The question whether strenuous endurance exercise is associated with structural or functional damage of the human heart is of utmost importance for physicians involved in the medical care and guidance of endurance athletes. The determination of cardiac Troponin T (cTnT) and brain natriuretic peptide (BNP) as indicators of myocardial damage (cTnT) and cardiac dysfunction (BNP) has reactivated the discussion about possible negative effects of prolonged, exhaustive exercise on the heart. In the past years, several studies have suggested myocardial damage after extreme endurance exercise due to increased postexercise levels of cTnT (2,4,11,15,18,20,28). This finding, however, could not be ascertained by other investigators (9,12,22). It has to be emphasized that most previous studies have applied cTnT assays of the first and second generation that show a considerable cross-reactivity with skeletal TnT. Therefore, the exercise-induced increase in TnT observed in these studies could well be derived from skeletal muscle cells (24,25). The highly cardiospecific third-generation cTnT assay does not show this cross-reactivity (7) and is thus most suitable for a clear differentiation between the cardiac and noncardiac origin of postexercise increases in creatine kinase (CK) and particularly creatine kinase MB (CKMB) (22). Skeletal muscle contains approximately 5% CKMB; this percentage can be higher in endurance trained athletes due to the larger amount of CKMB in slow-twitch fibers. Most recently, Shave et al. (23) have reported a slight increase in cTnT (third-generation assay) together with signs of reversible systolic and diastolic exercise-induced cardiac dysfunction. However, in all subjects, cTnT values were beyond the threshold indicating substantial myocardial damage. In addition, subjects investigated were relatively old (42 ± 11 yr), and both exercise intensity (Alpine Mountain Marathon) and duration (approximately 10 h) were extreme (23).
In the past years, BNP has turned out to be an excellent humoral marker for beginning or manifest cardiac dysfunction (13,14,21,26). This natriuretic peptide, mainly secreted from ventricular cells, has shown to be closely associated with increased left ventricular end diastolic pressure and impaired diastolic filling (1,6). Baseline levels of BNP and particularly the exercise-induced rise in BNP were proportional to the severeness of heart failure (10).
A marked increase in BNP has been described after a 100-km ultramarathon in apparently healthy athletes (18). In contrast, only small alterations in BNP were observed after symptom-limited bicycle exercise in healthy subjects (1,14,16,26). Recent echocardiographic investigations have shown a reversible diastolic and systolic dysfunction after long-lasting endurance events in trained individuals (20,28). It can be speculated that this exercise-induced myocardial dysfunction is pathogenetically responsible for an increase in BNP after such types of exercise.
Thus, there is a reasonable background to claim for more information regarding the exercise-induced myocardial stress reaction in athletes, particularly with the third-generation assay for cTnT. Moreover, different exercise intensities and durations have to be considered. Aside from the already mentioned problem regarding the cross-reactivity of the cTnT assay, an increase in postexercise cTnT levels or the marked rise in BNP were mostly observed after extreme ultra-endurance events (2,4,11,20,23,28). Although the authors reported that the majority of subjects investigated were well-trained endurance athletes, the question arises in how far any form of training can prepare the human organism and particularly the heart for such forms of exercise. In addition, some events took place under extreme environmental conditions (Hawaii Ironman triathlon (20)) or high altitude (Alpine bicycle ultramarathon (15,23)), thereby imposing additional cardiovascular stress.
In the present study, we investigated myocardial stress factors in highly trained professional road cyclists after long-lasting competitive endurance exercise. The hypothesis was that these athletes, training 34,000 ± 2,500 km·yr−1, would not show any form of myocardial damage or dysfunction because they were accustomed to this type of exercise.
MATERIAL AND METHODS
Subject population.
Eleven highly trained professional road cyclists (age: 27 ± 4 yr; height 180 ± 5.6 cm; weight 73.3 ± 5.4 kg; V̇O2peak 67 ± 4.7 mL·kg−1·min−1) were studied. V̇O2 was measured during an ergometry with stepwise increment of workload until exhaustion (initial power output 100 W; increases of 20 W every 3 min until exhaustion); therefore, the V̇O2 determined in the present investigation is V̇O2peak that underestimates V̇O2max by 10–15%. Most of the athletes studied have participated in the Tour de France or comparable large road cycling events; training volume averaged 34,000 ± 2,500 km·yr−1. All subjects were healthy and without previous history of cardiovascular disease; none was taking cardiovascular drugs. All athletes underwent a detailed cardiologic examination including echocardiography and stress ECG. The study was part of a program for health prevention in athletes, which was approved by the Ethical Committee of the University of Freiburg. All subjects gave written informed consent.
Testing schedule.
Blood samples were taken before and immediately after the finish of the fourth stage of a 5-d cycling race (UCI category 2.3; length 156 km; mean duration 5 h 13 min).
Blood measurements.
Blood was drawn from an antecubital vein. Whole blood for determination of hematocrit and hemoglobin was cooled at +8°C and examined within 4 h after venipuncture. Blood for determination of myocardial stress variables was spun, and plasma was stored on ice and transported to the laboratory within 1 h, where it was frozen at −20°C for later pooled analysis.
