CARDIOPULMONARY EXERCISE TESTING FOR VO₂MAX DETERMINING IN SUBJECTS OF DIFFERENT PHYSICAL ACTIVITY

Summary

Cardiopulmonary exercise testing (CPET) provides assessment of the integrative exercise responses involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system function. This non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the doctor with relevant information for clinical decision making. CPET is increasingly being used in a wide spectrum of clinical applications for the evaluation of undiagnosed exercise intolerance and for the objective determination of functional capacity and impairment. Its use in patient management is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that overall health status correlates better with exercise tolerance than with resting measurements. CPET involves measurements of respiratory oxygen uptake, carbon dioxide expenditure and pulmonary ventilation during a step-vice increased physical workload up to the maximum (or symptom-limited level in patients) on ergometer. In this paper the principle of CPET is described and results for VO_2max and VO_2max/kg of almost 3000 measurements in subjects of different physical activity are presented. These values characterizing cardiorespiratory capacity of the subjects were compared to the values of maximal performance achieved during stress test on bicycle ergometer (Wmax and Wmax/kg) and regression equations for VO_2max – W_max and VO_2max/kg – W_max/kg were calculated.

Keywords:
cardiopulmonary exercise testing, VO_2max, bicycle ergometer, regression equations, measuring system

Introduction

Cardiopulmonary exercise testing (CPET) provides assessment of the integrative exercise responses involving the pulmonary, cardiovascular, haema-topoietic, neuropsychological, and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system function. This non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the doctor with relevant infor-mation for clinical decision making. CPET is in-creasingly being used in a wide spectrum of clinical applications for the evaluation of undiagnosed exercise intolerance and for the objective determination of functional capacity and impairment. Its use in patient management is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that overall health status correlates better with exercise tolerance than with resting measu-rements. CPET involves measurements of respiratory oxygen uptake (VO₂), carbon dioxide expenditure (VCO₂), and pulmonary ventilation during a step-vice increased physical workload up to the maximum (or symptom-limited level in patients) on ergometer. In this paper the principle of CPET is described and results for VO_2max and VO_2max/kg of 2777 measurements in subjects of different physical activity are presented. These values characterizing cardiorespiratory capacity of the subjects were compared to the values of maximal performance achieved during stress test on bicycle ergometer (W_max and W_max/kg) and regression equations for VO_2max – W_max and VO_2max/kg – W_max/kg were calculated.

VO_2max and VO_2max/kg values were directly obtained during 2777 measurements in competitive athletes and active but not competing subjects. W170 and W170/kg characterize physical working capacity. W170 is the estimated performance in watts, corresponding to the heart rate 170 beats/min [74, 75].

The normatives of cardiorespiratory capacity for different age groups of male and female endurance athletes (Group A), team sport players (Group B) and other sports (group C) were established, and compared to normatives for Czech population based on the International Biological Program (IBP) results [62]. Group D in our study included subjects performing sport and physical activity in their leisure time, however, did not participated in any competitive sport (so called “hobby” athletes).

The most favorable values of cardiorespiratory capacity (both VO_2max; VO_2max/kg and W170; W170/kg) were found in the group A athletes (endurance trained) – both males and females. Their level highly exceeded the values of untrained Czech IBP population and also those obtained in control group D in this study.

The highest correlation was found between VO_2max and W_max and between VO_2max/kg and W_max/kg. This high correlation was very similarly high in the whole sample of 2777 examinations, in the sample of men (n=2015) and sample of women (n=762) and also in all age-groups in different athletic groups A to D.

It was proved that VO_2max and VO_2max/kg values could be calculated according to the maximal performance attained on bicycle ergometer [73].

During spiroergometric examination the values of stroke volume and cardiac output can also be calculated [52, 64]. These values represent additional data closely correlating with the adaptive changes of circulatory system.

Regular aerobic endurance exercise could reduce biological age of active individuals by 10 to 20 years with a correspondingly decreased likelihood of becoming dependent when a senior and an expressive improvement in the quality of the final years of life [7, 57, 71]. VO_2max and VO_2max/kg values represent important health quality marker. They also offer feedback information, positive and/or negative, about the effectiveness of physical activity influencing its development. Thus, aerobic fitness level has been strongly and positively associated with reduced disease and mortality rates, good quality of life, performance level, and functional ability.

