Introduction

Metabolic syndrome (MetS) is a constellation of interrelated metabolic risk factors with complex pathogenic mechanisms involving genetic and epigenetic factors and unhealthy lifestyles (such as a lack of physical activity, overeating and an imbalanced diet)1, which significantly increase the risk of diabetes and cardiovascular disease (CVD)2. As CVD is currently the main cause of death and low quality of life among the elderly population worldwide, it is important to study MetS prevention and treatment to reduce the risk of CVD progression3.

Exercise prescription can improve protective factors against CVD, such as cardiorespiratory fitness and increased muscle mass. Aerobic exercise is the foundation for the treatment of and recovery from MetS4,5,6,7. However, there is significant heterogeneity in the post-training response to aerobic exercise among both healthy individuals and patients with MetS8,9,10, which is caused by factors such as individual biological differences and methodological variations in exercise prescriptions, including modifications to exercise intensity, frequency, duration, and mode11. As a modifiable approach to reduce post-training response heterogeneity, methods for determining exercise intensity play crucial roles in practical applications.

Two related studies in 202012,13 reported poor agreement between the traditional standardized methods for determining exercise intensity on the basis of maximum physiological parameters (constant percentage) and the exercise intensity domains in which the body performs metabolism during practical exercise; standardized methods cannot control metabolic stimulation well. Among various individuals, the first ventilatory threshold (VT1) may correspond to different peak effort percentage intervals (%HRPeak, %VO2Peak, etc.), which correspond to various guideline-based exercise intensity domains14,15,16.

Prior to that, Peter Hofmann et al.17 had already pointed out that the method used to determine the physiological threshold is rarely mentioned in the relevant cardiac rehabilitation guidelines, and the target heart rate (THR) for prescribed exercise in individuals with disease and apparently healthy individuals should not be estimated only by relevant parameters of the maximum physiological value. In 2013, the European Association for Cardiovascular Prevention and Rehabilitation (EACPR), the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) and the Canadian Association of Cardiac Rehabilitation (CACR) released a joint position statement in which a method for prescribing exercise intensity on the basis of a physiological metabolic threshold was introduced to maximize the benefits of aerobic exercise in patients undergoing cardiac rehabilitation18. Subsequent studies showed that, compared with standardized exercise intensity prescriptions, physiological metabolic threshold-based exercise intensity prescriptions yielded a 100% response rate to maximum oxygen uptake in sedentary people19,20,21,22,23 and performed better at improving MetS severity24. In 2022, the European Association of Preventive Cardiology (EAPC) released a position statement that set the VT based on a cardiopulmonary exercise test (CPET) as the gold standard for determining aerobic exercise intensity25. By mainly using CPETs to evaluate VT1, VT2 and peak oxygen uptake, a system based on the physiological metabolic threshold classified exercise intensity into four levels. Although there is currently no consensus on the range of exercise intensity defined above26, the intensity range around VT1 is usually regarded as the “lower limit of moderate intensity”27,28. Patients with MetS are at high risk for CVD, including those who have recovered from a previous cardiovascular event. Therefore, VT1 can serve as a good initial marker for determining the actual exercise intensity of patients. Starting training near this point and then gradually increasing the exercise intensity to VT2 can ensure appropriate training benefits and prevent negative impacts on the heart and other metabolic indices29.

Despite existing problems, standardized methods are still irreplaceable because of their convenience and affordability. For patients with MetS, starting with low- to moderate-intensity exercise, with an intensity based on a fixed percentage range of heart rate reserve (e.g., 40–59% HRR), is usually recommended30. However, this range is relatively broad and does not fully consider the pathological features of MetS, such as insulin resistance and chronic inflammation3. These features lead to cardiovascular dysfunction during exercise in this group. Specifically, patients with MetS often have an imbalance in the autonomic nervous system, manifested as excessive sympathetic nerve activity at rest, impaired parasympathetic regulation of the heart, and a higher resting heart rate than healthy individuals31. During incremental load exercise, the ability of the heart to adjust its rate to meet the oxygen demand of the muscles is impaired, which in turn leads to a lower maximum heart rate (HRmax)32. With the progression of MetS components such as hypertension and hyperlipidemia, these adverse changes may lead to cardiac structural remodeling33, such as left ventricular hypertrophy and myocardial fibrosis, which in turn affect diastolic filling and reduce cardiac output during exercise. For many patients who are sedentary and have other unhealthy behaviors, their physical function further deteriorates, manifesting as reduced skeletal muscle mass, decreased mitochondrial function34, a low lactate clearance rate, and an earlier-onset anaerobic threshold35. These physiological disorders ultimately result in significantly lower exercise tolerance and cardiopulmonary fitness levels36,37.

