(Circulation. 2001;103:32.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Women’s Healthy Lifestyle Project: A Randomized Clinical Trial
Results at 54 Months
From the University of Pittsburgh, Departments of Epidemiology (L.H.K., L.R.S.-S., E.N.M., D.G.I.) and Psychiatry (R.R.W.), Pittsburgh, Pa.
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Abstract |
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Background—The Women’s Healthy Lifestyle Project Clinical Trial tested the hypothesis that reducing saturated fat and cholesterol consumption and preventing weight gain by decreased caloric and fat intake and increased physical activity would prevent the rise in LDL cholesterol and weight gain in women during perimenopause to postmenopause.
Methods and Results—There were 275 premenopausal women randomized into the assessment only group and 260 women into the intervention group. The mean age of participants at baseline was 47 years, and 92% of the women were white. The mean LDL cholesterol was 115 mg/dL at baseline, and mean body mass index was 25 kg/m2. The follow-up through 54 months was excellent. By 54 months, 35% of the women had become postmenopausal. At the 54-month examination, there was a 3.5-mg/dL increase in LDL cholesterol in the intervention group and an 8.9-mg/dL increase in the assessment-only group (P=0.009). Weight decreased 0.2 lb in the intervention and increased 5.2 lb in the assessment-only group (P=0.000). Triglycerides and glucose also increased significantly more in the assessment-only group than in the intervention group. Waist circumference decreased 2.9 cm in the intervention compared with 0.5 cm in the assessment-only group (P=0.000).
Conclusions—The trial was successful in reducing the rise in LDL cholesterol during perimenopause to postmenopause but could not completely eliminate the rise in LDL cholesterol. The trial was also successful in preventing the increase in weight from premenopause to perimenopause to postmenopause. The difference in LDL cholesterol between the assessment and intervention groups was most pronounced among postmenopausal women and occurred among hormone users and nonusers.
Key Words: obesity • exercise • trials • lipoproteins • diet
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Introduction |
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During the perimenopausal to postmenopausal years, women experience a substantial increase in their LDL cholesterol and total cholesterol and a small decrease in total HDL cholesterol.1 They gain an average of about 1 lb per year and increase their waist circumference.2 There are a decrease in bone mineral density and muscle mass and an increase in percent body fat even among women with no increase in total body weight.3
The Women’s Healthy Lifestyle Project (WHLP), a randomized clinical trial, tested the hypothesis that reducing consumption of saturated fat and cholesterol in their diet and preventing weight gain by decreasing both total and fat calories and moderately increasing physical activity among "healthy" women would prevent the rise in LDL cholesterol and weight gain from premenopause to perimenopause to postmenopause. This study tested an overall intervention and its effects on the risk factors, not the specific components on the risk factors (ie, the intervention to lower saturated fat and cholesterol versus weight gain prevention). This report focuses on change in LDL cholesterol levels.
The increase in total or LDL cholesterol during perimenopause to postmenopause has been noted in practically all populations, including those that have relatively low LDL cholesterol levels before menopause and consume very low levels of saturated fat and cholesterol in their diets. There is also a direct relationship between weight gain from perimenopause to postmenopause and rise in LDL cholesterol.4 5
The LDL cholesterol level in women, as well as in men, is reduced by a diet low in saturated fat and cholesterol.6 These changes in LDL cholesterol are similar for men and women and are consistent with the Keys or Hegstead equations for the effects of various dietary saturated fat, polyunsaturated fat, and LDL cholesterol levels.7 These dietary changes produce a greater decline in HDL cholesterol levels among women compared with men.6 In addition to diet, estrogen therapy reduces LDL cholesterol levels.8
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Methods |
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Descriptions of recruitment and eligibility criteria have been previously published.9 10 Women were between 44 to 50 years of age and were sampled from voter registration lists in Allegheny County, Pennsylvania, between 1992 and 1994.9 10 Women with a prior hysterectomy and those on hormone replacement therapy (HRT) were excluded from the trial.
Study Design and Procedures
Participants completed a telephone interview, a
screening visit, and a baseline visit to determine eligibility. The
study protocol was approved yearly by the Institutional Review Board at
the University of Pittsburgh. Written informed consent was obtained at
the screening visit. All participants were provided with a health
education pamphlet on reducing cardiovascular risk factors at baseline.
