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(Hypertension. 1996;27:408-413.)
© 1996 American Heart Association, Inc.
Articles |
Factors That Affect Calorie-Sensitive and Calorie-Insensitive Reduction in Blood Pressure During Short-term Calorie Restriction in Overweight Hypertensive Women
From the Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Correspondence to Minoru Kawamura, MD, Second Department of Internal Medicine, Iwate Medical University, Uchimaru 19-1, Morioka, Iwate, 020 Japan.
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Abstract |
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Abstract This study was performed to elucidate the factors that affect the reduction in blood pressure produced by calorie restriction in overweight women with essential hypertension. Fifty-one subjects were admitted to the metabolic ward of the hospital. After being fed a standard diet (6.3 to 8.4 MJ/d) for 2 weeks, the calorie-restricted group (n=34) was fed a low-calorie diet (1.9 MJ/d) for an additional 2 weeks. The calorie-nonrestricted group (n=17) was fed the standard diet for 4 weeks. Sodium and potassium intake was kept constant, as was the level of exercise activity. The calorie-restricted group was subdivided into "calorie-sensitive" and "calorie-insensitive" groups based on an average 5 mm Hg reduction in mean blood pressure during the low-calorie diet. The mean age was 51±6 years (mean±SD) in the calorie-sensitive group (n=16), which was significantly lower than the mean age of 61±6 years in the calorie-insensitive group (n=18). Multiple regression analysis indicated that age and change in body weight exhibited significant correlations with blood pressure reduction produced by calorie restriction among 17 parameters. Findings suggest that age can predict the extent of blood pressure reduction that would be obtained during 2 weeks of calorie restriction in overweight hypertensive women. The reduction in blood pressure may be related in part to the amount of weight loss.
Key Words: hypertension, essential • weight loss • calorie restriction • low-calorie diet • age • sodium balance
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Extensive studies1 2 have demonstrated an association between the overweight condition and hypertension. Prospective trials demonstrate that blood pressure is reduced by weight loss.3 Recent studies4 5 6 7 8 9 10 suggest that the blood pressure of hypertensive, overweight patients is reduced by calorie restriction during a constant intake of sodium. However, only limited information is available about the hypotensive mechanism involved. A decrease in sympathetic nervous system activity,11 suppression of the renin-angiotensin system,12 and suppression of insulin secretion13 have all been suggested as possible mechanisms of blood pressure reduction in patients who range over a spectrum of normotension to moderate hypertension. A decrease in sympathetic nervous system activity has been suggested to be the mechanism for the blood pressure reduction in overweight patients with hypertension who were placed on a low-calorie diet.9 However, since these studies did not use calorie-nonrestricted patients as control subjects, many factors that affect blood pressure besides caloric intake may be involved, including a change in environmental factors,14 physical activity,15 and acclimation to blood pressure measurement.16 We recently found in a randomized, 2-week controlled study that a calorie-restricted group experienced a significantly greater reduction in blood pressure than the control subjects under a constant intake of dietary sodium and potassium and physical activity.17 This strongly suggests that calorie restriction alone can rapidly reduce blood pressure. The extent of reduction obtained varies, which suggests that individuals may be calorie sensitive or calorie insensitive. However, the factors or mechanisms responsible for such "calorie sensitivity" remain to be elucidated.
We evaluated factors that affected the reduction in blood pressure produced by calorie restriction in calorie-restricted versus calorie-nonrestricted groups and also between calorie-sensitive versus calorie-insensitive groups while controlling for other dietary variables and physical activity. Changes in blood pressure were examined relative to baselines and changes in neuroendocrine and electrolyte parameters.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patients
We evaluated 57 Japanese women 40 to 70 years old with essential hypertension who were overweight (body weight, 50 to 80 kg; body mass index, 25 to 30 kg/m2). They were postmenopausal or had undergone hysterectomy for myomas, so that uninterrupted daily urine collection was feasible. To be admitted to the study, they were required to exhibit a systolic blood pressure >160 mm Hg and/or a diastolic blood pressure >95 mm Hg on at least three separate occasions in the absence of treatment or during treatment with antihypertensive medication. A complete medical workup was performed within 1 week of admission to exclude secondary forms of hypertension. Renal function was judged to be normal on the basis of normal serum creatinine, normal intravenous pyelography, and absence of proteinuria. Patients were categorized as stage 1 or stage 2 hypertensive according to World Health Organization classification. Antihypertensive agents were withdrawn 2 weeks before admission to the study and were withheld until the end of the study. This investigation was approved by the Ethical Supervisory Committee of Iwate Medical University. All subjects were provided with detailed information about the protocol and gave informed consent before participation.
