Download Randomized controlled trial of home-based

Clinical Science (2001) 101, 477–483 (Printed in Great Britain)
Randomized controlled trial of home-based
exercise training to evaluate
cardiac functional gains
Paul MARSHALL, Jawad AL-TIMMAN, Rhona RILEY, Jay WRIGHT, Simon WILLIAMS,
Roger HAINSWORTH and Lip-Bun TAN
Institute for Cardiovascular Research, University of Leeds, Yorkshire Heart Centre, Leeds General Infirmary, Leeds LS1 3EX, U.K.
A
B
S
T
R
A
C
T
There is evidence that multiple benefits can be obtained through exercise training that leads to
increases in peak oxygen consumption (VI O2). It is unclear whether significant improvements can
also be achieved through unsupervised low-budget home-based training regimes, especially in
terms of cardiac functional gains. A randomized cross-over trial was conducted to investigate the
effects of a home-based unsupervised exercise training programme of moderate intensity on
aerobic capacity, cardiac reserve and peak cardiac power output in healthy middle-aged
volunteers. Nine subjects with no known cardiovascular diseases performed symptom-limited
treadmill cardiopulmonary exercise tests after an 8-week period of exercise training, and results
were compared with those obtained after a similar ‘ non-exercising ’ control period. Cardiac
output was measured non-invasively during exercise tests using the CO2-rebreathing method.
With exercise training, resting heart rate decreased significantly from 88n3p3n4 to 78n7p
3n2 beats:min−1 (P 0n05), heart rate at a submaximal workload (VI O2 l 1n5 litres:min−1) decreased from 125n5p2n4 to 115n5p1n6 beats:min−1, and peak VI O2 increased by 9 % from 2n62p
0n19 to 2n85p0n18 litres:min−1 (P 0n01). Baseline cardiac power output was 1n11p0n05 W,
and this remained unchanged with training. Peak cardiac power output increased by 16 % from
4n1p0n3 to 4n7p0n3 W (P 0n001), and cardiac reserve increased by 21 % (P 0n01). A major contribution to these increases was from the 11 % increase in stroke volume, from 100n1p5n3
to 111n2p6n2 ml (P 0n001). All subjects reported more positive perceptions of their health
(P 0n05), fitness (P 0n01) and levels of activity (P 0n01) after the training period. These
results show that motivated subjects undergoing low-budget unsupervised home-based exercise training of moderate intensity can derive benefit in terms of symptoms, aerobic capacity and
cardiac functional reserve.
INTRODUCTION
There is evidence from classic studies involving normal
young and middle-aged adults [1–4], and from more
recent studies particularly involving older adults [5–9],
that benefits can be obtained through exercise training.
Although specific to the intensity and type of training
programme, exercise training can lead to an increase in
peak oxygen consumption (VI O max) [1–9], which may
#
be achieved through cardiac adaptation resulting in
increased peak cardiac output [10,11] and peripheral
adaptations leading to greater oxygen utilization [12], or
Key words: cardiac power output, cardiopulmonary exercise testing, oxygen consumption.
Abbreviations: CPO, cardiac power output ; VI , oxygen consumption ; VI max, peak oxygen consumption.
O#
O#
Correspondence: Dr L.-B. Tan (e-mail lbtan!ulth.northy.nhs.uk).
# 2001 The Biochemical Society and the Medical Research Society
477
478
P. Marshall and others
both. Regular aerobic exercise has many cardiovascular
effects in both men and women [13–15], and may even
reduce the risk of fatal or non-fatal myocardial infarction,
as well as other coronary events [16–18]. There is
increasing evidence that regular aerobic exercise provides
some degree of prognostic benefit in the prevention of
coronary events [16–18]. The costs of joining exercise
classes or clubs are often beyond the means of the
majority of populations. Therefore, for motivated individuals, the possibility of performing a low-budget
home-based exercise training regime is attractive, but it is
unclear whether such a regime can confer sufficient
benefit, especially in terms of cardiovascular function.
