Abstract

Background

There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. The purpose of this study was to explore the frequency of exercise electrocardiography (ECG) abnormalities and the corresponding exercise intensities, as well as the associated influencing factors, during a symptom-limited stepwise incremental cardiopulmonary exercise test (CPET) in an apparently healthy Chinese population.

Methods

A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited, 918 were eligible and completed demographic indicators, routine blood indicators, physical activity status, symptom-limited CPET and exercise ECG were included in the analysis.

Results

Of the exercise ECG outcomes, 10 (1.1%) were positive and occurred at exercise intensities鈥夆墺鈥�62.50% heart rate reserve (HRR); 44 (4.8%) were equivocal and 864 (94.1%) were normal. Individuals with Cardiovascular Disease Risk Factor (CVDRF)鈥�=鈥�3鈥�4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF鈥�=鈥�0鈥�2. Exercise ECGs of individuals with CVDRF鈥�=鈥�5鈥�7 were 5.4 times more likely to be positive and abnormal than exercise ECGs of individuals with CVDRF鈥�=鈥�0鈥�2.

Conclusions

The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in apparently healthy Chinese population; the greater the number of CVDRFs, the greater the likelihood of cardiovascular risk during exercise.

Introduction

Physical inactivity is a global pandemic that can lead to the early development of obesity, diabetes, hypertension and cardiovascular disease (CVD), and has been described as one of the most serious public health problems of the 21st century [1]. Although regular physical activity (PA) is associated with health benefits, physical inactivity is a global epidemic and is considered the closest risk factor for cardiovascular disease, along with poor dietary habits, smoking and hypertension [2]. To address these issues, public health strategies in various countries often encourage an increase in the physical activity levels of social populations. In addition, the recent discovery that regular exercise prevents cellular aging has led a growing number of adults, many of whom have known or hidden chronic diseases, to conclude that 鈥渕ore exercise is better鈥� [3]. For example, the marathon has grown in popularity over the past 40 years, with participation increasing from 25,000 in 1976 to about 5 million in 2020. As a result, an interesting phenomenon has emerged, whereby the number of people who are physically inactive is increasing, while at the same time the number of people participating in unprecedented levels of strenuous exercise is also increasing.

The benefits of PA in reducing cardiovascular risk factors and events, as well as its protective effects against a variety of other diseases, are well established. In fact, regular PA participants have longer life expectancy and lower morbidity rates [4]. In addition, animal model studies have shown that PA induces upregulation of cardiac beneficial biological signaling pathways [5]. Overall, PA is one of the major core components of primary and secondary prevention programs for cardiovascular disease. Although the benefits of exercise increase progressively with intensity, some data support the hypothesis of a U-shaped relationship between exercise intensity and mortality, and even the 鈥減hysical activity paradox鈥�. Studies have found that the risk of sudden cardiac death (SCD) in adults is even twice as high during vigorous exercise as at rest, especially when normally sedentary adults suddenly begin to engage in high-intensity exercise [6, 7]. Biochemical, structural, and functional evidence for the involvement of high-intensity PA in cardiovascular system injury has also been demonstrated in animals and humans [8]. Furthermore, given the increasing popularity of endurance sports programs such as marathons and other forms of extreme sports activities, these activities prompt many adults (who typically have low levels of cardiorespiratory fitness along with latent cardiovascular disease) to engage in inappropriately high-intensity physical activity and put themselves at increased risk of being exposed to a cardiac event during exercise [9]. Therefore, it is extremely important to identify and prevent cardiovascular risks during exercise in advance [10].