Participants who reported smoking were advised to quit. Participants
were randomly assigned to an assessment-only control group or to a
lifestyle intervention group. Both groups attended follow-up clinic
assessments at 6, 18, 30, 42, and 54 months after
randomization.
Lifestyle Intervention
The lifestyle intervention was a 5-year
cognitive-behavioral program aimed at preventing the increase in LDL
cholesterol levels, preventing weight gain, and increasing leisure-time
physical
activity.9 10
Participants were asked to lower their dietary fat intake to 25% of daily calories, lower their saturated fat intake to 7% of calories, and lower their dietary cholesterol to 100 mg daily. All women were given a modest weight loss goal of 5 to 15 lb, depending on baseline weight status, and they were asked to reduce daily caloric intake to 1300 kcal until the weight goal was achieved. A lifestyle approach to increasing physical activity to 1000 to 1500 kcal expended weekly was used to facilitate weight control. The specific aims were to prevent rise in LDL cholesterol and weight among women with "average" levels of risk factors. The intervention included an intensive group program during the first 6 months and follow-up individual/group sessions from 6 through 54 months.9
Statistical Methods
Descriptive statistics were used to describe baseline
and sociodemographic variables. We used
t tests and ANOVA to test the
differences between intervention and control groups on risk factors.
The primary end points of the trial were difference in the change in
LDL cholesterol and weight between intervention and assessment-only
groups at the end of the trial (54
months).
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Results |
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There were 275 women randomly assigned to the assessment only group and 260 in the lifestyle intervention group. The mean age of the participants was 47±1.6 years (Table 1
).
Table 1 summarizes selected baseline characteristics for
the lifestyle intervention and control groups. No significant
differences were found between groups on any of the
variables.
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The mean baseline LDL cholesterol was 116 mg/dL for the assessment group and 115 mg/dL for the intervention group. Mean baseline body mass index (BMI) was 25 kg/m2 for both the assessment and intervention groups; 92% of the participants were white; 49% had 0 to 4 years of college; and 36% had more than a college education. Attendance at the 5 clinic follow-up assessments averaged 93%; 95% returned for the 54-month assessment. There was 1 death resulting from an accident.
There was an 
10-mg/dL between-group difference in LDL
cholesterol at 6 months and an 5.4-mg/dL between-group difference at
54 months
(Table 2 and
Figure 1). LDL cholesterol increased over time from the
6-month visit for both the intervention and assessment groups
(Table 2). The comparison of the change in LDL cholesterol
between the intervention and control group was statistically
significant at each time point in this study
(Table 2).
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We also assessed the categorical distributions of LDL cholesterol at the 54-month visit. Twenty-seven percent of the intervention group compared with only 16% of the assessment-only group had LDL cholesterol levels <100 mg/dL, whereas 40% of the assessment-only group and only 32% of the intervention group had LDL cholesterol levels >130 mg/dL (P=0.007, Mantel-Haenszel test for linear comparison between the assessment and intervention groups).
We classified women as premenopausal, perimenopausal, or
postmenopausal for analysis. At the 54-month follow-up, 56% of the
participants in both the intervention and control groups were still
menstruating regularly and were considered to be premenopausal; 10%
were perimenopausal, having missed 3 to 11 consecutive periods; and
35% were postmenopausal, having missed 12 consecutive periods or
having had a hysterectomy. There were 27 women who had a hysterectomy
(13 in the intervention group and 14 in the assessment-only group), and
25 of the 27 also reported an oophorectomy. The difference in LDL
cholesterol at the 54-month examination between the assessment and
intervention groups was greater for the women who had become
postmenopausal (8.7 versus 4.0 mg/dL for women who had remained
premenopausal;
Table 3). The statistical test for interaction of change in
LDL cholesterol effect by menopausal status and treatment group,
however, was not significant.
