(Hypertension. 1997;29:976-979.)
© 1997 American Heart Association, Inc.
Articles |
Relative Influence of Menopausal Status, Age, and Body Mass Index on Blood Pressure
From the Hypertension Unit of the First Institute of Internal Medicine (F. Portaluppi, R.M.) and the Institute of Obstetrics and Gynecology (F. Pansini, G.M.), University of Ferrara, Italy.
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Abstract |
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Abstract The objective of this study was to assess the influence of menopausal status on blood pressure levels in a cross-sectional population study in the setting of a preventive health care program clinically conducted in Ferrara, Italy. The patients were 2397 healthy women 35 to 65 years old (489 in premenopause, 847 in perimenopause, 887 in spontaneous menopause, and 174 in surgical menopause); subgroups were also obtained with increasing duration of menopause (1 to >5 years) matched with premenopausal and perimenopausal women by chronological age at onset of menopause. Measurements of sphygmomanometric blood pressure, age, age at menopause, duration of menopause, and body mass index were made. Postmenopausal women had higher blood pressure than premenopausal and perimenopausal subjects. After adjustment for body mass index, the blood pressure changes with menopausal status were still significant, but not after correction by age. The increased risk of hypertension of postmenopausal women also lost statistical significance after adjustment for age and body mass index. At multivariate analysis, blood pressure showed no significant relation with the duration of menopause, whereas age was a significant covariant for systolic blood pressure, and body mass index for systolic and diastolic blood pressure. A transient initial rise in blood pressure and body mass index was detected in surgical but not in spontaneous menopause. Blood pressure rises after menopause appear to be due more to increased body mass index and aging than ovarian failure per se.
Key Words: spontaneous menopause • surgical menopause • blood pressure • age • body mass index
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Introduction |
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The influence of menopausal status on arterial blood pressure is still unclear. In the previous reports on this issue available in the Medline database, systolic blood pressure levels have been found to show either negative,1 2 3 positive,4 5 or no correlation6 7 8 9 10 11 12 13 with menopause. Contrasting evidence has also been reported for diastolic blood pressure, which has been found to be either decreased,2 increased,4 5 6 7 12 or unaffected1 3 8 9 10 11 13 by menopause. Even if we consider only the available prospective studies,2 3 7 10 13 the results are still contradictory.
This report focuses on the relative influence of menopausal status, age, and body mass index on the sphygmomanometric blood pressure levels of healthy women. This cross-sectional study is part of an ongoing, population-based, preventive healthcare program conducted in Ferrara, a small town of Northern Italy.
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Methods |
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Subjects
We screened 3394 women who volunteered in the preventive care program of the University of Ferrara between November 1990 and November 1994. The age range (35 to 60 years) was chosen to include the age span of women reporting the beginning of menopause plus 5 years necessary to assess the influence of the time from menopause on blood pressure levels. Those who satisfied the following criteria were selected: no tobacco consumption; a daily alcohol intake of less than either 100 mL of wine, 330 mL of beer, or 25 mL of distilled spirits; no history, symptoms, or signs of diabetes mellitus, secondary hypertension, familial dyslipidemia, or cardiovascular, cerebrovascular, or renal disease; normal fasting values of blood glucose, creatinine, sodium, and potassium; and normal complete blood cell count and urinalysis. Women taking antihypertensive medications were classified as hypertensive and were included in the study only for the analysis of the prevalence of hypertension but were excluded from the analysis of the blood pressure level. Women in current need of any other drug that might interfere with blood pressure levels or lipid metabolism were excluded from the study.
As a result of this selection and after exclusion of the subjects in
whom data collection was incomplete (47 subjects), the following groups
were included in this study: 489 premenopausal women with regular
menstrual periods and serum follicle-stimulating hormone <50 IU/L; 847
perimenopausal women with irregular periods or absence of menstruation
for not longer than 11 months and follicle-stimulating hormone <50
IU/L; 887 women in spontaneous menopause with last menstrual period at
least 12 months before they entered the study and follicle-stimulating
hormone 
50 IU/L; and 174 women in surgical menopause, who had
undergone hysterectomy with bilateral ovariectomy for uterine
leiomyomatosis and were menstruating with follicle-stimulating hormone
<50 IU/L at the time of surgery.