Exercise ECG is widely used for screening for coronary artery disease because of its non-invasive nature and low cost. In addition, it offers the possibility of detecting silent or inducible myocardial ischemia as well as cardiac rhythm and conduction disturbances. Although the diagnostic accuracy of exercise ECG is well established in symptomatic patients, data on apparently healthy adults are scarce [11]銆侫s exercise ECG can be used for diagnostic assessment of suspected CVD, it has been suggested that ECG could also be used to screen asymptomatic individuals to identify those who could benefit from more intensive early management of modifiable risk factors, preventive interventions, or both. An exercise ECG records the electrical activity of the heart during physical activity, usually at a preset level of exercise intensity. The most common method of exercise ECG is the treadmill test, but there are other methods such as those using cycle ergometer and power meters. Exercise ECG can be used to look for markers of previous myocardial infarction, myocardial ischemia, and other cardiac abnormalities (e.g., left ventricular hypertrophy, bundle branch block, or arrhythmias) that may be associated with CVD or predictive of future CVD events, as well as for exploring and detecting cardiovascular risk during exercise [12]. However, most of the current research on exercise-related cardiovascular risk comes from developed countries, while data from developing countries are still lacking [9, 13,14,15]. Racial differences may exist between study populations in these developed countries and developing countries and may be influenced by socioeconomic status; therefore, there is still a need for exercise-related cardiovascular risk studies in developing countries. In this context, the present study evaluated the frequency of exercise-induced abnormal ECG and cardiovascular responses, especially the frequency of abnormal exercise ECG and the corresponding exercise intensities, and explored the influencing factors of exercise ECG outcomes in apparently healthy Chinese people aged 20鈥�79 years during symptom-limiting CPET. The purpose of this study was to assess the upper limit of exercise intensity at which cardiovascular risk occurs during exercise in an apparently healthy population, and then to provide a reference for the development of safe and effective exercise prescriptions or guidelines and prevention of cardiovascular risk during exercise in apparently healthy Chinese adults.

Methods

Participants

A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited. In addition to measuring the blood pressure and pulse rate of each participant, the Exercise and Health Questionnaire [16], the Physical Activity Readiness Questionnaire+ (PAR-Q+) [17] and the International Physical Activity Questionnaire (Short Form) [18] were used to investigate the basic conditions of the subjects. And according to the following inclusion and exclusion criteria, all participants signed an informed consent form before testing. Inclusion criteria: (1) aged 20鈥�79 years; (2) no significant motor dysfunction; (3) voluntary participation. Exclusion Criteria: (1) neurological and musculoskeletal disorders that may be exacerbated during exercise; (2) definitively diagnosed cardiovascular and/or metabolic disorders (e.g., diabetes mellitus, fatty liver, etc.); (3) acute systemic infections with fever, generalized pain, or enlarged lymph nodes; (4) significantly low exercise capacity due to mental or physical disorders; (5) use of medications that affect the heart rate (e.g., beta-blockers); (6) illnesses for which the physician deems strenuous exercise to be contraindicated.

Testing program

Rest state indicator testing

Venous blood was drawn in a quiet state after 12 h of fasting to test for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and apolipoproteins A1 and B. Shuangjia SK-CK ultrasonic physical examination machine and TANITA (MC-180) body composition tester were used to measure the body morphology indexes of all the participants. BMI was calculated according to the formula: weight (kg)/height (m²). Waist and hip circumferences were measured with a tape. Rest heart rate and blood pressure were measured and recorded with an electronic sphygmomanometer (OMRON, Model HEM-7124) taken in the sitting position and on the right arm, and the average of the three measurements was taken as the final result.

CVDRFs

The participants鈥� clinical history was recorded and was based on the fulfillment of each of the following conditions [19]: age (鈮モ��45 years for men and 鈮モ��55 years for women); family history (myocardial infarction, coronary revascularization, sudden death of the father or other first-degree male relative before the age of 55 years; and sudden death of the mother or other first-degree female relative before the age of 65 years); smoking (smoking or quit for less than 6 months or inhaled secondhand smoke); physical activity (participated in moderate-intensity physical activity for at least 30 min at least 3 times per week); blood pressure (systolic blood pressure鈥夆墺鈥�140 mmHg and/or diastolic blood pressure鈥夆墺鈥�90 mmHg, or taking antihypertensive medication); dyslipidemia (LDL-C鈥夆墺鈥�130 mg/dL or HDL-C鈥�<鈥�40 mg/dL or taking lipid-lowering drugs or serum total cholesterol鈥夆墺鈥�200 mg/dL; if HDL-C鈥夆墺鈥�60 mg/dL, this can be subtracted from positive risk factors); diabetes mellitus (fasting glucose鈥夆墺鈥�126 mg/dL) and obesity [20] (by Asian criteria: WC鈥夆墺鈥�90 cm (men), WC鈥夆墺鈥�85 cm (women); or waist-to-hip ratio鈥夆墺鈥�0.9 (men), waist-to-hip ratio鈥夆墺鈥�0.85 (women) or BMI鈥夆墺鈥�27 kg/m²) was comprehensively assessed for cardiovascular risk using the Coronary Systematic Risk Assessment System [21]. If satisfied, 1 was added; if not, 0 was added, and finally the total CVDRFs was obtained by combined summing.