Procedures
The 57 women were admitted to the metabolic ward
of
the Iwate Medical University Hospital for this 4-week study. They were
assigned on study entry to either a calorie-restricted group or a
calorie-nonrestricted group. After being fed a standard diet (6.3
to 8.4 MJ/d) for 2 week (weeks 1 and 2), the calorie-restricted
group was fed a low-calorie diet consisting of Optifast (Sandoz
Nutrition) and vegetables for an additional 2 weeks (weeks 3 and 4).
The calorie-nonrestricted group was fed the standard diet for 4
weeks (weeks 1 through 4). Strenuous exertion was prohibited during
this period, and the extent of exercise (walking) was measured with a
pedometer (HJ-7, Omron Inc). Subjects were asked to walk a constant
distance ranging from 4000 to 8000 steps per day, as determined by
individual exercise capacity. They recorded the number of steps
walked each day in a diary. They were also asked to drink a constant
daily volume of water ranging from 1.0 to 1.5 L in addition to eating
their meals during the study. Patients who complained of constipation
during the study received cathartics. Three patients were discharged
before the end of the study because of unexpected business commitments,
and 3 patients discontinued the protocol because they disliked the
taste of Optifast. These 6 patients were subsequently excluded from
evaluation. Ultimately, 51 patients completed the protocol, and their
data were evaluated. Before entry, antihypertensive drugs were
administered to 41 patients, and the remaining 10 patients received no
antihypertensive medication. A calcium channel blocker was administered
to 28 patients, an angiotensin-converting enzyme
inhibitor to 11 patients, a diuretic to 4 patients,
and a ß-blocker to 3 patients (one drug was administered to 36
patients, and two drugs were administered to 5 patients).
Diet
Except for potassium content, constituents of the
standard diet
and the vegetables added in the low-calorie diet were determined
from standard tables.18 Constituents of Optifast were
determined from the manufacturer's manual. The potassium content of
the standard diet and vegetables added in the low-calorie diet was
obtained from measurements using a method of food
digestion.10 In our previous
reports,10 17
sodium intake in the standard diet varied widely day to day
(coefficient of variation, 0.23) because of the addition of salt during
cooking. In the present study, to maintain a constant sodium
intake, the standard diet contained no added sodium chloride. The daily
standard diet contained either 6.3, 7.1, or 8.4 MJ, with 85 to 90 g
protein, 45 to 60 g fat, 180 to 275 g carbohydrates, 30 to 50 mmol
sodium, and 40 to 60 mmol potassium. Each patient selected one of the
three different amounts of calorie intake within 7 days of admission,
although we recommended the amount of calorie intake as judged from the
body weight, age, and exercise activity of the individual patient. The
daily low-calorie diet consisted of Optifast and vegetables
containing 1.9 MJ, with 70 g protein, 2 g fat, 35 g carbohydrates, 40
mmol sodium, and 60 mmol potassium. Each diet contained equal amounts
of sodium (120 mmol) and potassium (60 mmol) per day, since the
standard diet was supplemented with 80 mmol sodium (NaCl) and 8 mmol
potassium (Slow K, Japan Ciba Geigy Pharmaceuticals) and the
low-calorie diet with 80 mmol sodium to equalize the mineral
content. All patients received 859±41 mmol sodium per week in the
standard diet and 847±9 mmol per week in the low-calorie diet. The
week-to-week coefficients of variation were 0.05 and 0.01,
respectively. The amount of calcium in each diet was 20 to 30 mmol per
day.
