Obesity Research (2000) 8, 12–19; doi: 10.1038/oby.2000.3
Bernard Gutin*, Paule Barbeau*, Mark S. Litaker†, Michael Ferguson* and Scott Owens*
1.
*Georgia Prevention Institute, Department of
Pediatrics, Medical
2.
†Office of Biostatistics, Medical
Correspondence: Bernard
Gutin, PhD, HS1640 Medical
Received
17 March 1999; Accepted 6 May 1999.
Objective: Heart rate variability provides
non-invasive information about cardiac parasympathetic activity (PSA). We
determined in obese children: (1) relations of baseline PSA to body composition
and hemodynamics; (2) effects of physical training
(PT) and cessation of PT; and (3) which factors explained individual
differences in responsivity of PSA to the PT.
Research Methods and
Procedures: The root mean
square of successive differences (RMSSD) was the index of PSA. Obese children (n
= 79) were randomly assigned to groups that participated in PT during the first
or second 4-month periods of the study.
Results: Baseline RMSSD was significantly (p
< 0.05) associated with lower levels of: fat mass, fat-free mass,
subcutaneous abdominal adipose tissue, resting heart rate (HR), resting
systolic blood pressure, and exercise HR. Stepwise multiple regression produced
a final model (R2 = 0.36) that included only resting HR. The
analysis of changes over the three time points of the study found a significant
(p = 0.026) time by group interaction, such that RMSSD increased during
periods of PT and decreased following cessation of PT. Greater individual
increases in response to the PT (p < 0.05) were seen in those who had
lower pre-PT RMSSD levels, showed the greatest decreases in resting HR, and
increased most in vigorous physical activity. The final regression model
retained only the change in resting HR as a significant predictor of the
changes in the RMSSD (R2 = 0.23).
Discussion: Regular exercise that improved fitness and
body composition had a favorable effect on PSA in obese children.
parasympathetic activity, exercise, body composition
Beat-to-beat
variability in heart rate, which is called heart period or heart rate
variability (HRV), provides non-invasively derived information about cardiac
autonomic activity (1).
Low levels of parasympathetic activity (PSA), as indicated by low HRV, are
powerful predictors of mortality after myocardial infarction (2).
The potential clinical importance of exercise is illustrated by a study in
which dogs that exercise-trained for 6 weeks increased their PSA substantially,
and were afforded protection against the ventricular fibrillation associated
with acute myocardial ischemia (3).
Some adult studies have
shown PSA to be relatively low in obese subjects (4)
and relatively high in endurance-trained subjects (5, 6, 7, 8, 9, 10).
Moreover, some studies (11,
12,
13,
14,
15)
have found it to increase as a result of physical training (PT). In a
preliminary study, we (16)
showed that obese children who engaged in 4 months of PT exhibited favorable
changes in PSA compared to non-exercising controls.
The primary purpose of
the present study was to investigate changes over an 8-month period in two
groups of obese children; one group participated in PT for 4 months and ceased
PT for the next 4 months, while the second group followed the opposite pattern.
This modified crossover design permitted us to see what would happen to PSA
during 8-month periods in the lives of obese children during which they were
engaged in more or less physical activity. It also permitted us to see what
happened when the first group discontinued the PT. To our knowledge no previous
study has used this approach. We hypothesized that PSA would increase during
periods of PT compared with periods of no-PT in both groups, and that it would
decline in the 4-month period following cessation of PT in the group that did
PT during the first 4-month period.
An additional component
of the study involved exploration of individual differences in the PSA at
baseline and in response to the PT. At baseline, the independent variables
included: age, gender, ethnicity, total body composition, visceral adipose
tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), resting heart rate
(HR), resting blood pressure (BP), cardiovascular (CV) fitness, and free-living
vigorous physical activity. Little is known about these relationships in black
and white obese children. To explore determinants of individual differences in
response to the PT, we calculated a pre-PT to post-PT change score in PSA for
each child, regardless of which group he/she was in. The independent variables
included: pre-PT values of variables used in the baseline analyses; pre- to
post-PT change scores for these variables; free-living diet and physical
activity during the 4-month PT period; and PT process variables (i.e.,
attendance in PT sessions, energy used in the PT sessions, and HR during the PT
sessions). These exploratory analyses of individual differences were designed
to generate hypotheses for future investigations.
Obese 7- to
11-year-old children were recruited via flyers and newspaper advertisements.
Interested children and parents signed informed consent documents in accordance
with the procedures of our Human Assurance Committee. To be included, a child
needed to have a triceps skinfold greater than the
85th percentile for age, gender, and ethnicity (17).
Because of the increased prevalence of obesity over the last 15 to 20 years (18),
the actual percentage of children in our region who are above this cutpoint is likely to be considerably greater than 15%.
