(Circulation. 1995;91:698-706.)
© 1995 American Heart Association, Inc.
Articles |
Comparison of Five Antihypertensive Monotherapies and Placebo for Change in Left Ventricular Mass in Patients Receiving Nutritional-Hygienic Therapy in the Treatment of Mild Hypertension Study (TOMHS)
From the Section of Cardiology, Department of Medicine, and the Department of Preventive Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill; the Division of Biostatistics and the Division of Cardiovascular Diseases, Department of General Medicine, University of Minnesota, Minneapolis; the Department of Epidemiology and Public Health, University of Miami (Florida); the Noninvasive Laboratory, Allegheny General Hospital, Pittsburgh, Pa; and the Department of Community Health and Preventive Medicine, Northwestern University, Chicago, Ill.
Correspondence to Greg Grandits, Division of Biostatistics, University of Minnesota, 2221 University Ave, Suite 200, Minneapolis, MN 55414.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Increased left ventricular mass (LVM) by echocardiography is associated with increased risk of cardiovascular disease. Thus, it is of interest to compare the effects of both pharmacological and nonpharmacological approaches to the treatment of hypertension on reduction of LVM.
Methods and Results Changes in LV structure were assessed by
M-mode echocardiograms in a double-blind, placebo-controlled clinical
trial of 844 mild hypertensive participants randomized to
nutritional-hygienic (NH) intervention plus placebo or NH plus one of
five classes of antihypertensive agents: (1) diuretic (chlorthalidone),
(2) ß-blocker (acebutolol), (3) 
-antagonist (doxazosin mesylate),
(4) calcium antagonist (amlodipine maleate), or (5)
angiotensin-converting enzyme inhibitor (enalapril maleate).
Echocardiograms were performed at baseline, at 3 months, and annually
for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the
active treatment groups and 9/9 mm Hg in the NH only group. All groups
showed significant decreases (10% to 15%) in LVM from baseline that
appeared at 3 months and continued for 48 months. The chlorthalidone
group experienced the greatest decrease at each follow-up visit
(average decrease, 34 g), although the differences from other groups
were modest (average decrease among 5 other groups, 24 to 27 g).
Participants randomized to NH intervention only had mean changes in LVM
similar to those in the participants randomized to NH intervention plus
pharmacological treatment. The greatest difference between groups was
seen at 12 months, with mean decreases ranging from 35 g
(chlorthalidone group) to 17 g (acebutolol group) (P=.001
comparing all groups). Within-group analysis showed that changes in
weight, urinary sodium excretion, and systolic BP were moderately
correlated with changes in LVM, being statistically significant in most
analyses.
Conclusions NH intervention with emphasis on weight loss and reduction of dietary sodium is as effective as NH intervention plus pharmacological treatment in reducing echocardiographically determined LVM, despite a smaller decrease in blood pressure in the NH intervention only group. A possible exception is that the addition of diuretic (chlorthalidone) may have a modest additional effect on reducing LVM.
Key Words: hypertension • antihypertensive agents • ventricles • lifestyle • echocardiography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Increased left ventricular mass (LVM) determined by echocardiography (echo) has been shown to be associated with increased risk of cardiovascular disease events.1 2 3 4 5 Even in mild hypertension, a significant proportion of patients have increased LVM compared with normotensive individuals.6 7 8 9 It might be expected that interventions that decrease LVM would decrease the risk for cardiovascular events, although it is possible that decreases in LVM without accompanying decreases in blood pressure (BP) could adversely affect LV performance, decrease coronary flow reserve, and thus possibly increase the risk of myocardial ischemia.10 11 12 13 14
Various classes of antihypertensive agents, as well as interventions to reduce weight and lower dietary sodium intake, have been evaluated for their effects on reduction of LVM. However, many of these studies have been uncontrolled, done on few patients (usually <15), and of relatively short duration (usually <1 year).15 16 A recent meta-analysis comparing the major classes of antihypertensive agents concluded that angiotensin-converting enzyme (ACE) inhibitors had a greater effect on reducing LVM than diuretics, ß-blockers, and calcium channel antagonists, although the authors cautioned that more controlled prospective trials were needed to confirm this finding.16
