Effects of Long-Term Endurance Exercise on Cardiac Morphology, Function, and Injury Indicators among Amateur Marathon Runners

he purpose of this study was to investigate the effects of long-term endurance exercise on cardiac morphology and function, as well as injury indicators, among amateur marathon runners. We recruited 33 amateur runners who participated in a marathon. Participants were divided into experimental and control groups according to their National Athletic Grade. The experimental group included participants with a National Athletic Grade of 2 or better, and the control group included participants who did not have a National Athletic Grade. Cardiac morphology, function, and injury indicators were assessed before and after the participants' involvement in the Changsha International Marathon. All cardiac morphology and function indicators returned to pre-race levels at 24 h post-race, and left ventricular end-diastolic volume and left ventricular end-systolic volume indicators showed similar trends. Both stroke volume (SV) and percent fractional shortening (%FS) indicators showed similar trends in changes in the measurements before and after the race. SV showed no change between the pre-race and post-race periods. On the other hand, %FS showed a signi cant increase in the immediate post-race period, followed by restoration of its level at 24 h post-race. Among myocardial injury indicators, serum

(SV) and percent fractional shortening (%FS) indicators showed similar trends in changes in the measurements before and after the race. SV showed no change between the pre-race and post-race periods. On the other hand, %FS showed a signi cant increase in the immediate post-race period, followed by restoration of its level at 24 h post-race. Among myocardial injury indicators, serum levels of cardiac troponin I, creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and N-terminal pro-b-type natriuretic peptide (NT-proBNP) measured before the race, immediately after the race, and 24 h after the race displayed similar trends in changes among CK, CK-MB, LDH, and AST, while NT-proBNP levels did not change. We concluded that high-level amateur marathon runners had greater heart volumes, as well as wall and septal thicknesses, than low-level marathon runners, with differences in heart volume being the most pronounced. Long-term high-intensity endurance exercise caused some damage to the hearts of amateur runners. High-level runners showed better myocardial repair ability, and their levels of myocardial injury markers showed greater decreases at 24 h post-race, while low-level runners had poorer myocardial repair ability. Keywords:heart volume; high-intensity endurance exercise; myocardial injury; stroke volume 1. Introduction In recent years, the number of people participating in endurance training, competi- tive long-distance endurance events, and high-intensity interval training has signi cantly increased worldwide [1]. However, with the increasing popularity of endurance and ultra- endurance sports programs, participants older than 35 years of age have become more susceptible to cumulative heart injury [2,3]. Although current physical activity guidelines suggest signi cant health bene ts from 150 min of moderate exercise or75 minof vigorous exercise per week, endurance athletes typically exercise 15 to 20 times more than the amount recommended by these guidelines [4,5]. This is problematic because excessive endurance exercise can lead to increased risks of atrial brillation (AF) and atrial utter [6]. More- over, vigorous-intensity exercises can be associated with cardiac maladaptation, including accelerated coronary artery calci cation, exercise-induced release of cardiac biomarkers, Int. J. Environ. Res. Public Health2023,20, 2600.

guidelines [4,5]. This is problematic because excessive endurance exercise can lead to increased risks of atrial brillation (AF) and atrial utter [6]. More- over, vigorous-intensity exercises can be associated with cardiac maladaptation, including accelerated coronary artery calci cation, exercise-induced release of cardiac biomarkers, Int. J. Environ. Res. Public Health2023,20, 2600.