Humoral markers of myocardial damage were cTnT, CK, CKMB, and myoglobin (Myo). Signs for myocardial dysfunction were assessed by determination of BNP. Urea served as a marker for the exercise-induced catabolic stress reaction (8,27). Hemoglobin and hematocrit were measured to detect signs for hemoconcentration after the race. BNP and cTnT were determined using electrochemiluminescence (ECL) technology employed within the Modular analytics E170 analyzer (Roche Diagnostics, Lewe, Sussex). CK, CKMB, Myo, and urea were determined using standard methods of clinical-chemistry routine (Roche Diagnostica, Hitachi modular system). Hemoglobin and hematocrit were analyzed with an automated Beckman Coulter Analyzer (Coulter, Miami, FL).
Echocardiographic measurements and stress ECG.
Left ventricular function and dimensions were assessed by two-dimensional and M-mode echocardiogram with a 2.5/3.0-MHz multifrequency transducer (Toshiba, SSA-380 A, Japan). All echocardiographic measurements were done by the same experienced sonographer, in accordance with the guidelines established by the American Society of Echocardiography (3). Subjects were instructed to lie in the left lateral decubitus position, and examination was performed after at least 15 min of rest. M-mode images taken at the tips of the mitral valve leaflets were used to determine interventricular septal thickness and posterior free wall during diastole as well as left ventricular internal diameter during diastole and systole, respectively. Pulsed-wave Doppler measurements were performed during the early rapid filling phase and atrial filling phase with the 4-mm Doppler sample positioned at the most apical portion of the mitral leaflet portion. Stress ECG was performed on a cycle ergometer in the sitting position using a 12-lead ECG. Initial power output was 100 W, followed by increases of 20 W every 3 min until exhaustion. Exercise testing equipment and result interpretation was in accordance with the guidelines established by the American Heart Association (5,19).
Statistical analysis.
All parameters were checked for normal distribution using the Kolmogorov-Smirnov test procedure. Groups were tested for significant differences using the t-test for independent samples. Correlational analysis was performed by using Pearson’s correlation coefficient. P values < 0.05 were considered as statistically significant. All statistics were performed with SPSS 10.0.
RESULTS
Cardiologic examinations including stress ECG and echocardiographic examination revealed no pathological findings. No athletes showed a wall diameter of the interventricular septum (IVSd) or the posterior free wall (LVPWd) of more than 12 mm (IVSd: 10.6 ± 0.5 mm; LVPWd: 10.7 ± 0.47 mm). Left ventricular end diastolic inner diameter was 59 ± 4.9 mm. No signs for diastolic dysfunction assessed by the transmitral flow pattern could be detected (E/A ratio: 1.8 ± 0.3).
Baseline values and postexercise alterations in humoral markers of myocardial stress are shown in Table 1. CK (85.3 ± 29.5; P < 0.01), CKMB (5.5 ± 1.7; P < 0.05), and Myo (27.3 ± 4.5; P < 0.01) increased after the race. The percentage of CKMB on total CK was less than 7%. No significant rise in cTnT was observed; only two subjects presented cTnT above the detection limit and only one subject showed a borderline elevation of cTnT (0.1 ng·mL−1; normal range < 0.1 ng·mL−1). In contrast, BNP rose significantly from 47.5 ± 37.5 to 75.3 ± 55.3 pg·mL−1 (P < 0.01). Pre- and postexercise values of BNP as well as the individual exercise-induced increase in BNP were significantly correlated with age (R2 = 0.68, R2 = 0.66, and R2 = 0.58, respectively; P < 0.05) (Fig. 1). All subjects exhibiting BNP levels above 88 pg·mL−1 (normal value for healthy subjects under resting conditions) were older than 30 yr. No associations between BNP and markers of cardiomyocyte damage or echocardiographic data were observed.
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TABLE 1:
Humoral markers of exercise-induced myocardial and peripheral muscle stress (troponin, BNP, creatine kinase, creatine kinase MB, myoglobine), metabolic stress (urea), and hemoconcentration (hematocrit, hemoglobine).
FIGURE 1:
Association between pre- and postexercise (Delta = postexercise minus preexercise) plasma concentrations of brain natriuretic peptide (BNP) and age in professional cyclists (N = 11). Fit line and R-squared (Rsq) were obtained by quadratic regression.
Hemoglobin and hematocrit were not significantly altered after competition. No significant correlations between changes in hemoglobin and hematocrit and humoral myocardial stress markers could be observed.
DISCUSSION
Data from the present study suggest that competitive, long-lasting endurance exercise does not induce significant myocardial damage in professional cyclists as assessed by the third-generation assay of cTnT. However, the comparatively high exercise-induced rise in BNP-levels in elderly athletes may indicate a temporal, reversible left ventricular dysfunction.
