(Hypertension. 1997;30:746.)
© 1997 American Heart Association, Inc.
Articles |
Left Ventricular Filling Profiles in Young White-Coat Hypertensive Patients Without Hypertrophy
From the Section of Cardiology, Department of Medicine, Taipei Medical College and Hospital (N.-C.C., Z.-Y.L., T.-C.W.), and the Section of Cardiology, Wang Fang Hospital, Taipei Medical College (P.C.), Taipei, Taiwan.
Correspondence to Nen-Chung Chang, MD, PhD, Section of Cardiology, Department of Medicine, Taipei Medical College Hospital, 2F, 29, Ln 13, Sec 2, Chin-San South Rd, Taipei 10603, Taiwan.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract This study was to assess left ventricular diastolic function in young white-coat hypertensive subjects <50 years of age without hypertrophy. Hypertensive patients (systolic or diastolic blood pressure
140 or 90 mm Hg on all
three visits) were defined as white coat if their average 24-hour blood
pressure was <127/81 mm Hg and at least 18/16 mm Hg lower
than their average office values. We chose three groups balanced for
sex, age, and body mass index: 50 sustained hypertensives, 25
white-coat hypertensives, and 25 normotensives. Office blood pressure
was similar in white-coat and sustained hypertensives. Ambulatory blood
pressure was comparable in white-coat hypertensives and normotensives.
Compared with normotensives, white-coat hypertensives had more impaired
diastolic function: increased ratio of late to early
filling velocities, raised ratio of late to early time-velocity
integral, prolonged deceleration time, and lengthened isovolumic
relaxation time (P<.001, P<.001,
P=.002, and P<.001, respectively). No difference
was noticed between white-coat and sustained hypertensives. Compared
with normotensives, white-coat hypertensives had higher values of
plasma and urine norepinephrine (P<.001 and
P<.001, respectively), plasma and urine
aldosterone (P<.001 and P=.002,
respectively), plasma renin activity (P=.04), total
cholesterol (P=.001), and LDL
cholesterol (P<.001). No difference was
observed between white-coat and sustained hypertensives. Within
white-coat hypertensives, 24-hour urinary aldosterone
closely correlated with the ratio of late to early filling velocities
(P=.008), and plasma and 24-hour urinary
norepinephrine correlated well with total
cholesterol (P=.037 and P=.006,
respectively). No correlation was detected within the sustained
hypertensives and normotensives. Heightened neurohumoral activity
clearly supported the progression of diastolic dysfunction
and metabolic abnormality in white-coat hypertensives.
Key Words: hypertension, white coat • ventricular function • echocardiography • blood pressure monitoring • angiotensin system
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The term white-coat hypertension has been used to describe patients who have elevated BP in the doctor’s office but normal values during 24-hour ambulatory recording.1 2 3 Although white-coat hypertension has been recognized for a long time and is known to be common in clinical settings, its etiology is still unknown.3 4 5 In fact, even the prognosis in this condition has not been established; moreover, the contributing factors to its cause are not yet clear.3 4 5 Measurement of 24-hour BP values among clinically hypertensive patients have become the cornerstone for diagnosing white-coat hypertension.1 2 3 4 5 Until long-term follow-up results of white-coat hypertension based on this technique are available, the detection of target-organ changes is the most useful parameters in the clinical handling of these subjects.1 2 3 4 5 6 LVH, the major target-organ damage, has been widely recognized as a predictor of cardiovascular morbidity and mortality in hypertensive patients.7 8 Indeed, most of the previously published articles9 10 11 12 13 14 15 have discussed whether white-coat hypertensives showing LV muscle mass differ from sustained hypertensives and normotensives. Recently, LV diastolic dysfunction has begun to attract attention since it has been detected early in the course of hypertension and precedes the development of LVH.16 17 18 To the best of our knowledge, no study has been performed concerning the LV diastolic filling profile in young patients with white-coat hypertension but without LVH. Furthermore, there are few reports5 12 15 in the literature that describe neurohumoral and metabolic measurements, which have been considered to be related to the development of the white-coat phenomenon, and the resulting cardiac status in clinically hypertensive patients.