Measurements and Calculations
Blood samples were collected at
7 AM after the
patients had rested 30 minutes in the supine position on day 3 or 4 of
each week of study. On each day of the study, 24-hour urine was
collected, blood pressure was measured, and body weight was determined.
The nursing staff measured the blood pressure and pulse rate on the
same arm with a standard mercury sphygmomanometer at 6 AM,
10 AM, 2 PM, and 6 PM after the
patients had rested 10 minutes in the supine position. The staff was
well trained in measuring blood pressure. The diastolic
pressure was taken as the level at which the Korotkoff sounds
disappeared. The mean blood pressure was calculated by adding one third
of the pulse pressure to the diastolic pressure. The pulse
rate was counted for 1 minute after the blood pressure had been
measured; blood was then drawn. Body weight was measured on an
electronic strain-gauge scale (EDI-303H, Yamato Co, Ltd) at 6:30
AM after voiding; the value recorded was considered the
body weight for the previous day. Blood pressure, pulse rate, and body
weight were expressed as average values of 7 days in each week. The
24-hour urine collection was done between 7 AM and 7
AM at 4°C. Each urine sample was poured into an
apparatus that divided the urine into two equal portions.
Concentrated hydrochloric acid was added to one portion to measure
norepinephrine. One fiftieth of each portion was stored at
-20°C. The samples obtained during each week were thawed, mixed
together, and then measured. Urinary norepinephrine was
estimated by high-speed ion-exchange
chromatography and the trihydroxyindole
method.19 Serum and urinary sodium concentrations were
measured by flame photometry. Urinary C peptide levels were determined
by radioimmunoassay using a commercial kit (Shionogi Laboratory). Serum
acetoacetate levels were estimated according to the method of Harano et
al20 with a commercial kit (Sanwakagaku Laboratory).
Statistical Methods
Values are expressed as mean±SD.
Significance of the
differences between the calorie-restricted and
calorie-nonrestricted groups, between the calorie-sensitive and
calorie-insensitive groups, and between the calorie-insensitive
and calorie-nonrestricted groups were determined by the
Mann-Whitney test. Taking change in mean blood pressure produced by
calorie restriction as the dependent variable and 17
parameters as independent variables, we performed
multiple regression analysis. A level of P<.05 was
accepted as statistically significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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There were no significant differences between the calorie-restricted group (n=34) and the calorie-nonrestricted group (n=17) in mean values for age (56±7 versus 57±8 years), body weight (66.6±6.6 versus 65.3±7.0 kg), body mass index (28.5±2.7 versus 29.0±3.0 kg/m2), calorie intake (7.5±0.9 versus 7.4±1.0 MJ/d), systolic/diastolic blood pressures (147±15/90±7 versus 149±10/91±6 mm Hg), urinary norepinephrine (4.11±1.32 versus 3.76±0.87 µmol/wk), C peptide (108±50 versus 105±40 nmol/wk) and sodium (700±77 versus 686±62 mmol/wk) excretions, and other parameters measured (data not shown) during week 2. Table 1
indicates
changes from week 2 to weeks 3 and 4 between the two groups. The
calorie-restricted group experienced a significant reduction in
systolic and diastolic blood pressures with weight
loss, elevated sodium excretion, and acetoacetate concentration and
reduced norepinephrine and C peptide excretions compared
with the calorie-nonrestricted group.
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The average reduction in mean blood pressure during weeks 3 and 4 in
the calorie-nonrestricted group was 1.0±2.0 mm Hg, and the 95%
confidence interval was a range of -3 to 5 mm Hg. Therefore, the
calorie-restricted group was subdivided into calorie-sensitive
and calorie-insensitive groups, with a criterion of 5 mm Hg of
reduction in mean blood pressure during weeks 3 and 4. Sixteen patients
belonged to the calorie-sensitive subgroup and 18 patients belonged
to the calorie-insensitive subgroup. The Figure
shows changes in mean blood pressure from week 2 to weeks 3 and 4. The
calorie-sensitive group experienced a significantly greater
reduction in blood pressure than did the calorie-insensitive and
calorie-nonrestricted groups, and no significant difference was
observed in the reduction between the calorie-insensitive and
calorie-nonrestricted groups.