Previous investigations have demonstrated increased cTnT levels in response to strenuous endurance exercise, and it has been hypothesized that this may reflect exercise-induced structural myocardial damage. However, the assays for cTnT applied in most of these studies show a considerable cross-reactivity with TnT derived from skeletal muscle cells (2,4,11,20,28). It is therefore not clear whether the documented increase in cTnT is of cardiac or musculoskeletal origin, because markers indicating damage of skeletal muscle cells increased in all previous studies as well. The method for determination of cTnT used in the present study does not show this cross-reactivity with skeletal TnT and can therefore be considered as highly cardiospecific (7). By using this third-generation assay for cTnT determination, Shave et al. (22) did not observe an increase in cTnT after an eccentric downhill protocol despite a considerable amount of skeletal muscle damage. In contrast, the most recent investigation of this group found a slight increase in cTnT (third-generation assay) after a very strenuous alpine mountain marathon. Although the rise in cTnT did not reach concentrations, indicating considerable myocardial damage, the cardiospecificity of this assay suggests that this type of exercise induced some form of cardiomyocyte stress. In addition, an echocardiographic examination showed a temporal exercise-induced impairment of cardiac function. Nevertheless, the cardiovascular stress of an alpine mountain-bike marathon lasting approximately 10 h in subjects aged 42 ± 11 yr is supposed to be immense. In most studies, significant increases in cTnT were limited to extreme ultra-endurance events. Although the authors reported that the participants investigated were well-trained endurance athletes, it could be assumed that this type of extreme competitional exercise can be designated as unaccustomed for the whole organism, and particularly for the heart. In contrast, the cyclists included in the present study were highly adapted to the type of exercise performed. Although it was a strenuous stage in a professional road-cycling race, the athletes investigated cycled about 35,000 km·yr−1 with approximately 15,000 km in competition. Therefore, we believe that these athletes are definitely accustomed to this type of strenuous exercise as evidenced by the relatively small increase in myoglobin, CK, CKMB, and most of all cTnT. The only cyclist showing a borderline increase in cTnT was a double Olympic champion in his discipline and exhibited—as all other study participants—absolutely no pathological findings in the baseline cardiological examinations.
Due to the aforementioned problems with the cardiospecificity of cTnT assays, it is difficult to compare our results with most of the previous investigations. Nevertheless, there is evidence to suggest that strenuous, long-lasting exercise in well-adapted cyclists does not induce considerable cardiomyocyte damage.
The postexercise increase in BNP (37%) was decisively lower than the increase described by Ohba et al. (18) after an ultramarathon (>500%). The rise in BNP observed in our investigation was within the range described for healthy subjects after exercise until exhaustion (between 0% and 41%) (1,16,26). It was, however, striking that pre- and postexercise BNP values as well as the individual exercise-induced increase in BNP were significantly associated with age (Fig. 1). Our findings suggest that older athletes (>30 yr) exhibit both higher resting and higher postexercise BNP levels and show a higher increase after competition. Mean postexercise BNP levels in younger athletes (<30 yr) were lower than the preexercise levels in those older than 30 yr. Athletes exhibiting BNP levels above the reference value (two preexercise; three postexercise) were older than 30 yr. It has to be pointed out that the baseline levels were determined on the fourth day of the stage race. Therefore, it could be speculated that the relatively high resting values in elderly athletes might be due to the functional cardiac stress imposed by the previous stage.
Although direct evidence is lacking, the assumption that the exercise-induced increase in BNP might be a marker of impaired left-ventricular function during exercise is supported by a recent investigation showing a reversible systolic and diastolic dysfunction after strenuous endurance exercise (28). It could be suggested that in the older athletes investigated in the present study, the exercise intensity of the road race induced a mild form of diastolic dysfunction associated with an increased end diastolic left ventricular pressure leading to an enhanced liberation of BNP from myocardial cells. It has to be pointed out that BNP was only correlated with age and not with any other stress markers investigated (CK, CKMB, Myo, and most particularly cTnT). The age-dependent increase in BNP could also be responsible for the distinctively higher BNP values described by Ohba et al. (17) after an ultramarathon, as the participants in this study were decisively older (mean age 46.2 yr) than in our investigation. Although only as a trend, higher BNP values were found with increasing age in the latter study as well.
Whether a marked exercise-induced rise in BNP can be considered as an early indicator of exercise-induced cardiomyocyte damage, particularly if age, intensity, or most probably both of them increase over a certain level, remains to be determined.
We acknowledge the limitations of this investigation due to the small number of athletes included. More studies investigating a larger number of subjects with different training expertise as well as a wider age range are needed. Furthermore, different exercise protocols and intensities have to be considered before certain types of exercise can be defined as potentially harmful to the heart.
CONCLUSION
Our results indicate that strenuous, yet accustomed, endurance exercise in professional road cyclists does not result in structural myocardial damage. Although mean postexercise BNP values were not pathologically elevated, the comparatively large increase in BNP in elderly athletes may reflect an exercise-induced, transient left ventricular dysfunction.
The authors thank the athletes of the “Team Telekom” for their cooperation and participation in this investigation.
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