528
Circadian Blood Pressure Changes and Left
Ventricular Hypertrophy in
Essential Hypertension
Paolo Verdecchia, MD, Giuseppe Schillaci, MD, Massimo Guerrieri, MD,
Camillo Gatteschi, MD, Guglielmo Benemio, MD,
Francesca Boldrini, MD, and Carlo Porcellati, MD
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The effects of circadian blood pressure (BP) changes on the echocardiographic parameters of
left ventricular (LV) hypertrophy were investigated in 235 consecutive subjects (137 unselected
untreated patients with essential hypertension and 98 healthy normotensive subjects) who
underwent 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) and crosssectional and M-mode echocardiography. In the hypertensive group, LV mass index correlated
with nighttime (8:00 PM to 6:00 Am) systolic (r=0.51) and diastolic (r=0.35) blood pressure
more closely than with daytime (6:00 AM to 8:00 PM) systolic (r=0.38) and diastolic (r-0.20) BP,
or with casual systolic (r=0.33) and diastolic (r=0.27) BP. Hypertensive patients were divided
into two groups by presence (group 1) and absence (group 2) of a reduction of both systolic and
diastolic BP during the night by an average of more than 10% of the daytime pressure. Casual
BP, ambulatory daytime systolic and diastolic BP, sex, body surface area, duration of
hypertension, prevalence of diabetes, quantity of sleep during monitoring, funduscopic changes,
and serum creatinine did not differ between the two groups. LV mass index, after adjustment
for the age, the sex, the height, and the daytime BP differences between the two groups (analysis
of covariance) was 82.4 g/m2 in the normotensive patient group, 83.5 g/m2 in hypertensive
patients of group 1 and 98.3 g/m2 in hypertensive patients of group 2 (normotensive patients vs.
group pNS roup 1 vs. group 2, p- 0.002). The other echocardiographic parameters of LV
anatomy (i.e., interventricular septum and posterior wall thickness, relative wall thickness,
cross-sectional area) differed between the groups as did LV mass index. A statistically
significant inverse correlation was found between LV mass index and percentage of nocturnal
reduction of daytime ambulatory systolic (r=-0.34; p<0.001) and diastolic (r=-0.30;
p<0.001) BP. These findings suggest that in unselected hypertensive patients, an ambulatory
BP decline from day to night is associated with a lo*ei LV muscle mass. In these patients, a
nocturnal reduction of systolic and diastolic BP by more than 104 of daytime values could delay
or prevent the development of cardiac LV hypertrophy. (Circulation 1990;gl:528-536)
L
eft ventricular hypertrophy (LVH) detected by
electrocardiography (ECG) is an important
predictor of cardiovascular morbidity and
mortality.
In the Framingham study about 45% of all cardiovascular deaths were preceded by left ventricular
hypertrophy detected by electrocardiography (ECGLVH), and the 5-year mortality rate in men with
From the Division of Medicine, Civic Hospital "Beato G. Villa,"'
Citta della Pieve (Perugia), Italy.
Address for correspondence: Dr. Paolo Verdecchia, Civic Hospital "Beato G. Villa," Division of Medicine, 06062 Citta della
Pieve PG, Italy.
Received December 29, 1988; revision accepted September 27,
-
1989.
ECG-LVH was about 35%, as compared with 1015% in the absence of ECG-LVH.1-3 LVH is a usual
consequence of arterial hypertension, and it has been
shown to appear within 12 years in about 50% of
See p 700
patients with systolic blood pressure (BP) above 180
mm Hg.2
Compared with ECG, echocardiography shows a
higher sensitivity and an equally high specificity for
the diagnosis of LVH.4 Echocardiography allows
quantitation of LV muscle mass and provides values
reasonably near to those found at necropsy.4-7 ECG
allowed detection of LVH in no more than 38% of
hypertensive patients with echocardiographic LVH.8
Verdecchia et al Nighttime Blood Pressure and Cardiac Hypertrophy
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Some findings suggest that echocardiographic LVH
could be an independent predictor of cardiovascular
morbidity9 and mortality.10
The weak relation of casual BP to echocardiographic LVH1" becomes closer by using 24-hour BP
averages obtained with noninvasive12'13 or intraarterial14 ambulatory blood pressure monitoring
(ABPM).
