exercise-induced CRP response was assessed. RESULTS: Two hundred seventy-four subjects reported regular use of omega-3 fatty acid supplements. One hundred seventy-three of these used cod liver oil (CLO). Regular users of omega-3 fatty acid supplements had significantly lower basal and exercise-induced CRP levels as compared to non-users (n = 348, p < 0.001). Compared to non-users, regular users had a 27% (95% confidence interval (CI): 14-40) reduction in Ln CRP response (unadjusted model, p < 0.001) and 16% (95% CI: 5-28, p = 0.006) reduction after adjusting for age, sex, race duration, body mass index, delta creatine kinase, MET hours per week, resting heart rate and higher education. CLO was the primary driver of this response with a 34% (95% CI: 19-49) reduction (unadjusted model, p < 0.001) compared to non-users. Corresponding numbers in the adjusted model were 24% (95% CI: 11-38, p < 0.001). CONCLUSION: Basal CRP levels were reduced, and the exercise-induced CRP response was attenuated in healthy recreational cyclists who used omega-3 fatty acid supplements regularly. This effect was only present in regular users of CLO. TRIAL REGISTRATION: NCT02166216 , registered June 18, 2014 - Retrospectively registered.

High-Sensitivity Cardiac Troponin I and T Response Following Strenuous Activity is Attenuated by Smokeless Tobacco: NEEDED (North Sea Race Endurance Exercise Study) 2014.

Background Use of snus, a smokeless tobacco product, is increasing in Scandinavia. Strenuous physical activity is associated with an acute increase in high-sensitivity cardiac troponin (swhs-cTn) concentrations. Current smoking is associated with lower hs-cTn, but whether this also holds true for smokeless tobacco and whether tobacco affects the hs-cTn response to exercise remain unknown. Methods and Results We measured hs-cTnI and hs-cTnT concentrations in 914 recreational athletes before and 3 and 24 hours after a 91-km bicycle race. Self-reported snus tobacco habits were reported as noncurrent (n=796) and current (n=118). The association between snus use and change in log-transformed hs-cTnI and hs-cTnT concentrations (ie, the differences between concentrations at baseline and 3 hours and 24 hours ) were assessed by multivariable linear regression analysis. Concentrations of hs-cTn at baseline were lower in current than in noncurrent snus users (hs-cTnI median, 1.7 ng/L; Q1 to Q3: 1.6-2.3 versus 2.0 ng/L; Q1 to Q3: 1.6-3.2 [P=0.020]; and hs-cTnT: median, 2.9 ng/L, Q1 to Q3: 2.9-3.5 versus 2.9 ng/L, Q1 to Q3: 2.9-4.3 [P=0.021]). In fully adjusted multivariable models, use of snus was associated with lower change in hs-cTn concentrations from baseline to 3 hours (hs-cTnI: -29% [P=0.002], hs-cTnT: -18% [P=0.010]) and 24 hours (hscTnI: -30% [P=0.010], hs-cTnT -19%, [P=0.013]). Conclusions Resting hs-cTn concentrations are lower and the exercise-induced cardiac troponin response is attenuated in current users of smokeless tobacco compared with nonusers. Further insight into the pathophysiological processes underlying the attenuated cardiac troponin response to exercise in tobacco users is needed. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02166216.

Endurance exercise training volume is not associated with progression of coronary artery calcification.

BACKGROUND: Recent cross-sectional studies have suggested a dose-dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. HYPOTHESIS: Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. METHODS: Sixty-one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re-assessed 4-5 years later, in 2018. RESULTS: Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0-20, 25th-75th percentile: 4-6) hours of high-intensity exercise per week. None of the included subjects smoked during follow-up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow-up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P = .002) and had higher levels of low-density lipoprotein at baseline (3.5 (2.9-4.3) vs 2.9 (2.3-3.5) mmol/L, P = .031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. CONCLUSION: No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle-aged recreational athletes.

Duration of Elevated Heart Rate Is an Important Predictor of Exercise-Induced Troponin Elevation.