The aim of this study was to ascertain the LV diastolic filling profiles and neurohumoral and metabolic findings in young patients with white-coat hypertension who do not have LVH and to compare them with sustained hypertensives and normotensives.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Study Population
We surveyed 235 successive clinically hypertensive patients from our hypertensive outpatient clinic and 76 healthy normotensive volunteers. All individuals fulfilled all of the inclusion criteria for this study and underwent 2-D, pulsed Doppler, and color Doppler echocardiographic examinations and 24-hour ambulatory BP monitoring. Of the 235 clinically hypertensive patients, 151 patients had never been treated previously, and 84 patients had discontinued their previous antihypertensive drug therapy at least 6 months prior to this study. The following criteria were used to define subject eligibility for inclusion in this study: (1) age <50 years old (mean, 39.1±8.5 years; age range, 28 to 49 years); (2) a diagnosis of clinical hypertension based on the average of three office readings at 5-minute intervals, taken at each of three different occasions during a 3- to 4-week period, excluding his/her first visit. All subjects were asked not to smoke or ingest caffeine within 2 hours of each visit. All subjects were ordered not to take herb drugs within 2 months prior to enrollment. Clinical hypertension was defined when all three visits showed an average systolic BP
140 mm Hg or
diastolic BP 90 mm Hg, as recommended by the Fifth
Joint National Committee on Detection, Evaluation and Treatment of High
Blood Pressure.19 Healthy normotensive subject had average
office systolic and diastolic BPs <140 and 90
mm Hg, respectively, at all three visits; (3) no evidence of
cardiovascular (coronary artery disease,
valvular heart disease, congestive heart failure, or rhythm
abnormality) or cerebrovascular disease detected by means of history
taking, physical examinations, resting
electrocardiogram, treadmill exercise test, chest
x-ray, and echocardiographic examination; (4) no
evidence of any kind of secondary hypertension; (5) no evidence of
renal and liver function abnormality or any metabolic
disease; (6) normal 2-D echo: normal systolic function
expressed as FS, no LVH expressed as normal LVMI and normal RWT, normal
LVDd and LVDs, normal LAD (the normal limits for these measurements
were established from 60 age- and sex-matched healthy volunteers. Data
were considered abnormal if they were 2 SDs greater than the mean in
the normal subjects), and no regional wall motion abnormality; (7) no
more than a mild degree of mitral or aortic
regurgitation as determined by color Doppler study;
(8) no obesity, expressed by normal BMI; (9) well hydrated; and (10)
subjects with adequate echocardiographic acoustic
windows and well-documented 24-hour BP recordings. Among 235
clinically hypertensive patients, 183 were defined as having sustained
hypertension, and 52 were classified as having white-coat hypertension
(see below for definition of white-coat hypertension). The prevalence
of white-coat hypertension was 22% in our study population. From all
of these participants, we chose three groups balanced for sex, age, and
BMI: 50 sustained hypertensives, 25 white-coat hypertensives, and 25
normotensives. These subjects were selected for a further comparative
study. Subjects who could not be matched appropriately were not used
for comparisons between groups, although they were used for the
within-group correlation study. The study was in accordance with the
Second Declaration of Helsinki. All procedures were approved by the
Committee on Human Studies of our College Hospital, and informed
consent was completed by all subjects.
Clinical and 24-Hour Blood Pressure Recording
Clinical BP recordings were performed on the nondominant
arm, with the patient in the supine position after 10 minutes of rest.
Twenty-four-hour BP recording was achieved by a portable
noninvasive recorder (SpaceLabs 90207), with cuffing on the
nondominant arm. Recording was done during an ordinary daily
activity within 2 weeks of the last office interview. BP readings and
pulse rates were recorded every 20 minutes from 6 AM to
11 PM and every 30 minutes from 11 PM to 6
AM. The data were edited to a 24 consecutive 1-hour
average. Systolic readings of >260 or <70 mm Hg,
diastolic readings of >150 or <40 mm Hg, and pulse
pressure readings of >150 or <20 mm Hg were automatically
deleted. The correctness of the recorder was confirmed by carrying
out three simultaneous readings with a standard mercury
manometer through a Y-tube at the beginning and end of the monitoring
time. We measured several parameters including average
24-hour, daytime, and nighttime systolic and
diastolic BPs and pulse rates. Average daytime and
nighttime BPs were recalculated according to each individual’s awake
and sleep periods, which were recorded in a diary. Twenty-four-hour
BP recordings that had more than four measurement deficits were
reexamined. All recordings were analyzed by an
investigator (Z.-Y.L.) who was unaware of other data of any
patient.