The Treatment of Mild Hypertension Study (TOMHS) evaluated five classes of antihypertensive monotherapy and placebo, in conjunction with lifestyle intervention, for changes in LVM and other factors in a randomized, double-blind study of 902 mild hypertensive participants over a 4-year period, 844 of whom had acceptable echo studies at entry for assessment of LVM. Lifestyle changes included intervention to reduce weight, dietary sodium, and alcohol consumption and increase physical activity. Each of these factors may influence echo LVM.9 17 18 19 20 21 22 23 24 The final results of TOMHS have been reported, including the average change from baseline in LVM, diastolic wall thickness, and chamber dimensions for each treatment group.25 The present report evaluates in detail the annual changes in LVM and components, including relative wall thickness (RWT), the effects of additional therapy on LVM, and the relation of change in BP and intervention factors with observed changes in LVM.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Population
TOMHS was a randomized, double-blind clinical trial of 902 mild hypertensive participants conducted in four clinical centers that compared five classes of antihypertensive agents and placebo, each given in conjunction with nutritional-hygienic intervention aimed at weight loss, lowering of sodium and alcohol intake, and increasing physical activity. Details of the BP and other eligibility criteria and of baseline characteristics have been reported.26 27 28 Briefly, participants not on antihypertensive medications at initial screening were eligible by BP criteria if they had an average diastolic BP of 90 to 99 mm Hg over three visits. Participants on a single antihypertensive agent at initial screening were eligible if they had an average diastolic BP of 85 to 99 mm Hg over three visits after medication withdrawal. Mean age of randomized participants was 55 years; 20% of participants were black, and 62% were on antihypertensive monotherapy at entry. Average BP for randomized participants was 140/91 mm Hg, based on the mean of the second and third eligibility visits. Average body mass index was 29 kg/m2, and average urinary sodium excretion was 54 mmol/8 h (overnight collection).
Cardiac assessment was performed at the second screening visit and included M-mode echocardiography and ECG. Participants with a history of cardiovascular disease or with ECG evidence of left ventricular hypertrophy (LVH) according to the Minnesota code,29 as judged by physician review of the ECG, were excluded from the study. On computer reading of the ECGs, 1.3% had LVH by Minnesota code criteria. Of the 1536 participants eligible after BP assessment at the second screening, 137 (8.9%) were excluded because of inability to obtain an adequate echo tracing of the LV. This exclusion was based primarily on the clinical center sonographers' assessment. Of the 902 participants eventually randomized, an additional 58 were determined by the physician's reading to have unacceptable LV tracings, leaving 844 participants with baseline readings of LVM. Criteria for an acceptable LV tracing have been given.9 30 Analyses relating baseline factors with baseline LVM have also been reported.9
Treatments
After providing informed consent, participants
were randomized
to one of the following six treatments at the given dose: (1) placebo
(n=234); (2) diuretic (chlorthalidone 15 mg/d, n=136); (3)
ß-blocker
(acebutolol 400 mg/d, n=132); (4) 1-antagonist
(doxazosin mesylate 1 mg/d for 1 month then 2 mg/d, n=134); (5) calcium
antagonist (amlodipine maleate 5 mg/d, n=136); or (6) ACE inhibitor
(enalapril maleate 5 mg/d, n=135). Initial medication assigned is
referred to as step 1 medication. Additional medication (step 2) was
added if BP was not controlled: chlorthalidone (15 mg/d) in all groups
except in the chlorthalidone group, in which enalapril (2.5 mg/d) was
added for step two. Criteria for adding additional medication have been
described.28 All drugs were administered once a day in the
morning.
Echocardiographic Procedure
A detailed methodology of the
echo assessment has been
reported.31 Echocardiograms were performed according to a
standard protocol by sonographers after a comprehensive training
session in techniques and criteria for measurement of tracings. To help
ensure quality of tracings, sonographers were required to measure all
tracings, but the measurements were not used for analyses.
Echocardiograms were obtained with the participant lying in a modified
left lateral decubitus position with head angled at 30° from the
horizontal. Recordings were made at end expiration, if possible, with a
Kontron Sigma 1SC sonographic recorder with a 3.5-MHz transducer.
M-mode studies of the LV were obtained from the parasternal short-axis
view with the M-mode cursor off the two-dimensional image. At least
five cycles were recorded on a fiber-optic L585 Honeywell recorder on
light-sensitive paper at 50 mm/s. Two-dimensional studies were recorded
on 1/2-in VHS videotape to evaluate the orientation of the M-mode
cursor.