Background The precise mechanisms causing cardiac troponin (cTn) increase after exercise remain to be determined. The aim of this study was to investigate the impact of heart rate (HR) on exercise-induced cTn increase by using sports watch data from a large bicycle competition. Methods and Results Participants were recruited from NEEDED (North Sea Race Endurance Exercise Study). All completed a 91-km recreational mountain bike race (North Sea Race). Clinical status, ECG, blood pressure, and blood samples were obtained 24 hours before and 3 and 24 hours after the race. Participants (n=177) were, on average, 44 years old; 31 (18%) were women. Both cTnI and cTnT increased in all individuals, reaching the highest level (of the 3 time points assessed) at 3 hours after the race (P<0.001). In multiple regression models, the duration of exercise with an HR >150 beats per minute was a significant predictor of both cTnI and cTnT, at both 3 and 24 hours after exercise. Neither mean HR nor mean HR in percentage of maximum HR was a significant predictor of the cTn response at 3 and 24 hours after exercise. Conclusions The duration of elevated HR is an important predictor of physiological exercise-induced cTn elevation. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02166216.

Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise.

BACKGROUND: Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease. DESIGN: Prospective observational study. METHODS: Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values. RESULTS: Study subjects (N = 120) were 45 (36-52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125-304) ng/L; cTnT, 89 (55-124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort (n = 109): cTnI, 151 (72-233) ng/L vs. 24 (19-82) ng/L, p = 0.005; cTnT, 39 (25-55) ng/L vs. 20 (14-31) ng/L, p = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p = 0.005 (cTnI) and 0.82, p = 0.002 (cTnT). CONCLUSION: In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.

Race duration and blood pressure are major predictors of exercise-induced cardiac troponin elevation.

BACKGROUND: The underlying mechanisms of the exercise-induced increase in cardiac troponins (cTn) are poorly understood. The aim of this study was to identify independent determinants of exercise-induced cTn increase in a large cohort of healthy recreational athletes. METHODS: A total of 1002 recreational cyclists without known cardiovascular disease or medication, participating in a 91-km mountain bike race were included. Median age was 47 years and 78% were males. Blood samples were obtained 24 h prior to, and 3 and 24 h after the race. RESULTS: Cardiac TnI concentrations increased markedly from baseline [1.9 (1.6-3.0) ng/L] to 3 h after the race [52.1 (32.4-91.8) ng/L], declining at 24 h after the race [9.9 (6.0-20.0) ng/L]. Similarly, cTnT increased from baseline [3.0 (3.0-4.2) ng/L] to 3 h after the race [35.6 (24.4-54.4) ng/L], followed by a decline at 24 h after the race [10.0 (6.9-15.6) ng/L]. The 99th percentile was exceeded at 3 h after the race in 84% (n = 842) of subjects using the cTnI assay and in 92% (n = 925) of study subjects using the cTnT assay. Shorter race duration and higher systolic blood pressure (SBP) at baseline were highly significant (p < 0.001) independent predictors of exercise-induced cTn increase both in bivariate and multivariable analysis. The age, gender, body mass index, training experience and cardiovascular risk of participants were found to be less consistent predictors. CONCLUSION: Systolic blood pressure and race duration were consistent predictors of the exercise-induced cTn increase. These variables likely reflect important mechanisms involved in the exercise-induced cTn elevation. TRIAL REGISTRATION NUMBER: NCT02166216 https://clinicaltrials.gov/ct2/show/NCT02166216.

The cardiac troponin response following physical exercise in relation to biomarker criteria for acute myocardial infarction; the North Sea Race Endurance Exercise Study (NEEDED) 2013.

