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Ambulatory Blood Pressure and Metabolic Abnormalities in
Hypertensive Subjects With Inappropriately High
Left Ventricular Mass
Vittorio Palmieri, Giovanni de Simone, Mary J. Roman, Joseph E. Schwartz,
Thomas G. Pickering, Richard B. Devereux
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Abstract—Appropriateness of left ventricular (LV) mass to cardiac workload can be evaluated by the ratio of observed LV
mass to the value predicted for an individual’s gender, height2.7, and stroke work at rest (%PLVM). It is unclear which
pathophysiological factors are associated with inappropriately high LV mass in hypertensive subjects. Adequate LV
mass was defined by the 90% confidence interval (73% to 128%) of the distribution of %PLVM in 393 normal-weight
normotensive subjects. In 185 hypertensive subjects (aged 56611 years; 60% male, 29% black), according to %PLVM,
164 (88%) had adequate LV mass, 16 (9%) had inappropriately high LV mass (%PLVM .128%), and 5 (3%) had
%PLVM ,73% (low LV mass). Age, gender, smoking habit, proportion of never-treated subjects, total cholesterol,
triglycerides, and creatinine levels did not differ significantly between subjects with adequate and inappropriately high
LV mass. Body mass index, fasting glucose, and proportion of black subjects were higher (all P,0.05), while HDL
cholesterol was lower (P,0.05) in subjects with inappropriately high LV mass. Blood pressure at the echocardiogram
was comparable between subjects with adequate and inappropriately high LV mass, but the latter group had higher
ambulatory blood pressure (P,0.01). Subjects with inappropriately high LV mass also had higher aortic root dimension
and LV relative wall thickness and relatively lower LV systolic performance than those with adequate LV mass (all
P,0.001). Larger aortic root diameter and lower systolic function were also found in hypertensive subjects with
inappropriate LV hypertrophy compared with those with adequate LV hypertrophy. In an exploratory case-control study
that compared subjects with low %PLVM with age-matched counterparts with adequate LV mass, low %PLVM was
associated with lower body mass index, more favorable metabolic profile, and higher LV myocardial contractility.
Higher body mass index, larger aortic root, and black race were independent correlates of increased %PLVM. Thus, in
arterial hypertension, levels of LV mass inappropriately high for gender, cardiac workload, and height2.7 are associated
with higher body mass index, higher ambulatory blood pressure, larger aortic root diameters, and relatively low
myocardial contractility. (Hypertension. 1999;34:1032-1040.)
Key Words: hypertrophy, left ventricular n hypertension, white coat n obesity n metabolism n echocardiography
A
lthough left ventricular (LV) hypertrophy is an adaptation that preserves cardiac pump function in arterial
hypertension, it also represents a preclinical disease strongly
predictive of cardiovascular morbidity and mortality.1,2 LV
mass growth is related to hemodynamic factors, such as
systolic blood pressure (BP), stroke volume, and body size.
The ideal amount of lean body mass genetically programmed
has been estimated to be proportional to height2.7 in adults.
Therefore, height2.7, cardiac workload, and gender have been
identified as major physiological determinants of LV
growth,3 and, in a reference sample of normal-weight normotensive subjects, they may be used to estimate ideal amount of
cardiac muscle. The observed/predicted LV mass ratio may
be used to evaluate correlates of the deviation of measured
LV mass from predicted LV mass. In a preliminary study,
hypertensive subjects with LV mass exceeding values predicted by major physiological correlates (termed “inappropriately high LV mass”) had a higher rate of subsequent
cardiovascular death.4
Evaluation of the 24-hour ambulatory BP profile explains
the variability of LV mass better than clinic BP5,6 and can
assess day-night BP variability,7,8 which is of interest because
lack of a nocturnal BP fall has been associated with increased
LV mass.8,9 Moreover, “white coat” hypertension can be
detected by ambulatory monitoring.10 Furthermore, lower LV
contractility,11,12 larger arterial size,13,14 and metabolic abnormalities15–17 have all been associated with higher LV mass.
However, whether 24-hour ambulatory BP profile, metabolic
Received May 11, 1999; first decision May 31, 1999; revision accepted July 6, 1999.
From the Division of Cardiology and Hypertension Center, Department of Medicine, New York Presbyterian Hospital, Joan and Sanford I. Well
Medical College of Cornell University, New York, NY.
