Download Relationship of Left Ventricular Structure to

Relationship of Left Ventricular Structure
to Maximal Heart Rate During Exercise*
William F. Graettinger, MD, FCCP; David H. G. Smith, MD;
Joel M. Neutel, MD; Jonathan Myers, PhD; Victor F. Froelicher, MD;
and Michael A. Weber, MD
Previous investigators using clinical, hemodynamic, or
exercise parameters to predict maximal exercise heart
rate (HRmax) have demonstrated age to be the major
determinant. Regression coefficients have ranged from
-0.3 to -0.6, leaving approximately two thirds of the
variance in HRmax unexplained. Because cardiac size
and function are directly related to stroke volume and
should influence HRmax, we studied 114 male subjects
(aged 19 to 73 years) with two-dimensional and M-mode
echocardiography who underwent maximal treadmill
testing with respiratory gas analysis. Seventy-three were
normotensive (diastolic BP<95 mm Hg) and 41 were
hypertensive. As in previous studies, HRmax was inversely related to age (HRmax= 199-0.63 [age], r= -0.47,
p<0.001). M-mode left ventricular (LV) diastolic dimension (LVD) added significantly to the explanation of the
variance in HRmax (r=-0.57, p<0.001) (HRmax=236-0.72 [age]-6.8 [LVD]). Thus, the larger the
heart, the lower the HRmax. No other echocardiographic measurement or derived parameter added significantly to the explanation of the variance in HRmax.
To evaluate the effects of hypertension on HRmax, we
studied hypertensives and normotensives separately.
Only age was significantly related to HRmax in the
normotensives (r=-0.50, p<0.001). In the hypertensive
subjects, however, both age and relative wall thickness
(RWT) (which describes LV wall thickness in relation to
3he physiologic response to aerobic exercise is a
complex cardiorespiratory, neurohumoral, vascular, and muscular process. The linear relationship
between oxygen consumption and cardiac output
throughout exercise is well known.1 The major factor
mediating the increase in cardiac output associated
with exercise is an increase in heart rate. Maximal
heart rate (HRmax) is directly correlated with maximal oxygen consumption and therefore, HRmax has
been used as an approximation for maximal cardiac
work. Age has been demonstrated to be the prime
*From the Cardiology and Hypertension Sections, Department of
Veterans Affairs Medical Center, Long Beach, Calif, and the
University of California, Irvine.
Presente in part at the 64th Scientific Sessions, American Heart
Association, Anaheim, Calif, Nov. 11-14, 1991
Supported in part by a Merit Review Grant from the Department of Veterans Aff airs.
Manuscript received January 11, 1994; revision accepted May 24.
Reprint requests: Dr. Graettinger, 1000 Locust Street (111), Reno,
NV 89520
LV chamber size) were significantly related to HRmax.
Age explained 45% of the observed variance in HRmax
(r=0.67, p<0.001) and RWT added modestly (9%O) but
significantly to the relationship (HRmax=173-0.96
[age]+94 [RWT], p<0.001), together explaining 54% of
the variance observed in HRmax. Thus, HRmax is
inversely related to LVD and patients with larger ventricles achieve lower HRmax. In hypertensives, the
amount of LV muscle mass in relation to chamber size
is an additional predictor of HRmax. However, despite
controlling for age, sex, and cardiovascular disease, and
the inclusion of echocardiographic indices of cardiac
size and function, a large portion of the variance in
HRmax could not be explained. The unexplained variance in HRmax is most likely due to intersubject variability in resting cardiac size, volume, function, and
other as yet undefined factors.
(Chest 1995; 107:341-45)
HRmax=maximal heart rate; IVS=interventricular septal
thickness; LV=left ventricular; LVD=left ventricular diastolic dimension; PW=posterior wall; RWT=relative wall
thickness
Key words: exercise; left ventricular size; maximal heart
rate; variance
determinant of maximal exercise heart rate. Regression coefficients for the inverse relationship between
HRmax age have ranged from -0.3 to -0.5.2-6 This
relationship explains only approximately one third of
the variance in maximal exercise heart rate. This
relatively poor relationship between HRmax and age
therefore limits the prediction of HRmax as an indicator of maximal effort during exercise testing, to
establish a target heart rate for exercise training, and
to identify individuals with a truly abnormal HRmax.
Previous studies have used age as the predictor of
HRmax. The potential effects of other clinical or
echocardiographic parameters remain unknown.
