the cardiopulmonary response to incremental exercise test: the effect of aging

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Aging Clin. Exp. Res. 6: 267-275, 1994 The cardiopulmonary response to incremental exercise test: The effect of aging L. Fuso 1 , R. Antonelli Incalzi 2 , R. Muzzolonl, M. Di Gennaro 2 , F. Gliozzil, R. Pistellil, and P.U. Carbonin 2 lOepartment of Respiratory Physiology, 20epartment of Geriatrics, Catholic University, Rome, Italy ABSTRACT The aims of the present study were to define the respective roles of the car- diac and respiratory response to exercise as de- terminants of the age-related physiological decrease in exercise performance, and to assess the relationship between aging and interindi- vidual variability in the response to effort. We studied.91 normal subjects recruited in three age-groups: Group A (42 children, aged 10±2 years); Group B (29 young adults, aged 27±5 years); Group C (20 elderly, aged 74±9 years). All the subjects underwent an incremental cy- cle ergometer exercise test with a work load in- crease of 15 W every 2 minutes in groups A and C, and 25 W every 2 minutes in group B, until they achieved 80% of the predicted max- imal heart rate. Ventilatory equivalent changes during exercise were significantly lower in group A than in the other two groups, and in group B compared to group C. Exercise-in- duced changes in oxygen pulse were signifi- cantly higher in group A, but no difference was found between groups Band C. Thus, gas- exchange function and overall exercise per- formance decrease with advancing age, where- as cardiovascular performance is well main- tained in normal elderly subjects. Discrimi- nant analysis showed that the exercise re- sponse conformed to the group-specific model in 74% and 79% of subjects in groups A and B, but only in 50% of the group C subjects; 5% and 45% of the elderly subjects were func- tionally classified in groups A and B, respec- tively. On the basis of these data, it may be concluded that aging accounts for a dramatic increase in interindividual variability in adap- tation to physical effort, and that the inverse relationship between age and exercise perfor- mance is mainly related to the declining effi- cacy of the respiratory response to effort with age. (Aging Clin. Exp. Res. 6: 267-275, 1994) INTRODUCTION The maximal oxygen uptake (V0 2 max) rep- resents the maximal ability of the cardiorespira- tory system to deliver oxygen to the periphery and the capacity of muscles to extract oxygen from the blood. Thus, both central and peripheral factors are the determinants of V0 2 max (1). The age-related physiological decrease in V0 2 max and exercise capacity has long been at- tributed to a progressively decreasing maximal cardiac output (2-4). However, it was recently rec- ognized that advancing age affects the maximal cardiac output only marginally, becau,se the Frank-Starling mechanism compensates for the age-related decrease in chronotropic response to effort (5-7). Accordingly, the previously reported negative effect of advancing age on maximal cardiac output is likely to depend on silent coro- nary artery disease and/or physical decondi- tioning (6). Therefore, attention should be focused on the other determinants of V0 2 max, Le., pul- monary and muscular factors, whose relative Key words: Aging, exercise test, interindividual variability, maximal oxygen uptake. Correspondence: Dr. Leonello Fuso, Fisiopatologia Respiratoria, Universita. Cattolica S. Cuore, Largo A. Gemelli 8, 00168 Roma, Italy. Received December 16, 1992; accepted October 5, 1993. Aging Clin. Exp. Res., Vol. 6, No.4 267

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Page 1: The cardiopulmonary response to incremental exercise test: The effect of aging

Aging Clin. Exp. Res. 6: 267-275, 1994

The cardiopulmonary response to incremental exercise test: The effect of aging L. Fuso1, R. Antonelli Incalzi2, R. Muzzolonl, M. Di Gennaro2, F. Gliozzil, R. Pistellil, and P.U. Carbonin2

lOepartment of Respiratory Physiology, 20epartment of Geriatrics, Catholic University, Rome, Italy

