(Hypertension. 1996;27:330-338.)
© 1996 American Heart Association, Inc.
Articles |
Effect of 1 Year of Lisinopril Treatment on Cardiac Autonomic Control in Hypertensive Patients With Left Ventricular Hypertrophy
From the Institute of Internal Medicine, Cardiology and Heart Surgery, University of Naples "Federico II," and the National Research Council (CNR), Institute of Cybernetics (F.M.), Naples, Italy.
Correspondence to Domenico Bonaduce, MD, Via Aniello Falcone 394, 80127, Napoli, Italy.
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Abstract |
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Abstract In this study we evaluated in hypertensive patients the effects of drug-induced left ventricular hypertrophy regression on cardiac autonomic control, as assessed by means of heart period variability analysis. Power spectral analysis of 24-hour electrocardiographic monitoring was performed in 30 hypertensive patients with left ventricular hypertrophy at baseline, after 1 year of lisinopril treatment, and after 1 month of drug withdrawal. At the same times, patients underwent 24-hour blood pressure monitoring, echocardiographic study, and plasma renin activity assessment. Lisinopril treatment increased plasma renin activity and reduced 24-hour systolic and diastolic pressures (from 159±14 to 121±8 and from 103±7 to 80±3 mm Hg, respectively) and left ventricular mass index (from 159±33 to 134±26 g/m2); moreover, in 12 of 30 patients, left ventricular mass normalization was achieved. Drug withdrawal was followed by an increase in blood pressure without left ventricular mass modification. In the total study population, only high-frequency power was higher after lisinopril treatment. In the subgroup of patients with left ventricular mass normalization, daytime and nighttime high-frequency powers as well as nighttime total and very-low-frequency powers were higher after 1 year of treatment than at baseline. In the remaining 18 patients, power spectral measures after treatment were slightly lower than at baseline and were even lower after drug withdrawal. Thus, in hypertensive hypertrophic patients, lisinopril treatment improves sympathovagal imbalance when left ventricular mass normalization is achieved. In patients without left ventricular mass normalization, drug withdrawal is followed by a worsening of neural cardiac control.
Key Words: angiotensin-converting enzyme inhibitors • antihypertensive therapy • heart rate • hypertrophy
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Introduction |
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Analysis of heart period variability on the basis of routine 24-hour Holter recordings has been shown to provide a sensitive, noninvasive measurement of cardiac autonomic control.1 Clinical studies have shown reduced heart period variability in patients with chronic heart failure, diabetes, and ventricular arrhythmias; moreover, decreased indexes of heart period variability have been shown to be an independent risk factor for mortality in patients after myocardial infarction.2 3 4 5 6 By this method, a sympathovagal imbalance with increased sympathetic activity and reduced vagal tone has been reported in patients with borderline hypertension as well as in hypertensive patients with LVH.7 8 9 10 11
Currently, the effects of LVH regression on cardiac autonomic control, as assessed by means of heart period variability analysis, have not been investigated. In this study, a group of hypertensive patients with echocardiographic evidence of LVH underwent 24-hour Holter recording, BP monitoring, and echocardiographic study at baseline, after 1 year of treatment with the angiotensin-converting enzyme inhibitor lisinopril,12 and after 1 month of drug withdrawal to clarify the relationship between cardiac autonomic control, LVH, and BP profile.
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Methods |
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Study Population
Thirty-five ambulatory patients with uncomplicated essential hypertension and echocardiographic evidence of LVH recruited from the outpatient hypertension clinic of our institute were included in the study. Patients older than 70 years and those with evidence of angina, previous myocardial infarction, valvular heart disease, congestive heart failure, atrial fibrillation, diabetes mellitus, renal failure, obesity (body mass index >27 kg/m2), poor exercise capacity as a result of lung disease, or musculoskeletal problems were excluded. Patients with decreased left ventricular systolic function at echocardiography or radionuclide angiography and those with abnormal or doubtful thallium stress test results were also excluded. Secondary hypertension was ruled out in all patients by appropriate laboratory and radiographic studies. The possible contribution of regular exercise to the genesis of LVH was excluded by history. In all patients, DBP had to be greater than or equal to 95 mm Hg on at least five visits on separate days without any antihypertensive drug. BP was measured with the subject seated, after a 10-minute rest in a darkened and quiet room, by means of a standard sphygmomanometer with a cuff of appropriate size, following the recommendations of the American Heart Association.13 No subject had any serological (blood urea nitrogen, creatinine, electrolytes, hematocrit, fasting plasma glucose, cholesterol, triglycerides) abnormality. Antihypertensive drugs and any medication known to influence heart period variability (digoxin, antiarrhythmic drugs, ß-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors) were withdrawn almost 2 weeks before the study.