White-Coat Hypertension
Clinically hypertensive patients were classified as white coat
if their average 24-hour BP was <127/81 mm Hg and at least
18/16 mm Hg less than their average office values. The remaining
hypertensive subjects were placed into the category of sustained
hypertension. Because geographic factors may contribute to the normal
limits of the 24-hour BP values, we did not use the previously reported
cutoff point.3 5 20 21 Instead, we chose the upper limit
as 2 SDs above the average 24-hour systolic and
diastolic BP values taken from 50 healthy clinically
normotensives in our geographic area (Shin-E area, Taipei, Taiwan).
These 50 subjects included 25 men and 25 women (age, 39.1±7.2 years;
age range, 30 to 50 years). The resulting upper limit for the average
24-hour BP values was 127/81 mm Hg. Hence, the major criterion of
white-coat hypertension was based on a clinically hypertensive patient
who showed an average 24-hour systolic BP <127 and
diastolic BP <81 mm Hg. The later criterion was
taken from examination of our normotensives in whom the mean±SD of
their average office and 24-hour systolic and
diastolic differences were 10±8 and 9±7 mm Hg,
respectively. The values of 18 and 16 mm Hg were measured as the
mean+SD. Intraindividual reproducibilities of white-coat and sustained
hypertension were determined from three successive 24-hour BP
monitorings in a randomly selected subsample of 20 sustained and 20
white-coat hypertensive subjects. We arranged 5 to 18 days (mean, 12±8
days) as the interval between recordings.
Echocardiography
Echocardiographic studies were performed on an
ATL (Advanced Technology Laboratories) Ultramark 7, phased-array,
ultrasound system with a 2.5-MHz transducer. 2-D echo, pulsed
Doppler, and color Doppler ultrasound images were recorded
within 2 weeks of the 24-hour BP recording in all subjects.
Mitral inflow velocity was recorded from the apical four-chamber
view by the pulsed Doppler technique with patients in passive
end-expiration. The sample volume was placed at the level of the mitral
leaflet tips. All parameters were calculated by the
averaging of at least five successive cardiac cycles. The LVMI
(g/m2) was calculated as
(Vepi-Vendo)x1.05/BSA, where BSA is the body
surface area. The LV epicardial enclosed volume (Vepi) and
endocardial enclosed volume (Vendo) were measured at
end-diastole (the R-wave peak of the
simultaneously recorded
electrocardiogram). Volume measurements were calculated
from apical four-chamber (A1) and two-chamber
(A2) views by use of the biplane area-length formula
(V=8A1A2/3
L), where L is the lesser of the
lengths of the long axes of these two views. The RWT was calculated as
2x(PWT/LVDd). LV PWT and LVDd were measured at
end-diastole from the parasternal long-axis view of the 2-D
echo image. FS was calculated as (LVDd-LVDs/LVDd)x100. LVDs was
measured as the shortest systolic dimension taken from the
parasternal long-axis view of the 2-D echo image. LAD was measured as
the largest systolic dimension taken from the parasternal
long-axis view of the 2-D echo image. LV diastolic filling
indexes22 included the following measurements: peak late
diastolic filling velocity (A) (cm/s), peak early
diastolic filling velocity (E) (cm/s), A:E ratio, atrial
time-velocity integral (Ai) (cm), early time-velocity integral (Ei)
(cm), Ai:Ei ratio, early filling time (EFT, ms), and deceleration time
of early filling (DT, ms). In addition, isovolumic relaxation time
(IVRT, ms) was also measured as the time interval from the Doppler
sampling information of aortic valve closure artifacts to the onset of
mitral valve flow. Echocardiography was carried out
and analyzed by the same operator (N.-C.C.) throughout the
study, who was blinded with regard to all other data of all subjects.
Intraobserver variations in calculating all
echocardiographic parameters were estimated
by a randomly selected subsample of 100 sustained hypertensives, 30
white-coat hypertensives, and 40 normotensives on two occasions by one
physician (N.-C.C.) with an interval of 2 months between measurements.
Variability in measurement was outlined as the difference between the
first and second readings divided by the first reading. Percentage
variabilities for the readings of two identical echocardiograms
were obtained.
Neurohumoral and Metabolic Measurements
The possible different impact of neurohumoral profiles, ie,
renin-angiotensin-aldosterone profile (plasma
renin activity, plasma aldosterone, and urinary
aldosterone) and the sympathetic nervous system profile
(plasma and urinary epinephrine and norepinephrine)
on the cardiac and metabolic changes between the white-coat
hypertensive group and the other two groups were evaluated. All
subjects were ordered to maintain a normal diet without sodium
restriction. We directed all subjects to take nothing at home after
midnight before obtaining a blood sample and to sit quietly for 30
minutes in the early morning after arriving at our laboratory. Fasting
blood samples were drawn for the measuring of lipid profiles, glucose,
insulin level, plasma renin activity, aldosterone,
norepinephrine, and epinephrine concentrations.