Protocol
The study was approved by the local ethics committee and
followed procedures in accordance with institutional guidelines.
Informed consent was obtained from each subject. Complete medical
history, physical examination, time from last menstruation, and body
mass index (calculated as weight in kilograms divided by the square of
height in meters) were recorded. Systolic and
diastolic blood pressures were measured by an experienced
nurse using a mercury sphygmomanometer and following the
recommendations of the American Heart Association.14
Caffeine ingestion in the 120 minutes before measurement was excluded.
An ECG tracing was recorded. The first determination was averaged
from three sitting readings (beginning after a 5-minute rest) separated
by at least 2 minutes. Two other determinations were obtained with the
same procedure on separate occasions within the following 4 weeks.
Subjects were classified as hypertensive if they were taking
antihypertensive medications or if blood pressure was 140 mm Hg
systolic or 90 mm Hg diastolic as the mean
value of these separate determinations. A chest roentgenogram was
always obtained, as well as a venous blood sample for estrone,
estradiol, and follicle-stimulating hormone determination. In
premenopausal and perimenopausal women, blood was drawn on days 5
through 10 of the cycle. The subject was then referred to the central
laboratory of the hospital for urinalysis, complete blood cell count,
and automated blood chemistry.
Laboratory Methods
Blood samples were drawn into glass tubes without additives and
were allowed to clot at room temperature. They were centrifuged
at 1500g for 30 minutes at 4°C. Serum concentrations of
estrone, estradiol, and follicle-stimulating hormone were immediately
determined in duplicate by conventional radioimmunoassays using
commercial kits (FSH MAIAClone kit, Ares Serono
Diagnostics; Estradiol Coat-A-Count Kit,
Diagnostic Products Corp; Estrone Kit,
Diagnostic Systems Laboratories). The minimal detectable
dose was 0.5 IU/L for follicle-stimulating hormone, 30 pmol/L for
estradiol, and 37 fmol/L for estrone. The intra-assay and interassay
coefficients of variation were 3% and 4% for follicle-stimulating
hormone, 6% and 7% for estradiol, and 7% and 8% for estrone,
respectively.
The quality control analysis of the determinations performed by the central laboratory of our hospital during the study period revealed intra-assay and interassay coefficients of variation always <5% and <8%, respectively.
Statistical Analysis
To minimize other possible confounding factors, only nonsmoking,
untreated, healthy women with low alcohol consumption were included in
the analysis of blood pressure levels. Subjects on
antihypertensive medications were classified as hypertensive and were
considered only for the analysis of the prevalence of
hypertension. Data were stored on a dBase III Plus data base (Borland)
and then exported to the statistical package Systat (Systat Inc) for
elaboration. After positive testing for gaussian distribution, mean and
SDs of the various parameters were calculated for each
menopausal category. To appreciate the influence of the duration of
menopause on blood pressure, we also selected subgroups of increasing
duration of menopause (1 to >5 years) matched with premenopausal and
perimenopausal women by chronological age at onset of menopause. The
differences among means were compared by ANOVA (both before and after
adjustment for the significant covariates, chronological age and/or
body mass index) and by Scheffé's test (as a post hoc procedure
when needed). Then relative risks of
systolic/diastolic hypertension (blood pressure
>140/90 mm Hg) were calculated by logistic regression
analysis in spontaneous and surgical menopause compared with
premenopause both before and after adjustment for age and body mass
index. Logistic regression coefficients and their standard errors were
estimated by the method of maximum likelihood,15 from
which adjusted estimates of relative odds with 95% CIs were calculated
to approximate relative risks.
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Results |
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The characteristics of the study population are given in Table 1
according to the menopausal status. Both
systolic and diastolic blood pressures changed
significantly with menopausal status. Systolic blood pressure
was significantly higher in both spontaneous and surgical menopause
than premenopause and perimenopause. Diastolic blood
pressure was significantly higher only in surgical menopause. After
adjustment for chronological age and body mass index, however, the
menopausal status per se showed no significant effect on blood pressure
levels (F values of 0.739 and 0.872 for systolic and
diastolic blood pressure, respectively, P=NS in
both cases). The relative influence on blood pressure variation was
higher for chronological age than body mass index, as demonstrated by
the more pronounced reduction of statistical significance after
adjustment for age (F values of 2.365 and 1.968, both P=NS)
than body mass index (F values of 5.886 and 2.989, P=.001
and .030).