Study Protocol
On 2 consecutive days, patients underwent
24-hour ambulatory BP
monitoring, 24-hour ECG Holter recording, and PRA assessment.
The recorders were applied between 9 and 11 AM on a
working day, and patients were asked to follow as closely as possible
their usual daily activities during each monitoring session. They were
asked to stay in bed from 11 PM to 7 AM, and
all reported to have slept normally during the nights they were
monitored.
After baseline evaluation, patients were placed on monotherapy with lisinopril starting at 10 mg once daily. Because lisinopril provides relatively constant plasma concentrations of the drug over 24 hours,14 patients were instructed to take the medication at a convenient but consistent time of day to ensure compliance. After 1 month of therapy, the patients returned to the outpatient hypertension clinic; if DBP was greater than or equal to 90 mm Hg, the lisinopril dosage was doubled. At the end of the second month, if DBP was still greater than or equal to 90 mm Hg, chlorthalidone (50 mg/d) was added to the regimen. After another month of therapy, if BP was well controlled, patients continued the treatment; if not, they were excluded from the study. Thereafter, patients were seen at 2-month intervals in the outpatient clinic.
Thirty of the 35 patients (18 men and 12 women; mean age, 48±8 years) completed the study. Reasons for dropout were poor therapy compliance (1 patient), development of side effect (cough, 1 patient), lost at follow-up (1 patient), and unsatisfactory BP control (2 patients). All patients who completed 1 year of treatment required 20 mg lisinopril; in 2 patients chlorthalidone administration was necessary. Of the 30 patients who completed the study, 14 were not on antihypertensive treatment at the time of the initial screening, and 16 were. Of these, 2 were treated with angiotensin-converting enzyme inhibitors but not with lisinopril, 6 with ß-blockers, and 8 with calcium channel blockers.
Ambulatory BP monitoring, Holter recording, echocardiographic study, and PRA assessment were repeated after 12 months of effective lisinopril treatment. Finally, the antihypertensive treatment was stopped, and after a 1-month washout period all patients repeated the study.
The study protocol was approved by the Institutional Committee on Human Research; all 35 patients enrolled gave written informed consent.
Echocardiographic Study
M-mode and 2-D echocardiography was
performed following standard techniques 48 to 72 hours before BP
monitoring and Holter recording with the use of a Biosound ND
2600 device equipped with a 3.5-MHz transducer. Patients were examined
in the left lateral recumbent position from the parasternal and apical
windows. All echocardiograms were coded and read independently by two
investigators unaware of the subjects' identity. Differences between
readers of 1 mm in the measurement of interventricular
septal and posterior wall thicknesses and of 2 mm in the measurement of
left ventricular internal diameter were averaged; greater
differences were resolved by review of the coded echocardiogram. Left
ventricular measurements were obtained at end
diastole, defined as the peak of the R wave of the QRS
complex, according to both the American Society of
Echocardiography15 and the Penn
convention.16 American Society of
Echocardiography measurements were used to
characterize the geometric pattern of LVH.17 LVM was
calculated from the Penn convention, according to the equation of
Devereux and Reichek.16 LVM was corrected for body surface
area and expressed in grams per meter squared to minimize the effect of
body size variations; the echocardiographic criterion
of LVH was an LVM index greater than 110 g/m2 for women and
greater than 134 g/m2 for men.18
Ambulatory BP Monitoring
Ambulatory BP monitoring was
performed with a portable,
automatic device (ICR 5200 Ambulatory Blood Pressure System, SpaceLabs
Inc). The monitor makes use of an occlusion cuff and a microphone or
oscillometer to determine SBP and DBP; the oscillometer intervenes
whenever the microphone fails to identify a recognizable Korotkoff
signal. The cuff is automatically inflated by a minipump. BP data are
stored in digital form on a RAM package by a built-in computer. In
our patients, the cuff (standard adult width of 12 cm) was applied to
the midportion of the nondominant arm; the microphone was taped over
the brachial artery above the antecubital fossa, and the proper
position was validated by the agreement (±5 mm Hg) of three
systolic and diastolic values, with values obtained
simultaneously in the contralateral arm by a
sphygmomanometer. Patients were instructed to perform their usual
activities but to keep their arms still at the time of each
measurement. The device was programmed to measure BP every 15 minutes
throughout 24 hours. 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, and after 1 minute a new
reading was performed. After the 24-hour monitoring was complete, three
SBP and DBP values provided by the SpaceLabs device were again compared
with those simultaneously obtained by sphygmomanometer to
ensure that the differences had remained within ±5 mm Hg and that no
gross alteration had occurred in the ability of the device to read BP.