Twenty-four-hour urine samples were also collected on the same day
during which ordinary daily activities were performed for examination
of urinary aldosterone, norepinephrine, and
epinephrine excretion. Correlations were estimated for the
relationships between plasma renin activity, plasma
aldosterone, plasma norepinephrine, plasma
epinephrine, 24-hour urinary aldosterone excretion,
24-hour urinary norepinephrine excretion, and 24-hour
urinary epinephrine excretion, with the values of total
cholesterol, triglyceride, LDL
cholesterol, and left ventricular
diastolic filling profiles in all subjects.
Statistics
Values were expressed as mean±1SD. All analyses were
executed with the SPSS/PC+ package. For multiple comparisons, the means
of continuous variables were compared with one-way ANOVA followed
by Scheffé’s test. Frequencies were analyzed by
Fisher’s exact test and continuity-adjusted 
2
test where suitable. Study of correlations was performed by
linear-regression analysis. A value of P<.05 was
considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Clinical Data and Blood Pressure Values
The demographic data for 50 sustained hypertensive patients, 25 white-coat hypertensive subjects, and 25 normotensive volunteers are summarized in Table 1. Age, sex distribution, and BMI did not differ among the three groups (ANOVA; P=.798, P=.707, P=.905, respectively). In addition, the mean duration of hypertension was virtually identical in both hypertension groups. Table 2 shows the clinical and ambulatory BP values in these three groups. The clinical systolic and diastolic BP values were not different between white-coat and sustained hypertensives. The average 24-hour, daytime, and nighttime systolic and diastolic BPs were similar in the white-coat hypertensives and normotensives. Intraindividual reproducibility among white-coat hypertensives and sustained hypertensives between the first and second and between the second and third 24-hour BP recordings were both 100% (sample size, 40).
|
|
Echocardiographic Findings
The LVMI, RWT, FS, LVDs, LVDd, LAD, and HR in 60 age- and
sex-matched healthy volunteers (age, 38.6±6.9 years; range, 31 to 49
years) on 2-D echo were 76±8 g/m2, 33±.03,
37±6%, 29±3 mm, 47±3 mm, 31±3 mm, and 73±6
beats/min, respectively. These data served to establish the normal
reference values for 2-D echo measurements. Transmitral peak A, E, A:E
ratio, Ai, Ei, Ai:Ei ratio, EFT, DT, and IVRT in healthy volunteers
were 47±5 cm/s, 65±9 cm/s, .75±.09, 6±2 cm, 14±3 cm, .44±.05,
271±39 ms, 183±28 ms, and 78±10 ms, respectively. Table 3 indicates the percentage variabilities
for LVMI, RWT, FS, LVDs, LVDd, LAD, and Doppler indexes of two
identical echocardiograms in 170 subjects. Table 4 demonstrates
echocardiographic data in these three groups. In our
study, no remarkable changes in LVMI, RWT, FS, LVDs, LVDd, and LAD were
identified among these three groups (ANOVAs are displayed in Table 4),
and the differences between any two of these three groups were within
the range of intraobserver variability. However, compared with the
normotensive group, the white-coat hypertensive group had significantly
more impaired left ventricular diastolic
filling profiles; it showed increased A (P=.023), decreased
E (P=.004), elevated A:E ratio (P<.001), raised
Ai (P=.029), reduced Ei (P<.001), heightened
Ai:Ei ratio (P<.001), prolonged DT (P=.0016),
and lengthened IVRT (P<.001). The diastolic
filling profiles were similar in both white-coat and sustained
hypertensive groups.
|
|
Laboratory Findings
Table 5 is a record of the
laboratory data. Compared with the normotensive group, the white-coat
hypertensive group showed significantly higher values for total
cholesterol (P=.001), LDL
cholesterol (P<.001), plasma renin activity
(P=.04), plasma and 24-hour urinary
norepinephrine (P<.001 and P<.001,
respectively), and plasma and 24-hour urinary aldosterone
(P<.001 and P=.0017, respectively). No
difference was observed between white-coat and sustained hypertensive
groups. The values for triglyceride, glucose, insulin, and
plasma and 24-hour urinary epinephrine excretion were
approximately similar between any two of these three groups. Table 6
demonstrates that 24-hour urinary
aldosterone excretion correlated significantly with
transmitral A:E ratio within the white-coat hypertensive group
(
=.353, P=.008) but not within either of the other two
groups. Furthermore, plasma and 24-hour urinary
norepinephrine correlated closely with total
cholesterol value within the white-coat hypertensive group
(=.327, P=.037 and =.388, P=.006,
respectively), although not within either of the other two groups.