Int. J. Environ. Res. Public Health2023,20, 2600 2 of 11 myocardial brosis, and right ventricular dilation anddysfunction [7,8] . Additionally, these exercises are associated with reduced left ventricular compliance [9]. Exercise-induced cardiac remodeling (EIRC) is the process by which long-term par- ticipation in exercise training results in signi cant changes in the structure and function of the heart [10]. This process is considered a physiological adaptation of the heart to exercise stimuli and is fundamentally different from cardiac remodeling caused by my- ocardial disease [11]. Exercise cardiac remodeling was rst believed to primarily involve left ventricular hypertrophy, including concentric and eccentric hypertrophy, accompanied by changes in cardiac systolic and diastolic function [12]. As research advanced, Weiner and Baggish reported exercise hypertrophy in the right ventricle [13]. Although long-term endurance exercise is believed to cause cardiac remodeling, quantitative research regarding its associated long-term effects is lacking. The indicators of cardiac injury and overload for different exercise types, dura- tions, and intensities remain controversial. For instance, researchers found that follow- ing high-intensity exercise, the levels of myocardial injury indicators, including crea- tine kinase (CK), myoglobin (Myo), and cardiac troponin (cTnT), were elevated in pro- fessionalathletes [14–17] and were restored to varying degrees after competition [17] con- trary to clinical cut-offs. Current investigations for high-intensity exercise mainly focus on laboratory examinations of professional athletes or of the general population on psycholog- ical impacts on participants. However, attention to natural post-race cardiac function in amateur marathon runners is limited. Thus, this study aimed to provide a theoretical basis to guide the general public on sports participation. Speci cally, this study examined changes in cardiac morphology and function, as well as myocardial injury indicators, among amateur marathon runners in China before and after participation in a race. In addition, we explored the preliminary ef- fects of long-term high-intensity endurance exercise on cardiac function in nonprofessional athletes without the psychological in uence of the laboratory environment. The ndings of this study have the potential to help athletes improve their cardiac functions and prevent unnecessary injuries during practice. 2. Materials and Methods 2.1. Study Design and Procedures

a race. In addition, we explored the preliminary ef- fects of long-term high-intensity endurance exercise on cardiac function in nonprofessional athletes without the psychological in uence of the laboratory environment. The ndings of this study have the potential to help athletes improve their cardiac functions and prevent unnecessary injuries during practice. 2. Materials and Methods 2.1. Study Design and Procedures This study employed a causal comparative study design, where participants were allocated to either experimental or control groups based on their National Athletic Grade. In detail, the marathon time for Grade 1 athletes is 2 h and 32 min, the time for Grade 2 athletes is 2 h and 53 min, and the time for Grade 3 athletes is 3 h and 2 min [18]. Participants were divided into experimental and control groups based on their National Athletic Grade. In detail, participants who were Grade 2 or better (i.e., Grade 1) were allocated to the experimental group, and those who did not meet the National Athletic Grade (i.e., lower than National Athletic Grade 3) were allocated to the control group. The study procedures were approved by the university's ethics committee at Hengyang Normal University (no.:180809P09), and written informed consent was obtained from all participants before data collection. All anthropometric data were collected by the researchers in a laboratory setting. Echocardiography and blood sample data were also collected in a highly controlled laboratory. The relevant procedures were performed in strict accordance with the reagent and instrument operating instructions. 2.2. Research Participants To detect a mean difference in primary outcomes between the experiment and control groups with 80% power and 5% signi cance, assuming a standard deviation of 10, this project required 15 subjects per group. This study recruited amateur marathon runners who met the following inclusion criteria: (1) had participated in and completed at least one international marathon; (2) were aged from 18 to 50 years of age; (3) were male amateur runners; (4) had no self-reported or diagnosed physical or mental disability; and (5) were

who met the following inclusion criteria: (1) had participated in and completed at least one international marathon; (2) were aged from 18 to 50 years of age; (3) were male amateur runners; (4) had no self-reported or diagnosed physical or mental disability; and (5) were

