Exercise characteristics and incidence of abnormal electrocardiogram response in long‐distance runners with exercise‐induced hypertension

ABSTRACT While long‐distance running has important health benefits, chronic elevation of blood pressure during exercise might induce cardiac events and sudden death. This study aimed to investigate characteristics of exercise and incidence of abnormal exercise electrocardiography findings in long‐distance runners with exercise‐induced hypertension. Long‐distance runners (n = 606) underwent a questionnaire survey, history taking, and exercise stress testing, and they were classified into the non‐exercise‐induced (n = 268) and exercise‐induced (n = 338) hypertension groups. Exercise‐induced hypertension was defined as systolic blood pressure ≥210 mm Hg during maximal exercise. Abnormal electrocardiogram response (AER) were defined as abnormal electrocardiography findings, such as arrhythmias or ST‐segment changes, during exercise stress testing. There were no differences in general and exercise‐related characteristics between the non‐exercise‐induced and exercise‐induced hypertension groups. The AER group (AERg, n = 37) had a significantly longer training history and total exercise time than the non‐AER group (non‐AERg, n = 569) (p < .05). Atrial arrhythmias and ST‐segment depression were more prevalent in the exercise‐induced hypertension group than in the non‐exercise‐induced hypertension group (atrial arrhythmias: 5% [17/338] vs. 1.9% [5/268]; ST‐segment depression: 2.7% [9/338] vs. .4% [1/268]; p < .05). The incidence of AER was significantly higher in the exercise‐induced hypertension group (n = 30, 8.8%) than in the non‐exercise‐induced hypertension group (n = 7, 2.6%) (p < .05). This study showed that long‐distance runners with AER had a longer training history and total exercise time than those without AER, and the exercise‐induced hypertension group had a higher rate of AER.

(n = 268) and exercise-induced (n = 338) hypertension groups. Exercise-induced hypertension was defined as systolic blood pressure ≥210 mm Hg during maximal exercise. Abnormal electrocardiogram response (AER) were defined as abnormal electrocardiography findings, such as arrhythmias or ST-segment changes, during exercise stress testing. There were no differences in general and exercise-related characteristics between the non-exercise-induced and exercise-induced hypertension groups. The AER group (AERg, n = 37) had a significantly longer training history and total exercise time than the non-AER group (non-AERg, n = 569) (p < .05). Atrial arrhythmias and STsegment depression were more prevalent in the exercise-induced hypertension group than in the non-exercise-induced hypertension group (atrial arrhythmias: 5% [17/338] vs. 1.9% [5/268]; ST-segment depression: 2.7% [9/338] vs. .4% [1/268]; p < .05). The incidence of AER was significantly higher in the exercise-induced hypertension group (n = 30, 8.8%) than in the non-exercise-induced hypertension group (n = 7, 2.6%) (p < .05). This study showed that long-distance runners with AER had a longer training history and total exercise time than those without AER, and the exercise-induced hypertension group had a higher rate of AER.

INTRODUCTION
Regular exercise and physical activity decrease the risk of cardiovascular events (CE), chronic heart disease, and mortality. 1,2 Therefore, long-distance runners, such as half-marathon or full-marathon runners, are at a low risk of heart attack and sudden death, 3 and walking and moderate-intensity running lower the incidence of arrhythmia. 4 However, endurance athletes may be vulnerable to fatal arrhythmias, such as atrial fibrillation (AF), atrial flutter, and ventricular tachycardia. [5][6][7] Indeed, the incidence of AF in endurance athletes is reported to be fivefold higher than that in the general population. 8,9 For example, a study found that among 50 middle-aged male long-distance runners, 50% had coronary artery stenosis, and 6% had a vessel with > 50% diameter stenosis. 10 Recently, a variety of CE have been reported in long-distance runners with exercise-induced hypertension (EIH). Runners with EIH have weakened ventricular diastolic functions, 11 with marked elevation of myocardial infarction and heart failure markers, such as cardiac troponin I and N-terminal pro b-type natriuretic peptide, following longdistance running. 12,13 In particular, runners with EIH show a high incidence of coronary artery plaque, 14 suggesting that EIH may be a risk factor for sudden death in long-distance runners.
EIH is defined as systolic blood pressure (SBP) ≥210 mm Hg for men and ≥190 mm Hg for women during exercise. 15,16 Excessive elevation of blood pressure during exercise is a risk factor for cerebral and cardiovascular diseases, 17,18 with a high likelihood of progressing to hypertension at rest. 19 Runners exhibiting excessive elevation of blood pressure during exercise would have a high rate-pressure product (RPP) due to the high volume pressure on the atria and ventricles. Because excessive elevation of blood pressure during every exercise session chronically strains the cardiac muscles, the incidence of abnormal electrocardiogram response (AER) such as arrhythmia or myocardial ischemia is anticipated to rise. Therefore, more exercise is not always good. The present study investigated the incidence of AER by examining abnormal exercise electrocardiography (ECG) findings in long-distance runners with EIH to make an indirect prediction of CE.

Participants and study protocol
The study protocol is illustrated in Figure 1. SSWUIRB-2020-048).

GXT
Heart rate and blood pressure were measured at rest, during exercise, and at 5 min after recovery. ECG was recorded at rest, once at 1 min before the end of each stage, every 1 min during recovery, and continuously during cardiac events, such as myocardial ischemia.