Echocardiographic Measurements
Echocardiograms were performed
at baseline, at 3 months, and
then annually. The number of participants who had echocardiograms
performed with acceptable LV tracings at baseline and at 3, 12, 24, 36,
and 48 months was 844, 806, 762, 746, 703, and 636, respectively. LV
measurements were obtained at end diastole. Measurement criteria
included both the American Society of Echocardiography (ASE) and Penn
conventions.32 33 LV measurements included
interventricular septal thickness (IVST), posterior LV wall thickness
(PWT), and LV internal dimension (LVID). LVM was calculated from the
Penn convention measurements33 and indexed by both body
surface area in square meters and height in
meters.34 35
Individual measurements reported are derived according to the ASE
convention. Relative wall thickness was calculated by the formula
100(IVST+PWT)/LVID.34 Cutoff points for LVH were >134
g/m2 for men and >110 g/m2 for women, based on
Penn measurements.34
Tracings were read by one of two physician readers, P.R.L. (85%) or S.D. (15%), blinded to treatment and other clinical data but not to study visit. All tracings for a given participant were read by the same reader. Interreader and intrareader comparabilities have been reported.31
Other Measurements
Blood pressure, body weight, urinary
sodium excretion, and
alcohol intake were assessed at each visit at which the echocardiogram
was performed. Physical activity was assessed at each of these visits
except at 3 months. Methods used for collecting these data have been
described.28
Statistical Methods
ANCOVA was used to compare changes in
echo measurements and
determinations between groups at each follow-up visit.36
Covariates were the two variables stratified at randomization (clinical
center and use of antihypertensive medication at the first screening
visit), echocardiographic reader, and the baseline level of the
variable considered. The actual mean changes (unadjusted) are reported
for each group. Significance levels were based on the analyses
including the covariates. Tests comparing all six groups (5
df), all five active treatment groups (4
df), and the combined active groups versus placebo
(1 df) are reported. Significant pairwise contrasts
are given in the footnotes of the tables. Since several comparisons are
made, such contrasts are reported only if the significance level was
P<.01.
In addition to comparisons at each visit, comparisons were made between groups using the average change from baseline. For this summary statistic, all follow-up values for each participant were averaged and the baseline measurements subtracted. Treatment differences were assessed by a random-effects model described by Laird and Ware,37 for which all measurements during follow-up were used. The same covariates were used as in the individual visit analyses. A separate longitudinal analysis was performed using only visits in which the participant was on step 1 medication only.
Multiple regression analysis was used to assess the relation between change in LVM and change in intervention factors. All models included clinical center, antihypertensive medication use at entry, sex, and an indicator for randomization to active drug treatment or placebo. Multiple regression analyses used changes at 3 months (when most of the change in LVM had occurred), and the average change over all follow-up in all variables. Analyses were concentrated on change in weight, change in urinary sodium, and change in systolic BP (SBP), because these factors were related cross-sectionally to LVM at baseline9 and because the most intensive nutritional-hygienic interventions were on reducing weight and dietary sodium. Three regression models were run: (1) adding each of the three factors individually to the base model, (2) adding change in weight and change in urinary sodium together to the base model, and (3) adding all three factors together to the base model. The last model assesses the impact on LVM change of weight and sodium change after consideration of their effects on BP change. Two participants with LVM >475 g at baseline were excluded from the change analyses. These participants had estimated reductions in LVM during follow-up of >250 g.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Table 1
shows mean levels of echocardiographic
measurements at baseline for each treatment group and for all
participants combined. Mean levels for echocardiographic measures were
similar among treatment groups, with the possible exception of LVM, for
which participants assigned to amlodipine had on average the smallest
LVM. The average LVM for all participants was 202 g: 224 g for men and
168 g for women. There was some variation between groups in the percent
with LVH when g/m2 was used, ranging from 7% with LVH in
the amlodipine group to 22% in the chlorthalidone group
(P=.04).
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Table 2 presents the average changes in intervention
measures, BP, and pulse rate by treatment group. Average decreases over
the follow-up period in weight, urinary sodium, and alcoholic drinks
per week were 7.9 lb, 10.2 mmol/8 h, and 1 drink/wk, respectively.
Average increase in physical activity was approximately 100 points
(approximately 400 kcal/wk). There were no significant differences
between study groups for any of these changes. The average decreases in
BP over the follow-up period were significantly greater
(P<.001) in each active group compared with placebo.