Exercise training has been shown to improve VI O max
#
[1–9] and skeletal muscle function [12,19,20]. The performance of each group of skeletal muscles can be readily
measured [12,19,20]. The enhanced peak performance of
all the exercising muscles contributes towards the higher
VI O max. The performance of cardiac and vascular
#
systems, however, is not as readily measured during
assessments of the impact of exercise training. Part of the
reason is that commonly measured clinical parameters of
cardiac function, such as left ventricular ejection fraction,
are unsatisfactory indicators of the efficacy of the effects
of training on cardiac function [21]. Increases in left
ventricular end-diastolic diameter at rest and at peak
exercise [22–25] following exercise training have been
demonstrated. Studies investigating changes in myocardial contractility have been inconsistent. Using the
extent or velocity of circumferential fibre shortening as
an index, increases [26] or decreases [27] in contractility
have been reported. In endurance-trained older men,
cardiac adaptations are characterized by volumeoverloaded left ventricular hypertrophy and enhancement of left ventricular peak systolic performance [23]. It
is also difficult to be certain that an observed improvement in a component function is not negated by a
deterioration in another component function (e.g. more
myocardial hypertrophy through power training in a
subject with hypertrophic cardiomyopathy, thereby
worsening ventricular diastolic dysfunction), giving an
overall lack of improvement or even a deterioration.
There is a need to use a reliable and representative
variable to evaluate overall cardiac function
The use of various indices to assess cardiac performance, particularly in relation to heart failure, has been
re-examined, and an alternative conceptual approach
of evaluating physiological cardiac reserve has been
proposed [30,31]. We have also developed a non-invasive
method of measuring such functional reserve [28] based
on the conceptual basis formulated [29–31]. Recent
investigations have shown that peak power cardiac
output is not only a major determinant of exercise
capacity [28,30], but is also the most powerful predictor
of prognosis in cohorts of heart failure patients [31–34].
To our knowledge, this form of cardiac evaluation has
# 2001 The Biochemical Society and the Medical Research Society
not been applied in the assessment of the cardiac response
to exercise training. The purpose of the present study was
to use this method to investigate how much cardiac
functional gain can be achieved through moderateintensity exercise training in healthy volunteers.
METHODS
Subjects
Nine middle-aged subjects (eight male and one female),
with a meanpS.D. age of 58n1p7n0 years and body
weight of 79n6p7n3 kg, who had no known history or
physical evidence of cardiovascular or respiratory diseases, volunteered to participate in the study. The age
and weight criteria were selected to reflect the age group and
weights of patient populations presenting with coronary
artery disease. All participants were fully informed about
the study, which had been approved by the local hospital
ethics committee, and all gave written consent.
Study protocol
This was a randomized cross-over study, during which
each subject was tested following 8 weeks of exercise
training (training phase) and 8 weeks of ‘ non-exercising ’.
All participants underwent the tests before and after
both the non-exercising control and training phases.
Exercise testing
All participants attended the laboratory before starting
the study, to undergo a period of familiarization in order
to improve the reproducibility of the exercise tests [35,36]
and to confirm the absence of any cardiovascular disease.
The subjects performed symptom-limited treadmill exercise tests, using a programmable treadmill (Quinton ;
model no. Q55). The participants performed a 1-min
incremental test developed in our laboratory. Blood
pressure was monitored every 3 min during exercise, and
heart rate was monitored continuously. On-line breathby-breath respiratory gas analysis was performed at rest,
during the incremental test and during the recovery
period, using the MedGraphics CardiO Cardio#
pulmonary Exercise testing system (Medical Graphics
Corporation, St. Paul, MN, U.S.A.).
Following a rest period of at least 30 min, to ensure
that VI O , end-tidal partial pressure of CO , heart rate and
#
#
blood pressure had returned to within 5 % of the preincremental test values, cardiac output was measured at
rest. Then, during a constant-load test, with the workload
set to achieve VI O levels within 5 % of the VI O max
#
#
attained during the incremental test, cardiac output was
again measured. At least three estimates of cardiac output
were taken both at rest and during the constant-load
exercise test. At rest, estimates of cardiac output were
Exercise training improves cardiac reserve
made using the equilibrium CO -rebreathing method,
#
while during peak exercise the exponential CO #
rebreathing method was employed [28].
Exercise training protocol
Participants trained for 8 weeks at home, on a static,
upright cycle (Tunturi F220). They were instructed to
exercise at 50 rev:min−" for a 20 min period on 5 days per
week, with the resistance on the flywheel set to produce
a heart rate that was consistent with a VO at 75–80 % of
#
the VI O max achieved during the control incremental test.