There were no significant correlations between plasma renin activity,
plasma aldosterone concentration, plasma
epinephrine concentration, or 24-hour urinary
epinephrine and any of the other metabolic
measurements or LV diastolic filling indexes within any of
these three groups.
|
|
When the chosen sustained and white-coat hypertensive subjects in our study were reclassified according to the reference limits suggested by the consensus document on noninvasive ambulatory BP monitoring, ie, 135/85 mm Hg,23 two subjects with sustained hypertension were reclassified as white-coat hypertensives. If the critical point was set at 146/91 mm Hg, as derived from a meta-analysis of 23 studies21 using both invasive and noninvasive ambulatory recordings in clinically normotensive subjects or in general populations, four subjects with sustained hypertension were reclassified as white-coat hypertensives. However, this redistribution did not affect the results in our present study.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
There are apparently perplexing results in the literature that deal with cardiac involvement in white-coat hypertension. Some investigators9 10 11 12 have reported that white-coat hypertension does not result in any cardiac damage, whereas others13 14 15 have shown that white-coat hypertension results in a greater LV muscle mass and should not be considered as completely harmless. In view of the fact that the ambulatory BP determines LV mass,9 24 25 26 this discrepancy might be due to the divergence of ambulatory BP levels between white-coat hypertensive and normotensive groups observed in these studies. To date, no article has reported on the status of LV diastolic filling profile in white-coat hypertension without increased LV muscle mass. Again, the causal relationships between neurohumoral status in this subset of hypertensive patients and their cardiac changes and metabolic profiles have never been examined.
There are complex interactions involved in the measurement of the
transmitral velocity profiles as Doppler indexes of
diastolic function. Many cardiac factors, such as
ischemic and valvular heart disease, LV size and mass,
LV systolic function, left atrial size, and heart rate, and
some extracardiac factors such as age, sex, and obesity, complicate the
interpretation.27 28 We selected a study population <50
years old with a normal LV muscle mass; normal systolic
function; normal LVDs, LVDd, and LAD; normal BMI; and regular sinus
rhythm to exclude these disconcerting influences. We also took care to
minimize the likelihood of ischemic and valvular heart
disease by clinical means. Left atrial pressure, another confounding
factor, was not an enigmatic problem in our study because in the
situation of an A:E 1, the LV hemodynamic abnormality
would be diastolic dysfunction, normal systolic
function, and normal left atrial pressure. An elevated left atrial
pressure would present an E-dominant or pseudonormalization
pattern, despite the coexistence of diastolic
dysfunction.29 We selected all subjects in our study who
showed no evidence of congestive heart failure and were well hydrated
to eliminate the possibility of alteration in left atrial pressure.
The criteria used for defining white-coat hypertension might influence
the study outcome. Weber and colleagues15 used a more
demanding diastolic BP criterion for defining white-coat
hypertension. The diagnosis of white-coat hypertension in their study
was based on an office diastolic BP 90 mm Hg, an
average 24-hour diastolic BP <85 mm Hg, and a
difference between average 24-hour diastolic and office
diastolic values of at least 15 mm Hg. The latter
standard was the result of the observance of the mean±SD between
office and 24-hour average diastolic difference in normal
volunteers of 9±6 mm Hg. The reason for this was due to the fact
that the 24-hour average, which included a low nighttime value, was
probably 10 mm Hg below the office reading; therefore, some truly
mild hypertensive patients would be misclassified as white-coat
hypertensive subjects. In our present study, the differences
between the average 24-hour and office systolic and
diastolic values in the white-coat hypertensive group were
40 and 30 mm Hg, respectively, which were much greater than the
mean+SD of the differences in our normal subjects of 18 and 16
mm Hg, respectively. Likewise, we determined the normalcy of the
ambulatory BPs by considering geographic factors rather than using
discretionary cutoff points and took an upper limit of mean+2 SD in our
normal control subjects to diminish the possibility of some patient
misnomers. Also, we conformed both average 24-hour systolic and
diastolic BP values, as well as standards named from
clinically normotensive subjects, rather than the general population.
Thus, the selection bias was minimal in our study.