Correspondence to Richard B. Devereux, MD, Division of Cardiology, Box 222, New York Presbyterian Hospital–Weill Medical College of Cornell
University, 525 E 68th St, New York, NY 10021. E-mail [email protected]
© 1999 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org
1032
Palmieri et al
abnormalities, and myocardial contractility may contribute to
explain levels of LV mass inappropriately high for hemodynamic stimuli, height2.7, and gender in hypertensive subjects
is unclear. Accordingly, this study was designed to investigate ambulatory BP and cardiovascular features in hypertensive subjects with adequate or inappropriate LV mass. In
addition, metabolic status (fasting glucose, total and HDL
cholesterol, and triglyceride levels), LV geometry, and systolic function were also evaluated.
Methods
Study Population
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A total of 185 hypertensive individuals were studied, of whom 76
were referred from the Hypertension Center of The New York
Hospital from January 1990 to July 1995, 104 were referred from a
worksite-based study,18,19 and 5 were identified in a population
survey of elderly volunteers from the community. Criteria for
diagnosis of hypertension were clinic systolic BP $140 (or
$160 mm Hg for subjects older than 65 years) or diastolic BP
$90 mm Hg. Subjects underwent 24-hour ambulatory BP monitoring, echocardiogram, and metabolic screening; 41% of the subjects
had not been previously treated, while the others had stopped
antihypertensive treatment 3 weeks to 6 years before the study
protocol. All subjects were free of clinical, echocardiographic, or
laboratory evidence of coronary or valvular heart disease, diabetes
mellitus, cerebrovascular disease, or secondary hypertension. Subjects with awake ambulatory BP ,134/90 mm Hg were considered
to have white coat hypertension.10 Informed consent was obtained
from all subjects included.
BP Determination
Clinic BP was estimated by a mercury sphygmomanometer as the
average of at least 3 measurements by a physician or qualified nurse.
Echo BP is BP measured at the end of the echocardiogram, after '30
minutes of supine rest in a dark room. Ambulatory BP monitoring
was recorded during a routine day by a SpaceLabs 90207 device.10
Briefly, the monitor was placed on the nondominant arm and set to
take BP readings every 15 minutes during the working day and every
30 or 60 minutes during sleep. Subjects were instructed to record
their activity and location after each awake in a diary to permit
identification of the awake and sleep time. The sleep-awake BP fall
was assessed as the absolute and relative changes between sleep and
awake systolic and diastolic BP.
Echocardiography
All subjects underwent standard M-mode and 2-dimensional echocardiography by a skilled research technician using commercially
available echocardiography equipped with 2.5- to 3.5-MHz transducers. LV dimensions were assessed from 2-dimensionally guided
M-mode tracings (American Society of Echocardiography)20 or, if
M-mode recordings were not technically adequate, by 2-dimensional
measurements.21 M-mode measurements of blinded tracings were
performed on up to 6 cycles with the use of a digitizing tablet and
were averaged. LV end-systolic, end-diastolic, and stroke volumes
were calculated with the use of Teichholz’s method.22,23 Aortic root
diameter was measured at end-diastole by the leading-edge-toleading-edge technique at the maximal diameter of the sinuses of
Valsalva.24 Observed LV mass was calculated by the adjusted
American Society of Echocardiography method25 and indexed for
height2.7 or body surface area. LV hypertrophy was defined with the
use of gender-specific cut points (LV mass/height2.7 .47 g/m2.7 in
women; LV mass/height2.7 .50 g/m2.7 in men).26 Predicted values of
LV mass were derived by an equation previously developed in a
reference population of 393 normal-weight, normotensive adults,
aged 18 to 85 years, which includes an indicator variable for gender
(men52; women51), height2.7, and stroke work as a measure of
cardiac workload [echo systolic BP3Doppler stroke volume30.01443]: predicted LV mass518.13gender10.643stroke
Inappropriate LV Mass in Arterial Hypertension
1033
work16.633height2.7155.7; (R250.60, SEE523.2 g, P,0.001).3
This equation provides estimates of LV mass expected for cardiac
workload, height2.7 (used as surrogate for genetically programmed
lean body mass for that specific height27–29), and gender. The
observed/predicted LV mass ratio3100 (%PLVM) was estimated in
the reference population to identify the 5th and 95th percentiles of its
distribution (73% to 128%). With the use of the aforementioned
equation, the %PLVM was then computed in hypertensive subjects.