Symptom-limited incremental CPET

Each participant received a detailed description of the benefits and risks associated with CPET and provided written informed consent to participate in the study. All subjects underwent a symptom-limited incremental CPET (GXT exercise protocol) using a cycle ergometer (Ergosana 320 F; Ergosana, Bitz, Germany), a ECG measurement (DMS 300-BTT01) and a benchtop gas analyzer (KORR CardioCoach). The protocol was based on a starting load of 25 W, incremented by 25 W every 3 min, with the rotational speed maintained at 50 r/min. A cardiac tester (DMS 300-BTT01) was used throughout the test to record seated torso lead ECGs at rest, during exercise, and during recovery. Blood pressure was measured and heart rate recorded at the end of each level of loading during the exercise phase, and the subjective fatigue perception of the subjects was assessed with the Borg CR20 Scale (Rating of Perceived Exertion on scale from 6 to 20 [RPE_{6鈥夆垝鈥�20}]). During the test, the researchers continuously observed the participants鈥� physical condition and various measurements, intermittently asking them how they felt and encouraging them. Researchers recorded exercise duration, peak heart rate, RPE, and blood pressure. At the end of the exercise phase, participants were asked to actively recover for 2 min and then sit still for 3 min, during which time heart rate and blood pressure were continuously measured every minute. The test continued until volitional exhaustion while the participant met the following termination criteria before. Criteria for termination of the test (presence of one of the following): (1) 85% of the maximum predicted heart rate for age (207鈥夆垝鈥�0.7 脳 age) or 70% of the HRR ([peak heart rate-rest heart rate]/[maximum predicted heart rate for age-rest heart rate] 脳 100%) was reached or exceeded; (2) RPE鈥夆墺鈥�17; (3) respiratory exchange ratio (RER)鈥夆墺鈥�1.10; (4) blood pressure during the test reached鈥夆墺鈥�230/110 mmHg; (5) abnormal exercise ECG; (6) heart rate not rising or falling with the increase of exercise load; (7) the subject develops signs or symptoms such as myocardial ischemia, signs of hypoperfusion, central nervous system symptoms, dyspnea, abnormal fatigue, muscle cramps, and other signs or symptoms; and (8) subject voluntarily requests to stop the test [7, 22]. The above tests were performed under the supervision of an exercise physiologist trained in cardiology and in accordance with exercise testing standards.

Exercise-induced clinically relevant ECG abnormalities

Exercise ECGs were categorized into 3 endings: normal, equivocal and positive. All ECGs were reviewed and interpreted by a physician experienced in cardiac rehabilitation. To validate the findings, a second physician experienced in cardiac rehabilitation reviewed all ECGs considered to have abnormal findings and 1 of every 10 exercise ECGs without abnormal findings. Differences in interpretation were resolved by the discussion of physicians. Exercise ECG judgment criteria were as follows [23]:

Criteria for the positive exercise ECG (with one of the following changes)

(1) During or after exercise in R-wave-dominated leads, ST-segment depression occurs in at least two or more adjacent leads with horizontal or downward-sloping depression of 鈮モ��0.1 mV (60鈥�80 ms after the J-point) for 鈮モ��2 min; those with pre-existing ST-segment depression prior to exercise should have 鈮モ��0.1 mV of depression on top of the original one for 鈮モ��2 min. (2) An upward-sloping ST-segment decrease of 0.20 mV or more, accompanied by ST-segment elevation of 0.10 mV or more in the aVR lead.