Exercise capacity and oxygen uptake measuring

Peak exercise capacity is defined as “the maximum ability of the cardiovascular system to deliver oxygen to exercising skeletal muscle and of the exercising muscle to extract oxygen from the blood”. Consequently, exercise tolerance is determined by three factors: pulmonary gas exchange; cardiovascular performance, including the peripheral vascular tree; and skeletal muscle metabolism.

Understanding the Fick equation is of paramount importance for appreciating the utility of functional exercise testing. At rest, the Fick equation states that oxygen uptake (VO₂) equals cardiac output times the arterial minus mixed venous oxygen content:

where SV is the stroke volume, HR is the heart rate, CaO₂ is the arterial oxygen content, and CvO₂ is the mixed venous oxygen content. Oxygen uptake is often normalised for body weight and expressed in units of ml O₂·min^-1·kg^-1. One metabolic equivalent (MET) is the resting oxygen uptake in a sitting position and equals 3.5 ml·min^-1·kg^-1.

This reflects the maximal ability of a person to take in, transport and use oxygen. It defines that person’s functional aerobic capacity. VO₂max has become the preferred laboratory measure of cardiorespiratory fitness and is the most important measurement during functional exercise testing. In healthy people, a VO₂ plateau occurs at near maximal exercise. This plateau in VO₂ has traditionally been used as the best evidence of VO_2max. It represents the maximal achievable level of oxidative metabolism involving large muscle groups.

Cardiopulmonary exercise testing measuring principles

Several different methods exist for measuring ventilation and respiratory gas parameters during exercise. Some clinical systems rely on breath-by-breath analysis techniques because they provide the best measures of the metabolic response to exercise.

The block diagram of measuring system is shown in Fig. 1. The exercise tests were performed on an electro-nically braked cycle ergometer (or treadmill) controlled by computer. Subjects were familiarized with the apparatus and performed a continuous incremental symptom-limited maximal test for determination of VO_2max and lactic acidosis threshold (LAT).

A non-rebreathing valve is connected to a mouth-piece to prevent mixing of inspired and expired air. Oxygen and carbon dioxide gas analysers are usually incorporated in a "metabolic cart" designed specifically for functional testing. Respiratory volumes are compu-ted by integrating the air flow signals over the time of inspiration and expiration. Average minute volumes are derived from the breath-by-breath data multiplied by the respiratory rate [65].

Many different protocols are used for functional testing. The purpose of the test and the functional capabilities of the patient determine the choice of protocol. In evaluating patients with congestive heart failure (CHF), both bicycle and treadmill protocols have been used. The rate of workload progression is somewhat arbitrary, although it has been suggested that optimal exercise duration for functional assessment on the bicycle is between 8 and 17 minutes. Bicycle work is quantified in watts (W) or in kilopondmetres/min (kpm/min; 1 W = ~ 6 kpm·min^-1). The initial workload for patients with CHF is usually 20–25 W and increased by 15–25 W every 2 minutes until maximal exertion (symptom limited maximum) is reached. Alternatively, the workload can be computer controlled for electronically braked bicycle ergometers, and a ramp protocol (eg. 10 W·min^-1) is often used.

Testing protocol in our laboratory was based on the testing protocol used in the IBP [42, 62]. In healthy and average fit subjects three submaximal workloads of 3-min duration were used. The first workload corresponded approximately to 1 W·kg^-1 body weight of the subject, the second workload to 1.5 W·kg^-1 body weight and the third workload to 2 W·kg^-1 body weight respectively. After 9 minutes warming up the workload was consecutively increased every half minute by 20 to 30 W (dependant on body weight and age of the subjects) until exhaustion. In highly fit subjects the initial warming up submaximal workloads were 1.5 W·kg^-1, 2 W·kg^-1 and 2.5 W·kg^-1 of body weight respectively.

Equipment for cardiorespitatory capacity evaluation is shown on Fig. 2. The electrical signals from sensors were connected to microcontroller systems (KARD SYSTEM). The expired gas samples were connected to respiratory gas analyzer (O₂-CO₂ analyzer). All electrical signals from sensors and from gas analyzer were processed in personal computer. Both patients with heart disease and healthy subjects require continuous ECG monitoring and frequent blood pressure measurements during exercise testing. Since verbal communication is usually not possible with the mouthpiece apparatus, hand signals are usually used during exercise.