The reading, editing, and analysis of data provided by the unit
were done by an ABP5600 interface installed on a personal computer
(EPS30, Epson-Seiko Corp Ltd). SBP, DBP, mean arterial
pressure, and heart rate values stored in the SpaceLabs 5200 monitor
were also visually screened for artifactual readings that the computer
had not rejected. Only the recordings showing at least two
validated measurements per hour were considered. The values eliminated
by the computer over the 24 hours amounted to 7% of the total, and
those eliminated by visual editing to a further 3%. Overall, there
were 105±6 BP readings per recording, of which 96±3 readings
per recording fulfilled the editing criteria. The error
percentage was 11% at baseline, 10% after 1 year of treatment, and
12% after drug withdrawal. The readings were averaged for the entire
24 hours of the recording and for daytime (7:30 AM
to 9:30 PM) and nighttime (midnight to 5
AM).
Processing 24-Hour Holter Recordings
All 24-hour Holter
recordings were analyzed at
the National Research Council Laboratory of Cybernetics with a custom
analyzer built around a 50-MHz microprocessor (Motorola 68030).
The two ECG analog channels, read via a modified tape deck (Teac-Tascam
234 Syncaset, Teac Corp) at 60 times the recording speed, were
sampled at 10 kHz. Besides evaluation of the usual ECG
parameters, including identification of QRS widths and
shapes and of RR interval abnormalities, the sequence of all RR
intervals was stored, and each RR interval was labeled with a code
number identifying its normality or class of abnormality. Premature
ventricular complexes and their adjacent RR intervals, used
only for timekeeping purposes, were rejected by the software, as were
electrical noise and other aberrant ECG signals. Data losses for each
patient did not exceed 9% (mean, 6%) of the recording. The
sequence of normal RR intervals was analyzed for computation of
frequency domain measures of heart period variability19
for the entire 24-hour recording as well as for daytime and
nighttime.
Frequency Domain Measures of Heart Period Variability
The
24-hour heart period power spectrum was computed by means of
the fast Fourier transform algorithm, averaging at least 51 spectra for
a total of 21 hours and 30 minutes. A smooth shape for fast Fourier
transform estimates, reducing side lobe leakage, was obtained by cosine
tapering the original time series at each end over one tenth of the
window.20 The problem of obtaining an RR interval
function of time from the sequence of RR
intervals21 22
was resolved as follows: From the sequence of normal RR interval
(NN) values, the other sequence of
NNi=NNi+1-NNi=f(NNi, NNi+1)
was evaluated, and from the latter the temporal sequence NN=f(i),
where i=100, 200, 300 ... milliseconds, was computed by linear
interpolation with a time step of 100
milliseconds.23 24
Fifteen consecutive NNi values were averaged to obtain samples at
the required sampling frequency. The final average spectrum provided
total power and average power per band in milliseconds squared.
The frequency bands explored were (1) total power: the energy in heart period power spectrum between 0.00066 and 0.40 Hz; (2) ultralow frequency: the energy in heart period power spectrum between 0.00066 and 0.0033 Hz; (3) very low frequency: the energy between 0.0033 and 0.04 Hz; (4) low frequency: the energy between 0.04 and 0.15 Hz; and (5) high frequency: the energy between 0.15 and 0.40 Hz. Since the range of frequencies was very wide, an epoch of 1516 seconds and a sampling period of 1.48 seconds (1024 samples per epoch) were chosen for the 24-hour analysis to cover the entire range with a sufficient number of frequency samples in each band as follows: ultralow frequency, 5 samples; very low frequency, 55 samples; low frequency, 167 samples; and high frequency, 285 samples.