We speculate that the above factors may lead to the HRR and HRmax in patients with MetS being lower than the predicted values. When HRmax prediction equations and fixed percentage ranges applicable to healthy individuals are used, the THR of patients with MetS may deviate from the individual’s true lower limit of moderate-intensity exercise (VT1).

Therefore, on the basis of the fixed percentages indicating low and moderate exercise intensity domains in the existing guidelines, we selected several potentially reasonable percentages for this study, aiming to compare the THR for aerobic exercise determined by standardized methods with the HRVT1 measured via the CPET to determine a safe, effective and simple way to guide patients with MetS in performing aerobic exercise when CPET data are not available.

Materials and methods

Materials

From November 2022 to June 2023, a total of 56 participants were consecutively enrolled through advertising at local hospitals, doctor recommendations, and health lectures. This study combined a single-center, cross-sectional observational study with a method comparison. The potential subjects underwent screening at Taiyuan Central Hospital within a 48-h period. The data that could be included in the final analysis were then determined.

The inclusion criteria were as follows: ① Patients aged 18 to 65 years with a sedentary lifestyle and a confirmed diagnosis of MetS (the diagnostic criteria released by the Chinese Diabetes Society were adopted in this research)38. Patients who had three or more of the following five symptoms met the diagnostic criteria: abdominal obesity, defined as an abdominal perimeter equal to or greater than 90 cm in males and equal to or greater than 85 cm in females; hyperglycemia, defined as a fasting blood glucose level equal to or greater than 6.1 mmol/L, a blood glucose level equal to or greater than 7.8 mmol/L two hours after glucose loading or a diabetes diagnosis; hypertension, defined as blood pressure equal to or greater than 130/85 mmHg or a hypertension diagnosis; a fasting triglyceride level equal to or greater than 1.70 mmol/L; and fasting high-density lipoprotein cholesterol lower than 1.04 mmol/L; ② patients who did not use beta blockers or other drugs that could impact their heart rate or exercise tolerance; and ③ patients who signed the informed consent form.

The exclusion criteria were as follows: absolute exercise contraindications, including the acute stage of various diseases, lower limb fracture, organ system failure, tumors, the acute phase of myocardial infarction, cardiac insufficiency, myocarditis, or chronic lung disease.

The shedding and rejection criteria were as follows: ① poor compliance; ② a CPET peak respiratory exchange ratio (RERpeak) lower than 1.10; and ③ unable to sustain 60 r/min during power cycling while following the metronome during the CPET.

All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This research was reviewed and approved by the Taiyuan Central Hospital Ethics Committee (No. 2022026). All study participants signed informed consent forms.

Testing scheme

The study participants underwent medical body composition analysis (770, InBody, Seoul, Korea), abdominal perimeter measurements, and blood draws to screen indices such as fasting blood glucose and blood lipid levels at Taiyuan Central Hospital one day before the start of the CPET. Those who met the inclusion criteria and did not meet any of the exclusion criteria were invited by phone to participate in the subsequent testing.

On the testing day, the premeasured weight and other data of the patients were input into the CPET operation system (CPX-770, HeartGym, Beijing, China). Gas and volume calibrations were conducted according to the manufacturer’s instructions, and the environmental temperature was maintained between 19 and 21 °C. Before the formal test, patients sat on the chair silently for 5 min, with their back against the chair, their feet on the floor, and their arms supported at heart level. An automatic upper arm sphygmomanometer (M5 professional, Omron, Mannheim, Germany) was used to measure the resting heart rate and blood pressure30. Within the doctor ward, a 12-lead electrocardiogram (ECG) system (EC-12S, Labtech, Debrecen, Hungary) was connected to continuously monitor the ECG and blood pressure during the exercise test period. Patients rested for 3 min before power cycling (Ergoselect 100, Ergoline, Germany) and then performed a 3-min zero-load warm-up at 60 r/min. According to sex and age, a proper incremental power (8–30 W/min) was chosen to ensure that the patients reached symptom-limited peak exercise within 6–10 minutes39. Then, the patients could rest and recover for 5–10 min, after which the test ended. All patients were encouraged to reach their maximum effort level.