Average pulse rate decreased by 10 beats per minute in the acebutolol
group, compared with decreases of 1 to 3 beats per minute in the other
groups.
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Table 3 gives the percentage of participants on
initially assigned medication alone by treatment group for each
follow-up visit in which an echocardiogram was performed. More than
90% of participants were on their initially assigned treatment alone
at 3 months. This declined steadily over the 4-year period to 72% in
the active groups and to 59% in the placebo group after 48 months. At
48 months, participants in the acebutolol and amlodipine groups were
approximately 10 to 15 percentage points higher than the other active
treatment groups. Among placebo participants at 48 months, 33% were
prescribed active medication, either TOMHS medication (chlorthalidone)
(13%) or medication from their private physicians (20%).
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Table 4 presents the mean change in LVM among
treatment groups at each visit and the average change over all
follow-up visits. Significant changes from baseline of approximately
10% (20 g) were observed in each treatment group beginning at 3 months
and were maintained through 48 months. The greatest changes in LVM were
observed in the chlorthalidone group at each visit. The average change
in LVM over follow-up was nearly identical, approximately 25 g, in all
groups except chlorthalidone, which had a slightly larger
decrease, 34 g. There was a significant difference (P<.01)
among all groups and among active groups in change in LVM at 12 months.
The amlodipine and chlorthalidone groups had significantly greater
decreases in LVM than both the placebo and acebutolol groups.
Differences were also significant between the chlorthalidone and
enalapril groups at 12 months. There was an approximately 5 g greater
decrease in LVM in the combined active groups than the placebo group at
12 months (P=.04). Differences between groups were smaller
at subsequent visits, mostly because of additional decreases in the
acebutolol and placebo groups after 12 months. The percent of
participants with a decrease of >10% using the average change over
follow-up was similar between the active groups and the placebo group
(60% in each; data not shown).
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To explore further the between-group differences at 12 months, analyses
were conducted for each component in the formula for LVM as well as
relative wall thickness and LVM index. The results are presented in
Table 5. Some of the additional decrease in LVM in the
chlorthalidone group at 12 months can be attributed to a decrease
in the LVID (1.6 mm), in which the other groups experienced little
change (P<.01, chlorthalidone versus acebutolol, doxazosin,
and enalapril). There were significant differences (P<.01)
between groups for PWT, with the amlodipine group having a
significantly greater decrease in PWT than the placebo group, although
the difference was small (decrease of 1 mm in the amlodipine group
versus a decrease of 0.7 mm in the placebo group). Differences in LVM
index between groups, using both g/m2 and g/m, paralleled
those of LVM. Relative wall thickness decreased in all groups, with
slightly greater decreases in the active groups than in the placebo
group (P=.04), but with chlorthalidone and placebo groups
showing a similar decrease in relative wall thickness.
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As previously reported,25 there were no significant
differences between groups in the incidence of echocardiographically
determined LVH through 48 months, ranging from 9% in the doxazosin
group to 16% in the enalapril group. Analyses at any single visit also
showed no significant differences, although participants randomized to
enalapril had the greatest incidence of LVH at most visits. Among
participants with LVH at baseline, 27%, 24%, 15%, 28%, and 21% had
LVH at 3, 12, 24, 36, and 48 months, respectively (data not shown). The
Figure displays these data for the combined active and
placebo groups. Differences between groups were inconsistent between
visits and did not differ significantly.
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Because withdrawal of or change in medication during the study could
influence treatment effects, a longitudinal analysis was conducted
using only visits in which the participant was prescribed initial
medication alone. The results from this restricted analysis are
compared with the longitudinal analysis using all visits,
regardless of medication prescription (Table 6). The
contrast between the chlorthalidone and placebo group was larger
(-10.5 g) in the restricted analysis than in the unrestricted
analysis (-6.8 g). Because step 2 medication for placebo
participants was chlorthalidone, this larger effect when the
analysis was restricted to visits in which participants were on
initial medication only is consistent with chlorthalidone's having an
independent effect on reduction of LVM. A comparison was also made
among participants who were prescribed step 2 medication sometime
during the study, contrasting LVM while on step 1 alone with LVM while
on step 2 medication (alone or with step 1) by randomized treatment
group. For the 53 participants in all groups in which
chlorthalidone was given as step 2, there was a decrease of 16 g
in LVM when chlorthalidone was given (Table 7).