Daytime BP, particularly that recorded during
recurring stressful situations,13 seems to be more
closely related to LVH than nighttime BP,1213 but in
other studies, both awake and sleep BP correlated
equally well with LV muscle mass,14 or nighttime BP
showed a better relation to LV muscle mass than did
daytime BP.15
ABPM shows that, in hypertensive patients, daytime BP usually decreases during night.16"17 The
degree and duration of nocturnal BP and wall stress
reduction could, thus, influence development of cardiac structural changes in hypertensive patients but
such hypothesis has never been specifically investigated.
Consequently, the present study was designed to
examine the relation of BP decline from day to night
to the echocardiographic parameters of LV anatomy
in a large population of unselected hypertensive
patients and healthy normotensive subjects undergoing 24-hour noninvasive ABPM.
Methods
Patient Population
One-hundred thirty-seven patients with essential
hypertension (47% female) and 98 healthy normotensive subjects (49% female) were studied. They
were consecutively chosen from patients with documented essential hypertension and healthy normotensive subjects examined in our laboratory and
meeting all the following criteria: 1) no antihypertensive drugs from at least 4 weeks, 2) good quality of
echocardiographic tracings, 3) agreement within 5
mm Hg between ambulatory BP recording unit and
mercury sphygmomanometer in at least three consecutive measurements taken simultaneously on the
same arm, 4) absence of clinical, ECG, or echocardiographic evidence of coronary artery disease, valvular disease (Doppler echocardiography), or renal
disease. Seven patients with mitral valve prolapse
and mild (grade 118) mitral regurgitation were
included.
Hypertensive patients were identified in a rather
restricted rural area of 6,500 inhabitants by a group
of general practitioners who referred all the subjects
with supine diastolic BP of 90 mm Hg or higher to
our hypertension clinic.
To be admitted to the study, supine diastolic BP
had to be 90 mm Hg or higher in at least three visits
at 1-week intervals, and all the four aforementioned
criteria had to be fulfilled.
Healthy normotensive patients were voluntary subjects chosen among medical students, hospital staff,
529
and other subjects examined for clinical check-up
and found healthy.
Experimental Procedures
Blood pressure measurements. Clinic BP was measured after 10 minutes of supine rest by using a
Hawksley Random Zero manometer (phase 1 and 5)
(Hawksley and Sons, Ltd., Lancing, West Sussex,
England). Ambulatory BP was recorded by using the
fully automatic unit ICR 5200 system (Spacelabs,
Redmond, Washington) that, in our laboratory,
showed a correlation of 0.97 with both systolic and
diastolic pressures measured simultaneously on the
same arm (by a Y connector) with a mercury sphygmomanometer.19 Others have reported a similar correlation using the same unit.20
The reading, editing, and analysis of data provided
by the unit was done by the ABP5600 interface
(Spacelabs, Redmond, Washington) installed on an
IBM/XT personal computer. Systolic readings
greater than 260 or less than 70 mm Hg, diastolic
readings greater than 150 or less than 40 mm Hg, and
pulse pressure readings greater than 150 or less than
20 mm Hg were automatically discarded. The unit
was set to take readings automatically every 15
minutes throughout the 24 hours. Overall, there were
107.4 (SD, 12) BP readings per patient, with 89.5
(SD, 11) readings per patient fulfilling the editing
criteria. Error percentage was 15.9% (SD, 12).
Echocardiographic Methods
M-Mode echocardiograms were performed under
cross-sectional control, with the patient in partial left
decubitus position, using an ATL Ultramark 8 system
(Advanced Technology Laboratories, Bellevue,
Washington) with an ATL 3.00 MHz mechanical
transducer. LV measurements were made at enddiastole and end-systole according to the recommendations of the American Society of Echocardiography (ASE).21
LV mass was calculated using the following equation, based on necropsy validation studies7: LV
mass=0.80(ASE-cube LV mass)+0.6 g, where ASEcube LV mass= 1.04* 1 {(IVSd+LVIDd+PWd)3 LVIDd3 D }; IVSd is interventricular septal thickness
at end-diastole, LVIDd is left ventricular internal
dimension at end diastole, and PWd is posterior wall
thickness at end diastole.