Low-frequency and high-frequency components of the RR interval spectrum were evaluated in both absolute and normalized units. The normalization procedure, obtained by expressing the power of each of these two components as the percentage of total power, allows comparisons among different subjects or different conditions, especially when a large interindividual variability exists.25
There is a body of knowledge about the behavior and significance of the different frequency domain measures of heart period variability assessment. High-frequency power is a pure measure of the modulation of vagal tone by respiratory frequency and depth.25 26 Low-frequency power is a measure of the modulation of vagal and sympathetic tones by baroreflex activity27 and, under unrestricted conditions, reflects more parasympathetic than sympathetic activity.19 Very-low-frequency and ultralow frequency powers together account for more than 90% of total power and have a strong association with all-cause mortality, cardiac death, and arrhythmic death after myocardial infarction.6 These two components are of uncertain origin, and hypotheses about their modulation include thermoregulation28 and the renin-angiotensin system29 ; moreover, it has been recently reported that angiotensin-converting enzyme inhibition improves ultralow frequency and very-low-frequency powers in myocardial infarction patients.30 In our study, 24-hour power spectra were computed on periods of about 25 minutes so that the effective lower end of the frequency range was 0.00066 Hz. Therefore, the ultralow frequency power we measured is quite different from that calculated on 24-hour total RR intervals6 ; in fact, with this latter method, the effective lower end of the frequency range was 0.0000116 Hz (ie, 1.16x10-5 Hz) if the recording was 24 hours long.
When the analysis was performed separately for daytime (awake) and nighttime (asleep), the epoch duration was 300 seconds, and at least 50 spectra were averaged for each period; according to the epoch duration, the lower limit of the frequency range was 0.0033 Hz, and ultralow frequency power was not measurable. To obtain 1024 samples per epoch, the sampling period for daytime and nighttime was 0.29 seconds and the numbers of frequency samples in each band were 12 for very low frequency, 34 for low frequency, and 75 for high frequency.
PRA Assessment
Blood samples for PRA measurements were
obtained in all patients
and control subjects after they had been 4 hours in a supine position.
PRA was measured by radioimmunoassay (sensitivity, 50 pg per tube of
angiotensin I; intra-assay and interassay variability
coefficients, 5.3% and 9.3%, respectively).
Statistical Analysis
Categorical variables are expressed as
percentages and were
compared by the 
2 test. Continuous data are
expressed as mean±SD and were analyzed with the SPSS
statistical package.31 Data comparison was performed with
repeated measures ANOVA32 ; if the F test was significant,
a paired t test with the Bonferroni correction
(two-tailed) was performed to evaluate differences among the three
steps, and an unpaired t test was used to evaluate
differences between patient subgroups. Because the distribution of the
frequency domain measures of heart period variability was extremely
skewed, for comparison of the absolute values the log transformation of
each measure, which produces nearly normal distributions, was applied
before statistical analysis was performed. Statistical
significance was defined by a value of P<.05.
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Results |
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Effects of 1 year of lisinopril treatment and 1 month of drug withdrawal on LVM, ambulatory BP, and PRA values are reported in Table 1
. As expected, PRA increased after
lisinopril treatment and reduced to control values after
drug withdrawal.
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Ambulatory BP Monitoring
Lisinopril treatment reduced mean
24-hour SBP from
159±14 to 121±8 mm Hg (P<.01) and DBP from
103±7 to
80±3 mm Hg (P<.01). Drug withdrawal was associated with
an increase in SBP (162±12 mm Hg) and DBP (100±7 mm Hg)
comparable
to baseline values. A similar pattern was detectable for daytime and
nighttime values (Table 1
).
Effects on LVH
All patients fulfilled diagnostic
echocardiographic criteria of LVH, and none had
eccentric dilated hypertrophy defined by left
ventricular internal diameter (American Society of
Echocardiography) indexed to body surface area
greater than or equal to 3.2 cm/m2 for women and 3.1
cm/m2 for men.17 After 12 months of effective
treatment, mean LVM index was significantly reduced. Moreover, in 12
patients (8 men and 4 women), LVM index was reduced below the cutoff
point used to define the presence of
echocardiographically detectable LVH (110
g/m2 for women and 134 g/m2 for men). After
lisinopril withdrawal, LVM index did not change.
Heart Period Variability
The results of frequency domain
analysis performed in the
total study population are reported in Table 2. After 1
year of lisinopril treatment, only nighttime
high-frequency power increased significantly from baseline, an
increase also detectable after drug withdrawal. No difference was
detectable in the average normal RR interval and other power spectral
measures for the entire 24-hour recording and for the daytime
and nighttime periods at each of the three steps of the study
protocol.