Subjects with %PLVM .128% (16 of 185 subjects [9%]) were
classified as having inappropriately high LV mass, whereas LV mass
was considered adequate if %PLVM was between 73% and 128%
(164 of 185 subjects [88%]). Subjects with %PLVM ,73% (5 of 185
subjects [3%]) were classified as having inadequate LV mass but
were not considered in primary analyses because of the likelihood of
unstable results with such small cell size. Relative wall thickness was
calculated as twice posterior wall in diastole divided by internal
diameter1 and was used as an estimate of LV geometry. Midwall
circumferential end-systolic stress (ESS) was assessed as previously
reported.26 Endocardial fractional shortening (FS), midwall fractional shortening (MWS), as well as 2 estimates of afterloadindependent LV systolic function, the percentage of predicted
midwall shortening for a given circumferential ESS (termed stresscorrected MWS), a measure of myocardial contractility, and the ratio
ESS/LV end-systolic volume index (ESS/ESVi), a measure of LV
systolic chamber function, were derived as previously described.11,26
Statistical Analysis
Data were stored and analyzed with SPSS 8.0 (SPSS Inc). Continuous variables, expressed as mean6SD, were log-transformed when
necessary to better satisfy distributional assumptions before parametric tests were used. Student’s t test for independent groups was
used to compare subjects with inappropriately high or adequate LV
mass. ANCOVA was used to adjust the results for age, body mass
index (BMI), gender, and race (blacks versus nonblacks), and
adjusted means and SDs are provided in parentheses in the tables.
Two-tailed Fisher’s exact tests were used to test the null hypothesis
for categorical variables. Pearson correlations were used to investigate relationships between LV mass, %PLVM, and demographic,
metabolic, and echocardiographic data. The relationships of
%PLVM to aortic root diameter and LV systolic performance,
controlling for age, BMI, and diastolic ambulatory BP, were investigated with partial correlation. In an exploratory analysis, the small
group classified as having inadequate LV mass was matched by age
61 year with subjects having adequate LV mass. Gender was not
considered because it was included in the equation to predict LV
mass. To maximize statistical power, we matched on average 7
subjects with adequate LV mass to each subject having relatively low
LV mass. ANOVA, weighted to simulate an equal number of control
subjects per case, was used to test differences between these 2
groups. A 2-tailed P,0.05 was considered statistically significant.
Results
Comparisons Between Hypertensive Subjects With
Adequate Versus Inappropriately High LV Mass
Demographic and Metabolic Characteristics
The sample for the primary analyses comprised 180 clinically
hypertensive subjects (mean age, 56611 years; range, 30 to 81
years; 111 men [62%]; 54 blacks [30%]), of whom 164 had
adequate and 16 inappropriately high LV mass (Table 1). No
significant differences were found in age, gender, height2.7, proportion of never-treated subjects, or smoking habit. BMI and the
proportion of blacks were higher in subjects with inappropriately
high LV mass. Total cholesterol, triglyceride, and creatinine levels
were comparable between the 2 groups, while fasting glucose was
higher and HDL cholesterol was lower in subjects with inappropriately high LV mass. Adjustment for covariates eliminated differences in fasting glucose and HDL cholesterol.
1034
Hypertension
November 1999
TABLE 1. Demographic and Metabolic Characteristics of Hypertensive Subjects With Adequate vs
Inappropriately High LV Mass
Variables
Age, y
Male, %
Adequate LV Mass
(n5164)
Inappropriately High LV
Mass (n516)
P
56611
5468
NS
zzz
60
81
NS
zzz
P*
BMI, kg/m2
26.463.8
30.364.1
0.000
Height [m]2.7
4.260.6 (4.260.6)
4.260.5 (4.260.6)
NS
zzz
NS†
Black, %
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27
63
0.006
zzz
Current smokers, %
9
13
NS
zzz
Never-smokers, %
56
63
NS
zzz
Former smokers, %
35
25
NS
zzz
Never-treated patients, %
42
25
NS
Fasting glucose, mmol/L
4.960.8 (4.960.9)
5.360.8 (5.160.8)
0.03
zzz
NS
Total cholesterol, mmol/L
5.8461.14 (5.8461.16)
5.5961.06 (5.7461.14)
NS
NS
HDL cholesterol, mmol/L
1.3760.39 (1.3760.39)
1.1660.34 (1.1460.36)
0.03
NS
Triglycerides, mg/dL
1436112 (1436114)
142696 (1386111)
NS
NS
Creatinine, mmol/L
88619 (88617)
96615 (89616)
NS
NS
Values are mean6SD unadjusted (and adjusted).
*P adjusted for covariates (age, gender, BMI, and race) (ANCOVA).
†P adjusted for gender and race.