Criteria for the equivocal exercise ECG (with one of the following changes)

(1) Horizontal-type or downward-sloping depression of the ST segment鈥夆墺鈥�0.05mV but <鈥�0.1mV during or after exercise on an original basis. (2) U-wave inversion during or after exercise. (3) Presence of frequent ventricular pre-systoles (polymorphic premature ventricular beats鈥夆墺鈥�3 out of 10 beats), ventricular pre-systolic dysthymia or ventricular tachycardia, second- or third-degree atrioventricular block, sinus block, atrial fibrillation, atrial flutter.

Normal exercise ECG

Other than these abnormalities, the exercise ECG is normal.

Statistical analysis

Excel 2010 and SPSS 20.0 software were used to input and analyze the collected data. The exercise ECG endings of normal, equivocal, and positive were assigned the values of 2, 1, and 0, respectively, and were used as strain variables. The number of CVDRFs was assigned as 3, 2, and 1 according to 0鈥�2, 3鈥�4, and 5鈥�7, respectively. Then one-way ANOVA was performed with ECG endings categorized into 3 categories. If this factor is a categorical variable, then choose chi-square test for one-way analysis of variance. If this factor is a continuous numerical variable, first test for normality, obeying normal distribution, select one-way ANOVA for one-way test and choose the expression of Mean鈥壜扁�塖tandard Deviation (Mean鈥壜扁�塖D); if it is non-normal, then select the non-parametric test of K independent samples and choose the expression of Median (Lower Quartile鈥�鈭�鈥塙pper Quartile). Variables that were significant in the univariate analysis were included in the multivariate analysis, and the statistical method chosen for the multivariate analysis was multicategorical logistic regression [24, 25]. Frequency values were used to describe the prevalence of exercise-induced exercise ECG abnormalities or serious adverse events during symptom-limited CPET. The significance level 蓱 = 0.05 was set.

Results

Basic characteristics of participants

A total of 1642 subjects were recruited for this study, and 918 (males鈥�=鈥�414, females鈥�=鈥�504) met the inclusion criteria and completed all tests. Of the ECG findings, 10 (1.1%) were positive, 44 (4.8%) were equivocal, and 864 (94.1%) were normal. Refer to Fig. 1 for the criteria used in determining who was included or excluded. Their demographics are described in Table 1.

Fig. 1

The flowchart for inclusion and exclusion of participants in the study

After univariate analysis, only age, %HRR, %HRmax and CVDRF were found to be statistically significant (all P鈥塿alues鈥�<鈥�0.05), while no other variables were statistically significant. Since the age variable was included in CVDRF, age was included in the calculation of both HRR and HRmax, and %HRR was more reflective of the level of heart rate variability in an individual compared to %HRmax, %HRR and CVDRF were chosen to be included in the multifactorial logistic regression.

Table 1 Baseline characteristics of participants according to exercise ECG outcomes

Termination of CPET and related main reasons

Termination in CPET for both genders and the main reasons for termination are shown in Tables 2 and 3. Of the 918 participants who completed the CETP test, 87.8% met at least one of the stopping criteria. Of note, the three aspects of peak heart rate鈥夆墺鈥�85% age-predicted maximum heart rate, HRR鈥夆墺鈥�70%, and RER鈥夆墺鈥�1.1 were more prevalent in women than in men. In contrast, both RPE score鈥夆墺鈥�17 and maximum systolic blood pressure鈥夆墺鈥�230 mmHg were more prevalent in men than in women. The number of men with systolic blood pressure鈥夆墺鈥�230 mmHg was twice as high as that of women.

Table 2 Reasons for CPET termination (by number and percent)

Table 3 CPET responses at maximal effort

Exercise-induced adverse events and clinically relevant ECG abnormalities

No serious adverse events were recorded during the exercise trial. Analysis of exercise-induced ECG abnormalities showed that of the 918 CPETs, 10 developed a positive exercise ECG (2 males, 8 females), with an incidence of 1.1%, i.e., the presence of horizontal or downward-sloping ST-segment depression (鈮モ��1 mm) suggestive of the onset of myocardial ischemia. Of the 10 cases of a positive exercise ECG, 9 of them appeared in the phase of increased exercise loading, 1 in the recovery phase, the heart rate at which positive ECG changes appeared was 鈮モ��62.50% HRR. Those who developed a positive ECG during the recovery period accomplished a maximum power of 100 w, had a maximum heart rate of 172 bpm during exercise, and developed a positive ECG when the heart rate returned to 148 bpm. No clinically significant exercise-induced arrhythmias were observed. The specific conditions are shown in Table 4.