#
Heart rate was monitored using a commercial shortdistance telemetry system (Polar Fitness Watch, Polar,
Finland). Heart rate was used as there were no facilities to
monitor VI O in the home. Compliance to the training
#
protocol was assessed from a measure of the ‘ distance
covered ’ during the training, based on a count of the
number of cycle wheel revolutions. Poor compliance was
judged as a training distance of less than 60 % of a
potential maximum distance. Participants also completed
a daily exercise diary. Additional exercise, e.g. walking,
cycling and swimming, was also allowed, but the extent
of this was not quantified formally. Following 4 weeks of
exercise, participants underwent an incremental test to
assess for any training effect and to allow for the setting
of a new target heart rate for the remainder of the training
period.
Non-exercising control phase
During this period, all participants were instructed to
carry out their pre-baseline activities and to avoid any
additional exercise. Individuals who performed weekly
activities, such as swimming and golf, were asked to avoid
such activities until after the non-exercising control
period.
Self-assessment questionnaire
During each visit a self-assessment questionnaire, based
on a Likert scale (see Table 2), was completed.
Calculations
Treadmill workload was estimated using the following
equation [37] :
Workload (W) l (weightispeedisin β)\6n12
where weight is in kg, speed is in m:min−" and β is the
angle of elevation.
Cardiac power output (CPO) was calculated from the
averaged cardiac output and mean arterial pressure using
the following equation [29] :
CPO l (QiMAP)iK
where CPO is in W, Q is cardiac output in litres:min−",
MAP is mean arterial pressure in mmHg, and K is the
conversion factor (2n22i10−$). Cardiac reserve is equal
to the difference between baseline resting CPO and peak
CPO.
Arteriovenous O content difference, expressed as ml
#
of O \dl, was calculated as (VI O \Q)i100. The anaerobic
#
#
threshold was calculated off-line on completion of the
exercise test, using the V-slope method proposed by
Beaver et al. [38].
Statistical analysis
For data with a normal distribution, comparisons between each period of the study were compared using
ANOVA and Student’s t-test. The self-assessment
questionnaires were analysed using the Mann–Whitney
U test. Statistical significance was taken to be P 0n05 in
all cases. Data are presented as meanspS.E.M. unless
otherwise indicated. The presence of a training effect was
determined by analysing the heart rate–VI O relationship
#
[39,40]. A statistically significant decrease in the elevation
of the computed regression line relating heart rate to VI O
#
after training was regarded as evidence of a training
effect. In addition, the heart rates at a fixed submaximal
VI O before and after training were also compared to
#
confirm the presence of a training effect [41].
RESULTS
Following the training period, when compared with the
non-exercise control period, all subjects had a lower
heart rate at rest (78n7p3n2 and 88n3p3n4 beats:min−"
respectively ; P 0n05). In addition, at a submaximal
workload (VI O 1n5 litres:min−") the mean heart rate
#
was lower after training (115n5p1n6 beats:min−") than
after the ‘ non-exercising control ’ phase (125n5p
2n4 beats:min−" ; P 0n001). Only three of the nine subjects showed a significant decrease in the heart rate–VI O
#
relationship.
Following training, VI O max was increased significantly
#
by 9 %, to 2n85p0n18 litres:min−", compared with values
of 2n62p0n19 litres:min−" after the non-exercising control phase (P 0n01) and 2n64p0n17 litres:min−" at
baseline (P 0n05). Mean body weight did not alter
significantly throughout the study. Baseline mean body
weight was 80n11 kg, compared with 79n89 kg following
the non-exercising control period and 79n67 kg following exercise training. After training, subjects exercised
for significantly longer [762p34 s, compared with 679p
27 s following the non-exercising control phase (P
0n001) and 642p29 s at baseline (P 0n001)]. They also
achieved a higher peak workload after training [333p
25 W, compared with 272p22 W following the nonexercising control phase (P 0n001) and 252p26 W at
baseline (P 0n001)].
# 2001 The Biochemical Society and the Medical Research Society
479
480
P. Marshall and others
Table 1
Summary of haemodynamic, respiratory and exercise data for normal subjects
Values are presented as means (S.E.M.) (n l 9). Abbreviations : HR, heart rate ; SBP, systolic blood pressure ; DBP, diastolic blood pressure ; MAP, mean arterial pressure ;
Q, cardiac output ; SV, stroke volume ; SVR, systemic vascular resistance ; CPO, cardiac power output ; a-vdO2, arteriovenous O2 content difference ; AT, anaerobic threshold ;
AT ( %), anaerobic threshold as a percentage of VOI 2max ; ET, exercise time ; WLmax, maximum workload. Significance of differences : **P 0n01, ***P 0n001 postexercise training compared with baseline ; †P 0n05, ††P 0n01 and †††P 0n001 post-exercise training compared with non-exercising period.