For the 6 participants randomized to chlorthalidone in whom enalapril
was added as step 2, there was an increase of 19 g.
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The average change in LVM during follow-up was calculated for each
randomized group, stratified by various baseline variables to determine
whether there were any subgroups in which there was a differential
treatment effect on LVM (Table 8). There were no
significant interactions of treatment with baseline SBP, sex, age,
race, entry antihypertensive medication status (stratum), or
echo-determined LVH, although the effect of chlorthalidone on LVM was
greater in participants with higher levels of SBP (P=.15 for
interaction).
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The relation between nutritional-hygienic changes and changes in LVM
was explored by use of multiple regression. Analyses were concentrated
on changes in weight and urinary sodium excretion (the two major
intervention variables) and change in SBP. Separate analyses were done
at 3 months, when most of the drop in LVM occurred, and used the
average of follow-up values through 48 months. At 3 months, a decrease
in weight of 10 lb was associated with a decrease in LVM of 8 g
(P<.001) (Table 9). Adjusting for change in
urinary sodium and/or change in SBP only slightly decreased the
estimated effect. Smaller positive associations, which were not
statistically significant, were seen for change in urinary sodium and
SBP.
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When the average change in follow-up was used, all three change factors when entered alone into the model were significantly related to change in LVM, although the estimated effect of weight loss was only about one-half that at 3 months. Estimated effects of change in weight and change in urinary sodium excretion were only slightly smaller when both variables were entered into the model. When all three change factors were entered into the model, only change in urinary sodium and change in SBP remained significant. Changes in number of alcoholic drinks per week and in physical activity points were not significantly related to change in LVM, either at 3 months or over the entire follow-up period.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The results of this study demonstrate that, in mildly hypertensive persons without evidence of underlying structural heart disease, nutritional-hygienic therapy alone is equally effective as nutritional-hygienic therapy combined with a diversity of classes of pharmacological agents in reducing LVM, with changes appearing as early as 3 months and being maintained through 4 years. Changes in LVM were nearly identical in each group, with the exception that the chlorthalidone group displayed a slightly larger mean decrease in LVM than other groups, being significantly different from placebo at 12 months. Differences at 48 months were small and nonsignificant, possibly in part because of an increased percentage of placebo participants taking active medications, often chlorthalidone. In the participants with chlorthalidone added as a second agent, the demonstration of an additional decrease in LVM further suggests an independent effect of chlorthalidone on reduction of LVM. This was not the case when the ACE inhibitor enalapril was added as a second agent to the chlorthalidone group.
Although some previous reviews and editorials spanning the past decade have emphasized the variable effects of different classes of antihypertensive agents on changes in LVM, notably a presumed lack of effect of diuretics on reduction of LVM despite adequate BP response,38 39 40 41 42 our results support the more recent conclusion based on the recent meta-analysis16 and a review of the diuretic literature43 that diuretics are indeed effective in reducing LVM. Our data do not support the conclusion from the meta-analysis that ACE inhibitors produce a greater reduction in LVM than other classes of antihypertensive drugs,16 at least in the presence of nutritional-hygienic intervention in mildly hypertensive patients. Our findings with regard to diuretics are relevant for black hypertensive patients, who appear to have a good BP response to diuretics and have demonstrated in some studies a greater degree of LVH for a given level of BP elevation compared with whites. These data indicate that diuretics are at least as efficacious in reducing LVM as other monotherapy agents and are important first-line agents for treatment of hypertension in blacks.