It was observed by us that impaired LV diastolic filling profiles were similar in both hypertensive groups. These findings support the concept of pathophysiologic similarities between patients with white-coat and sustained hypertension. According to the article of Stoddard and colleagues,30 the influence of impaired LV relaxation and increased chamber stiffness on Doppler filling profiles are different. Impairment of relaxation impedes early filling with a compensatory increase in late filling, whereas increased chamber stiffness impairs atrial filling and may enhance early filling. The increased A:E ratio observed in both hypertension groups in our study indicates an abnormal LV relaxation. This early change in LV is due to a loading condition that might have been exerted by clinical hypertension.30 31
The causality between neurohumoral profiles and the cardiac and metabolic changes in white-coat hypertensive patients has not been clarified but might be related to increased activities in the sympathetic and renin-angiotensin-aldosterone systems. Julius et al1 5 and Weber et al15 previously have noted a connection between sympathetic thrust and increased lipid level in borderline and white-coat hypertensives, respectively. However, there were disparities among several authors5 12 15 dealing with the lipid profiles in white-coat hypertension. These discriminations may be contingent on different populations studied, eating and smoking habits, and sample size. Furthermore, overweight might modify cardiovascular performance as well as some metabolic features. Thus, we have balanced the groups for this potential determinant. Our data about lipids, however, are partly in agreement with earlier observations.1 5 15 In addition, Weber et al15 reported that plasma norepinephrine correlated significantly with plasma cholesterol and triglyceride levels within the white-coat hypertensive patients but not in either the normal control subjects or established hypertensive patients. Our data are consistent with the recent report by Weber et al15 indicating that plasma and 24-hour urinary norepinephrine values correlated significantly with total cholesterol level within the white-coat hypertensive group only. These findings suggest that sympathetic activity plays a key role in defining the features of white-coat hypertension. Further, Weber et al15 have verified that white-coat hypertensive patients may be distinguished by a plasma aldosterone level similar to that in sustained hypertensive patients and reported a correlation between plasma aldosterone level and LV muscle mass within the white-coat hypertensive group but not in either the sustained hypertensive or normotensive group. Our data, however, are partially in accord with those reported by Weber et al.15 We have observed equivalent increased plasma and 24-hour urinary aldosterone and plasma renin activity in white-coat and sustained hypertensive groups and noticed a crucial correlation between 24-hour urinary aldosterone level and LV diastolic filling profile, specifically the transmitral A:E ratio, within the white-coat hypertensive group only. This is supported by the work by Weber and Brilla,32 who suggested that aldosterone directly stimulates LV remodeling in hypertensive patients. Moreover, several previous investigators33 34 35 have suggested that myocardial angiotensin II may lead to a change in the ratio of collagen phenotypes and increase in collagen content, which result in deterioration in the diastolic function in experimental rats with LVH. Extrapolating from the results from laboratory animals, we suggest that the alterations in the quantity and quality of the myocardial collagen matrix occur in white-coat hypertension mediated at least partly by increased activity in the renin-angiotensin-aldosterone system, before the development of a clinically detectable LVH, are related to LV diastolic dysfunction.
White and colleagues36 indicated that LV filling rate is more dependent on age and 24-hour ambulatory BP. In our present study, the ages of the subjects in these three groups were identical; thus, the influence of aging on LV diastolic function was considered to be similar. Furthermore, the 24-hour ambulatory BP values were similar in white-coat hypertensive and normotensive groups. Therefore, the abnormal filling profiles in the white-coat hypertensives are not dependent on ambulatory BP values. Our results indicate that office systolic and diastolic BPs in white-coat hypertensives are similar to those in sustained hypertensives and significantly higher than those in normotensives. Thus, the temporary increase in BP due to enhanced BP responsiveness to visiting a doctor may play a role in the development of cardiac functional change in white-coat hypertension. Neurohumoral determination in the white-coat hypertensive group might support a part in mediating these findings. It should be stressed that neurohumoral indexes are more important than the level of BP itself in characterizing white-coat hypertension, since the urinary level of aldosterone and norepinephrine represents an integrated value over the 24-hour ambulatory monitoring, whereas elevated BP are only temporary and sporadic.