All echocardiographic examinations were performed by the same experienced sonographer. Reading of echocardiographic tracings was made in random order by two investigators who had no
knowledge of patients' BPs and other clinical data.
Both investigators marked locations on stop frames
on the screen of the ATL Ultrasound System, and the
mean values from at least five measurements for each
parameter for observer were computed. Only frames
with optimal visualization of LV interfaces and showing
simultaneous visualization of interventricular septal
thickness (IVS), posterior wall thickness (PW), and left
ventricular internal dimension (LVID) throughout the
whole cardiacccycle were considered for reading.
530
Circulation Vol 81, No 2, February 1990
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TABLE 1. Main Findings in the Study Population
Normotensive patients
Hypertensive patients
Parameter
(n =98)
(n = 137)
51.9 (14)
Age (yr)
52.5 (11)
Height (cm)
165.6 (8)
166.6 (9)
Weight (kg)
73.0 (13)
75.2 (14)
BSA (m2)
1.80 (0.19)
1.83 (0.20)
Casual BP (mm Hg)
Systolic
142.6 (18)
159.5 (19)
Diastolic
79.6 (7)
97.8 (7)
Average 24-hr BP (mm Hg)
128.7 (18)
141.8 (16)
Systolic
79.6 (8)
Diastolic
92.0 (8)
BP
Daytime
(mm Hg)
133.3 (18)
147.6 (16)
Systolic
Diastolic
83.6 (9)
96.3 (8)
Nighttime BP (mm Hg)
121.9 (18)
Systolic
134.5 (18)
Diastolic
74.4 (9)
86.1 (10)
Heart rate (beats/min)
72.2 (10)
Casual
76.8 (13)
72.7 (7)
76.8 (8)
Average 24-hr
76.7 (9)
80.3 (9)
Daytime
72.9 (9)
68.8 (8)
Nighttime
Data are expressed as mean (SD). Daytime is 6:00 AM to 8:00 PM; nighttime is 8:00 PM to
BSA, body surface area; BP, blood pressure.
Forty-three subjects, most of whom were affected
by long-term obstructive lung disease or obesity, were
excluded from the study because of unsatisfactory
echocardiographic tracings. Forty-two treated
patients with complicated or severe hypertension
were not investigated because it would have been
unethical to discontinue therapy.
Relative wall thickness (RWT)22 and crosssectional area (CSA)23 were calculated as previously
described. Fractional shortening (FS) was calculated
according to the formula: FS(%)= {(LVIDdLVIDs)/LVIDd }*100.
Nocturnal Blood Pressure Behavior
Study subjects were divided into two groups by the
presence (group 1) or absence (group 2) of significant
nocturnal BP reduction, defined as daytime (6:00 AM to
8:00 PM) systolic and diastolic BP averages decreasing
by more than 10% during night (8:00 PM to 6:00 AM).
Statistical Analysis
All data were handled and stored by using the
DBASE III software, and analyzed by using the BMDP
package24 (1985 version) installed on an IBM AT/3
personal computer. One-way analysis of variance
(ANOVA) and nonparametric tests were used to
compare the groups in their demographic, blood
pressure, and heart rate findings. Analysis of covariance (ANCOVA) (age, sex, height, and daytime
ambulatory systolic and diastolic BP acting as simultaneous covariates) was used to compare the nor-
F
0.10
0.80
1.57
1.89
p
0.74
0.36
0.21
0.169
<0.0001
47.36
417.52
<0.0001
36.35
127.40
<0.0001
<0.0001
43.38
138.34
<0.0001
<0.0001
27.93
86.58
<0.0001
<0.0001
8.36
15.46
10.12
13.32
6:00 AM.
0.0042
0.0001
0.0017
0.0003
motensive group, the hypertensive subgroup with,
and the hypertensive subgroup without nocturnal BP
fall in the echocardiographic parameters (Plv routine of BMDP). Multiple comparison between the
groups were performed on the adjusted data by using
the t statistics.24p values less than 0.05 were considered statistically significant.
Results
The main characteristics of the study population,
including the statistical significance of differences
between hypertensives and normotensives, are
reported in Table 1. Hypertensive patients and normotensive controls did not differ for age, height,
weight, sex prevalence, and body surface area. The
heart rate, both casual and ambulatory, was slightly
higher in the hypertensive group. Prevalence of
LVH, defined as LV mass index above 120 g/m2 25,26
was 14.6% in the hypertensive groups.
