(Hypertension. 1999;34:1026-1031.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
From the Georgia Prevention Institute (G.K.K., F.A.T., H.C.D., G.A.H., G.A.M.), Departments of Medicine (G.A.M.), Pediatrics (F.A.T., G.A.H., B.B.C.), and Psychiatry (F.A.T.), and Office of Biostatistics (H.C.D.), Medical College of Georgia, Augusta.
Correspondence to Frank A. Treiber, PhD, Medical College of Georgia, Georgia Prevention Institute, HS-1640, Augusta, GA 30912-3710. E-mail ftreiber{at}mail.mcg.edu
| Abstract |
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Key Words: blood pressure left ventricular mass ventricular function youth
| Introduction |
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Ambulatory blood pressure (ABP) monitoring has been recognized to be superior to resting blood pressure (BP) in the prediction of cardiovascular morbidity.14 To the best of our knowledge, the value of ABP in predicting future LVM and LV function has not been evaluated in normotensive youth. Therefore, the purpose of this study was to evaluate comprehensively the individual and relative contributions of hemodynamic functioning at rest, during laboratory stress, and in the natural environment (ie, ABP monitoring) in the prediction of cardiac structure and function 2 years later in a sample of normotensive youth in whom the majority (ie, 96%) had a family history of cardiovascular disease. Individuals with a positive family history of essential hypertension and/or premature myocardial infarction are at increased risk for development of cardiovascular disease.15 Thus, identification of early predictors of cardiac structure and function is particularly important in such youth before manifestation of significant end-organ damage and cardiovascular disease.
| Methods |
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Procedure
The study was approved by the institutional review committee. On
each visit after informed consent was obtained, with rare exception,
all anthropometric and hemodynamic evaluations were
conducted by a female research assistant of the same race as the
subject. Subjects height (in centimeters) and weight (in kilograms)
were measured without shoes with a Health-O-Meter medical scale, which
was calibrated daily. Waist circumferences were measured at the
center of the umbilicus, and hip circumference was measured at the
level of the greater trochanters. Two sets of readings were
recorded and averaged. The subject was then escorted to a quiet
temperature-controlled room (20°C to 22°C) and fitted with
equipment for recording BP (Dinamap model 1846 SX, Critikon
Inc) and cardiac output with the use of thoracic bioimpedance (NCCOM-3,
Bo Med Medical Manufacturing Ltd), as previously
described.16 17 Body mass index (BMI) was calculated as
weight/height2.
Hemodynamic Evaluations
Stroke volume and heart rate were measured and cardiac output
was calculated (stroke volumexheart rate; L/min) every successive 12
QRS intervals while the Dinamap device was inflating and calculating
pressure. Total peripheral resistance (TPR) was calculated
with the use of concurrently derived systolic BP (SBP) and
diastolic BP (DBP) and cardiac output as follows:
[(SBP+2xDBP)/3]/Cardiac Output, expressed in Wood units (mm Hg/L
per minute). The subject was placed in a supine position and given
standardized instructions to relax as completely as possible for 15
minutes. During minutes 11, 13, and 15 of the baseline rest period,
hemodynamic measurements were obtained and averaged to
provide 1 reading per blood pressure evaluation. After the baseline
evaluation, the subject engaged in 4 laboratory stressors (ie,
orthostasis, video game, car-driving simulation, and forehead cold) in
which standardized protocols were used.16 17 18 With the
exception of the video game, all protocol instructions were conducted
live by a female of the same race as the subject.
The orthostasis test was administered first with hemodynamics measured at 1, 2, and 3 minutes after the subject assumed a standing position with the right arm relaxed at a 90-degree angle across the trunk. The remaining 3 stressors were presented in a counterbalanced order, with the subject in the supine position. A minimum 5-minute prestressor period preceded each stressor, during which all hemodynamic data were concomitantly obtained every other minute. Prestressor periods continued until the subjects blood pressure returned to within ±5 mm Hg of the baseline values.
The 5-minute video game stressor Break Out (Atari Inc) was presented under a monetary incentive challenge via videotaped instructions by a female of the same race as the subject. The BP cuff was placed on the nondominant arm, and the video game controller was secured at a position comfortable for use with the subjects dominant hand. The game was presented on a 635-mm-diagonal color television, located 2000 mm from the subject at a position comfortable for viewing.