Int. J. Environ. Res. Public Health2023,20, 2600 3 of 11 willing to provide informed consent to participate in the study. The exclusion criteria for participation in this study were: (1) physical disabilities that limited his or her engagement in physical activities; (2) mental conditions that limited his or her engagement in physical activities; and (3) declined completion of the informed consent form. Due to the in uence of subjective and objective factors, such as epidemics and offsite conditions, a total of 33 participantscompleted the study, including 15 participants from the experimental group and 18 participants from the control group. Signed informed consent was provided prior to the start of the experiment. The sample descriptive data are shown in Table. Table 1.Baseline parameters of amateur marathon runners in Hengyang (mean standard deviation). Parameter Control Group ( n= 18) Experimental Group ( n= 15)p-Values Age (years) 38 7 35 9 >0.05 Body mass index (kg/m 2 ) 24 3 23 2 >0.05 Left ventricular mass index (g/m 2 ) 118 18.12 115 28.26 >0.05 Blood pressure (mm Hg) Systolic 126 18 123 23 >0.05 Diastolic 81 8 84 6 >0.05 Basal heart rate (beats/min) 68 5.21 58 8.52 <0.05 * Average weekly training distance (km) 35 14.31 53 17.61 <0.05 * Duration of long-distance training (years) 9 3.52 14 3.17 <0.05 * Number of marathons participated in 9 6.44 12 8.25 >0.05 Most recent marathon completion time (min)293 48 233 48 <0.01 ** *p< 0.05, **p< 0.01 compared to the control group. There was a particular rationale for the age range of participants investigated in this study. In detail, we obtained the performance data of amateur marathon runners in China between 2014 and 2017, with data taken from the website RunChina (www. runchinamarathon.com, accessed on 22 January 2023) [ 19]. The average performance of the different age groups in the same year showed no differences in the decline of performance in the 35–39, 40–44, and 45–49 year age groups, regardless of sex, compared to the performance of the 18–34 year age group for average performance in all races in all years from

runchinamarathon.com, accessed on 22 January 2023) [ 19]. The average performance of the different age groups in the same year showed no differences in the decline of performance in the 35–39, 40–44, and 45–49 year age groups, regardless of sex, compared to the performance of the 18–34 year age group for average performance in all races in all years from 2014 to 2017 (p> 0.05). The decreased performance in the other age groups showed greater differences with increasing age. Among the functions involved in the maintenance of health, cardiovascular function plateaued during the decline: runners aged 35–49 years showed a slow decline, while those over 49 years of age showed a trend of signi cant decline with increasing age every 5 years. Therefore, in this study, we recruited only adults aged from 18 to 50 years to investigate the effects of marathon exercise on the cardiovascular system. 2.3. Measures 2.3.1. Anthropometric and Demographic Information The participants' height and weight were measured to calculate their body mass index (BMI; kg/m 2 ). Height was assessed using a Seca stadiometer (Seca, Hamburg, Germany). Weight was measured to the nearest 10th of a kilogram using a Tanita BC-558 IRONMAN ® Segmental Body Composition Monitor (Tanita, Tokyo, Japan). In addition, participants' age and general information about their training (i.e., average weekly training distance, duration of long-distance training) and past marathon experiences (i.e., number of participations, most recent completion time) were self-reported. 2.3.2. Echocardiography Echocardiography was performed with the participants at rest in the lateral decubitus position, with a probe placed between the third and fourth intercostal space of the left sternal margin [20]. The electrocardiogram readings were recorded simultaneously to determine diastolic and systolic phases. All echocardiographic data were stored and analyzed with respect to the current standardized measurements and analysis in China. The left ventricular morphological indicators included: (1) left ventricular end-diastolic