Exercise ECG positivity occurred in 7 participants (>鈥�50%) when exercise intensity was 鈮モ��70% HRR, suggesting that the selection of 70% HRR as the CPET endpoint can lead to an underestimation of exercise capacity and inducible ischemic events.

Of the 918 CPET cases, a total of 44 cases were found to have a equivocal exercise ECG, 16 of which appeared in the recovery phase and 28 in the exercise phase. Analysis of the 28 cases in the exercise phase revealed that equivocal in the exercise ECG accounted for 3.05% of the total and appeared at exercise intensities鈥夆墺鈥�49.38% HRR. The heart rate at which the equivocal appeared was 71.01% 卤 16.22% HRR, with a minimum value of 49.38% HRR and a maximum value of 100% HRR.

Table 4 Characteristics of the population with positive exercise-induced ECG

Multifactorial logistic analysis of exercise ECG-related conditions

A multifactorial logistic analysis revealed that individuals with CVDRF鈥�=鈥�3鈥�4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF鈥�=鈥�0鈥�2. Individuals with CVDRF鈥�=鈥�3鈥�4 tended to have a equivocal exercise ECG but not a normal one; individuals with CVDRF鈥�=鈥�0鈥�2 tended to be normal but not a equivocal one. The number of CVDRFs influences whether an individual鈥檚 exercise ECG is normal or equivocal.

Individuals with CVDRF鈥�=鈥�5鈥�7 are 5.4 times more likely to have a positive and abnormal exercise ECG than those with CVDRF鈥�=鈥�0鈥�2. Individuals with CVDRF鈥�=鈥�5鈥�7 tend to have a positive exercise ECG but not a normal one, and those with CVDRF鈥�=鈥�0鈥�2 tend to have a normal one but not a positive one. The number of CVDRFs affects whether an individual鈥檚 exercise ECG is normal or positive.

The higher the HRR%, the more likely the exercise ECG was to be suspiciously positive rather than normal (P鈥�=鈥�0.002鈥�<鈥�0.05 and the effect coefficient鈥�=鈥�0.029鈥�>鈥�0). The higher the HRR%, the more likely the exercise ECG was to be positive rather than normal (P鈥�=鈥�0.037鈥�<鈥�0.05 and the effect coefficient鈥�=鈥�0.036鈥�>鈥�0). For details, as shown in Table 5.

Table 5 Multifactorial analysis - normal Exercise ECG as a reference category

Discussion

There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. This study is to explore the safety of participation in a aerobic exercise trial in an apparently healthy Chinese population. The present study was based on data from apparently healthy Chinese adults in one urban and one rural area in northern and southern China by analyzing clinically relevant abnormal signs or symptoms that occurred during their participation in symptom-limited stepwise incremental CPET. It was found that no serious adverse events occurred throughout the test, and a very small number of participants (10/918; 1.1%) had exercise-induced positive ECGs during sub-extreme exercise; all ECG changes occurred during the exercise period, except for one subject who developed ECG changes during the recovery period. In addition, it was found that the number of CVDRF affects the outcome of exercise ECG, with the risk of cardiovascular events increasing dramatically as the number of CVDRF increases. Therefore, aerobic exercise can be safely prescribed for apparently healthy Chinese populations even in the absence of ECGs through symptom-limited CPET, which prescribes a heart rate range that is at the upper limit of the percentage of safe exercise heart rate achieved in CPET, but not beyond. Second, to reduce cardiovascular risk during exercise, efforts should be made to reduce the number of CVDRFs.