Reproducibility of Ambulatory Blood Pressure
Figure 1 shows the hourly ambulatory BP profile on
the two recording sessions in a subgroup of 32 hypertensive patients who repeated ABPM within 3-5 days
in the absence of therapy. Average 24-hour systolic/
diastolic BP values were 164.4/97.9 mm Hg (SD, 19/7)
on the first session, and 158.2/95.8 mm Hg (SD, 19/8)
on the second session (all, p=NS). A statistically
significant difference (p<0.05) between the two sessions was found only from hours 1:30 to 2:30 PM in the
Verdecchia et al Nighttime Blood Pressure and Cardiac Hypertrophy
170
160
150
140
531
X_
120
100
110
80
90J
60
18
20
0
22
2
4
6
8
10
12
14
16
18
20
22
0
2
4
6
8
10
12
14
16
Time of day (hour)
Time of day (hour)
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FIGURE 1. Graph showing 24-hour blood pressure profile in
32 off-therapy hypertensive patients who repeated noninvasive
ambulatory blood pressure monitoring within 3-5 days. Overall, blood pressure was slightly lower on second session,
particularly in first hours after application of system. Statistically significant differences were found only between 1:30 and
2:30 PM on hourly averages of systolic blood pressure.
hourly averages of systolic BP, the values recorded on
the second occasion being slightly lower.
Relation of Blood Pressure to Left Ventricular
Hypertrophy
As shown in Table 2, nighttime systolic BP showed
the best correlations with LV mass (r=0.54), LV
mass index (r=0.51), RWT (r=0.38), CSA (r=0.57),
and CSAI (r=0.51) in the hypertensive group. Overall, in the hypertensive population, the relations
between the echocardiographic indexes of LVH and
BP values were slightly closer with the nighttime
values, and progressively weaker with the daytime
and casual values.
FIGURE 2. Graph showing 24-hour blood pressure profile in
hypertensive patients with noctumal reduction of systolic and
diastolic blood pressure by 10% or less of daytime values
(n=55) (-), and in patients with greater noctumal reduction (n=82) (----).
Effects of Noctumal Blood Pressure Reduction
Figure 2 shows the hourly ambulatory BP profile in
hypertensive patients with and without significant
nocturnal BP reduction. The main demographic,
blood pressure, and heart rate values in either of the
two subgroups are reported in Table 3.
The two subgroups differed slightly for age
(p=0.03), but did not differ for height, weight, body
surface area, duration of hypertension (5.72 vs. 5.84
years,p=NS), prevalence of diabetes mellitus (10.1%
vs. 14.8%,p=NS) and serum creatinine (0.78 vs. 0.79
mg/dl, p=NS). There were slightly more women in
group 1 (53.7%) than in group 2 (36.9%), a difference bordering statistical significance (x2=3.9,
p =0.05).
Casual and daytime BPs were slightly higher in the
group of hypertensive patients with a smaller noctur-
TABLE 2. Relation of Casual and Ambulatory Blood Pressure to Left Ventricular Mass, Left Ventricular Mass Index, Relative Wall
Thickness, Cross-sectional Area, and Cross-sectional Area Index
All subjects (n =235)
LVM LVMI RWT CSA
0.34* 0.38* 0.26* 0.36*
0.32* 0.29* 0.24* 0.34*
Hypertensive patients (n=137)
Normotensive patients (n=98)
CSAI LVM LVMI RWT CSA CSAI LVM LVMI RWT CSA CSAI
0.41* 0.26* 0.36* 0.26* 0.28* 0.37* 0.29* 0.33* 0.16t 0.30* 0.35*
0.29* 0.27* 0.17t 0.32* 0.28*
0.10 0.04 0.01
0.02
0.30* 0.02
Casual SBP
Casual DBP
Average 24-hr
0.51* 0.48* 0.38* 0.53* 0.47* 0.36* 0.33* 0.34* 0.39* 0.33*
SBP
Average 24-hr
DBP
0.41* 0.36* 0.30* 0.43* 0.35* 0.23t 0.15 0.26* 0.25* 0.15t
0.43* 0.40* 0.31* 0.45* 0.40* 0.35* 0.31* 0.31* 0.37* 0.30*
Daytime SBP
0.24* 0.28* 0.15
Daytime DBP 0.33* 0.28* 0.23* 0.35* 0.28* 0.26* 0.16
Nighttime SBP 0.50* 0.47* 0.38* 0.52* 0.46* 0.31* 0.29* 0.28* 0.32* 0.27*
0.24* 0.22t 0.17
Nighttime DBP 0.41* 0.37* 0.30* 0.42* 0.36* 0.22t 0.17
AM.