Rest
Variable
HR (beats:min−1)
SBP (mmHg)
DBP (mmHg)
MAP (mmHg)
Q (l:min−1)
SV (ml)
CPO (W)
a-vdO2 (ml of O2/dl)
SVR (dynes:s:cm−5)
VOI 2 (l:min−1)
VOI 2/kg (ml:min−1:kg−1)
AT (l:min−1)
AT ( %)
ET (s)
WLmax (W)
Baseline
Maximum exercise
Non-exercise control
86n67 (5n21)
125n56 (4n12)
76n67 (2n36)
92n96 (2n48)
5n39 (0n17)
64n23 (4n66)
1n11 (0n05)
88n33 (3n44)
130n60 (5n92)
78n89 (2n98)
96n12 (3n77)
5n40 (0n16)
61n92 (3n15)
1n15 (0n06)
1397 (59n00)
0n37 (0n03)
4n66 (0n31)
1462 (77n60)
0n42 (0n03)
5n22 (0n34)
Post-exercise training
78n67 (3n19)†
128n33 (4n17)
81n11 (2n17)
96n82 (2n71)
5n44 (0n18)
70n28 (4n14)
1n18 (0n05)
1436 (52n40)
0n40 (0n03)
5n11 (0n40)
Baseline
Non-exercise control
Post-exercise training
169n11 (2n83)
170n56 (5n92)
76n11 (2n98)
107n30 (2n76)
17n14 (1n26)
101n11 (6n82)
4n13 (0n38)
15n52 (0n31)
517 (32n40)
2n64 (0n17)
32n79 (1n77)
1n74 (0n08)
66n63 (2n60)
642 (29)
252 (26)
168n67 (3n40)
173n33 (6n29)
75n56 (2n69)
108n06 (3n31)
16n88 (0n95)
100n06 (5n33)
4n05 (0n30)
15n41 (0n42)
519 (26n80)
2n62 (0n19)
32n42 (2n24)
1n72 (0n09)
66n12 (3n13)
679 (27)
272 (22)
170n11 (3n93)
179n44 (7n70)
77n22 (2n22)
111n26 (2n63)
18n92 (1n11)**, ††
111n23 (6n18)***, †††
4n70 (0n35)***, †††
15n05 (0n21)
482 (26n70)
2n85 (0n18)**, ††
36n10 (2n26)**, ††
1n74 (0n12)
61n41 (3n81)
762 (34)***, †††
333 (25)***, †††
Figure 2 CPO at rest and at VI O2max in normal subjects
following the non-exercising control phase and the training
phase
Figure 1 Mean peak CPO and individual CPO estimates for
normal subjects in the various phases of the study
Post-training values were significantly greater than the baseline (P 0n001) and
non-exercise control (P 0n001) values. Individual data are presented, along
with the meanpS.E.M. The * symbol denotes the female participant.
Table 1 shows measured and derived values obtained at
the baseline study and following the non-training and
training phases. Apart from heart rate showing a significantly lower value (P 0n05) after the training compared
with the non-training period, comparison of other values
# 2001 The Biochemical Society and the Medical Research Society
obtained while the subjects were at rest showed no other
significant differences after the training compared with
the non-exercising control period.
Peak heart rate and anaerobic threshold did not alter
with training status. However, CPO, stroke volume and
cardiac output at peak exercise were significantly greater
following exercise training (Table 1 and Figures 1 and 2)
compared with baseline and non-exercising control
values. Peak CPO increased by 16 % from 4n05p0n30 W
following the non-exercising control period to
4n70p0n35 W after exercise training (P 0n001), and
cardiac reserve increased by 21 % (P 0n01). A major
Exercise training improves cardiac reserve
Table 2
Summary of the responses by normal subjects to the self-assessment questionnaire
Scoring key : for all questions, the lower the score, the more positive the response. Median values are shown. Significance was assessed using the Mann–Whitney
U-test ; NS, not significant.