Int. J. Environ. Res. Public Health2023,20, 2600 4 of 11 volume (EDV); (2) left ventricular end-systolic volume (ESV); (3) interventricular septum thickness in diastole (IVSD); (4) interventricular septum thickness in systole (IVSS); (5) left ventricular posterior wall thickness in diastole (LVPWD); (6) left ventricular posterior wall thickness in systole (LVPWS); and (7) left ventricular posterior wall motion (LVPWM). The higher the values of the aforementioned outcomes, the better the cardiac morphological indicators would be. The left ventricular function indicators were fractional shortening (FS), ejection fraction (EF), stroke volume (SV), and cardiac output (CO) [21,22]. The higher the values of FS, EF, SV, and Co, the better the cardiac function would be. 2.3.3. Blood Markers Blood was drawn intravenously to measure levels of cardiac troponin I (cTnI), creatine kinase (CK), creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), aspar- tate aminotransferase (AST), and N-terminal pro-b-type natriuretic peptide (NT-proBNP). Phlebotomy was performed by a lab technician. The technician held the participant's middle or ring nger in an upward position and then lanced the palm-side surface of the nger. The technician pressed rmly on the nger when making the puncture. These blood outcomes were the cardiac injury indicators. The lower the values of the abovementioned outcomes, the better the cardiac injury indicators would be. 2.4. Statistical Analysis All data were processed using IBM SPSS Statistics for Windows (Version 21.0, Armonk, NY, USA). First, descriptive statistics were used to describe the participants' demographic outcomes (i.e., age and sex) and BMI, as well as means and standard deviations of the study outcome variables. One-way repeated measures analysis of variance (ANOVA) was used, with data expressed as mean standard deviation. Ap< 0.05 was de ned as a signi cant difference, andp< 0.01 as a highly signi cant difference. 3. Results 3.1. Descriptive Analysis The participants' demographic information, basic indicators of physical tness, and exercise training conditions are shown in Table. The data in Table longer distances each week and had participated in more marathons compared to the control group (p< 0.05). Participants in the experimental group also had shorter race com- pletion times compared to the control

difference. 3. Results 3.1. Descriptive Analysis The participants' demographic information, basic indicators of physical tness, and exercise training conditions are shown in Table. The data in Table longer distances each week and had participated in more marathons compared to the control group (p< 0.05). Participants in the experimental group also had shorter race com- pletion times compared to the control group for the most recent marathon they participated in (p< 0.05). The ndings were consistent with the levels of each group. 3.2. Cardiac Morphology and Functional Indicators in Amateur Marathon Runners Analysis of cardiac morphological indicators before participation in the marathon race (Table) showed signi cantly higher EDV, ESV, IVSD, and IVSS in the experimental group compared to those in the control group (p< 0.01). Furthermore, signi cant differences in EDV, ESV, and IVSD immediately after the race (p< 0.05) and signi cantly higher EDV, ESV, and IVSS values at 24 h after the race (p< 0.01) were observed. Compared to their respective pre-race values, EDV, ESV, and IVSS were highly signi cantly elevated in the immediate post-race period for those in the control group (p< 0.01). In the experimental group, the participants' EDV, ESV, and LVPWM were signi cantly elevated in the immediate post-race period (p< 0.01). In both the control and experimental groups, all indicators returned to pre-race levels at 24 h post-race, with EDV and ESV indicating similar trends in changes (i.e., highly signi cant decreases in the immediate post-race period and a return to pre-race levels at 24 h post-race).