ABSTRACT The aims of the present study were to define the respective roles of the car­diac and respiratory response to exercise as de­terminants of the age-related physiological decrease in exercise performance, and to assess the relationship between aging and interindi­vidual variability in the response to effort. We studied.91 normal subjects recruited in three age-groups: Group A (42 children, aged 10±2 years); Group B (29 young adults, aged 27±5 years); Group C (20 elderly, aged 74±9 years). All the subjects underwent an incremental cy­cle ergometer exercise test with a work load in­crease of 15 W every 2 minutes in groups A and C, and 25 W every 2 minutes in group B, until they achieved 80% of the predicted max­imal heart rate. Ventilatory equivalent changes during exercise were significantly lower in group A than in the other two groups, and in group B compared to group C. Exercise-in­duced changes in oxygen pulse were signifi­cantly higher in group A, but no difference was found between groups Band C. Thus, gas­exchange function and overall exercise per­formance decrease with advancing age, where­as cardiovascular performance is well main­tained in normal elderly subjects. Discrimi­nant analysis showed that the exercise re­sponse conformed to the group-specific model in 74% and 79% of subjects in groups A and B, but only in 50% of the group C subjects; 5% and 45% of the elderly subjects were func­tionally classified in groups A and B, respec-

tively. On the basis of these data, it may be concluded that aging accounts for a dramatic increase in interindividual variability in adap­tation to physical effort, and that the inverse relationship between age and exercise perfor­mance is mainly related to the declining effi­cacy of the respiratory response to effort with age. (Aging Clin. Exp. Res. 6: 267-275, 1994)

INTRODUCTION

The maximal oxygen uptake (V02max) rep­resents the maximal ability of the cardiorespira­tory system to deliver oxygen to the periphery and the capacity of muscles to extract oxygen from the blood. Thus, both central and peripheral factors are the determinants of V02max (1). The age-related physiological decrease in V02max and exercise capacity has long been at­tributed to a progressively decreasing maximal cardiac output (2-4). However, it was recently rec­ognized that advancing age affects the maximal cardiac output only marginally, becau,se the Frank-Starling mechanism compensates for the age-related decrease in chronotropic response to effort (5-7). Accordingly, the previously reported negative effect of advancing age on maximal cardiac output is likely to depend on silent coro­nary artery disease and/or physical decondi­tioning (6). Therefore, attention should be focused on the other determinants of V02max, Le., pul­monary and muscular factors, whose relative

Key words: Aging, exercise test, interindividual variability, maximal oxygen uptake. Correspondence: Dr. Leonello Fuso, Fisiopatologia Respiratoria, Universita. Cattolica S. Cuore, Largo A. Gemelli 8, 00168 Roma, Italy. Received December 16, 1992; accepted October 5, 1993.

Aging Clin. Exp. Res., Vol. 6, No.4 267

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L. Fuso, R. Antonelli Incolzi, R. Muzzolon, et 01.

importance has not been well defined in older people.

That interindividual variability also increases with age is true for many physiological func­tions (8) and exercise capacity as well (9, 10). This finding may be relevant to the actual value and use of normal standards and reference equa­tions for the incremental exercise test (11). How­ever, the proportion of elderly normal subjects whose exercise performance does not conform to a model considered typical for their age is not clear from the literature.

The present study was designed to clarify the effects of aging on the respiratory and cardiac re­sponse to exercise, and the relationship between aging and interindividual variability in adapta­tion to effort.

SUBJECTS AND METHODS Study population Three groups of normal subjects were studied: - Group A consisted of 42 male children, aged

10.3± 1.8 years, range 8-14 years; - Group B was made up of 29 young adults,

14 males and 15 females, aged 26.9±4.8 years, range 19-40 years; and

- Group C comprised 20 elderly persons, 10 males and 10 females, aged 73.6±9.1 years, range 61-90 years.

Three subjects in group B and six in group C had stopped smoking for more than 5 years; two subjects in group B were still smoking less than 10 cigarettes a day.

A written informed consent was obtained from all study participants, or their parents. All subjects underwent a complete cardiac and respiratory evaluation based on clinical history, physical ex­amination, ECG recording, 20 echocardiogram, and spirometry. For these last two tests, normal reference values were obtained from Feigen­baum (12) and Knudson (13), respectively. The folloWing parameters were also determined in groups Band C: hemoglobin, red and white blood cell counts, hematocrit, corpuscular values, serum glucose, nitrogen, creatinine, sodium, potassium, calcium, phosphorus, albumin, amino­transferases, ammonia, bilirubin, cholesterol, and triglycerides.

Exclusion criteria were:

268 Aging Clin. Exp. Res., Vol. 6, No.4

1) any evidence of cardiac and/or pulmonary diseases according to history, clinical findings, ECG, 20 echocardiogram, spirometry;

2) any abnormality in one or more of the bio­chemical or hematologic parameters;

3) historical evidence of a completely sedentary life-style or heavy physical activity. Both B and C subjects walked daily for about two miles in 1 hour;

4) historical data and/or symptoms or physical findings of neurologic or orthopedic disease;

5) signs of malnutrition according to Mitchell et al. (14).