Score
Question
Baseline
Non-exercise control
Post-training
Over the past 2 weeks how do you feel about :
Your health
Your level of fitness
Your outlook on life in general
Your ability to perform your daily activities
Your ability to sleep
Your level of energy
Your social life, going out and seeing friends
Your sexual activity
2
3
2
1
1
2
2
3
2
3
1
1
1
2
2
3
1
2
1
1
1
2
2
2
Since your last visit have you noticed any difference in your :
Quality of life
Outlook on life
Level of fitness
Level of activity
3
3
3
3
3
3
3
3
3
3
2
2
contribution to these improvements was observed in the
significant 11n2 % rise in peak stroke volume, from
100n1p5n3 to 111n2p6n2 ml (P 0n001). In the absence
of significant changes in peak heart rate, this increase was
similar to the 12 % increase in peak cardiac output (from
16n9p0n95 to 18n9p1n1 litres:min−" ; P 0n01). There
were non-significant increases in mean arterial pressure
and decreases in systemic vascular resistance and arteriovenous O content difference.
#
With regard to the responses to the self-assessment
questionnaire, as shown in Table 2, subjects were
significantly more positive in their perceptions of their
health (P 0n05), fitness (P 0n01) and levels of activity
(P 0n01).
DISCUSSION
This randomized controlled study has demonstrated that,
in motivated volunteers, a home-based unsupervised
8-week exercise training programme of moderate intensity significantly increased exercise capacity, VI O max and
#
exercise duration, and led to a subjective improvement in
quality of life. The increase in VI O max of 9 % was due to
#
a large extent to the improvements in overall cardiac
function, as shown by a 16 % increase in peak CPO and
a 21 % increase in cardiac reserve. The largest contribution to the enhanced cardiac function was through
the 11 % increase in peak exercise stroke volume, with
smaller (non-statistically significant) increases in peak
exercise heart rate and mean arterial pressure.
These results are notable for two reasons. First, CPO
at rest and during peak exercise has not been
P value
0n05
0n01
NS
NS
NS
NS
NS
NS
NS
NS
0n01
0n01
characterized non-invasively in healthy middle-aged
volunteers, and the effect of exercise training on peak
CPO has also never been assessed in this category of
human subjects. Consistent with a previous estimation
[30], the resting CPO of an average European adult
was found to be between 1n1 and 1n2 W (Table 1). The
peak exercise CPO of the cohort of healthy volunteers
before training was approx. 4n1 W, and this increased to
4n7 W after a period of moderate unsupervised training.
Secondly, the present study has demonstrated that, in
appropriately motivated individuals, low-budget homebased unsupervised exercise training programmes can
provide significant functional and cardiac benefits.
Whether the improvement could be greater with supervised exercise training programmes in healthy middleaged individuals has not been evaluated systematically.
The observed 9 % increase in VI O max was not as high
#
as the increases of 18 % reported by Saltin et al. [1], 16 %
by Ekblom et al. [2] or 17–21 % by Stratton et al. [25].
The differences in the magnitude of the increment may be
explained by differences in the age range of the subjects
and in the mode and intensity of the exercise training
programmes. In all the quoted cases, the training was
supervised in training centres and lasted longer. Ekblom
et al. [2] studied young men aged between 19 and 27 years
and used a 16-week programme involving cross-country
running ; VI O max increased by 16 %. The mean baseline
#
peak CPO of these subjects was 5n7 W, which was 1n6 W
greater than that in our study population, suggesting that
these subjects also had superior cardiac function. After
training, their power output increased to 6n8 W, an
increment of 17 %, which was similar in magnitude to
that found in our study population. Stratton et al. [25]
# 2001 The Biochemical Society and the Medical Research Society
481
482
P. Marshall and others
studied younger and older subjects, and adopted a
6-month training programme, incorporating walking,
jogging and cycling. In their older age group (mean age
68p6 years), VI O max increased by 21 %, compared with
#
an increase of 17 % in the younger group (age 28p
3 years). In our study the duration of training was shorter.
Saltin et al. [1] showed that the largest increases in V} O
#
occurred in the students who were less fit at the start of
the study. Peak VI O only increased by 4 % in their active
#
subjects [1]. Some of the volunteers in our study were
reasonably fit at the start, and this could explain the
relatively modest degree of improvement.
In the present study we have demonstrated that central
haemodynamic adaptations to training can occur in
healthy middle-aged subjects. We did not set out to
address the effects of training on skeletal muscle physiology, which has been extensively investigated and
reported [12,19,20]. We have shown that moderateintensity exercise training does have beneficial effects on
the performance of the heart itself. Consistent with
previous studies [2,3,25] there was a significant fall in
resting heart rate and a 12 % increase in cardiac output.