Determination of the testing data

Determination of VT1

VT1 was jointly determined by three verified methods28 in the operation system. These three methods include the V-slope method (the comparatively increased slope inflection point of the VCO2 in comparison with the VO2 during the test), the VE/VO2 method, and the end-expiratory O2 pressure method. The V-slope method was the main calibration method, whereas the other two methods were used for validation to exclude V-slope inflection points caused by nonphysiological hyperventilation40. The data were evaluated by two professional cardiac rehabilitation physicians, and the corresponding heart rate of VT1 determined in the system was considered HRVT1. When the patient’s VT1 could not be effectively determined, the researchers jointly reviewed the case and determined the cause. If the cause was a human factor that could be corrected, the patient was retested with their consent.

Standardized HRR% method and HRmax% method

The HRR% method recommended by the American College of Sports Medicine (THR = (HRmax—resting heart rate) × exercise intensity percentage + resting heart rate) was used30, and the Fox equation (HRmax = 220—age), Miller equation (HRmax = 200 − 0.48 × age) and Tanaka equation (HRmax = 208 − 0.7 × age) were applied to calculate the HRmax. The THR of the 35% HRR, 40% HRR, and 45% HRR and the 55% HRmax, 60% HRmax, and 65% HRmax were calculated separately. Additionally, since the HRmax of the patients was measured during the CPET (HRPeak), standardized method calculation results were also used for agreement testing in this case.

Statistical analysis

The data were processed with SPSS 27.0 (IBM, Armonk, NY, USA), and the SPSSAU data analysis platform (https://spssau.com/) was used to construct the diagrams. The data are presented as the mean and standard deviation (SD). The Kolmogorov‒Smirnov test for normality was performed, and the significance level α was equal to 0.05. The paired-sample t test was used for preliminary testing of differences. The Bland‒Altman test and the interclass correlation coefficient (ICC) were used for further agreement testing to ensure that the results had the highest reliability and validity41. The ICC model selected was a two-way random effects model.

Results

Clinical characteristics

Among the 56 screened participants, 8 were excluded (5 due to the use of beta-blockers and 3 for an RERpeak lower than 1.10). A total of 48 patients with MetS were ultimately included in the final analysis, including 32 males and 16 females aged 24–64 years (44.3 ± 10.6 years). In the CPET used in this study, all patients terminated the test because of muscle fatigue, resulting in the inability to maintain a power cycling rate of 60 r/min. Table 1 presents the basic clinical characteristics and physiological variables of the patients.

Table 1 Basic information of the study group.
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Comparison of the % HRR standardized method and the HRVT1

The THRs calculated by combining the 40% HRR or 45% HRR with any prediction equation were greater than the HRVT1 (P < 0.001), whereas there were no statistically significant differences between any of the calculated results of the 35% HRR and HRVT1 values (P > 0.05) (Table 2). Compared with that of the other equations, the THR calculated by combining the 35% HRR with the Fox equation resulted in the smallest significant difference compared with the HRVT1 (t = − 0.528, P = 0.600). The results of the Bland‒Altman agreement test revealed that the mean difference between the 35% HRR determined by the Fox equation and the HRVT1 was -0.350, which was close to the 0th line (SD: ± 4.595; 95% CI − 1.684–0.984), with 95% limits of agreement ranging from − 9.356 to 8.656 (Fig. 1a). After considering the results of the ICC test (0.862; 95% CI 0.766–0.920) (Table 3), the combination of the 35% HRR and the Fox equation showed good reliability and excellent agreement with the HRVT1.

Table 2 Target heart rate values calculated from various maximum heart rate prediction equations and the CPET measurements, as well as the differences between these values and HRVT1.
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Fig. 1
figure 1

Bland‒Altman agreement tests between the HRVT1 and %HRR calculated by the prediction equations. (a) Data calculated with the Fox equation; (b) data calculated with the Miller equation; (c) data calculated with the Tanaka equation. Abbreviations: HRR = heart rate reserve; HRVT1 = heart rate of VT1.

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Table 3 ICC analysis of the THR determined by the standardized reserve heart rate method and the HRVT1 (n = 48).
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Comparison of the % HRmax standardized method and the HRVT1

The THRs calculated by combining the 55% HRmax or 60% HRmax with any prediction equation were lower than the HRVT1 (P < 0.001) (Table 2). For the 65% HRmax, only the difference between the THR calculated with the Miller equation and that calculated with the HRVT1 was significant (t = − 2.764, P = 0.008), whereas the difference in the THR calculated with the Fox equation was the smallest (t = − 0.994, P = 0.326). The results of the Bland‒Altman agreement test revealed that the mean difference between the 65% HRmax determined by the Fox equation and the HRVT1 was -0.989, which was close to the 0th line (SD: ± 6.894; 95% CI − 2.990–1.013), with 95% limits of agreement ranging from − 14.500 to 12.523 (Fig. 2c). After including the ICC results (0.639; 95% CI 0.435–0.780) (Table 4), the combination of the 65% HRmax and the Fox equation had only moderate reliability and moderate agreement with the HRVT1.