We recruited 81
children, but two were dropped for medical reasons before randomization to
experimental groups. Children underwent baseline testing and were randomly
assigned, within gender and ethnicity, to Group 1 or Group 2. Group 1 engaged
in PT for the first 4-month period and then ceased PT for the next 4 months,
while Group 2 did not engage in PT for the first 4 months and then engaged in
PT for the next 4 months. Testing sessions were conducted at baseline, after 4
months, and after 8 months. No lifestyle or nutritional counseling of any kind
was provided. Approximately 50% of the children underwent the protocol in the
first year of the project (Cohort 1) and the other 50% participated in the
second year (Cohort 2); the possibility that there might be a cohort effect was
taken into account in the statistical analyses.
The mean (SD)
age of the 79 experimental subjects was 9.5 (
1.0)
years; 26 were male and 53 were female. With respect to self-designated
ethnicity, 34 were white, 44 were black, and 1 was Asian. Because we wanted to
include ethnicity as a correlate of baseline HRV values and as a possible
determinant of change in HRV, the Asian child was omitted from these analyses.
However, he was randomly assigned to Group 2 and was included in the
within-subject analyses of changes over the 8-month intervention period. Of the
79 subjects who began the intervention period, three from Group 2 did not
return for 4-month testing; thus 76 were tested at the 4-month time point.
Three children dropped from each group in the next 4 months, with the result
that 70 completed the 8-month testing. Table 1
shows the baseline descriptive characteristics of the entire group.
Resting measures
were made in a supine position after 10 minutes of quiet rest. HRV parameters
were measured as previously described (16)
with a Schiller ECG system (
Exercise hemodynamic measures were made during submaximal
cycling at a work rate of 49 W (300 kpm/minute) on a
supine ergometer (Quinton 486T,
CV fitness was
expressed as the average HR over the 5-minute period (submaxHR).
We decided to omit a test of peak oxygen consumption because we wanted to
minimize the unpleasantness of a maximal effort in obese children who would be
required to return repeatedly for testing and PT, and because we have found
that it is frequently difficult to elicit a "true" peak effort from
obese children (20).
Moreover, by measuring HR in a supine position, changes due to PT would not be
influenced by alterations in body weight; i.e., if measured in a task such as
treadmill walking, weight change would result in altered energy expenditure
which might lead to a change in HR that was not necessarily a reflection of
changed CV fitness.
Total body
composition was measured with DXA (QDR-1000; Hologic,
Magnetic resonance
imaging (MRI) was used to measure VAT and SAAT, as described in detail
elsewhere (22).
Briefly, images were acquired on a 1.5-T MRI system (General Electric Medical
Systems,
Physical activity
was estimated from 7-day recalls (23)
using a semistructured interview format during the 7
days just before the interview: i.e., before the baseline testing and the week
before the 4- and 8-month test sessions. Thus, the 7-day recall included the PT
associated with the exercise classes for the group involved in the PT during
these periods. The child was asked to recall the intensity of the activities as
being either moderate ("those that make you breathe as hard as during
normal walking"), very hard ("those that make you breathe as hard as
when running"), or hard ("those activities that are between walking
and running"). Only those activities that were engaged in for at least 10
minutes were included. Time spent in hard and very hard categories were summed
to derive an index of vigorous activity; we analyzed the relations of the RMSSD
to both moderate and vigorous activity.
Diet assessment was
designed to assist in interpretation of changes in outcome measures of the
study; no dietary information was involved in the intervention. We obtained a
2-day recall at baseline to familiarize the children with the procedure. Then
2-day recalls were obtained after 2, 4, 6, and 8 months, providing 4 days of
diet information for each child during his/her period of PT and 4 days for the
period of no-PT. The child was given a form on which to record all food eaten
for the 2 days before the interview; this information was used to assist the
child in remembering what he/she ate. The Nutrition Data System of the
Details about the
PT program are provided elsewhere (24).
Briefly, the program was designed to provide a substantial stimulus to the CV
system, while providing an enjoyable experience for the children. The 40-minute
PT sessions were offered 5 days each week and were designed to keep HR above
150 bpm. The first 20 minutes were spent on machines
(e.g., treadmill, cycle, Nordic ski machine), and the next 20 minutes were
devoted to games modified to maintain a high rate of energy expenditure. Each
child wore a heart rate monitor (Polar Vantage,
All statistical
analyses were performed using SAS 6.12 (SAS Institute Inc,
To assess the effects
of the PT and cessation of PT over the three time points of the study, we used
a mixed-model ANOVA, with subject as the random factor, and group and time as
fixed factors. For this analysis, all 79 subjects (including the Asian subject)
were used. This procedure allowed unequal sample sizes at different time
points, so that the maximum number of subjects could be utilized in each
analysis. Measurements that were not available at a given time point did not
cause other observations for that subject to be excluded from the analysis,
because least-squares estimates of the missing observations were utilized.