This study was undertaken to (1) evaluate further
which factors, alone or in combination with age,
might have a significant relationship with HRmax,
thus more accurately predicting the HRmax response
to exercise, and (2) what effect, if any, untreated
hypertension has on this relationship.
CHEST / 107 / 2 J FEBRUARY, 1995
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341
METHODS
Study Group
The study group consisted of 114 healthy male subjects (aged
19 to 73 years). Of these, 41 were hypertensive (diastolic BP>95
mm Hg) and 73 were normotensive based on the mean of six
resting blood pressure readings. Two measurements were made
in the sitting position by standard mercury sphygmomanometer
after 3 min of quiet sitting. Measurements were obtained at each
of three office visits and all readings were averaged. No patient
was receiving antihypertensive medication. The hypertensive
subjects either had never been treated with antihypertensive
medication or had not been receiving medication for greater than
8 months. Subjects were without any known medical conditions
(other than hypertension in 41) and had normal results of physical examinations. All subjects gave written informed consent
approved by the Institutional Review Board.
Echocardiography
Cardiac structure and function were assessed by two-dimensional guided M-mode echocardiography utilizing a commercially available phased-array echocardiograph (GE Pass II or RT
5000, Milwaukee). M-mode data were recorded on strip-chart at
a paper speed of 50 mm/s. M-mode measurements were made
utilizing the standards of the American Society of Echocardiography.7 M-mode tracings were accepted only for inclusion after
two-dimensional echo analysis revealed normal left ventricular
(LV) contractile pattern and function. Relative wall thickness
(RWT) was computed by the following equation:
RWT=(IVS+PW)/LVD, where IVS=interventricular septal
thickness, PW=LV posterior wall thickness, and LVD=left ventricular diastolic dimension. The LV mass was calculated by the
formula of Troy et al.8 All measurements were made by two observers who were unaware of the patients' blood pressure or exercise data and any disagreement was resolved by consensus.
Exercise Protocol
Two cardiopulmonary exercise treadmill tests separated by 7 to
14 days were performed by each patient. The first utilized a
modified Balke-Ware protocol.9 Its purpose was to familiarize the
subject with the procedures of treadmill exercise and expired gas
analysis and to measure the subject's maximal oxygen consumption as previously described.'0 These data were utilized to
perform a second test from which the data described herein were
derived. Subjects were exercised to exhaustion using a ramp
treadmill protocol during which treadmill speed and grade were
individualized to achieve maximal workload corresponding to
maximal oxygen consumption as determined by the first test11 in
approximately 10 min. Maximal heart rate was calculated from
the R-R intervals using a 6-s rhythm strip'2 at maximal exercise
recorded on the peak exercise electrocardiogram. Blood pressure
was measured immediately prior to the test, every 2 min during
exercise, at peak exercise, and immediately after exercise. Perceived effort was reported throughout and at maximal exertion.13
Catecholamines
Blood for epinephrine and norepinephrine was drawn via
heparin lock after a 30-min supine rest period, standing immediately before the treadmill, and standing immediately after the
treadmill.
Statistical Analysis
Statistical analysis was done using software (SPSS/PC+) on a
microcomputer. Correlations between variables were obtained by
stepwise multiple linear regression analysis. Variables were
included in the regression equation if the f-test for inclusion was
342
Table 1-Clinical Characteristics
Normotensive
Hypertensive
Group
Group
n=73
n=41
43±13
Age, yr
Weight, kg
83+12
129 ± 13
Resting systolic BP, mm Hg
86 + 6
Resting diastolic BP, mm Hg
67 ± 10
Resting heart rate, bpm
SBP max, f mm Hg
195 +21
DBP max,f mm Hg
81±14
HR max, bpm
170±18
*p<0.05.
fDBP max=maximal diastolic BP; SPP max=maximal
50±14*
88±12*
149 + 15*
101 ± 4*
74 ± 10*
209 ± 22*
94 ± 16*
165 ±18
systolic BP.
significant at the p value<0.05 level. Only variables that made
statistically significant contributions to the explanation of the
variance observed in the dependent variable are reported. Comparisons between groups were made with unpaired Student's t
tests. A two-tailed t test with a p value <0.05 was required for
significance. Results are presented as mean ± 1 SD.
RESULTS
Clinical characteristics of the study groups are
given in Table 1. The hypertensive subjects tended to
be older and slightly heavier than normotensive
subjects. Their resting and maximal exercise blood
pressures were significantly higher than those in
normotensive subjects. Resting heart rate was slightly
higher and HRmax tended to be slightly but not significantly lower in the hypertensive group. Maximal
perceived effort was similar in both groups (19.2 ± 1
vs 19.2 ± 1 Borg units).