There are potential limitations of this study. To determine conclusively whether white-coat hypertension differs from either sustained hypertension or normotension, precisely matched pairs of patients with identical office systolic and diastolic BP values should be enrolled for comparison between white-coat and sustained hypertensive groups. Likewise, matched pairs of subjects with the same average 24-hour, daytime, and nighttime BP values should be selected for comparison between white-coat hypertensive and normotensive groups. A larger sample size would be necessary to achieve such stringent matching criteria. An important issue should be addressed: ie, that diastolic dysfunction may be a consequence of myocardial tissue injury and only partly related to the neurohumoral profiles. Multiple scattered foci of myocardial damage may be present, although they are not detectable by the limited resolution of the procedure employed here. In addition, angiotensin II measurement may be essential for a more apparent appraisal of the causality between the renin-angiotensin-aldosterone axis and diastolic function in white-coat hypertension.
In summary, the present study clearly demonstrates for the first time some data about the young white-coat hypertensive population without LVH, showing that in these subjects the impaired LV diastolic function is similar to that in sustained hypertensive subjects. Our present studies also indicate that white-coat hypertensive patients present with intensified neurohumoral activities similar to an early form or a variant form of sustained hypertension. Therefore, we conclude that white-coat hypertension may not represent a group at low risk for organ damage. A longitudinal study is necessary to reveal more clearly the long-term prognostic value of impaired diastolic function in white-coat hypertension.
|
Selected Abbreviations and Acronyms |
|---|
|
Received March 15, 1997; first decision April 15, 1997; accepted April 30, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Julius S, Jamerson K, Mejia A, Krause L, Schork N, Jones K. The association of borderline hypertension with target organ changes and higher coronary risk. JAMA. 1990;264:354-358.
2. White WB. Assessment of patients with office
hypertension by 24-hour noninvasive ambulatory blood pressure
monitoring. Arch Intern Med. 1986;146:2196-2199.
3. Pickering TG, James GD, Boddie C, Harshfield GA, Blank
S, Laragh JH. How common is white coat hypertension?
JAMA. 1988;259:225-228.
4. Siegel WC, Blumenthal JA, Divine GW.
Physiological, psychological, and behavioral
factors and white coat hypertension. Hypertension. 1990;16:140-146.
5. Julius S, Mejia A, Jones K, Krause L, Schork N, van de
Ven C, Johnson E, Petrin J, Sekkarie A, Kjeldsen SE, Schmouder R, Gupta
R, Ferraro P, Nazzaro P, Weissfeld J. ‘White coat’ versus
‘sustained’ borderline hypertension in Tecumseh, Michigan.
Hypertension. 1990;16:617-623.
6. Verdecchia P, Porcellati C, Schillaci G, Borgioni C,
Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A,
Santucci C, Reboldi G. Ambulatory blood pressure: an independent
predictor of prognosis in essential hypertension.
Hypertension. 1994;24:793-801.
7. Levy D, Garrison RJ, Savage D, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham heart study. N Engl J Med. 1990;322:1561-1566.[Abstract]
8. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114;345-352.
9. White WB, Schulman P, MacCabe EJ, Dey HM.
Average daily blood pressure, not office pressure, determines cardiac
function in patients with hypertension. JAMA. 1989;261:873-877.
10. Hoegholm A, Kristensen KS, Bang LE, Nielsen JW, Nielsen WB, Madsen NH. Left ventricular mass and geometry in patients with established hypertension and white coat hypertension. Am J Hypertens. 1993;6:282-286.[Medline] [Order article via Infotrieve]
11. Gosse P, Promax H, Durandet P, Clementy J.
‘White coat’ hypertension: no harm for the heart.
Hypertension. 1993;22:766-770.
12. Pierdomenico SD, Lapenna D, Guglielmi MD, Antidormi T,
Schiavone C, Cuccurullo F, Mezzetti A. Target organ status and
serum lipids in patients with white coat hypertension.
Hypertension. 1995;26:801-807.
13. Cardillo C, De Felice F, Campia U, Folli G.
Psychophysiological reactivity and cardiac
end-organ changes in white coat hypertension.
Hypertension. 1993;21:836-844.
14. Kuwajima I, Suzuki Y, Fujisawa A, Kuramoto K. Is
white coat hypertension innocent? Structure and function of the heart
in the elderly. Hypertension. 1993;22:826-831.
15. Weber MA, Neutel JM, Smith DHG, Graettinger WF.
Diagnosis of mild hypertension by ambulatory blood pressure
monitoring. Circulation. 1994;90:2291-2298.