The 5-minute car-driving simulation stressor used virtual reality technology and was based on a protocol established in our laboratory.18 The subject wore a Kaiser Electro-Optics Vision Immersion headset (model 500, Kaiser Aerospace and Electronics Company) interfaced with a Panasonic 3DO system (model FZ-1, Matsushita Electric Corporation of America) that played the car-driving simulation task Need for Speed (Pioneer Production and Electronic Arts, Inc). This system immersed the subject into the cockpit of a virtual car. A small control pad permitted control over steering, acceleration, and braking while driving in pursuit of another car. During the video game and car-driving stressors, hemodynamic measurements were evaluated every other minute.
The forehead cold stimulation task was based on a protocol used in our laboratory.17 A plastic bag containing 6 cups of crushed ice and 1.5 cups of water was placed on the subjects forehead for 1 minute. Hemodynamic measurements were obtained at the end of 1 minute, after which the bag was removed.
Echocardiographic Studies
Echocardiographic evaluations were performed
after completion of the laboratory stressors and a brief rest.
Sector-guided M-mode echocardiograms were performed with a Hewlett
Packard Sonos 1500 echocardiograph. Left
ventricular posterior wall in diastole (LVPWD),
interventricular septum in diastole (IVSD), and
LV internal diameter in diastole (LVIDD) were measured
according to the American Society of
Echocardiography convention.19 LVM was
derived with the use of the formula of Devereux,20 which
has been validated for use in individuals with normal hearts. On the
basis of the recommendation of de Simone et al,6 LVM was
divided by height2.7 to adjust for normal growth
without removing the effect of obesity.
A second index LVM/BSA was used to allow easy comparison with previous reports. Relative wall thickness (RWT) was calculated with the use of the following equation: RWT=(2xLVPWD)/LVIDD.
To assess LV contractile function, circumferential end-systolic
stress (cESS), midwall fractional shortening (MFS), and MFS ratio were
calculated according to established formulas.21
Specifically, we calculated cESS at the midwall level of the left
ventricle as an index of afterload using a cylindrical model, as
follows:
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MFS was calculated following the method described by de Simone et al,21 as follows: MFS=(LVIDD+LVPWD/2+IVSD/2)-(LVIDS+Hs/2)/LVIDD+LVPWD/2+IVSD/2, where LVIDS is LV internal diameter in systole and Hs/2 is the assumed LV inner shell myocardial thickness at end systole, taking into account the epicardial migration of midwall during systole in a spherical model. To evaluate midwall LV performance independently of afterload, the ratio between MFS calculated from the echocardiographic measurement and the value predicted for a given level of cESS was calculated (ie, MFS ratio).
ABP Assessment
After completion of the laboratory evaluation, the subject was
fitted with an ABP monitor cuff on the nondominant arm (model 90207,
Space Labs, Inc). The subject wore the monitor for 24 hours, with
measurements obtained every 20 minutes during the day (ie, 6
AM to 10 PM) and every 30 minutes at night (ie,
10 PM to 6 AM). The transitional periods from 6
AM to 8 AM and 10 PM to midnight
were not included in the analyses by time period but were
included in the 24-hour analyses. Measures of SBP and DBP
nocturnal dip were calculated as the differences between average
daytime minus nighttime readings, expressed as a percentage of the
daytime average. Ambulatory data were edited according to established
criteria described by Treiber et al.22
Data Reduction and Statistical Analyses
All baseline and prestressor hemodynamic
measurements were averaged. Hemodynamic stress measures
used in the analyses included both peak and change score (ie,
peak-mean prestressor) responses. Initially, a series of 2 (race)x2
(gender)x2 (visit: initial, follow-up) repeated-measures ANOVAs were
conducted on all demographic, anthropometric, resting, and
echocardiographic parameters. A series of 2
(race)x2 (gender) ANOVAs were also conducted on 24-hour, daytime, and
nighttime ABP.