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Use of HRT was not affected by study intervention groups. At
the 54-month examination, 30% (80 of 263) in the assessment group and
32% (79 of 245) in the intervention group were on HRT
(Table 4). A high percentage of women who had become
postmenopausal (56% of control subjects, 61% of intervention) were on
HRT. Many of the women were started on HRT before 12 months of
amenorrhea and remained amenorrheic on HRT (almost always a combination
of estrogen and continuous progesterone [medroxyprogesterone]). After
12 months of amenorrhea, the women were classified as postmenopausal,
although it is likely that some were still premenopausal at the end of
12 months of HRT. Among the 159 women on HRT at the 54-month visit, 20
(13%) were on estrogen only, 127 (80%) were on estrogen and
progesterone, 2 (1%) were on progesterone only, and 10 (6%) were on
other therapies.
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Hormone users had a smaller increase in LDL cholesterol, as
expected for both the assessment and intervention groups. The
difference between the assessment and intervention groups was similar
(ie, 4.9 and 5.3 mg/dL for hormone uses and nonusers, respectively;
Table 5). There was an 14-mg/dL difference in LDL
cholesterol between the assessment group not on HRT and the
intervention group also on hormone therapy. There was no significant
interaction between treatment group and use of HRT and changes in LDL
cholesterol and other coronary heart disease risk factors.
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There was a substantial increase in other risk factor levels
to 54 months in the assessment versus intervention group
(Table 2
). Triglycerides increased 18 mg/dL in the
intervention and 30 mg/dL in the assessment-only group
(P<0.01). Increases in
triglycerides were similar among hormone users and nonusers
(Table 5). There was a greater increase in triglycerides in
the women who became menopausal for both the intervention and
assessment-only groups
(Table 3). HDL cholesterol levels
(Table 2) decreased at 6 months in the intervention group,
with little change in the assessment group. At 54 months, there was an
increase in both the assessment and intervention groups
(P=NS). The increase in HDL
cholesterol levels was limited to women on HRT for both the assessment
and intervention groups
(Table 5).
Changes in apoB, apoA-1, and apoA-2 parallel the changes in
LDL cholesterol, triglycerides, and HDL cholesterol. There was a
significant decline in apoB for the intervention versus assessment-only
group of 6.7 mg/dL at 6 months, 4.5-mg/dL difference at 18 months, and
4.6-mg/dL difference at 54 months
(Table 2).
There was an increase in blood glucose levels for both the
intervention and assessment-only groups, but the increase was
significantly greater for the assessment-only compared with
intervention group. At 54 months
(Table 2), fasting blood glucose had increased 3.3 mg/dL in
the assessment compared with 1.6 mg/dL in the intervention group
(P<0.05). At 6 months,
systolic blood pressure was 3.5 mm Hg and diastolic blood pressure was
2.2 mm Hg lower (P<0.01) in
the intervention compared with assessment-only group. The statistical
significant differences in blood pressure, however, had disappeared by
54 months
(Table 2). At 54 months, 15 women (9 in the assessment-only
group, 6 in the intervention group) reported that they were being
treated with drugs for hypertension. Seven other women (5 in the
assessment group, 2 in the intervention group) reported use of
diuretics.
Blood insulin levels were measured in 2 laboratories over
the time of the study, so it was impossible to compare the change from
baseline. Baseline insulin levels were the same in both groups. At both
6 and 54 months, the blood insulin levels were significantly lower in
the intervention compared with the assessment group (13.5 versus 11.6
mmol/mL at 6 months and 11.3 versus 10.5 mmol/mL at 54 months). Very
few women smoked cigarettes at baseline, 9% in both groups and
8% in both groups at 54 months (not shown).
There was about a 5.2-lb weight gain in the assessment
group, consistent with our previous observation of about 1 lb per year,
and a 1-lb decrease in weight in the intervention group
(Table 2 and
Figure 2). The significant decrease in waist circumference
is consistent with weight change. At baseline, the intervention and
comparison groups were both consuming about 11.5% to 11.8% saturated
fat of total calories. At 6 months, the saturated fat intake had
dropped to 7.9% in the intervention and 11.2% in the control group;
at 54 months, it dropped to 9% in the intervention and 10.9% in the
assessment group
(Table 6). Total fat intake was 32% in both the
assessment and intervention groups and dropped at 54 months to 30.4%
in the assessment-only and 25.6% in the intervention group
(Table 6). Oleic acid, monounsaturated fat, and dietary
linoleic acid as measures of polyunsaturates decreased significantly
more at 54 months in the intervention group compared with the
assessment group, consistent with efforts to reduce the total fat
intake. No attempt was made to increase omega-3 fatty acids, except to
substitute fish for meat in the diet to reduce saturated fat
consumption.