Echocardiographic characteristics of the groups
are given in Table 2. There were no significant differences between the two groups in any of the measured or derived parameters.
The catecholamine data are given in Table 3.
There were no differences in the mean epinephrine
or norepinephrine levels between the normotensive
and hypertensive groups at rest or immediately after
exercise. Both groups demonstrated a similar rise in
Table 2-Echocardiographic Characteristics*
LVD, cm
IVS, cm
PW, cm
LA, cm
LVM, g
LVMI, g/m2
Normotensive
Hypertensive
Group
Group
n=73
n=41
5.1±0.4
1.05±0.12
1.06± 0.12
4.0± 0.5
259 ± 57
128 ±25
LVM/HT, g/cm
1.45±0.32
RWT
0.41 ± 0.05
5.1±0.4
1.09±0.11
1.09 ±0.11
4.0±0.5
265 ±52
130±25
1.5±0.29
0.43 ± 0.06
*LA=left atrium;
LVM=LV mass; LVMI=LV mass index; LVM/
HT=LV mass/height
LV Structure and Maximal Heart Rate During Exercise (Graettinger et al)
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REFERENCES
1
2
3
4
5
6
7
8
Astrand PO. Textbook of work physiology. New York: McGraw
Hill, 1977; 188
Hammond HK, Kelly TL, Froelicher VF. Radionuclide imaging correlates of heart rate impairment during maximal exercise testing. J Am Coll Cardiol 1983; 2:826-33
Scheffield LT, Malouf JA, Sawyer JA, Roitman D. Maximal
heart rate and treadmill performance of healthy women in relation to age. Circulation 1978; 57:79-84
Bruce RA, Fischer FD, Cooper MN, Gey GO. Separation of
effects of cardiovascular disease and age on ventricular function
with maximal exercise. Am J Cardiol 1974; 34:757-63
Froelicher VF, Yanowitz F, Thompson AJ, Longo MR, Triebwasser JH. Treadmill exercise testing at the USAF School of
Aerospace Medicine: physiologic responses in aircrewmen and
the detection of latent coronary artery disease. Advisory Group
for Aerospace Research and Development 1975; 210:1-37
Lester M, Sheffield LT, Trammell P, Reeves TJ. The effect of
age and athletic training on the maximal heart rate during
muscular exercise. Am Heart J 1968; 76:370-76
Sahn DJ, DeMaria A, Kisslo J, Weyman A. Committee on
M-mode standardization of the American Society of Echocardiography: recommendations regarding quantization in
M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58:1072-83
Troy BL, Pombo J, Rackley CE. Measurement of ventricular
wall thickness and mass by echocardiography. Circulation
1972; 45:602-11
9 Wolthuis RA, Froelicher VF, Fischer J, Noguera I, Davis G,
Stewart AJ, et al. New practical treadmill protocol for clinical
use. Am J Cardiol 1977; 39:697-700
10 Myers J, Walsh D, Froelicher VF. Effect of sampling on vari-
ability and plateau in oxygen uptake. J Appl Physiol 1990;