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The increased hypertensive risk of postmenopausal women (Table 2) also lost statistical significance after adjustment
for age and body mass index. Again, the highest relative influence was
attributable to chronological age.
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ANCOVA performed in subgroups of increasing duration of menopause (1 to
>5 years) matched with premenopausal and perimenopausal women by
chronological age at onset of menopause (Table 3)
demonstrated no significant influence of duration of menopause on blood
pressure levels. In both spontaneous and surgical menopause,
chronological age was a significant covariant of time after
onset of menopause for systolic (but not diastolic)
blood pressure, whereas body mass index covaried highly significantly
for both systolic and diastolic blood pressures. A
transient initial rise in blood pressure and body mass index was
apparent in surgical menopause but absent in spontaneous menopause.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The main finding of this study is that sphygmomanometric blood pressure is increased in postmenopausal women as a result of chronological aging and higher body mass index. Menopause per se does not appear to be a risk factor for hypertension.
Previous studies on this subject have led to contradictory results.1 2 3 4 5 6 7 8 9 10 11 12 13 Insufficient sample size in relation to the great number of possible determinants of blood pressure changes, lack of control (premenopausal) groups, and different subject selection criteria may explain these inconsistencies. To minimize the effect of possible confounding factors, we studied only healthy women with no association of other cardiovascular risk factors or hypertensive target-organ damage. Racial influence was also absent in our study, since the whole Ferrara population is white. We avoided misclassification of hypertensive cases by adopting the standard procedure recommended by the official guidelines to define presence of hypertension.
Conversely, a possible concern about our findings comes from the cross-sectional nature of its design, which has known disadvantages compared with longitudinal studies. To partially overcome this limitation, we assessed the influence of menopause duration on blood pressure by comparing subgroups of increasing duration of menopause matched with premenopausal and perimenopausal women by chronological age at onset of menopause. Although not conclusive, this analysis further indicates that no significant influence of duration of menopause was present on the blood pressure levels of our population.
The separate analysis of a large group of women ovariectomized for therapeutic reasons led to the observation of a transient rise in blood pressure after occurrence of surgical menopause, which was related primarily to an increased body mass index. Our data permit no explanation of such a finding. We can only hypothesize that abrupt withdrawal of ovarian function in these women might create a transient hormonal and psychological imbalance that might be reflected by the observed blood pressure and weight changes.
Conversely, the changes in vascular physiology that may lead to
increasing blood pressure, particularly systolic blood
pressure, may occur during the perimenopausal to early postmenopausal
period but may be noted only as an increase in blood pressure later in
menopause, thus becoming statistically indistinguishable from an aging
effect. Cross-sectional observations indicate that systolic
blood pressure may increase faster in older women than men, at least in
industrial societies.16 17 18 Were this confirmed by
longitudinal studies, a causal effect or at least a hormonal influence
of menopause on blood pressure could still be possible. Against this
hypothesis, however, is our finding that duration of menopause showed
no significant relation with blood pressure levels when the effect of
chronological age was excluded by matching the age at onset of
menopause (Table 3
). Again, the cross-sectional type of our study
limits the interpretation of these data. Further longitudinal studies
specifically designed to address this issue are needed.
In conclusion, this study suggests that ovarian failure and duration of menopause are not direct determinants of blood pressure rise in middle-aged women. However, weight gain could be an important and potentially preventable determinant of increased blood pressure and risk of hypertension in these women.
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Acknowledgments |
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This study was supported by grants from the Italian Ministry of University and Scientific and Technological Research (60%).
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Footnotes |
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Reprint requests to Francesco Portaluppi, MD, Hypertension Unit, First Institute of Internal Medicine, University of Ferrara, via Savonarola 9, I-44100 Ferrara, Italy.
Received August 26, 1996; first decision September 12, 1996; accepted October 10, 1996.
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