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Patients With and Without LVM Normalization
Patients with and
without LVM normalization were comparable with
regard to age and sex as well as prevalence of antihypertensive
treatment at the time of the initial screening. However, despite
comparable BP and PRA values, patients without LVM normalization showed
higher LVM index values at baseline (Table 3).
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The
effects of lisinopril treatment and drug withdrawal on
BP values were comparable in the two groups (Table 3). As to
frequency
domain analysis (Table 4), in patients with
normalized LVM, daytime and nighttime high-frequency powers
increased after lisinopril. This increase was also
detectable after drug withdrawal; furthermore, nighttime total and
very-low-frequency powers were higher than baseline after 1
year of treatment but not after drug withdrawal.
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The results of power
spectral analysis were markedly different
in patients with LVM reduction without normalization (Table 4):
Power
spectral measures for the entire 24-hour recording were reduced
slightly at 1 year from baseline and further after drug
withdrawal.
According to the different patterns, power spectral measures at the 1-year evaluation differed between the two groups and were lower in patients without LVM normalization. The difference was more evident after drug withdrawal.
Effects of 1 year of lisinopril treatment and 1
month of
drug withdrawal on low-frequency and high-frequency powers,
expressed as normalized units, for overall 24-hour recording
and for daytime and nighttime periods are reported in Table 5.
As shown, the results are similar to those observed
with log transformation of absolute units.
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Discussion |
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LVH is an independent and powerful predictor of future cardiovascular morbidity and mortality in patients with uncomplicated arterial hypertension.33 The mechanism by which LVH predisposes hypertensive patients to morbid events is not known; an alteration of sympathovagal balance has been proposed.7 8 9
The present study first evaluated the effect of drug-induced LVH regression on neural cardiac control, as assessed by means of heart period variability. The results are consistent with the hypothesis of an improvement of neural cardiac control after LVM normalization.
LVH and Cardiovascular Reflexes
It has been demonstrated that
in hypertensive patients with LVH,
stimulation and deactivation of cardiopulmonary receptors
induce changes in forearm vascular resistance that are markedly
reduced compared with those in control subjects.34 After
regression of LVH, the changes in vascular resistance induced by
cardiopulmonary receptor manipulation improve markedly;
similarly, baroreceptor control of heart rate is impaired in
hypertensive patients with LVH and is improved by regression of
LVH.34
Baroreflex sensitivity correlates positively with heart rate variability35 but shows a negative correlation with BP variability.36 Thus, baroreflexes reduce BP variations but enhance heart rate variations; this enhancement seems to represent a means through which baroreflexes alter cardiac output to achieve BP stabilization.37
Heart Period Variability
Heart period variability analysis
has been applied
clinically as a measure of autonomic tone in several
diseases38 39 or as a prognostic
index.5 6
Previous studies performed to characterize heart period variability in
hypertension gave somewhat conflicting results because of differences
in patient selection, methods, and algorithms used for power spectral
analysis. However, an altered pattern in the markers of neural
activities modulating heart rate with the prevalence of sympathetic
tone seems to characterize hypertensive
patients.7 8 9 10 11
In
particular, Chakko et al9 compared measures of heart
period variability between hypertensive patients with LVH and
age-matched normotensive control subjects and found lower values of
high-frequency and low-frequency powers, suggesting a
parasympathetic withdrawal. In our hypertensive patients, measures of
heart period variability were lower than those recently reported by
Bigger et al40 in healthy middle-aged subjects, except
for high-frequency power; however, it must be considered that heart
rate variability decreases with age, and in our patients mean age was
lower than in the population of Bigger et al (48±8 versus 57±8
years).
LVH Regression and Heart Period Power Spectrum
Our data
confirm earlier observations that once-daily
lisinopril administration is effective in controlling BP
over a 24-hour period, with a significant reduction in
LVM.41 In fact, after 1 year of treatment, we observed a
reduction in LVM index values (mean, 16±7%); moreover, in 12
patients, complete regression of LVH occurred. The reduction in LVM was
followed by very slight modifications in power spectral measures. In
fact, in the total study population, after 1 year of treatment only
high-frequency power was higher than at baseline, suggesting an
improvement in cardiac vagal control. However, considering separately
the patients with LVM normalization, the changes in heart period
variability were markedly different. In fact, in patients with LVM
normalization, daytime and nighttime high-frequency powers and
nighttime total and very-low-frequency powers were higher after
lisinopril treatment than at baseline.