16. Philips RA, Goldman ME, Ardeljan M, Arora R, Eison HB, Buyan YU, Krakoff LR. Determinants of abnormal left ventricular filling in early hypertension. J Am Coll Cardiol. 1989;14:979-985.[Abstract]
17. Bonow RO, Udelson JE. Left ventricular diastolic dysfunction as a cause of congestive heart failure: mechanisms and management. Ann Intern Med. 1992;117:502-510.[Medline] [Order article via Infotrieve]
18. Faggiano P, Rusconi C, Orlando G, Pavia L, Ghizzoni G, Maestri M, Gardini A, Simoncelli U, Sorgato A. Assessment of left ventricular filling in patients with systemic hypertension: a Doppler echocardiographic study. J Human Hypertens. 1989;3:149-156.[Medline] [Order article via Infotrieve]
19. Joint National Committee on Detection, Evaluation, and
Treatment of High Blood Pressure. The fifth report of the Joint
National Committee on Detection, Evaluation, and Treatment of High
Blood Pressure (JNCV). Arch Intern Med. 1993;153:154-183.
20. Verdecchia P, Schillaci G, Boldrini F, Zampi I,
Porcellati C. Variability between current definitions of
‘normal’ ambulatory blood pressure: implications in the assessment of
white coat hypertension. Hypertension. 1992;20:555-562.
21. Staessen JA, Fagard RH, Lijnen PJ, Thjis L, Van Hoof R, Amery AK. Mean and range of the ambulatory pressure in normotensive subjects from a meta-analysis of 23 studies. Am J Cardiol. 1991;67:723-727.[Medline] [Order article via Infotrieve]
22. Danford DA, Huhta JC, Murphy DJ. Doppler echocardiographic approach to ventricular diastolic function. Echocardiography. 1986;3:33-40.
23. The Scientific Committee. Consensus document on non-invasive ambulatory blood pressure monitoring. J Hypertens. 1990;8(suppl 6):S135-S140.
24. Devereux RB, Pickering TG. Relationship between the level, pattern and variability of ambulatory blood pressure and target organ damage in hypertension. J Hypertens. 1991;9(suppl 8):S34-S38.
25. Drayer JIM, Weber MA, DeYoung JL. Blood pressure as a determinant of cardiac left ventricular muscle mass. Arch Intern Med. 1982;143:90-92.
26. Devereux RB, Pickering TG, Harshfield GA, Kleinert HD,
Denby L, Clark L. Left ventricular
hypertrophy in patients with hypertension: importance of
blood pressure response to regularly recurring stress.
Circulation. 1983;68:470-476.
27. Voutilainen S, Kupari M, Hippeläinen M, Karppinen K, Ventilä M, Heikkilä J. Factors influencing Doppler indexes of left ventricular filling in healthy persons. Am J Cardiol. 1991;68:653-659.[Medline] [Order article via Infotrieve]
28. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988;12:426-440.[Abstract]
29. Nagano R, Masuyama T, Lee JM, Yamamoto K, Naito J, Mano T, Kondo H, Hori M, Kamada T. Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease: combined analysis of mitral and pulmonary venous flow velocity patterns. J Am Soc Echocardiogr. 1994;7:493-505.[Medline] [Order article via Infotrieve]
30. Stoddard MF, Labovitz AJ, Pearson AC. The role of Doppler echocardiography in the assessment of left ventricular diastolic function. Echocardiography. 1992;9:387-406.[Medline] [Order article via Infotrieve]
31. Shepherd RF, Zachariah PK, Shub C. Hypertension and left ventricular diastolic function. Mayo Clin Proc. 1989;64:1521-1532.[Medline] [Order article via Infotrieve]
32. Weber KT, Brilla CG. Pathological
hypertrophy and cardiac interstitium: fibrosis and
renin-angiotensin-aldosterone system.
Circulation. 1991;83:1849-1865.
33. Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS. Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. J Clin Invest. 1990;86:1913-1920.[Medline] [Order article via Infotrieve]
34. Lorell BH, Weinberg EO, Ngoy S, Apstein CS. Angiotensin II directly impairs diastolic function in pressure overload hypertrophy. Circulation. 1990;82(suppl III):III-112.
35. Mukherjee D, Sen S. Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats. Circulation. 1989;80(suppl II):II-595.
36. White WB, Schulman P, Dey HM, Katz AM. Effects of age and 24-hour ambulatory blood pressure on rapid left ventricular filling. Am J Cardiol. 1989;63:1343-1347.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  A. M. Grandi, R. Broggi, S. Colombo, R. Santillo, D. Imperiale, A. Bertolini, L. Guasti, and A. Venco Left Ventricular Changes in Isolated Office Hypertension: A Blood Pressure-Matched Comparison With Normotension and Sustained Hypertension Arch Intern Med, December 10, 2001; 161(22): 2677 - 2681. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||