Least-squares means provided estimates of the expected
values of the group means if the design was balanced.
To explore what factors
might explain individual differences in responsivity
to the PT, we derived a change score for each child from before to after the
PT, regardless of which group he/she was in. Thus, for Group 1 the baseline
value was subtracted from the 4-month value, while for Group 2, the 4-month
value was subtracted from the 8-month value. To determine if the RMSSD
increased significantly across all subjects during the 4-month PT period, a
paired observations t test was applied to the change scores; because an
increase had been hypothesized, a one-sided test was used. Correlations were
computed between change in the RMSSD and the possible determinants of change,
including: (1) demographics (age, ethnicity, gender, cohort, and group); (2)
changes in adiposity and hemodynamics; (3) physical
activity and diet during the 4-month PT period; and (4) individual differences
in aspects of the PT itself (attendance in PT sessions, and HR and energy
expenditure during the PT sessions). Again, the first regressions were run
separately for each domain, the variables retained from each domain were then
run together, and interactions were tested when required.
At baseline, the
ethnicity and gender subgroups did not differ significantly in the RMSSD, and
there was no significant interaction between ethnicity and gender. Because age,
group, and cohort were also not significantly associated with the RMSSD,
subsequent analyses were done across all subjects together. Table 1
shows the baseline descriptive statistics and the correlations between the
RMSSD and the independent variables. Percent body fat was not significantly
associated with the RMSSD, whereas higher levels of both fat
mass and fat-free mass were significantly associated with lower RMSSD values.
With respect to abdominal adipose tissue, SAAT, but not VAT, was significantly
correlated with the RMSSD. With respect to hemodynamic
variables, higher resting HR and SBP were significantly associated with lower
RMSSD values. The index of CV fitness, (i.e., lower submaxHR),
was associated with higher values of the RMSSD. The final stepwise multiple
regression analysis, in which each variable was adjusted for other variables in
the model, produced the following final model (R2 = 0.36):
Figure 1
shows the RMSSD pattern over the three points in the intervention period. The
significant group-by-time interaction (p = 0.026) indicates that the
pattern for the two groups differed. Group 1 increased during the first 4-month
period when it was engaged in PT, while Group 2 remained stable during that
period. When the groups changed assignments during the next 4-month period,
Group 1 declined and Group 2 increased in the RMSSD.
Pattern of
changes in the RMSSD over the three time points of the study. The thicker lines denote the periods of
physical training for each group.
With respect to the
analysis of individual differences in pre-PT to post-PT change scores, the
demographic factors of age, gender, ethnicity, cohort, and group were not found
to be significantly correlated with the change in RMSSD. Thus, subsequent
analyses were done across all subjects together. Table 2
shows the pre-PT to post-PT change scores and the correlations between the
change in RMSSD and the independent variables. The change in RMSSD from pre-PT
to post-PT was significant for the group as a whole (p = 0.035).
However, there was a great deal of variability in the individual response to
the PT, as evidenced by the large standard deviation, prompting the exploration
of which factors might explain this variation. The variables that were
significantly associated with individual differences in responsivity
to the PT were: (1) the pre-PT RMSSD level—higher pre-PT values were associated
with lower change scores (r = -0.28, p = 0.018); (2) the change
in vigorous physical activity (r = 0.25, p = 0.040)—those who
increased most in vigorous activity increased most in RMSSD; and (3) the change
in resting HR—smaller increases in resting HR were associated with greater
increases in the RMSSD (r = -0.48, p = 0.0001). When stepwise
multiple regression was applied, only the change in
resting HR remained in the final model (R2 = 0.23):
The primary result of
this study was that the RMSSD increased during 4-month periods during which the
obese children were engaged in PT, and declined in the 4-month period following
cessation of PT in Group 1. This demonstration of what occurred as a result of
increases and decreases in controlled vigorous activity supports the idea that
regular exercise has a favorable influence on PSA in this population. The pattern
of change for PSA is consistent with the pattern for body composition and submaxHR; i.e., improvements during periods of PT compared
to periods of no-PT (26).
Our findings are consistent with those of the studies that showed positive
effects of PT on PSA (11,
12,
13,
14,
15).