Abnormal ECG response
Participants were classified into the AER group (AERg) and non-AER group (non-AERg) according to the presence of abnormal exercise ECG, such as arrhythmias or ST-segment changes. Atrial arrhythmias were frequent atrial premature contractions (APCs), AF, and atrial flutter (AFL). AF/AFL included both AF/AFL observed during the GXT and AF/AFL diagnosed based on a historical review, and frequent APC was defined as two or more APCs per 10 s (sec). 21 Non-sustained ventricular tachycardia (NSVT) was defined as three or more premature ventricular contractions within 30 s. 20 Those parameters mentioned above and ST-segment depression (STD) (upslope type ≥ 2 mm, horizontal type ≥ 1.4 mm, and downslope type ≥ 1 mm) were determined in accordance with the American College of Cardiology/American Heart Association guidelines. 20

Statistics
Between-group analysis was performed using kurtosis and skewness of the data and the Kolmogorov-Smirnov test. Based on the results, an independent t-test was used as a parametric method, and the Mann-Whitney U test was used as a nonparametric method. A 2 × 2 crosstabulation analysis was performed to analyze the percentages between the groups. The significance level was set at 0.05, and statistical analyses were performed using SPSS version 21.

Baseline characteristics
There were no differences in general characteristics between the were no significant differences in maximum oxygen uptake, total exercise time, or maximal metabolic equivalents between the two groups.

Exercise characteristics
Exercise characteristics of included marathoners are shown in Table 2.

DISCUSSION
This study investigated the incidence of abnormal exercise ECG response and the factors related to exercise history in long-distance runners with EIH to determine whether EIH is a risk factor for AER. Of the 606 long-distance runners included in this study, 44% were in the NEIHg with normal blood pressure response during the maximal exercise, while 56% were in the EIHg with EIH during the maximal exercise.
Notably, more than half of the long-distance runners had EIH, and their SBP remained high even during the recovery phase after the maximal exercise. While the two groups did not differ in exercise characteristics, the training history was approximately 18 months longer in the group with AER, such as AF/AFL, frequent APC, NSVT, and STD, than in the group with non-CE. Hence, EIH might be due to cardiac overload during and after exercise.
AF has been observed in athletes with a training history of ≥ 10 years at ≥ 3 h training per week 22 and those with more than 1500 h of training. 8 The etiological mechanism of AF in long-distance runners involves increased vagal tone caused by excessive chronic exercise that stretches the atria; atrial enlargement is accompanied by inflammation and atrial scar formation during healing progresses to fibrosis, thereby causing AF. 6 Based on this hypothesis, high atrial volume pressure during exercise in runners with EIH would accelerate the onset of AF.
Although EIH is an independent risk factor for cerebral and cardiovascular diseases, 17,18 Joint National Committee-8 only presents an algorithm for blood pressure at rest and does not take into account EIH. 23 Recently, Kim and coworkers 14 demonstrated that long-distance runners with EIH have a higher rate of coronary artery plaque formation on multi-detector computed tomography (MDCT) than runners with normal SBP during exercise. The present study also observed that ST-segment depression positivity, which indicates myocardial ischemia, was significantly higher in the EIHg during the GXT, suggesting that EIH may be another risk factor in longdistance runners. The mechanism which runners with exercise-induced hypertension have more prevalence of ST-segment depression is that increased oxidative stress by chronical(prolonged) excessive blood pressure elevation during running induces endothelial dysfunction in the coronary arteries, which could increase plaque formation in coronary arteries. 24 EIH is induced by elevated afterload due to impaired peripheral vascular contractility, which in turn leads to excessive elevation of blood pressure. 25,26 Long-distance runners are exposed to such chronic excessive elevation of blood pressure for longer periods than the general population, even if their blood pressure is normal at rest. Indeed, the amount of exercise in marathoners is 5-10 times higher than that of exercise recommended in the guidelines for the cardiovascular disease prevention, and even marathoners without EIH have a higher coronary artery calcium score than the general population. 27 If runners with EIH have potential myocardial ischemia, as shown in our study, the excessive elevation of RPP would be further promoted during exercise. Considering that a common cause of sudden death is congenital hypertrophic cardiomyopathy in athletes aged 35 years or younger and acquired coronary artery disease in those aged 35 years or older, 28 EIH might further facilitate the onset of coronary artery diseases in middle-aged long-distance runners. Consistently, the overall incidence of abnormal ECG response was also significantly higher in the EIHg than in the NEIHg. Even though the AER is an indirect prediction of various CEs, this finding suggests that EIH may be a new risk factor for sudden death in long-distance runners. Although excessive exercise poses a risk of sudden death, physical activity should still be encouraged because the health benefits outweigh the risk, 29 and the desire for such exercise should not be suppressed because the risk of mortality does not increase even with excessive exercise 10 times greater than the amount of recommended exercise. 30

CONCLUSIONS
This study found that long-distance runners with AER had a longer training history and total training time than their counterparts without AER, and the incidence of AER, such as atrial arrhythmias and STD, was higher in the EIHg than in the NEIHg.

ACKNOWLEDGMENT
This work was supported by a grant from the Sungshin Women's University, Republic of Korea.

CONFLICT OF INTEREST
The authors have indicated that they have no conflicts of interest regarding the content of this review paper.