Exercise test An incremental work test was performed on a

calibrated, electrically braked cycle ergometer Dynavit Conditronic 30 (Keiper Oynavit, Kaisers­lautern, Germany). The initial work rate of 25 Watts was increased by 15 Watts every 2 minutes in groups A and C, and by 25 Watts every 2 min­utes in group B. Subjects exercised until they achieved 80% of the calculated maximal heart rate; the corresponding V02 (V02-80%HR) rather than V02max was employed as the last stage of the exercise in an attempt to obtain linear relationships between work power and physiological variables and, thus, improve dis­crimination among groups.

Additional criteria to stop the test were serious cardiac arrhythmias, hypotension, severe exer­cise-related symptoms, and muscular exhaus­tion.

Data collection and analysis Subjects breathed through a low resistance,

unidirectional valve (Hans Rudolph Inc, Kansas City, MO, U.S.A.) connected to a 5-L mixing chamber, and to a Fleisch No.3 pneumotacho­graph for respiratory flow measurement. Ex­pired gas samples from the mixing chamber were analyzed for oxygen (02) and carbon diox­ide (C02) content by a quadrupole mass spec­trometer Airspec 2000 (Airspec Ltd, Biggin Hill, Kent, u.K.). Measurements were taken before ex­ercise, while each subject was comfortably seat­ed on the cycle ergometer, and during the last 30 seconds of each work step. Automatically ac­quired data were processed on line by an HP-9825A computer, running an original software

Page 3: The cardiopulmonary response to incremental exercise test: The effect of aging

program for the measurement of pulmonary ventilation (VE) , frequency of breathing (f), tidal volume (VT), alveolar ventilation (VA), inspiratory to total respiratory cycle duration ratio (TIff TOT), mean inspiratory flow (VTffI), O2 uptake (V02), CO2 output (VC02), and VC02/V02 ratio, i.e., respiratory quotient (QR). Blood pressure was recorded at each work step; the heart rate (HR) and the electrocardiogram were continuously monitored.

The exercise-related changes in ventilatory equivalent for oxygen (VE/V02) and oxygen pulse (V02/HR) were calculated from the previ­ous variables, and were both corrected for body weight. It is noteworthy that a relatively low VE/V02 value states that a given V02 can be achieved without a very large increase in VE,

which is consistent with an efficient respiratory re­sponse to exercise (15-18). The efficiency of the cardiac response to exercise is directly pro­portional to V02/HR, since high V02/HR values mean that no large increase in HR is required to achieve a given V02 (15-18).

Statistical analysis Linear regression analysis was used to assess

the relationship between the physiological vari­ables and the work load. The validity of the linear models was estimated on the basis of r-squared values (19).

Differences between groups were assessed by one-way analysis of variance (ANOVA) and Tukey's multiple range test (19).

Effect of aging on exercise response

We used the discriminant analysis in order to define the correct classification of the subjects in­to the three age groups (19,20).

This technique proVided a cross-tabulation of the actual group membership us the predicted group membership, as identified by the effects of exercise on independent variables recorded dur­ing the test. Linear combinations of these vari­ables are formed in discriminant functions, and serve as the basis for classifying cases into one of the groups. Wilks' lambda coefficient was used to test the significance of the discriminant func­tions. The homogeneity of the exercise response of each group was expressed by the percentage of concordance between actual and predicted group membership (20).

RESULTS Table 1 reports the anthropometric variables

and respiratory functional parameters in each group of subjects.

The test was stopped before completing the 2-minute last stage in 2 subjects of group B, in 4 of group C because of muscular exhaustion, and in 1 subject of group C because of repetitive ventricular premature complexes. However, these subjects were not excluded from the study because they reached 80% of the calculated maximal HR.

The results of linear regression analysis are summarized in Table 2. The physiological re­sponse to work load of almost all the variables was accurately described by the linear models (r-

Table 1 - Anthropometric and respiratory functional data of the population studied.