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P<.001 versus calorie-sensitive group in week
4.
Table 2 indicates no significant differences between the
calorie-sensitive and calorie-insensitive groups for any
parameter except age. In the calorie-sensitive group, 4
patients had undergone hysterectomy at the ages of 35, 38, 39, and 43
years, respectively; in the calorie-insensitive group, 3 patients
had undergone hysterectomy at the ages of 39, 40, and 46 years,
respectively. Except for these 7 women, there was no significant
difference in the age of menopause (50±2 versus 50±3 years)
between
the two groups. Twelve patients (75%) in the calorie-sensitive
group and 15 patients (83%) in the calorie-insensitive group had
received antihypertensive drug(s) before entry.
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Table 3 indicates changes between week 2 and weeks 3 and
4 in the calorie-sensitive and calorie-insensitive groups. The
calorie-sensitive group lost more weight and evidenced higher serum
levels of acetoacetate than did the calorie-insensitive group
during weeks 3 and 4. Norepinephrine and C peptide
excretion did not differ between the two groups.
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To evaluate the reduction in blood pressure produced by calorie
restriction and any relation to any other variables, multiple
regression analysis was performed in the calorie-restricted
group. With change in mean blood pressures taken as the dependent
variable and 17 parameters as independent
variables, age and change in body weight exhibited significant
inverse correlations with blood pressure reduction (Table 4).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Results of the present study confirmed that after 2 weeks on the regimen, the calorie-restricted group of overweight, hypertensive women experienced a significantly greater reduction in blood pressure than those given unrestricted calories. The results of this carefully designed and implemented study suggest that calorie restriction lowered blood pressure independently of the intake of sodium, potassium, or calcium and of exercise (walking). This observation corresponds with findings of recent studies4 5 6 7 8 9 10 except for those reported by Andersson et al21 in overweight patients with hypertension.
To the best of our knowledge, this is the first report to find age to be a predictive factor in the reduction of blood pressure produced by calorie restriction over a constant period of time in overweight women with hypertension. Although reduction in the body weight of overweight hypertensive patients is a recommended lifestyle modification,22 23 poor compliance is a major problem.24 The present finding may be especially useful in encouraging younger overweight patients with hypertension to undergo weight reduction.
The reduction of blood pressure produced by calorie restriction can be explained in part by differences in the amount of weight lost. Several long-term studies5 25 26 27 indicate a statistically significant difference between the reduction in body weight attained by calorie restriction and the reduction in blood pressure. Staessen et al,28 who conducted a meta-analysis of 11 studies reported between 1954 and 1985, estimated that the effect of a 1-kg reduction in body weight was a reduction of 1.6 mm Hg in systolic blood pressure and 1.3 mm Hg in diastolic blood pressure. Our study resulted in similar values: reductions of 2.5 mm Hg in systolic blood pressure and 1.3 mm Hg in diastolic blood pressure.
What mechanisms are involved in the reduction in blood pressure
produced by calorie restriction? Sympathetic nervous system activity
and/or insulin secretion are thought to be involved in the renal and
cardiovascular mechanisms of hypertension in
obesity.29 Judging from the present data on urinary
excretions of norepinephrine and C peptide showing no
differences in these substances between the calorie-sensitive and
calorie-insensitive groups (Table 3
) and no significant
correlations between these substances and reduction in blood pressure
(Table 4), there was no indication that sympathetic nervous
system
activity or insulin secretion was involved in a lowering of blood
pressure. These changes could merely reflect calorie restriction, since
significant differences in urinary excretion of
norepinephrine and C peptide were observed between the
calorie-restricted and calorie-nonrestricted groups (Table 1).