Fig. 2
figure 2

Bland‒Altman agreement tests between the HRVT1 and % HRmax calculated by the prediction equations. (a) Data calculated with the Fox equation; (b) data calculated with the Miller equation; (c) data calculated with the Tanaka equation. Abbreviations: HRmax = maximum heart rate; HRVT1 = heart rate of VT1.

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Table 4 ICC analysis of the THR determined by the standardized maximum heart rate method and the HRVT1 (n = 48).
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Comparison of the HRVT1 and THR obtained by combining the measured HRmax with the standardized method

After the THR was calculated by combining the measured values with the %HRR, the results revealed that the 40% HRR had the greatest reliability and greatest agreement with the HRVT1; that is, the mean difference between the two was -0.421, which was close to the 0th line (SD: ± 5.184; 95% CI − 1.926–1.084), with 95% limits of agreement ranging from − 10.581 to 9.739 (Fig. 3b), as demonstrated by the Bland‒Altman agreement test. The ICC was 0.850 (95% CI 0.747–0.913) (Table 3). The results also indicated good agreement between the other %HRRs (35% and 45%) and the HRVT1 (ICC: 0.787, 95% CI 0.659–0.873; and ICC: 0.757, 95% CI 0.619–0.853, respectively) (Table 3). This may indicate the heterogeneity of HRVT1 among individuals with MetS.

Fig. 3
figure 3

Bland‒Altman agreement tests between HRVT1 and THRs calculated from measured heart rate values and standardized methods. Abbreviations: CPET = cardiopulmonary exercise test; HRPeak = actual maximum heart rate measured in the CPET.

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According to the CPET results in this study, which revealed that patients typically did not reach their predicted HRmax, the HRPeak percentages were increased. The results revealed that 70% HRPeak had the smallest statistical difference with the HRVT1 (t = − 1.328, P = 0.191), while 65% HRPeak was significantly lower than HRVT1, and 75% HRPeak was significantly higher than HRVT1 (Table 2). The results of the Bland‒Altman agreement test revealed that the mean difference between the 70% HRPeak and HRVT1 was − 1.358, which was close to the 0th line (SD: ± 7.086; 95% CI − 3.416–0.699), with 95% limits of agreement ranging from − 15.246 to 12.529 (Fig. 3e), and the ICC was 0.719 (95% CI 0.551–0.832) (Table 4).

Discussion

The cardiopulmonary endurance levels of the patients in this study were lower than those of the MetS population in previous studies and the healthy population36, with lower VT1 (13.22 ± 1.93 ml/kg/min) and HRPeak (164 ± 14 bpm) values and a higher resting heart rate (80 ± 9 bpm). All the agreement test results indicated that regardless of which HRmax prediction equation was used, the 35% HRR had excellent agreement with the HRVT1, whereas the 40% HRR had only moderate agreement and significant differences with the HRVT1. Although the Bland–Altman test indicated good agreement between the 65% HRmax (Fox equation) and HRVT1, the ICC analysis showed relatively poor reliability of the %HRmax method in practical applications. This is likely due to the inherent mathematical error of the %HRmax method16. When the intercept correction is not used and the HRmax predicted value is used, the higher the HRVT1 of an individual is, the lower the HRVT1 calculated by a fixed %HRmax; the opposite is true for a lower HRVT1. This also explains the asymmetry of the error distribution shown in Fig. 2 in this study, where there are more negative errors at lower HR values and more positive errors at higher HR values. At the macro level, this may be related to the mismatch between HR and workload in incremental exercise, which is caused by poor heart rate dynamics in some patients with MetS32,42. In fact, as early as 1978, researchers questioned the method of determining exercise intensity on the basis of the HRmax percentage43. The HR is a poor VT1 indicator, and it is necessary to use the external load power and other indicators. In a recent study, it was also confirmed that the %HRR method performs better than the %HRmax method in terms of measurement quality and agreement with the HRVT144.