Cardiovascular diseases are the most common cause of death in adults and the elderly, and aerobic exercise has been recognized as an effective way to improve them [26]. However, the effectiveness of aerobic exercise depends on how the components of the FITT-VP principle (including frequency, intensity, type, time, volume and progression) are combined [10]. Of these components, the selection of appropriate exercise time (i.e., duration) and intensity is critical in aerobic exercise prescription. In fact, exercise intensity is the most critical indicator of the safety and efficacy of aerobic exercise prescription. Exercise intensity has received particular attention in the literature because of its relatively significant efficacy in improving cardiorespiratory fitness and weight management programs. Studies have shown that under isocaloric training conditions, high-intensity exercise is more effective than low-intensity exercise in reducing percent body fat and fat mass. In addition to cardiorespiratory fitness, high-intensity aerobic training was more effective than low- and moderate-intensity training in eliciting favorable changes in physical fitness, anaerobic threshold, lipids, waist circumference, insulin sensitivity, and glycemic control [27]. However, an effective exercise prescription should not only ensure adequate training stimulation to produce relevant health benefits, but should also be performed without undue exertion and non-essential discomfort, thus promoting safe and sustained exercise. For safety reasons, guidelines usually advise the general population not to exercise at too high an intensity to avoid cardiovascular events. However, if the intensity is not appropriate, the desired exercise effect will not be achieved. Therefore, it seems crucial to choose the appropriate intensity to both maximize the beneficial effects of aerobic training, such as improving cardiorespiratory fitness, while minimizing the cardiovascular risks associated with exercise.

Depending on the method of classification of exercise intensity, heart rate (HR) or oxygen uptake (VO2) can be used to represent and monitor the intensity of aerobic exercise (HRmax and VO2max, respectively) or the percentage of reserve (HRR and VO2R) values [10]. From a theoretical standpoint, it is more accurate to use a percentage of reserve value to characterize the intensity of aerobic exercise than to use a percentage of maximum value. Because the reserve value is calculated as the difference between the maximal value and the resting value, it takes into account the individual variability in resting HR and VO2 and allows for correction for nonzero resting values (nonzero resting values). Several studies have found that the percentages of HRR and VO2R during incremental exercise have been found to be highly correlated and are currently considered to be 1:1 [28], suggesting that the %HRR-%VO2R relationship is indistinguishable from a constant line (i.e., a regression line with a slope鈥�=鈥�1 and an intercept鈥�=鈥�0). It is important to note that the concept of 鈥淰O2 reserve鈥� is very much in line with the need for a precise definition of exercise intensity, as it describes the true amount of energy that can be achieved using one鈥檚 maximum effort, taking into account the baseline levels. However, it requires the use of specialized cardiorespiratory equipment or the performance of a maximal exercise test to obtain it, making it less accessible to the general population. In addition, a systematic review confirmed the validity of %HRR for indirectly assessing and characterizing the intensity of aerobic training [27]. Therefore, %HRR has been adopted by the ACSM as a recommended index for indirectly assessing exercise intensity, while moderate-intensity exercise (40鈥�59% HRR) has been used as a safe starting intensity for participation in aerobic exercise in apparently healthy populations [10]. However, since most of the current research on exercise-related cardiovascular risk comes from developed Western countries [9, 13]. There are huge differences in ethnicity and socioeconomic status between Eastern and Western populations. Furthermore, in China, the 鈥淗ealthy China Initiative鈥� was launched in 2016, one of the goals of which is to increase the number of people who regularly participate in physical activity from 360 million in 2015 to 530 million in 2030. However, the safety of participation in physical activity is a real obstacle to the implementation of this policy. Therefore, there is a strong need for research on exercise-related cardiovascular risk in China.