Blood Pressure
Subjects with inappropriately high or adequate LV mass had
comparable systolic BP at the end of the echocardiogram,
whereas diastolic BP tended to be higher (P50.1) in those with
inappropriately high LV mass (Table 2). In contrast, 24-hour,
awake, and sleep systolic and diastolic ambulatory BPs were
consistently higher in subjects with inappropriately high than in
those with adequate LV mass. After adjustment for covariates
(age, gender, race, and BMI), differences in ambulatory systolic
BP did not reach statistical significance (24 hour, P50.08;
awake, P50.07; and sleep, P50.09), while differences in
diastolic BP remained statistically significant. The day-night
TABLE 2.
difference in BP was similar in the 2 groups, even when genders
were analyzed separately (data not shown; all P.0.1). Pulse
pressure was also comparable in subjects with adequate versus
inappropriately high LV mass (clinic pulse pressure, 60616
versus 58612 mm Hg; awake pulse pressure, 55611 versus
56611 mm Hg; all P.0.1).
All 23 subjects (13% of 180) with white coat hypertension,
according to previously defined criteria,10 exhibited adequate
LV mass; none had clear-cut LV hypertrophy.
Echocardiographic Findings
As partially expected from the study design, LV mass/
height2.7 as well as LV mass/body surface area, used to
Rest and Ambulatory BP in Patients With Adequate or Inappropriately High LV Mass
Variables
Adequate LV Mass
Inappropriately High
LV Mass
Echo systolic BP, mm Hg
150619 (150617)
151620 (150617)
NS
NS
Echo diastolic BP, mm Hg
90610 (90610)
95616 (92611)
NS
NS
24-hour systolic BP, mm Hg
144615 (144615)
152617 (151616)
0.03
NS
24-hour diastolic BP, mm Hg
89610 (89610)
98612 (96611)
0.001
0.009
P
P*
Awake systolic BP, mm Hg
148615 (148615)
157618 (156615)
0.03
NS
Awake diastolic BP, mm Hg
92610 (92610)
101613 (100610)
0.001
0.009
Sleep systolic BP, mm Hg
131617 (131616)
140616 (137616)
0.03
NS
Sleep diastolic BP, mm Hg
78611 (78611)
87613 (85611)
0.001
0.03
Systolic BP, mm Hg
217610 (217610)
216610 (218610)
NS
NS
Diastolic BP, mm Hg
21567 (21467)
21466 (21567)
NS
NS
Systolic BP, %
21267 (21267)
21066 (21267)
NS
NS
Diastolic BP, %
21668 (21667)
21467 (21567)
NS
NS
Sleep-Awake difference
D% Sleep vs awake
Values are mean6SD unadjusted (and adjusted).
*P adjusted for covariates (age, gender, BMI, and race) (ANCOVA).
Palmieri et al
TABLE 3.
Inappropriate LV Mass in Arterial Hypertension
1035
Echocardiographic Findings in Patients With Adequate or Inappropriately High LV Mass
Adequate LV Mass
Inappropriately High LV
Mass
LV mass index, g/m2.7
4068
5768
zzz
zzz
LV mass index, g/m2
88617
121619
LVIDd, cm
5.060.5 (5.060.4)
5.260.5 (5.160.5)
zzz
0.02
zzz
NS
LVIDs, cm
3.160.5 (3.160.4)
3.560.5 (3.560.5)
,0.0005
0.002
0.3760.05 (0.3760.05)
0.4360.05 (0.4260.06)
,0.0005
0.001
Aortic root diameter, cm
3.360.4 (3.360.4)
3.760.4 (3.760.04)
,0.0005
,0.0005
Left atrial dimension, cm
3.460.5 (3.560.5)
3.660.6 (3.460.5)
NS
NS
ESS, kdyne/cm2
146633 (146634)
151640 (151635)
NS
NS
3865 (3865)
3365 (3365)
0.002
0.001
,0.0005
Variables
Relative wall thickness
FS, %
P
P*
1862 (1862)
1562 (1562)
,0.0005
Stress-corrected MWS, %
107612 (107612)
87610 (89612)
,0.0005
,0.0005
ESS/ESVi, kdyne/cm3
7.461.5 (7.561.4)
5.660.8 (5.661.4)
,0.0005
,0.0005
68612 (68612)
72613 (70612)
NS
NS
MWS, %
Heart rate, bpm
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Values are mean6SD unadjusted (and adjusted). LVIDd indicates LV internal diameter at end-diastole; LVIDs, LV internal diameter at end-systole.