Group A Group B Group C Children Adults Elderly

(mean±SD) (mean±SD) (mean±SD)

No. 42 29 20

Height (em) 14S.6±13.7 169.1±10.8 161.3±8.7

Weight (kg) 40.6±11.3 63.7±11.2 69.9±9.1

FVC (% pred) 94.9±9.S 106.3±13.6 109.1±21.6

FEVI (% pred) 89.6±8.9 100.4±13.1 101.7±21.3

FEVl/FVC (%) 86.2±S.4 81.4±S.8 74.6±9.7

FVC=forced vital capacity; FEVl=forced expiratory volume in 1 second.

Aging Clin. Exp. Res., Vol. 6, No.4 269

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L. Fuso, R. Antonelli Incalzi, R. Muzzolon, et al.

Table 2 - Mean values of r-squared derived from linear re-gressions having work load as independent variable.

r-squared Group A Group B Group C Children Adults Elderly

VE 0.96 0.96 0.96

VT 0.86 0.89 0.86

0.74 0.70 0.71

VTff, 0.95 0.95 0.95

T,ffTOT 0.42 0.22 0.65

V02 0.97 0.98 0.95

VC02 0.96 0.96 0.94

HR 0.96 0.94 0.94

VE=pulmonary ventilation; VT=tidal volume; f=frequency of breath­ing; VTffI=mean inspiratory flow; TIff TOT=inspiratory to total res­piratory cycle duration ratio; VOz=Oz uptake; VCOz=COz output; HR=heart rate.

LminfmL x kg-1/Walt

2.5

2

1.5

0.5

O...l...---

ANOVA: 71.2; p<O.001

_ Children c::J Adults DElderly

Values expressed as mean ± SD

Figure 1 - Comparison between groups in the exercise-re­lated changes of ventilatory equivalent.

270 Aging Clin. Exp. Res., Vol. 6, No.4

mUHR x kg-1/Watt

0.5

0.4

NS

0.3

0.2

0. 1

0--'------

ANOVA: 17.8; p<O.001

Children o Adults o Elderly

Values expressed as mean ± SD

Figure 2 - Comparison between groups in the exercise-re­lated changes of oxygen pulse. NS: not significant dif­ference between adults and elderly (Tukey's multiple range test).

squared >0.70). Only the exercise-related changes in T,/TToT were poorly correlated with work load. The facial mask supporting the Hans Rudolph valve may have contributed to increase the well-known interindividual variability in T,/TTOT (21, 22), and to weaken the correlation between this parameter and work load (23). For this reason, this variable was not further used in the discriminant analysis. The linear relation­ship between almost all variables and the work load (Table 2), and the achievement of 80% of the predicted maximal HR in all subiects, are reliable indicators that effective tests have be~· performed (15). ~I

Figure 1 shows that the exercise-induced changes in ventilatory equivalent were signifi~ cantly lower in group A than in group B, and in group B than in group C (group A: 1.16±0.3; group B: 1. 73±0.3; group C: 2.11±0.4 L­min/mL x kg-l/Watt; ANOVA: 71.2, p<O.OOl).

Page 5: The cardiopulmonary response to incremental exercise test: The effect of aging

Exercise-induced changes in oxygen pulse were higher in group A than in groups Band C (group A: 0.37±0.1; group B: 0.27±0.1; group C: 0.28±0.1 mL/HRxkg-1/Watt; ANOVA: 17.8, p<O.OOl) , but no significant difference was found between groups Band C (Fig. 2).

Figure 3 shows that the breathing pattern of group A subjects during the test was characterized by a significantly higher increase in f compared to groups Band C (group A: 0.18±0.04; group B: 0 .04±0.05; group C: 0 .09±0.05 f-min/Watt; ANOVA: 20.7, p<O .OOl) . In these two latter groups, the exercise-induced increase in VT was significantly higher than in group A (group A: 0.0051±0.001, group B: 0.0086±0.003; group C: 0.0083±0.003 L/Watt; ANOVA: 23.8 , p<O.OOl). Groups Band C did not differ either in f or in VT effort-related changes.

FREQUENCY OF BREATHING

f-minlWatt

0.25

0.2

0.15 NS

0 .1

005

0 ...1....---

ANOVA: 20.7; p<0.001

Effect of aging on exercise response

Figures 4 and 5 show the linear relationships between VE and V02 and between VE and VT in the elderly group, where these relations were significant.