Exercise ECG is a diagnostic test tool for detecting myocardial ischemia and arrhythmias in CPET, especially changes in ST-segment depression [29]. If the exercise ECG is positive, it generally suggests that there is local ischemia of myocardial tissue, which may be caused by emotional excitement, anemia, myocardial ischemia, angina pectoris, coronary atherosclerotic heart disease, etc., and needs to be targeted to improve according to the cause. A suspected positive exercise ECG means that the patient鈥檚 ECG has shown a certain degree of abnormality even though the positive standard has not been reached under the premise of increased exercise intensity. Suspicious positive means that the test result cannot diagnose or exclude coronary artery disease, and needs to be combined with the patient鈥檚 symptoms and other tests, and if necessary, further improve the coronary artery CT or imaging examination, to clarify whether there is a coronary artery stenosis [24, 25]. The Multiple Risk Factor Intervention Trial (MRFIT), published in 1985, showed that the presence of ST-segment depression predicted an increased risk of coronary events and cardiac death in 6,438 asymptomatic healthy men who were followed for 7 years after CPET [30]. Several subsequently published studies have demonstrated a similar relationship, i.e., the risk ratio (RR) for a positive exercise ECG test in asymptomatic healthy participants ranged from 2 to 5 [31]. Gianrossi et al. published a meta-analysis containing 147 articles published before 1989, including 24,074 patients, and compared the correspondence between exercise-induced ST-segment depression and coronary angiography [32]. It was found that exercise ECG had a mean sensitivity of 68% and a mean specificity of 77% for the detection of coronary artery disease and produced reliable and reproducible results [33]. Therefore, asymptomatic ST-segment depression can be considered a very strong predictor of sudden cardiac death in people with any conventional CVDRFs but undiagnosed coronary artery disease [34]. The exercise ECG results of this study were reviewed and interpreted by physicians experienced in cardiac rehabilitation with strict reference standards. The results of this study found that the incidence of positive exercise ECG was 1.1%. This result is similar to the results of Francesco Sofi et al. [35] who tested more than 30,000 athletes in Italy, and is also in line with a systematic review published in 2016 by Danny on the prevalence of abnormal exercise test results in asymptomatic athletes of 0.6% (0鈥�29%) [11]. Therefore, the test results of the present study can be considered reliable. In addition, the present study found that exercise ECG positivity occurred in 7 (>鈥�50%) of exercise intensities鈥夆墺鈥�70% HRR. It is suggested that the selection of 70% HRR as the GXT exercise endpoint can lead to an underestimation of exercise capacity and inducible ischemic events.

Exercise intensity, its importance as a risk modifier for exercise-related cardiovascular events during pre-exercise health screening has been emphasized in the new edition of ACSM鈥檚 guidelines for exercise testing and prescription [10]. Although evidence suggests that the absolute risk of cardiovascular complications during high-intensity exercise is low, there is an increased relative risk of sudden cardiac death and/or acute myocardial infarction during or after exercise (independent of age, current physical health or functional capacity) [36]. Furthermore, based on the exercise heart rate corresponding to the occurrence of a positive exercise ECG, it is possible to determine the intensity of the exercise at which the positive ECG occurred at that time. The 10 cases of positive ECG in this study, 9 of which appeared during the exercise phase and 1 during the recovery phase, had a heart rate of 鈮モ��62.50% HRR at the time of positive ECG changes. Therefore, it can be assumed that it is relatively safe to exercise within the range of exercise target heart rate鈥�<鈥�62.50% HRR. This result is similar to the safe starting exercise heart rate (<鈥�60% HRR) specified in the guideline, so it further validates the reliability and practical application of the results of this experiment. The results of this study may have a positive impact on the development of exercise prescriptions or exercise guidelines in China. By clarifying the maximum exercise intensity at which cardiovascular risk during exercise occurs, it is possible to consider the most effective maximum exercise intensity while taking into account the safety of exercise when formulating exercise prescriptions or exercise guidelines. It is hoped that the results of this study can be used as a reference for the subsequent development of exercise prescriptions or exercise guidelines in China.