Oxygen uptake (VO₂) is determined by cellular O₂ demand up to some level that equates to maximal rate of O₂ transport, which then is determined by that maximal rate of transport. As VO₂ increases with increasing external work, one or more of the determinants of VO₂ approach limitations (eg, stroke volume, heart rate, or tissue extraction), and VO₂ versus work rate may begin to plateau. This plateau in VO₂ has traditionally been used as the best evidence of VO_2max. The main determinants of a normal VO_2max are genetic factors [10, 11], quantity of exercising muscle, age, gender and body size [5]. Other important factors are previous training and patient motivation. VO_2max should be expressed in absolute values (l·min^-1) and as a percentage of the predicted value. VO₂ can increase from a resting value of about 3.5 ml·min^-1·kg^-1 (about 250 ml·min^-1 in an average person) to VO_2max values about 15 times the resting value (30–50 ml·min^-1·kg^-1). Athletes may attain values over 20 times their resting values (up to 90 ml·min^-1·kg^-1).

The ratio of carbon dioxide output/oxygen uptake (VCO₂/VO₂) is called the respiratory exchange ratio (RER). Under steady state conditions, the RER equals the respiratory quotient (RQ). The RQ value is determined by the fuels used for metabolic processes. RQ of 1.0 indicates covering the metabolic demands exclusively by carbohydrates, while RQ 0.7 indicates metabolism only by free fatty acids. Normal resting values of RQ~0.8 indicates that metabolic demands are by third covered by carbohydrates and by two thirds by free fatty acids. During step-vice increased workload RQ increases up to 1.0 and more due to higher utilization of carbohydrates in muscle metabolism and buffering processes connected to metabolic acidosis evoked by near maximal and/or maximal intensity workload.

Example of HR and VO₂ dependence on workload intensity is shown in Fig. 3 and 4.

Indications for terminating CPET

Symptoms during step-vice increased workload up to the maximum during ergometer stress test can rarely result in premature test termination. There are several absolute indications for termination of an exercise test, such as: suspicion of a heart attack, onset of moderate-to-severe angina (chest pain), drop in systolic blood pressure below standing resting pressure, signs of poor perfusion, including pallor, cyanosis, or cold and clammy skin, severe or unusual shortness of breath, CNS symptoms e.g. ataxia, vertigo, visual or gait problems, or confusion, serious arrhythmias e.g. second/third degree AV block, atrial fibrillation with fast ventricular response, increasing premature ventricular contractions or sustained ventricular tachycardia, and also technical inability to monitor the ECG. Cardiac arrhythmias are usually not an indication to stop the test unless sustained tachyarrhythmias develop. Other indications for CPET terminating might be any chest pain that is increasing, physical or verbal manifestations of shortness of breath or severe fatigue, wheezing, leg cramps or intermittent claudication, hypertensive response (SBP>260 mm Hg; DBP>115 mm Hg) and others.

Oxygen uptake estimation

Bicycle ergometer is nowadays a very common device for testing fitness level of the subject. However, accurate estimation of the VO_2max is exclusively dependent on direct availability to analyze O₂ and CO₂ content in the expired air. Equipment for O₂-CO₂ analysis is relatively expensive and mostly only in specialized stress test laboratories available. It was the purpose of this study to find the posibility for accurate indirect determination cardiorespiratory capacity without need for the O₂-CO₂ anylysis. Hence, the values of direct VO_2max and VO_2max/kg were compared with other fitness values, obtained without the need need for the O₂-CO₂ anylysis: W170 and W170/kg, and W_max and W_max/kg.

The highest correlation was found between the values of VO_2max and W_max, and between VO_2max/kg and W_max/kg. Fig. 5 and Fig. 6 illustrate this correlation in the group of 2015 healthy men. Regession equations were calculated to obtain approximate values of VO₂ and VO_2max indirectly without any need for additional equipment. Similarly, the regression equation could be calculated for individual age subgroups in each group of different level of physical aktivity (for example see Table 1 and 2).

There are other approaches for VO₂ estimation [27]. According to the Fick principle, eq. (1), VO_2max may be expressed as the product of cardiac output (Q) and the arterio-venous O₂ difference

Thus, since Q is the product of HR and stroke volume (SV), VO_2max can be expressed as

When applied to rest VO_2max can be expressed as:

implying that

During maximal exercise the Fick equation reads:

By multiplying the right side of eq. 6 with 1 in the form of eq. 5 it follows that:

therefore

VO_2rest is dependent on and increases with the individual’s body mass. Relative to body mass (BM), resting VO_2rest equals about 3.5 ml·min^-1·kg^-1 (one MET), but slightly lower values were reported by other researchers (e.g. 3.3 for men and 3.1 for women, respectively [27]). As a compromise is possible take 3.4 ml·min⁻¹·kg⁻¹ to represent the mass-specific resting VO_2max. Accordingly, VO_2rest may be expressed as 3.4 ml·min^-1·kg^-1 times BM in kg.