*P adjusted for covariates (age, gender, BMI, and race) (ANCOVA).
minimize the influence of obesity, were higher in subjects
with inappropriately high LV mass than in those with
adequate LV mass (Table 3). LV systolic and diastolic
dimensions and relative wall thickness were also higher in
subjects with inappropriately high LV mass. ESS was similar
between the 2 groups. LV endocardial FS, MWS, stresscorrected MWS, and ESS/ESVi ratio were lower in subjects
with inappropriately high LV mass, even when we controlled
for covariates.
The aortic root diameter was also significantly larger in
subjects with inappropriately high LV mass even with adjust-
ment for covariates. In subjects with adequate LV mass,
aortic root diameter did not differ between those with or
without LV hypertrophy (3.29 versus 3.25 cm; P.0.1).
Adequate and Inappropriate LV Hypertrophy
A separate analysis was performed among subjects with LV
hypertrophy, comparing those with inappropriately high LV
mass (inappropriate LV hypertrophy, n512) with those with
adequate LV mass (adequate LV hypertrophy, n519) (Table
4). Subjects with inappropriate LV hypertrophy tended to be
younger and have higher BMI than those with adequate LV
TABLE 4. Comparison Between Patients With Adequate vs Inappropriately High
LV Mass Among Hypertensive Subjects With LV Hypertrophy
Variables
Age, y
BMI, kg/m2
Women, n (%)
Black, n (%)
Adequate LV
Hypertrophy
(n519)
Inappropriate
LV Hypertrophy
(n512)
6069
5469
27.663.7
30.164.2
10 (53)
1 (8)
zzz
0.02
Difference
26
2.5
P
0.09
0.09
7 (37)
7 (58)
156614
161618
zzz
5
0.07
Awake diastolic BP, mm Hg
94612
103613
10
0.06
LV mass index, g/m2.7
5566
6165
6
LVIDd, cm
5.460.4
5.460.3
zzz
NS
0.3760.05
0.4260.04
Aortic root diameter, cm
3.360.4
3.960.3
FS, %
3865
3165
Awake systolic BP, mm Hg
Relative wall thickness
zzz
0.05
0.6
27
NS
0.03
0.001
0.03
1862
1462
24
0.003
Stress-corrected MWS, %
109614
8869
211
,0.0005
ESS/ESVi, kdyne/cm3
6.661.5
5.660.8
21
0.03
Creatinine, mmol/L
83616
96614
13
0.04
Fasting glucose, mmol/L
5.160.4
5.360.8
0.2
HDL cholesterol, mmol/L
1.4260.47
1.1160.39
20.31
MWS, %
Abbreviations are as defined in Table 3.
NS
0.09
1036
Hypertension
November 1999
TABLE 5. Comparison Between Age-Matched Patients With Inappropriately Low
vs Adequate LV Mass
Variables
2
BMI, kg/m
Women, n (%)
Black, n (%)
Awake SBP, mm Hg
Inappropriately Low
LV Mass (n55)
Adequate LV Mass
(Age-Matched Group)
(n536)
25.463.1
24.863.0
4 (80)
21 (58)
zzz
NS
0
7 (19)
zzz
8
NS
158638
150615
Difference
0.6
P
NS
NS
Awake DBP, mm Hg
88612
89613
21
NS
LV mass index, g/m2.7
36615
4069
24
4.760.6
4.960.5
20.2
zzz
NS
0.3560.04
0.3760.04
20.02
NS
Aortic root diameter, cm
3.060.1
3.360.4
20.3
NS
FS, %
4466
3865
6
0.06
LVIDd, cm
Relative wall thickness
MWS, %
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Stress-corrected MWS, %
3
2162
1862
4
0.006
12968
109613
20
0.002
ESS/ESVi, kdyne/cm
11.063.6
7.761.7
Creatinine, mmol/L
94644
84620
10
NS
Fasting glucose, mmol/L
4.160.3
4.960.7
20.8
0.05
HDL cholesterol, mmol/L
1.7360.44
1.4260.47
73638
1516104
Triglycerides, mg/dL
4.3
0.31
278
0.02
NS
0.02
Abbreviations are as defined in Table 3.
hypertrophy, but those differences did not reach statistical
significance. Women predominated among subjects with
adequate LV hypertrophy, whereas no difference was found
in race prevalence. Echo BPs (not shown) were similar
between groups. However, ambulatory BP tended to be
higher in subjects with inappropriate LV hypertrophy. LV
mass/height2.7 or LV mass/body surface area to account for
the impact of obesity, relative wall thickness, and aortic root
diameter were higher in subjects with inappropriate than
adequate LV hypertrophy. Endocardial FS, MWS, stresscorrected MWS, and ESS/ESVi were lower, while creatinine
level was higher, in subjects with inappropriate LV hypertrophy. Fasting glucose level tended to be higher and HDL
cholesterol lower in subjects with inappropriate LV hypertrophy (P5NS).