Compared with our study, Ekblom et al. [2] reported a
smaller increase in peak cardiac output (8 %), whereas the
increase reported by Stratton et al. [25] was larger (16 %).
The differences quoted in the literature may be explained
by the fact that different exercise testing protocols were
used, along with different training protocols. Exercise
testing on a bicycle ergometer imposes a greater demand
on the contractile power of the exercising leg muscles,
thereby putting a different strain on the cardiopulmonary
system than testing on a treadmill. Ekblom et al. [2] used
cycle ergometry, whereas Stratton et al. [25] used
treadmill testing. The degree of central haemodynamic
adaptation may be directly related to the intensity and
duration of training. As shown in patients with chronic
heart failure [42] and in patients following myocardial
infarction [43], high-intensity training is required to
produce central training effects.
Spina et al. [44] demonstrated that gender differences
may also affect changes in cardiac output following
exercise training. They demonstrated that, in older
women (60–69 years), the increase in VI O was accounted
#
for by an increase in the arteriovenous oxygen content
difference. In contrast with their findings, the one female
participant in the present study did increase her cardiac
output, by 13n0 %. Indeed, her 5n0 % increase in VI O was
#
achieved as a result of the increase in cardiac output, as
her arteriovenous oxygen content difference was slightly
lower following exercise training compared with values
at baseline and after the non-exercise phase. However,
our female participant was much younger (50 years old)
than the female subjects in the study of Spina et al. [44]
It is worth mentioning that our investigation found
that exercise training produced beneficial effects on
cardiac function and, of all the indicators of cardiac
# 2001 The Biochemical Society and the Medical Research Society
function, the greatest percentage improvements were
observed in peak exercise CPO and cardiac reserve. This
finding is consistent with the concept that the overall
peak function of the heart is best represented by the peak
CPO, which reflects the cumulative sum of the (positive
and negative) changes in various component functions of
the heart. The feasibility of achieving improvements in
CPO through physiological means, i.e. exercise training,
may also have important implications, in the light of
findings indicating that peak CPO is the most powerful
predictor of prognosis in cohorts of patients with heart
failure [29,32–34,45]. Whether comparable improvements in peak CPO can be achieved through pharmacological or surgical therapy requires further study.
In conclusion, we have shown that, in motivated
participants, home-based unsupervised exercise training
on cycle ergometers can improve exercise capacity,
VI O max, exercise duration, cardiac functional gains, and
#
perceived fitness and health. The results also suggest that
evaluation of peak CPO and cardiac reserve provides a
useful index for directly quantifying the overall cardiac
functional gain obtainable through exercise training.
Further research is required to investigate whether
patients with cardiac disease and heart failure can acquire
similar gains, and whether the functional gain is due to
any improvement in the intrinsic function of the heart.
ACKNOWLEDGMENTS
This study was supported in part by a research grant
awarded by the British Heart Foundation.
REFERENCES
1
Saltin, B., Blomqvist, G., Mitchell, J. H., Johnson, Jr.,
R. L., Wildenthal, K. and Chapman, C. B. (1968) Response
to exercise after bed rest and after training : a longitudinal
study of adaptive changes in oxygen transport and body
composition. Circulation 38 (Suppl. VII), VII-1–VII-78
2 Ekblom, B., AH strand, P.-O., Saltin, B., Stenberg, J. and
Wallstro$ m, B. (1968) Effect of training on circulatory
response to exercise. J. Appl. Physiol. 24, 518–528
3 Clausen, J. P., Klausen, K., Rasmussen, B. and TrapJensen, J. (1973) Central and peripheral circulatory
changes after training of the arms and legs. Am. J.
Physiol. 225, 675–682
4 Hanson, J. S., Tabakin, B. S., Levy, A. M. and Nedde, W.
(1968) Long term physical training and cardiovascular
dynamics in middle aged men. Circulation 38, 783–799
5 Stein, P. K., Ehsani, A. A., Domitrovich, P. P., Kleiger,
R. E. and Rottman, J. N. (1999) Effect of exercise training
on heart rate variability in healthy older adults.
Am. Heart J. 138, 567–576
6 Steinhaus, L. A., Dustman, R. E., Ruhling, R. O. et al.
(1990) Aerobic capacity of older adults : a training study.