 

From a simplified test only the HR_max to HR_rest ratio is readily obtainable. The other two ratios in the equation involve complicated measurements, in fact more complicated than the measurement of VO₂ itself.

The average SV_max/SV_rest is approximately 1.29 when measured in the supine position. Thus, according the SV_max/SV_rest may be replaced by a dimensionless value of approximately 1.3. The arterio-venous oxygen difference increases from rest to maximal exercise. It was found the average ratio between maximal and resting

 

to be approx. 3.4. Therefore

 

can be replaced with 3.4.

Altogether, based on previous derivation suggest that eq. 9 may be simplified to final approximations

or for VO_2max/kg is

Estimation VO_2max according another approach [68] can be calculated according:

where sex is 1 for male and 0 for female, BM weight (kg), W_max is maximal workload (W) and HR_max is maximal heart rate (beats per minute).

Several other attempts with different accuracy were used for indirect calculation of VO_2max [16, 40, 43].

Example:

Male triathlete, age 20 years, body weight = 64.7 kg

Measured values:

Estimated values (calculated only from W_max and W_max/kg):

VO₂max and age

Edvardsen et al. [20] demonstrated that the VO_2max relative to body mass (VO_2max/kg) decreased 8% per decade. The decline  had already started after the first age cohort (20–29 years) and was linear throughout all age cohorts  until the last one (70–85 years). VO_2max was about 25% higher in men than in women. Rogers et al. [58] found that the sedentary subjects’ VO_2max declined by an average of 12% per decade. The master athletes’ VO_2max decreased by 5.5% decline per decade. These findings provided evidence that the age-related decrease in VO_2max of master athletes who continue to engage in regular vigorous endurance exercise training is approximately one-half the rate of decline seen in age-matched sedentary subjects.

The decline of VO_2max and VO_2max/kg was observed also in all age groups in our study. The highest values in both men and women were achieved by endurance trained athletes, followed by game sport athletes and other athletes. VO_2max and VO_2max/kg in the groups of non-competitive sportsmen (and sportswomen) was significantly lower that in all athletic groups and the age-related decline was faster. Compared to the values, valid like normatives for Czecho-slovak population [62], the data of the „non-competitive" groups both men and women are almost identical (see Fig. 7 to Fig. 10). They prove that non-competitive sporting activity is effective for maintaning the average level of fitness, however, does not evoke higher level of cardirespiratory capacity.

 

The example of  different values obtained from the whole cohort of all 2777 examinations (men and women) is presented in Table 3 {in Appendix}.

Discussion

Oxygen consumption (VO₂) is considered the most accurate variable to measure the intensity of physical activity, and it can be measured directly in the laboratory with metabolic carts or respiratory gas analysers. Portable devices are available for field
measurements, but they can be used only for limited periods of time and for limited number of subjects. Therefore, many efforts have been made to find more feasible ways to estimate VO₂ in field studies.

Maximal oxygen uptake or consumption (VO_2max) means the maximal capacity of an individual to perform aerobic work. It is the product of cardiac outputand arteriovenous oxygen difference at exhaustion, and represents the golden standard measure for a person’s aerobic fitness [63].

Aerobic fitness is related to a person’s ability to perform dynamic, moderate-to-high intensity physical activity with large muscle groups for prolonged periods. Thus, it expresses the abilities of both cardiorespiratory and muscular systems to
transport and utilize oxygen. It is one of the most fundamental measures of human physiology with remarkable health, wellbeing, life quality, work ability, and performance-related associations.

In addition to oxygen consumption (VO₂), the energy cost of physical activities can be expressed as metabolic equivalents (MET; Metabolic Equivalent of Task). MET is defined as the ratio of metabolic rate (and therefore, the rate of energy consumption) during a specific physical activity to a resting metabolic rate. One MET is defined as 1 kcal·kg^-1·hour^-1 or VO2 equal to 3.5 ml·min^-1·kg^-1, and it is roughly equivalent to the energy cost of sitting quietly.