Results of discriminant analysis are reported in Tables 3 and 4. Two discriminant functions were obtained, functions 1 and 2, accounting for 70% and 30% of the total between group variability, respectively. The Eigenvalue, i.e., the ratio of in­tergroup to intragroup sums of squares, was higher for function 1 (0.87 us 0.37), which is consistent with function 1 achieving a better dis­crimination. Wilks ' lambda, i.e. , the ratio of the intragroup sum of squares to the total sum of squares, was lower for function 1. This finding means that the intragroup variability was small compared to total variability, the latter depending mostly upon differences among groups (20) .

TIDAL VOLUME

lJWatt

0.010

0.008

0.006

0.004

0 .002

0...1....---

ANOVA: 23.8; p<0.001

_ Children c:::::=J Adu Its c:::::=J Elderly

Values expressed as mean ± SD

Figure 3 - Comparison between groups in the exercise-related changes of breathing pattern: frequency of breathing (left panel) and tidal volume (right panel). NS: not significant difference between adults and elderly (Tukey 's multiple range test).

Aging Clin. Exp. Res. , Vol. 6 , No. 4 271

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L. Fuso, R. Antonelli Incalzi, R. Muzzolon, et af.

r=O.88 2.1

0

1.5

~ '" 0

> 0.9

0

0.3 (;I

0.13 0.21 0.29 0.37 0.45

VEIW

Figure 4 - Experimental points, regression line, and cor­relation coefficient of the linear relationship between VE and V02 exercise-related changes, in the elderly group.

Both functions discriminated the groups sig­nificantly, although function 1 had a better dis­criminant power (Table 3). Exercise-related

Table 3 - Variables and discriminant functions used to dis­criminate groups.

Function Function 1 2

Coefficients

V E exercise-related changes 0.568 0.701

VTffj exercise-related changes 0.125 0.089

VOz exercise-related changes 0.491 -0.165

VCOz exercise-related changes -1.045 -0.494

HR exercise-related changes -0.623 -0.315

f exercise-related changes -0.618 0.658

Eigenvalue 0.87 0.37

Relative percentage of the total between groups variability 70.37 29.63

Wilks'lambda 0.39 0.73

p <0.0001 <0.0001

VE=pulmonary ventilation; VTifj=mean inspiratory flow; V02=02 uptake; VC02=C02 output; HR=heart rate; f=frequency of breath­ing.

272 Aging Clin. Exp. Res., Vol. 6, No.4

r=O.71 1.4

0

0 0

1.0 0 0 0 0 0

~ >

0.6

0

0 0.2

0

0.13 0.21 0.29 0.37 0.45

VEIW

Figure 5 - Experimental points, regression line, and cor­relation coefficient of the linear relationship between VE

and VT exercise-related changes, in the elderly group.

changes in VC02, HR, f and VE were the main determinants of the discriminant functions, i.e., of the differences among groups, as reflected by the magnitude of their respective discrimi­nant function coefficients (20).

Table 4 shows a cross-tabulation of the actual group membership us the group membership predicted by the comparative analysis of exercise­related changes in VE, VTffJ, V02, VC02, HR, and f. The concordance between actual and pre­dicted group membership was high in both groups A (73.8%) and B (79.4%). On the other hand, the response to exercise conformed to

Table 4 - Percentages of concordance between actual and predicted group membership.

Actual No. of Predicted group group cases membership

Group A Group B Group C

Group A 42 31 (73.8%) 10 (23.8%) 1 (2.4%) (Children)

Group B 29 3 (10.3%) 23 (79.4%) 3 (10.3%) (Adults)

Group C 20 1 (5%) 9(45%) 10 (50%) (Elderly)

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the group-specific pattern in only SO% of the group C subjects, whereas in the remaining 4S% and S% it conformed to group B and A pat­tern, respectively.

DISCUSSION

The Widely recognized inverse relationship between maximal exercise performance and age is generally attributed to a progressive decline in the functional capacity of the cardiovascular and respiratory systems and to a loss of muscle mass. Our results show a significant decline in overall respiratory efficiency with advancing age. In fact, the exercise test was performed by elderly subjects with a maximum increase in ventilatory equivalent (Fig. 1). On the contrary, in children, the srri~ller increase in ventilation needed to achieve a given increase in oxygen consump­tion, clearly indicates low resistances to oxygen flow, and a better exercise performance. Thus, the ventilatory equivalent can also be consid­ered as an indicator of overall exercise capacity (IS, 18).