In the exercise intensity domain, which is divided on the basis of the maximum physiological value percentage, the 35% HRR is in the light intensity zone. When the HRmax prediction equations are used, the previous moderate intensity zone of the 40–59% HRR30 or the 40–69% HRR25, which is based on the maximum physiological value percentage, results in an increase in the actual exercise intensity for patients with MetS to levels greater than the VT1. In fact, the guidelines for exercise testing and exercise prescription by the American College of Sports Medicine already recommend that unhealthy people carry out exercise at 30 ~ 39% HRR or VO2R30, which is basically consistent with the results of this research. However, when the measured HRmax is used, the lowest value in the moderate exercise intensity domain (40% HRR) may still be applicable, whereas the baseline value of the 65% HRPeak may underestimate the HRVT1 of patients with MetS. The 70% HRPeak may be a better choice for estimating the HRVT1.

The widely promoted and applied Fox equation and Tanaka Eq. 45 were used in this research. Because the average body fat percentage of the participants in this study was greater than 30%, the Miller equation, which is recommended for overweight people with sedentary lifestyles, was also tested46. Many improved equations are suitable for different individuals30, but an HRmax prediction equation that is suitable for patients with MetS has yet to be developed. The purpose of this study was not to develop HRmax prediction equations. The three HRmax prediction equations were used only to test the corresponding standardized exercise intensity in the VT1 exercise intensity domain in patients with MetS. Compared with the other two HRmax prediction equations, the 35% HRR (113.56 ± 8.20) values calculated by the Fox equation showed the highest agreement with the HRVT1, which might be due to the average age of the participants in this study being 40–50 years47. Additionally, the HRmax predicted by the Fox equation decreases rapidly with increasing age, so it can be underestimated in healthy individuals48; however, it might conform to the situation where the HRmax of patients with MetS is generally lower than in healthy populations.

There are significant differences in physiological responses among individuals during exercise, and even with the use of measured values, this difference still exists. This once again indicates that an objective physical exercise ability assessment for patients with MetS is necessary for developing personalized exercise prescriptions49. We believe that even in situations where gas exchange analysis is not available, it is still necessary for patients to perform a treadmill exercise test (or other ergometric test) to obtain a measured HRmax value for calculating the optimal exercise intensity. Although this study included a standardized exercise domain with high agreement with the VT1, it should serve only as a reference when the CPET cannot be obtained, and it should be the minimum exercise intensity for patients with MetS undergoing rehabilitation. In practical applications, subjective methods of setting the exercise intensity, such as the talk test and Borg scale, should be used to continuously adjust the exercise prescriptions to meet the needs of patients16.

Limitations

The limitations of this research include the small sample size and wide age range. Future studies should validate our findings by expanding the sample size with a detailed differentiation by age group and sex. Owing to the limited sample size, we did not conduct any subgroup analyses with patients with MetS as the reference. We excluded patients with MetS who were using drugs that could impact their heart rate, which may limit the applicability of the results. In addition, no equations for predicting the HRmax of the MetS population were developed in this study, and only the Fox equation was used as a substitute.

Perspective

The first ventilatory threshold is the baseline for moderate-intensity continuous exercise, and most exercise prescriptions require a gradual increase in exercise intensity and volume in practical applications. Our study provides a way to approximate the VT1 in the CPET in patients with metabolic syndrome using traditional exercise intensity determination methods. Without CPET equipment and related technical operators, patients with MetS can start effective and safe endurance training in this exercise intensity domain on the basis of our results, and guardians should use subjective methods for monitoring the exercise intensity at any time. The consistency between the exercise intensity determined by the 35% HRR calculated by the Fox equation and the exercise intensity determined by the VT1 in the practical application of exercise prescriptions for improving cardiovascular risk factors and cardiovascular fitness in patients with MetS needs to be verified. By verifying the consistency of the two methods for determining the exercise intensity in practical applications, it may be possible to further refine the percentage of the HRR corresponding to VT1, which is suitable for patients with MetS. In addition, an HRmax prediction equation suitable for adult patients with MetS needs to be developed, and given the heterogeneity of the MetS clinical cohort, individuals using β-blockers should be evaluated separately from those who do not50.

Conclusion

In the field of clinical rehabilitation medicine, the method of prescribing exercise intensity based on the percentage of maximum physiological values has been gradually replaced by a method based on thresholds; however, when guiding patients with MetS to exercise without obtaining CPET, it is still necessary to use the 35% HRR standardization method combined with the Fox equation to estimate the HRVT1 or to use the 40% HRR and 70% HRPeak when the measured HRmax can be obtained, but gas exchange analysis cannot be performed.