Cardiac and Renal Function in Amateur Marathon Runners
Cardiac and Renal Function in Amateur Marathon Runners
All data were collected during our marathon studies in 2006 and 2007 as described previously.
The organizers of the 2006 and 2007 BERLIN-MARATHON invited all registered male (2006) and female (2007) contestants in all age-groups from the Berlin-Brandenburg area by e-mail to participate in our study. The first 88 positive responses from male and 111 positive responses from female runners who had previously completed at least one marathon were screened and enrolled in the study. The maximum number of study participants in each year was limited by the logistics situation immediately after the races. Written informed consent was obtained from each participant. The Ethics Committee of the Charité-Universitätsmedizin Berlin hospital approved the study protocol. The study complied with the Declaration of Helsinki.
Exclusion criteria were recent pathological results from a previous bicycle stress test (bicycle stress test was mandatory for inclusion of participants older than 50 years), history or symptoms of coronary artery disease (e.g. angina pectoris or shortness of breath) or chronic cardiovascular disorders (atrial fibrillation, permanent pacemaker, bypass surgery, prosthetic valves or congenital heart disease).
The participants were examined at least 10 days prior to the marathon at rest by a questionnaire, blood test, blood pressure and heart rate measurements, ECG and echocardiography (baseline, pre). The questionnaire comprised detailed questions on running experience, previous completed marathons, average training kilometers per week, other sporting activities, present and past medical history (including chronic diseases, physical injuries, previous hospitalizations and surgeries), allergies, alcohol consumption, medications, cardiovascular risk factors such as history of smoking or family history of cardiovascular disease/risk factors. All subjects were advised to suspend training for at least 2 days before the baseline examination. Immediately after the marathon, runners were examined in a medical tent 100 m behind the finish line by a blood test and echocardiography (post); notably, the examinations of each individual runner were completed within approximately 20 minutes after the runner crossed the finish line with subsequent offline analysis of the digitally stored echocardiographic data (EchoPac PC, GE Vingmed, Horton, Norway). A follow-up examination was performed two weeks after the marathon at rest including blood test and echocardiography.
Thirty-two runners were excluded from the study for the following reasons: positive bicycle stress test results (4); a troponin T (TnT) level above the lower limit of detection (LLD) not explained by profound exercise training prior to sampling (2); uncontrolled arterial hypertension (1); hypermobile interatrial septum (1); premature ventricular contractions (2); history of a recent stroke (1); gynaecological operation before the marathon (1); anaemia due to resistance to common therapies treated with erythropoietin (1); leg cramps (1) or acute febrile disease, any of which led to non-attendance of the marathon race (5); and personal constraints in 6 runners. One runner did not reach the finish line, sufficient blood samples for all designated analyses could not be drawn from six athletes after the marathon (after 3 unsuccessful attempts by a medical assistant). Runners with positive baseline troponin or stress tests were encouraged to undergo further cardiac diagnostics. Finally, a total of 167 healthy male (n = 78) and female (n = 89) marathon runners were included.
There were no fluid or pace restrictions for the runners during the race.
Blood samples were collected in a supine position from cubital veins at the time points mentioned above. EDTA blood was collected for haematological parameters and measured immediately after collection. For the other markers, serum was prepared by centrifugation, immediately frozen and stored at −20°C until processing. None of the specimens demonstrated signs of haemolysis. Laboratory results from the post-marathon time points were corrected intra-individually for dehydration, as previously described. The change in plasma volume between the pre- and post-marathon time points was calculated using the method of Dill and Costill. Cardiac troponin T (cTnT) measurements were performed using an Elecsys-2010 bench top analyser with the fourth generation assay (Roche Diagnostics GmbH, Mannheim, Germany). The LLD is 10 pg/mL, which is equal to the 99th percentile of the reference population. NT-proBNP measurements were performed using an Elecsys-2010 bench top analyser (Elecsys proBNP, Roche Diagnostics, Mannheim, Germany). Age-adjusted cut-off values were set according to Hess et al.. Serum cystatin C levels were determined using a particle-enhanced nephelometric immunoassay according to the manufacturer's instructions (Dade Behring, Marburg, Germany). Glomerular filtration rate (GFR) was estimated using the following equation: estimated GFR (mL/min) = 74.835/cystatin C (mg/L).