The decreased efficacy of pulmonary gas-ex­change is the most likely explanation for the Significant increase with aging of the ventilatory equivalent changes during exercise. Indeed, the age-related decrease in the elastic properties of the lungs can explain an increased closing ca­pacity of the airways and a lower arterial oxygen tension in elderly normal subjects (24, 2S). Our results confirm that aging affects the efficacy of the pulmonary gas-exchange mechanisms (26), and indicate that aging plays an important role in work capacity decline.

However, peripheral factors may partly ac­count for the direct relationship between aging and ventilatory equivalent. It is known that the age-related changes in muscle power and metabolism, as well as oxygen transport mech­anisms are important factors in decreasing the maximal work capacity with aging (6) because they reduce the arteriovenous O2 difference and diminish the capacity of exercising muscles to ex­tract O2 from the blood (1). The oxygen supply pathway may be altered with advancing age in this way, and consequently cause a ventilation ex­cess per unit of oxygen consumption, i.e., an in­crease in the ventilatory equivalent during exer-

Effect of aging on exercise response

cise. However, our results do not allow us to assess the role of the peripheral determinants of the ventilatory equivalent.

Our data exclude that a deficiency in stroke vol­ume is able to explain the decline in exercise per­formance with aging. Stroke volume is related to the oxygen pulse during exercise (IS, 27) and, in our sample, no significant difference in oxygen pulse was found between young adult and el­derly subjects during exercise (Fig. 2). These da­ta confirm recent reports (S-7), and suggest that the cardiac response to exercise is fairly good in healthy elderly subjects.

Finally, it is likely that the ventilatory response, as defined by f and VT , is uninvolved in the de­crease in exercise performance with aging, as no difference was found between adult and elderly subjects in the breathing pattern changes during exercise (Fig. 3).

The second goal of this study was to assess in­terindividual variability in response to effort in old­er people. For this reason, although the sample studied was not very large, care was taken to re­cruit subjects with a wide age distribution to ob­tain a good separation between groups. More­over, subject fitness and level of habitual activity were quite homogeneous within each age-group, as was sex distribution, except for the pediatric group in which all subjects were male. However, this absolute predominance of males in group A did not affect the comparison between groups, as it is known that the response to exercise is un­related to sex until puberty (IS). Our data confirm the increase in variability with aging, and show that the percentage of variability is considerable in the geriatric population. The results of dis­criminant analysis clearly indicated that the chil­dren and young adults were correctly classified in the proper functional group with quite compa­rable accuracy. On the contrary, elderly subjects suffered from a significant misclassification; only SO% of these subjects showed a response to ef­fort which conformed to that considered typical for this age group, whereas 4S% performed like young adults and, in one case, as children (Table 4). A careful analysis of the basic anatomic and physiologic features and life-style of the misclas­sified elderly subjects could not detect any dif­ference between these and the correctly classified elderly persons. Thus, the individual response of

Aging Clin. Exp. Res., Vol. 6, No.4 273

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L. Fuso, R. Antonelli Incalzi, R. Muzzolon, et al.

the healthy elderly person to exercise seems to be unpredictable.

Exercise-related changes in VC02, HR, f and V E were the main determinants of intergroup variability (Table 3). The well-known inverse re­lationship between aging and exercise-related increase in VC02 (18), and the age-related dif­ferences between cardiac and respiratory adap­tation to exercise account for the high discrimi­nant power of these variables.

The increase in interindividual variability with aging lends support to the findings of Jones et al. (9) that the prediction equations for maximal ex­ercise capacity lose their value when used on populations at age and height extremes. Consid­ering these results, these workers derived new ref­erence equations based on an interactive and nonlinear influence of age on exercise capacity (9).

Some limitations in our study deserve mention. Firstly, silent coronary artery disease could not be completely excluded because myocardial scintig­raphy was not performed. However, cardiac performance, as indicated by the oxygen pulse, corresponded to a normal heart function. Sec­ondly, the cardiac response to exercise was not assessed in as much detail as the respiratory re­sponse, because only noninvasive measurements were taken.

Despite these limitations, the present study confirms that age is characterized by a large in­crease in interindividual variability and a decreased efficacy of the respiratory response, and thus helps to clarify the relationship between age and exercise capacity. These findings should be con­sidered when exercise test results are interpreted. Future studies should aim at confirming the role possibly played by muscle factors and the O2 transport mechanisms in influencing the age-re­lated decrease in V02max and exercise capacity.

ACKNOWLEDGEMENT The authors wish to thank Miss Julie A. Karimi for her

help in preparing the manuscript.

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