This corresponds to the results of a study by Weinsier et
al8 that evaluated the separate effects of energy
restriction and weight reduction, but it is inconsistent
with the findings of Kushiro et al9 that the change in
blood pressure was correlated with the percent change in
norepinephrine during calorie restriction in overweight,
hypertensive patients. The change in blood pressure in that study may
have been due, at least in part, to the spontaneous reduction related
to hospitalization, since the blood pressure of patients with essential
hypertension often decreases upon admission to the hospital, especially
in the initial week.14 Subjects in their study were
switched to a low-calorie diet on day 6 after admission.
The lack of difference in the urinary excretion of norepinephrine between the calorie-sensitive and calorie-insensitive groups may be explained by a possible problem in the method used to estimate sympathetic nervous system activity. Urinary norepinephrine excretion presents an indirect index of sympathetic nervous system activity, since a considerable amount of the norepinephrine released is taken up again.30 The role of sympathetic nervous system activity in such patients should be evaluated by a microneurographic technique that allows the direct measurement of sympathetic neural discharge in humans.31
The renin-angiotensin system is also thought to be
involved in the weight-related changes in blood
pressure.12 The present controlled study
indicated no statistically significant difference in the change in
renin activity during calorie restriction between the
calorie-sensitive and calorie-insensitive groups (Table 3). The
absolute renin activities were comparatively low (Table 2),
suggesting
that the renin-angiotensin system may not be involved
in the hypotensive mechanism of calorie restriction over the short
term, although the role of the tissue renin-angiotensin
system32 remains to be elucidated.
The present study indicated a negative sodium balance during
calorie restriction (Table 1), as previously reported by
Weinsier et
al.8 Although a low-sodium diet produces a negative
sodium balance33 and thus probably plays some role in the
reduction of blood pressure, the hypotensive response to
diuretic administration is unrelated to the extent of the
negative sodium balance.34 We observed no difference in
the quantitative balance between the calorie-sensitive and
calorie-insensitive groups (Table 2) and no correlation between
the
quantitative balance and the blood pressure reduction (Table
4), which
suggests that the hypotensive response to calorie restriction is
unrelated to the extent of negative sodium balance, an idea that
corresponds with previous reports.8 10
Thus, although in the present study blood pressure was found to be reduced by calorie restriction, neurohormonal data did not explain the mechanism. It is possible that the release of other vasoactive substances, including endothelium-derived relaxing factors and atrial natriuretic peptide, is involved. Alternatively, differences in vascular reactivity may be involved in the differences in changes in blood pressure through aging, because aging is associated with changes in the structure and function of the arteries35 ; the vascular responses of endothelium-derived relaxing factors36 and atrial natriuretic peptide37 are all reduced with age. In addition, differences in vascular reactivity may reflect the changes in the structure and function of arteries caused by hypertension, although whether endothelium-dependent relaxation is diminished in hypertensive patients remains controversial.38
We found no difference between the calorie-sensitive and
calorie-insensitive groups in menopausal age, which corresponded to
average menopausal age in Japanese women.39 In both
groups, 
80% of patients had taken antihypertensive drugs before the
study, most commonly a calcium channel blocker. It is therefore
unlikely that these two factors influenced the results between the
calorie-sensitive and calorie-insensitive groups.
We emphasize that the present study involved a short period of severe calorie restriction and that we excluded patients with organ damage from the study. Accordingly, the effect of prolonged, mild calorie restriction as well as the effects of organ damage on the reduction in blood pressure achieved on a restricted diet remain to be elucidated.
In summary, our results suggest that age was a predictor of the extent of blood pressure reduction during 2 weeks of marked calorie restriction in overweight, hypertensive women. The reduction in blood pressure may be related in part to the amount of weight loss.
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Acknowledgments |
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This work was supported by a Research Grant for Cardiovascular Diseases (3C-5) from the Ministry of Health and Welfare of Japan.
Received May 16, 1995; first decision June 30, 1995; accepted November 24, 1995.
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