BACKGROUND: The aim of this study was to investigate troponin (cTn) dynamics for both genders, compared the different release patterns to the gender specific 99th percentile and to current biomarker criteria for diagnosing myocardial infarction (MI). METHODS: Serum was collected from 97 recreational cyclists 24 h before and immediately, 3 and 24 h following a 91-km bike race. hs-cTnI (Abbott) and hs-cTnT (Roche) were measured. Conventional or CT coronary angiography was performed in the 13 participants with the highest hs-cTnI (>140 ng/L). Three subjects with obstructive coronary artery disease were excluded from the statistical analysis. RESULTS: There was a significant (p < 0.001) post-race increase in cTnI and cTnT; cTnT peaked immediately, cTnI peaked after 3 h. Relative to the gender specific 99th percentile values, women had the largest increase. The biomarker criteria for MI were met in 76-87% for hs-cTnI, and 96-95% for hs-cTnT (p value <0.05), within the first 3 h post-race. CONCLUSION: Post-race cardiac troponin concentrations exceeded diagnostic criteria for MI in the majority of subjects, more often for hs-cTnT than for hs-cTnI, and more pronounced in women than in men. The current biomarker criteria for MI discriminate poorly between an exercise induced troponin increase and acute MI.

The copeptin response after physical activity is not associated with cardiac biomarkers or asymptomatic coronary artery disease: The North Sea Race Endurance Exercise Study (NEEDED) 2013.

BACKGROUND: Copeptin concentrations increase both during acute coronary syndrome and following physical exercise. The relationship between copeptin increase following physical exercise and coronary artery disease (CAD) is uncertain. The aim of this study was to 1) describe the copeptin response following strenuous physical exercise, and 2) investigate the determinants of exercise induced copeptin concentrations, particularly in relation to cardiac biomarkers and CAD. METHODS: Serum samples were collected from 97 recreational cyclists 24h before, and immediately, 3 and 24h after a 91-km bike race. Three subjects were subsequently diagnosed with significant asymptomatic CAD. Delta copeptin concentrations were correlated to patient characteristics and to biomarker concentrations. RESULTS: Participants were 42.8±9.6years, and 76.3% were male. Copeptin concentrations increased to maximal levels immediately after the race and were normalized in >90% after 3h. A total of 53% and 39% exceeded the 95th and 99th percentile of the assay (10 and 19pmol/L) respectively. In multivariate models, race time, serum sodium, creatinine and cortisol were significant predictors of copeptin levels. There was no correlation between changes in copeptin and changes in cardiac biomarkers (hs-cTnI, hs-cTnT and BNP). Copeptin concentrations were normal in the subjects with asymptomatic CAD. CONCLUSIONS: The moderate, short-term, exercise induced copeptin increase observed in the present study was not related to hs-cTn or BNP levels. Copeptin was normal in three asymptomatic recreational athletes with significant CAD.

Highly increased Troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: The North Sea Race Endurance Exercise Study (NEEDED) 2013.

Background Circulating cardiac troponin levels increase following prolonged intense physical exercise. The aim of this study was to identify participants with highly elevated cardiac troponins after prolonged, high intensity exercise, and to evaluate these for subclinical coronary artery disease. Methods and results Ninety-seven recreational cyclists without known cardiovascular disease or diabetes, participating in a 91 km mountain bike race were included, 74 (76%) were males, age: 43 ± 10 years, race duration: 4.2 (3.6-4.7) h. Blood samples, rest electrocardiogram and physical examination were obtained 24 h prior to, and at 0, 3 and 24 h following the race. Median cardiac troponin I level at baseline: 3.4 (2.1-4.9) ng/l (upper limit of normal: 30.0 ng/l). There was a highly significant ( p < 0.0001) increase in circulating cardiac troponin I in all participants: immediately following the race; 50.5 (28.5-71.9) ng/l, peaking at 3 h 69.3 (42.3-97.7) ng/l and declining at 24 h: 14.2 (8.5-27.9) ng/l. No cyclist had symptoms or rest electrocardiogram changes compatible with coronary artery disease during or following the race. Coronary artery disease was detected by coronary angiography in the three cyclists with the three of the four highest cardiac troponin values (>370 ng/l) at 3 and 24 h following the race. Computed tomographic coronary angiography was performed in an additional 10 riders with the subsequently highest cardiac troponin I values, without identifying underlying coronary artery disease. Conclusions This study suggests that there is a pathologic cardiac troponin I response following exercise in individuals with subclinical coronary artery disease. This response may be associated with an excessive cardiac troponin I increase at 3 and 24 h following prolonged high-intensity exercise.