J. Sports Med. Phys. Fitness 30, 163–172
7 Posner, J. D., Gorman, K. M., Windsor-Landsberg, L.
et al. (1992) Low to moderate intensity endurance
training in healthy older adults : physiological responses
after four months. J. Am. Geriatr. Soc. 40, 1–7
8 Melanson, E. L., Freedson, P. S. and Jungbluth, S. (1996)
Changes in V} max and maximal treadmill time after
O#
9 weeks of running
or in-line skate training. Med. Sci.
Sports Exercise 28, 1422–1426
Exercise training improves cardiac reserve
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Dunn, A. L., Garcia, M. E., Marcus, B. H., Kampert,
J. B., Kohl, H. W. and Blair, S. N. (1998) Six-month
physical activity and fitness changes in Project Active, a
randomised trial. Med. Sci. Sports Exercise 30, 1076–1083
Blomqvist, C. G. and Saltin, B. (1983) Cardiovascular
adaptations to physical training. Annu. Rev. Physiol. 45,
169–189
Ehsani, A. A., Ogawa, T., Millar, T. R., Spina, R. J. and
Jilka, S. M. (1991) Exercise training improves left
ventricular function in older men. Circulation 83, 96–103
Holloszy, J. O. and Coyle, E. F. (1984) Adaptations to
skeletal muscle endurance exercise and their metabolic
consequences. J. Appl. Physiol. 56, 831–838
Paffenbarger, Jr., R. S., Hyde, R. T., Wing, A. L., Lee,
I.-M., Jung, D. L. and Kampert J. B. (1993). The
association of changes in physical-activity level and
other lifestyle characteristics with mortality among men.
N. Engl. J. Med. 328, 538–545
Sandvik, L., Erikssen, J., Thaulow, E., Erikssen, G.,
Mundal, R. and Rodahl, K. (1993). Physical fitness as a
predictor of mortality among healthy, middle-aged
Norwegian men. N. Engl. J. Med. 328, 533–537
Kushi, L. H., Fee, R. M., Folsam, A. R., Mink, P. J.,
Anderson, K. E. and Sellers, T. A. (1997). Physical
activity and mortality in postmenopausal women. JAMA,
J. Am. Med. Assoc. 277, 1287–1292
Kohl, H. W., Powell, K. E., Gordon, N. F., Blair, S. N.
and Paffenbarger, Jr., R. S. (1992). Physical activity,
physical fitness and sudden cardiac death. Epidemiol.
Rev. 14, 37–58
Lemaitre, R. N., Siscovick, D. S., Raghunathan, T. E.,
Weinmann, S., Arbogast, P. and Lin, D. Y. (1999)
Leisure-time physical activity and the risk of primary
cardiac arrest. Arch. Intern. Med. 159, 686–690
Berlin, J. A. and Colditz, G. A. (1990) A meta-analysis of
physical activity in the prevention of coronary heart
disease. Am. J. Epidemiol. 132, 612–628
Wibom, R., Hultman, E., Johansson, M., ConstantinTeodosiu, D. and Schantz, P. G. (1992) Adaptation of
mitochondrial ATP production in human skeletal muscle
to endurance training and detraining. J. Appl. Physiol. 73,
2004–2010
Turner, D. L., Hoppeler, H., Claassen, H. et al. (1997)
Effects of endurance training on oxidative capacity and
structural composition of human arm and leg muscles.
Acta Physiol. Scand. 161, 459–464
Crawford, M. H., Petru, M. A. and Rabinowitz, C. (1985)
Effect of isotonic exercise training on left ventricular
volume during upright exercise. Circulation 72,
1237–1243
Rerych, S. K., Scholz, P. M., Sabiston, D. C. and Jones,
R. H. (1980) Effects of exercise training on left ventricular
function in normal subjects : a longitudinal study by
radionuclide angiography. Am. J. Cardiol. 45, 244–252
Seals, D. R., Hagberg, J. M., Spina, R. J., Rogers, M. A.,
Schechtman, K. B. and Ehsani, A. A. (1994) Enhanced left
ventricular performance in endurance trained older men.