Pearson product moment correlations were used to examine univariate relationships between all initial visit demographic, anthropometric, and hemodynamic data and echocardiographic data collected 2.3 years later. Variables found to be significantly related to echocardiographic variables (P<0.05) from this analysis were used in hierarchical stepwise multiple linear regression analyses using blocks of predictor variables. The blocks of possible predictor variables, in order, were as follows: (1) initial echocardiographic parameters (eg, LVM/BSA, LVM/height2.7); (2) demographics/anthropometrics (eg, gender, race, weight, BMI); (3) resting hemodynamics; (4) ABP measures; (5) peak hemodynamic stress responses; (6) hemodynamic change scores to stress; and (7) interactions of gender or race with resting hemodynamics, hemodynamic stress responses, and ABP variables. This form of regression is similar to analyzing a change score in that for all blocks of variables subsequent to the first block, the dependent variable is, in effect, the unexplained difference between the baseline and follow-up measure of interest.
| Results |
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Table 2 presents resting hemodynamic and ABP data for initial and follow-up visits. Resting TPR decreased from the initial to the follow-up value. Black youth exhibited greater SBP and TPR on both visits. For ambulatory SBP, significant race by gender interactions were found. At both visits, black males had the highest levels of BP during daytime, nighttime, and the 24-hour period.
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Echocardiographic data at initial and follow-up visits are presented in Table 3. At both visits, males had greater IVSD, LVPWD, LVIDD, LVM unindexed and indexed by either height2.7 or BSA, and cESS (P<0.001 for all). At both visits, black youth had higher relative wall thickness (P<0.003) and higher LVM indexed by either BSA or height2.7 (P<0.01 for both) and lower MFS ratio (P<0.05) compared with white youth.
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Univariate Relationships
Both indices of LVM at follow-up were related to their respective
baseline measurement (LVM/height2.7
r=0.62; LVM/BSA r=0.54; P<0.001 for
both). All baseline anthropometric parameters were related
to follow-up LVM/height2.7 (r range,
0.19 to 0.56; P<0.01 for all) and to LVM/BSA
(r range, 0.25 to 0.33; P<0.01 for all). With
respect to resting hemodynamic measures, both follow-up
LVM indices were positively related to baseline SBP and TPR
(r range, 0.20 to 0.27; P<0.05) and baseline
heart rate (r=-0.29 for both; P<0.01).
With respect to hemodynamic stress responsivity, SBP responsivity to each of 4 stressors was significantly positively related to both indices of LVM 2.3 years later (r range, 0.22 to 0.33; P<0.01 for all). TPR peak and/or change score responsivity to car-driving simulation, video game, and cold stressors was positively related to both indices of LVM (r range, 0.19 to 0.23; P<0.05 for all). Finally, the DBP peak responsivity to postural change was positively related to follow-up LVM/BSA (r=0.18, P<0.05).
Ambulatory SBP measured during daytime, nighttime, or 24 hours was significantly positively related to all echocardiographic measurements except RWT (r range, 0.18 to 0.35; P<0.05 for all). RWT was positively correlated with nighttime ambulatory DBP (r=0.18; P<0.03). When partial correlations were tested, no gender- or race-related differences were found for the relationships between indices of follow-up LVM with hemodynamic stress responsivity and ambulatory BP. Of all nocturnal dip comparisons, only the SBP dip was significantly correlated with any follow-up echocardiographic measure (ie, r=-0.16 with LVM/height2.7; P<0.05).
Multivariate Relationships
The hierarchical stepwise regression analysis predicting
future LVM/height2.7 found initial
LVM/height2.7 to be the single best predictor
(R2=0.38). This was followed in the
second block by BMI (R2 increase=0.11)
and gender (R2 increase=0.02) and
finally in the third block by the supine resting TPR readings from the
initial evaluation (R2 increase=0.02;
total R2=0.53; P<0.001).
No other variables added significantly (P<0.05) to the
model.
Follow-up LVM/BSA was predicted by baseline LVM/BSA (R2=0.29), followed in the second block by weight (R2 increase=0.06), gender (R2 increase=0.11), and in the third block by mean supine resting TPR (R2 increase=0.02). SBP change score to car-driving simulation was the only other parameter to enter the model in the final block (R2 increase=0.03; total R2=0.48). Follow-up MFS was predicted by baseline MFS (R2=0.04), followed by race (white more than black; R2 increase=0.04) and mean supine TPR (ie, negative relationship) in the second block (R2 increase=0.06; total R2=0.13).
| Discussion |
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Prediction of Future LV Myocardial Function
To the best of our knowledge, this is the first study in youth to
reveal an interaction between LV midwall performance and race.
Blacks had relatively lower MFS ratio than white youth. The reason for
this difference is not fully understood. This finding is, however,
consistent with the known association of increased RWT, TPR,
and LVM index on the one hand and lower MFS ratio on the
other.21 Although a direct clinical relevance is not
implied, this finding in black youth may be a preclinical marker of
adverse prognosis. In view of recent findings that subtle decreases in
MFS are associated with increased cardiovascular risk
profile in asymptomatic adults,24 follow-up
studies are needed to determine whether a lower MFS ratio in
normotensive youth predicts earlier onset of
cardiovascular events.