to
6:00
PM
is
8:00
time
AM
8:00
is
to
6:00
night
PM;
Daytime
LVM, left ventricular mass; LVMI, left ventricular mass index; RWT, relative wall thickness;
sectional area index; SBP, systolic blood pressure; DBP, diastolic blood pressure.
*p<0.01;
tp<0.05.
0.54*
0.51*
0.34*
0.56*
0.50*
0.41*
0.41*
0.24*
0.54*
0.40*
0.34*
0.38*
0.20*
0.51*
0.35*
0.22*
0.23*
0.09
0.38*
0.23*
0.41*
0.33*
0.38*
0.43*
0.25*
0.57*
0.41*
0.19t
0.51*
0.34*
CSA, cross sectional area; CSAT, cross
532
Circulation Vol 81, No 2, February 1990
TABLE 3. Main Findings in Hypertensive Patients With (Group 1) and Without (Group 2) Significant Nocturnal Blood
Pressure Fall*
Hypertensive patients (n=137)
Group 1
Group 2
Parameter
Age (yr)
Height (cm)
Weight (kg)
BSA (m2)
Casual BP (mm Hg)
(n=82)
(n=55)
50.7 (11)
165.9 (9)
74.4 (15)
1.81 (0.21)
55.2 (12)
167.5 (7)
76.5 (13)
1.85 (0.18)
F
4.92
1.13
0.71
0.87
p
0.03
0.28
0.39
0.35
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160.4 (18)
1.12
163.8 (20)
Systolic
97.8 (8)
Diastolic
98.8 (7)
1.06
Average 24-hr BP (mm Hg)
137.3 (14)
148.5 (16)
18.05
Systolic
96.6 (6)
Diastolic
88.9 (8)
35.35
Daytime BP (mm Hg)
148.9 (16)
0.64
146.7 (16)
Systolic
96.7 (9)
97.4 (7)
1.67
Diastolic
Nighttime BP (mm Hg)
127.2 (15)
145.3 (17)
43.72
Systolic
Diastolic
80.8 (8)
94.1 (7)
92.51
Heart rate (beats/min)
77.5 (13)
75.9 (14)
Casual
0.45
77.3 (8)
75.9 (8)
0.85
Average 24-hr
81.6 (9)
79.4 (9)
0.78
Daytime
72.3 (9)
73.9 (10)
0.94
Nighttime
Data are expressed as mean (SD). Daytime is 6:00 AM to 8:00 PM; nighttime is 8:00 PM to 6:00 AM.
BSA, body surface area; BP, blood pressure.
*Nighttime systolic and diastolic blood pressure more than 10% lower as compared with daytime values.
nal BP decline but the differences from the other
statistically significant.
No funduscopic changes, focal or generalized narrowing of the retinal arteries, or retinal haemorrages
and exudates were found, respectively, in 48, 26, and
eight hypertensive patients with, and in 34, 15, and
group were not
0.29
0.32
<0.0001
<0.0001
0.426
0.199
<0.0001
<0.0001
0.506
0.357
0.402
0.332
six patients without significant nocturnal BP reduction (2=O .32, p=NS).
In comparison with the usual sleeping habits, there
were no changes in the duration of sleep, or a
reduction up to 2 hours, or of 2-4 hours, or of more
than 4 hours in 36, 13, 26, and seven patients with,
TABLE 4. Echocardiographic Findings in the Normotensive and Hypertensive Groups*
Multiple comparisons (p)
Normotensive
patients
Hypertensive patients
Group 1
Group 2
of
Analysis
covariance
Normotensives vs.
Group 1
vs.