The TOMHS study is by far the largest and most comprehensive study of
the effects of pharmacological and nonpharmacological therapy on change
in LVM. Advantages of the study include the large sample size per
group, the long period of follow-up, and the high percentage of
participants remaining on monotherapy. Compared with the vast majority
of other monotherapy trials of LVM changes with antihypertensive
therapy, at least 10 times as many subjects were evaluated in each
monotherapy drug group and 20 times as many in the placebo group (for
those studies that included placebo groups).15 16 In
the
Dahlöf meta-analysis of 109 predominantly monotherapy studies
identified between 1977, when echo evaluation of LVM in the treatment
of hypertension was first reported, and December 1990, only one study
group consisted of more than 38 participants, the average being 21
patients, and more than 50% evaluated changes for 
6
months.28 The reduction in LVM in these studies was
approximately 12%, similar to the reduction of 13% found in TOMHS,
despite entry mean BP being considerably lower in TOMHS (107 versus 123
mm Hg). As in other studies, the decrease in LVM was seen within 3
months; as with the few long-term studies (beyond 1 year of treatment),
most of the reduction in LVM was completed within 12 months, although
changes in LVID and LV wall thicknesses may continue to
evolve.44 45 46 47
The only other large-scale placebo-controlled monotherapy study of which we are aware, presented in abstract form, evaluated 452 men with higher initial BPs (mean BP, 117 mm Hg versus 107 mm Hg in TOMHS) and much higher LVM (329 versus 202 g in TOMHS).48 Six classes of monotherapy and placebo were compared. At 1 year, those on placebo had a slight but nonsignificant increase in LVM, with no described difference of LVM from entry with any of the active agents. At 2 years, LVM decreased only with the diuretic. However, only one third of the initial group was evaluated at 2 years (J. Gottdiener, MD, personal communication, 1994). This study reinforces the long-term results on decrease in LVM seen with diuretics in TOMHS.
The group in TOMHS receiving nutritional-hygienic therapy alone had a
decrease in LVM similar to that of the active treatment groups despite
a smaller decrease in BP. This suggests that in mild hypertensives, the
effects of weight and sodium reduction may be more significant in
reducing LVM than BP changes. Three studies have demonstrated
effectiveness of salt reduction or weight reduction on reducing BP and
LVM.49 50 51 MacMahon et
al,50 in one of the few
placebo-controlled studies, demonstrated not only a significant
reduction in LVM over a 21-week period with weight reduction compared
with placebo in overweight hypertensive patients but also a slightly
greater reduction than a parallel ß-blocker–treated group. In
TOMHS, the addition of active medication to nutritional-hygienic
intervention had little if any additional effect on reducing LVM.
Because this was also true for the subgroup with higher SBPs (
150
mm Hg) (Table 7
), this dominant effect of weight and sodium
reduction
on LVM change may hold even in more moderate hypertensive patients.
Within-group analyses showed that weight, BP, and urinary sodium changes were positively and in most models significantly related to change in LVM and supported earlier analyses from TOMHS.52 At 3 months, a 10-lb loss in weight was associated with an 8-g loss in LVM. When data throughout follow-up were used, the magnitude of the associations of weight, urinary sodium, and SBP change with change in LVM were similar. The emergence of change in sodium as a significant factor related to change in LVM may be due in part to the averaging of multiple measures and hence greater precision for estimating reduction of urinary sodium excretion. The lack of correlation of changes in LVM with changes in physical activity and change in alcohol intake may be related to the limited, although definite, increase in activity in the study participants and small changes in alcohol intake.
With regard to the echocardiographic technique and quality control, an individual reader read batches of coded studies throughout the duration of the study. Quality of individual technician performance at each of the four centers was monitored on a regular basis, and corrective efforts were made when necessary to improve performance. An individual participant's serial studies were read by one of the two readers without knowledge of the results from previous visits, and 10% of studies were reread by an individual reader to evaluate consistency. The finding of the greatest mean LVID decrease in the chlorthalidone group and the greatest mean LVID increase in the acebutolol group would indicate that measurements reflected expected pharmacological effects.
In conclusion, the study results indicate that in mild hypertension, nutritional-hygienic therapy alone, specifically weight reduction and limitation of salt intake, is as effective in decreasing LV wall mass as combinations of nutritional-hygienic therapy with low doses of antihypertensive monotherapy, despite greater BP lowering with combined drug and nutritional-hygienic therapy. A possible exception would be a moderate additional lowering of LVM with use of chlorthalidone. The study results emphasize the importance of efforts to decrease weight and modify salt intake in mild hypertensive patients. Moreover, there is no evidence for an adverse effect in any of the antihypertensive monotherapy groups on the reduction in LVM. The significance of a reduction of LVM concomitant with a decrease in BP for cardiovascular and total mortality awaits further study.
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Acknowledgments |
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This study was supported by National Heart, Lung, and Blood Institute grant NIH-5KO7HL-01716-05 (Dr Liebson), National Institutes of Health grant NIH-7801-HL-34707, Pfizer, Inc, and Merck, Sharp, and Dohme Research Laboratories. The authors wish to thank Sue Meger, Connell Wilkinson, and Carmen Trujillo for their excellent secretarial support.
Received May 9, 1994; accepted August 29, 1994.
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References |
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