The failure of some studies to find improvements (27,
28,
29,
30)
may be due to factors such as: small sample sizes; use of subjects who were not
especially fat and/or unfit at baseline; relatively short periods of PT; or
inadequate control and documentation of the PT stimulus. This project used a
relatively large number of youths who were obese and unfit at baseline,
conducted the PT for 17 weeks, achieved a mean attendance of 4 days per week,
and clearly documented the PT stimulus. Our use of a modified crossover design
allowed us to demonstrate the influence of both increases and decreases in
vigorous activity on PSA. To our knowledge, no previous studies have utilized
this approach.
At baseline, higher
levels of both total body fat mass and fat-free mass, as well as SAAT, were
associated with lower RMSSD levels, whereas VAT was not significantly
associated with the RMSSD. Thus, it appears that visceral adiposity is not
especially deleterious to PSA as it seems to be for other aspects of CV health
(31).
Higher levels of RMSSD were significantly associated with lower levels of
resting HR. These cross-sectional associations are consistent with adult
studies that found higher PSA levels in leaner and more fit
subjects (6, 13,
14,
15).
Urbina et al. (32)
found that black male adolescents had higher PSA than white boys, while we did
not find an ethnic difference. It is important to note that our study was not
designed specifically to examine ethnic differences in PSA; i.e., subjects were
chosen on the basis of being obese and were not chosen to be representative of
their ethnic groups. Thus, we are not prepared to draw any conclusions about
ethnic differences in PSA. However, the absence of ethnic or gender differences
at baseline or in response to the PT suggests that our results may be
generalized across these subgroups.
To our knowledge, this
is the first study to explore correlates of individual differences in the responsivity of PSA to exercise training. It is noteworthy
that those who increased most in vigorous activity during the 4-month PT period
tended to increase the most in PSA. The correlation between change in submaxHR, our main index of CV fitness, and change in the
RMSSD was r = -0.23, which just failed to reach significance (p =
0.069). The change in resting HR was the only variable that was retained in the
final regression model; this is consistent with the concept that resting HR is
controlled to a large extent by PSA ((33),
p. 289). A parsimonious generalization for these results is that greater
changes in the RMSSD were associated with a pattern that included more
free-living vigorous exercise and greater reductions in resting and exercise
heart rates. None of the body composition changes or dietary variables were associated with individual variation in HRV change;
this suggests that the changes in HRV were due more to the PT and/or the
free-living exercise.
Although the exact
mechanism through which increased PSA contributes to CV health is unclear,
increased vagal activity seems to antagonize
sympathetic effects at the ventricular level, concomitantly improving cardiac
electrical stability and protecting against experimentally induced myocardial
infarction (3).
Of course, the risk of death associated with lower HRV is ordinarily seen much
later in life (2),
making the clinical significance of our findings unclear. However, even during
childhood, low levels of PSA are associated with: cardiac autonomic neuropathy
in diabetics with poor metabolic control (34);
duration of diabetes (35);
elevated BP (36);
and risk of the sudden infant death syndrome (37).
It is not known whether low HRV levels are causes, consequences, or merely
markers for these abnormalities. Because HRV declines with age from the years
of 10 to 99 (38),
it is tempting to speculate that a lifestyle that enables children to develop
higher levels of HRV early in life will carry over into the adult years,
thereby enabling them to slow this aspect of the aging process.
The clinical
significance of the magnitude of change elicited by the 4 months of PT is
difficult to assess, partly because different studies use different ways of
quantifying HRV. From before to after the PT, we saw an increase in the mean
RMSSD from 54 to 60 msec, which is comparable to the
change seen in 23- to 69-year-old smokers several weeks after they quit
smoking, in whom the mean RMSSD increased significantly from 30 to 38 msec (39);
the lower values in the subjects of this study compared with the values in our
subjects may reflect the differences in age. Changes in response to short-term
interventions are smaller than the cross-sectional differences that may be
observed between normal and diseased groups in whom the impact of the disease
has had longer to manifest itself; for example, one study found that, in youths
slightly older than our sample, the healthy children had a mean RMSSD value of
76 msec, whereas children with diabetes under good
and poor glycemic control had mean values of 64 and
30 msec, respectively (34).
The higher mean value in the healthy youths of this study (76 msec) compared with the pre-PT mean of our subjects (54 msec) may reflect the fact that our subjects were obese and
sedentary before the PT. Because it is difficult to assess the clinical
importance of the magnitude of change we elicited with the PT, it may be
reasonable simply to conclude that 4 months of PT in obese children led to
improvements in PSA that are not likely to have occurred by chance variation.
Moreover, upon cessation of PT, the values declined. This pattern provides
rather strong evidence of the positive influence of higher levels of physical
activity on PSA, supporting the idea that obese youths who increase their
regular exercise levels are likely to improve this aspect of CV health.
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Supported by the
National Heart, Lung and Blood Institute (HL49549) and the American Heart
Association–Parke Davis Company.