Int. J. Environ. Res. Public Health2023,20, 2600 5 of 11 Table 2. Characteristics of changes in morphological indicators before, immediately after, and 24 h after the marathon. Indicator Control Group (n= 18) Experimental Group ( n= 15) Pre-Race Immediate Post-Race Period 24 h Post-Race Pre-Race Immediate Post-Race Period 24 h Post-Race EDV (mL) 101.63 9.27 94.32 11.49FF 99.98 4.98 139.24 9.56 ** 115.83 12.31 *FF 138.91 15.46 ** ESV (mL) 34.51 3.21 26.71 4.01FF 30.34 2.78 45.15 4.52 ** 24.89 3.21 *FF 40.26 4.82 ** IVSD (cm) 0.61 0.21 0.63 0.41 0.65 0.29 0.87 0.22 * 0.76 0.19 * 0.83 0.61 IVSS (cm) 1.16 0.31 1.39 0.51FF 1.23 0.37 1.29 0.53 * 1.36 0.29 1.31 0.94 ** LVPWD (cm) 0.86 0.23 0.86 0.33 0.86 0.24 0.80 0.12 0.87 0.16 0.86 0.19 LVPWS (cm) 0.86 0.14 0.88 0.22 0.87 0.18 0.87 0.26 0.89 0.12 0.87 0.19 LVPWM (cm) 0.86 0.13 0.85 0.12 0.85 0.17 0.81 0.11 0.87 0.14F 0.87 0.11 *p< 0.05, **p< 0.01 compared to the control group for the particular indicator;Fp< 0.05,FFp< 0.01 compared to the pre-race value for the particular group. The analysis of cardiac function before and after participating in the marathon (Table) showed that the SV in participants in the experimental group was signi cantly higher than that in participants in the control group in the quiet state before the race (p< 0.01). Immediately after the race, participants' SV, EF, and percent fractional shortening (%FS) values in the experimental group were signi cantly higher than those in the control group (p< 0.01). Participants' SV, CO, and %FS remained signi cantly different at 24 h after the race (p< 0.05/0.01). Compared to pre-race values, participants' CO and %FS in the control group were signi cantly higher (p< 0.01), with no differences between pre-race and 24 h post-race levels. In the experimental group, participants' CO, EF, and %FS were signi cantly higher than their pre-race values (p< 0.05/0.01), while only CO was signi cantly higher at 24 h post-race (p< 0.05). Table 3. Changes in cardiac functional indicators before, immediately after, and 24 h after the marathon race.

0.01), with no differences between pre-race and 24 h post-race levels. In the experimental group, participants' CO, EF, and %FS were signi cantly higher than their pre-race values (p< 0.05/0.01), while only CO was signi cantly higher at 24 h post-race (p< 0.05). Table 3. Changes in cardiac functional indicators before, immediately after, and 24 h after the marathon race. Indicator Control Group (n= 18) Experimental Group ( n= 15) Pre-Race Immediately Post-Race 24 h Post-Race Pre-Race Immediately Post-Race 24 h Post-Race SV (mL) 71.6 1 9.79 72.71 11.21 72.36 16.56 90.31 19.21 ** 95.34 9.98 ** 90.63 18.48 ** CO (L) 5.72 10.21 13.31 2.99FF 6.76 8.91 6.21 1.56 18.35 2.75FF 9.76 2.95 *F EF (%) 70.12 6.21 75.71 7.84 71.84 3.89 70.12 3.38 81.54 6.32 **FF 70.52 5.24 %FS (%) 40.32 4.91 52.12 10.21FF 42.55 7.71 39.52 3.57 48.13 5.93 **F 38.84 6.24 ** Note: *p< 0.05, **p< 0.01 compared to the control group;Fp< 0.05,FFp< 0.01 compared to pre-race levels for the particular group. Among cardiac function indicators, both SV and %FS in the control and experimental groups showed the same trends in changes at the three time points, with SV showing no change before and after the race and %FS showing a signi cant increase in the immediate post-race period, followed by recovery at 24 h. 3.3. Changes in Myocardial Injury Indicators in Amateur Marathon Runners Our data (Table) showed no differences between the experimental and control groups before the race. However, the experimental group participants' cTnI, CK, CK-MB, LDH, and AST levels were signi cantly lower during the immediate post-race and 24 h post-race periods (p< 0.01). Compared to pre-race values, the cTnI, CK, CK-MB, LDH, and AST values in the immediate post-race and 24 h post-race periods in the control group showed signi cantly greater increases (p< 0.01). Participants from the experimental group showed similar changes in the immediate post-race period as those in the control group, with only CK, CK-MB, LDH, and AST levels signi cantly increased in the 24 h post-race period compared to pre-race levels (p< 0.05/0.01).

This study examines cardiac changes in amateur marathon runners due to long-term endurance exercise.