68:404-10
11 Myers J, Buchanan N, Walsh D, Kraemer M, McAuley P,
Hamilton-Wessler M, et al. A comparison of the ramp versus
standard exercise protocols. J Am Coll Cardiol 1991; 17:1334-42
12 Drayer JIM, Gardin JM, Brewer DD, Weber MA. Disparate
relationships between blood pressure and LV mass in patients
with and without LVH. Hypertension 1987; 9(suppl 2):11611164
13 Borg G. Perceived exertion as an indicator of somatic stress.
Scand J Rehabil Med 1970; 23:92-8
14 Longhurst JC. Arterial baroreceptors in health and disease.
Cardiovasc Rev Rep 1982; 3:271-99
15 Bainbridge FA. The influence of venous filling upon the rate of
the heart. J Physiol 1915; 50:65-84
16 Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of
heart rate by the autonomic nervous system: studies in man on
the interrelation between baroreceptor mechanisms and exercise. Circ Res 1966; 19:400-11
17 Atwood JE, Myers J, Sandhu S, Lachterman B, Friis R, Oshita
A, et al. Optimal sampling interval to estimate heart rate at rest
and during exercise in atrial fibrillation. Am J Cardiol 1989;
63:45-8
18 Neutel JM, Smith DHG, Graettinger WF, Weber MA. Heredity and hypertension: impact on metabolic characteristics. Am
Heart J 1992; 124:435-40
19 Neutel JM, Smith DHG, Graettinger WF, Weber MA. Depen-
dency of arterial compliance on circulating neuroendocrine
and metabolic factors in normal subjects. Am J Cardiol 1992;
69:1340-44
20 Hammond HK, Froelicher VF. Normal and abnormal heart
rate responses to exercise. Progress Cardiovasc Dis 1985;
27:271-96
A Practicum: Exercise Testing and Interpretation
March 23 - 25, 1995; Harbor-UCLA Medical Center, Torrance, California
Sponsored by the Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical
Center. Contact: Shirley Zagala, Box 405, Harbor-UCLA Medical Center, RB2, Room 319, 1000 W. Carson
Street, P.O. Box 2910, Torrance, CA 90509-2910. Tel: 310 222-3803.
CHEST / 107/21 FEBRUARY, 1995
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21708/ on 05/02/2017
345
A
ber size is inversely related to HRmax. The addition
of LV dimension to the regression equation explained
M
. an additional 4% of the variance in HRmax. These
A
o- ~ .
*
.
x
data confirm a previous study from our group that
*.
suggested that hypertensive subjects with larger
M
A
hearts might have reduced LV performance during
L
exercise.12 However, RWT, a measure of appropriH
ateness of hypertrophy in relation to LV size, was a
E
predictor of HRmax in the hypertensive subjects; the
A
D
.-.
R
greater the wall thickness recorded for a given LV
T
size, the greater the HRmax. That is, increased wall
D
R
A
r * -0.5, p <0.001
thickness in proportion to LV chamber size appears
T
to
be associated with increased ability to do maximal
D_
E
45
55
35
65
25
15
75
work in hypertensive patients. In contrast, LV enAGE
largement without an appropriate increase in wall
thickness results in decreased ability to do maximal
B
work.
M
The reasons for the varying degrees of myocardial
A
x
0
hypertrophy in relation to ventricular size are poorly
understood. Intrinsic or secondary myocardial
M
o
. . *
.
A
changes related to hypertension and its concomitant
L
*
*
* .
*.
.metabolic'8 and neuroendocrine changes'9 may play
H
a role. A possible explanation for the relationship
E
.
between
0
*
*
HRmax and RWT is that catecholamines,
A
R
which
have
growth-promoting effects on myocardial
T
also
mediate
the heart rate response to exercise.
cells,
D
R
As the subjects in this study had only minimal
r * -0.67, p <0.001
A
amounts of LV hypertrophy and normal to miniT
D0
E
E
28
35
85
45
65
75
15
mally dilated ventricles, it is unlikely that these
AGE
changes would be associated with diminished function or exercise capacity.
FIGURE 1. The linear regression of maximal heart rate on age is
plotted in the normotensive (top, A) and hypertensive (bottom, B)
subjects
or de]monstrable cardiovascular disease; they reportedI similar activity levels; and all subjects were
exercihsed utilizing the same type of exercise. The
hyperltensive subjects tended to be heavier than the
normc tensive subjects, but weight has not been
demoiastrated to have an influence on HRmax in
previo)us studies. There was no difference in the perceived[ maximal effort as assessed by the Borg scale
and mieasured Vo2max was similar in the two groups
indicaLting that even if true maximal effort was not
attain(ed, both groups at least achieved a similar level
of exertion.
Heart rate continuously increases throughout exercise and does not achieve a steady-state. It then
drops rapidly on stopping exercise and then gradually decreases during the recovery phase. To avoid
inaccuracies in HRmax measurement induced by
these phenomena, HRmax was calculated from R-R
intervals on a 6-s rhythm strip'7 recorded at peak
exercise, thus providing a close representation of the
instantaneous maximal rate attained.
The current data also demonstrate that LV cham344
Our findings are also in agreement with the
observation of reduced HRmax in aerobically trained
individuals, especially younger individuals who may
experience an increase in LV mass.20
The large portion of the variance in HRmax that
remains unexplained by age appears to be partially
attributable to intersubject variability, including cardiac size, LV hypertrophy relative to the LV size, and
the presence of hypertension. The inclusion of these
factors improved the prediction of HRmax, especially in hypertensive subjects. Additional factors that
may influence HRmax need to be identified and may
allow better description of the physiologic attributes
involved.