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Total dietary cholesterol was 196 mg/d at baseline in both
the assessment and intervention groups, increased to 212 mg/d in the
control subjects, and declined to 154 mg/d in the intervention group
(P=0.000). There was no
significant change in either dietary protein or carbohydrate
consumption as percent of total calories
(Table 6).
At 54 months, there was a positive correlation between change in weight (R2=0.31, P=0.000) and change in LDL cholesterol within the intervention group and a significant association between change in LDL cholesterol and the percent decrease in saturated fat (R2=0.19, P=0.002). Furthermore, there was a strong correlation between change in weight and reported change in saturated fat (R2=0.19, P=0.002; not shown).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The WHLP clinical trial has demonstrated that a lifestyle intervention that combines dietary changes, a reduction in calories and total fat calories, and a decrease in both saturated fat and dietary cholesterol, along with increasing leisure time physical activity, resulted in a significantly smaller increase in LDL cholesterol levels over 54 months in the intervention compared with the assessment group. There were also significant differences in triglycerides, systolic and diastolic blood pressures, blood glucose, and insulin for the intervention compared with assessment-only group. Differences in weight gain were also maintained over the 54 months of the trial.
The rise in LDL cholesterol during perimenopause to
postmenopause was blunted in the intervention group but not totally
prevented, as was hoped in the original hypothesis. Still, the
8.7-mg/dL difference between groups (7% from baseline levels) among
menopausal women is impressive.
We have previously shown in the Healthy Women Study that LDL
cholesterol levels measured during premenopause to perimenopause were
significant predictors of coronary and aortic calcification as measured
by electron beam CT among women mean who were 61 years of age, 8 to
10 years postmenopausal. The relationship between LDL cholesterol and
coronary and aortic calcification was linear from a relatively low
level of LDL cholesterol, probably 100 to 120
mg/dL.11
The very high percentage of women on HRT (31%) as they became menopausal affects some of the analysis of the 54-month data. The women in the study were generally well educated, and none had a prior hysterectomy or oophorectomy or history of coronary heart disease or diabetes. No information was provided by the study staff to encourage or discourage use of HRT. Questions regarding the use of HRT were referred back to the women’s primary care or speciality physicians. Women were often placed on HRT before cessation of menses.
We originally hypothesized that the intervention group would
be more likely to develop menopausal symptoms such as hot flashes
because of their weight loss or failure to gain weight during
perimenopause to postmenopause and would be much more likely to use
HRT. In the Healthy Women Study, as well as in other studies, there is
a strong inverse relationship between BMI and likelihood of use of HRT.
The prevalence of symptoms (not shown) and use of HRT
(Table 4) were similar for the intervention and assessment
groups. Thus, it does not appear that the intervention, in spite of the
prevention of weight gain, resulted in greater use of HRT to manage
symptoms. We have, however, previously published data showing that
there was greater bone loss in the intervention group compared with the
assessment group at 18 months and that the degree of bone loss was
related to the amount of weight
loss.12 There were also
higher levels of markers of bone loss in the intervention compared with
the assessment group at 18
months.12
The trial was not designed, as noted, to determine the efficacy of specific intervention components: prevention of weight gain through caloric reduction, low fat diet, and increased physical activity compared with fatty acid composition (ie, decreased saturated fat and cholesterol in the diet).
Clearly, the intervention is labor intensive. Prevention of weight gain and a rise in LDL cholesterol could have a major impact in reducing cardiovascular morbidity and mortality among women.13 14 15 Newer nutritional approaches became available since the beginning of the trial that may further enhance the reduction of LDL cholesterol levels.16 17
In conclusion, this trial has shown the efficacy of this intervention in preventing or reducing the rise in LDL cholesterol and weight, the 2 primary end points of the trial.
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Acknowledgments |
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This research was supported by NIH grant HL-45167.
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Footnotes |
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Reprint requests to Dr Lewis H. Kuller, University of Pittsburgh, Department of Epidemiology, GSPH, 130 DeSoto St, Pittsburgh, PA 15261.
Received May 30, 2000; revision received August 16, 2000; accepted August 17, 2000.
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