Echocardiography was performed by experienced physicians of the echocardiography laboratory of the Cardiology Department, Charité-Universitätsmedizin Berlin, Germany. The echocardiographic parameters were obtained in the left decubitus position according to the guidelines of the American Society of Echocardiography (ASE) using Vivid 7 Dimension (pre-race and follow-up echocardiograms) and portable Vivid-i ultrasound machines (post-race echocardiograms) (GE Vingmed, Horton, Norway, M3S 1.5–4.0 MHz transducer). Three beats were stored digitally and analyzed offline (EchoPac PC, GE Vingmed). Left heart dimensions were acquired by M-mode echocardiography or directly from 2D images according to Lang et al.. LV mass was calculated using the Devereux formula and was indexed to the calculated body surface area using the Mosteller formula. Left ventricular ejection fraction (LVEF) was estimated by Simpson's biplane approach. Right heart dimensions were obtained according to Rudski et al.. The frame rate for tissue Doppler (TDI) measurements was >100/s. For 2D strain analysis, frame rates of 60 to 80/s were used. Transmitral pw-Doppler inflow at the tips of the mitral leaflets was measured to obtain E, E deceleration time (DT), A and E/A ratio. 2D strain variables and TDI measurements were assessed in the apical 4-chamber view. Peak early diastolic (E'), late diastolic (A') and systolic (S') velocities were measured at the basal septum. The position of the sample volume for velocity and TDI strain measurements was manually positioned in the myocardium throughout the cardiac cycle. The LV and RV myocardial performance index (MPI) were determined as markers of global myocardial function of each chamber. Tricuspid annular plane systolic excursion (TAPSE) was acquired by M-mode echocardiography according to Kaul et al. and the longitudinal velocity of excursion (RV S') was assessed by pulsed-wave TDI placed in the tricuspid annulus.
Results are generally expressed as mean value ± standard deviation (SD) for normally distributed data or as median with interquartile range (IQR = 25th - 75th percentile) for non-normally distributed data. Assumption of normal distribution of data was verified by the Shapiro-Wilk test. The Mann–Whitney U-test was used for comparison of two independent groups and the Wilcoxon-test for comparison of paired observations. Correlations were calculated with the Spearman's rank correlation coefficient. Frequencies of various groups were compared with chi-square test. Comparisons of changes in parameters at the pre- and post-marathon time points of the individual training groups were analyzed with pre-marathon variables as covariates. Statistical analyses were performed using SPSS 20.0 (SPSS Inc.) and SAS 9.2 (Statistical Analysis System Institute Inc.) software; p < 0.05 was considered statistically significant.
Methods
All data were collected during our marathon studies in 2006 and 2007 as described previously.
Study Design
The organizers of the 2006 and 2007 BERLIN-MARATHON invited all registered male (2006) and female (2007) contestants in all age-groups from the Berlin-Brandenburg area by e-mail to participate in our study. The first 88 positive responses from male and 111 positive responses from female runners who had previously completed at least one marathon were screened and enrolled in the study. The maximum number of study participants in each year was limited by the logistics situation immediately after the races. Written informed consent was obtained from each participant. The Ethics Committee of the Charité-Universitätsmedizin Berlin hospital approved the study protocol. The study complied with the Declaration of Helsinki.
Exclusion criteria were recent pathological results from a previous bicycle stress test (bicycle stress test was mandatory for inclusion of participants older than 50 years), history or symptoms of coronary artery disease (e.g. angina pectoris or shortness of breath) or chronic cardiovascular disorders (atrial fibrillation, permanent pacemaker, bypass surgery, prosthetic valves or congenital heart disease).
The participants were examined at least 10 days prior to the marathon at rest by a questionnaire, blood test, blood pressure and heart rate measurements, ECG and echocardiography (baseline, pre). The questionnaire comprised detailed questions on running experience, previous completed marathons, average training kilometers per week, other sporting activities, present and past medical history (including chronic diseases, physical injuries, previous hospitalizations and surgeries), allergies, alcohol consumption, medications, cardiovascular risk factors such as history of smoking or family history of cardiovascular disease/risk factors. All subjects were advised to suspend training for at least 2 days before the baseline examination. Immediately after the marathon, runners were examined in a medical tent 100 m behind the finish line by a blood test and echocardiography (post); notably, the examinations of each individual runner were completed within approximately 20 minutes after the runner crossed the finish line with subsequent offline analysis of the digitally stored echocardiographic data (EchoPac PC, GE Vingmed, Horton, Norway). A follow-up examination was performed two weeks after the marathon at rest including blood test and echocardiography.