Relationship of ABP to Future LVM
To our knowledge, only 1 study has examined the relationship
between ABP and LVM in youth. Using a cross-sectional design, Belsha et
al25 found daytime and nighttime SBP but not DBP to be
moderately significantly correlated with LVM indexed by height cubed in
a sample of normotensive and mildly hypertensive adolescents. Several
cross-sectional studies in adults found 24-hour SBP to be positively
associated with unindexed LVM.26 27 The present
findings extend these previous cross-sectional studies in that daytime,
nighttime, and 24-hour ambulatory SBP were all positively related to
both measures of indexed LVM 2.3 years later. Similar to the findings
of Belsha et al25 and the few adult
studies,26 27 ambulatory DBP was not related to
either measure of indexed LVM. In the present study, no racial or
gender-related differences were found for the LVM and ambulatory SBP
relationships, suggesting that the predictive value of ambulatory SBP
did not vary by race or by gender.
Relation of Hemodynamics at Rest and During Acute
Stress to Future LVM
The present results corroborate other recent longitudinal
findings in youth in that resting SBP was correlated positively with
follow-up LVM indexed either by height2.7 or
BSA.10 11 12 Likewise, resting heart rate was negatively
correlated to both follow-up measures of indexed LVM. It has been
hypothesized that this inverse relationship may be partly related to
increased aerobic fitness, which is associated with lower heart rate
and increased LVM. The present findings lend support to this in
that baseline resting heart rate was also correlated negatively with
the LVIDD at follow-up (r=-0.37; P<0.01).
Several recent pediatric studies have observed significant associations between hemodynamic responsivity to acute laboratory stressors and LVM. Cross-sectional studies have shown the SBP and/or TPR responsivity to video game challenge, forehead cold stimulation, and mirror tracing to be positively related to indexed and unindexed measures of LVM.7 9 Longitudinal studies have found the SBP, cardiac output, and/or TPR responsivity to physical (ie, dynamic exercise, orthostasis, cold pressor) and interpersonal behavioral stressors (ie, social stressor interview, car-driving simulation) to be associated with indexed LVM 2 to 3 years later.11 12 13 Our findings corroborate these studies in that SBP and/or TPR responses to a variety of passive physical or challenging behavioral stressors were positively related to measures of indexed LVM 2.3 years later.
This is the first study to evaluate comprehensively the independent contributions of hemodynamic functioning at rest, during acute stress, and in the field (ABP) in the prediction of LVM. Similar to other recent longitudinal findings,11 12 the present results confirm that male gender, adiposity, vasoconstrictive tone, and hemodynamic stress responsivity are independent predictors of indexed LVM.
Unexpectedly, ABP was not found to be a significant independent predictor of indexed LVM. Findings concerning the relationship between ABP and LVM have been mixed. Some adult studies have reported positive correlations, while others failed to establish such associations.26 27 28 29 The lack of independent predictive power in the present study may have been due in part to the moderate correlations between ABP and measures of weight, adiposity, and resting TPR, all of which were independent predictors of both measures of indexed LVM.
In summary, baseline LVM index and MFS predicted cardiac structure and function 2.3 years later in these youth. Increased TPR consistently predicted future decreased MFS and increased LVM indexed by height2.7 or BSA. This would suggest that increased vascular tone leading to increased TPR plays a primary role in cardiac remodeling (increased mass and/or increased RWT) and function (lower MFS). The relative clustering of these findings (increased RWT, LVM index, TPR, and lower MFS ratio) in black youth with family histories of cardiovascular diseases may provide a possible explanation for the excess cardiovascular morbidity and mortality in black adults. It may be that these black youth with higher LVM index, resting SBP, and RWT exhibit an exaggerated BP responsivity to daily recurring psychosocial stress, which over time may elicit future increases in BP and LVM and lower midwall shortening. Future studies are necessary to evaluate these proposed mechanisms. Equally importantly, long-term follow-up is needed to determine whether the racial difference in MFS ratio observed herein is associated with significant racial differences in clinical outcomes.
| Acknowledgments |
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Received May 3, 1999; first decision May 18, 1999; accepted June 21, 1999.
| References |
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