Parameter
F
(n=98)
(n=82)
(n=55)
Group 1 Group 2 Group 2
p
0.82 (0.27)
End-diastolic IVS thickness (cm)
0.83 (0.24)
0.93 (0.25) 3.63
0.028
NS
0.021
0.0143
End-diastolic PW thickness (cm)
0.74 (0.18)
0.73 (0.15)
0.83 (0.16) 7.44
0.01
NS
0.002
0.0003
LV end-diastolic diameter (cm)
5.38 (0.66)
5.33 (0.60)
5.37 (0.62) 0.15
0.86
NS
NS
NS
40.60 (7.6)
37.9 (6.9)
38.3 (7.2)
2.70
0.07
Shortening fraction (%)
NS
NS
NS
LV mass (Penn) (g)
151.1 (59)
151.8 (53)
179.7 (55)
5.41
0.005
NS
0.007
0.002
LV mass index (Penn) (g/m2)
82.4 (31)
83.5 (28)
98.3 (29)
5.72
0.004
NS
0.004
0.002
Relative wall thickness
0.28 (0.08)
0.28 (0.07)
0.32 (0.07) 5.05
0.007
NS
0.008
0.004
Cross-sectional area (cm2)
15.2 (4.6)
15.2 (4.1)
5.67
17.5 (4.4)
0.004
NS
0.006
0.002
Cross-sectional area index (cm2/m2)
8.29 (2.4)
8.36 (2.2)
9.63 (2.3)
0.002
NS
6.55
0.002
0.001
Data are expressed as mean (SD).
IVS, interventricular septum; PW, posterior wall; LV, left ventricular.
*Hypertensive group divided by presence (group 1) and absence (group 2) of significant nocturnal blood pressure reduction (nighttime
systolic and diastolic blood pressure more than 10% lower as compared with daytime values). For either of three groups, data are adjusted
for age, sex, height, and daytime systolic and diastolic blood pressure differences between groups (see text for explanation).
Verdecchia et al Nighttime Blood Pressure and Cardiac Hypertrophy
1
GrCoil)
n
A
Croup B
Group
C
90
so
Left ventricular mass index (g/m2)
70
100
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FIGURE 3. Bar graph showing adjusted values (age-, sex-,
height-, and daytime systolic and diastolic BP differences
between groups acting as simultaneous covariates) of left
ventricular mass index in the normotensive group (Group A),
in hypertensive subgroup with noctumal blood pressure reduction by more than 10% of daytime values (Group B), and in
subgroup with a smaller noctumalpressure decline (Group C).
There is significant overall difference between three groups
(one-way ANCOVA, F=5. 72, p=0.0004) as well as between
Group B and Group C (p=0.002), and between Group A and
Group C (p=0.004). Group A and Group B did not differ
significantly.
and in 27, nine, 14, and five patients without significant nocturnal BP reduction (X2=0.65, p=NS).
Table 4 shows the age-, sex-, height-, and daytime
systolic and diastolic BP-adjusted echocardiographic
findings in the normotensive group and both hypertensive groups. All the echocardiographic indexes of
LV hypertrophy differed in the overall comparison
between the three groups. None of the differences
between normotensive and hypertensive patients
with nocturnal BP reduction by more than 10%
yielded statistical significance. In contrast, all differences between the two groups of hypertensive
patients were statistically significant. FS and LV
end-diastolic diameter did not differ among the three
groups. Adjusted values of LV mass index in the
three groups are also depicted in Figure 3. A score of
five or more by Romhilt-Estes criteria27 was found in
46% of patients with echocardiographic LVH.
An inverse relation was found (all, p<0.01) in the
hypertensive group between percentage of nocturnal
decline of systolic BP and LV mass (r= -0.35), LV
mass index (r=-0.34), RWT (r=-0.29), CSA
(r= -0.37), CSA index (r= -0.34), IVSd (r= -0.30),
PWd (r= -0.38).
In the hypertensive group, there was also an
inverse relation (all, p<0.01) between percentage of
nocturnal decline of diastolic BP and LV mass
(r=-0.32), LV mass index (r=-0.30), RWT
(r=-0.22), CSA (r=-0.31), CSA index (r=-0.27),
IVSd (r= -0.22), PWd (r= -0.32).
None of the relations between percentage of nocturnal decline of systolic or diastolic BP and echocardiographic measures of LV anatomy was statistically significant in the normotensive group.