Thirty-two runners were excluded from the study for the following reasons: positive bicycle stress test results (4); a troponin T (TnT) level above the lower limit of detection (LLD) not explained by profound exercise training prior to sampling (2); uncontrolled arterial hypertension (1); hypermobile interatrial septum (1); premature ventricular contractions (2); history of a recent stroke (1); gynaecological operation before the marathon (1); anaemia due to resistance to common therapies treated with erythropoietin (1); leg cramps (1) or acute febrile disease, any of which led to non-attendance of the marathon race (5); and personal constraints in 6 runners. One runner did not reach the finish line, sufficient blood samples for all designated analyses could not be drawn from six athletes after the marathon (after 3 unsuccessful attempts by a medical assistant). Runners with positive baseline troponin or stress tests were encouraged to undergo further cardiac diagnostics. Finally, a total of 167 healthy male (n = 78) and female (n = 89) marathon runners were included.
There were no fluid or pace restrictions for the runners during the race.
Biochemical Studies
Blood samples were collected in a supine position from cubital veins at the time points mentioned above. EDTA blood was collected for haematological parameters and measured immediately after collection. For the other markers, serum was prepared by centrifugation, immediately frozen and stored at −20°C until processing. None of the specimens demonstrated signs of haemolysis. Laboratory results from the post-marathon time points were corrected intra-individually for dehydration, as previously described. The change in plasma volume between the pre- and post-marathon time points was calculated using the method of Dill and Costill. Cardiac troponin T (cTnT) measurements were performed using an Elecsys-2010 bench top analyser with the fourth generation assay (Roche Diagnostics GmbH, Mannheim, Germany). The LLD is 10 pg/mL, which is equal to the 99th percentile of the reference population. NT-proBNP measurements were performed using an Elecsys-2010 bench top analyser (Elecsys proBNP, Roche Diagnostics, Mannheim, Germany). Age-adjusted cut-off values were set according to Hess et al.. Serum cystatin C levels were determined using a particle-enhanced nephelometric immunoassay according to the manufacturer's instructions (Dade Behring, Marburg, Germany). Glomerular filtration rate (GFR) was estimated using the following equation: estimated GFR (mL/min) = 74.835/cystatin C (mg/L).
Echocardiography and Doppler Measurements
Echocardiography was performed by experienced physicians of the echocardiography laboratory of the Cardiology Department, Charité-Universitätsmedizin Berlin, Germany. The echocardiographic parameters were obtained in the left decubitus position according to the guidelines of the American Society of Echocardiography (ASE) using Vivid 7 Dimension (pre-race and follow-up echocardiograms) and portable Vivid-i ultrasound machines (post-race echocardiograms) (GE Vingmed, Horton, Norway, M3S 1.5–4.0 MHz transducer). Three beats were stored digitally and analyzed offline (EchoPac PC, GE Vingmed). Left heart dimensions were acquired by M-mode echocardiography or directly from 2D images according to Lang et al.. LV mass was calculated using the Devereux formula and was indexed to the calculated body surface area using the Mosteller formula. Left ventricular ejection fraction (LVEF) was estimated by Simpson's biplane approach. Right heart dimensions were obtained according to Rudski et al.. The frame rate for tissue Doppler (TDI) measurements was >100/s. For 2D strain analysis, frame rates of 60 to 80/s were used. Transmitral pw-Doppler inflow at the tips of the mitral leaflets was measured to obtain E, E deceleration time (DT), A and E/A ratio. 2D strain variables and TDI measurements were assessed in the apical 4-chamber view. Peak early diastolic (E'), late diastolic (A') and systolic (S') velocities were measured at the basal septum. The position of the sample volume for velocity and TDI strain measurements was manually positioned in the myocardium throughout the cardiac cycle. The LV and RV myocardial performance index (MPI) were determined as markers of global myocardial function of each chamber. Tricuspid annular plane systolic excursion (TAPSE) was acquired by M-mode echocardiography according to Kaul et al. and the longitudinal velocity of excursion (RV S') was assessed by pulsed-wave TDI placed in the tricuspid annulus.
Statistical Analysis
Results are generally expressed as mean value ± standard deviation (SD) for normally distributed data or as median with interquartile range (IQR = 25th - 75th percentile) for non-normally distributed data. Assumption of normal distribution of data was verified by the Shapiro-Wilk test. The Mann–Whitney U-test was used for comparison of two independent groups and the Wilcoxon-test for comparison of paired observations. Correlations were calculated with the Spearman's rank correlation coefficient. Frequencies of various groups were compared with chi-square test. Comparisons of changes in parameters at the pre- and post-marathon time points of the individual training groups were analyzed with pre-marathon variables as covariates. Statistical analyses were performed using SPSS 20.0 (SPSS Inc.) and SAS 9.2 (Statistical Analysis System Institute Inc.) software; p < 0.05 was considered statistically significant.