CONCLUSIONS
It is of physiologic interest that LV measurements
inversely related to HRmax. However, the improvement in prediction of HRmax by the addition
of LV size to age is not great enough to be meaningful for clinical application, and there remains too
much unexplained variance to establish normalcy or
to set heart rate goals during exercise using modified
regression equations. Age-adjusted goals still have
are
significant clinical utility.
LV Structure and Maximal Heart Rate
During Exercise (Graettinger et al)
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21708/ on 05/02/2017
REFERENCES
1
2
3
4
5
6
7
8
Astrand PO. Textbook of work physiology. New York: McGraw
Hill, 1977; 188
Hammond HK, Kelly TL, Froelicher VF. Radionuclide imaging correlates of heart rate impairment during maximal exercise testing. J Am Coll Cardiol 1983; 2:826-33
Scheffield LT, Malouf JA, Sawyer JA, Roitman D. Maximal
heart rate and treadmill performance of healthy women in relation to age. Circulation 1978; 57:79-84
Bruce RA, Fischer FD, Cooper MN, Gey GO. Separation of
effects of cardiovascular disease and age on ventricular function
with maximal exercise. Am J Cardiol 1974; 34:757-63
Froelicher VF, Yanowitz F, Thompson AJ, Longo MR, Triebwasser JH. Treadmill exercise testing at the USAF School of
Aerospace Medicine: physiologic responses in aircrewmen and
the detection of latent coronary artery disease. Advisory Group
for Aerospace Research and Development 1975; 210:1-37
Lester M, Sheffield LT, Trammell P, Reeves TJ. The effect of
age and athletic training on the maximal heart rate during
muscular exercise. Am Heart J 1968; 76:370-76
Sahn DJ, DeMaria A, Kisslo J, Weyman A. Committee on
M-mode standardization of the American Society of Echocardiography: recommendations regarding quantization in
M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978; 58:1072-83
Troy BL, Pombo J, Rackley CE. Measurement of ventricular
wall thickness and mass by echocardiography. Circulation
1972; 45:602-11
9 Wolthuis RA, Froelicher VF, Fischer J, Noguera I, Davis G,
Stewart AJ, et al. New practical treadmill protocol for clinical
use. Am J Cardiol 1977; 39:697-700
10 Myers J, Walsh D, Froelicher VF. Effect of sampling on vari-
ability and plateau in oxygen uptake. J Appl Physiol 1990;
68:404-10
11 Myers J, Buchanan N, Walsh D, Kraemer M, McAuley P,
Hamilton-Wessler M, et al. A comparison of the ramp versus
standard exercise protocols. J Am Coll Cardiol 1991; 17:1334-42
12 Drayer JIM, Gardin JM, Brewer DD, Weber MA. Disparate
relationships between blood pressure and LV mass in patients
with and without LVH. Hypertension 1987; 9(suppl 2):11611164
13 Borg G. Perceived exertion as an indicator of somatic stress.
Scand J Rehabil Med 1970; 23:92-8
14 Longhurst JC. Arterial baroreceptors in health and disease.
Cardiovasc Rev Rep 1982; 3:271-99
15 Bainbridge FA. The influence of venous filling upon the rate of
the heart. J Physiol 1915; 50:65-84
16 Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of
heart rate by the autonomic nervous system: studies in man on
the interrelation between baroreceptor mechanisms and exercise. Circ Res 1966; 19:400-11
17 Atwood JE, Myers J, Sandhu S, Lachterman B, Friis R, Oshita
A, et al. Optimal sampling interval to estimate heart rate at rest
and during exercise in atrial fibrillation. Am J Cardiol 1989;
63:45-8
18 Neutel JM, Smith DHG, Graettinger WF, Weber MA. Heredity and hypertension: impact on metabolic characteristics. Am
Heart J 1992; 124:435-40
19 Neutel JM, Smith DHG, Graettinger WF, Weber MA. Depen-
dency of arterial compliance on circulating neuroendocrine
and metabolic factors in normal subjects. Am J Cardiol 1992;
69:1340-44
20 Hammond HK, Froelicher VF. Normal and abnormal heart
rate responses to exercise. Progress Cardiovasc Dis 1985;
27:271-96
A Practicum: Exercise Testing and Interpretation
March 23 - 25, 1995; Harbor-UCLA Medical Center, Torrance, California
Sponsored by the Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical
Center. Contact: Shirley Zagala, Box 405, Harbor-UCLA Medical Center, RB2, Room 319, 1000 W. Carson
Street, P.O. Box 2910, Torrance, CA 90509-2910. Tel: 310 222-3803.
CHEST / 107/21 FEBRUARY, 1995
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345