Discussion
In agreement with previous investigations,12-14 our
findings confirm that ambulatory BP is more closely
related to LV muscle mass than is casual BP. The most
important finding, however, of this study was the
inverse relation between nocturnal BP decline and LV
muscle mass in a large population of unselected and
untreated patients with essential hypertension.
TABLE 5. Correlations Between Casual or Ambulatory Blood Pressure (24-Hour, Daytime, and Nighttime) and Left
Ventricular Mass Index in Hypertensive Patients
Reference
Devereux et al13
Drayer et al12
Rowlands et al'4
(n=12)
(n=100)
(n=50)
Blood pressure
Casual blood pressure
0.55
0.45*
0.24t
Systolic
0.10
0.46*
0.20t
Diastolic
Ambulatory blood pressure
0.81*
0.38*
0.60*
Average 24-hr systolic
0.56
0.31*
0.35*
Average 24-hr systolic
0.82*
...
0.57*
Daytime systolic
...
0.49
0.41*
Daytime diastolic
0.10
0.70t
0.56*
Nighttime systolic
0.60
0.49*
0.24t
Nighttime diastolic
and
Rowlands
et al'4
19
normotensive
is
of
81
et
mixed
Devereux al13 (n=100)
patients.
hypertensive
population
(n =50) gives daytime systolic and diastolic ambulatory blood pressure reported as awake blood pressure. Rowlands et
al'4 (n =50) and Devereux et al13 (n = 100) gives nighttime systolic and diastolic ambulatory blood pressure reported as
sleep blood pressure. Devereux et al'3 (n=100) gives daytime systolic and diastolic ambulatory blood pressure
separately reported for clinic, work, and home blood pressure. Drayer et al'2 (n = 12) gives daytime systolic and diastolic
ambulatory blood pressure reported as blood pressure averages from 6 AM to 8 PM. Drayer et al'2 (n = 12) gives nighttime
systolic and diastolic ambulatory blood pressure reported as blood pressure averages from 8 PM to 6 AM.
*p<0.01;
tp<0.05.
533
534
Circulation Vol 81, No 2, February 1990
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Relation of Blood Pressure to Left Ventricular Mass
Table 5 shows the correlation coefficients between
LV mass index and casual or ambulatory BP in the
three main investigations comparable with our own.
In the study by Rowlands et a114 who performed
intra-arterial BP monitoring in 50 patients with mild
to moderate hypertension, the relations of casual and
ambulatory BP to LV mass index were similar as in
this study (see Table 2).
In the study by Devereux et al,13 the correlation
coefficients between casual or ambulatory BP and LV
mass index were generally lower, and in that by Drayer
et al,12 generally higher than our values. As we could
not differentiate between work, clinic, and home
ambulatory BP measurements, our findings about the
inverse relation of nocturnal BP decline to LV muscle
mass do not rule out the possibility that daytime BP
during stress can be an independent determinant of
LVH development in hypertensive patients.
Prevalence of Left Ventricular Hypertrophy in
Essential Hypertension
Our prevalence figure (14.6%) is comparable with
that reported by Hammond et al,28 who studied an
unselected group of hypertensive patients drawn
from an employed population (prevalence of LVH
approximating 12% in borderline hypertension and
20% in sustained hypertension). In another study
done in 93 patients with mild-to-moderate hypertension, prevalence of LVH was 16%.29
Prevalence of echocardiographic LVH was higher
in other studies1,"'330 presumably done on more
selected hypertensive populations. In the study by
Hammond et a128 as well as in our own, several
treated patients (about 30% of the study population)
with complicated or severe hypertension and, presumably, a higher prevalence of LVH,2 3could not be
included in the study, it being unethical to discontinue antihypertensive therapy.
These findings suggest that the prevalence of LVH
in essential hypertension is strongly influenced by the
recruiting criteria of the study population, and implicate that prevalence figures in different studies might
not always be comparable.
Relation of Daytime and Nighttime Blood Pressure to
Left Ventricular Hypertrophy
Both in the study by Devereux et al13 and in that by
Drayer et al,'2 daytime BP showed a generally closer
relation to LV mass than did nighttime BP. In the
study by Rowlands et al,14 awake BP and sleep BP
correlated equally well with LV mass, whereas in
another study performed on a mixed population of
hypertensive and normotensive patients, sleep BP
showed a closer relation to LV mass than did awake
BP.1' Therefore, the available data do not allow to
draw definite conclusions about the possible predominance of daytime or nighttime BP on LVH development in hypertensive patients.