Circulation 89, 198–205
Stein, R. A., Michielli, D., Diamond, J. et al. (1980) The
cardiac response to exercise training : echocardiographic
analysis at rest and during exercise. Am. J. Cardiol. 46,
219–225
Stratton, J. R., Levy, W. C., Ceriqueira, M. D., Schwartz,
R. S. and Abrass, I. B. (1994) Cardiovascular responses to
exercise : effects of aging and exercise training in healthy
men. Circulation 89, 1648–1655
Anholm, J. D., Foster, C., Carpenter, J. et al. (1982)
Effect of habitual exercise on left ventricular response to
exercise. J. Appl. Physiol. 52, 1648–1651
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
Nishimura, T., Yamada, Y. and Kawai, C. (1980)
Echocardiographic evaluation of long-term effects of
exercise on left ventricular hypertrophy and function in
professional bicyclists. Circulation 61, 832–840
Cooke, G. A., Al-Timman, J. K., Marshall, P., Wright,
D. J., Hainsworth, R. and Tan, L. B. (1998) Physiological
cardiac reserve : development of a non-invasive method
and first estimates in man. Heart 79, 289–294
Tan, L. B. (1986). Cardiac pumping capability and
prognosis in heart failure. Lancet ii, 1360–1363
Tan, L. B. (1991) Evaluation of cardiac dysfunction,
cardiac reserve and inotropic response. Postgrad. Med. J.
67 (Suppl. 1), S10–S20
Tan, L. B. (1987) Clinical and research implications of
new concepts in the assessment of cardiac pumping
performance in heart failure. Cardiovasc. Res. 21, 615–622
Roul, G., Moulichon, M. E., Bareiss, P. et al. (1995)
Prognostic factors of chronic heart failure in NYHA class
II or II : value of invasive exercise haemodynamic data.
Eur. Heart J. 16, 1387–1398
Tabet, J.-Y., Logeart, D., Bourgoin, P., Guiti, C., Alonso,
C. and Cohen-Solal, A. (2000) Prognostic value of the
‘‘ circulatory ’’ power during exercise in patients with
heart failure. J. Am. Coll. Cardiol. 35 (Suppl.),
181A–182A
Williams, S. G., Cooke, G. A., Wright, D. J. et al. (2001)
Peak cardiac power output : a powerful prognostic
indicator in chronic heart failure. Eur. Heart J., in the
press
Elborn, J. S., Stanford, C. F. and Nicholls, D. P. (1990)
Reproducibility of cardiopulmonary parameters during
exercise with chronic cardiac failure. The need for a
preliminary test. Eur. Heart J. 11, 75–81
Bingisser, R., Kaplan, V., Scherer, T., Russi, E. W. and
Bloch, K. E. (1997) Effect of training on repeatability of
cardiopulmonary exercise performance in men and
women. Med. Sci. Sports Exercise 29, 1499–1504
Jones, N. L. (1988) Clinical Exercise Testing, 3rd edn,
WB. Saunders Co., Philadelphia
Beaver, W. L., Wasserman, K. and Whipp, B. J. (1986)
A new method for detecting anaerobic threshold by gas
exchange. J. Appl. Physiol. 60, 2020–2027
Swaine, I. L. and Mary, D. A. S. G. (1989) Early detection
of changes in cardiorespiratory fitness during exercise
training. Med. Sci. Res. 17, 939–941
Swaine, I. L., Linden, R. J. and Mary, D. A. S. G. (1992)
Indices for detection of changes in cardiorespiratory
fitness during exercise training in man. Exp. Physiol. 77,
65–78
Cotes, J. E., Davies, C. T. M., Edholm, O. G., Healy,
M. J. R. and Tanner, J. M. (1969) Factors relating to the
aerobic capacity of 46 healthy British males and females
ages 18 to 28 years. Proc. R. Soc. London B 174, 91–114
Belardinelli, R. B., Georgiou, D., Scocco, V., Barstow,
T. J. and Purcaro, A. (1995) Low intensity exercise
training in patients with chronic heart failure. J. Am.
Coll. Cardiol. 26, 975–982
Adachi, H., Koike, A., Obayashi, T. et al. (1996) Does
appropriate endurance exercise training improve cardiac
function in patients with prior myocardial infarction.
Eur. Heart J. 17, 1511–1521
Spina, R. J., Ogawa, T., Kohrt, W. M., Martin, III, W. H.,
Holloszy, J. O. and Ehsani, A. A. (1993) Differences in
cardiovascular adaptations to endurance exercise training
between older men and women. J. Appl. Physiol. 75,
849–855
Tan, L. B. and Littler, W. A. (1990) Measurement of
cardiac reserve in cardiogenic shock : implications for
prognosis and management. Br. Heart J. 64, 121–128
Received 4 January 2001/2 April 2001; accepted 13 June 2001
# 2001 The Biochemical Society and the Medical Research Society
483