Individual VO_2max values can range from about 10 ml·min^-1·kg^{-1 in cardiac patients to over 90} ml·min^‑1·kg^-1 among world-class endurance athletes. Average values for men and women in different age groups have been used to establish reference fitness categories, as aerobic fitness generally declines with age.

There are numerous reports that higher level of cardiorespiratory fitness is associated not only with maintaining a healthy weight, but also with increased muscle tone and increased basal metabolic rate.  Participating in cardiovascular exercise and maintaining and/or even increasing cardiorespiratory capacity leads to reduced risk of several chronic and life-threatening diseases, such as coronary heart disease [4, 9, 12, 18, 19, 30, 34, 35, 39, 46, 48, 54, 61, 69, 72], type 2 diabetes [1, 2, 3, 13, 45], cardio-metabolic syndrome [6, 36, 37, 67], hypertension [15, 17, 21, 23, 24, 31, 32, 33, 41, 70], respiratory diseases [29, 44] and some cancers, such as colon cancer, breast cancer, lung cancer and multiple myeloma cancers [22, 38, 49,  64]. The American College of Sports Medicine states that higher levels of cardiovascular fitness are associated with a 50 percent reduction in cardiovascular disease risk [25, 27]. Regular cardiovascular exercise increases insulin sensitivity and glucose metabolism, reducing chances for developing type 2 diabetes [53, 55] and plays important role in treating obesity [14, 59].

Being active is an effective way to combat anxiety, stress and even depression [47, 50, 60]. Exercise triggers the release of endorphins, which can elevate mood. Finding time to exercise several times per week can also lead to an increase in self-esteem.

It would be extremely beneficial to measure VO_2max accurately in real-life. VO_2max is a marker of optimal health. If it's critical decrease is diagnosed in time, numerous later health problems could be efficiently prevented. While laboratory tests require expensive equipment and trained personnel, and are thus difficult and expensive to perform, simple estimation of maximal performance on the treadmill ergometer could predict VO_2max with sufficient accuracy.

Conclusion

The most important marker of cardiorespiratory capacity is VO_2max. Also the concept of so called “fitness age” is based on the knowledge of personal VO_2max. If somebody's VO_2max is below average compared to age normative, his fitness age is actually greater than his chronological age.

On the other hand, a better-than-average VO_2max could mean that fitness age is younger than subject's age in years. It's possible to improve VO_2max by proper training, which means that the fitness age can actually get younger.

The primary problem with using VO_2max to gauge longevity is that very few people know what theirs is, and finding out typically requires high-tech testing on
a bicycle and/or treadmill ergometers and analyzing expired air for O₂ and CO₂ content. Our results on large cohorts of subjects demonstrate that simple bicycle ergometer with accurate measurement of performance reached by step-vice increased workload can offer reliable data (W_max and W_max/kg), which can be used for calculation VO_2max and VO_2max/kg with sufficient enough exactness. Regression equations for men and women and also for different age groups can be used for this purpose.

Fitness age may predict premature death better than risk factors like overweight, high blood pressure, or smoking [51]. If the subject is not satisfied with his fitness age, he is motivated to improve it by regular training program. The recommendation regarding physical activity are available from principle guidelines [8, 25, 26, 27, 56, 63], however, general practitioner and/or sports medical doctor should give personalized advice about the optimal volume, form and intensity.

Acknowledgement

This research has been supported by the Ministry of Education, Youth and Sports of the Czech Republic under the RICE – New Technologies and Concepts for Smart Industrial Systems, project No. LO1607.

M. Stork is with University of West Bohemia, Faculty of Electrical Engineering, Regional Innovation Centre for Electrical Engineering (RICE), Univerzitní 8, 306 14 Plzeň, Czech Republic.

Prof. Ing. Milan Stork, CSc.

Department of Applied Electronics

Faculty of Electrical Engineering

University of West Bohemia, Univerzitni 22, Plzen, CZ

Email: stork@kae.zcu.cz

MUDr. Jaroslav Novak, Ph.D.

Faculty of Medicine, Charles University, Plzen, CZ

Email: Jaroslav.Novak@lfp.cuni.cz

Prof. MUDr. Vaclav Zeman, CSc.

Faculty of Medicine, Charles University, Plzen, CZ

Email: Vaclav.Zeman@lfp.cuni.cz