A constant finding in this and other studies12-15 is
the generally closer relation of systolic over diastolic
BP to the degree of hypertrophy, another evidence
that wall stress, which is mostly related to systolic BP,
is a key factor influencing LVH development.
In our normotensive population, the relation of
ambulatory BP to the echocardiographic parameters
of LV anatomy was slightly closer using daytime
values, whereas in the hypertensive population, it was
closer with nighttime values. We referred to nighttime BP, and not to sleep BP, because in our
experience, sleep can be interrupted by cuff inflation
and accompanying noise. Thus, one cannot be confident that all indirect BP measurements over a given
nocturnal period have been really obtained during
sleep.
As shown with intra-arterial16 and noninvasive31
monitoring, ambulatory BP decreases during night by
an average of 20% of the waking values. Individual
profiles, however, can diverge widely with some
patients showing greater nocturnal changes associated with normal BP values even for several hours
and some others showing negligible changes.16 To
our knowledge, the possibility that nocturnal BP
reduction might tend to outweigh the effect of daytime hypertension on LV hypertrophic response to
increased afterload has never been investigated.
In one study,32 intra-arterial BP variation from day
to night in 23 untreated hypertensive patients was
apparently similar in the presence versus absence of
LVH.32 An inspection to individual data of such
study, however, shows that BP decreased by less than
10% from day to night in one of six patients with
LVH, against one of 17 patients without LVH.
Another study33 with intra-arterial BP monitoring
reported no difference in the diurnal rhythm of BP in
patients with and without LVH.
In another study13 with noninvasive monitoring,
BP reduction from day to night was similar in the
presence versus absence of LVH. In a recent preliminary report, Lang et a134 have shown increased
values of LV mass in 20 patients diagnosed as having
both diurnal and nocturnal hypertension, in comparison with values in 10 patients with only daytime
hypertension. In our study, patients with and without
nighttime BP reduction by more than 10% of daytime
values slightly differed for age, but not for other
variables that might have independently influenced
LV muscle mass, such as sex, height, weight, body
surface area, duration of hypertension, renal function, prevalence of diabetes mellitus, and funduscopic changes. Also, casual BP and ambulatory BP
during the day did not differ significantly between the
groups, however, both being slightly higher in the
group with a smaller nocturnal BP decline.
Therefore, only nighttime ambulatory BP disclosed
a very evident differentiation between the two hypertensive groups. All the echocardiographic indexes of
LVH, after adjustment for age differences, sex differences, height differences, and daytime systolic and
diastolic BP differences, were increased in the group
Verdecchia et al Nighttime Blood Pressure and Cardiac Hypertrophy
of hypertensive patients with a smaller nocturnal BP
decline, and the prevalence of LVH was increased in
this latter group.
Thus, the differences in LV muscle mass between
the groups appeared to be mostly explained by the
different nocturnal BP decline. The inverse relation
between percentage of nocturnal reduction of systolic and diastolic BP and degree of LVH gives
further support to this point.
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Conclusions
The prognostic and therapeutic implications of the
changes in blood pressure from day to night are still
unknown. It has been suggested that hypertensive
patients losing nocturnal BP reduction as detected
with noninvasive monitoring might be at higher risk
of stroke.35
The findings of this study support the concept that
the duration of exposure to increased levels of BP
and wall stress over the 24 hours can play an important role in the pathogenesis of LVH in unselected
patients with arterial hypertension. In these patients,
a nocturnal reduction of systolic and diastolic BP by
more than 10% of daytime values can exert the
beneficial effect of delaying or preventing development of cardiac LVH.
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KEY WORDS * echocardiography * ambulatory blood pressure
monitoring * hypertension * left ventricular hypertrophy
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Circadian blood pressure changes and left ventricular hypertrophy in essential
hypertension.
P Verdecchia, G Schillaci, M Guerrieri, C Gatteschi, G Benemio, F Boldrini and C Porcellati
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Circulation. 1990;81:528-536
doi: 10.1161/01.CIR.81.2.528
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