Although the overall prevalence of exercise-related SCD is low, these data suggest that there is heterogeneity in the risk of SCD during exercise, which may be driven by susceptibility in subpopulations [37]. The positive exercise ECG results in this study were found to be 20% in men and 80% in women. Although it has been shown that the rate of cardiovascular events is higher in men than in women during exercise, capturing exercise-related SCD is difficult, making the current outcome data very somewhat limited. This is because it will underestimate events in those who engage in unorganized, recreational exercise, and elucidating cardiovascular versus non-cardiovascular causes of death may be difficult in the absence of the autopsy. In addition, specific groups are underrepresented in the exercise-related cardiology literature; up to half of published data exclude female participants altogether [38]. Besides, the present study found that peak heart rate as a percentage of reserve heart rate was much higher in women than in men during CPET, suggesting that women may be exerting a much higher level of effort during the test than men. Since the greater the intensity of exercise, the greater the likelihood of an intra-exercise cardiovascular event, this may also partially explain the emergence of this result. Of course, it may also due to the fact that false-positive results of exercise ECG may be more common in women than in men [39], and subsequent expansion of the sample size is needed to explore the reasons for this result in depth.

A one-way ANOVA of ECG outcomes found a statistically significant difference in the indicator of age (P鈥�<鈥�0.001). Although increasing age is a risk factor for cardiovascular disease (鈮モ��45 years in men; 鈮�55 years in women), there was no evidence that age per se was a strong predictor of exercise-related SCD [40]. Moreover, Age was included in the calculation of the HRR, and if both were included in the multifactor logistic analysis, there may have been a problem of covariance. Therefore, age was not included in the subsequent multifactorial logistic analysis. The results of this study showed that the higher the HRR%, the more likely the individual was to have a positive and equivocal exercise ECG, a finding that is consistent with existing findings [41]. Furthermore, the beneficial effects of physical activity are mediated in part by altering the number of CVDRFs. In the present study, we found that the number of CVDRFs influenced the outcome of exercise ECG, with individuals with CVDRF鈥�=鈥�3鈥�4 being 2.6 times more likely to have a equivocal exercise ECG than individuals with CVDRF鈥�=鈥�0鈥�2, and those with CVDRF鈥�=鈥�5鈥�7 being 5.4 times more likely to have a positive exercise ECG than those with CVDRF鈥�=鈥�0鈥�2. In fact, Gibbons et al. conducted a study at the Cooper Clinic in the United States that followed 25,927 healthy men aged 20鈥�鈭�鈥�82 years with a mean follow-up of 8.4 years [42]. The results of the study found that the age-adjusted RR of ST segment changes during exercise testing to predict coronary heart disease death was 21 for no CVDRF, 27 for one CVDRF, 54 for two CVDRFs, and 80 for three or three CVDRFs. Again, it is argued that the higher the number of CVDRFs, the more likely an individual is to develop exercise ECG abnormalities. It also illustrates that PA is relatively safe when performed at <鈥�60% HRR in apparently healthy populations. If the exercise intensity of PA is 鈮モ��60% HRR, the safety of cardiovascular events participating in PA should be combined with the number of CVDRFs. Therefore, CVD prevention can be facilitated by reducing the number of individual CVDRFs.

Study limitations

Our sample was relatively healthy at baseline and the sample size was relatively small in number, and it is unclear whether our findings are applicable to other apparently healthy populations in China. In addition, it is unlikely that the small sample size will lead to biased findings; therefore, follow-up studies are needed to expand the sample size as a means of confirming the reliability of this study鈥檚 findings. Besides, we only conducted a cross-sectional study of exercise ECG because cross-sectional studies exist that cannot explain clearly the causal relationship between the results; therefore, a follow-up cohort study is needed to further explore the specific reasons affecting exercise ECG. Finally, this study used a cycle ergometer as the instrument for testing. However, it was shown that the exercise-induced myocardial ischemic response differed between the two testing methods, with the power bicycle exercise test resulting in less exercise-induced myocardial ischemia compared with the treadmill exercise test [43]. Therefore, this may also be one of the reasons for the low detection rate of exercise ECG abnormalities in this study.

Conclusions

(1) The incidence of positive ECGs in CPET is low, but when exercise intensity is 鈮モ��62.5% HRR, the probability of exercise ECG positivity increases, as does the probability of cardiovascular risk during exercise. The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in an apparently healthy Chinese population.

(2) The number of CVDRFs affects the outcome of exercise ECG; the higher the number of CVDRFs, the greater the likelihood of a positive or equivocal ECG during exercise, suggesting a greater likelihood of cardiovascular risk during exercise.