Normalization of both LVM and BP seems necessary to obtain the improvement in heart period variability. In fact, after drug withdrawal when BP rose to values comparable with baseline without changes in LVM, measures of heart period variability worsened. The decrease of measures of heart period variability in the patient subgroup with satisfactory BP control but without LVM normalization supports this hypothesis.
Bigger et al35 evaluated the correlations between baroreflex sensitivity and power spectral measures of vagal activity and found that baroreflex sensitivity correlated with daytime and nighttime high-frequency powers. Accordingly, in our patients the increase in high-frequency power may be related to an improvement in baroreflex sensitivity due to LVH regression. It is possible that the regression of vascular hypertrophy and the increase in vascular compliance induced by antihypertensive treatment could make baroreceptors more sensitive to mechanical stimuli and enhance their overall reflex control.
In patients without LVM normalization, 24-hour values of frequency domain measures showed a slight decrease from baseline after 1 year of treatment that was more evident after drug withdrawal. Why these patients did not demonstrate complete reversal of cardiac hypertrophy despite excellent BP control is unclear. However, it must be considered that patients without LVM normalization showed higher LVM values just at baseline; therefore, in these patients after treatment, LVM remained above normal values despite a significant reduction from baseline (mean, 15±7%) comparable to that observed in patients with LVM normalization (mean, 17±6%). Currently, the determinants of LVM regression in patients on antihypertensive therapy are not firmly established; however, in agreement with our data and also in other studies,42 43 LVM normalization was not achieved in all patients despite the significant reduction in BP. We hypothesize that in patients without LVM normalization, the derangement in neural cardiac control persists despite effective antihypertensive treatment so that after drug withdrawal when BP increases, measures of heart period variability worsen. The results obtained with low-frequency and high-frequency power values normalized for total variance confirm those observed with absolute values.
Our results differ from those reported by Pagani et al44 and de Champlain et al,45 who used two different angiotensin-converting enzyme inhibitors, cilazapril and trandolapril, respectively. Pagani et al found a selective inhibitory modulation of the drug on vascular sympathetic control but were unable to demonstrate any effect on low-frequency or high-frequency components of heart rate variability. De Champlain et al observed that responders to trandolapril were characterized by lower basal parasympathetic tone that was nonetheless unaffected by trandolapril administration. It must be considered that in these two studies LVM and the effects of drug administration on this variable were not evaluated and patients were followed for only 4 weeks.
Slow trends of heart period variability are reported to be influenced by the renin-angiotensin system, which normally damps the amplitude of the lower part of the power spectrum.29 In the present study after lisinopril treatment, very-low-frequency power increased in patients with LVM normalization and it decreased in those without. This finding confirms the clinical relevance of obtaining LVM normalization.
Study Limitations
At the time of the initial screening, many
patients were on
antihypertensive treatment, which could have reduced LVM; furthermore,
the withdrawal period was probably not long enough to allow restoration
of LVH. However, it must be emphasized that it is unlikely that
never-treated hypertensive patients would be selected in an
outpatient clinic; accordingly, all previous studies performed in
hypertensive patients with LVH enrolled treated patients, and
thereafter the antihypertensive drugs were withdrawn for different
periods, ranging from 2 to 4
weeks.9 46 47 It must be
considered that in our study hypertensive patients with or without LVM
normalization after lisinopril treatment were comparable
with respect to the prevalence of antihypertensive treatment and drugs
used at the time of the initial screening; therefore, it seems unlikely
that previous treatment could have influenced our results. A further
limitation is that we did not measure circulating
catecholamines; therefore, we were unable to determine
whether the patients who did not show a regression of LVH were also
characterized by a higher sympathetic drive.
Conclusions
Our study demonstrates that LVH reversal induced
by
antihypertensive treatment is associated with an improvement in neural
cardiac control. This improvement may help to explain the beneficial
effects of antihypertensive treatment on cardiac mortality.
Furthermore, it demonstrates that antihypertensive drug withdrawal may
worsen neural cardiac control, particularly in patients without LVM
normalization.
The effects of the LVH reduction obtained with other antihypertensive drugs on neural cardiac control remain to be defined.
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Selected Abbreviations and Acronyms |
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Received July 19, 1995; first decision September 6, 1995; accepted November 20, 1995.
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