Comparisons Between Hypertensive Subjects With
Inappropriately Low LV Mass and Age-Matched
Hypertensive Subjects With Adequate LV Mass
An age-matched pilot case-control study was designed to
compare the 5 subjects with relatively low LV mass
(%PLVM ,73%) with age-matched hypertensive subjects
with adequate LV mass (n536) (Table 5). After weighting,
subjects with low LV mass and those with adequate LV mass
had similar mean age (68 years) by design. BMI and the
proportion of women were similar between the 2 groups.
There were no black hypertensive subjects in the group with
low LV mass, although there were 7 (19%) among those with
adequate LV mass (P5NS). Echo systolic and diastolic BP
tended to be higher in subjects with low LV mass (185/94
versus 159/89 mm Hg; all P.0.05), while 24-hour, awake,
and sleep BPs were similar between groups. None of the
subjects with low LV mass had white coat hypertension. LV
mass, indexed for either height2.7 or body surface area, and
relative wall thickness were statistically indistinguishable
between groups. Aortic root diameter tended to be lower and
FS higher in subjects with inappropriately low LV mass,
without reaching statistical significance (P$0.06). Of note,
MWS, stress-corrected MWS, and ESS/ESVi were significantly higher and fasting glucose and triglyceride (P,0.05)
levels were lower in subjects with inappropriately low LV
mass. The difference in HDL cholesterol was not statistically
significant.
Relationships of Observed/Predicted LV Mass
Ratio to Aortic Root and LV Function
LV mass was not significantly related to age, but %PLVM
showed a negative relationship to age, probably reflecting the
positive relationships between age and stroke work (r50.27,
P,0.01) that may tend to reduce the increment of observed/
predicted LV mass ratio with increasing age (Table 6). BMI
was more strongly related to LV mass than to %PLVM.
Ambulatory (awake or sleep) and echo diastolic BP were
positively related to LV mass, whereas %PLVM showed a
positive relationship to ambulatory diastolic BPs (both awake
or sleep) but not to echo diastolic BP. After adjustment for
age and BMI, awake diastolic BP showed a significant
positive relationship to LV mass (partial r50.36, P,0.001)
and %PLVM (partial r50.20, P,0.005). No significant
associations were found between LV mass or %PLVM with
systolic or diastolic day-night BP differences. A positive
relationship was found between ESS and LV mass but not
with %PLVM. Of interest, parameters of LV systolic function
(endocardial FS, MWS, stress-corrected MWS, and ESS/
Palmieri et al
TABLE 6.
Inappropriate LV Mass in Arterial Hypertension
1037
Correlates of LV Mass and Observed/Predicted LV Mass Ratio
Bivariate Correlation
Partial Correlation
Variables
LV Mass
%PLVM
LV Mass
%PLVM
Age
20.10
20.18*
zzz
zzz
BMI
0.43‡
0.33‡
zzz
zzz
Echo diastolic BP
0.35‡
0.11
zzz
zzz
Awake diastolic BP
0.33‡
0.25‡
zzz
zzz
Sleep diastolic BP
0.35‡
0.25‡
zzz
zzz
DAsleep vs awake systolic BP
0.08
0.02
zzz
zzz
DAsleep vs awake diastolic BP
0.13
0.04
Aortic root diameter
0.55‡
0.35‡
zzz
0.46*
zzz
0.27‡
ESS
0.22†
0.02
0.21*
0.01
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FS
20.23‡
20.47‡
20.21*
20.45‡
MWS
20.34‡
20.75‡
20.25†
20.73‡
Stress-corrected MWS
20.29‡
20.78‡
20.19*
20.76‡
ESS/ESVi
20.49‡
20.51‡
20.60‡
20.52‡
*P,0.05, †P,0.01, ‡P,0.001 (partial correlation controlling for age, BMI, and awake diastolic BP).
ESVi ratio) had moderate negative correlations to LV mass
but were even more strongly negatively related to %PLVM.
After adjustment for age, BMI and awake diastolic BP, high
values of LV mass, and %PLVM were associated with higher
aortic root diameters and lower LV systolic function.
Discussion
In the present study we investigated cardiovascular features
associated with values of LV mass that are higher than those
predicted by gender, height2.7, and cardiac workload,3 a
condition we termed inappropriately high LV mass.4 This
study provides initial evidence that inappropriately high LV
mass is associated with high BMI even though the formula to
predict LV mass accounts for ideal lean body mass for given
height (that is, height2.7) and hemodynamic factors (stroke
volume and systolic BP) that mediate obesity-associated
increases of LV mass.30 Within this clinically hypertensive
sample, diastolic ambulatory BP slightly discriminated those
with inappropriately high LV mass, even after controlling for
obesity and systolic BP (included in stroke work). Inappropriately high LV mass was also associated, independently of
age, diastolic awake BP, and BMI, with relatively depressed
LV systolic performance, which is documented to have
adverse prognostic significance. The association of metabolic
abnormalities (high fasting glucose levels and worse lipid
profile) with inappropriately high LV mass could be explained by the confounding effect of obesity. The fact that a
similar pattern was found in the subset of subjects with LV
hypertrophy suggests that inappropriateness of LV mass may
represent a marker of a transition from a compensatory to a
pathological phenotype of severe LV hypertrophy.
In continuity with our main results, an additional casecontrol study performed to explore differences between
subjects with inappropriately low LV mass and age-matched
hypertensive subjects with adequate LV mass provided initial
evidence of associations of relatively low LV mass with
lower BMI, higher LV systolic performance, and a favorable
metabolic profile, characterized by lower fasting glucose and
triglyceride levels and higher HDL cholesterol.
Inappropriately High LV Mass, Obesity, and
Metabolic Findings
Subjects with inappropriately high LV mass had higher BMI,
higher fasting glucose levels, and lower mean HDL cholesterol than subjects with adequate LV mass. The strong
association of overweight with the observed/predicted LV
mass ratio in hypertensive subjects might not be purely an
extension of an association between relative body weight and
LV mass in apparently normal adults but may reflect, at least
in part, the importance of overweight/obesity in the pathophysiology of hypertension. The equation used to predict LV
mass was derived in normal-weight subjects and includes
body height to the power of 2.7 but not weight. Height2.7 is a
marker of the individual’s “ideal” lean body mass programmed for the size of skeleton27–29 for which the cardiac
muscle might be also genetically programmed and is linearly
related to LV mass. However, height2.7 does not account for
the additional increase in lean body mass that usually occurs
in obese subjects. Thus, the ratio of observed/predicted LV
mass may be particularly sensitive to the effect of
overweight-related metabolic abnormalities and hemodynamic impact of increased lean body mass. However, the equation
to predict adequacy of LV mass includes both systolic BP and
stroke volume, which we have previously shown to increase
in parallel with body size in overweight and obese individuals.30 Therefore, the equation to predict LV mass accounts for
hemodynamic stimulus for LV growth in obesity. Obesityrelated insulin resistance (as suggested by metabolic findings)
and/or elevated blood viscosity31 might contribute to increase
the ratio of observed/predicted LV mass. Obesity has been
repeatedly associated with increased LV mass32–34 as well as
with hyperinsulinemia and insulin resistance.15,35
In contrast, subjects with relatively low LV mass tended to
be lean and to have low fasting glucose, total cholesterol, and
1038
Hypertension
November 1999
triglyceride levels as well as high HDL cholesterol, which are
hallmarks of potentially optimal glucose tolerance. Furthermore, differences in BMI and other metabolic findings
between subjects with adequate versus inappropriately high
LV mass approached statistical significance among the small
subgroup (n531) of subjects with LV hypertrophy, which
suggested associations of a magnitude that could be pathophysiologically important.17
Contribution of Ambulatory Blood Pressure to
Inappropriately High LV Mass
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LV mass is more closely correlated with ambulatory BP than
conventional clinic BP measurements.5,6,8 –10 Although BP
evaluated at the end of the echocardiogram under standardized resting conditions may be more reliable than usual
measures of clinic BP, in our study only ambulatory BP
statistically differentiated the 2 groups, independently of age,
gender, race, and BMI. In the analysis of subjects with LV
hypertrophy, ambulatory BPs tended to be higher
('10 mm Hg) in subjects with inappropriate LV mass than
adequate LV mass, with a loss of statistical significance that
may have been due to the small cell size. Thus, our study
provides evidence of a better definition of cardiac hemodynamic load by ambulatory than clinical BP. On the other
hand, subjects with inappropriately high LV mass did not
exhibit a different day-night BP profile than subjects with
adequate LV mass, either in the entire sample or in analyses
performed separately in women and men. However, men
predominated in our sample, reducing power to detect abnormalities in the smaller subset of hypertensive women. Relations of day-night BP difference to absolute or indexed LV
mass are debated,6 –9,36 – 43 and further investigation is required
to address relationships of inappropriate levels of LV mass to
day-night BP profile in hypertensive as well as in populationbased samples.
Blood Pressure and Relatively Low LV Mass
Hypertensive subjects with low %PLVM exhibited high echo
BPs, and none of them had white coat hypertension, while the
levels of 24-hour and awake BPs were similar to those in
age-matched subjects with adequate LV mass, leading to a
greater difference between clinical BP and ambulatory BP. In
this small group, therefore, resting stroke work may overestimate the average daily stroke work, leading to low observed/predicted LV mass ratio. The small cell size represents
a major limitation for conclusive physiological inference, and
further studies are needed.
Echocardiographic Findings
The larger aortic root diameters in subjects with inappropriate
as opposed to adequate LV mass suggest morphological and
functional relationships between the proximal arterial tree
and appropriateness of LV mass. The difference in aortic root
diameter remained significant (P,0.01, data not shown) after
adjustment for age, gender, race, and BMI as potential
covariates of aortic root diameter, as well as in alternative
analyses that considered systolic, diastolic, or pulse pressure
alternatively as covariates. Thus, the between-group difference in aortic root diameter is independent of BP differences
between subjects with inappropriate or adequate LV mass. It
is also notable that this difference was still present in the
subset of subjects with LV hypertrophy. Mean aortic root
diameter showed a significant positive trend (from 3.0 to 3.3
to 3.8 cm) from subjects with relatively low %PLVM, to
subjects with adequate LV mass, and to those with inappropriate LV hypertrophy. Parallel changes in cardiac and
large-artery structure have been previously documented for
smaller-capacitance arteries,44 and a positive relationship
between BP and aortic root size has also been reported.45,46 A
relationship between aortic root diameters and LV mass has
been recently reported in a population-based study.14 Although pulse pressure was comparable in the 2 groups, the
association between larger aortic root size and inappropriately high LV mass may depend on increased proximal aortic
stiffness, by enhancing LV wall stress in early systole as a
result of loss of aortic elastic reserve.47 Changes in the arterial
pressure waveform because of vascular stiffening48 may
mediate the stronger relation of LV mass with aortic root
dimension than with BP, with possible additional contributions of a nonhemodynamic nature.13,49
Additionally, inappropriately high LV mass was associated
with lower myocardial function as well as lower afterloadindependent LV systolic chamber function, which are strong
independent predictors of cardiovascular events.50,51 Those
differences remained highly significant even when we compared inappropriate LV hypertrophy with adequate LV hypertrophy, while subjects with relatively low observed/predicted LV mass had high LV systolic performance. Our
findings support previous observations of a potentially bidirectional relationship between myocardial contractility and
adaptation of LV muscle to growth stimuli.11,14,26
Conclusions
In hypertensive adults, values of LV mass that exceeded the
ones predicted by individual gender, height2.7, and stroke
work were associated with higher BMI, metabolic abnormalities, black race, higher ambulatory BP (but not with different
day-night BP profile), larger aortic root diameter, concentric
LV geometry, and lower LV systolic performance. These
characteristics were also confirmed in the subgroup of subjects with LV hypertrophy. Our findings also extend previous
observations in which lower myocardial contractility was
associated with less favorable metabolic profile, impaired
arterial compliance, and higher arterial wall thickness.52
Genetic factors may have an additional role in LV adaptation
to workload and body size.53
Acknowledgments
This work was supported in part by grants HL-18323 and HL-47540
from the National Heart, Lung, and Blood Institute, Bethesda, Md.
We would like to thank Mariane Spitzer, RDMS, for performing
echocardiograms and Virginia Burns for assistance in preparation of
the manuscript.
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Ambulatory Blood Pressure and M;etabolic Abnormalities in Hypertensive Subjects With
Inappropriately High Left Ventricular Mass
Vittorio Palmieri, Giovanni de Simone, Mary J. Roman, Joseph E. Schwartz, Thomas G.
Pickering and Richard B. Devereux
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Hypertension. 1999;34:1032-1040
doi: 10.1161/01.HYP.34.5.1032
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1999 American Heart Association, Inc. All rights reserved.
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